Diabetic eye: Associated diseases, drugs in clinic, and role of self-assembled carriers in topical treatment. - Kattar, Axel; Concheiro, Angel; Alvarez-Lorenzo, Carmen (Expert opinion on drug delivery, 2021)
INTRODUCTION: Diabetes is a pandemic disease that causes relevant ocular pathologies. Diabetic retinopathy, macular edema, cataracts, glaucoma or keratopathy strongly impact the quality of life of the patients. In addition to glycemia control, intense research is devoted to find more efficient ocular drugs and improved delivery systems that can overcome eye barriers., AREAS COVERED: The aim of this review is to revisit first the role of diabetes in the development of chronic eye diseases. Then, commercially available drugs and new candidates in clinical trials are tackled together with the pros and cons of their administration routes. Subsequent sections deal with self-assembled drug carriers suitable for eye instillation combining patient friendly administration with high ocular bioavailability. Performance of topically administered polymeric micelles, liposomes and niosomes for the management of diabetic eye diseases are analyzed on the light of ex vivo and in vivo results and outcomes of clinical trials., EXPERT OPINION: Self-assembled carriers are being shown useful for efficient delivery of not only a variety of small drugs but also macromolecules (e.g. antibodies) and genes. Successful design of drug carriers may offer alternatives to intraocular injections and improve the treatment of both anterior and posterior segments diabetic eye diseases.

Anterior segment imaging in minimally invasive glaucoma surgery - A systematic review. - Kan, John Tsia-Chuen; Betzler, Bjorn Kaijun; Lim, Sheng Yang; Ang, Bryan Chin Hou (Acta ophthalmologica, 2021)
Minimally invasive glaucoma surgery (MIGS) has grown in popularity over the past decade. This systematic review explores the peri-operative and intraoperative application of anterior segment imaging to maximize the efficacy and safety of MIGS. A review of the PubMed, EMBASE and CINAHL databases was conducted, with inclusion criteria restricted to MIGS that had received United States Food and Drug Administration (FDA) premarket approval, FDA 510(K) premarket notification, or were listed as a class 1 device exempt from FDA approval or notification. 21 manuscripts from 21 unique studies were identified pertaining to MIGS devices including the XEN Gel Stent, Trabectome, iStent Inject, 1st-generation iStent and the Kahook Dual Blade (KDB). Anterior segment imaging modalities included anterior segment optical coherence tomography (AS-OCT), ultrasound biomicroscopy (UBM), aqueous angiography, OCT volumetric scans and in vivo confocal microscopy. Identification and evaluation of aqueous outflow pathways before and after MIGS have potential for improving patient preoperative patient selection and postoperative outcomes. Intraoperative imaging potentially provides the resolution needed for good visualization of angle anatomy and accurate evaluation of surgical endpoints in angle-based MIGS. Anterior segment imaging has been used to identify procedural complications, provide objective information on implant location in relation to surrounding anatomy, assess the post implantation structural impact of MIGS devices and manage bleb failure and scarring. Technical difficulties in incorporating imaging modalities into the surgical microscope, variable quality of images and optical interference from ocular structures or surgical instruments are remaining barriers, which discourage the widespread clinical use of this technology. Copyright © 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Characteristics Associated With New Patient Appointment No-Shows at an Academic Ophthalmology Department in the United States. - Chiam, Mckenzee; Kunselman, Allen R; Chen, Michael C (American journal of ophthalmology, 2021)
PURPOSE: This study aimed to identify patient and appointment characteristics associated with no-shows to new patient appointments at a US academic ophthalmology department., DESIGN: Cross-sectional study., METHODS: This was a study of all adult patients with new patient appointments scheduled with an attending ophthalmologist at Penn State Eye Center between January 1st and December 31st of 2019. A multiple logistic regression model was used to assess the association between characteristics and no-show status., RESULTS: Of 4,628 patients, 759 (16.4%) were no-shows. From the multiple logistic regression model, characteristics associated with no-shows were age (Odds Ratio (OR) for 18-40 years vs. >60 years: 3.41, 95% Confidence Interval (CI) 2.57, 4.51, p <0.001 and OR for 41-60 years vs. >60 years: 2.14, 95% CI 1.67, 2.74, p<0.001), median household income (OR for <$35,667 vs. >$59,445: 1.59, 95% CI 1.08, 2.34, p<0.001), insurance (OR for None vs. Medicare: 6.92, 95% CI 4.41, 10.86, p<0.001 and OR for Medicaid vs. Medicare: 1.54, 95% CI 1.18, 2.01, p=0.002), race (OR for Black vs. White: 2.62, 95% CI 2.00, 3.43, p<0.001 and OR for Other vs. White: 2.02, 95% CI 1.58, 2.59, p<0.001), and commute distance (OR for 5-10 mi vs. <=5 mi: 1.73, 95% CI 1.17, 2.55, p=0.006). Appointments with longer lead times and scheduled with glaucoma or retina specialists were also significantly associated with greater no-shows., CONCLUSION: Certain patient and appointment characteristics were associated with no-show status. These findings may assist in the development of targeted interventions at the patient, practice, and health system levels to improve appointment attendance. Copyright © 2021 Elsevier Inc. All rights reserved.

Health Literacy and Success with Glaucoma Drop Administration. - Kang, J Minjy; Chatterjee, Ayan; Rosdahl, Jullia A; Bosworth, Hayden B; Woolson, Sandra; Olsen, Maren; Sexton, Malina; Kirshner, Miriam; Muir, Kelly W (Ophthalmology. Glaucoma, 2021)
PURPOSE: To assess the relationship between health literacy and successful glaucoma drop administration., DESIGN: Substudy of a single-site interventional randomized controlled trial., PARTICIPANTS: Veterans receiving care at the Durham Veterans Affairs Eye Clinic who had a diagnosis of open-angle glaucoma were recruited if they endorsed poor drop adherence., METHODS: Participants underwent a health literacy evaluation using the Rapid Estimate of Adult Literacy in Medicine (REALM) as well as a qualitative assessment of eye drop administration technique using 3 different criteria: (1) the drop was instilled in the eye, (2) only 1 drop was dispensed, and (3) the bottle was not potentially contaminated. A multivariate logistic regression model was used to assess the association of REALM score and successful drop administration, adjusting for age, disease severity, and Veterans Administration Care Assessment Needs (CAN) score., MAIN OUTCOME MEASURES: Successful drop administration., RESULTS: Of the 179 participants with REALM scores and observed drop administration, 78% read at a high school level (HSL) or more and 22% read at less than HSL. Of the 179 participants, 87% (n = 156) successfully instilled the drop into the eye (criterion 1). A greater proportion of participants who read at HSL or more successfully instilled the drop in the eye compared with those reading at less than HSL (90.6% vs. 75.0%; P = 0.02). Rates of success with criterion 1 were similar across different levels of visual field severity. Care Assessment Needs scores were not statistically significant between those who did and those did not have successful overall drop technique., CONCLUSIONS: Poor health literacy may be associated with decreased successful drop instillation in the eye in patients with glaucoma. Screening for and considering health literacy in developing interventions to improve glaucoma self-management may improve treatment adherence in a vulnerable population. Copyright Published by Elsevier Inc.

Improved Glaucoma Medication Adherence in a Randomized Controlled Trial. - Muir, Kelly W; Rosdahl, Jullia A; Hein, Aaron M; Woolson, Sandra; Olsen, Maren K; Kirshner, Miriam; Sexton, Malina; Bosworth, Hayden B (Ophthalmology. Glaucoma, 2021)
PURPOSE: To test the effectiveness of an intervention designed to improve glaucoma medication adherence., DESIGN: Randomized, controlled trial at a Veterans Affairs (VA) eye clinic., PARTICIPANTS: Veterans with medically treated glaucoma who reported poor adherence and their companions if applicable., METHODS: Participants, and their companions if applicable, were randomized to receive an intervention to improve medication adherence that included glaucoma education, personalized disease management suggestions, and a reminder aid, or the control arm that received education regarding general eye health., MAIN OUTCOME MEASURES: The average proportion of prescribed glaucoma medication doses taken on schedule over the 6 months after randomization according to an electronic monitor between participants in the 2 arms., RESULTS: The mean proportion of prescribed doses taken on schedule was higher in the intervention group compared with controls (0.85 vs. 0.62, P < 0.0001). The difference in proportions between the 2 groups did not vary in regressions models adjusted for companion status, frequency of dosing, and race. The longitudinal model indicated that the intervention group had significantly higher adherence during the first month after randomization and continued to stay higher through 6 months (month by treatment interaction, P = 0.003)., CONCLUSIONS: A multifaceted intervention can help improve glaucoma medication adherence. Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Emergence of non-AI digital health innovations in ophthalmology: A systematic review. - Tseng, Rachel Marjorie Wei Wen; Tham, Yih-Chung; Rim, Tyler Hyungtaek; Cheng, Ching-Yu (Clinical & experimental ophthalmology, 2021)
The prominent rise of digital health in ophthalmology is evident in the current age of Industry 4.0. Despite the many facets of digital health, there has been a greater slant in interest and focus on artificial intelligence recently. Other major elements of digital health such as mobile health could also substantially impact patient-focused outcomes but have been relatively less explored and discussed. In this review, we adopted a narrative approach to comprehensively evaluate the use of non-AI digital health tools in ophthalmology. 53 papers were included in this systematic review, with 25 papers dealing with virtual or augmented reality, 14 with mobile applications, and 14 with wearables. Most papers focused on the use of these technologies to detect or rehabilitate visual impairment, glaucoma and age-related macular degeneration. Overall, the findings present encouraging improvements on patient-focused outcomes with the adoption of these technologies. Further validation or large-scale studies and earlier consideration of real-world barriers are warranted to enable better real-world implementation. Copyright This article is protected by copyright. All rights reserved.

Impact of pharmacist-led interventions in improving adherence to glaucoma medications in the geriatric population. - Aleem, Ayesha; Amin, Fatima; Asim, Mulazim Hussain; Farooq, Nayab; Arshad, Shumaila; Raziq, Mairah (European journal of hospital pharmacy : science and practice, 2021)
OBJECTIVES: Geriatric patients can be non-adherent to ophthalmic glaucoma medications because of complex eye drops instillation techniques and forgetfulness, so pharmacists can play their part in improving the clinical outcomes of patients by acting as care providers. The purpose of the current study was to implement various pharmacist-led interventions to improve adherence to glaucoma medications and to evaluate the outcomes of interventions in the geriatric population., METHODS: The Morisky Green Levine (MGL) adherence scale was used for analysis because it measures the extent of non-adherence and analyses the reasons for it. The interview-based sessions were conducted with control and interventional groups followed by educational interventions, including techniques for eye drop instillation, graphical images, precautionary measures, and individual patient counselling for the interventional group. Patients were asked to complete the adherence scale after the conclusion of every follow-up session for a duration of 6 months., RESULTS: After 6 months of pharmacist-led interventions, a significant shift was found in the interventional group from low to high adherence according to MGL scale evaluation. Moreover, the number of patients in the interventional group whose intraocular pressure was in the safe range significantly increased and follow-up sessions significantly improved the patient's knowledge about glaucoma., CONCLUSION: The results of this pharmacist-led educational interventional study showed it was effective in improving adherence to glaucoma medications in the geriatric patients, who showed better adherence scores and improved intraocular pressure. Copyright © European Association of Hospital Pharmacists 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Surface Engineering of FLT4-Targeted Nanocarriers Enhances Cell-Softening Glaucoma Therapy. - Vincent, Michael P; Stack, Trevor; Vahabikashi, Amir; Li, Guorong; Perkumas, Kristin M; Ren, Ruiyi; Gong, Haiyan; Stamer, W Daniel; Johnson, Mark; Scott, Evan A (ACS applied materials & interfaces, 2021)
Primary open-angle glaucoma is associated with elevated intraocular pressure (IOP) that damages the optic nerve and leads to gradual vision loss. Several agents that reduce the stiffness of pressure-regulating Schlemm's canal (SC) endothelial cells, in the conventional outflow pathway of the eye, lower IOP in glaucoma patients and are approved for clinical use. However, poor drug penetration and uncontrolled biodistribution limit their efficacy and produce local adverse effects. Compared to other ocular endothelia, FLT4/VEGFR3 is expressed at elevated levels by SC endothelial cells and can be exploited for targeted drug delivery. Here, we validate FLT4 receptors as clinically relevant targets on SC cells from glaucomatous human donors and engineer polymeric self-assembled nanocarriers displaying lipid-anchored targeting ligands that optimally engage this receptor. Targeting constructs were synthesized as lipid-PEGx-peptide, differing in the number of PEG spacer units (x), and were embedded in micelles. We present a novel proteolysis assay for quantifying ligand accessibility that we employ to design and optimize our FLT4-targeting strategy for glaucoma nanotherapy. Peptide accessibility to proteases correlated with receptor-mediated targeting enhancements. Increasing the accessibility of FLT4-binding peptides enhanced nanocarrier uptake by SC cells while simultaneously decreasing the uptake by off-target vascular endothelial cells. Using a paired longitudinal IOP study in vivo, we show that this enhanced targeting of SC cells translates to IOP reductions that are sustained for a significantly longer time as compared to controls. Confocal microscopy of murine anterior segment tissue confirmed nanocarrier localization to SC within 1 h after intracameral administration. This work demonstrates that steric effects between surface-displayed ligands and PEG coronas significantly impact the targeting performance of synthetic nanocarriers across multiple biological scales. Minimizing the obstruction of modular targeting ligands by PEG measurably improved the efficacy of glaucoma nanotherapy and is an important consideration for engineering PEGylated nanocarriers for targeted drug delivery.

Demographic, Clinical, and Psychosocial Predictors of Change in Medication Adherence in the Support, Educate, Empower Program. - Miller, David J; Niziol, Leslie M; Elam, Angela R; Heisler, Michele; Lee, Paul P; Resnicow, Kenneth; Musch, David C; Darnley-Fisch, Deborah; Mitchell, Jamie; Newman-Casey, Paula Anne (Ophthalmology. Glaucoma, 2021)
PURPOSE: To investigate whether demographic, clinical, or psychosocial factors act as moderators of change in medication adherence in the Support, Educate, Empower (SEE) program., DESIGN: Prospective, single-arm pilot study with a pre-post design., PARTICIPANTS: Patients with glaucoma aged >= 40 years and taking >= 1 glaucoma medication were recruited from the University of Michigan Kellogg Eye Center. Those who had electronically measured adherence <= 80% in the 3-month eligibility monitoring period were enrolled in the SEE program., METHODS: Medication adherence was monitored electronically during the 7-month intervention and calculated as the percentage of doses taken correctly. Change in adherence at different points in the SEE program and cumulative change in adherence were modeled with linear regression, and baseline demographic, clinical, and psychosocial factors were investigated for significant associations., MAIN OUTCOME MEASURES: Demographic, clinical, and psychosocial variables associated with change in medication adherence in the SEE program., RESULTS: Thirty-nine participants completed the SEE program. These participants were on average 63.9 years old (standard deviation [SD], 10.7 years), 56% (n = 22) were male, 44% (n = 17) were White, and 49% (n = 19) were Black. Medication adherence improved from an average of 59.9% (SD, 18.5%) at baseline to 83.6% (SD, 17.5%) after the final SEE session, for an increase of 23.7% (SD, 17.5%). Although participants with lower income (< $25 000 and $25 000-50 000 vs. >$50 000) had lower baseline adherence (48.4% and 64.1% vs. 70.4%), these individuals had greater increases in adherence during the first month of medication reminders (19.6% and 21.6% vs. 10.2%; P = 0.05 and P = 0.007, respectively). Participants taking fewer glaucoma medications also had significantly greater increases in adherence with medication reminders (P < 0.001). Those with higher levels of glaucoma-related distress (GD) had lower baseline adherence and greater increases in adherence with glaucoma coaching (P = 0.06)., CONCLUSIONS: Patient-level factors associated with relatively greater improvements in medication adherence through the SEE Program included lower income, fewer glaucoma medications, and increased GD. These findings demonstrate that the SEE program can improve glaucoma self-management even among participants with social and psychological barriers to medication adherence. Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Phase Transition Microemulsion of Brimonidine Tartrate for Glaucoma Therapy: Preparation, Characterization and Pharmacodynamic Study. - Gautam, Nivedita; Kesavan, Karthikeyan (Current eye research, 2021)
Purpose: The aim of this study was to formulate brimonidine tartrate loaded phase transition microemulsions (PMEs), which undergo phase transition from water in oil (W/O) microemulsions to liquid crystalline (LC) and then oil in water (O/W) microemulsions after instilled into the eye and prolong the precorneal residence time and ocular bioavailability for the effective treatment of glaucoma. Methods: The pseudo-ternary phase diagram was developed and various PMEs were prepared using Tween 80 and Span 80 with isopropyl myristate and water. Globule size and shape, physicochemical parameters, in vitro and ex vivo drug release of PMEs were studied. The in vivo anti-glaucoma efficacy of optimized PMEs was studied in an experimental rabbit eyes model and compared with marketed formulation (MF). Results: Globule size of PMEs was found less than 200 nm, which was confirmed by both dynamic light scattering technique and Transmission Electron Microscopy. Physicochemical properties such as pH, refractive index, percentage transparency, viscosity and conductivity were also found in the acceptable ranges. In vitro release studies of PMEs exhibited sustained release property. Ex vivo permeation study also supported the enhanced drug flux through cornea from PMEs as compared with MF. In pharmacodynamic study, a greater reduction in intraocular pressure was seen in PMEs as compared to MF. Conclusion: PMEs as ocular drug delivery system offer a promising approach to enhance the corneal contact, higher permeation and prolonged precorneal retention time in the eye leading to sustained drug release, enhanced bioavailability and patient compliance.

Risk factors for previously undiagnosed primary open-angle glaucoma: the EPIC-Norfolk Eye Study. - Chan, Michelle P Y; Khawaja, Anthony P; Broadway, David C; Yip, Jennifer; Luben, Robert; Hayat, Shabina; Peto, Tunde; Khaw, Kay-Tee; Foster, Paul J (The British journal of ophthalmology, 2021)
BACKGROUND AND AIM: Undiagnosed glaucoma is an invisible but important public health issue. At least half of glaucoma cases are estimated to be undiagnosed in western populations. The aim of this study is to examine risk factors for previously undiagnosed primary open-angle glaucoma (POAG)., DESIGN: Cross-sectional study within the European Prospective Investigation of Cancer-Norfolk Eye Study, a large-scale cohort study in the UK., PARTICIPANTS: 314 study participants with POAG in either eye., METHODS: Logistic regression was used to examine associations with previously undiagnosed POAG compared with previously diagnosed POAG. The factors examined included sociodemographic, ocular, physical and economic factors that could be barriers to eye care access., RESULTS: 217 participants had previously diagnosed POAG and 107 participants were newly diagnosed with POAG during the study. After adjusting for covariables, the factors significantly associated with previously undiagnosed POAG were: a lower pretreatment intraocular pressure (IOP) (OR 0.71/mm Hg, 95% CI 0.63 to 0.80, p<0.0001), and to have reported no problems with their eyesight (OR 0.03, 95% CI 0.01 to 0.10, p<0.0001)., CONCLUSIONS: The risk factors for previously undiagnosed POAG identified in this study highlight the over-reliance on IOP level in glaucoma screening and the risk of missing glaucoma among lower IOP cases. It also suggests a role in improving glaucoma awareness in the community. Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.

A hypotonic gel-forming eye drop provides enhanced intraocular delivery of a kinase inhibitor with melanin-binding properties for sustained protection of retinal ganglion cells. - Kim, Yoo Chun; Hsueh, Henry T; Shin, Matthew D; Berlinicke, Cynthia A; Han, Hyounkoo; Anders, Nicole M; Hemingway, Avelina; Leo, Kirby T; Chou, Renee Ti; Kwon, HyeYoung; Appell, Matthew B; Rai, Usha; et al. (Drug delivery and translational research, 2021)
While eye drops are the most common ocular dosage form, eye drops for treating diseases of the posterior segment (retina, choroid, optic nerve) have yet to be developed. In glaucoma, eye drops are used extensively for delivering intraocular pressure (IOP)-lowering medications to the anterior segment. However, degeneration of retinal ganglion cells (RGCs) in the retina may progress despite significant IOP lowering, suggesting that a complementary neuroprotective therapy would improve glaucoma management. Here, we describe a hypotonic, thermosensitive gel-forming eye drop for effective delivery of sunitinib, a protein kinase inhibitor with activity against the neuroprotective targets dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK), to enhance survival of RGCs after optic nerve injury. Further, binding of sunitinib to melanin in the pigmented cells in the choroid and retinal pigment epithelium (RPE) led to prolonged intraocular residence time, including therapeutically relevant concentrations in the non-pigmented retinal tissue where the RGCs reside. The combination of enhanced intraocular absorption provided by the gel-forming eye drop vehicle and the intrinsic melanin binding properties of sunitinib led to significant protection of RGCs with only once weekly eye drop dosing. For a chronic disease such as glaucoma, an effective once weekly eye drop for neuroprotection could result in greater patient adherence, and thus, greater disease management and improved patient quality of life.

A Retrospective Comparison of Trabeculectomy, Baerveldt Glaucoma Implant, and Microinvasive Glaucoma Surgeries in a Three-Year Follow-Up. - Nuzzi, Raffaele; Gremmo, Giulia; Toja, Francesca; Marolo, Paola (Seminars in ophthalmology, 2021)
Purpose: This retrospective study aimed to evaluate the safety and efficacy of MIGS (Xen R and Cypass R) compared to trabeculectomy and Baerveldt R implants. Patients and Methods: This single-center study included patients from the Ophthalmic Hospital of Turin between January 2015 and 2018.Efficacy was assessed based on the intraocular pressure and the number of medications necessary to control IOP at 1, 3, 6, 12, 24, and 36 months and the potential complications. Complete surgical success was defined as IOP <= 21 mmHg, with no medication or additional glaucoma surgery. Qualified success was defined as IOP <= 21 mmHg with the reintroduction of topical medications. Our third measure of success was a delta IOP reduction greater than 20% compared to baseline. Results: The delta IOP compared to the baseline was significant at every instance, except in the Xen R implant group. The average IOP distribution at different time points was significant, except at 1 and 12 months. The delta of the medication number compared to the baseline was significant at every instant. All three methods of success were analyzed using a Kaplan-Meier survival curve that identified a significant difference on the success rates of Xen R-trabeculectomy, Xen R-Baerveldt R, and Cypass R-Baerveldt R. Conclusion: MIGS can reduce the number of medication classes, thus increasing patient compliance and reducing topical ocular toxicity and general costs. Trabeculectomy remains the most effective option but still presents a percentage of failures that might increase during follow-up.

Effectiveness of a Teleophthalmology Vision Center in Treating Corneal Disorders and Its Associated Economic Benefits. - Komal, Sangoi; Radhakrishnan, Naveen; Vardhan S, Ashok; Prajna, N Venkatesh (Cornea, 2021)
PURPOSE: The aim of this study was to study the clinical and economic impact of a teleophthalmology-based vision center (VC) in the management of corneal diseases in rural south India., METHODS: Data of patients with corneal disorders who visited the VC in the year 2019 were analyzed for the total number of outpatient visits, the proportion of corneal cases that were treated at the VC, those referred to the base hospital (BH), and the costs of treatment., RESULTS: In 2019, 1131 (10%) of 10,850 patients who visited the VC were diagnosed with corneal disorders. Of these, 950 (84%) patients were treated at the VC itself and did not require to be referred. The remaining 181 (16%) were referred to the BH. Of these 1131 patients, 836 (74%) patients presented with a painful acute corneal disorder. The most common painful acute corneal disorders included corneal foreign body (376, 33%), epithelial abrasions (205, 18%), and infectious keratitis (124, 11%). A patient can save approximately a minimum of INR 1200 (USD 16) by attending the VC rather than the BH. In 2019, by treating 950 patients, the VC saved approximately INR 114,0000 (USD 15,200) for the community. A similar calculation extrapolated to a 10-year period (2009-2019) revealed that by providing care for these corneal disorders at the community level, the VC saved approximately INR 705,8400 (USD 94,112) for the community., CONCLUSIONS: VC reduces the barriers to care by increasing the accessibility and affordability of treatment for patients with corneal disorders, resulting in a significant cost saving to the community. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

The Burden of Caring for and Treating Glaucoma: The Patient Perspective. - Stagg, Brian C; Granger, Alison; Guetterman, Timothy C; Hess, Rachel; Lee, Paul P (Ophthalmology. Glaucoma, 2021)
PURPOSE: To understand the treatment burden experienced by patients receiving care for primary open-angle glaucoma., DESIGN: Semistructured, one-on-one, qualitative interviews., PARTICIPANTS: Patients with primary open-angle glaucoma and age >=40 years who were scheduled for a follow-up glaucoma appointment at the Kellogg Eye Center. Researchers used purposeful sampling to ensure that there was representation of a range of ages, disease stages, total number of medical conditions, distance traveled to clinic, history of glaucoma surgery, employment, and education. Interviews were conducted until thematic saturation was obtained., METHODS: Participants were interviewed using a semi-structured interview guide that addressed aspects of glaucoma care that give them burden, how this burden impacts their lives, and factors that influence the burden and its impact. Researchers analyzed the transcripts using inductive thematic analysis and grounded theory to generate themes that emerged from the interviews and to map these themes into a conceptual model of glaucoma treatment burden., MAIN OUTCOME MEASURES: Themes related to glaucoma treatment burden generated by qualitative analysis., RESULTS: A total of 22 patients participated in the study. Study participants described 10 categories of glaucoma care activities that cause treatment burden, 8 themes for consequences of glaucoma treatment burden, and 25 themes of factors that influenced the workload created by the various glaucoma care activities and the consequences that they experienced because of these activities., CONCLUSIONS: Participants expressed that the treatment of glaucoma creates a burden for patients that is distinct from the burden of the disease process itself and that this burden negatively affects their quality of life and can potentially cause vision-threatening issues with medication and appointment adherence. We observed considerable variation in the extent to which participants experienced this burden and its consequences, much of which was explained by the influencing factors the participants described. Understanding glaucoma treatment burden and its influencing factors is important as we work to deliver patient-centered care and prevent vision loss. Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effect of Prostaglandin Analogues on Corneal Biomechanical Parameters Measured with a Dynamic Scheimpflug Analyzer. - Yasukura, Yuichi; Miki, Atsuya; Maeda, Naoyuki; Koh, Shizuka; Nishida, Kohji (Journal of glaucoma, 2021)
PRECIS: Treatment with topical prostaglandin analogues induces increased corneal compliance in glaucoma eyes measured with a dynamic Scheimpflug analyzer., PURPOSE: To evaluate the effect of topical prostaglandin analogues (PGAs) on the corneal biomechanical properties., METHODS: We retrospectively studied the biomechanical parameters of 31 eyes of 19 consecutive patients with glaucoma measured using a dynamic Scheimpflug analyzer (Corvis ST) before and after initiation of treatment with topical PGAs. No patients had a history of glaucoma treatment before the study and no other antiglaucoma medication was used during the study period. Nine biomechanical parameters were evaluated before and 61.6+/-28.5 (range: 21-105) days after initiation of the treatment. The changes in the corneal biomechanical parameters before and after treatment were analyzed using multivariable models adjusting for intraocular pressure (IOP) and central corneal thickness. The Benjamini-Hochberg method was used to correct for multiple comparison., RESULTS: In multivariable models, PGA treatment resulted in shorter inward applanation time (P=0.016, coefficient=-0.151) and larger deflection amplitude (P=0.023, coefficient=0.055), peak distance (P=0.042, coefficient=0.131), and deformation amplitude ratio at 1mm (P =0.018, coefficient=0.028). These associations consistently indicated increased corneal compliance (deformability) after PGA treatment., CONCLUSION: Topical PGAs resulted in greater corneal compliance, suggesting that the changes in the corneal biomechanical properties may lead to overestimation of the IOP-lowering effects. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Development and usability evaluation of an application for patients with glaucoma. - Valente, Paula Soares de Mattos Carneiro; Carneiro, Carolina Lyra Barreira; de Aguiar, Ridson Guilherme Parente; de Souza Junior, Francisco Emanoel Albuquerque; Maciel, Alex Andrade; Marcal, Edgar; Barbosa Neto, Jose de Paula; Ribeiro, Joao Crispim (International ophthalmology, 2021)
INTRODUCTION: Glaucoma is a progressive optic neuropathy that requires continuous monitoring. The purpose of the study was to develop and evaluate the usability of a mobile application, for iOS and Android platforms, containing functionalities to improve patients' knowledge about glaucoma and facilitate their treatment., METHODS: The application was developed by a multidisciplinary team using an adapted version of a co-design methodology. Volunteers were selected, among patients and patients' relatives, from the Instituto Cearense de Oftalmologia, chosen by rational choice sampling, to answer the system usability scale after having prior orientation. The results extracted from the questionnaire were analyzed quantitatively. After grouping by age, a proportions test (z-test) was performed., RESULTS: It was possible to develop an application for mobile devices named "GlaucoCheck." Of the 36 interviewees, the average age was 51 (22-69) years old, 56% were women, and 30.5% had a university degree. The average APP score for usability in the SUS questionnaire was 75.6 (95% CI 74.1-77.2)., CONCLUSION: There was an appropriate acceptance of patients to the "GlaucoCheck", as it was considered easy to handle, exhibiting interactive and uncomplicated layout. It was possible to develop an application and to register a positive acceptance by the users, encompassing functions that permits better adherence to treatments and additional knowledge about glaucoma.

Advances in the discovery of novel agents for the treatment of glaucoma. - Mincione, Francesco; Nocentini, Alessio; Supuran, Claudiu T (Expert opinion on drug discovery, 2021)
INTRODUCTION: Glaucoma, a neuropathy characterized by increased intraocular pressure (IOP), is the major cause of blindness worldwide and its treatment aims at reducing IOP., AREAS COVERED: The authors review the design of the main classes of anti-glaucoma agents. Drugs which interfere with the aqueous humor secretion (adrenergic agonists/antagonists, carbonic anhydrase inhibitors) and with its outflow, by means of both conventional and non-conventional pathways (prostaglandin (PG) analogs, rho kinase inhibitors, nitric oxide (NO) donors) as well as new agents (adenosine receptors modulators, melatonin - fatty acid amide hydrolase hybrids, tyrosine kinase activators, natriuretic peptide analogs) are considered., EXPERT OPINION: The anti-glaucoma drug field has undergone several developments in recent years with the approval of at least three new drugs belonging to novel pharmacological classes, the rho kinase inhibitors ripasudil and netarsudil, and the PG-NO donor hybrid latanoprostene bunod. Eye drops with combinations of two different drugs are also available, allowing for effective IOP control, with once daily administration for some of them, which assures a better patient compliance and ease of administration. Overall, after more than a decade without new anti-glaucoma drugs, the last year afforded interesting new pharmacological opportunities for the management of this disease.

Real-World Clinical Impact of Netarsudil 0.02% at an Urban Safety-Net Hospital. - Fridman, Gabrielle; Sadlak, Natalie; Eliassi-Rad, Babak; Desai, Manishi A (Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2021)
Purpose: To analyze the efficacy, safety, and accessibility of netarsudil 0.02% in patients with glaucoma (suspect, open or closed) at a safety-net academic medical center, Boston Medical Center (BMC). Methods: Retrospective chart review of patients prescribed netarsudil 0.02% for uncontrolled glaucoma at BMC between December 2017 and September 2019. Outcome measures included change in intraocular pressure (IOP) from baseline and evaluation of adverse events (AEs). Results: One hundred thirty patients (60% severe stage) were analyzed. The IOP reduction from baseline was about 3 mmHg. Fifty-four patients (42%) experienced an AE (eg, conjunctival hyperemia). Thirty-eight patients (29%) started netarsudil 0.02% in lieu of laser or surgery. Ninety-nine patients (71%) required prior authorization for insurance coverage of netarsudil 0.02%. Ten patients (7%) were unable to obtain netarsudil 0.02% due to issues with insurance coverage. Conclusion: Netarsudil 0.02% yielded significant IOP reduction in our cohort, however, to a smaller degree compared with prior studies that bore equivocal IOP reduction regardless of baseline IOP. Conjunctival hyperemia was the most common AE. In a limited number of patients, netarsudil 0.02% was not covered by insurance.

Patient and Clinician Satisfaction With Shared Medical Appointments for Glaucoma. - Tam, Emily K; De Arrigunaga, Sofia; Shah, Madhura; Kefella, Haben; Soriano, Scarlet; Rowe, Susannah (Seminars in ophthalmology, 2021)
Shared Medical Appointments (SMAs) are patient-centered care tools designed to administer patient counseling and education, typically delivered individually, in a group setting. SMAs are effective in facilitating peer-learning, resulting in improvement in knowledge and health behavior. This study aimed to implement what we know of as the first ophthalmology SMA done in the United States. We evaluated the implementation feasibility, patient and provider experience, changes in patient knowledge, and provider stress. Five glaucoma patients who expressed issues with adherence during their clinic visit at Boston Medical Center (BMC) who were interested in the SMA were recruited. Patients and staff had a positive experience with the SMA. There was a marked increase in patient glaucoma knowledge and a decrease in average staff member stress level score during the SMA. From all standpoints, including billing and management, we conclude that SMA implementation is feasible in ophthalmology departments in academic settings.

Manhattan Vision Screening and Follow-Up Study in Vulnerable Populations: 1-Month Feasibility Results. - Hark, Lisa A; Tan, Camille S; Kresch, Yocheved S; De Moraes, C Gustavo; Horowitz, Jason D; Park, Lisa; Auran, James D; Gorroochurn, Prakash; Stempel, Stella; Maruri, Stefania C; Besagar, Sonya; Saaddine, Jinan B; et al. (Current eye research, 2021)
Purpose/Aim: In the United States, high rates of vision impairment and eye disease disproportionately impact those who lack access to eye care, specifically vulnerable populations. The objective of our study was to test instruments, implement protocols, and collect preliminary data for a larger 5-year study, which aims to improve detection of eye diseases and follow-up eye care in vulnerable populations using community health workers (CHW) and patient navigators. In the study, trained CHWs conducted vision screening and patient navigators scheduled on-site eye exams and arranged appointments for those referred to ophthalmology to improve adherence to follow-up eye care. Materials and Methods: Eligible individuals age 40-and-older were recruited from the Riverstone Senior Center in Upper Manhattan, New York City. Participants underwent on-site vision screening (visual acuity with correction, intraocular pressure measurements, and fundus photography). Individuals who failed the vision screening were scheduled with an on-site optometrist for an eye exam; those with ocular pathologies were referred to an ophthalmologist. Participants were also administered the National Eye Institute Visual Function Questionnaire-8 (NEI-VFQ-8) and Stopping Elderly Accidents, Deaths, and Injuries (STEADI) test by community health workers. Results: Participants (n = 42) were predominantly older adults, with a mean age of 70.0 +/- 9.8, female (61.9%), and Hispanic (78.6%). Most individuals (78.6%, n = 33) failed vision screening. Of those who failed, 84.8% (n = 28) attended the on-site eye exam with the optometrist. Ocular diagnoses: refractive error 13/28 (46.4%), glaucoma/glaucoma suspect 9/28 (32.1%), cataract 7/28 (25.0%), retina abnormalities 6/28 (21.4%); 13 people required eyeglasses. Conclusion: This study demonstrates the feasibility of using CHWs and patient navigators for reducing barriers to vision screening and optometrist-based eye exams in vulnerable populations, ultimately improving early detection of eye disease and linking individuals to additional eye care appointments. The full five-year study aims to further examine these outcomes.

Review of glaucoma medication adherence monitoring in the digital health era. - Erras, Alaa; Shahrvini, Bita; Weinreb, Robert N; Baxter, Sally L (The British journal of ophthalmology, 2021)
Current glaucoma treatments aim to lower intraocular pressure, often with topical ocular hypotensive medications. Unfortunately, the effectiveness of these medications depends on sustained patient adherence to regimens which may involve instilling multiple medications several times daily. Patient adherence to glaucoma medications is often low. Recent innovations in digital sensor technologies have been leveraged to confirm eyedrop medication usage in real-time and relay this information back to providers. Some sensors have also been designed to deliver medication reminders and notifications as well as assist with correct eyedrop administration technique. Here, we review recent innovations targeted at improving glaucoma medication adherence and discuss their limitations. Copyright © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

The impact of patient behaviour and care system compliance on reusable soft contact lens complications. - Yee, Alan; Walsh, Karen; Schulze, Marc; Jones, Lyndon (Contact lens & anterior eye : the journal of the British Contact Lens Association, 2021)
Reusable soft daily wear contact lenses (CLs) remain popular and were fit to just over half of all wearers in the most recent international CL prescribing survey. Unlike daily disposable CLs, reusables require cleaning and disinfecting after every use, along with storage in a CL case. These additional requirements add a number of steps to the daily wear and care routine, increasing the opportunities for CL wearers to exhibit non-compliant behaviour. The impact of non-compliance ranges from poor lens comfort through to potentially sight-threatening infective keratitis. The coronavirus pandemic has refocused the profession on the importance of hand hygiene in particular, and the need for promoting safe CL wear in general. This review summarises typical non-compliant behaviour related to reusable CLs, and examines strategies and opportunities to better support wearers. Patient education has a central role in encouraging compliant behaviour, although patient recall of information is low, and personal belief systems may result in continuation of non-compliant behaviour despite awareness of the risks. CL care solutions are required for the daily disinfection of lenses, however misuse of multipurpose solutions (MPS) and hydrogen peroxide (H2O2)-based care systems can challenge their ability to be fully efficacious. Standard efficacy testing is reviewed, with consideration of how well current protocols model real-world use of CL solutions. Although some recommendations are in place for the inclusion of additional variables such as lens cases, CL materials, organic soil and efficacy against Acanthamoeba, opportunity still exists to reevaluate global standards to ensure consistency of testing in all markets. Finally, potential future innovations are discussed which may further support increased safety in reusable lens wear through novel antimicrobial additions to both CL materials and cases. Copyright © 2021 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Increased Near Activities Function Associated with Increased Glaucoma Medication Adherence among Support, Educate, Empower (SEE) Participants. - Cho, Juno; Niziol, Leslie M; Heisler, Michele; Newman-Casey, Paula Anne (Journal of glaucoma, 2021)
PRCIS: Higher levels of near-vision related quality of life were associated with higher adherence to glaucoma medications after adjusting for important confounding variables among participants in the SEE personalized glaucoma coaching pilot study., PURPOSE: To investigate the association between vision-related quality of life (VRQoL) and glaucoma medication adherence., MATERIALS AND METHODS: Subjects were recruited for the Support, Educate, Empower (SEE) program, a prospective non-controlled cohort study examining the impact of a personalized coaching program on glaucoma medication adherence. Glaucoma patients seen at the University of Michigan over 40 years old, taking >=1 glaucoma medication, and self-reported poor adherence on two validated scales were recruited. Demographic details and VRQoL using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were collected. Participants ' medication use for each prescribed glaucoma medication was captured electronically using a medication events monitoring system (Adheretech, New York, NY). The association between VRQoL and medication adherence was assessed with Pearson's correlation coefficient (r) and linear regression., RESULTS: Among the 95 eligible participants 49.5% were female, 55.3% were Caucasian, and mean age (+/-standard deviation) was 63.8+/-10.5 years. Mean adherence to glaucoma medication was 73.8%+/-21.0%. Mean NEI VFQ-25 composite score was 81.6+/-14.5. Better medication adherence was significantly and positively correlated with better functioning in domains of ocular pain (r=0.20, P=0.048), near activities (r=0.29, P=0.004), and role difficulties (r=0.22, P=0.036). Linear regression models adjusting for known correlates of medication adherence (age, gender, race, income), showed a 10-unit increase in self-perceived near activities function was associated with a 2.2% increase in medication adherence (95% confidence interval 1.0%-5.4%; P=0.0056)., CONCLUSION: Better self-perceived near activities function was associated with increased glaucoma medication adherence. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Cost-related nonadherence with glaucoma medications in Ontario. - Buys, Yvonne M; Kagan, Dov; Jin, Ya-Ping; Trope, Graham E (Canadian journal of ophthalmology. Journal canadien d'ophtalmologie, 2021)
OBJECTIVE: To determine the proportion of glaucoma patients in Ontario aged 25-64 who lack insurance coverage for glaucoma medications and to assess the frequency of cost-related nonadherence to glaucoma medications., DESIGN: Cross-sectional study., PARTICIPANTS: Glaucoma patients on medication from 2 glaucoma clinics in Toronto, Ontario., METHODS: 100 consecutive glaucoma patients aged 25-64 (not entitled to provincial drug benefit) and 100 consecutive glaucoma patients aged 65+ (entitled to provincial drug benefit), all on topical glaucoma therapy, completed a standardized questionnaire. Questions included insurance coverage for glaucoma medications, cost concerns when paying for glaucoma medications, cost-related nonadherence, and sociodemographics., RESULTS: 25.8% of those aged 25-64 express concerns about the cost of their glaucoma medications compared to 7.1% of those aged 65+ (p < 0.001). Patients aged 25-64 were also significantly more likely to report at least one form of cost-related nonadherence (15.5% vs 2.0%, p=0.001) and significantly more likely to report missing eye drops in a given week than patients aged 65+ (32.0% vs 16.7%, p=0.01). 17% (95% confidence interval 11%-26%) of patients aged 25-64 self-reported having no insurance coverage for their glaucoma medications. Of those with coverage, the most common source of insurance was employer-sponsored (68.6%) with 44% requiring a copayment. The average copayment was $18 (range $2-$250) for those aged 25-64 compared with $5 in the 65+ group (range $0.62-$100)., CONCLUSIONS: 17% of glaucoma patients aged 25-64 do not have coverage for their drops. One in four expressed concerns about the cost of their glaucoma medications, and 15.5% reported cost-related nonadherence. Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Vision and Ocular Surface Salvage in Extreme Post-Burn Cicatricial Ectropion with Infectious Exposure Keratitis. - Behera, Geeta; Sangaraju, Suneel; Thiruvoth, Friji M; Kasturi, Nirupama; Babu, Krishna Ramesh (Journal of burn care & research : official publication of the American Burn Association, 2021)
Prevention and early management of post-burn cicatricial ectropion is the best strategy to avoid ocular complications, with poor visual prognosis in extreme cases. A 51-year old man presented with diminution of vision and absolute inability to close both eyes, three months after thermal burn injuries to face, upper limbs and trunk. His best corrected visual acuity (BCVA) was 1/60 in BE. He had bilateral extremely severe ectropion involving both upper and lower lids with complete inability to close the eyes. The ensuing exposure keratitis developed secondary infection by Methicillin resistant Staphylococcus aureus (MRSA) in the right eye and multi-drug resistant Pseudomonas aeruginosa in the left eye. His extreme ectropion prevented infection healing, so its release and full-thickness skin grafting was done when partial resolution of infection was noted. After three months, he had moderate residual ectropion in BE; vascularised corneal scar in the inferior part of the right eye (BCVA:20/40) and adherent leucoma in left eye (BCVA:HM). Prioritising ectropion surgery in our extreme case for infection control, facilitated corneal healing. Our case highlights the extreme consequences of not taking preventive measures or of managing incident ectropion following thermal injury to the face. Copyright © The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Screening first-degree relatives of glaucoma patients reveals barriers to participation. - Shroff, Sujani; Gu, Sophie Z; Vardhan S, Ashok; Mani, Iswarya; Aziz, Kanza; P, Namperumalsamy; Datta, Dipankar; Friedman, David S (The British journal of ophthalmology, 2021)
PURPOSE: To report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India., METHODS: 1598 glaucoma patients were contacted via letter or letter and phone call and asked to bring their siblings and children to a glaucoma screening. Participants underwent standardised eye examinations and completed questionnaires that assessed barriers to participation and awareness of glaucoma risk. Two-proportion z-tests were used to compare categorical data. Costs associated with the screening were recorded., RESULTS: 206 probands (12.9%) attended the screening along with 50 siblings and children. Probands were nearly twice as likely to attend if they had been contacted via both letter and phone call rather than letter only. Over half of probands reported that their relatives could not participate because they did not live in the region, and one-fifth reported that their relatives had other commitments. Fifty-eight per cent of the siblings and children who attended did not know that they were at increased risk for glaucoma due to their family history, and 32.0% did not know that the relative who had invited them to the screening had glaucoma. Thirteen siblings and children (26.0% of those who attended) were found to have findings concerning for glaucoma. The average cost per first-degree relative who was screened was INR2422 (26)., CONCLUSION: Participation in this glaucoma screening campaign was poor. The major barrier to participation was distance from the screening site and associated indirect costs. Better strategies for bringing first-degree relatives in for examinations are needed. Copyright © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

Topical Bimatoprost Insert for Primary Open-Angle Glaucoma and Ocular Hypertension Treatment - A Phase II Controlled Study. - Rubiao, Francine; Araujo, Alan Cezar Faria; Sancio, Joao Bernardo; Nogueira, Barbara Silva; Franca, Jucara Ribeiro; Nogueira, Jose Carlos; Ferreira, Anderson Jose; Faraco, Andre Augusto Gomes; Foureaux, Giselle; Cronemberger, Sebastiao (Current drug delivery, 2020)
BACKGROUND: The most common treatment for primary open-angle glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and ocular hypertension (OH)., METHODS: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and <=30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP<=14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, we used a two-way analysis of variance (ANOVA), Student t-test, and paired t-test., RESULTS: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5+/-2.2 mmHg and 16.9+/-3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference., CONCLUSIONS: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Macromolecular Platform with Super-Cation Enhanced Trans-Cornea Infiltration for Noninvasive Nitric Oxide Delivery in Ocular Therapy. - Jia, Fan; Li, Liping; Fang, Yu; Song, Maomao; Man, Jiaping; Jin, Qiao; Lei, Yuan; Ji, Jian (ACS nano, 2020)
The cornea provides important protection for human eyes from invasion of alien substances. However, its blockage on the infiltration of molecules also constitutes a great challenge for noninvasive trans-cornea delivery of drugs. Here we report polyamino acid-based S-nitrosothiols with high cationic charge density as a NO carrier to overcome cornea associated blockage in ophthalmological therapy. Our results demonstrate that the cationic nature of the polymer promoted transcytosis, which greatly enhances the trans-cornea delivery of the NO donor and bypasses cornea barriers on passive drug diffusion. The combination of super cation and glutathione responsiveness synergistically enhanced intraocular delivery of topically administered poly(2-acetamido-N-triethylenetetramine-3-nitrosothiol-3-methylbutanamide)aspartamide, effectively alleviating high intraocular pressure in mice with glaucoma. Such a noninvasive "barrier hopping" approach not only serves as an inspiration in improving the efficiency of trans-cornea drug delivery but also has great potential in overcoming drug transporting barriers in other biomedical applications.

Impact of Adherence (Compliance) to Oral Acyclovir Prophylaxis in the Recurrence of Herpetic Keratitis: Long-Term Results From a Pediatric Cohort. - Luccarelli, Saverio V; Lucentini, Stefano; Martellucci, Cecilia Acuti; Marelli, Luca; Sacchi, Matteo; Nucci, Paolo (Cornea, 2020)
PURPOSE: To evaluate the long-term role of adherence to oral acyclovir prophylaxis in reducing the risk for recurrent herpes simplex virus keratitis (HSK) in children., METHODS: A retrospective cohort study was performed including all pediatric patients 16 years or younger) with their first HSK diagnosis and treatment at our center. Children were started on a standardized oral acyclovir prophylactic regimen after the acute phase. Adherence to prophylaxis was assessed monthly through parent interviews. The possible association between any recurrence (not only the first) and exposure to acyclovir prophylaxis was evaluated using random-effects multivariate logistic regression., RESULTS: A total of 20 eyes of 17 patients (8 boys and 9 girls) were included. The mean follow-up time was 3.5 years. Adherence to acyclovir prophylaxis was registered in 100% of patients with no recurrences and in 36.4% of patients with 1 or more recurrences (P = 0.035). All other tested variables (time of follow-up, sex, age, infectious diseases, underlying hematological diseases, eye, and HSK type) did not differ between the 2 groups. The multivariate model confirmed the lower risk for recurrence in patients who were compliant to therapy (adjusted odds ratio 0.04, 95% confidence intervals 0.00-0.42, P = 0.008). No adverse effects were recorded during follow-up., CONCLUSIONS: Oral acyclovir prophylaxis is a safe and an effective medical treatment for recurrent HSK and its long-term efficacy is associated with compliance to the therapy.

Relationship between mean follow-up intraocular pressure, rates of visual field progression and current target intraocular pressure guidelines. - Melchior, Bruna; De Moraes, Carlos Gustavo; Paula, Jayter S; A Cioffi, George; Girkin, Christopher A; Fazio, Massimo A; N Weinreb, Robert; M Zangwill, Linda; M Liebmann, Jeffrey (The British journal of ophthalmology, 2020)
AIMS: To investigate if eyes presenting intraocular pressure (IOP) within the limits of current guideline-driven target IOP indeed experience slow rates of glaucomatous visual field (VF) progression., METHODS: A total of 8598 24-2 VF tests from 603 eyes from the African Descent and Glaucoma Evaluation Study with manifest glaucoma were included. The sample was split into three groups based on baseline VF mean deviation (MD): G1 (better than -5.0 dB), G2 (-5.0 to -10 dB) and G3 (worse than -10 dB). We investigated the relationship between existing target IOP guidelines and rates of MD progression in these groups., RESULTS: For stable eyes, the medians and IQR of the mean follow-up IOP were G1=15.0 mmHg (IQR: 13.1 to 17.7), G2=13.2 mmHg (IQR: 11.6 to 14.3) and G3=11.9 mmHg (IQR: 10.1 to 13.8) (p<0.01). When considering the mean follow-up IOP within the limits proposed by current guidelines, the median MD slopes were: -0.20 dB/y (IQR: -0.43 to -0.02) for G1<21 mmHg, -0.19 dB/y (IQR: -0.51 to -0.01) for G2<18 mmHg and -0.15 dB/y (IQR: -0.47 to 0.05) for G3<15 mmHg (p=0.63). There were no significant differences between racial groups., CONCLUSION: In a sample of patients with manifest glaucoma, despite substantial variability between eyes, adherence to treatment guidelines helped slow the rates of global VF progression at various stages of disease., TRIAL REGISTRATION NUMBER: clinicaltrials.gov Identifier: NCT00221923. Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

A review of the clinical applications of drug delivery systems for the treatment of ocular anterior segment inflammation. - Wong, Chee Wai; Metselaar, Josbert M; Storm, Gert; Wong, Tina T (The British journal of ophthalmology, 2020)
Ocular anterior segment inflammation is a medical problem that is seen in cases of cataract surgery and non-infectious anterior uveitis. Inadequately treated anterior segment inflammation can lead to sight-threatening conditions such as corneal oedema, glaucoma and cystoid macular oedema. The mainstay of treatment for anterior segment inflammation is topical steroid eye-drops. However, several drawbacks limit the critical value of this treatment, including low bioavailability, poor patient compliance, relatively difficult administration manner and risk of blurring of vision and ocular irritation. A drug delivery system (DDS) that can provide increased bioavailability and sustained delivery while being specifically targeted towards inflamed ocular tissue can potentially replace daily eye-drops as the gold standard for management of anterior segment inflammation. The various DDS for anti-inflammatory drugs for the treatment of anterior segment inflammation are listed and summarised in this review, with a focus on commercially available products and those in clinical trials. Dextenza, INVELTYS, Dexycu and Bromsite are examples of DDS that have enjoyed success in clinical trials leading to FDA approval. Nanoparticles and ocular iontophoresis form the next wave of DDS that have the potential to replace topical steroids eye-drops as the treatment of choice for anterior segment inflammation. With the current relentless pace of ophthalmic drug delivery research, the pursuit of a new standard of treatment that eliminates the problems of low bioavailability and patient compliance may soon be realised. Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Deep learning for automated glaucomatous optic neuropathy detection from ultra-widefield fundus images. - Li, Zhongwen; Guo, Chong; Lin, Duoru; Nie, Danyao; Zhu, Yi; Chen, Chuan; Zhao, Lanqin; Wang, Jinghui; Zhang, Xulin; Dongye, Meimei; Wang, Dongni; Xu, Fabao; et al. (The British journal of ophthalmology, 2020)
BACKGROUND/AIMS: To develop a deep learning system for automated glaucomatous optic neuropathy (GON) detection using ultra-widefield fundus (UWF) images., METHODS: We trained, validated and externally evaluated a deep learning system for GON detection based on 22 972 UWF images from 10 590 subjects that were collected at 4 different institutions in China and Japan. The InceptionResNetV2 neural network architecture was used to develop the system. The area under the receiver operating characteristic curve (AUC), sensitivity and specificity were used to assess the performance of detecting GON by the system. The data set from the Zhongshan Ophthalmic Center (ZOC) was selected to compare the performance of the system to that of ophthalmologists who mainly conducted UWF image analysis in clinics., RESULTS: The system for GON detection achieved AUCs of 0.983-0.999 with sensitivities of 97.5-98.2% and specificities of 94.3-98.4% in four independent data sets. The most common reasons for false-negative results were confounding optic disc characteristics caused by high myopia or pathological myopia (n=39 (53%)). The leading cause for false-positive results was having other fundus lesions (n=401 (96%)). The performance of the system in the ZOC data set was comparable to that of an experienced ophthalmologist (p>0.05)., CONCLUSION: Our deep learning system can accurately detect GON from UWF images in an automated fashion. It may be used as a screening tool to improve the accessibility of screening and promote the early diagnosis and management of glaucoma. Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Postoperative treatment compliance rate and complications with two different protocols after pterygium excision and conjunctival autografting. - Sabater-Cruz, Noelia; Dotti-Boada, Marina; Rios, Jose; Carrion, Maria Teresa; Chamorro, Lillian; Sanchez-Dalmau, Bernardo F; Casaroli-Marano, Ricardo-Pedro (European journal of ophthalmology, 2020)
AIM: To evaluate compliance rate to pterygium postoperative treatment with two different protocols., METHODS: Review of clinical data of patients submitted to pterygium excision and conjunctival autografting in a single centre (and a single surgeon) in Barcelona between March 2014 and December 2017. Initial postoperative protocol (protocol 1) consisted of 4 months of topical steroids in a tapering fashion. Protocol 2 consisted of topical steroids tapered over 5 weeks. Compliance rate, complications and clinical outcomes were evaluated, and statistical comparisons were made., RESULTS: 120 surgeries were performed in 99 patients. Protocol 1 was applied in 63 cases and the next 57 followed protocol 2. Compliance with protocol 1 (57.6%) was lower than with protocol 2 (84.9%) (p = 0.002). Intraoperative complications (graft tear, corneal thinning, corneal perforation and bleeding) were found in 10 cases of protocol 1 and three cases of protocol 2, p = 0.08. Postoperative complications (graft dislocation, graft haematoma, ocular hypertension and recurrence) were found in 31 cases of protocol 1 (46.2%) and eight cases of protocol 2 (14%), p = 0.001. Six weeks after surgery, ocular hypertension was detected in eight cases corresponding to protocol 1 (13.6%) and two cases of protocol 2 (3.8%), p = 0.099. Recurrence rate during first year was higher in protocol 1 (26.3%) compared to protocol 2 (7.6%), p = 0.011. No cases of visual acuity worsening or infection were registered., CONCLUSION: Protocol 2 has shown to have higher compliance rate than protocol 1 and less postoperative complications, proving to be a safe and effective postoperative treatment after pterygium surgery.

Prostaglandin analogues: A double-edged sword in orbital glaucoma disease management. - Joganathan, Varajini; Cannon, Paul S; Mercieca, Karl (European journal of ophthalmology, 2020)
INTRODUCTION: The authors describe benefits of the recognised adverse effects of prostaglandin analogues on periocular structures in patients with unilateral proptosis and intraocular pressure rise. This case points to intentional consideration of prostaglandin analogue therapy in this selected cohort of patients with secondary ocular hypertension and proptosis., CASE DESCRIPTION: A 70-year-old gentleman who presented with a 1-week history of a red and painful right eye associated with tortuous and dilated episcleral blood vessels. Visual acuity was unaffected. A diagnosis of idiopathic orbital inflammatory disease was made by extraocular muscle biopsy. Two weeks later, the patient presented with worsening pain, reduced vision and raised intraocular pressure. The secondary ocular hypertension was successfully treated with topical preserved eye drops, including latanoprost, a prostaglandin analogue. Over 6 months, the patient developed drop intolerance and punctate keratopathy leading to therapy non-adherence. Interestingly, the patient reported improvement in periocular appearance related to prostaglandin-associated periorbitopathy. Ocular surface disease and intraocular pressures were subsequently managed with preservative-free eye drops., CONCLUSION: Secondary ocular hypertension is not an uncommon consequence of orbital disease. Prostaglandin analogue can act as a double-edged sword in the management of raised intraocular pressure by reducing eye pressure at the cost of developing adverse effects of prostaglandin-associated periorbitopathy. These adverse effects however can be beneficial in the aesthetic rehabilitation of proptosis and associated exposure keratopathy in patients with unilateral orbital disease and probably should be sought as first line treatment in those with proptosis and raised intraocular pressure.

(untitled) - De Angelis, Floriana; Connick, Peter; Parker, Richard A; Plantone, Domenico; Doshi, Anisha; John, Nevin; Stutters, Jonathan; MacManus, David; Prados, Ferran; Marshall, Ian; Solanky, Bhavana; Samson, Rebecca S; et al. (NIHR Journals Library, 2020)
BACKGROUND: Neuroprotective drugs are needed to slow or prevent neurodegeneration and disability accrual in secondary progressive multiple sclerosis. Amiloride, fluoxetine and riluzole are repurposed drugs with potential neuroprotective effects., OBJECTIVES: To assess whether or not amiloride, fluoxetine and riluzole can reduce the rate of brain volume loss in people with secondary progressive multiple sclerosis over 96 weeks. The secondary objectives that were assessed were feasibility of a multiarm trial design approach, evaluation of anti-inflammatory effects, clinician- and patient-reported efficacy and three mechanistic substudies., DESIGN: A multicentre, multiarm, randomised, double-blind, placebo-controlled, parallel-group Phase IIb trial with follow-up at 4, 8, 12, 24, 36, 48, 72 and 96 weeks. Patients, investigators (including magnetic resonance imaging analysts), and treating and independent assessing neurologists were blinded to the treatment allocation. The target sample size was 440 patients., SETTING: Thirteen UK clinical neuroscience centres., PARTICIPANTS: Participants were aged 25-65 years, had secondary progressive multiple sclerosis with evidence of disease progression independent of relapses in the previous 2 years, and had an Expanded Disability Status Scale score of 4.0-6.5. Patients were ineligible if they could not have a magnetic resonance imaging scan; had a relapse or steroids in the previous 3 months; or had epilepsy, depression, bipolar disorder, glaucoma, bleeding disorders or significant organ comorbidities. Exclusion criteria were concurrent disease-modified treatments, immunosuppressants or selective serotonin reuptake inhibitors., INTERVENTIONS: Participants received amiloride (5 mg), fluoxetine (20 mg), riluzole (50 mg) or placebo (randomised 1 : 1 : 1 : 1) twice daily., MAIN OUTCOME MEASURES: The primary end point was magnetic resonance imaging-derived percentage brain volume change at 96 weeks. Secondary end points were new/enlarging T2 lesions, pseudoatrophy, and clinician- and patient-reported measures (including the Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Symbol Digit Modalities Test, low-contrast letter visual acuity, Multiple Sclerosis Impact Scale 29 items, version 2, Multiple Sclerosis Walking Scale, version 2, and questionnaires addressing pain and fatigue). The exploratory end points included measures of persistent new T1 hypointensities and grey matter volume changes. The substudies were advanced magnetic resonance imaging, optical coherence tomography and cerebrospinal fluid analyses., RESULTS: Between December 2014 and June 2016, 445 patients were randomised (analysed) to amiloride [n = 111 (99)], fluoxetine [n = 111 (96)], riluzole [n = 111 (99)] or placebo [n = 112 (99)]. A total of 206 randomised patients consented to the advanced magnetic resonance imaging substudy, 260 consented to the optical coherence tomography substudy and 70 consented to the cerebrospinal fluid substudy. No significant difference was seen between the active drugs and placebo in percentage brain volume change at week 96 as follows (where negative values mean more atrophy than placebo): amiloride minus placebo 0.0% (Dunnett-adjusted 95% confidence interval -0.4% to 0.5%), fluoxetine minus placebo -0.1% (Dunnett-adjusted 95% confidence interval -0.5% to 0.3%); riluzole minus placebo -0.1% (Dunnett-adjusted 95% confidence interval -0.6% to 0.3%). There was good adherence to study drugs. The proportion of patients experiencing adverse events was similar in the treatment and placebo groups. There were no emergent safety issues., LIMITATIONS: There was a lower than expected uptake in the cerebrospinal fluid substudy., CONCLUSIONS: A multiarm Phase II paradigm is efficient in determining which neuroprotective agents to take through to Phase III trials. Amiloride, fluoxetine and riluzole were not effective in reducing the brain atrophy rate in people with secondary progressive multiple sclerosis. Mechanistic pathobiological insight was gained., FUTURE WORK: To use the information gained from the Multiple Sclerosis-Secondary Progressive Multi-Arm Randomisation Trial (MS-SMART) to inform future trial design as new candidate agents are identified., TRIAL REGISTRATION: Current Controlled Trials ISRCTN28440672, NCT01910259 and EudraCT 2012-005394-31., FUNDING: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 3. See the NIHR Journals Library website for further project information. This trial also received funding from the UK MS Society and the US National Multiple Sclerosis Society. Copyright © Queen's Printer and Controller of HMSO 2020. This work was produced by De Angelis et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

A Metric to Consider on the Global Accessibility of Glaucoma Surgery. - Mansouri, Kaweh; Gillmann, Kevin; Bravetti, Giorgio Enrico (JAMA ophthalmology, 2019)

(untitled) - Anonymous (Canadian Agency for Drugs and Technologies in Health, 2018)
Lowering intraocular pressure (IOP) is the only clinically established method of treating glaucoma, and the Canadian Ophthalmological Society's clinical practice guidelines for glaucoma recommend an initial target IOP based on the severity of glaucoma, to be modified based on patients' age, life expectancy, quality of life, and risk factors for progression. Pharmacologic therapy is the most common method of lowering IOP, and the most common first-line therapy in Canada is topical prostaglandin analogues (PGAs), including latanoprost. Since patients with open-angle glaucoma (OAG) require lifetime therapy, they are at greater risk of ocular surface disease (OSD), which is associated with the long-term use of topical ophthalmic antiglaucoma medications. Patients with OSD may experience dry eye or sensations of burning, stinging, itching, or discomfort in the eye. Preservatives in topical ophthalmic solutions, of which the most common is benzalkonium chloride (BAK), have been implicated in OSD. Glaucoma medical therapy is often characterized by nonadherence, and the availability of preservative-free PGAs would address an unmet need for patients who do not tolerate preserved PGAs well. The objective of this report is to perform a systematic review of the beneficial and harmful effects of preservative-free latanoprost 50 mug/mL ophthalmic solution (Monoprost) for the reduction of IOP in patients with OAG or ocular hypertension. Copyright © 2018 Canadian Agency for Drugs and Technologies in Health.

(untitled) - National Institute for Health and Care Excellence (UK) (National Institute for Health and Care Excellence (UK), 2017)
The scope of this NICE guideline on diagnosing and managing chronic open-angle glaucoma has been extended to cover referral. This includes the most effective service models for referral-filtering schemes (repeat measures, enhanced case finding and referral refinement), the tests to be used for finding people with chronic open-angle glaucoma (COAG), suspected chronic open-angle glaucoma and ocular hypertension (OHT), and thresholds for onward referral. We have also updated the guidance on tests for diagnosis and reassessment, pharmacological treatments for lowering intraocular pressure and preserving visual field and reassessment intervals, which depend on prognosis. The update has provided an opportunity to re-evaluate the clinical effectiveness, cost effectiveness and indications for treating OHT. Knowledge of corneal thickness is no longer needed to decide whether or not to treat OHT, and a single threshold of 24 mmHg is now recommended for both onward referral and treatment. Changes in the costs of pharmacological treatments, acknowledgement of short- and long-term variations in intraocular pressure and the uneven relationship between rising pressure and increased risk have allowed a simplification of the indications for OHT treatment. Control of intraocular pressure remains critical to the therapeutic approach, with intensity of treatment and ongoing management being guided by disease severity and progression as shown by visual field change, morphological change in the optic disc, and the likelihood of progressive sight loss. Reassessment at each visit is emphasised, encouraging flexible clinical judgement about the frequency of visits and options for treatment, including stopping treatment when the perceived risk to a sighted lifetime is low. Where fresh evidence was not found the guideline has not been updated, that is, accuracy of visual field tests, surgical interventions, laser procedures and information, education and support needed to achieve adherence to treatment. Updating significant elements of the guideline has required an intensive effort from both the professional members of the National Guideline Centre and the guideline committee, who are thanked for their expertise, thoughtful work and in-depth discussions at and between guideline committee meetings. Copyright © NICE 2017.

Exploring the influence of patient-provider communication on intraocular pressure in glaucoma patients. - Carpenter, Delesha M; Tudor, Gail E; Sayner, Robyn; Muir, Kelly W; Robin, Alan L; Blalock, Susan J; Hartnett, Mary Elizabeth; Giangiacomo, Annette L; Sleath, Betsy L (Patient education and counseling, 2015)
OBJECTIVE: We examined whether six patient-provider communication behaviors directly affected the intraocular pressure (IOP) of glaucoma patients or whether patient medication adherence and eye drop technique mediated the relationship between self-efficacy, communication, and IOP., METHODS: During an 8-month, longitudinal study of 279 glaucoma patients and 15 providers, two office visits were videotape-recorded, transcribed, and coded for six patient-provider communication behaviors. Medication adherence was measured electronically and IOP was extracted from medical records. We ran generalized estimating equations to examine the direct effects of communication on IOP and used bootstrapping to test whether medication adherence and eye drop technique mediated the effect of communication on IOP., RESULTS: Provider education about medication adherence (B=-0.50, p<0.05) and inclusion of patient input into the treatment plan (B=-0.35, p<0.05) predicted improved IOP. There was no evidence of significant mediation., CONCLUSION: The positive effects of provider education and provider inclusion of patient input in the treatment plan were not mediated by adherence and eye drop technique., PRACTICE IMPLICATIONS: Providers should educate glaucoma patients about the importance of medication adherence and include patient input into their treatment plan. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Determinants of Self-Reported Barriers to Glaucoma Medicine Administration and Adherence: A Multisite Study. - Sleath, Betsy L; Blalock, Susan J; Muir, Kelly W; Carpenter, Delesha M; Lawrence, Scott D; Giangiacomo, Annette L; Goldsmith, Jason A; Hartnett, Mary Elizabeth; Slota, Catherine; Robin, Alan L (The Annals of pharmacotherapy, 2014)
BACKGROUND: Many factors influence glaucoma medication adherence. A better understanding of the relationships between health literacy, depressive symptoms, and patient-reported problems in using glaucoma medications may reveal opportunities for intervention that could improve patients' clinical outcomes., OBJECTIVE: To examine the relationship between patient characteristics (demographics, health literacy, and depressive symptoms) and patient-reported problems in using glaucoma medications and to assess factors related to patients' self-reported adherence to glaucoma medications., METHODS: Patients diagnosed with primary open-angle glaucoma (n = 228) currently taking intraocular pressure-lowering medications were recruited at 6 ophthalmology clinics. Patients were interviewed to identify problems using glaucoma medications, and self-reported medication adherence was determined using a Visual Analog Scale. Questionnaires were administered to assess health literacy, depressive symptoms, outcome expectations, and medication self-efficacy., RESULTS: Younger patients (P = 0.03), patients with depressive symptoms (P = 0.02), and patients who reported more medication problems (P = 0.005) were significantly less adherent to their glaucoma medications. Patients with higher glaucoma medication self-efficacy adherence scores (P = 0.003) and higher outcome expectations (P = 0.03) were significantly more adherent., CONCLUSIONS: Providers should consider using tools to screen glaucoma patients for depressive symptoms and for problems in using medications to identify patients who are at higher risk of nonadherence to treatment and who might benefit from follow-up with primary care providers. Copyright © The Author(s) 2014.

Prevalence and risk factors for ocular surface disease among patients treated over the long term for glaucoma or ocular hypertension. - Baudouin, Christophe; Renard, Jean-Paul; Nordmann, Jean-Philippe; Denis, Philippe; Lachkar, Yves; Sellem, Eric; Rouland, Jean-Francois; Jeanbat, Viviane; Bouee, Stephane (European journal of ophthalmology, 2012)
Purpose . To determine the prevalence of ocular surface diseases and identify risk factors in a population of patients receiving antiglaucomatous eyedrops over the long term. Methods. An observational cross-sectional study was designed to investigate ocular surface signs and symptoms using simple clinical tools. An ocular surface disease intensity score was calculated based on 10 questions regarding ocular surface symptoms and signs with a 4-grade scale. Patients were classified into 3 groups (A, B, and C) according to this total score. A multinomial logistic regression was performed in order to identify risk factors for surface disease. Results . In an overall population of 516 patients, 49% belonged to group A, 30% to group B, and 21% to group C. The multivariate analysis showed that the following factors were correlated with the severity of ocular surface disease: patient age, number of daily eyedrops, past topical treatment changes for ocular intolerance (found in the history of 40% of the patients), intraocular pressure (found to be significantly higher in patients with more severe ocular surface disease), and glaucoma severity. Conclusions . Patients treated for primary open-angle glaucoma or ocular hypertension often have ocular surface diseases, more often and more severely in older patients receiving more drugs and presenting with more severe glaucoma. These high prevalence values might therefore have consequences on the burden of the disease in terms of adherence to treatment and quality of life.

Delayed Suprachoroidal Hemorrhage after Reinstitution of Warfarin in Combined Procedure. - Rumelt, Shimon; Trevino, Aaron (Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye, 2010)
A 79-year-old non-compliant male with pseudoexfoliative glaucoma and cataract in the left eye underwent uneventful combined phacoemulsification, posterior chamber intraocular lens insertion and trabeculectomy with mitomycin C through one port a week after replacement of warfarin with subcutaneous injections of enoxaparin (Clexane; Sanofi-Aventis, Netaniya, Israel). The intraocular pressure (IOP) following surgery was zero. Four days later, warfarin was restarted because of short ventricular tachycardia when the patient developed suprachoroidal hemorrhage and later hyphema and vitreous hemorrhages. The patient underwent drainage of the suprachoroidal hemorrhage. His IOP increased to 10 to 12 mm Hg while the bleb was functioning, but visual acuity remained poor because of chorioretinal retinal scarring from age-related macular degeneration. Premature reinstitution of warfarin may cause delayed hemorrhages if the postoperative IOP is low. Preoperative approval from the internist for a prolonged replacement of warfarin with lesser potent agents, or tightening of the scleral flap and releasing the sutures later in trabeculectomy in combined procedures may be warranted. Copyright 2010, SLACK Incorporated.

Nail-Patella Syndrome. - Sweeney, Elizabeth; Hoover-Fong, Julie E; McIntosh, Iain (University of Washington, Seattle, 1993)
CLINICAL CHARACTERISTICS: Nail-patella syndrome (NPS) (previously referred to as Fong's disease), encompasses the classic clinical tetrad of changes in the nails, knees, and elbows, and the presence of iliac horns. Nail changes are the most constant feature of NPS. Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into two halves by a longitudinal cleft or ridge of skin; and thin or (less often) thickened. The patellae may be small, irregularly shaped, or absent. Elbow abnormalities may include limitation of extension, pronation, and supination; cubitus valgus; and antecubital pterygia. Iliac horns are bilateral, conical, bony processes that project posteriorly and laterally from the central part of the iliac bones of the pelvis. Renal involvement, first manifest as proteinuria with or without hematuria, occurs in 30%-50% of affected individuals; end-stage renal disease occurs up to 15% of affected individuals. Primary open-angle glaucoma and ocular hypertension occur at increased frequency and at a younger age than in the general population., DIAGNOSIS/TESTING: The diagnosis of nail-patella syndrome is established in a proband with suggestive findings and/or a heterozygous pathogenic variant in LMX1B identified by molecular genetic testing, MANAGEMENT: Treatment of manifestations: Orthopedic problems may be helped by analgesics, physiotherapy, splinting, bracing, or surgery; MRI of joints to identify abnormal anatomy is important prior to surgery so that appropriate surgical treatment can be planned in advance; ACE inhibitors to control blood pressure and possibly to slow progression of proteinuria; renal transplantation as needed; standard treatment for decreased bone mineral density, hypertension, constipation/inflammatory bowel disease, glaucoma, epilepsy, and dental anomalies. Surveillance: At least annually: monitoring of blood pressure for hypertension; assessment of urinalysis and first-morning urine albumin:creatinine ratio for renal disease; screening for glaucoma (as soon as a child is compliant). Dental examination at least every six months and DEXA scan as needed. Agents/circumstances to avoid: Chronic use of NSAIDs because of the detrimental effect on kidney function. Pregnancy management: The risk of developing preeclampsia may be increased in pregnant women with NPS; hence, frequent urinalysis and blood pressure measurement is recommended during pregnancy. For women taking an ACE inhibitor, transitioning to an alternative treatment ideally prior to pregnancy, or at least as soon as pregnancy is recognized, is recommended to avoid potential adverse effects of ACE inhibitors on the developing fetus., GENETIC COUNSELING: Nail-patella syndrome is inherited in an autosomal dominant manner. Eighty-eight percent of individuals with NPS have an affected parent; 12% of affected individuals have a de novo pathogenic variant. The offspring of an affected individual are at a 50% risk of inheriting NPS. Prenatal testing and preimplantation genetic testing are possible if the pathogenic variant in the family has been identified. Copyright © 1993-2020, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Alteration of corneal biomechanical properties in patients with dry eye disease. - Satitpitakul, Vannarut; Taweekitikul, Parichart; Puangsricharern, Vilavun; Kasetsuwan, Ngamjit; Reinprayoon, Usanee; Kittipibul, Thanachaporn (PloS one, 2021)
PURPOSE: To evaluate the association between symptoms and signs of dry eye diseases (DED) with corneal biomechanical parameters., METHODS: This cross-sectional study enrolled 81 participants without history of ocular hypertension, glaucoma, keratoconus, corneal edema, contact lens use, diabetes, and ocular surgery. All participants were evaluated for symptoms and signs of DED using OSDI questionnaire, tear film break-up time (TBUT), conjunctival and corneal staining (NEI grading) and Schirmer test. Corneal biomechanical parameters were obtained using Corvis ST. Mixed-effects linear regression analysis was used to determine the association between symptoms and signs of DED with corneal biomechanical parameters. Difference in corneal biomechanical parameter between participants with low (Schirmer value <=10 mm; LT group) and normal (Schirmer value >10mm; NT group) tear production was analyzed using ANCOVA test., RESULTS: The median OSDI scores, TBUT, conjunctival and corneal staining scores as well as Schirmer test were 13+/-16.5 (range; 0-77), 5.3+/-4.2 seconds (range; 1.3-11), 0+/-1 (range; 0-4), 0+/-2 (ranges; 0-9) and 16+/-14 mm (range; 0-45) respectively. Regression analysis adjusted with participants' refraction, intraocular pressure, and central corneal thickness showed that OSDI had a negative association with highest concavity radius (P = 0.02). The association between DED signs and corneal biomechanical parameters were found between conjunctival staining scores with second applanation velocity (A2V, P = 0.04), corneal staining scores with second applanation length (A2L, P = 0.01), Schirmer test with first applanation time (A1T, P = 0.04) and first applanation velocity (P = 0.01). In subgroup analysis, there was no difference in corneal biomechanical parameters between participants with low and normal tear production (P>0.05). The associations were found between OSDI with time to highest concavity (P<0.01) and highest displacement of corneal apex (HC-DA, P = 0.04), conjunctival staining scores with A2L (P = 0.01) and A2V (P<0.01) in LT group, and Schirmer test with A1T (P = 0.02) and HC-DA (P = 0.03), corneal staining scores with A2L (P<0.01) in NT group., CONCLUSIONS: According to in vivo observation with Corvis ST, patients with DED showed more compliant corneas. The increase in dry eye severity was associated with the worsening of corneal biomechanics in both patients with low and normal tear production.

Teleophthalmology in the Era of COVID-19: Characteristics of Early Adopters at a Large Academic Institution. - Aguwa, Ugochi T; Aguwa, Chibuzo J; Repka, Michael; Srikumaran, Uma; Woreta, Fasika; Singman, Eric L; Jenkins, Sabrina G; Srikumaran, Divya (Telemedicine journal and e-health : the official journal of the American Telemedicine Association, 2021)
Introduction: COVID-19 led to rapid policy changes to expand telemedicine adoption. We examined rates of early telemedicine adoption among surgical departments at a large academic institution and compared provider characteristics associated with teleophthalmology. Methods: With data from departmental and electronic medical records across surgical departments at Johns Hopkins Medicine, we performed a retrospective analysis using the Fisher test and binomial logistic regression. Results: Telemedicine adoption in ophthalmology was disproportionately lower than other surgical departments. Providers who were female [odds ratio, OR, 2.42 (95% confidence interval, CI, 1.03-5.67)], clinical assistants, clinical associates, or instructors [OR 12.5 (95% CI 2.63-59.47)], associate professors [OR 4.38 (95% CI 1.42-13.52)], practiced for >=36 years [OR 0.20 (95% CI 0.06-0.66)], cornea [OR 0.13 (95% CI 0.04-0.47)], glaucoma [OR 0.18 (95% CI 0.04-0.93)] or retina [OR 0.04 (95% CI 0.01-0.17)] specialists, or had a MD/MBBCh/MBBS [OR 0.30 (95% CI 0.10-0.94)] or second degree [OR 0.28 (95% CI 0.08-0.99)] were significantly more or less likely to adopt. When adjusted, cornea [adjusted OR 0.10 (95% CI 0.02-0.57)] or retina [adjusted OR 0.01 (95% CI 0.002-0.12)] specialists or providers who practiced for 12-18 years [adjusted OR 0.22 (95% CI 0.05-0.91)] or >=36 years [adjusted OR 0.13 (95% CI 0.03-0.68)] were significantly more or less likely to adopt. Discussion: Subspecialty among other provider characteristics influences the likelihood of teleophthalmology adoption. As the pandemic continues, strategies to reduce adoption barriers are needed to ensure the provision of health care services.

Randomized controlled trial of an education-based intervention to improve medication adherence: Design considerations in the medication adherence in glaucoma to improve care study. - Rosdahl, Jullia A; Hein, Aaron M; Bosworth, Hayden B; Woolson, Sandra; Olsen, Maren; Kirshner, Miriam; Hung, Anna; Muir, Kelly W (Clinical trials (London, England), 2021)
BACKGROUND: Glaucoma treatment requires patients to follow daily, often times complex, eye drop regimens, but adherence is poor for many patients, putting them at risk for irreversible vision loss. A comprehensive approach is needed to address the challenges in the self-management of glaucoma. The purpose of this study is to improve glaucoma medication adherence in Veterans with medically treated glaucoma using an education-based intervention., METHODS/DESIGN: This study is a single-site randomized controlled trial enrolling 200 Veterans and their companions, if companions are involved in their care. It has two arms: an intervention group and a control group. Participants in the intervention group receive an educational session with a non-physician interventionist and are provided with an AdhereTech smart bottle with the reminder functions activated. The control group is designed as an attention control such that they have a session on general eye health and are provided with a smart bottle but without the reminder functions activated. The primary outcome is the proportion of prescribed doses taken on schedule over 6 months following randomization according to the smart bottle. Secondary outcomes include intensification of glaucoma treatment, cost of intervention delivery, and cost-effectiveness of the intervention over 12 months., DISCUSSION: The education-based intervention that we are testing is comprehensive in scope, to encompass a variety of barriers to adherence that glaucoma patients encounter, but personalized to address issues facing individual patients. Particular attention was given to feasibility in the real-world setting, as the high throughput of patients and lack of reimbursement for educational encounters in ophthalmology would limit implementation of a resource-intensive intervention.

Soft contact lens wearers' compliance during the COVID-19 pandemic. - Vianya-Estopa, Marta; Wolffsohn, James S; Beukes, Eldre; Trott, Mike; Smith, Lee; Allen, Peter M (Contact lens & anterior eye : the journal of the British Contact Lens Association, 2021)
AIM: Contact lens wearers need to maintain optimal hygiene practices during the COVID-19 pandemic to minimise contact-lens complications including microbial keratitis and corneal infiltrative events. This online survey (UK and Ireland) explored contact lens wearers' compliance behaviours, attitudes and concerns during the pandemic., METHOD: The 60-item anonymous online survey was distributed during a 1-month period via Qualtrics (starting on 14/04/20). The survey captured: a) demographic information, b) type of lenses worn and compliance with lens wear and care procedures, c) adherence to recommendations and d) concerns associated with contact lens wear during the pandemic., RESULTS: Two hundred and forty seven responses were received (34.3+/-11.7 years old, 79% female). Seventy nine percent of participants reported that they were self-isolating or rigorously following social distance advice. Fifty-six percent of participants reported using their lenses less during the pandemic. Eighty-seven percent of respondents reported following the recommended 20-second rule most times/every time and 96% used soap and water during handwashing. Eleven percent of respondents admitted not following recommendations regarding disposal of lenses and 18% would not consider ceasing lens wear if unwell (with flu/cold) during the pandemic., CONCLUSION: Respondents reported wearing their contact lenses less than usual. Good compliance with handwashing was observed but soft reusable lens wearers showed a statistically significant lower compliance with lens wear and care compared to daily disposable lens wearers (p=<0.001). Copyright © 2020 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Retinal Ganglion Cell Transplantation: Approaches for Overcoming Challenges to Functional Integration. - Zhang, Kevin Y; Aguzzi, Erika A; Johnson, Thomas V (Cells, 2021)
As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To functionally restore vision, lost RGCs must be replaced. Despite tremendous advancements in experimental models of optic neuropathy that have elucidated pathways to induce endogenous RGC neuroprotection and axon regeneration, obstacles to achieving functional visual recovery through exogenous RGC transplantation remain. Key challenges include poor graft survival, low donor neuron localization to the host retina, and inadequate dendritogenesis and synaptogenesis with afferent amacrine and bipolar cells. In this review, we summarize the current state of experimental RGC transplantation, and we propose a set of standard approaches to quantifying and reporting experimental outcomes in order to guide a collective effort to advance the field toward functional RGC replacement and optic nerve regeneration.

The Impact of the Support, Educate, Empower Personalized Glaucoma Coaching Pilot Study on Glaucoma Medication Adherence. - Newman-Casey, Paula Anne; Niziol, Leslie M; Lee, Paul P; Musch, David C; Resnicow, Kenneth; Heisler, Michele (Ophthalmology. Glaucoma, 2020)
PURPOSE: To assess the efficacy of the Support, Educate, Empower (SEE) glaucoma coaching program on medication adherence among glaucoma patients with low adherence., DESIGN: Uncontrolled intervention study with a pre-post design., PARTICIPANTS: Glaucoma patients >= age 40, taking >=1 medication, who self-reported poor adherence were recruited from the University of Michigan Kellogg Eye Center. Adherence was monitored electronically for a 3-month baseline period; participants with median adherence of <=80% were enrolled in the SEE program., METHODS: Participants' adherence was monitored electronically (AdhereTech, New York, NY) during the 7-month program. Adherence was calculated as the percentage of doses taken on time of those prescribed. The SEE program included (1) automated medication reminders, (2) 3 in-person counseling sessions with a glaucoma coach who had training in motivational interviewing (MI), and (3) 5 phone calls with the same coach for between-session support. The coach used a web-based tool to generate an education plan tailored to the patient's glaucoma diagnosis, test results, and ophthalmologist's recommendations (www.glaucomaeyeguide.org). The tool guided an MI-based conversation between coach and patient to identify barriers to adherence and possible solutions. Descriptive statistics were used to summarize baseline patient characteristics, and differences between those who did and did not complete the SEE program were tested with 2-sample t tests, chi-square tests, and Fisher exact tests. Adherence was compared before and after the SEE program with paired t tests., MAIN OUTCOME MEASURE: Change in electronically monitored medication adherence., RESULTS: A total of 48 participants were enrolled. The participants were 54% male, 46% white, and on average 64 years of age (standard deviation [SD], 10.8 years), with an average worse-eye mean deviation (MD) of -7.9 dB (SD, 8.8 dB). Those completing the SEE program (n = 39) did not differ significantly from those who dropped out (n = 9) on gender, race, age, MD, or baseline adherence. Medication adherence improved from 59.9% at baseline to 81.3% (P < 0.0001) after completing the SEE program. Ninety-five percent of participants showed an improvement in adherence (mean relative improvement, 21.4%; SD, 16.5%; range, -3.2% to 74.4%; median, 20.1%). Fifty-nine percent of participants showed adherence of >80% on completing the SEE program., CONCLUSIONS: The SEE program participants showed clinically meaningful, statistically significant improvement in glaucoma medication adherence. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
Comment in (CIN)

Patient Experience during the Support, Educate, Empower Glaucoma Coaching Program to Improve Medication Adherence: A Pilot Study. - Hollenhorst, Cecilia N; Elliott, Vanessa; Heisler, Michele; Schneider, Kevin; Resnicow, Ken; Newman-Casey, Paula Anne (Ophthalmology. Glaucoma, 2020)
PURPOSE: To understand patients' qualitative experiences with the Support, Educate, Empower (SEE) personalized glaucoma coaching program, provide a richer understanding of the components of the intervention that were useful in eliciting behavior change, and understand how to improve the SEE Program., DESIGN: A concurrent mixed-methods process analysis., PARTICIPANTS: Thirty-nine patients with a diagnosis of any kind of glaucoma or ocular hypertension who were aged >=40 years, were taking >=1 glaucoma medication, spoke English, self-administered their eye drops, and had poor glaucoma medication adherence (defined as taking <=80% of prescribed medication doses assessed via electronic medication adherence monitors) who completed the 7-month SEE Program., METHODS: All participants who completed the study were interviewed in-person using a semistructured interview guide after the intervention. Coders conducted qualitative analysis of transcribed interviews using Grounded Theory. Participants were then stratified into groups based on change in adherence, and thematic differences between groups were examined., MAIN OUTCOME MEASURES: Themes that emerged from interviews categorized by the number of participants who expressed a theme and the number of representative citations., RESULTS: Participants expressed positive views toward the program overall (95%, n = 37/39). They perceived program components as working together to improve their medication adherence. Interactions with the glaucoma coach (38 participants, 184 citations), motivation to aid personal change (38 participants, 157 citations), personalized glaucoma education (38 participants, 149 citations), electronic reminders, and hearing their adherence score (37 participants, 90 citations) were most commonly cited by participants as helpful program elements contributing to improved adherence. Patients expressed a desire for personalized education to be a standard part of glaucoma care. Participants who demonstrated more improvement in adherence had a more trusting attitude toward the adherence score and a greater magnitude of perceived personal need to improve adherence., CONCLUSIONS: Participants reported a highly positive response to the in-person glaucoma education and motivational interviewing intervention used in conjunction with automated adherence reminders. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Low-energy Selective Laser Trabeculoplasty Repeated Annually: Rationale for the COAST Trial. - Realini, Tony; Gazzard, Gus; Latina, Mark; Kass, Michael (Journal of glaucoma, 2021)
The recent Laser in Glaucoma and Ocular Hypertension Trial provided the evidentiary basis for a paradigm shift away from the historical medication-first approach to glaucoma--which has numerous limitations, the most important of which is poor adherence to therapy --and toward a laser-first approach. Now 20 years after its commercialization, selective laser trabeculoplasty (SLT) is routinely performed consistently with its initial description, with energy titrated to the appearance of fine, champagne-like cavitation bubbles. A recent data set suggested that lower energy SLT, applied as primary therapy and repeated annually irrespective of intraocular pressure--rather than pro re nata when its effect wanes and irrespective of intraocular pressure rises --yields longer medication-free survival than standard energy SLT repeated pro re nata. A new study--Clarifying the Optimal Application of SLT Therapy --has been initiated to explore this preliminary finding in a pair of consecutive randomized trials. Herein, we provide an evidence-based rationale for the use of low-energy SLT repeated annually as primary therapy for mild to moderate primary open-angle glaucoma or high-risk ocular hypertension. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Critical role of mass spectrometry proteomics in tear biomarker discovery for multifactorial ocular diseases (Review). - Ma, Jessica Yuen Wuen; Sze, Ying Hon; Bian, Jing Fang; Lam, Thomas Chuen (International journal of molecular medicine, 2021)
The tear film is a layer of body fluid that maintains the homeostasis of the ocular surface. The superior accessibility of tears and the presence of a high concentration of functional proteins make tears a potential medium for the discovery of non-invasive biomarkers in ocular diseases. Recent advances in mass spectrometry (MS) have enabled determination of an in-depth proteome profile, improved sensitivity, faster acquisition speed, proven variety of acquisition methods, and identification of disease biomarkers previously lacking in the field of ophthalmology. The use of MS allows efficient discovery of tear proteins, generation of reproducible results, and, more importantly, determines changes of protein quantity and post-translation modifications in microliter samples. The present review compared techniques for tear collection, sample preparation, and acquisition applied for the discovery of tear protein markers in normal subjects and multifactorial conditions, including dry eye syndrome, diabetic retinopathy, thyroid eye disease and primary open-angle glaucoma, which require an early diagnosis for treatment. It also summarized the contribution of MS to early discovery by means of disease-related protein markers in tear fluid and the potential for transformation of the tear MS-based proteome to antibody-based assay for future clinical application.

The Minimal Clinically Important Difference in Glaucoma Medication Adherence: Interviews of Glaucoma Experts. - Kolli, Ajay; Daniel-Wayman, Shelby; Newman-Casey, Paula Anne (Ophthalmic research, 2021)
Poor adherence to glaucoma medications is associated with progressive vision loss. While many interventions have sought to increase glaucoma medication adherence, the amount by which adherence must increase to have a clinically significant effect remains unknown. To generate a hypothesized minimal clinically important difference (MCID) for glaucoma medication adherence, we conducted interviews with glaucoma experts. Semi-structured interviews were conducted with members of the American Glaucoma Society. MCID was defined in 2 ways: (1) the incremental increase in the average percentage of eye drops a patient takes at roughly the correct time and (2) the incremental increase in the proportion of a patient population who attain good adherence. Good adherence was defined as taking more than 80% of drops at approximately the prescribed dose time. Expert opinions on the MCID for glaucoma medication adherence and open-ended responses were recorded through field notes. Twenty-five experts were interviewed. They estimated the MCID for average individual adherence levels as 17.7% (95% CI: 14.6, 20.8). Experts estimated the MCID for the proportion of patients in a practice who attain good adherence (defined as >80% of eye drops taken as prescribed) as 18.5% (95% CI: 15.6, 21.5). The most common identified themes were that the MCID should take into account the cost of the intervention and the burden to the ophthalmologist and to the practice, where experts thought that more costly interventions or those that required more physician time should have larger MCIDs. Based on expert opinion, we hypothesized that the MCID for glaucoma medication adherence is between 15 and 20%. However, the MCID for a given intervention must take into account several factors, including intervention cost and physician burden. This hypothesis may facilitate the design and implementation of future studies to objectively determine an MCID for glaucoma medication adherence. Copyright © 2020 S. Karger AG, Basel.

Efficacy and Safety of Preservative-free Latanoprost Eyedrops Compared with Preserved Prostaglandin Analogues in Patients with Open-angle Glaucoma. - Seong, Hyo Jin; Lee, Kwanghyun; Lee, Seung Jae; Kim, Sangah; Park, Jong Woon (Korean journal of ophthalmology : KJO, 2021)
PURPOSE: To evaluate the safety and efficacy of preservative-free (PF) latanoprost in glaucoma patients., METHODS: In this prospective, open-label, observational study, a total of 27 primary open-angle glaucoma patients who used benzalkonium chloride-preserved prostaglandin analogues for at least 6 months were enrolled. After changing the eye drops to PF lataprost, the intraocular pressure (IOP) and ocular surface symptoms and signs were evaluated in all patients on days 0 (first visit, D0), 45 (D45), and 90 (D90)., RESULTS: Mean IOP remained stable during the study period (14.0 +/- 2.4 mmHg at D0, 13.9 +/- 2.0 mmHg at D45, 13.7 +/- 2.2 mmHg at D90; p = 0.603). Mean deviation, pattern standard deviation, and best-corrected visual acuity were similar before and after eye drops replacement. Bulbar conjunctival hyperemia, corneal staining, and conjunctival staining were significantly decreased over 90 days (p = 0.025, p < 0.001, p = 0.020, respectively). The ocular surface disease index score showed a statistically significant improvement from 26.4 +/- 18.5 at D0 to 19.8 +/- 17.0 at D45 and 15.7 +/- 15.6 at D90 (p < 0.001). In the evaluation of ocular tolerability, burning symptoms and dryness were significantly decreased (p = 0.001, p = 0.040)., CONCLUSIONS: The effects of PF latanoprost on reducing IOP were comparable with those of benzalkonium chloride-preserved prostaglandin analogues, but side effects on the ocular surface were much less pronounced when PF latanoprost was used. With this efficacy, PF latanoprost could slow the progression of glaucoma by increasing patient compliance.

Contact lens complications among wearers in Ghana. - Kobia-Acquah, Emmanuel; Akowuah, Prince Kwaku; Antwi-Adjei, Ellen Konadu; Forkuo, Philip Mensah; Koomson, Nana Yaa; Odotei, Samuel Odoi; Alabi, Emmanuel; Donkor, Richard (Contact lens & anterior eye : the journal of the British Contact Lens Association, 2021)
PURPOSE: Contact lens (CL) practice is relatively new in Ghana; a country where the geographical location (warm climate) lends itself to harsh environmental conditions (high humidity) known to influence CL wear. Recent studies suggest an increase in CL wear (corrective and cosmetic), yet, there are no studies about CL-related complications. This study sought to determine the complications associated with CL wear in Ghana., METHODS: This was a retrospective cohort study. The medical records of contact lens wearers from five CL clinics in the two largest metropolises in Ghana, Accra and Kumasi, were reviewed. Included in the study were records of individuals who visited the clinics within the period of 2013-2016. Data on patients with contact lens-related complications were analyzed., RESULTS: The prevalence of CL complications was 29.06 %. The mean+/-SD age of patients with CL complications was 35+/-15 years. Contact lens complications were more common in females (52.90 %). The majority of complications were in soft contact lens wearers (82.35 %). Refractive error correction was the most common indication for CL wear (61.76 %) among those with complications, followed by keratoconus (14.71 %), scarred blind eye (14.71 %), corneal ulcer (5.88 %) and anterior staphyloma (2.94 %). Contact lens complications reported were giant papillary conjunctivitis (41.18 %), corneal infiltrates (23.53 %), bacterial keratitis (14.71 %), corneal abrasion (11.76 %), dry eye (5.88 %) and corneal oedema (2.94 %). The causes of CL complication were inappropriate lens cleaning (29.41 %), poor hygiene (23.53 %), overnight contact lens wear (17.64 %), poor lens fit (14.71 %) and reaction to contact lens solution (14.71 %)., CONCLUSION: Contact lens complications were more common in soft contact lens wearers in Ghana. Giant papillary conjunctivitis was the most common contact lens complication reported. Adherence to CL wear care regimen and good personal hygiene may prevent the majority of CL complications observed in Ghana. Copyright © 2019 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Cost-Related Medication Nonadherence in a Nationally Representative US Population with Self-Reported Glaucoma. - Gupta, Divakar; Ehrlich, Joshua R; Newman-Casey, Paula Anne; Stagg, Brian (Ophthalmology. Glaucoma, 2021)
PURPOSE: To determine the rates of cost-related nonadherence to medications among US adults with glaucoma and to determine if participants with glaucoma have more cost-related medication nonadherence than those without glaucoma., DESIGN: Cross-sectional study., PARTICIPANTS: Participants in the 2016-2017 National Health Interview Survey (NHIS), a cross-sectional survey regarding health topics that is administered annually to a nationally representative sample of noninstitutionalized adults in the United States., METHODS: We calculated proportions of NHIS participants with and without self-reported glaucoma who reported cost-related nonadherence over the previous 12 months. We analyzed responses to 7 survey items that dealt with medication cost-related issues to any/all of a participants' medication: couldn't afford a prescribed medication; skipped medication doses to save money; took less medicine to save money; delayed filling a prescription to save money; asked doctor for lower cost medication to save money; bought prescription drugs from another country to save money; used alternative therapies to save money. We performed univariable and multivariable logistic regression to evaluate the association between self-reported glaucoma diagnosis and responses to these selected questions., MAIN OUTCOME MEASURES: Proportion of participants with and without self-reported glaucoma who reported cost-related nonadherence., RESULTS: Participants with glaucoma reported they could not afford prescribed medication more frequently than participants without glaucoma (8.2% vs. 6.4% P = 0.024). Adjusted predicted proportions from a multivariable model demonstrated that participants with glaucoma responded that they had greater cost-related barriers to medication access., CONCLUSIONS: In this nationally representative sample of the US population, after adjustment for confounding variables, participants with glaucoma more frequently reported cost-related nonadherence to medications compared with participants without glaucoma. Providers prescribing medication to patients with glaucoma should be aware of these findings and consider the impact of medication cost on their patients' ability to adhere to therapy. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Impact of the Support, Educate, Empower Personalized Glaucoma Coaching Program Pilot Study on Eye Drop Instillation Technique and Self-Efficacy. - Schneider, Kevin J; Hollenhorst, Cecilia N; Valicevic, Autumn N; Niziol, Leslie M; Heisler, Michele; Musch, David C; Cain, Stephen M; Newman-Casey, Paula-Anne (Ophthalmology. Glaucoma, 2021)
PURPOSE: To assess the Support, Educate, Empower (SEE) personalized glaucoma coaching program impact on (1) eye drop instillation technique and (2) eye drop instillation self-efficacy., DESIGN: Prospective pre-post pilot study., PARTICIPANTS: Patients with a diagnosis of glaucoma or ocular hypertension taking >=1 glaucoma medication, >=40 years old, spoke English, self-administered their eye drops, and <=80% adherent to their glaucoma medication by electronic monitoring., METHODS: Eye drop administration was video recorded before the first SEE in-person coaching session, which included teaching eye drop instillation techniques using a motivational interviewing-based approach. At the third and final in-person counseling session 6 months later, eye drop administration was video recorded. Participants ' self-efficacy was assessed using the validated Eye Drop Technique Self-Efficacy Scale (EDTSES) survey at baseline and 1 month after completion of the program. Before and after intervention videos were assessed by an observer masked to time point. Before versus after intervention comparisons were made using McNemar's and paired t tests., MAIN OUTCOME MEASURES: The main outcome was change in participants' eye drop instillation technique as measured by (1) accuracy of an eye drop landing on the eye, (2) ability to instill an eye drop on the first attempt, and (3) contaminating the bottle by contact with ocular surface, eyelashes, and skin. The secondary outcome measure was before versus after change in the EDTSES score (6 items, each assessed on a 3-point Likert scale, with higher scores indicating better self-efficacy)., RESULTS: Thirty-nine participants completed the SEE intervention, 38 with before and after EDTSES scores and 31 with video recordings. Six of 31 participants instilling drops outside the eye before intervention improved their technique after intervention, whereas 2 participants worsened (P = 0.157). From before to after intervention, participants demonstrated significant improvement in not touching the ocular surface (P = 0.046), the eyelashes (P = 0.020), or the skin (P = 0.025) with the bottle tip. A significant increase was found in eye drop instillation self-efficacy from an average score of 2.6 (standard deviation [SD], 0.3) to 2.8 (SD, 0.2) on the EDTSES score (P = 0.007)., CONCLUSIONS: The SEE program significantly decreased eye drop bottle contamination, increased eye drop instillation self-efficacy, and demonstrated an insignificant increase in ability to instill drops successfully and accurately. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Human Umbilical Cord-Derived Mesenchymal Stem Cells Promote Corneal Epithelial Repair In Vitro. - Kacham, Santhosh; Bhure, Tejal Sunil; Eswaramoorthy, Sindhuja D; Naik, Gaurav; Rath, Subha Narayan; Parcha, Sreenivasa Rao; Basu, Sayan; Sangwan, Virender Singh; Shukla, Sachin (Cells, 2021)
Corneal injuries are among the leading causes of blindness and vision impairment. Trauma, infectious keratitis, thermal and chemical (acids and alkali burn) injuries may lead to irreversible corneal scarring, neovascularization, conjunctivalization, and limbal stem cell deficiency. Bilateral blindness constitutes 12% of total global blindness and corneal transplantation remains a stand-alone treatment modality for the majority of end-stage corneal diseases. However, global shortage of donor corneas, the potential risk of graft rejection, and severe side effects arising from long-term use of immunosuppressive medications, demands alternative therapeutic approaches. Umbilical cord-derived mesenchymal stem cells can be isolated in large numbers using a relatively less invasive procedure. However, their role in injury induced corneal repair is largely unexplored. Here, we isolated, cultured and characterized mesenchymal stem cells from human umbilical cord, and studied the expression of mesenchymal (CD73, CD90, CD105, and CD34), ocular surface and epithelial (PAX6, WNT7A, and CK-8/18) lineage markers through immunofluorescence. The cultured human limbal and corneal epithelial cells were used as controls. Scratch assay was used to study the corneal epithelial repair potential of umbilical cord-derived mesenchymal stem cells, in vitro. The in vitro cultured umbilical cord-derived mesenchymal stem cells were plastic adherent, showed trilineage differentiation and expressed: mesenchymal markers CD90, CD105, CD73; epithelial marker CK-8/18, and ocular lineage developmental markers PAX6 and WNT-7A. Our findings suggest that umbilical cord-derived mesenchymal stem cells promote repair of the injured corneal epithelium by stimulating the proliferation of corneal epithelial cells, in vitro. They may serve as a potential non-ocular source of stem cells for treating injury induced bilateral corneal diseases.

Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma. - Kompella, Uday B; Hartman, Rachel R; Patil, Madhoosudan A (Progress in retinal and eye research, 2021)
Although once daily anti-glaucoma drug therapy is a current clinical reality, most therapies require multiple dosing and there is an unmet need to develop convenient, safe, and effective sustained release drug delivery systems for long-term treatment to improve patient adherence and outcomes. One of the first sustained release drug delivery systems was approved for the reduction of intraocular pressure in glaucoma patients. It is a polymeric reservoir-type insert delivery system, Ocusert TM, placed under the eyelid and on the ocular surface for zero-order drug release over one week. The insert, marketed in two strengths, released pilocarpine on the eye surface. While many clinicians appreciated this drug product, it was eventually discontinued. No similar sustained release non-invasive drug delivery system has made it to the market to date for treating glaucoma. Drug delivery systems under development include punctal plugs, ring-type systems, contact lenses, implants, microspheres, nanospheres, gels, and other depot systems placed in the extraocular, periocular, or intraocular regions including intracameral, supraciliary, and intravitreal spaces. This article discusses the advantages and disadvantages of the various routes of administration and delivery systems for sustained glaucoma therapy. It also provides the reader with some examples and discussion of drug delivery systems that could potentially be applied for glaucoma treatment. Interestingly, one intracamerally injected implant, Durysta TM, was approved recently for sustained intraocular pressure reduction. However, long-term acceptance of such devices has yet to be established. The ultimate success of the delivery system will depend on efficacy relative to eye drop dosing, safety, reimbursement options, and patient acceptance. Cautious development efforts are warranted considering prior failed approaches for sustained glaucoma drug delivery. Neuroprotective approaches for glaucoma therapy including cell, gene, protein, and drug-combination therapies, mostly administered intravitreally, are also rapidly progressing towards assessment in humans. Copyright © 2020 Elsevier Ltd. All rights reserved.

American Academy of Optometry Microbial Keratitis Think Tank. - Szczotka-Flynn, Loretta B; Shovlin, Joseph P; Schnider, Cristina M; Caffery, Barbara E; Alfonso, Eduardo C; Carnt, Nicole A; Chalmers, Robin L; Collier, Sarah; Jacobs, Deborah S; Joslin, Charlotte E; Kroken, Abby R; Lakkis, Carol; et al. (Optometry and vision science : official publication of the American Academy of Optometry, 2021)
SIGNIFICANCE: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies., PURPOSE: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting., METHODS: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives., RESULTS: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed., CONCLUSIONS: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain. Copyright © 2021 American Academy of Optometry.

Baicalein Protects Against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting TSLP-Induced Inflammatory Response. - Zhu, Yunan; Peng, Xudong; Zhang, Yingxue; Lin, Jing; Zhao, Guiqiu (Investigative ophthalmology & visual science, 2021)
Purpose: To investigate the antifungal and anti-inflammatory effects of baicalein on Aspergillus fumigatus (A. fumigatus) keratitis and the underlying mechanisms., Methods: The noncytotoxic antifungal concentration of baicalein was determined using CCK8, cell scratch assay, minimum inhibitory concentration, biofilm formation, scanning electron microscopy, propidium iodide uptake test and adherence assay in vitro and Draize test in vivo. In fungal keratitis (FK) mouse models, clinical score and plate count were used to evaluate FK severity, and myeloperoxidase assay and immunofluorescence staining were performed to examine neutrophil infiltration and activity. Real-time PCR, ELISA, and Western blot were performed to explore the anti-inflammatory activity of baicalein and the underlying mechanisms in vivo and in vitro., Results: Baicalein at 0.25 mM (noncytotoxic) significantly inhibited A. fumigatus growth, biofilm formation, and adhesion in vitro. In A. fumigatus keratitis mice, baicalein mitigated FK severity, reduced fungal load, and inhibited neutrophil infiltration and activity. Baicalein not only suppressed mRNA and protein levels of proinflammatory factors IL-1beta, IL-6, and TNF-alpha, but also inhibited the expression of thymic stromal lymphopoietin (TSLP) and TSLP receptor (TSLPR) in vivo and in vitro. In HCECs, mRNA and protein levels of IL-1beta, IL-6, and TNF-alpha were significantly lower in the TSLP siRNA-treated group, while higher in the rTSLP-treated group than in the corresponding control. Baicalein treatment significantly inhibited rTSLP induced the expression of IL-1beta, IL-6, and TNF-alpha., Conclusions: Baicalein plays a protective role in mouse A. fumigatus keratitis by inhibiting fungal growth, biofilm formation, and adhesion, and suppressing inflammatory response via downregulation of the TSLP/TSLPR pathway.

Primary open angle glaucoma management in a tertiary eye care center in Saudi Arabia: a best practice implementation pilot project. - Alshowaeir, Daniah; Almasoud, Nouf; Aldossari, Sheikhah; Alsirhy, Ehab Y; Osman, Essam; Turjoman, Abdulsalam; Amer, Yasser; Munn, Zachary; McArthur, Alexa (JBI evidence implementation, 2020)
AIM: Primary open angle glaucoma (POAG) is a leading cause of permanent visual loss affecting significant numbers in Saudi Arabia. There is no cure for glaucoma but there is mounting evidence to guide ophthalmologists in diagnosing and managing this disease. The aim of this pilot project was to assess the compliance with evidence-based criteria and to implement an adapted clinical practice guideline (CPG) for the management of patients with POAG at a tertiary eye care center in Riyadh, Saudi Arabia that will lead to improving quality, consistency and optimizing patients' care., METHODS: The project consisted of three phases using audit and feedback strategy. It has utilized the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice audit and feedback tool. Eleven evidence-based audit criteria were developed. A baseline audit was then conducted. Barriers behind areas of noncompliance were identified and a number of strategies were implemented to overcome them. A follow-up postimplementation audit was then conducted., RESULTS: Twenty electronic medical files were randomly selected for baseline audit. The results of the audit have identified a number of possible areas to improve in the diagnosis and management of POAG in compliance with the adapted CPG with compliance rate as low as 20% (4/20) in some criteria. Multifaceted interventions were implemented targeting mainly attitude and lack of knowledge and time and resource barriers. Significant improvement occurred in most criteria audited postimplementation., CONCLUSION: The project demonstrates that audit and feedback is a feasible and effective tool to change glaucoma practice in a teaching hospital in Saudi Arabia. The success was due to multifaceted interventions including clear communication to promote awareness, an easily accessible CPG, and regular reminders to improve knowledge and change behavior. We propose our pilot implementation to be generalized to promote implementing evidence-based ophthalmology. Copyright © 2020 University of Adelaide, Joanna Briggs Institute.

A Randomized Trial to Improve Adherence to Follow-up Eye Examinations Among People With Glaucoma. - Leiby, Benjamin E; Hegarty, Sarah E; Zhan, Tingting; Myers, Jonathan S; Katz, L Jay; Haller, Julia A; Waisbourd, Michael; Burns, Christine; Divers, Meskerem; Molineaux, Jeanne; Henderer, Jeffrey; Brodowski, Charles; et al. (Preventing chronic disease, 2021)
INTRODUCTION: Appointment nonadherence is common among people with glaucoma, making it difficult for eye care providers to monitor glaucoma progression. Our objective was to determine whether the use of patient navigators, in conjunction with social worker support, could increase adherence to recommended follow-up eye appointments., METHODS: A randomized, controlled trial evaluated the effectiveness of an intervention that used patient navigators and social workers to improve patient adherence to follow-up eye care compared with usual care. Participants with glaucoma and other eye diseases (N = 344) were identified at primary care clinics in community settings through telemedicine screening of imaging and then randomized to enhanced intervention (EI) or usual care (UC). Data on participants' visits with local ophthalmologists were collected for up to 3 years from randomization. Groups were compared for timely attendance at the first visit with the local ophthalmologist and adherence to recommended follow-up visits., RESULTS: Timely attendance at the first visit was higher for EI than UC (74.4% vs 39.0%; average relative risk [aRR] = 1.85; 95% CI, 1.51-2.28; P < .001). Rates of adherence to recommended annual follow-up during year 1 were 18.6% in the EI group and 8.1% in the usual care group (aRR = 2.08; 95% CI, 1.14-3.76; P = .02). The aRR across years 2 and 3 was 3.92 (95% CI, 1.24-12.43; P = .02)., CONCLUSION: An intervention using patient navigators and social workers doubled the rate of adherence to annual recommended follow-up eye care compared with usual care in community settings, and was effective at increasing connections with local ophthalmologists. Interventions to further improve long-term adherence are needed.

Updates and challenges of axon regeneration in the mammalian central nervous system. - Qian, Cheng; Zhou, Feng-Quan (Journal of molecular cell biology, 2020)
Axon regeneration in the mammalian central nervous system (CNS) has been a long-standing and highly challenging issue. Successful CNS axon regeneration will benefit many human diseases involving axonal damage, such as spinal cord injury, traumatic brain injury, glaucoma, and neurodegenerative diseases. The current consensus is that the diminished intrinsic regenerative ability in mature CNS neurons and the presence of extrinsic inhibitors blocking axon regrowth are two major barriers for axon regeneration. During the past decade, studies targeting the intrinsic axon growth ability via regulation of gene transcription have produced very promising results in optic nerve and/or spinal cord regeneration. Manipulations of various signaling pathways or the nuclear transcription factors directly have been shown to sufficiently drive CNS axon regrowth. Converging evidence reveals that some pro-regenerative transcriptomic states, which are commonly accomplished by more comprehensive epigenetic regulations, exist to orchestrate the complex tasks of injury sensing and axon regeneration. Moreover, genetic reprogramming achieved via transcriptome and epigenome modifications provides novel mechanisms for enhancing axon regeneration. Recent studies also highlighted the important roles of remodeling neuronal cytoskeleton in overcoming the extrinsic inhibitory cues. However, our knowledge about the cellular and molecular mechanisms by which neurons regulate their intrinsic axon regeneration ability and response to extrinsic inhibitory cues is still fragmented. Here, we provide an update about recent research progress in axon regeneration and discuss major remaining challenges for long-distance axon regeneration and the subsequent functional recovery. Copyright © The Author(s) (2020). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

Michigan Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (MI-SIGHT): Baseline Methodology for Implementing and Assessing a Community-based Program. - Newman-Casey, Paula A; Musch, David C; Niziol, Leslie M; Elam, Angela R; Zhang, Jason; Moroi, Sayoko E; Johnson, Leroy; Kershaw, Martha; Saadine, Jinan; Winter, Suzanne; Woodward, Maria A (Journal of glaucoma, 2021)
PRECIS: The Michigan Screening and Intervention for Glaucoma and eye Health through Telemedicine (MI-SIGHT) program leverages community-engaged research, telemedicine, and health coaching to overcome key logistical and psychosocial barriers to improve glaucoma screening in underserved communities., PURPOSE: To describe the methodology of the implementation and evaluation of the MI-SIGHT Program., METHODS: The MI-SIGHT Program uses community engagement, telemedicine, and health coaching to overcome key logistical and psychosocial barriers to glaucoma identification and care among underserved populations. The MI-SIGHT Program will be evaluated in 2 community clinics: Hamilton Community Health Network, a federally qualified health center in Flint, Michigan, and the Hope Clinic, a free clinic in Ypsilanti, Michigan. A Community Advisory Board including the research team and health care providers, administrators, and patients from both clinics will guide program implementation. An ophthalmic technician at the community clinics will conduct screening tests for glaucoma and eye disease. The data will be transmitted through electronic health record to be reviewed by an ophthalmologist who will make recommendations for follow-up care. The ophthalmic technician will conduct a return visit to fit low-or no-cost glasses, help arrange follow-up with an ophthalmologist, and provide education. Those diagnosed with glaucoma or suspected glaucoma will be randomized to standard education or personalized glaucoma education and coaching. Costs will be assessed., RESULTS: The authors hypothesize that the MI-SIGHT Program will detect a higher prevalence rate of glaucoma than that found in the general population, improve upon presenting visual acuity, enhance vision-related quality of life, and demonstrate that personalized glaucoma education and coaching improve adherence to follow-up care., CONCLUSION: The MI-SIGHT Program may serve as a model for glaucoma screening and care in high-risk communities. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Alabama Screening and Intervention for Glaucoma and Eye Health Through Telemedicine (AL-SIGHT): Study Design and Methodology. - Rhodes, Lindsay A; Register, Shilpa; Asif, Irfan; McGwin, Gerald Jr; Saaddine, Jinan; Nghiem, Van Thi Ha; Owsley, Cynthia; Girkin, Christopher A (Journal of glaucoma, 2021)
PRCIS: This paper presents the methods and protocol of a community-based telemedicine program to identify glaucoma and other eye diseases., PURPOSE: To describe the study rationale and design of the Alabama Screening and Intervention for Glaucoma and eye Health through Telemedicine project., METHODS: The study will implement and evaluate a telemedicine-based detection strategy for glaucoma, diabetic retinopathy, and other eye diseases in at-risk patients seen at federally qualified health centers located in rural Alabama. The study will compare the effectiveness of the remote use of structural and functional ocular imaging devices to an in-person examination. Study participants will receive a remote ocular assessment consisting of visual acuity, intraocular pressure, visual field testing, and imaging of the retina and optic nerve with spectral-domain optical coherence tomography, and the data will be reviewed by an ophthalmologist and optometrist. It will also compare the effectiveness of financial incentives along with a validated patient education program versus a validated patient education program alone in improving follow-up adherence. Finally, cost and cost-effectiveness analyses will be performed on the telemedicine program compared with standard in-person care using effectiveness measured in numbers of detected eye disease cases., CONCLUSIONS: The study aims to develop a model eye health system using telemedicine to prevent vision loss and address eye health among underserved and at-risk populations. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Facilitators and Barriers to Glaucoma Screening Identified by Key Stakeholders in Underserved Communities: A Community-engaged Research Approach. - Ballouz, Dena; Cho, Juno; Woodward, Maria A; Elam, Angela R; Musch, David C; Zhang, Jason; Moroi, Sayoko E; Johnson, Leroy; Cederna, Jean; Newman-Casey, Paula A (Journal of glaucoma, 2021)
PRCIS: Community-engaged research (CER) enables researchers to identify community-specific barriers and facilitators to program implementation. Broadly applicable barriers to glaucoma care, such as Cost, Transportation, and Trust, and community-specific barriers, such as Language and Convenience/Access, were identified., PURPOSE: The aim was to identify the facilitators and barriers to implementing glaucoma screening programs in 2 community clinics., METHODS: A concurrent mixed-methods process analysis using CER. Key stakeholders-including patients, providers, and staff members-from 2 community clinics were interviewed using a semistructured interview guide. Interviews had 2 parts: (1) asking patients about community-based facilitators and barriers to implementing glaucoma screening and care and (2) eliciting feedback about a personalized coaching program. The transcripts were coded using Grounded Theory. Number of participants and number of representative citations were counted per theme. The qualitative analysis was coded using Dedoose 8.3.17 (Los Angeles, CA)., RESULTS: Thematic saturation was reached after coding 12 interviews. 30 participants were interviewed, 13 from Hamilton Clinic (Flint, MI; 8 patients, 5 providers and staff members) and 17 from Hope Clinic (Ypsilanti, MI; 6 patients, 11 providers and staff members). The most commonly cited themes were: Priorities (98 citations, 30 participants), Knowledge (73, 26) Transportation (63, 26), Cost (60, 23), and Convenience/Access (63, 22). Broadly applicable barriers to glaucoma care, such as Cost, Transportation, and Trust were identified alongside community-specific barriers such as Language and Convenience/Access. Participants rated their likelihood to follow up with an ophthalmologist after participating in the personalized coaching program at a mean of 8.83 (on a scale of 1 to 10 with 10 being the most confident)., CONCLUSIONS: CER enables researchers to identify community-specific barriers and facilitators, allowing more effective program implementation. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

A novel EyePhone© App for improving adherence to glaucoma therapy. - Leshno, Ari; Gaton, Dan; Singer, Reut; Eliasi, Elior; Vorobichik-Berar, Ofri; Madgar, Shiran; Stern, Ori; Jaber, Wasim; Kapelushnik, Noa; Skaat, Alon (Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2021)
PURPOSE: Despite advances in glaucoma treatment options, patient adherence and compliance remain very low. The EyePhone© App is a free non-commercial reminder application designed specifically for the needs of glaucoma patients. In this study, we evaluated its usefulness in improving adherence to medical treatment among glaucoma patients., METHODS: This is a prospective multicenter interventional study. Glaucoma patients were recruited from a tertiary center and a large community glaucoma service center. After a short explanation, the EyePhone© App was installed on their smartphone device, and the notifications for the current medical treatment were entered. After enrollment and at 1-month follow-up, subjects completed the Morisky Medication Adherence Scale (MMAS-8) and the Quality of Life and Glaucoma 17-item (GlauQOL-17) questionnaires for evaluation of adherence and QOL, respectively., RESULTS: In the study, 133 patients (71 men and 62 women) aged 62+/-15.5 years and using 2.0+/-0.9 IOP-lowering drugs participated. The proportion of highly adherent subjects improved from 29.3% (39/133) at baseline to 42.1% (56/133) at follow-up (P < 0.001), and the proportion of poorly adherent subjects decreased from 29.3 (39/133) to 20.3% (27/133) at follow-up (P = 0.012). QOL also improved, as evidenced by a significant increase in the GlauQOL-17 score (P < 0.05). In a subgroup of patients for whom IOP measurements were available, IOP reduced by 0.92 mmHg (P = 0.069)., CONCLUSIONS: Significant improvements in glaucoma adherence and QOL were achieved among poorly adherent glaucoma patients after 1 month of using the EyePhone© App.

Safety and efficacy of microinvasive glaucoma surgery with cataract extraction in patients with normal-tension glaucoma. - Chang, Enchi Kristina; Gupta, Sanchay; Chachanidze, Marika; Hall, Nathan; Chang, Ta Chen; Sola-Del Valle, David (Scientific reports, 2021)
This study assesses the safety and efficacy of microinvasive glaucoma surgery (MIGS) with cataract extraction in patients with normal-tension glaucoma (NTG). In our sample of 45 NTG patients, mean intraocular pressure (IOP) decreased from 13.7 to 12.3 mmHg at 2.5 years, and mean medication burden decreased from 2.0 to 1.1 at 1.5 years. For success defined as IOP reduction >= 30% from baseline IOP with medication burden reduction from preoperative levels, success probability was 5.4% at 1.5 years. For success defined as medication burden reduction with an IOP reaching goal IOP as determined by the glaucoma specialist, success probabilities were 67.2% at 1.5 years and 29.4% at 2.5 years. At the last follow-up visit, eyes with two MIGS procedures with different mechanisms of action achieved successful medication reduction 68.8% of the time versus 35.7% achieved by a single MIGS procedure (p = 0.052). At their last visit, visual acuity was unchanged or improved in all eyes (100%). MIGS with cataract surgery results in modest reductions in IOP and medication burden in NTG patients, which may lead to lower costs and better therapeutic compliance. A combination of two MIGS procedures with different mechanisms of action may potentially be more effective in reducing medication burden than a single MIGS procedure in NTG patients. Further research is necessary to ascertain whether MIGS for NTG patients may help decrease medication burden while helping achieve goal IOP.

Depression and Severity of Glaucoma Among Older Adults in Urban and Suburban Areas. - Tharmathurai, Sangeetha; Muhammad-Ikmal, Mohamad K; Razak, Asrenee A; Che-Hamzah, Jemaima; Azhany, Yaakub; Fazilawati, Qamaruddin; Liza-Sharmini, Ahmad T (Journal of glaucoma, 2021)
PRCIS: Depression increases with severity of visual field defect in older adults with primary open-angle glaucoma (POAG)., PURPOSE: This study aimed to determine the prevalence of depression among patients with POAG and examine the relationship between depression and the severity of POAG in older adults., MATERIALS AND METHODS: Three hundred and sixty patients with POAG aged 60 years or above were recruited from 2 tertiary centers located in an urban and suburban area. The participants were stratified according to the severity of their glaucoma based on the scores from the modified Advanced Glaucoma Intervention Study (AGIS) to mild, moderate, severe, and end stage. Face-to-face interviews were performed using the Malay Version Geriatric Depression Scale 14 (mGDS-14) questionnaire. Depression is diagnosed when the score is >=8. One-way analysis of variance was used to compare the subscores between the groups. Multifactorial analysis of variance was also applied with relevant confounding factors., RESULTS: Depression was detected in 16% of older adults with POAG; a higher percentage of depression was seen in those with end stage disease. There was a significant increase in the mean score of mGDS-14 according to the severity of POAG. There was evidence of an association between depression and severity of visual field defect (P<0.001). There was a significant difference in mGDS-14 score between the pairing of severity of POAG [mild-severe (P=0.003), mild-end stage (P<0.001), moderate-severe (P<0.001), and moderate-end stage (P<0.001)] after adjustment to living conditions, systemic disease, and visual acuity., CONCLUSION: Ophthalmologists should be aware that older adults with advanced visual field defects in POAG may have depression. The detection of depression is important to ensure adherence and persistence to the treatment of glaucoma. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Comparison of the Intraocular Pressure-Lowering Effect and Safety of Preservative-Free And Preservative-Containing Brimonidine/Timolol Fixed-Combination Ophthalmic Solutions in Patients with Open-Angle Glaucoma. - Kim, Joon Mo; Kim, Tae-Woo; Park, Sang-Woo; Park, Hae-Young Lopilly; Hwang, Young Hoon; Jeoung, Jin Wook; Kim, Chan Yun (Seminars in ophthalmology, 2021)
Purpose: To compare the therapeutic efficacy and safety of newly developed preservative-free (PF) brimonidine/timolol fixed-combination (BTFC) ophthalmic solutions and a preservative-containing (PC) BTFC ophthalmic solution in patients with open-angle glaucoma. Methods: This study was conducted as a multicenter, randomized, open-label, parallel-group clinical trial to evaluate the efficacy and safety of PF BTFC as compared with PC BTFC in adult patients (aged >= 19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). A total of the 106 patients were enrolled, with 53 patients each randomized to the two treatment groups and included in the analysis of the safety set (SS). After a washout period, patients with an IOP below 35 mmHg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, a total of 106 OAG and OHT patients were randomized to the PF group or PC group.All subjects were examined 4 and 12 weeks after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 11 a.m. and the efficacy, safety, and compliance were evaluated. Throughout the study, all adverse events were recorded and monitored by the investigators. Results The mean IOP changes from baseline to 12 weeks at 11:00 a.m. were -3.45 +/- 2.53 mmHg in the PF group and -3.65 +/- 2.76 mmHg in the PC group (p < .0001 for both). The difference in mean IOP change between the two groups was 0.20 +/- 2.65 mmHg, which was not significantly different. The proportion of patients with IOP reductions of >= 15% and >= 20% and IOP at all-time points in the PF group were not significantly different when compared with in the PC group. There were no specific differences between the two groups regarding the incidence of adverse events. Conclusions PF BTFC ophthalmic solution shows a similar efficacy and safety profile to that of PC BTFC.

Adherence and Persistence with First-Line Therapy and Compliance with Glaucoma Guidelines Using Japanese Health Care/Pharmacy Claims Database. - Shirai, Chikako; Matsuoka, Nobushige; Nakazawa, Toru (Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2021)
Purpose: This study evaluated Japanese patients' adherence to first-line therapy and physicians' compliance with the guidelines (GLs) for glaucoma in daily practice. Methods: This retrospective, noninterventional cohort study used a Japanese health care/pharmacy claims database from 2011 to 2016. We compared adherence based on the primary outcomes assessed as proportion of days covered (PDC) and persistence between patients who received first-line monotherapy followed by second-line fixed-combination therapy (GL-compliant cohort) and those who received first-line fixed-combination therapy (GL-noncompliant cohort). Furthermore, we explored treatment patterns, glaucoma consultation, and key factors associated with GL noncompliance. Results: Among 11,666 patients who received first-line therapy, 1,183 (10.1%) and 542 (4.6%) were in the GL-compliant and GL-noncompliant cohorts, respectively. Prostaglandin (70.7%) and subsequent prostaglandin/beta blocker (BB) (20.9%) within 12 months were most used by the GL-compliant cohort. Prostaglandin/BB (48.9%) and carbonic anhydrase inhibitor/BB (51.1%) were prescribed for the GL-noncompliant cohort. The mean PDC [standard deviation (SD)], persistence rate (95% confidence interval), and consultation (SD) over 12 months were 60.9% (34.0), 16.0% (14.0-18.1), and 5.23 (3.21) times, respectively, in the GL-compliant cohort and 59.7% (35.8), 22.0% (18.6-25.5), and 4.76 (3.19) times, respectively, in the GL-noncompliant cohort. No significant differences were observed between the 2 cohorts. No clinically relevant factor associated with GL noncompliance was found. Conclusions: Around 5% of patients were prescribed a fixed-combination eye drop as first-line therapy not in accordance with GLs. The similarity of adherence and persistence between the 2 cohorts indicates that first-line fixed-combination therapy could be considered for glaucoma treatment.

New considerations for the clinical efficacy of old and new topical glaucoma medications. - MacIver, Sarah; Stout, Nicole; Ricci, Olivia (Clinical & experimental optometry, 2021)
Glaucoma is the most common form of irreversible blindness in the world. Lowering intraocular pressure (IOP) remains the only clinically established method of treatment to slow the progression of glaucoma. Primary open angle glaucoma is a disease of the optic nerve head and often is associated with changes to the trabecular meshwork that cause a reduction to aqueous humour outflow and an increase in intraocular pressure. Until recently, topical IOP lowering medication has been limited to the mechanisms of action of decreasing aqueous production and/or redirecting outflow to the unconventional uveoscleral outflow pathway. Both of these mechanisms neglect to treat or act on tissue that becomes altered from glaucoma. Latanoprostene-bunod 0.024%, a nitric-oxide donating prostanoid, netarsudil 0.02%, a potent Rho-associated protein kinase (ROCK) inhibitor and norepinephrine transporter inhibitor, and a once daily dosed fixed combination medication with netarsudil 0.02% and latanoprost 0.005% have recently come on the market. This paper will discuss and review the limitations to traditional IOP lowering glaucoma medications as well as the mechanism of actions and clinical efficacy of the new glaucoma medications. It will also discuss how the new class of glaucoma medications might help to overcome some known limitations in treatment and barriers to patient adherence.

Sympathetic context of the disease - a new era in glaucoma management. - Vasile, Potop; Valeria, Coviltir; Speranta, Schmitzer; Catalina, Ioana Ionescu; Miruna, Gabriela Burcel; Maria, Corbu; Dana, Margareta Cornelia Dascalescu (Romanian journal of ophthalmology, 2021)
Primary open angle glaucoma (POAG) is a multifactorial optic neuropathy, which progresses in a chronic manner. Several etiological factors are involved, including genetic factors, race, age, IOP or vascular, systemic factors. IOP has an established role in the initiation and evolution of glaucoma, but its interactions with additional risk factors are complex. We propose the notion of the Glaucoma Etiological Area (GEA), as a representation of all the elements acting in collaboration in the physiopathology of each glaucoma case. When combined in different proportions, these elements may trigger the typical glaucomatous optic neuropathy (GON). We know that the statistical values of IOP are valid for normal eyes, but the glaucoma eye is not a normal eye. The notion of GEA can open a new perspective to interpret IOP values and to assess the true value of IOP control as a treatment for glaucoma. Applying the GEA theory allows us to tune the role of IOP. Additional factors, such as ocular properties (RGCL status, CCT, IOP fluctuation curve), ocular comorbidities (PEX, PDS), systemic comorbidities (arterial hypertension, vasospastic diseases such as migraines or Reynaud's syndrome) or patient's attitude towards glaucoma management (treatment compliance, access to follow-up and treatment) may greatly influence the evolution of GON and should be viewed holistically when developing a management plan for each patient. Applying the notion of GEA in clinical practice allows a more realistic approach of the pathophysiology of the disease and for a glaucoma treatment that is tailored to each patient. Abbreviations: AG = advanced glaucoma, BP = blood pressure, CCT = central corneal thickness, CIGTS = Collaborative Initial Glaucoma Treatment Study, CNTGS = Collaborative Normal-Tension Glaucoma Study, EMGT = Early Manifest Glaucoma Trial, GEA = glaucoma etiological area, GON = glaucomatous optic neuropathy, IOP = intraocular pressure, NTG = Normal Tension Glaucoma, OHTS = Ocular Hypertension Study, PDS = Pigmentary dispersion syndrome, PEX = Pseudoexfoliation syndrome, POAG - primary open-angle glaucoma, RGCL = retinal ganglion cell layer, VFL = visual field loss. Copyright ©Romanian Society of Ophthalmology.

Depression and Medical Treatment Adherence in Mexican Patients With Glaucoma. - Gamiochipi-Arjona, Jorge E; Azses-Halabe, Yael; Tolosa-Tort, Paulina; Lazcano-Gomez, Gabriel; Gonzalez-Salinas, Roberto; Turati-Acosta, Mauricio; Garcia-Huerta, Magdalena; Jimenez-Roman, Jesus (Journal of glaucoma, 2021)
PRECIS: The prevalence of depression in Mexican patients with glaucoma is higher than that reported in the general population. Depression prevalence and severity are directly associated with glaucoma severity and lower adherence to medical treatment., PURPOSE: To determine the prevalence of depression in patients with glaucoma and to describe the correlation between the severity of depression, glaucoma, and treatment adherence., PATIENTS AND METHODS: This cross-sectional study included 111 patients with glaucoma who answered the Beck Depression Inventory (BDI)-II and the Morisky-Green questionnaire that evaluated their depression severity and medical treatment adherence. Low treatment adherence was defined as having a score of >2 on the Morisky-Green questionnaire. Analysis of variance, Fisher exact test, and linear regression models were used for statistical analyses. The main outcomes were prevalence of depression, prevalence of depression according to glaucoma damage, and the association between depression severity, medical treatment adherence, and glaucoma damage., RESULTS: The average patient age was 67.6+/-13.8 years. The prevalence of depression was 50.4%. Analysis of variance revealed a statistically significant association between glaucoma severity of the "worse eye" and the BDI raw score. In the "better eye," there was no statistically significant difference in mean BDI raw scores across glaucoma severity categories. There was a statistically significant association between the presence of depression and the level of treatment adherence after adjusting for age, sex, type of glaucoma, and the glaucoma severity in both eyes. The risk of low treatment adherence in patients with depression was 38 times that of patients with no depression., CONCLUSION: Glaucoma is associated with a prevalence of depression nearly 10 times higher than that in the general population. Glaucoma, depression severity, and lower adherence to medical treatment are associated. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Surgical Management of Pseudoexfoliative Glaucoma: A Review of Current Clinical Considerations and Surgical Outcomes. - Gillmann, Kevin; Meduri, Enrico; Niegowski, Laetitia J; Mermoud, Andre (Journal of glaucoma, 2021)
INTRODUCTION: Pseudoexfoliative glaucoma (PEXG) is the most common cause of secondary open-angle glaucoma worldwide. It is more aggressive and often more resistant to conventional treatments than primary open-angle glaucoma, yet there is currently no clear consensus on best management practices. This review explores current literature on PEXG to assess the safety and efficacy of currently available surgical techniques, and discusses clinical considerations on the diagnosis and management of the disease., METHODS: A PubMed and Google Scholar search identified 2271 articles. These were reviewed to exclude irrelevant or duplicate data. A total of 47 studies reporting specifically on PEXG were retained and analyzed., REVIEW: One of the most significant ophthalmic consequences of pseudoexfoliative (PEX) syndrome is the compromising of the blood-aqueous barrier resulting in the leakage of inflammatory cytokines and extracellular matrix material into the anterior chamber. Considering the high risk of developing PEXG and the aggressive nature of this type of glaucoma, accurate and timely diagnosis of PEX is critical. Therefore, systematic attentive examination for PEX deposits is crucial. Patients diagnosed with PEX need frequent glaucoma assessments. Patient information is key to improving compliance. Gonioscopy and diurnal tension curves or 24-hour intraocular pressure (IOP) monitoring are integral part of the diagnostic work-up and risk-assessment of PEXG. Because of the lability of IOP in PEX, clinical decisions on the basis of single IOP measurements should be avoided. Cataract extraction was shown to provide persistent IOP-lowering effect in the order of 10% in PEXG. A number of other surgical options may offer wider IOP reduction, and both XEN 45 gel stents and angle-based glaucoma procedures were suggested to achieve better outcomes in PEXG than in primary open-angle glaucoma. Yet, more significant IOP reductions may be achieved with filtering surgery or glaucoma drainage device. Same day postoperative IOP monitoring is recommended to treat the frequent IOP spikes following surgery, and more aggressive anti-inflammatory therapy may reduce the rates of postoperative adverse events in PEXG., CONCLUSION: Specific studies of the surgical management of PEXG remain scarce in the medical literature, and more long-term and comparative studies are warranted to define more robust recommendations. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Medical anti-glaucoma therapy: Beyond the drop. - Miller, Paul E; Eaton, Joshua Seth (Veterinary ophthalmology, 2021)
Barriers to effective medical therapy are numerous and include difficulties with effective and sustained control of intraocular pressure (IOP) and adherence to prescribed anti-glaucoma drop regimens. In an effort to circumvent these challenges, a number of new anti-glaucoma therapies with sustained effects have emerged. Methods for sustained delivery of prostaglandin analogs are being intensely investigated and many are in human clinical trials. Intracameral devices include the following: Allergan's Durysta TM Bimatoprost SR, Envisia Therapeutics' ENV515 travoprost implant, Glaukos' iDose TM , Ocular Therapeutix's OTX-TIC travoprost implant, and Santen's polycaprolactone implant with PGE2-derivative DE-117. Other prostaglandin-based technologies include Allergan's bimatoprost ring (placed in the conjunctival fornix), Ocular Therapeutics' OTX-TP intracanalicular travoprost implant, subconjunctival latanoprost in a liposomal formulation, and the PGE2 derivative PGN 9856-isopropyl ester that is applied to the periorbital skin. Exciting breakthroughs in gene therapy include using viral vectors to correct defective genes such as MYOC or to modulate gonioimplant fibrosis, CRISPR technology to edit MYOC or to alter aquaporin to reduce aqueous humor production, and siRNA technology to silence specific genes. Stem cell technology can repopulate depleted tissues or, in the case of Neurotech's Renexus R NT-501 intravitreal implant, serve as a living drug delivery device that continuously secretes neurotrophic factors. Other unique approaches involve nanotechnology, nasal sprays that deliver drug directly to the optic nerve and noninvasive alternating current stimulation of surviving cells in the optic nerve. Over time these modalities are likely to challenge the preeminent role that drops currently play in the medical treatment of glaucoma in animals. Copyright © 2020 American College of Veterinary Ophthalmologists.

Improved Treatment Options for Glaucoma with Brimonidine-Loaded Lipid DNA Nanoparticles. - Schnichels, Sven; Hurst, Jose; de Vries, Jan Willem; Ullah, Sami; Frosl, Katharina; Gruszka, Agnieszka; Loscher, Marina; Bartz-Schmidt, Karl-Ulrich; Spitzer, Martin S; Herrmann, Andreas (ACS applied materials & interfaces, 2021)
Glaucoma is the second leading cause of irreversible blindness worldwide. Among others, elevated intraocular pressure (IOP) is one of the hallmarks of the disease. Antiglaucoma drugs such as brimonidine can lower the IOP but their adherence to the ocular surface is low, leading to a low drug uptake. This results in a frequent dropping regime causing low compliance by the patients. Lipid DNA nanoparticles (NPs) have the intrinsic ability to bind to the ocular surface and can be loaded with different drugs. Here, we report DNA NPs functionalized for loading of brimonidine through specific aptamers and via hydrophobic interactions with double stranded micelles. Both NP systems exhibited improved affinity toward the cornea and retained release of the drug as compared to controls both in vitro and in vivo. Both NP types were able to lower the IOP in living animals significantly more than pristine brimonidine. Importantly, the brimonidine-loaded NPs showed no toxicity and improved efficacy and hence should improve compliance. In conclusion, this drug-delivery system offers high chances of an improved treatment for glaucoma and thus preserving vision in the aging population.

Tolerance and Adherence to Cationic 0.1% Cyclosporine in Ocular Graft-versus-Host Disease. - Gehlsen, Uta; Siebelmann, Sebastian; Steven, Philipp (Ophthalmic research, 2021)
INTRODUCTION: Anti-inflammatory, topical therapy of severe keratitis in dry eye disease (DED) and ocular graft-versus-host disease (oGvHD) includes steroids, cyclosporine (Cs), and others. In Germany, a commercial product containing 0.1% Cs in a cationic formulation is available since 2015., OBJECTIVE: The aim of this study was to present real-life data using cationic 0.1% Cs in oGvHD patients., METHODS: This was a retrospective study of 26 oGvHD and 41 DED patients with corneal staining of at least Oxford grade III. Parameters analyzed were Ocular Surface Disease Index, corneal staining, intraocular pressure, tear film break-up time, Schirmer, and visual acuity. In addition, it was evaluated how different Cs formulations were tolerated., RESULTS: Corneal staining improved significantly in 1 eye in DED but not in oGvHD. In DED, cationic 0.1% Cs was not tolerated by 32% of the patients, in contrast to 0.05% Cs in castor oil not tolerated by 47% and liposomal 0.05% Cs by 63%. In oGvHD patients, cationic 0.1% Cs was not tolerated by 62%, 0.05% Cs in castor oil by 33%, and liposomal 0.05% Cs by 39% of the patients., CONCLUSIONS: This study demonstrates differences between the tolerance of different Cs formulations depending on the underlying cause of severe keratitis. Cationic 0.1% Cs is considerably less tolerated in oGvHD, and its use should be considered with care. Copyright © 2020 S. Karger AG, Basel.

Is Mental Stress the Primary Cause of Glaucoma?. - Sabel, Bernhard A; Lehnigk, Luisa (Klinische Monatsblatter fur Augenheilkunde, 2021)
The prognosis of going blind is very stressful for patients diagnosed with "glaucoma". Worries and fear of losing independence is a constant mental burden, with secondary risks of depression and social isolation. But stress is not only a result of glaucoma but also a possible cause (risk factor). This should not be surprising, given that chronic stress can trigger "psychosomatic" organ dysfunctions anywhere in the body. Why should the organ "eye" be an exception? Indeed, glaucoma patients often suspect that severe emotional stress caused their visual field loss or "foggy vision". The hypothesis that stress is a possible cause of glaucoma is supported by different observations: (i) acute and chronic stress increases intraocular pressure and (ii) long-term stress can lead to vascular dysregulation of the microcirculation in the eye and brain ("Flammer's syndrome"), leading to partial hypoxia and hypoglycaemia (hypo-metabolism). Even if nerve cells do not die, they may then become inactive ("silent" neurons). (iii) Degenerative changes have been reported in the brain of glaucoma patients, affecting not only anterograde or transsynaptic areas of the central visual pathway, but degeneration is also found (iv) in brain areas involved in emotional appraisal and the physiological regulation of stress hormones. There are also psychological hints indicating that stress is a cause of glaucoma: (v) Glaucoma patients with Flammer's syndrome show typical personality traits that are associated with low stress resilience: they often have cold hands or feet, are ambitious (professionally successful), perfectionistic, obsessive, brooding and worrying a lot. (vi) If stress hormone levels and inflammation parameters are reduced in glaucoma patients by relaxation with meditation, this correlates with normalisation of intraocular pressure, and yet another clue is that (vii) visual field improvements after non-invasive current stimulation therapy, that are known to improve circulation and neuronal synchronisation, are much most effective in patients with stress resilient personalities. An appreciation of stress as a "cause" of glaucoma suggests that in addition to standard therapy (i) stress reduction through relaxation techniques should be recommended (e.g. meditation), and (ii) self-medication compliance should not be induced by kindling anxiety and worries with negative communication ("You will go blind!"), but communication should be positive ("The prognosis is optimistic"). Copyright Thieme. All rights reserved.

Integral role for lysyl oxidase-like-1 in conventional outflow tissue function and behavior. - Li, Guorong; Schmitt, Heather; Johnson, William M; Lee, Chanyoung; Navarro, Iris; Cui, Jenny; Fleming, Todd; Gomez-Caraballo, Maria; Elliott, Michael H; Sherwood, Joseph M; Hauser, Michael A; Farsiu, Sina; et al. (FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020)
Lysyl oxidase-like-1 (LOXL1), a vital crosslinking enzyme in elastin fiber maintenance, is essential for the stability and strength of elastic vessels and tissues. Variants in the LOXL1 locus associate with a dramatic increase in risk of exfoliation syndrome (XFS), a systemic fibrillopathy, which often presents with ocular hypertension and exfoliation glaucoma (XFG). We examined the role of LOXL1 in conventional outflow function, the prime regulator of intraocular pressure (IOP). Using Loxl1-/- , Loxl1+/- , and Loxl1+/+ mice, we observed an inverse relationship between LOXL1 expression and IOP, which worsened with age. Elevated IOP in Loxl1-/- mice was associated with a larger globe, decreased ocular compliance, increased outflow facility, extracellular matrix (ECM) abnormalities, and dilated intrascleral veins, yet, no dilation of arteries or capillaries. Interestingly, in living Loxl1-/- mouse eyes, Schlemm's canal (SC) was less susceptible to collapse when challenged with acute elevations in IOP, suggesting elevated episcleral venous pressure (EVP). Thus, LOXL1 expression is required for normal IOP control, while ablation results in altered ECM repair/homeostasis and conventional outflow physiology. Dilation of SC and distal veins, but not arteries, is consistent with key structural and functional roles for elastin in low-pressure vessels subjected to cyclical mechanical stress. Copyright © 2020 Federation of American Societies for Experimental Biology.

Acceptability, adherence and economic analyses of a new clinical pathway for the identification of non-responders to glaucoma eye drops: a prospective observational study. - Waterman, Heather; Read, Simon; Morgan, James Edwards; Gillespie, David; Nollett, Claire; Allen, Davina; Weiss, Marjorie; Anderson, Pippa (The British journal of ophthalmology, 2020)
BACKGROUND/AIMS: Assess whether a new clinical pathway for glaucoma was acceptable to patients and healthcare professionals and whether it provided useful clinical information on non-responsiveness and non-adherence to the treatment of elevated intraocular pressure with latanoprost eye drops., METHODS: A single arm non-randomised prospective observational study incorporating new glaucoma/ocular hypertension patients. To assess issues of acceptability, qualitative observation and interviews were conducted with patients and healthcare professionals. To determine clinical responsiveness, intraocular pressures were measured before and 4 hours after a clinician-instilled eye drop over two distinct appointments. Adherence data were collected using a Medicine Event Monitoring System. Economic analyses compared the costs between novel and standard care pathways., RESULTS: Of 72 patients approached, 53 entered the study (74.3%) and 50 completed all procedures (94.3%). Intraocular pressure was reduced more than 15% in 83 out of 92 study eyes by final visit (90.2%). The non-response rate was 5.1% once the effect of low adherence was minimised. For the 1376 drop instillation days under observation, eye drops were instilled as prescribed on 1004 days (73.0%), over-instilled on 137 days (9.9%) and not instilled on 235 days (17.1%). The Cardiff Model of Glaucoma Care involved negligible cost, although acceptance for healthcare professionals showed variation., CONCLUSIONS: The Cardiff Model of Glaucoma Care offers novel clinical and adherence insights at marginal costs while acceptable to patients. Healthcare professionals felt that 4 hour and 4 week follow-up appointments could cause administrative problems. A streamlined version of the pathway has therefore been developed to facilitate clinical adoption., TRIAL REGISTRATION NUMBER: ISRCTNID:ISRCTN75888393. Copyright © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

The Effect of Patient Education and Telemedicine Reminders on Adherence to Eye Drops for Glaucoma. - Lai, Yien; Wu, Yanlong; Chai, Charmaine; Yen, Ching-Chiuan; Ho, Yvonne; Eng, Teng Chuan; Jain, Pravar; Koh, Victor (Ophthalmology. Glaucoma, 2020)
PURPOSE: To determine the improvement in patient adherence to topical ocular hypotensive therapy by introducing a personalized illustrated medication reference chart and telereminder., DESIGN: Prospective randomized controlled clinical trial., PARTICIPANTS: Fifty-nine patients with glaucoma who were using at least 3 or more eye drops were recruited from the ophthalmology clinic at the National University Hospital of Singapore., METHODS: Participants were randomized into 3 groups: control, reference chart only, and reference chart with telereminder. They completed a survey on demographics, barriers to glaucoma medication adherence, and self-adherence (measured by the Morisky adherence scale) before and 6 weeks after intervention. Logistic regression analysis was performed on the barriers that contribute to nonadherence and paired t tests were conducted for the preimplementation and postimplementation effects of intervention on adherence score., MAIN OUTCOME MEASURES: Changes in mean adherence score based on the Morisky adherence scale before and after intervention in participants from all 3 groups., RESULTS: In our study, 71% of participants who were nonadherent to medications had multiple barriers to adherence, with lack of self-efficacy and forgetfulness being the most common factors. Only the reference chart with telereminder group showed a statistically significant increase in mean adherence score, from 7.18 to 7.69 (P = 0.047)., CONCLUSIONS: Adherence to medication in chronic diseases like glaucoma is an important healthcare issue to address. Most of these patients have poor adherence because of multiple factors, and hence interventions aimed at improving adherence should be multifaceted to target these barriers. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Inpatient Adherence to Topical Glaucoma Medications before and after an Educational Intervention. - Mammo, Danny A; Strampe, Margaret; Naravane, Ameay; Mallory, Paul W; Boysen, Jess; Wright, Martha M (Ophthalmology. Glaucoma, 2020)
PURPOSE: To assess the inpatient adherence rate and factors associated with adherence to topical glaucoma medications (TGMs) at a single academic institution throughout hospitalization before and after an educational intervention., DESIGN: Nonrandomized, comparative, retrospective study., PARTICIPANTS: Inpatients 18 years of age and older admitted to a single academic hospital from January 2014 through June 2019 with a diagnosis of glaucoma who also received TGMs., METHODS: The medication administration record during admission was examined closely to determine if the TGMs were reconciled and administered correctly before and after an educational intervention with inpatient providers. A simple intervention reached various health care providers through an educational e-mail, communication in a weekly newsletter, and a morning report presentation. Adherence was defined as administration of more than 75% of recommended doses during the inpatient stay. Other collected variables included length of stay and primary diagnosis on admission., MAIN OUTCOME MEASURES: Adherence rate to inpatient administration of TGMs., RESULTS: One hundred eighty-four patients (n = 142 before intervention; n = 42 after intervention) were included. The preintervention group had a total of 275 TGMs, of which 207 (75.3%) were administered in accordance with the adherence definition of this study. After the intervention phase, 49 of 56 (87.5%) TGMs were administered with appropriate adherence (P = 0.047). Adherence was associated significantly with a known outpatient medication regimen (P = 0.006) and correct admission reconciliation (P < 0.001)., CONCLUSIONS: When glaucoma patients requiring topical treatment are admitted, approximately one quarter of patients seem to not receive their medications appropriately. In this study, a simple educational intervention was able to improve adherence. To prevent daily fluctuations in intraocular pressure for vulnerable glaucoma patients, inpatient adherence to appropriate medication administration should be stressed continuously. While in the care of health care providers, inpatients should be afforded at least the opportunity to maintain adequate adherence, just as is carried out for other medications related to other chronic medical conditions. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Phase 3, Randomized, 20-Month Study of Bimatoprost Implant in Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 1). - Medeiros, Felipe A; Walters, Thomas R; Kolko, Miriam; Coote, Michael; Bejanian, Marina; Goodkin, Margot L; Guo, Qiang; Zhang, Jane; Robinson, Michael R; Weinreb, Robert N; ARTEMIS 1 Study Group (Ophthalmology, 2020)
PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10- and 15-mug bimatoprost implant in subjects with open-angle glaucoma (OAG) and ocular hypertension (OHT) after initial and repeated administrations., DESIGN: Randomized, 20-month, multicenter, subject- and efficacy evaluator-masked, parallel-group, phase 3 clinical study., PARTICIPANTS: Adults with OAG or OHT in each eye, open iridocorneal angle inferiorly in the study eye, and study eye baseline IOP (hour 0; 8 am) of 22-32 mmHg after washout., METHODS: Study eyes received bimatoprost implant 10 mug (n = 198) or 15 mug (n = 198) on day 1 with readministration at weeks 16 and 32, or twice-daily topical timolol maleate 0.5% (n = 198). Intraocular pressure was measured at hours 0 and 2 at each visit., MAIN OUTCOME MEASURES: Primary end points were IOP and change from baseline IOP through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD)., RESULTS: Both dose strengths of bimatoprost implant were noninferior to timolol in IOP lowering after each administration. Mean diurnal IOP was 24.0, 24.2, and 23.9 mmHg at baseline and from 16.5-17.2, 16.5-17.0, and 17.1-17.5 mmHg through week 12 in the 10-mug implant, 15-mug implant, and timolol groups, respectively. The incidence of corneal and inflammatory TEAEs of interest (e.g., corneal endothelial cell loss, iritis) was higher with bimatoprost implant than timolol and highest with the 15-mug dose strength. Incidence of corneal TEAEs increased after repeated treatment; with 3 administrations at fixed 16-week intervals, incidence of >=20% CECD loss was 10.2% (10-mug implant) and 21.8% (15-mug implant). Mean best-corrected visual acuity (BCVA) was stable; 3 implant-treated subjects with corneal TEAEs had >2-line BCVA loss at their last visit., CONCLUSIONS: Both dose strengths of bimatoprost implant met the primary end point of noninferiority to timolol through week 12. One year after 3 administrations, IOP was controlled in most subjects without additional treatment. The risk-benefit assessment favored the 10-mug implant over the 15-mug implant. Ongoing studies are evaluating other administration regimens to reduce the potential for CECD loss. The bimatoprost implant has potential to improve adherence and reduce treatment burden in glaucoma. Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Treatment of glaucoma among elderly patients in Sofia. - Marinova, Milcheva Evelina; Naseva, Krasimirova Emilia; Zdravkov, Todorov Yani; Dabov, Stoimenov Dimitar (Romanian journal of ophthalmology, 2020)
Objective: To analyze therapy of glaucoma among the elderly population, 65 years old and above, in Sofia city, the capital of Bulgaria. Methods: Two prophylactic ophthalmic campaigns were realized in the summer of 2016 and 2017, in Sofia city. All patients passed thorough ophthalmic examinations and filled pen-and-paper questionnaires. The results and files were collected and statistically analyzed to estimate current antiglaucoma therapy among the elderly citizens of Sofia city. Results: The predominant number of persons who were diagnosed with glaucoma, was treated with conservative monotherapy. Prostaglandin analogues have been prescribed to more than half of the patients in both studies. Fixed combinations have been used in 86% of the cases who needed combined therapy with two substances and in 100% of those with three medications. Conclusions: The therapeutic scheme used for treating glaucoma among elderly citizens of Sofia city is similar and corresponding to practice worldwide. Conservative monotherapy is used in mean 45%. When combined therapy is necessary, fixed combinations are predominantly prescribed with a target to minimize adverse events and to ensure better patients' compliance. A tendency of usage of preservative-free formulas to benefit patients' eye health has been noticed. Abbreviations: POSE = prophylactic ophthalmic screening among elderly people, GSW = glaucoma screening week, EGS = European Glaucoma Society, PEX= pseudoexfoliative syndrome, PGAs = Prostaglandin analogues, CAIs = Carbonic Anhydrase Inhibitors. Copyright ©Romanian Society of Ophthalmology.

Generics versus brand-named drugs for glaucoma: the debate continues. - Bhartiya, Shibal; Dhingra, Deepika (Romanian journal of ophthalmology, 2020)
There are three options for a given class of drugs, including brand name drugs, generic and branded generic drugs. Brand name drugs are costlier as compared to generic and branded generic drugs because they are innovator molecules developed by a company after many years of research and come into the market with a patent, whereas branded generic drugs are produced by a different company once the patent of innovator company expires. Given that glaucoma is a chronic, largely asymptomatic disease, the choice of drugs is extremely important: the duration of medication is often lifelong, and the cost of drugs, side effects and efficacy affect compliance and adherence to therapy. This review is a brief overview of the available brand name and branded generic drugs for the management of glaucoma, in terms of efficacy and side effect profiles. It also aimed to guide rational and pragmatic drug choices in different clinical scenarios. Copyright ©Romanian Society of Ophthalmology.

Naturally occurring neuroprotectants in glaucoma. - Patel, Radhika Pooja; Shamsher, Ehtesham; Hill, Daniel; Cordeiro, Maria Francesca (Progress in brain research, 2020)
With the increasing global burden of glaucoma-caused blindness there is a significant need to develop therapies that both enable early detection of retinal neurodegeneration, and help protect cells from the neurodegenerative processes of glaucoma. In this chapter, we discuss potential neuroprotective agents that are present naturally and examine their role and suitability as therapies in glaucoma. These agents have been found to have anti-apoptotic and anti-inflammatory mechanisms of action which may aid the resilience of retinal ganglion cells and enable them to withstand potential insults that trigger cell death. We highlight how these properties could be translated into clinical practice and the barriers needing to be overcome in order to achieve this. Copyright © 2020 Elsevier B.V. All rights reserved.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review. - Nijm, Lisa M; De Benito-Llopis, Laura; Rossi, Gemma Caterina; Vajaranant, Thasarat Sutabutr; Coroneo, Minas Theodore (Asia-Pacific journal of ophthalmology (Philadelphia, Pa.), 2020)
Glaucoma-related ocular surface disease (G-OSD) is a significant, yet often underdiagnosed, ocular co-morbidity affecting 40% to 59% of glaucoma patients worldwide. Although the use of topical glaucoma medications represents a proven strategy to control the untoward effects of high intraocular pressure, this treatment can profoundly disrupt the homeostasis of the tear film. The cumulative effect of medications, preservatives, and excipients alter underlying cellular structures which results in tear film abnormalities and instability of the ocular surface. Furthermore, these chronic inflammatory changes have been shown to impact efficacy of glaucoma treatment, patient compliance with therapy and overall quality of life. The pathogenesis of G-OSD is multifactorial and involves a vicious self-perpetuating cycle of inflammatory cytokines and proteins. The diagnosis of such disease is based on similar tests used in assessing traditional dry eye, taking into consideration findings specific to this patient population. The hallmark of treatment for these patients is to minimize the ocular surface inflammatory response by choosing glaucoma therapies that spare the ocular surface such as preservative free formulations and initiating dry eye treatment early in the course of care. In summary, glaucoma affects millions of patients around the world and chronic use of topical glaucoma medications may negatively impact the patient's ocular surface, symptoms, and vision. Understanding the pathogenesis of G-OSD, recognizing its risk factors and incorporating diagnostic and therapeutic strategies that restore and maintain ocular surface homeostasis will result in improved care for our patients.

Comparison of the Safety and Efficacy between Preserved and Preservative-Free Latanoprost and Preservative-Free Tafluprost. - Kim, Joon Mo; Park, Sang Woo; Seong, Mincheol; Ha, Seung Joo; Lee, Ji Woong; Rho, Seungsoo; Lee, Chong Eun; Kim, Kyoung Nam; Kim, Tae-Woo; Sung, Kyung Rim; Kim, Chan Yun (Pharmaceuticals (Basel, Switzerland), 2021)
In this study, we investigated the effect of preservative-free (PF) 0.0015% tafluprost (TA), to the preservative containing (PC) and the PF 0.005% latanoprost (LA) in Korean subjects. This study was conducted as a multi-center, randomized, investigator-blind, active controlled, parallel-group, clinical trial in adult patients (>=19 years) with open-angle glaucoma (OAG) and ocular hypertension (OHT). After a washout period, patients with an IOP between 15 and 35 mmHg were enrolled and evaluated the efficacy, safety, and compliance at 4, 8 and 12 weeks after the first administration. A total of 137 OAG and OHT patients were randomized. Statistically significant reductions in IOP were observed in all groups. Twelve weeks after each eye drop instillation, the mean IOP reduction was -4.59 +/- 2.70 mmHg (-24.57 +/- 13.49%) in the PC-LA group, -4.52 +/- 2.17 mmHg (-24.41 +/- 11.38%) in the PF-LA, and -3.14 +/- 2.83 mmHg (-17.22 +/- 14.57%) in the PF-TA group. The PF-LA showed significantly better responsiveness than did PF-TA. PF-LA was better tolerated than was PC-LA. There were no adverse events that led to cessation of eye drop use in any of the groups. In conclusion, IOP decreased similarly across the groups. PF-LA may provide a good choice for OAG patients with ocular surface diseases.

Improving Adherence to Topical Medication in Patients with Glaucoma. - Tapply, Ian; Broadway, David C (Patient preference and adherence, 2021)
The glaucomas form a heterogenous group of conditions, which collectively account for one of the most common irreversible causes of blindness worldwide. The only treatment, for which there is evidence, to stop or slow glaucomatous disease progression is to lower intraocular pressure (IOP); this is most often initially achieved with topical medication. Adherence to anti-glaucoma therapy is known to be low even when compared with adherence to therapy for other chronic conditions. We performed a PubMed search to review evidence as to how adherence to and persistence with anti-glaucoma medications might be improved. Approaches to improving adherence include technological (such as using smart drop bottles or automated reminders) use of instillation aids, improving communication with patient education and improving tolerability of eye drop formulations. There is limited short-term evidence that automated reminders can be effective and, unfortunately, instillation aids have not proved to be efficacious with respect to improving adherence. A range of factors have been identified which affect adherence and persistence, although only a multi-faceted approach has proven evidence of efficacy, compared to improved patient education alone. There is now a wider range of available preservative-free eye drops, which have been shown to be non-inferior in achieving IOP control, with fewer side effects and improved short-term adherence. Further studies relating to adherence are warranted, particularly given the projected increase in glaucoma prevalence worldwide. Copyright © 2021 Tapply and Broadway.

Searching for the Antioxidant, Anti-Inflammatory, and Neuroprotective Potential of Natural Food and Nutritional Supplements for Ocular Health in the Mediterranean Population. - Valero-Vello, Mar; Peris-Martinez, Cristina; Garcia-Medina, Jose J; Sanz-Gonzalez, Silvia M; Ramirez, Ana I; Fernandez-Albarral, Jose A; Galarreta-Mira, David; Zanon-Moreno, Vicente; Casaroli-Marano, Ricardo P; Pinazo-Duran, Maria D (Foods (Basel, Switzerland), 2021)
Adherence to a healthy diet offers a valuable intervention to compete against the increasing cases of ocular diseases worldwide, such as dry eye disorders, myopia progression, cataracts, glaucoma, diabetic retinopathy, or age macular degeneration. Certain amounts of micronutrients must be daily provided for proper functioning of the visual system, such as vitamins, carotenoids, trace metals and omega-3 fatty acids. Among natural foods, the following have to be considered for boosting eye/vision health: fish, meat, eggs, nuts, legumes, citrus fruits, nuts, leafy green vegetables, orange-colored fruits/vegetables, olives-olive oil, and dairy products. Nutritional supplements have received much attention as potential tools for managing chronic-degenerative ocular diseases. A systematic search of PubMed, Web of Science, hand-searched publications and historical archives were performed by the professionals involved in this study, to include peer-reviewed articles in which natural food, nutrient content, and its potential relationship with ocular health. Five ophthalmologists and two researchers collected the characteristics, quality and suitability of the above studies. Finally, 177 publications from 1983 to 2021 were enclosed, mainly related to natural food, Mediterranean diet (MedDiet) and nutraceutic supplementation. For the first time, original studies with broccoli and tigernut (chufa de Valencia) regarding the ocular surface dysfunction, macular degeneration, diabetic retinopathy and glaucoma were enclosed. These can add value to the diet, counteract nutritional defects, and help in the early stages, as well as in the course of ophthalmic pathologies. The main purpose of this review, enclosed in the Special Issue "Health Benefits and Nutritional Quality of Fruits, Nuts and Vegetables," is to identify directions for further research on the role of diet and nutrition in the eyes and vision, and the potential antioxidant, anti-inflammatory and neuroprotective effects of natural food (broccoli, saffron, tigernuts and walnuts), the Mediterranean Diet, and nutraceutic supplements that may supply a promising and highly affordable scenario for patients at risk of vision loss. This review work was designed and carried out by a multidisciplinary group involved in ophthalmology and ophthalmic research and especially in nutritional ophthalmology.

Ultra-thin, high strength, antibiotic-eluting sutures for prevention of ophthalmic infection. - Parikh, Kunal S; Omiadze, Revaz; Josyula, Aditya; Shi, Richard; Anders, Nicole M; He, Ping; Yazdi, Youseph; McDonnell, Peter J; Ensign, Laura M; Hanes, Justin (Bioengineering & translational medicine, 2021)
Sutures are applied almost universally at the site of trauma or surgery, making them an ideal platform to modulate the local, postoperative biological response, and improve surgical outcomes. To date, the only globally marketed drug-eluting sutures are coated with triclosan for antibacterial application in general surgery. Loading drug directly into the suture rather than coating the surface offers the potential to provide drug delivery functionality to microsurgical sutures and achieve sustained drug delivery without increasing suture thickness. However, conventional methods for drug incorporation directly into the suture adversely affect breaking strength. Thus, there are no market offerings for drug-eluting sutures, drug-coated, or otherwise, in ophthalmology, where very thin sutures are required. Sutures themselves help facilitate bacterial infection, and antibiotic eye drops are commonly prescribed to prevent infection after ocular surgeries. An antibiotic-eluting suture may prevent bacterial colonization of sutures and preclude patient compliance issues with eye drops. We report twisting of hundreds of individual drug-loaded, electrospun nanofibers into a single, ultra-thin, multifilament suture capable of meeting both size and strength requirements for microsurgical ocular procedures. Nanofiber-based polycaprolactone sutures demonstrated no loss in strength with loading of 8% levofloxacin, unlike monofilament sutures which lost more than 50% strength. Moreover, nanofiber-based sutures retained strength with loading of a broad range of drugs, provided antibiotic delivery for 30 days in rat eyes, and prevented ocular infection in a rat model of bacterial keratitis. Copyright © 2020 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers.

Case Report: Clinical Remission in a Cat With Severe Bilateral Eosinophilic Keratitis Receiving Combined Immunosuppressive Therapy (Triamcinolone Acetonide and Tacrolimus). - Romaneck, Amanda K; Sebbag, Lionel (Frontiers in veterinary science, 2021)
A 2-year-old domestic shorthair cat was examined for severe keratitis of 10 months duration, non-responsive to 0.1% dexamethasone q8-12h. Patient and owner compliance were poor given ocular discomfort and hiding behavior. On presentation, both eyes (OU) had severe ulcerative keratitis that masked examination of deeper structures and resulted in absent menace response OU. Corneal cytology was consistent with eosinophilic keratitis (EK) OU. Initial therapy included subcutaneous triamcinolone acetonide injection (0.2 mg/kg), 0.3% ciprofloxacin OU q12h, and two compounded drugs started 5 days later upon receipt: 0.5% tacrolimus OU q6h, 0.5% cidofovir OU q12h. Visual behavior and ocular comfort were reportedly much improved within 24 h. At the first recheck (Day 11), patient and owner compliance were reported to be excellent, menace response was positive OU, and keratitis was dramatically reduced OU with absent fluorescein uptake. Subcutaneous triamcinolone acetonide was repeated (0.2 mg/kg), ciprofloxacin was discontinued, cidofovir was continued q12h, and tacrolimus was slowly tapered (q8h x 3 weeks then q12h). Keratitis was nearly 100% resolved at the second recheck (Day 38); cidofovir was discontinued and tacrolimus was slowly tapered (q12h x 1 week, q24h x 4 weeks, q48h x 4 weeks) then discontinued. A third recheck (Day 101) confirmed clinical remission OU, and disease did not reoccur within a 1 year follow up period (photographic documentation by owner). In sum, adjunct use of triamcinolone acetonide greatly improved therapeutic compliance and helped control severe EK in a rapid and effective manner. Copyright © 2021 Romaneck and Sebbag.

Computational Methods for Continuous Eye-Tracking Perimetry Based on Spatio-Temporal Integration and a Deep Recurrent Neural Network. - Grillini, Alessandro; Hernandez-Garcia, Alex; Renken, Remco J; Demaria, Giorgia; Cornelissen, Frans W (Frontiers in neuroscience, 2021)
The measurement of retinal sensitivity at different visual field locations-perimetry-is a fundamental procedure in ophthalmology. The most common technique for this scope, the Standard Automated Perimetry, suffers from several issues that make it less suitable to test specific clinical populations: it can be tedious, it requires motor manual feedback, and requires from the patient high levels of compliance. Previous studies attempted to create user-friendlier alternatives to Standard Automated Perimetry by employing eye movements reaction times as a substitute for manual responses while keeping the fixed-grid stimuli presentation typical of Standard Automated Perimetry. This approach, however, does not take advantage of the high spatial and temporal resolution enabled by the use of eye-tracking. In this study, we introduce a novel eye-tracking method to perform high-resolution perimetry. This method is based on the continuous gaze-tracking of a stimulus moving along a pseudo-random walk interleaved with saccadic jumps. We then propose two computational methods to obtain visual field maps from the continuous gaze-tracking data: the first is based on the spatio-temporal integration of ocular positional deviations using the threshold free cluster enhancement (TFCE) algorithm; the second is based on using simulated visual field defects to train a deep recurrent neural network (RNN). These two methods have complementary qualities: the TFCE is neurophysiologically plausible and its output significantly correlates with Standard Automated Perimetry performed with the Humphrey Field Analyzer, while the RNN accuracy significantly outperformed the TFCE in reconstructing the simulated scotomas but did not translate as well to the clinical data from glaucoma patients. While both of these methods require further optimization, they show the potential for a more patient-friendly alternative to Standard Automated Perimetry. Copyright © 2021 Grillini, Hernandez-Garcia, Renken, Demaria and Cornelissen.

Voriconazole in the successful management of a case of Acanthamoeba-Cladosporium keratitis. - Raghavan, Anita; Nair, Arjun Velayudhan; N, Kavitha; Venkatapathy, Narendran; Rammohan, Ram (American journal of ophthalmology case reports, 2021)
Purpose: Acanthamoeba and fungal infections can be recalcitrant to therapy - more so when the deeper layers of the corneas are involved. We describe the diagnosis and successful management strategies employed in a case of deep keratitis due to co-infection with Acanthamoeba and Cladosporium sp., Observations: Once the diagnosis of co-infection with both Acanthamoeba and Cladosporium was made, treatment was initiated with a combination of PHMB, chlorhexidine, natamycin, and voriconazole; to which the response was favorable. Signs of relapse with spread of the infection to the deeper plane and the presence of endothelial exudates were noted at 5 weeks. This was attributed to poor compliance. Though the response to re-initiation of therapy under direct supervision was once again favorable; it was only after the introduction of intrastromal voriconazole repeated at timely intervals that rapid and complete resolution was obtained., Conclusions: Severe keratitis due to fungi or Acanthamoeba very often requires surgical intervention. Complete resolution with medical therapy was obtained only after the introduction of intrastromal voriconazole; thereby avoiding a therapeutic keratoplasty. The addition of voriconzole both topically and particularly intrastromally facilitated faster resolution as well as restricted the duration of therapy with more toxic drugs such as phmb and chlorhexidine. Copyright © 2021 The Authors.

Smarce1 and Tensin 4 Are Putative Modulators of Corneoscleral Stiffness. - Boazak, Elizabeth M; King, Rebecca; Wang, Jiaxing; Chu, Cassandra M; Toporek, Aaron M; Sherwood, Joseph M; Overby, Darryl R; Geisert, Eldon E; Ethier, C Ross (Frontiers in bioengineering and biotechnology, 2021)
The biomechanical properties of the cornea and sclera are important in the onset and progression of multiple ocular pathologies and vary substantially between individuals, yet the source of this variation remains unknown. Here we identify genes putatively regulating corneoscleral biomechanical tissue properties by conducting high-fidelity ocular compliance measurements across the BXD recombinant inbred mouse set and performing quantitative trait analysis. We find seven cis-eQTLs and non-synonymous SNPs associating with ocular compliance, and show by RT-qPCR and immunolabeling that only two of the candidate genes, Smarce1 and Tns4, showed significant expression in corneal and scleral tissues. Both have mechanistic potential to influence the development and/or regulation of tissue material properties. This work motivates further study of Smarce1 and Tns4 for their role(s) in ocular pathology involving the corneoscleral envelope as well as the development of novel mouse models of ocular pathophysiology, such as myopia and glaucoma. Copyright © 2021 Boazak, King, Wang, Chu, Toporek, Sherwood, Overby, Geisert and Ethier.

Potential of Stimuli-Responsive In Situ Gel System for Sustained Ocular Drug Delivery: Recent Progress and Contemporary Research. - Pandey, Manisha; Choudhury, Hira; Binti Abd Aziz, Azila; Bhattamisra, Subrat Kumar; Gorain, Bapi; Su, Jocelyn Sziou Ting; Tan, Choo Leey; Chin, Woon Yee; Yip, Khar Yee (Polymers, 2021)
Eyesight is one of the most well-deserved blessings, amid all the five senses in the human body. It captures the raw signals from the outside world to create detailed visual images, granting the ability to witness and gain knowledge about the world. Eyes are exposed directly to the external environment; they are susceptible to the vicissitudes of diseases. The World Health Organization has predicted that the number of individuals affected by eye diseases will rise enormously in the next decades. However, the physical barriers of the eyes and the problems associated with conventional ocular formulations are significant challenges in ophthalmic drug development. This has generated the demand for a sustained ocular drug delivery system, which serves to deliver effective drug concentration at a reduced frequency for consistent therapeutic effect and better patient treatment adherence. Recent advancement in pharmaceutical dosage design has demonstrated that a stimuli-responsive in situ gel system exhibits the favorable characteristics for providing sustained ocular drug delivery and enhanced ocular bioavailability. Stimuli-responsive in situ gels undergo a phase transition (solution-gelation) in response to the ocular environmental temperature, pH, and ions. These stimuli transform the formulation into a gel at the cul de sac to overcome the shortcomings of conventional eye drops, such as rapid nasolacrimal drainage and short contact time with the ocular surface This review highlights the recent successful research outcomes of stimuli-responsive in situ gelling systems in treating in vivo models with glaucoma and various ocular infections. Additionally, it also presents the mechanism, recent development, and safety considerations of stimuli-sensitive in situ gel as the potential sustained ocular delivery system for treating common eye disorders.

Patterns and Facilitators for the Promotion of Glaucoma Medication Adherence-A Qualitative Study. - Frech, Stefanie; Guthoff, Rudolf F; Gamael, Amin; Helbig, Christian; Diener, Annette; Ritzke, Manuela; Wollny, Anja; Altiner, Attila (Healthcare (Basel, Switzerland), 2021)
Primary open-angle glaucoma (POAG) is a chronic optic neuropathy causing irreversible nerve fiber damage. Initially asymptomatic, it progresses slowly without any notable sign of vision loss, thus early detection and treatment is essential. The standard treatment being non-invasive topical administration of eye drops harbors the problem of patients not being adherent. This study aimed to explore the experiences and thoughts of glaucoma patients about their medication management to improve our knowledge on how adherence works for the individual patient. Narrative interviews were conducted with 21 glaucoma patients. Data were analyzed using inductive content analysis and the documentary method. Different patterns of adherence were identified which depended on personal biographies, living conditions, or the patient's knowledge about the disease. Interpreting eye drop medication as a ritual, a task, or routine was helpful for some patients, whereas other patients, who were aware of the consequences of not taking the drops, were motivated by intrinsic or extrinsic factors. The patterns identified here represent strategies for managing and adhering to daily glaucoma medication at an individual level. Linking daily drop application or medication intake to these patterns may help to promote correct medication management of patients with chronic diseases who lack a regular medication regimen.

Contact Lens Use Patterns, Behavior and Knowledge Among University Students in Thailand. - Supiyaphun, Chantaka; Jongkhajornpong, Passara (Clinical ophthalmology (Auckland, N.Z.), 2021)
Purpose: Little is known about contact lens (CL) use in young generation. This study aimed to investigate the patterns, behavior and knowledge of CL wear and care in Thai university students., Methods: A cross-sectional study using online questionnaires was conducted during July 2019 to February 2020 in two Rajabhat universities, Bangkok, Thailand. Participant characteristics, CL information, knowledge and behaviors were collected. Factors associated with poor behaviors and CL-related corneal ulcers were analyzed using logistic regression., Results: Of 493 students participating in the survey, 336 students (66.78%) were current CL users and completed the questionnaires. Mean age was 19.2 +/- 1.4 years with female predominance (80.36%). All students wore soft CL with a major replacement schedule of monthly disposable (90.18%). Good CL wear and care behaviors were found in 190 students (56.55%). The most common poor CL behavior and poor CL knowledge were CL overuse (44.64%) and sleeping with lenses (31.85%), respectively. There were no correlations between behaviors and knowledge (r = 0.03). Purchasing lens from internet, wearing experience over one year, and long wear duration (> 12 hours) were significantly associated with poor CL behavior. Male gender and swimming with lens were significantly associated with history of corneal ulcers., Conclusion: The study pointed out a low compliance of CL wear and care in Thai university students. Good CL practices, awareness of CL-related complications and purchasing place should be carefully informed and regularly stressed to minimize preventable visual damage in young population. Copyright © 2021 Supiyaphun and Jongkhajornpong.

Medical History, Clinical Features, Treatment Outcome and Its Predictors Among Infectious Keratitis Patients in Jimma University Medical Center, Southwest Ethiopia: Prospective Observational Study. - Dago, Tolcha Regasa; Woldemichael, Dagmawit Kifle; Daba, Fekede Bekele (Clinical ophthalmology (Auckland, N.Z.), 2021)
Background: Infectious keratitis is a major global cause of visual impairment and irreversible blindness among the corneal diseases. Its diagnosis and management remain getting challenge. The clinical and visual outcome remains poor in developing countries. The aim of this study was to determine treatment outcome and its predictors among patients with infectious keratitis., Methods: Prospective observational study was conducted among adult patients diagnosed with infectious keratitis at the Ophthalmology Department in Jimma University Medical Center from April 1 to September 30, 2019. The primary outcome indicator was response of the ulcer to empirical treatment. Ulcers that did not heal and required surgery had a poor outcome. Variables with a p-value of <0.25 were entered into a multivariate logistic regression model to determine the independent predictors of poor treatment outcome and variables with a p-value of <0.05 were considered statistically significant., Results: The research involved 131 adult patients. Eighty-seven (66.4%) were males. The mean age was 39.38 (+/-18.9) years. Eighty-three (63.4%) patients had poor treatment outcome. Mean length of hospital stay was 17.38 (+/-12.563) days. Poor visual outcome was observed among 71 (54.2%) participants. Evisceration was done for seven (5.3%) patients. Independent predictors of poor treatment outcome include perforation at admission (AOR=6.1, 95%CI: 1.5-25.1), presence of comorbidity (AOR=7.7, 95%CI: 2.16-27.3), poor adherence (AOR=5.3, 95%CI: 1.8-25.9), traditional medicine use (AOR=6.7, 95%CI: 1.8-25.4), ulcer depth >1/3 (AOR=7.6, 95%CI: 2.48-48.23) and farm workers (AOR=3.59, 95%CI: 1.09-11.77). Major complications occurred after admissions were perforation (14.5%), followed by endophthalmitis (7.63%) and corneal opacity (6.87%)., Conclusion and Recommendation: Our study found high poor treatment outcomes and high poor visual outcomes. Presence of comorbidity, perforation at admission, traditional medicine use, working on a farm, poor adherence, and ulcer depth were the predictors of poor treatment outcome. This high poor outcome requires a nationwide interventional study and urgent intervention that may reach rural communities. Copyright © 2021 Dago et al.

Nanosponge-Mediated Drug Delivery Lowers Intraocular Pressure. - Lambert, Wendi S; Carlson, Brian J; van der Ende, Alice E; Shih, Grace; Dobish, Julia N; Calkins, David J; Harth, Eva (Translational vision science & technology, 2015)
PURPOSE: We examined the efficacy of an extended-release drug delivery system, nanosponge (NS) encapsulated compounds, administered intravitreally to lower intraocular pressure (IOP) in mice., METHODS: Bilateral ocular hypertension was induced in mice by injecting microbeads into the anterior chamber. Hypertensive mice received NS loaded with ocular hypotensive drugs via intravitreal injection and IOP was monitored. Retinal deposition and retinal ganglion cell (RGC) uptake of Neuro-DiO were examined following intravitreal injection of Neuro-DiO-NS using confocal microscopy., RESULTS: Brimonidine-loaded NS lowered IOP 12% to 30% for up to 6 days (P < 0.02), whereas travoprost-NS lowered IOP 19% to 29% for up to 4 days (P < 0.02) compared to saline injection. Three bimatoprost NS were tested: a 400-nm NS and two 700-nm NS with amorphous (A-NS) or amorphous/crystalline (AC-NS) crosslinkers. A single injection of 400 nm NS lowered IOP 24% to 33% for up to 17 days compared to saline, while A-NS and AC-NS lowered IOP 22% to 32% and 18% to 26%, respectively, for up to 32 days (P < 0.046). Over time retinal deposition of Neuro-DiO increased from 19% to 71%; Neuro-DiO released from NS was internalized by RGCs., CONCLUSIONS: A single injection of NS can effectively deliver ocular hypotensive drugs in a linear and continuous manner for up to 32 days. Also, NS may be effective at targeting RGCs, the neurons that degenerate in glaucoma., TRANSLATIONAL RELEVANCE: Patient compliance is a major issue in glaucoma. The use of NS to deliver a controlled, sustained release of therapeutics could drastically reduce the number of patients that progress to vision loss in this disease.

Real-World Study on Patient Satisfaction and Tolerability After Switching to Preservative-Free Latanoprost. - Erb, Carl; Stalmans, Ingeborg; Iliev, Milko; Munoz-Negrete, Francisco Jose (Clinical ophthalmology (Auckland, N.Z.), 2021)
Purpose: Patient satisfaction is important in the treatment of glaucoma. Suboptimal compliance and impaired long-term outcome are a likely result of poor tolerability. The present multicentre, international, transverse, epidemiological survey was conducted to assess the satisfaction of patients who had received preservative-free latanoprost (PFL) for at least 3 months., Patients and Methods: A total of 1872 patients from 6 European countries, treated with PFL for at least 3 months, were included in this survey. Prior to PFL treatment, patients were to be treatment naive or currently treated for their glaucoma. During a single routine consultation, patients completed a questionnaire concerning global satisfaction and satisfaction based on tolerability., Results: In total, 76.2% had been previously treated; 69.4% had received preserved and 6.8% preservative-free (PF) topical treatment. After 3 months of PFL treatment, a large majority of patients (95.3%) were satisfied or very satisfied with their PFL treatment and were, overall, significantly (p<0.0001) more satisfied with PFL than with their previous treatment; 4.2% were either unsatisfied or very unsatisfied. Overall, 97.3% of originally treatment-naive patients were satisfied (50.1%) or very satisfied (47.2%) with their PFL. Ocular surface disease was diagnosed in 9.2% of patients (n=173) and was mainly mild (76.9%). Patient satisfaction with PFL was very high., Conclusion: PFL may be considered a valuable first-choice treatment in glaucoma patients. Copyright © 2021 Erb et al.

The role of gap junctions in cell death and neuromodulation in the retina. - Szarka, Gergely; Balogh, Marton; Tengolics, Adam J; Ganczer, Alma; Volgyi, Bela; Kovacs-Oller, Tamas (Neural regeneration research, 2021)
Vision altering diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, myopia, retinal vascular disease, traumatic brain injuries and others cripple many lives and are projected to continue to cause anguish in the foreseeable future. Gap junctions serve as an emerging target for neuromodulation and possible regeneration as they directly connect healthy and/or diseased cells, thereby playing a crucial role in pathophysiology. Since they are permeable for macromolecules, able to cross the cellular barriers, they show duality in illness as a cause and as a therapeutic target. In this review, we take recent advancements in gap junction neuromodulation (pharmacological blockade, gene therapy, electrical and light stimulation) into account, to show the gap junction's role in neuronal cell death and the possible routes of rescuing neuronal and glial cells in the retina succeeding illness or injury.

Evaluating Alternate Methods of Determining the Antimicrobial Efficacy of Contact Lens Care Products against Acanthamoeba Trophozoites. - Campolo, Allison; Shannon, Paul; Crary, Monica (Pathogens (Basel, Switzerland), 2021)
Acanthamoeba keratitis (AK) is a serious ocular infection caused by a ubiquitous free-living amoeba, Acanthamoeba. This infection often results in extensive corneal damage and blindness, and is notoriously difficult to cure. While Acanthamoeba is an abundant organism, AK is most associated with contact lens hygiene noncompliance and inadequate contact lens care (CLC) disinfection regimens. Thus, accurate and timely antimicrobial efficacy testing of CLC solutions is paramount. Published methods for antimicrobial efficacy testing of Acanthamoeba trophozoites requires 14 days for results. Presently, alternate and/or rapid methods for evaluating CLC products rarely demonstrate equivalent results compared to commonly-reported methods. Propidium iodide is a cellular stain that can only bind to cells with damaged outer membranes. We evaluated propidium iodide staining as an alternative method for determining the relative antimicrobial efficacy of 11 different CLC products against Acanthamoeba trophozoites. Following exposure to a CLC product, the fluorescence intensity of propidium iodide in an Acanthamoeba population demonstrated a strong correlation to the log reduction determined by established, growth-based Acanthamoeba testing used to evaluate the antimicrobial efficacy of CLC products. Thus, propidium iodide was found to be an effective rapid tool for determining cell death in Acanthamoeba trophozoites following exposure to CLC solutions.

Therapeutic Ophthalmic Lenses: A Review. - Toffoletto, N; Saramago, B; Serro, A P (Pharmaceutics, 2020)
An increasing incidence of eye diseases has been registered in the last decades in developed countries due to the ageing of population, changes in lifestyle, environmental factors, and the presence of concomitant medical conditions. The increase of public awareness on ocular conditions leads to an early diagnosis and treatment, as well as an increased demand for more effective and minimally invasive solutions for the treatment of both the anterior and posterior segments of the eye. Despite being the most common route of ophthalmic drug administration, eye drops are associated with compliance issues, drug wastage by lacrimation, and low bioavailability due to the ocular barriers. In order to overcome these problems, the design of drug-eluting ophthalmic lenses constitutes a non-invasive and patient-friendly approach for the sustained drug delivery to the eye. Several examples of therapeutic contact lenses and intraocular lenses have been developed, by means of different strategies of drug loading, leading to promising results. This review aims to report the recent advances in the development of therapeutic ophthalmic lenses for the treatment and/or prophylaxis of eye pathologies (i.e., glaucoma, cataract, corneal diseases, or posterior segment diseases) and it gives an overview of the future perspectives and challenges in the field.

Effect of Intranasal Corticosteroids on Intraocular Pressure and Nerve Fiber Layer Thickness: A Cross-Sectional Study at a Tertiary Care Hospital in Western Saudi Arabia. - Marzouki, Hani Z; AlThomali, Rahaf K Jr; Hefni, Lujain; Almarzouki, Nawaf; Alhejaili, Faris; Merdad, Mazin; Zawawi, Faisal; Alkhatib, Talal (Cureus, 2021)
Background Rhinitis represents a global health problem, affecting 10%-20% of the population in Saudi Arabia. Topical intranasal corticosteroids (INCS) are widely used by otolaryngologists to treat patients with rhinitis for long periods. Although the effects of orally administered corticosteroids on intraocular pressure (IOP) and lens opacity are well established, the impact of INCS is not well defined. In the present study, we aimed to assess the effect of using INCS on IOP over a six-month period in patients with rhinitis. Methodology In this study, a questionnaire was distributed to 93 patients diagnosed with rhinitis in the Ear, Nose, and Throat Clinic of King Abdulaziz University Hospital, Saudi Arabia, between February and July 2019. Thereafter, each patient was evaluated in the Ophthalmology Clinic with optical coherence tomography of the optic nerve using Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA, USA) optic disc scans, visual acuity testing, and Goldmann applanation tonometry. Pearson correlation coefficients and two-tailed tests of significance were used to assess the relationships between variables. Results All 93 patients were using a dose of two puffs at least twice daily for each nostril. Their IOPs, as depicted by Goldman applanation tonometry, were found to be within normal limits. Retinal nerve fiber layer thickness was also found to be normal in 95% of the participants. Conclusions Our study showed no correlation between INCS and IOP. As an increase in IOP can lead to glaucoma, our data demonstrate the safety profile of INCS use. For patients with rhinitis, this finding could change compliance to medication and reduce the burden of the disease. Copyright © 2021, Marzouki et al.

The role of Piezo1 in conventional aqueous humor outflow dynamics. - Zhu, Wei; Hou, Fei; Fang, Jingwang; Bahrani Fard, Mohammad Reza; Liu, Yani; Ren, Shouyan; Wu, Shen; Qi, Yunkun; Sui, Shangru; Read, A Thomas; Sherwood, Joseph M; Zou, Wei; et al. (iScience, 2021)
Controlling intraocular pressure (IOP) remains the mainstay of glaucoma therapy. The trabecular meshwork (TM), the key tissue responsible for aqueous humor (AH) outflow and IOP maintenance, is very sensitive to mechanical forces. However, it is not understood whether Piezo channels, very sensitive mechanosensors, functionally influence AH outflow. Here, we characterize the role of Piezo1 in conventional AH outflow. Immunostaining and western blot analysis showed that Piezo1 is widely expressed by TM. Patch-clamp recordings in TM cells confirmed the activation of Piezo1-derived mechanosensitive currents. Importantly, the antagonist GsMTx4 for mechanosensitive channels significantly decreased steady-state facility, yet activation of Piezo1 by the specific agonist Yoda1 did not lead to a facility change. Furthermore, GsMTx4, but not Yoda1, caused a significant increase in ocular compliance, a measure of the eye's transient response to IOP perturbation. Our findings demonstrate a potential role for Piezo1 in conventional outflow, likely under pathological and rapid transient conditions. Copyright © 2021 The Authors.

Drug-Free, Nonsurgical Reduction of Intraocular Pressure for Four Months after Suprachoroidal Injection of Hyaluronic Acid Hydrogel. - Chae, J Jeremy; Jung, Jae Hwan; Zhu, Wei; Gerberich, Brandon G; Bahrani Fard, Mohammad Reza; Grossniklaus, Hans E; Ethier, C Ross; Prausnitz, Mark R (Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2021)
Glaucoma is the leading cause of irreversible blindness. Current treatments use drugs or surgery to reduce intraocular pressure (IOP). In this study, a drug-free, nonsurgical method is developed that lowers IOP for 4 months without requiring daily patient adherence. The approach involves expanding the suprachoroidal space (SCS) of the eye with an in situ-forming hydrogel injected using a microneedle. This study tests the hypothesis that SCS expansion increases the drainage of aqueous humor from the eye via the unconventional pathway, which thereby lowers IOP. SCS injection of a commercial hyaluronic acid (HA) hydrogel reduces the IOP of normotensive rabbits for more than 1 month and an optimized HA hydrogel formulation enables IOP reduction for 4 months. Safety assessment by clinical ophthalmic examinations indicate the treatment is well tolerated. Histopathology shows minor hemorrhage and fibrosis at the site of injection. Further analysis by ultrasound biomicroscopy demonstrates a strong correlation of IOP reduction with SCS expansion. Outflow facility measurements show no difference in pressure-dependent outflow by the conventional pathway between treated and untreated eyes, supporting the hypothesis. In conclusion, SCS expansion with an in situ-forming hydrogel can enable extended IOP reduction for treating ocular hypertension and glaucoma without drugs or surgery. Copyright © 2020 The Authors. Published by Wiley-VCH GmbH.

Novel Drug Delivery Systems Fighting Glaucoma: Formulation Obstacles and Solutions. - Rahic, Ognjenka; Tucak, Amina; Omerovic, Naida; Sirbubalo, Merima; Hindija, Lamija; Hadziabdic, Jasmina; Vranic, Edina (Pharmaceutics, 2020)
Glaucoma is considered to be one of the biggest health problems in the world. It is the main cause of preventable blindness due to its asymptomatic nature in the early stages on the one hand and patients' non-adherence on the other. There are several approaches in glaucoma treatment, whereby this has to be individually designed for each patient. The first-line treatment is medication therapy. However, taking into account numerous disadvantages of conventional ophthalmic dosage forms, intensive work has been carried out on the development of novel drug delivery systems for glaucoma. This review aims to provide an overview of formulation solutions and strategies in the development of in situ gel systems, nanosystems, ocular inserts, contact lenses, collagen corneal shields, ocular implants, microneedles, and iontophoretic devices. The results of studies confirming the effectiveness of the aforementioned drug delivery systems were also briefly presented.

Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation. - Pandey, Manisha; Choudhury, Hira; Abdul-Aziz, Azila; Bhattamisra, Subrat Kumar; Gorain, Bapi; Su, Jocelyn Sziou Ting; Tan, Choo Leey; Chin, Woon Yee; Yip, Khar Yee (Pharmaceutics, 2020)
The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs' poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended.

Sustained-release drug delivery systems for the treatment of glaucoma. - Kesav, Natasha P; Young, Cara E Capitena; Ertel, Monica K; Seibold, Leonard K; Kahook, Malik Y (International journal of ophthalmology, 2021)
Glaucoma, a leading cause of irreversible blindness, affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection. Although topical therapies are often effective when used as prescribed, the drawbacks of current medical management methods include poor patient adherence, local and systemic side effects, and in some cases, limited therapeutic efficacy. Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration. Several platforms are in various stages of development with promising pre-clinical and clinical data. The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020, making it the first long-term injectable therapy available for the treatment of glaucoma. This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years. Copyright International Journal of Ophthalmology Press.

A Mussel-Inspired Facile Method to Prepare Multilayer-AgNP-Loaded Contact Lens for Early Treatment of Bacterial and Fungal Keratitis. - Liu, Xiaoqi; Chen, Jiang; Qu, Chao; Bo, Gong; Jiang, Lang; Zhao, Hui; Zhang, Jing; Lin, Yin; Hua, Yu; Yang, Ping; Huang, Nan; Yang, Zhenglin (ACS biomaterials science & engineering, 2018)
The use of contact lenses for the early treatment of bacterial or fungal keratitis has become a new research focus. Two main requirements of the therapeutic contact lenses are antimicrobial ability and visible light transmittance. Silver nanoparticles (AgNPs), as a nonspecific antimicrobial component, have been loaded onto contact lenses for the treatment of bacterial and fungal keratitis. Recently, it was reported that, via a simple immersion method, AgNPs can be synthesized and fixed onto the surface of polydopamine (PDA)-coated materials. However, in this study, we found that the above traditional method has the disadvantages of poor AgNP loading and low visible light transmittance, which could be induced by a limited amount of phenolic hydroxyl groups on and second oxidation of the PDA coating, respectively. To overcome these disadvantages, in this paper, we provided a facile and novel method to robustly bind multilayer-AgNPs on contact lens surfaces by using dopamine as a reducing agent and bioglue. In comparing with the monolayer-AgNP-loaded contact lenses fabricated by the traditional method, the multilayer-AgNP-loaded contact lenses had excellent antimicrobial ability and better visible light transmittance. Moreover, the multilayer-AgNP-loaded contact lens had low cytotoxicity to human corneal epithelial cells and anti-inflammation properties. Furthermore, the shortcoming of decreasing visible light transmittance induced by excess adherence of AgNPs on the multilayer-AgNP-loaded contact lens was alleviated by decreasing the size of AgNPs through altering the concentration of dopamine and AgNO3. Contact lenses loaded with small AgNPs (Ag@PDA-2.5, diameter = 25-50 nm) had approximately the same Ag+ release and antimicrobial abilities, but significantly better visible light transmittance and anti-inflammatory properties than the contact lenses loaded with large AgNPs (Ag@PDA-5, diameter = 50-75 nm). After that, in vivo testing indicated the promising therapeutic strategy of multilayer-AgNP-loaded contact lenses (Ag@PDA-2.5) for early bacterial keratitis and fungal keratitis. In addition, PDA coating could provide reactive sites to immobilize other biomolecules or drugs on this multilayer-AgNP-loaded contact lens for further combination therapies in treating bacterial or fungal keratitis. Finally, the stability of the visible light transmittance of the multilayer-AgNP-loaded contact lens was detected. The visible light transmittance of Ag@PDA-2.5 was weakened after being cultured with an extremely high concentration of bacteria, while it was stable in the moderate work environment. Though PDA coating had been wildly used to modify implantation devices, however, few studies about PDA coating modified contact lenses have been reported so far. Therefore, this research also provides an important basis for using PDA coating to modify a therapeutic contact lens.

Collagen-Based Artificial Corneal Scaffold with Anti-Infective Capability for Prevention of Perioperative Bacterial Infections. - Riau, Andri K; Mondal, Debasish; Aung, Thet T; Murugan, Elavazhagan; Chen, Liyan; Lwin, Nyein C; Zhou, Lei; Beuerman, Roger W; Liedberg, Bo; Venkatraman, Subbu S; Mehta, Jodhbir S (ACS biomaterials science & engineering, 2015)
Bacterial infection following implantation of an artificial corneal scaffold is a serious complication. Conventional antibiotic prophylaxis, which includes topical vancomycin application, is limited by low bioavailability, high dosing requirement, and poor patient compliance. The ideal option to overcome these issues is an antibiotic-eluting corneal prosthesis that sustains the local release of drug. In this study, we incorporated vancomycin in thick 15% collagen hydrogels to create an artificial corneal scaffold with anti-infective capability. The incorporation of vancomycin did not significantly alter the Young's modulus, transparency and refractive index of the vancomycin-loaded hydrogel (VH), which were 0.79 +/- 0.04 MPa (p = 0.233 compared to blank hydrogel), 94.3 +/- 2.3% (p = 0.115) and 1.346 +/- 0.005 (p = 0.264), respectively. In vitro, the drug elution was sustained for up to 7 days. The VH was subsequently implanted intrastromally in rabbit corneas, replacing stromal tissue that was removed following femtosecond laser-assisted small incision lenticule extraction procedure. In vivo, the vancomcyin could be detected in the aqueous humor for up to 10 days. We then created a corneal infectious keratitis model by intrastromal injection of 1 x 108 CFU/ml of Staphylococcus aureus inoculate on day 2 postimplantation. On day 3 postinfection, the VH-implanted corneas were clear and nonedematous and showed a substantial reduction of log 2.5 in S. aureus compared to the blank hydrogel-implanted corneas, which appeared hazy, edematous, and had excessive inflammation. Immunohistochemistry of inflammatory marker, CD18, demonstrated a significant reduction in inflammatory cells in VH-implanted corneas (49 +/- 9 cells/unit area) compared to blank hydrogel-implanted corneas (523 +/- 15 cells/unit area) (p < 0.001). In conclusion, we have demonstrated the efficacy of a drug-eluting corneal implant in preventing perioperative bacterial infections.

Open-Angle Glaucoma: Burden of Illness, Current Therapies, and the Management of Nocturnal IOP Variation. - Sheybani, Arsham; Scott, Rachel; Samuelson, Thomas W; Kahook, Malik Y; Bettis, Daniel I; Ahmed, Iqbal Ike K; Stephens, J David; Kent, Delaney; Ferguson, Tanner J; Herndon, Leon W (Ophthalmology and therapy, 2020)
Glaucoma is a chronic, debilitating disease and a leading cause of global blindness. Despite treatment efforts, 10% of patients demonstrate loss of vision. In the US, > 80% of glaucoma cases are classified as open-angle glaucoma (OAG), with primary open-angle (POAG) being the most common. Although there has been tremendous innovation in the surgical treatment of glaucoma as of late, two clinical variants of OAG, normal-tension glaucoma (NTG) and severe POAG, are especially challenging for providers because patients with access to care and excellent treatment options may progress despite achieving a "target" intraocular pressure value. Additionally, recent research has highlighted the importance of nocturnal IOP control in avoiding glaucomatous disease progression. There remains an unmet need for new treatment options that can effectively treat NTG and severe POAG patients, irrespective of baseline IOP, while overcoming adherence limitations of current pharmacotherapies, demonstrating a robust safety profile, and more effectively controlling nocturnal IOP.Funding The Rapid Service Fees were funded by the corresponding author, Tanner J. Ferguson, MD.

Brinzolamide/Brimonidine Fixed Combination: Simplifying Glaucoma Treatment Regimens. - Moosavi, Reza; Ansari, Ejaz (Ophthalmology and therapy, 2018)
INTRODUCTION: To simplify the medical treatment of glaucoma for patients on multiple drops by introducing brinzolamide/brimonidine tartrate fixed combination (BBFC) ophthalmic suspension 1%/0.2% (SIMBRINZA R; Alcon Laboratories, Inc., Fort Worth, TX, USA) to the drop regimen and to establish its efficacy. To demonstrate that fixed combination (FC) therapies are associated with improvements in treatment adherence and persistence with reduced exposure to preservative-related ocular surface problems., METHODS: Retrospective study: 76 patients were identified as taking BBFC following a switch in treatment regimen. Intraocular pressure (IOP) prior to and 2-17.5 months (average 5.4 months) after the introduction of BBFC was measured. The change in the average number of bottles used per eye was recorded. The rate of adverse effects (AEs) of BBFC was recorded. A two-tailed paired sample t test was used to compare IOP prior to and after the introduction of BBFC for each eye., RESULTS: Mean change in IOP after BBFC introduction BBFC: - 2.76 mmHg (p < 0.0001). BBFC intolerance: 13%. On average there was a 0.24 reduction in the number of bottles of IOP-lowering medication used per eye (p < 0.0064)., CONCLUSION: A switch to BBFC in the drop regimen is associated with a significant drop in IOP with reduced drop burden. Instead of a third IOP-lowering medication and bottle, a practitioner should consider using BBFC + prostaglandin analogue/FC drop for effective IOP control, reduced drop burden, reduced preservative load and increased likelihood of adherence. This study promotes the concept that any treatment should principally be assessed from the patients' perspective and quality of life.

A survey of attitudes of glaucoma subspecialists in England and Wales to visual field test intervals in relation to NICE guidelines. - Malik, Rizwan; Baker, Helen; Russell, Richard A; Crabb, David P (BMJ open, 2013)
OBJECTIVES: To establish the attitudes of glaucoma specialists to the frequency of visual field (VF) testing in the UK, using the NICE recommendations as a standard for ideal practice., DESIGN: Interview and postal survey., SETTING: UK and Eire Glaucoma Society national meeting 2011 in Manchester, UK, with a second round of surveys administered by post., PARTICIPANTS: All consultant glaucoma specialists in England and Wales were invited to complete the survey., PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Compliance of assigned follow-up VF intervals with NICE guidelines for three hypothetical patient scenarios, with satisfactory treated intraocular pressure and (a) no evidence of VF progression; (b) evidence of VF progression and (c) uncertainty about VF progression, and respondents were asked to provide typical follow-up intervals representative of their practice; (2) attitudes to research recommendations for six VF in the first 2 years for newly diagnosed patients with glaucoma., RESULTS: 70 glaucoma specialists completed the survey. For each of the clinical scenarios a, b and c, 14 (20%), 33 (47%) and 28 (40%) responses, respectively, fell outside the follow-up interval recommended by NICE. Nearly half of the specialists (46%) agreed that 6 VF tests in the first 2 years was ideal practice, while 16 (28%) said this was practice 'not possible', with many giving resources within the NHS setting as a limiting factor., CONCLUSIONS: The results from this survey suggest that there is a large variation in attitudes to follow-up intervals for patients with glaucoma in the UK, with assigned intervals for VF testing which are, in many cases, inconsistent with the guidelines from NICE.

Patient Centricity and the Ethics of Glaucoma Care. - Bhartiya, Shibal (Journal of current glaucoma practice, 2020)
The ultimate goal of glaucoma therapy, as of any other therapeutic intervention, is to achieve superior clinical outcomes, patient satisfaction, and patient adherence to treatment. In a chronic asymptomatic disease, such as, glaucoma, where diagnostic and therapeutic algorithms may have multiple acceptable treatment arms, patient centricity becomes increasingly important. Shared decision-making, patient participation, quality of life (QoL) concerns, and risk-benefit analyzes further complicate this decision-making. In addition, the ethics of research in glaucoma and also that of glaucoma screening may often be in conflict with the ethics of patient care. This article aims to highlight the ethical dilemmas that confound decision-making in current glaucoma practice, and the doctors' fiduciary duties to the patient. How to cite this article: Bhartiya S. Patient Centricity and the Ethics of Glaucoma Care. J Curr Glaucoma Pract 2020;14(2):68-71. Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.

Biomechanical Modulation Therapy-A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns. - Gouveia, Ricardo M; Connon, Che J (Translational vision science & technology, 2020)
Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed. Copyright 2020 The Authors.

Patients' Experience of Using Eye Drop Guide Device to Aid Self-Administration of Glaucoma Medications. - Sakiyalak, Darin; Kobwanthanakun, Sirinya (Clinical ophthalmology (Auckland, N.Z.), 2020)
Purpose: To determine the characteristics of the patients who preferred using the eye drop guide (EDG) regularly and their opinions toward the guide in order to select the patients for prescribing the EDG appropriately., Patients and Methods: Fifty-seven glaucoma patients who completed the primary study, "The effect of 'eye drop guide' on the success rate of eye drop self-instillation in glaucoma patients", were included. Patients' instillation techniques, routine instillation or using the EDG, were chosen independently. After 4-6 months, they were interviewed about the frequency of EDG use and their rating scores toward the guide in 4 aspects including aiming aids, contamination prevention, reduction of drop waste, and ease of use. The differences in opinion scores between each frequency group and the factors associated with the regularity of EDG use were statistically analyzed., Results: Of fifty-seven patients completing the interview, 19.3% used the EDG everyday, while 45.6% had never used the EDG. The nonusers rated significantly lower scores in all aspects (p-value < 0.005). From multivariate analysis, the factors associated with the preference not to use the EDG were administering in supine position (p-value < 0.001, adjusted OR 34.866, 95% CI 4.974-244.412) and more than one eye drop use (p-value = 0.048, adjusted OR 5.280, 95% CI 1.018-27.396)., Conclusion: The EDG should be selectively prescribed for the particular patients who had one medication and performed instillation in sitting or standing position. Although the regular EDG users tended to have positive opinions on the EDG, their long-term compliance with the guide was underinvestigated. Copyright © 2020 Sakiyalak and Kobwanthanakun.

Panophthalmitis and Orbital Inflammation with Cavernous Sinus Thrombosis Following Cataract Surgery. - Marinos, Emmanuel; McCall, Dominic; Tumuluri, Krishna; Rowe, Neil; Do, Helen (International medical case reports journal, 2020)
Background: Panophthalmitis is a severe inflammation of the globe that can result as a rare complication of ophthalmic surgery. In severe cases, it may also be associated with orbital inflammation and cavernous sinus thrombosis., Purpose: This case demonstrates a rare and life-threatening post-operative complication of cataract surgery. We also hope to highlight the importance of considering the relevant risk factors associated with developing potential infections after cataract surgery, including the use of corneal sutures, high-risk behaviours such as excessive eye-rubbing, and non-compliance with appointments and post-operative medications., Case Report: We report the case of a 35-year-old female with severe autism and developmental delay who developed panophthalmitis, orbital inflammation and cavernous sinus thrombosis 6 weeks post cataract surgery. The likely cause was corneal suture-related microbial keratitis, and the patient required enucleation due to sepsis., Conclusion: Post-surgical panophalmitis is a rapidly progressive disease that is not only sight- but life-threatening and demands urgent and intensive treatment. Consideration of early enucleation may be required to prevent deterioration in such patients. Copyright © 2020 Marinos et al.

Impact of Medication Regimen Simplification on Medication Adherence and Clinical Outcomes in Patients with Long-Term Medical Conditions. - Elnaem, Mohamed Hassan; Irwan, Nor Afifah; Abubakar, Usman; Syed Sulaiman, Syed Azhar; Elrggal, Mahmoud E; Cheema, Ejaz (Patient preference and adherence, 2020)
Background: This study aims to identify interventions used to reduce medication regimen complexity and to assess their impact on medication adherence and clinical outcomes., Methods: A literature search was conducted using pre-defined search terms in three scientific databases, including ScienceDirect, ProQuest and MEDLINE. Original research articles published in English between 2009 and 2020 that assessed the impact of medication regimen simplification on medication adherence in patients with long-term medical conditions were eligible for inclusion. Review articles, meta-analysis studies and conference proceedings were excluded. Data charting was done in an iterative process using a study-specific extraction form., Results: Of the 684 studies identified through initial searches, 17 studies were included in the review. Nine studies involved simplification of medication regimen related to HIV, while three studies focused on patients with diabetes with or without coronary artery disease. The remaining five studies included medications used among elderly patients or medications related to hypertension, psychiatric disorders, glaucoma and kidney diseases. Three medication regimen simplification strategies were identified; fixed-dose combination (n = 7), once-daily dosing (n = 4) and the combination of both fixed-dose and once-daily dosing (n = 6). Overall, most of the regimen simplification strategies (14 out of 17) were found to be useful in improving medication adherence. There was no assessment of clinical outcomes in four out of 17 studies. Furthermore, more than half of the studies that assessed clinical outcomes did not show any additional impact on clinical outcomes., Conclusion: The findings suggest that there was an equal utilization of the three main approaches of regimen simplifications; fixed-dose combination, once-daily dosing and a combination of both. Overall, most of the regimen simplification strategies were found to be effective in improving medication adherence. However, the associated improvement in medication adherence did not extend to improvement in the clinical outcomes. Copyright © 2020 Elnaem et al.

Signs and Symptoms of Ocular Surface Disease: The Reasons for Patient Dissatisfaction with Glaucoma Treatments. - Stalmans, Ingeborg; Lemij, Hans; Clarke, Jonathan; Baudouin, Christophe; GOAL study group (Clinical ophthalmology (Auckland, N.Z.), 2020)
Ocular Surface Disease (OSD) and hyperemia are the most common adverse events of topical ocular medications. While active compounds may cause allergic reactions or irritation, preservatives, which are intended to prevent bacterial growth, are toxic as well. Therefore, the most recent glaucoma medications no longer contain preservatives. Despite this, local tolerability may still impact treatment compliance and patient quality of life. We conducted an observational, multi-center, international, cross-sectional study in 793 treated and stabilized glaucoma patients to assess patient satisfaction and local tolerability of their treatment. The vast majority (93.7%) of patients was satisfied or very satisfied with their treatment in terms of tolerability and only 6.3% were dissatisfied. However, ophthalmological examination showed a high frequency of ocular signs: conjunctival hyperemia (32%), OSD (42.5%) and positive conjunctival fluorescein staining (10.3%). Additionally, patients reported symptoms upon instillation (31.4%) and between instillations (57.3%); 25.1% of patients were using tear substitutes. All signs and symptoms were significantly (p<0.001) associated with patient dissatisfaction. A logistic regression model indicated that dissatisfaction was higher in patients with symptoms upon instillation and in those using tear substitutes (OR: 3.03 and 4.63, respectively). The mean patient tolerability score to treatment was 82.7+/-16.1 on a 100-point visual analogue scale. In conclusion, even if patients may be highly satisfied with their current treatment, most of them present ocular signs and symptoms. A treatment change should be considered in case of clinical signs or patient-reported symptoms. Copyright © 2020 Stalmans et al.

Level of Glaucoma Drug Adherence and Its Associated Factors Among Adult Glaucoma Patients Attending Felege Hiwot Specialized Hospital, Bahir Dar City, Northwest Ethiopia. - Assem, Abel Sinshaw; Fekadu, Sofonias Addis; Yigzaw, Amsal Ambaw; Nigussie, Zelalem Mehari; Achamyeleh, Anemaw Asrat (Clinical optometry, 2020)
Background: Glaucoma is a chronic optic nerve disease, often asymptomatic in an early stage, which is usually associated with elevated intraocular pressure. Good adherence to ocular hypotensive agents is essential to control the intraocular pressure and optic nerve damage. There is limited information on glaucoma drug adherence and associated factors in Ethiopia, particularly in the study area., Objective: To determine the level of glaucoma drug adherence and associated factors among adult glaucoma patients attending Felege Hiwot Specialized Hospital, Northwest Ethiopia, 2019., Materials and Methods: A hospital-based cross-sectional study was conducted at Felege Hiwot specialized Hospital from March 2019 to May 2019. A systematic random sampling method was used to select 402 study participants. A structured questionnaire was prepared, and adherence was assessed by using self-report questions. The collected data were entered into Epi data version 4.2.2.1 and exported into Statistical Package for Social Science version 23 for analysis. Tables, graphs, frequency, mean, and standard deviation were used for descriptive statistics. Variables with a p-value of <0.2 in the bivariable logistic regression were entered in the multivariable logistic regression, and variables with a p-value of <0.05 under multivariable analysis were taken as statistically significant factors for glaucoma drug adherence., Results: Among a total of 390 study participants, 212 (56.2%) were adherent to their topical medication. Early glaucoma (AOR=2.8: 95% CI =1.29-5.91), normal vision (AOR=1.9: 95% CI=1.15-3.09), urban residence (AOR=1.6: 95% CI=1.03-2.51), family support (AOR=1.7: 95% CI=1.06-2.76) and information from pharmacist (AOR=1.8: 95% CI=1.11-2.99) were significantly associated with adherence., Conclusion: The level of glaucoma drug adherence was 56.2% among patients attending Felege Hiwot Specialized Hospital. Early glaucoma, normal visual acuity, family support, information on medication from the pharmacist, and urban residence were positively associated with adherence. Copyright © 2020 Assem et al.

On the Generation and Regeneration of Retinal Ganglion Cells. - Oliveira-Valenca, Viviane M; Bosco, Alejandra; Vetter, Monica L; Silveira, Mariana S (Frontiers in cell and developmental biology, 2020)
Retinal development follows a conserved neurogenic program in vertebrates to orchestrate the generation of specific cell types from multipotent progenitors in sequential but overlapping waves. In this program, retinal ganglion cells (RGCs) are the first cell type generated. RGCs are the final output neurons of the retina and are essential for vision and circadian rhythm. Key molecular steps have been defined in multiple vertebrate species to regulate competence, specification, and terminal differentiation of this cell type. This involves neuronal-specific transcription factor networks, regulators of chromatin dynamics and miRNAs. In mammals, RGCs and their optic nerve axons undergo neurodegeneration and loss in glaucoma and other optic neuropathies, resulting in irreversible vision loss. The incapacity of RGCs and axons to regenerate reinforces the need for the design of efficient RGC replacement strategies. Here we describe the essential molecular pathways for the differentiation of RGCs in vertebrates, as well as experimental manipulations that extend the competence window for generation of this early cell type from late progenitors. We discuss recent advances in regeneration of retinal neurons in vivo in both mouse and zebrafish and discuss possible strategies and barriers to achieving RGC regeneration as a therapeutic approach for vision restoration in blinding diseases such as glaucoma. Copyright © 2020 Oliveira-Valenca, Bosco, Vetter and Silveira.

Late Spontaneous Reabsorption of Interface Fluid after Descemet's Stripping Automated Endothelial Keratoplasty Surgery. - Romanazzi, Filippo; Morano, Anna; Caccavale, Antonio (Case reports in ophthalmology, 2020)
An 80-year-old male was referred to our hospital for chronic bullous keratopathy in the right eye. Ten years before, he was affected by an attack of primary acute angle closure glaucoma in high hyperopia and Fuchs' endothelial dystrophy. A bilateral iridotomy was performed. Thereafter, the patient developed an endothelial decompensation in the left eye, and, in another hospital, he underwent an open-sky combined cataract extraction and penetrating keratoplasty. Our surgical approach for the right eye consisted of phacoemulsification and, after 1 month, a Descemet's stripping automated endothelial keratoplasty (DSAEK). After the procedure, an interface fluid was suspected, and an anterior segment optical coherence tomography (OCT) confirmed it. The graft was well centered but thickened, showing no movement in the anterior chamber, adherent to the periphery of the recipient cornea but with a pool of fluid in the center. Seven days postoperatively, an anterior segment OCT showed initial signs of reabsorption of the fluid. On day 45, the graft was adherent with normal thickness and the interface fluid had completely disappeared. The corneal stroma was clear, but a faint interface opacity appeared and is still present. We obtained a good surgical result and best corrected visual acuity was 7/10 at postoperative month 4. No further surgical procedures are scheduled. Copyright © 2020 by S. Karger AG, Basel.

Personal hygiene risk factors for contact lens-related microbial keratitis. - Stellwagen, Anna; MacGregor, Cheryl; Kung, Roger; Konstantopoulos, Aristides; Hossain, Parwez (BMJ open ophthalmology, 2020)
Objective: Microbial keratitis is a sight-threatening complication of contact lens wear, which affects thousands of patients and causes a significant burden on healthcare services. This study aims to identify compliance with contact lens care recommendations and identify personal hygiene risk factors in patients who develop contact lens-related microbial keratitis., Methods and analysis: A case-control study was conducted at the University Hospital Southampton Eye Casualty from October to December 2015. Two participant groups were recruited: cases were contact lens wearers presenting with microbial keratitis and controls were contact lens wearers without infection. Participants underwent face-to-face interviews to identify lens wear practices, including lens type, hours of wear, personal hygiene and sleeping and showering in lenses. Univariate and multivariate regression models were used to compare groups., Results: 37 cases and 41 controls were identified. Showering in contact lenses was identified as the greatest risk factor (OR, 3.1; 95% CI, 1.2 to 8.5; p=0.03), with showering daily in lenses compared with never, increasing the risk of microbial keratitis by over seven times (OR, 7.1; 95% CI, 2.1 to 24.6; p=0.002). Other risks included sleeping in lenses (OR, 3.1; 95% CI, 1.1 to 8.6; p=0.026), and being aged 25-39 (OR, 6.38; 95% CI, 1.56 to 26.10; p=0.010) and 40-54 (OR, 4.00; 95% CI 0.96 to 16.61; p=0.056)., Conclusion: The greatest personal hygiene risk factor for contact lens-related microbial keratitis was showering while wearing lenses, with an OR of 3.1, which increased to 7.1 if patients showered daily in lenses. The OR for sleeping in lenses was 3.1, and the most at-risk age group was 25-54. Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Imprinted Contact Lenses for Ocular Administration of Antiviral Drugs. - Varela-Garcia, Angela; Gomez-Amoza, Jose Luis; Concheiro, Angel; Alvarez-Lorenzo, Carmen (Polymers, 2020)
A variety of ocular diseases are caused by viruses, and most treatments rely on the use of systemic formulations and eye drops. The efficient ocular barriers that oppose antiviral drug penetration have prompted the development of improved topical delivery platforms. The aim was to design hydrogel contact lenses endowed with an affinity for acyclovir (ACV) and its prodrug valacyclovir (VACV), first-choice drugs against herpes simplex virus (HSV) ocular keratitis, and that can sustain the release of therapeutic doses during daily wearing. Functional monomers suitable for interaction with these drugs were screened using computational modeling. Imprinted and non-imprinted hydrogels were prepared with various contents in the functional monomer methacrylic acid (MAA) and characterized in terms of swelling, transmittance, mechanical properties, and ocular compatibility (hen's egg test on chorioallantoic membrane (HET-CAM) assay). The values were in the range typical of soft contact lenses. Compared to ACV, the capability to load VACV was remarkably higher due to stronger electrostatic interactions with MAA. The advantages of the imprinting technology were evidenced for VACV. Stability of VACV loading solution/hydrogels under steam heat sterilization and subsequent drug release was investigated. Permeability studies through bovine and porcine cornea and sclera of the drug released from the hydrogels revealed that VACV accumulates in the cornea and can easily cross the sclera, which may facilitate the treatment of both anterior and posterior eye segments diseases.

The Human Touch: Using a Webcam to Autonomously Monitor Compliance During Visual Field Assessments. - Jones, Pete R; Demaria, Giorgia; Tigchelaar, Iris; Asfaw, Daniel S; Edgar, David F; Campbell, Peter; Callaghan, Tamsin; Crabb, David P (Translational vision science & technology, 2020)
Purpose: To explore the feasibility of using various easy-to-obtain biomarkers to monitor non-compliance (measurement error) during visual field assessments., Methods: Forty-two healthy adults (42 eyes) and seven glaucoma patients (14 eyes) underwent two same-day visual field assessments. An ordinary webcam was used to compute seven potential biomarkers of task compliance, based primarily on eye gaze, head pose, and facial expression. We quantified the association between each biomarker and measurement error, as defined by (1) test-retest differences in overall test scores (mean sensitivity), and (2) failures to respond to visible stimuli on individual trials (stimuli -3 dB or more brighter than threshold)., Results: In healthy eyes, three of the seven biomarkers were significantly associated with overall (test-retest) measurement error (P = 0.003-0.007), and at least two others exhibited possible trends (P = 0.052-0.060). The weighted linear sum of all seven biomarkers was associated with overall measurement error, in both healthy eyes (r = 0.51, P < 0.001) and patients (r = 0.65, P < 0.001). Five biomarkers were each associated with failures to respond to visible stimuli on individual trials (all P < 0.001)., Conclusions: Inexpensive, autonomous measures of task compliance are associated with measurement error in visual field assessments, in terms of both the overall reliability of a test and failures to respond on particular trials ("lapses"). This could be helpful for identifying low-quality assessments and for improving assessment techniques (e.g., by discounting suspect responses or by automatically triggering comfort breaks or encouragement)., Translational Relevance: This study explores a potential way of improving the reliability of visual field assessments, a crucial but notoriously unreliable clinical measure. Copyright 2020 The Authors.

Noninvasive and Noncontact Sequential Imaging of the Iridocorneal Angle and the Cornea of the Eye. - Hong, Xun Jie Jeesmond; Suchand Sandeep, C S; Shinoj, V K; Aung, Tin; Barathi, Veluchamy Amutha; Baskaran, Mani; Murukeshan, Vadakke Matham (Translational vision science & technology, 2020)
Purpose: High-resolution imaging of the critical anatomic structures of the eye, especially of the anterior chamber, in vivo, remains a challenge, even with currently available state-of-the-art medical imaging techniques. This study aims for the noninvasive and noncontact sequential imaging of the iridocorneal angle, especially the trabecular meshwork (TM) and the cornea of the eye in high-resolution using a newly developed imaging platform., Methods: Bessel beam scanned light sheet fluorescence microscopy is used to attain high-resolution images of the TM. The ability of the Bessel beam to self-reconstruct around obstacles increases the image contrast at the TM region inside eye by reducing scattering and shadow artifacts. With minimal modifications, the excitation arm of the developed imaging system is adapted for noncontact, high-resolution corneal imaging., Results: High-resolution images of the TM structures and cellular-level corneal structures are obtained in ex vivo porcine eyes, and subsequently in New Zealand white rabbit, in vivo. The spatial resolution of the developed system is 2.19 microm and has a noncontact working distance of 20 mm., Conclusions: A high-resolution imaging platform for noncontact sequential imaging of the TM and the cornea of the eye is developed. This imaging system is expected to be of potential interest in the evaluation and diagnosis of glaucoma and corneal diseases., Translational Relevance: The developed prototype offers the plausibility of in vivo, noncontact, and high-resolution imaging of the iridocorneal angle and cornea of the eye that will aid clinicians in diagnosing open-angle glaucoma and corneal diseases better. Copyright 2020 The Authors.

Neuro-Ophthalmological Manifestations of Obstructive Sleep Apnea: Current Perspectives. - Farahvash, Armin; Micieli, Jonathan A (Eye and brain, 2020)
Obstructive sleep apnea (OSA) is a disease of obstructed airways during sleep that significantly impacts the quality of life and increases the risk of various systemic diseases. OSA has been studied as a risk factor for a number of neuro-ophthalmic conditions and a strong relationship has been established with non-arteritic anterior ischemic optic neuropathy (NAION). The incidence of glaucoma and stroke have also been significantly associated with OSA and are conditions that may also be seen by neuro-ophthalmologists. Patients with NAION have a significantly higher incidence of OSA and OSA diagnosis significantly increases the risk for NAION development. Non-compliance with continuous positive airway pressure (CPAP) in OSA patients has also been found to be a risk factor for fellow-eye involvement and there is increasing evidence to suggest that every patient with NAION should be formally evaluated with polysomnography. The relationship between OSA and idiopathic intracranial hypertension (IIH) has also been studied, but the relationship between these two conditions is less clear. There is insufficient evidence to recommend routine eye examinations in OSA patients for papilledema and conducting a sleep study for a newly diagnosed IIH patient should be left to the discretion of the clinician based on other symptoms and risk factors of OSA. Copyright © 2020 Farahvash and Micieli.

Microinvasive Glaucoma Surgical Training in United States Ophthalmology Residency Programs. - Yim, Cindi K; Teng, Christopher C; Warren, Joshua L; Tsai, James C; Chadha, Nisha (Clinical ophthalmology (Auckland, N.Z.), 2020)
Purpose: The emergence of microinvasive glaucoma surgeries (MIGS) has expanded glaucoma management options. Resident experience with these novel procedures is unclear as no residency minimums exist for them, nor are they part of Accreditation Council for Graduate Medical Education (ACGME) procedure logs. The purpose of this study was to assess resident experience with MIGS in ACGME ophthalmology residency programs across the United States., Methods: This was a cross-sectional survey study of resident MIGS experience. A survey was mailed to program directors of ACGME-accredited ophthalmology residency programs (N = 118) in January 2017. Descriptive analyses were used to characterize the respondent demographics. Chi-square, paired t-tests, and McNemar's tests were used to analyze the geographical distribution and frequency of MIGS experience., Results: A total of 30 out of 118 (25%) residency program directors across all geographic regions responded. Most incorporated both MIGS lecture (87%) and wet lab (73%) didactics into their curriculum. Only 27% felt that MIGS should be part of ACGME requirements. The most common MIGS taught were iStent (70%), endoscopic cyclophotocoagulation (50%), and trabectome (40%). Few residents had completed MIGS procedures as the primary surgeon by graduation. Eleven out of 30 program directors (37%) did not feel that the experience was adequate for independent practice., Conclusion: This study suggests that residents are exposed to some MIGS procedures during training, but program directors did not feel that the experience was adequate for independent practice. Further research is necessary to understand the barriers to integrating MIGS training into residency programs. Copyright © 2020 Yim et al.

Outcomes of Combined iStent Trabecular Micro-Bypass and Cataract Surgery for the Treatment of Open-Angle Glaucoma in a Saudi Population. - Al Habash, Ahmed; Khan, Omar (Clinical ophthalmology (Auckland, N.Z.), 2020)
Purpose: To assess the effectiveness and safety of a single iStent trabecular micro-bypass stent implantation in combination with cataract surgery in lowering the intra ocular pressure (IOP) and number of anti-glaucoma medications in Saudi patients with open-angle glaucoma (OAG)., Setting: King Fahad Hospital of the University, Al Khobar, Saudi Arabia., Design: Prospective, non-comparative, uncontrolled, non-randomized interventional case series., Methods: One iStent was implanted during phacoemulsification cataract surgery for adult patients with OAG by a single surgeon over a period of 3 years. Main outcome measures include number of anti-glaucoma medications, IOP, corrected distance visual acuity (CDVA) and complications., Results: Thirty-six eyes of 33 patients with OAG underwent the surgery. The pre-operative mean IOP and mean anti-glaucoma medications were 17.47 +/- 5.44 mmHg and 2.69 +/- 0.92, respectively. At 1 year of follow-up mean, IOP decreased to 13.44 +/- 1.99 (23.1% reduction) (P<0.001) and mean anti-glaucoma medications decreased to 1.47+/-1.13 (45.4% reduction) (P<0.001)., Conclusion: After 12-month follow-up, phacoemulsification with the implantation of a single iStent seems to be an effective and safe procedure to lower IOP and the number of anti-glaucoma medications, and to overcome the problems associated with medication nonadherence in OAG patients with cataracts. Copyright © 2020 Al Habash and Khan.

Ocular co-Delivery of Timolol and Brimonidine from a Self-Assembling Peptide Hydrogel for the Treatment of Glaucoma: In Vitro and Ex Vivo Evaluation. - Taka, Elissavet; Karavasili, Christina; Bouropoulos, Nikolaos; Moschakis, Thomas; Andreadis, Dimitrios D D; Zacharis, Constantinos K K; Fatouros, Dimitrios G G (Pharmaceuticals (Basel, Switzerland), 2020)
Effective pharmacotherapy during glaucoma treatment depends on interventions that reduce intraocular pressure (IOP) and retain the IOP lowering effect for sufficient time so as to reduce dosing frequency and enhance patient adherence. Combination anti-glaucoma therapy and dosage forms that increase precorneal residence time could therefore constitute a promising therapeutic intervention. The in-situ gel forming self-assembling peptide ac-(RADA)4-CONH2 was evaluated as carrier for the ocular co-delivery of timolol maleate (TM) and brimonidine tartrate (BR). The hydrogel's microstructure and mechanical properties were assessed with atomic force microscopy and rheology, respectively. Drug diffusion from the hydrogel was evaluated in vitro in simulated tear fluid and ex vivo across porcine corneas and its effect on the treated corneas was assessed through physicochemical characterization and histological analysis. Results indicated that TM and BR co-delivery affected hydrogel's microstructure resulting in shorter nanofibers and a less rigid hydrogel matrix. Rapid and complete release of both drugs was achieved within 8 h, while a 2.8-fold and 5.4-fold higher corneal permeability was achieved for TM and BR, respectively. No significant alterations were induced in the structural integrity of the corneas treated with the hydrogel formulation, suggesting that self-assembling peptide hydrogels might serve as promising systems for combination anti-glaucoma therapy.

Fluocinolone acetonide (0.19 mg) intravitreal implant reduces treatment burden and improves practice resource utilisation for patients with diabetic macular oedema. - Byun, Matthew; Osher, James; Riemann, Christopher D (BMJ open ophthalmology, 2020)
Objective: Patients with diabetic macular oedema (DME) are known to have significantly greater medical treatment burden than patients with non-DME. Frequent injections and office visits can have a substantial impact on patient adherence and quality of life. This analysis assesses the impact of the 0.19 mg fluocinolone acetonide (FAc) implant (or injection) on treatment burden and practice resource utilisation in patients with DME., Methods and analysis: This study is a single-centre retrospective chart review of 30 eyes (23 patients) that received a single FAc implant. Data was collected for a 12-month period pre-injection and post-injection of the FAc implant. Primary outcomes included the frequency of injections and ophthalmology office visits. Secondary outcomes included visual acuity (VA), intraocular pressure (IOP) and central subfield thickness (CSFT)., Results: The injection frequency significantly decreased from one injection every 2.6 months pre-injection to one injection every 8.8 months post-injection of the FAc implant (p<0.001). Sixty-three percent of the subjects did not require additional injections post-FAc implant. The mean number of ophthalmology office visits significantly decreased from 12.7 visits pre-FAc to 9.3 visits post-FAc implant (p<0.001). The mean VA (p=0.24) and CSFT (p=0.39) showed a mild numerical improvement that was not statistically significant. Thirty-seven percent of the eyes required additional IOP lowering drops. No eyes required incisional glaucoma surgeries., Conclusions: The FAc implant significantly decreased the treatment burden and improved practice resource utilisation while maintaining or improving VA and CSFT. IOP events were mostly well-controlled with drops and no eyes required incisional glaucoma surgery. Copyright © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Short-Term Efficacy and Safety of Switching from a Latanoprost/Timolol Fixed Combination to a Latanoprost/Carteolol Fixed Combination. - Inoue, Kenji; Piao, Hua; Iwasa, Mayumi; Ishida, Kyoko; Tomita, Goji (Clinical ophthalmology (Auckland, N.Z.), 2020)
Purpose: To investigate the short-term intraocular pressure-lowering efficacy and safety of switching from a fixed combination of latanoprost/timolol to a fixed combination of latanoprost/carteolol., Patients and Methods: The subjects were 30 eyes of 30 adult patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who were using a latanoprost-/timolol-fixed combination with insufficient intraocular pressure-lowering efficacy or adverse reactions. The subjects were switched from once-daily latanoprost/timolol to once-daily latanoprost/carteolol with no washout interval. Intraocular pressure, tear film break-up time, corneal epithelial defects, conjunctival hyperemia, blood pressure, and pulse rate were measured and compared before and 1 and 3 months after switching. Patients were monitored for adverse reactions at each visit, and dropouts were recorded., Results: The mean intraocular pressure at 1 month (15.9+/-3.1 mmHg) and 3 months (16.3+/-3.8 mmHg) was not significantly different from that at baseline (16.1+/-3.1 mmHg). The tear film break-up time and corneal epithelial defects were significantly improved after switching (p<0.01 and p<0.0001, respectively). There was a significant decrease in systolic blood pressure after 1 month and diastolic pressure after 3 months (p<0.05). There was no significant change in pulse rate during the study. Adverse reactions (blurred vision, blepharitis, and conjunctival hyperemia) occurred in 3 patients (10.0%). Four patients (13.3%) discontinued treatment during the 3-month study period., Conclusion: A switch from a fixed combination of latanoprost/timolol to that of latanoprost/carteolol can maintain intraocular pressure and adherence with once-daily administration while improving tear film break-up time and corneal epithelial defects. Copyright © 2020 Inoue et al.

Peripheral Latanoprost Administration Lowers Intraocular Pressure in the Wistar Rat. - Swiatkiewicz, Maciej; Welniak-Kaminska, Marlena; Fiedorowicz, Michal; Kaminska, Agnieszka; Rejdak, Robert; Grieb, Pawel (Ophthalmology and therapy, 2020)
PURPOSE: Instillation of latanoprost eye drops into the conjunctival sac to lower intraocular pressure (IOP) is the most frequently used treatment for primary open-angle glaucoma. The aim of this study was to evaluate the influence of latanoprost on IOP in the rat when applied peripherally., METHODS: A rodent-dedicated tonometer was used to measure IOP in conscious adult male normotensive Wistar rats habituated to the measurement procedure. Commercially available 0.005% latanoprost solutions were continuously delivered to the periphery of the eye over 7 days using mini-pumps inserted subcutaneously in the animal's back, and IOP was measured daily. For comparison, a solution containing an equimolar concentration of latanoprost acid, an active compound of latanoprost, was similarly infused into the eyes of different Wistar rats., RESULTS: Continuous subcutaneous infusion of latanoprost gradually decreased the IOP; the stable nadir of IOP, which was 20% lower than that prior to the start of infusion, was reached on day 3. The effect was statistically significant and fully reversed 2 days after cessation of drug delivery. Continuous subcutaneous application of the solution containing an equimolar amount of latanoprost acid did not appreciably influence the IOP., CONCLUSION: Subcutaneous continuous delivery of latanoprost decreased the IOP in the conscious normotensive Wistar rats in this study. If this effect is confirmed in humans, it may open the possibility of using peripheral systems of drug delivery, which could significantly improve patient compliance.

Influence of Cost of Care and Adherence in Glaucoma Management: An Update. - Meier-Gibbons, Frances; Toteberg-Harms, Marc (Journal of ophthalmology, 2020)
The costs for glaucoma care are rising worldwide. The main reason is the increase of life expectancy and the increasing variety of diagnostic tests and therapeutically options by implants and devices. How can we influence the increase in costs? Does a relationship exist between the rising costs and the behavior of patients especially in regard to adherence of patients to the prescribed therapy? Are there ways to improve adherence? The costs of a disease can be estimated by adding the direct costs and the indirect costs deriving from the disease. Many studies have been looking at the direct costs, for example, the costs of diagnostic tests and treatment modalities. Unfortunately, not many studies investigated the indirect costs, i.e., costs related to the need of a person to accompany the patient during his or her outpatient visits or the costs deriving from loss of work capacity because of the disease itself or the outpatient visits. Adherence or the synonym compliance has been discussed since many years, and it seems that it remains a major problem in the management of many chronic diseases. Despite all efforts to improve adherence, the adherence rate in chronic diseases such as glaucoma or arterial hypertension remains considerably low. One of the main factors in improving adherence is raising patient's awareness of the disease by providing general understanding of their disease. Other important factors are simplified therapeutic regimens, e.g., fixed combination drops, sustained drug release techniques, or new glaucoma surgical procedures with a more favorable risk profile. Copyright © 2020 Frances Meier-Gibbons and Marc Toteberg-Harms.

The Use of Generic Medications for Glaucoma. - Tatham, Andrew J (Journal of ophthalmology, 2020)
The use of generic medicines has grown considerably in recent years providing considerable cost savings. In England, generic items represented 11.7% of prescriptions for glaucoma and ocular hypertension in 2009, increasing to 55.2% of prescriptions in 2018. Generics can be brought to the market quickly and at low cost as manufacturers are not required to repeat animal or clinical research on active ingredients already approved for safety and efficacy. Although there is no regulatory requirement for studies comparing branded and generic eye drops, several randomised crossover studies have been performed comparing branded and generic prostaglandin analogues. While most have shown similar intraocular pressure lowering, studies are of short duration and have not evaluated visual field endpoints. Furthermore, differences in inactive ingredients, pH, viscosity, levels of particulate matter, and degradation over time have been reported. Other potential problems with generic eye drops include differences in bottle design affecting adherence, problems with supply, and the possibility that reduced revenue for innovator companies will lead to reduced investment in new drug development. This article reviews the potential advantages and disadvantages of generic antiglaucoma medications. Copyright © 2020 Andrew J. Tatham.

Promising therapeutic drug delivery systems for glaucoma: a comprehensive review. - Singh, Rohan B; Ichhpujani, Parul; Thakur, Sahil; Jindal, Sumeet (Therapeutic advances in ophthalmology, 2020)
The delivery of ophthalmic drugs is challenging despite easy accessibility via the ocular surface. Topical instillation of eye drops is a relatively easy and most commonly used as a conduit for drug delivery for treating a myriad of ocular morbidities, particularly involving the anterior segment, and has an additional benefit of avoiding the first-pass metabolism while passing through the systemic circulation. The primary challenges of drug administration through traditional methods include-inadequate patient education for proper drug instillation technique, compliance, adherence, and persistence. Various dynamic (choroidal and conjunctival blood flow, lymphatic clearance, and tear dilution) and static (namely, different layers of cornea, sclera, and retina including blood aqueous and blood-retinal barriers) ocular barriers limit drug delivery to the target ocular tissues. The maintenance of the therapeutic drug levels on the ocular surface for a prolonged duration is an added challenge, thus preventing persistent delivery for longer durations. These factors result in inadequate management, leading to poor prognosis in vision loss in as many as 27% of the patients diagnosed with glaucoma. We have reviewed the research and advancements in the development of novel and well-tolerated drug delivery systems with the common goal of overcoming the factors limiting adequate drug delivery to the target tissues in glaucomatous patients with traditional techniques. In the recent past, multiple research groups have successfully designed noninvasive, sustained drug delivery systems, promoting the efficacy as well as the feasibility of delivering topical drugs to the anterior segment. Copyright © The Author(s) 2020.

Phylogenetic Grouping of Human Ocular Escherichia coli Based on Whole-Genome Sequence Analysis. - Ranjith, Konduri; SaiAbhilash, Chinthala Reddy; Sai Prashanthi, Gumpili; Padakandla, Shalem Raj; Sharma, Savitri; Shivaji, Sisinthy (Microorganisms, 2020)
Escherichia coli is a predominant bacterium in the intestinal tracts of animals. Phylogenetically, strains have been classified into seven phylogroups, A, B1, B2, C, D, E, and F. Pathogenic strains have been categorized into several pathotypes such as Enteropathogenic (EPEC), Enterotoxigenic (ETEC), Enteroinvasive (EIEC), Enteroaggregative (EAEC), Diffusely adherent (DAEC), Uropathogenic (UPEC), Shiga-toxin producing (STEC) or Enterohemorrhagic (EHEC) and Extra-intestinal pathogenic E. coli (ExPEC). E. coli also survives as a commensal on the ocular surface. However, under conditions of trauma and immune-compromised states, E. coli causes conjunctivitis, keratitis, endopthalmitis, dacyrocystitis, etc. The phylogenetic affiliation and the pathotype status of these ocular E. coli strains is not known. For this purpose, the whole-genome sequencing of the 10 ocular E. coli strains was accomplished. Based on whole-genome SNP variation, the ocular E. coli strains were assigned to phylogenetic groups A (two isolates), B2 (seven isolates), and C (one isolate). Furthermore, results indicated that ocular E. coli originated either from feces (enteropathogenic and enterotoxigenic), urine (uropathogenic), or from extra-intestinal sources (extra-intestinal pathogenic). A high concordance was observed between the presence of AMR (Antimicrobial Resistance) genes and antibiotic resistance in the ocular E. coli strains. Furthermore, several virulent genes (fimB to fimI, papB to papX, etc.) and prophages (Enterobacteria phage HK97, Enterobacteria phage P1, Escherichia phage D108 etc.) were unique to ocular E. coli. This is the first report on a whole-genome analysis of ocular E. coli strains.

Current Knowledge and Attitudes Concerning Cost-Effectiveness in Glaucoma Pharmacotherapy: A Glaucoma Specialists Focus Group Study. - Feldman, Robert M; Cioffi, George A; Liebmann, Jeffrey M; Weinreb, Robert N (Clinical ophthalmology (Auckland, N.Z.), 2020)
Background: Rising healthcare costs motivate continued cost-reduction efforts. To help lower costs associated with open-angle glaucoma (OAG), a prevalent, progressive disease with substantial direct and indirect costs, clinicians need to understand the cost-effectiveness of intraocular pressure (IOP)-lowering pharmacotherapies. There is little published information on clinicians' knowledge and attitudes about cost-effectiveness in glaucoma treatment., Purpose: This pilot focus group study aimed to explore clinician attitudes and perspectives around the costs and cost drivers of glaucoma therapy; the implementation of cost-effectiveness decisions; the clinical utility of cost-effectiveness studies; and the cost-effectiveness of available treatments., Methods: Six US glaucoma specialists participated in two separate teleconferencing sessions (three participants each), managed by an independent, skilled moderator (also a glaucoma specialist) using a discussion guide. Participants reviewed recent publications (n=25) on health economics outcomes research in glaucoma prior to the sessions., Results: Participants demonstrated a clear understanding of the economic burden of glaucoma therapy and identified medications, diagnostics, office visits, and treatment changes as key cost drivers. They considered cost-effectiveness an appropriate component of treatment decision-making but identified the need for additional data to inform these decisions. Participants indicated that there were only a few recent studies on health economics outcomes in glaucoma which evaluate parameters important to patient care, such as quality of life and medication adherence, and that longitudinal data were scant. In addition to efficacy, participants felt patient adherence and side-effect profile should be included in economic evaluations of glaucoma pharmacotherapy. Recently approved medications were evaluated in this context., Conclusion: Clinicians deem treatment decisions based on cost-effectiveness data as clinically appropriate. Newer IOP-lowering therapies with potentially greater efficacy and favorable side-effect and adherence profiles may help optimize cost-effectiveness. Future studies should include: clinicians' perspectives; lack of commercial bias; analysis of long-term outcomes/costs; more comprehensive parameters; real-world (including quality-of-life) data; and a robust Markov model. Copyright © 2020 Feldman et al.

Adherence to Medical Treatment and Its Determinants Among Adult Saudi Glaucoma Patients in Riyadh City. - Shadid, Asem; Alrashed, Waleed; Bin Shihah, Abdulelah; Alhomoud, Abdulrahman; Alghamdi, Mushref; Alturki, Abdulaziz; Shadid, Abdulaziz; Osman, Essam; Alfaris, Alanoud; Khandekar, Rajiv (Cureus, 2020)
Background Glaucoma in adults is a leading eye disease that causes blindness. Its management is life long and both surgical and medical treatment options are available to manage this ailment. Patients and their caregiver's cooperation in instilling timely eye drops is crucial for the effective reduction of intraocular pressure (IOP) and by halting/delaying the progression of visual disabilities due to glaucoma. Periodic assessment and strict adherence to medical treatment has been found to be less than desired. It is influenced by the severity of the disease, the duration of the ailment, the number of eye drops being used, the literacy level, and the cost of medication. We present the adherence rate of topical medications and its determinants among adult Saudi glaucoma patients getting treated in 2017 in a tertiary eye center in Saudi Arabia. Methodology This cross-sectional survey was carried out from January to March 2017 at a tertiary eye hospital in Riyadh, Saudi Arabia. To undertake a cross-sectional study, we assumed that among 1300 patients visiting the eye department of a tertiary eye hospital, the level of non-adherence to glaucoma medication would be in 27% of glaucoma patients. To achieve a 95% confidence interval and an acceptable error margin of 5% for a survey, we needed to interview at least 253 participants. Results We interviewed 263 randomly selected glaucoma patients among 1236 patients visiting the eye department of the tertiary eye hospital in Riyadh, Saudi Arabia. Two-thirds of participants were school graduates, Saudi nationals, and had undergone surgery for glaucoma in the past; perhaps only YAG laser peripheral iridotomy (PI). Less than half of the participants (43%) had less than a one-year duration of glaucoma. The client-perceived subjective adherence rate to glaucoma medication was noted in 191/263 = 72.6% (95% Confidence Interval 67.2 -78.0). Of the 263 glaucoma patients, 229 judiciously abided with their follow-up appointments with ophthalmologists. Thus, the compliance to follow-up for glaucoma treatment was 87.1% (95% CI 83.0 - 91.1). Conclusion Our study with a large sample is perhaps the first one to assess compliance with medical treatment among adult Saudi glaucoma patients. The adherence rate for topical glaucoma medication measured using the subjective method was 72% among adult glaucoma patients. Adherence with the follow-up appointment with the glaucoma specialist was as high as 87%. Adherence with medical treatment found in the present study versus the literature review suggested that despite different sets of barriers, the adherence rate in Saudi adult glaucoma patients noted in our study was high. Knowledge, beliefs, and attitude are known to affect the adherence rate. In our study, education level and relatives having glaucoma were not associated with the adherence rate. This indirectly suggests that knowledge about the use of medication in the treatment of glaucoma that is gained by patients had a limited influence on adherence in our glaucoma patients. Modes of dispersing knowledge to elderly glaucoma patients and their impact on the adherence rates of medications for glaucoma management need to be further studied. Copyright © 2020, Shadid et al.

Adherence with Medical Therapy for Primary Open-Angle Glaucoma in Kenya - A Pilot Study. - Murdoch, Ian; Nyakundi, David; Baker, Helen; Dulku, Simon; Kiage, Daniel (Patient preference and adherence, 2020)
Background/Objectives: Adherence is a major challenge in topical glaucoma therapy, particularly in an African context. We report a pilot study assessing adherence independently for the first time in an African context., Subjects/Methods: Participants with newly diagnosed open-angle glaucoma received a weighed bottle of Lumigan 0.01% with counselling on therapy. The bottles were returned monthly for renewal and weighed on return to estimate drops taken during the period. Data collection was for one year with a short compliance questionnaire., Results: 11 patients participated. 5 (45%) failed to complete one full year of topical therapy. The overall mean number of drops per eye per day was 1.74 (SD 0.69) for the 6 with one year of monthly returned bottles and controlled IOPs at each visit. Self-perception of compliance in these patients was good., Conclusion: The signs of poor adherence based on both self-report (previous literature), and in this small-scale study of an objective measure suggest medication may not be the first-line treatment of choice in this environment. Our report does, however, raise the possibility that those patients who return for repeat prescriptions and review are indeed adhering to their treatment regimens. Copyright © 2020 Murdoch et al.

Necrotic scleral melt and fungal keratitis-a complication of subtenon triamcinolone acetonide injection. - Agarwal, Manisha; Ranjan, Richa; Mathur, Umang (Journal of ophthalmic inflammation and infection, 2020)
PURPOSE: Subtenon triamcinolone acetonide injection (STAI) is a safe drug delivery method for various ocular conditions. We report two cases of necrotic scleral melt, a rare complication of STAI., METHODS: The first patient received STAI for post-operative inflammation control and developed necrotic scleral melt at the site of STAI with superadded fungal keratitis. The second patient received three STAI for non-necrotizing, non-infectious anterior scleritis and developed scleral necrosis at the site of her last STAI. Noncompliance with medications resulted in the progression of scleral necrosis to a new area., RESULTS: In the first patient, surgical removal of triamcinolone deposit resulted in healing of the scleral melt while the second patient was managed conservatively with corticosteroids and immunosuppressants., CONCLUSION: Scleral melt is a rare complication of STAI; however, an early diagnosis and management of any predisposing factor along with surgical debridement should be considered as a potential critical treatment option to salvage the eye.

Smartphone-Assisted Glaucoma Screening in Patients With Type 2 Diabetes: a Pilot Study. - Bilong, Yannick; Domngang, Christelle Noche; Nwanlih Gimma, Gebding; Katte, Jean-Claude; Afetane, Ted Evina; Kagmeni, Gilles; Mbanya, Jean Claude; Kumar, Nilesh; Sharma, Ashish; Sobngwi, Eugene (Medical hypothesis, discovery & innovation ophthalmology journal, 2020)
We aimed to determine true and false positives of glaucoma screening, relying solely on photos of the retina, taken with a smartphone. We performed a descriptive and analytical study on patients with type 2 diabetes at the National Obesity Centre, Yaounde, Cameroon. Participating patients had retinal photography sessions using an iPhone 5s (iOS 10.3.3; Apple, Cupertino, CA) coupled to the Make in India Retinal Camera (MIIRetCam; MIIRetCam Inc., Coimbatore, TN, India). Obtained pictures of the retina were stored and transferred via the internet to an ophthalmologist to assess glaucoma. Selected patients were then invited to undergo a conventional ophthalmological examination to confirm the diagnosis. A total of 395 patients were screened, 39 (including 20 women) were diagnosed with suspicion of glaucoma based on retinal photos, a prevalence rate of 9.87%. The following signs were found; Cup/Disc ratio (C/D) >=0.5 in 64.1% (25/39), asymmetric C/D >0.2 in 35.9% (14/39), papillary haemorrhage in 10.2% (4/39) and retinal nerve fibre deficiency in 2.5% (1/39). Only 14 of 39 patients with suspicion of glaucoma were examined, giving a lost-to-follow-up rate of 64.1%. Chronic open-angle glaucoma was confirmed in 8 patients (true positives) and absent in 6 patients (false positives). The prevalence of smartphone-detected glaucoma and lost-to-follow-up rates were high. So we need to improve this type of screening, with additional tests like transpalpebral applanation tonometer and the smartphone Frequency Doubling Technique visual field combined with better education of patients to increase their adherence to follow-up. Copyright © 2020, Author(s).

The Effects of 3% Diquafosol Sodium Eye Drops on Tear Function and the Ocular Surface of Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice Treated with Antiglaucoma Eye Medications. - Yagi-Yaguchi, Yukari; Kojima, Takashi; Higa, Kazunari; Dogru, Murat; Ibrahim, Osama Ma; Shimizu, Takahiko; Tsubota, Kazuo; Shimazaki, Jun (Diagnostics (Basel, Switzerland), 2020)
Anti-glaucoma eye drop treatment often induces dry eyes and can lead to poor medication adherence. This study aimed to investigate the effects of 3% diquafosol sodium eye drops on tear function and the ocular surface epithelium in Sod1-/- mice after treatment with anti-glaucoma eye drops. The mice were divided into four groups: group 1, control group; group 2, anti-glaucoma eye drop; group 3, anti-glaucoma eye drops followed by a secretagogue eye drop (3% diquafosol); and group 4, simultaneous anti-glaucoma and secretagogue eye drop. Mice underwent assessments of tear quantity, tear film breakup time, and vital staining score. Mice in groups 3 and 4 showed significantly better tear stability and lower corneal staining scores than mice in group 2 after eye drop instillations (p < 0.05). Mice in group 4 showed significantly better tear stability, lower corneal staining scores, and higher goblet cell densities than those in group 1 after eye drop instillations (p < 0.05). The conjunctival epithelium showed stratification and abundance of Muc5AC-positive goblet cells in group 4, whereas thinning with desquamation was observed with a few goblet cells in group 2. Thus, simultaneous administration of 3% diquafosol sodium eye drops with topical anti-glaucoma drops showed favorable effects on tear stability and the corneal epithelium against the ocular surface toxicity inflicted by the anti-glaucoma eye drops.

Preserved Versus Preservative-Free Latanoprost for the Treatment of Glaucoma and Ocular Hypertension: A Post Hoc Pooled Analysis. - Harasymowycz, Paul; Hutnik, Cindy; Rouland, Jean-Francois; Negrete, Francisco J Munoz; Economou, Mario A; Denis, Philippe; Baudouin, Christophe (Advances in therapy, 2021)
INTRODUCTION: To compare the tolerability and efficacy of a preservative-containing latanoprost (PCL) to a preservative-free formulation of latanoprost (PFL) in patients with open-angle glaucoma or ocular hypertension., METHODS: A pooled analysis was performed of data from five published studies. The primary outcome was tolerability as evaluated by the severity of hyperemia. The secondary objectives were patient tolerance based on a composite ocular surface disease (OSD) score arising from ocular signs and symptoms, patient and investigator satisfaction, and a comparison of IOP-lowering efficacy., RESULTS: There were three randomized controlled trials and two observational studies included in the analysis. Conjunctival hyperemia improved significantly in 25.6% (388) of patients switched to the PFL group versus 11.7% (117) of patients switched to the PCL group (p < 0.001). PFL was two times superior to PCL in reducing ocular hyperemia (odds ratio = 1.96; p < 0.001). The mean OSD composite score decreased by 32.2% in patients switched to the PFL group and 14.1% in the PCL group (p < 0.001). At 3 months, the mean IOP was similar between groups (p = 0.312)., CONCLUSION: This post hoc pooled analysis confirmed the findings of the individual studies that PFL is as efficacious at reducing IOP as PCL but better tolerated. After switching to PFL, there was twice the improvement in the OSD composite score. PFL was twice as effective at reducing ocular hyperemia and other ocular signs. These findings suggest that PFL has features that may improve patient compliance, thereby potentially improving the IOP-lowering efficacy on a long-term basis.
Keywords: Antihypertensive Agents/tu [Therapeutic Use]; Glaucoma/dt [Drug Therapy]; *Glaucoma; Glaucoma, Open-Angle/dt [Drug Therapy]; *Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension/dt [Drug Therapy]; *Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic/tu [Therapeutic Use]; *Prostaglandins F, Synthetic; Treatment Outcome

Self-assembled DNA nanoparticles loaded with travoprost for glaucoma-treatment. - Schnichels, Sven; Hurst, Jose; de Vries, Jan Willem; Ullah, Sami; Gruszka, Agnieszka; Kwak, Minseok; Loscher, Marina; Dammeier, Sascha; Bartz-Schmidt, Karl-Ulrich; Spitzer, Martin S; Herrmann, Andreas (Nanomedicine : nanotechnology, biology, and medicine, 2020)
Lipid DNA nanoparticles (NPs) exhibit an intrinsic affinity to the ocular surface and can be loaded by hybridization with fluorophore-DNA conjugates or with the anti-glaucoma drug travoprost by hybridizing an aptamer that binds the medication. In the travoprost-loaded NPs (Trav-NPs), the drug is bound by specific, non-covalent interactions, not requiring any chemical modification of the active pharmaceutical ingredient. Fluorescently labeled Trav-NPs show a long-lasting adherence to the eye, up to sixty minutes after eye drop instillation. Biosafety of the Trav-NPs was proved and in vivo. Ex vivo and in vivo quantification of travoprost via LC-MS revealed that Trav-NPs deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug. The data successfully show the applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of a major retinal eye disease, i.e. glaucoma. Copyright © 2020 Elsevier Inc. All rights reserved.
Keywords: Animals; Aptamers, Nucleotide/ch [Chemistry]; Aptamers, Nucleotide/pd [Pharmacology]; Containment of Biohazards; *DNA/ch [Chemistry]; DNA/pd [Pharmacology]; Disease Models, Animal; *Drug Delivery Systems; *Glaucoma/dt [Drug Therapy]; Humans; Lipids/ch [Chemistry]; Lipids/pd [Pharmacology]; Mice; *Nanoparticles/ch [Chemistry]; Rats; Swine; Travoprost/ch [Chemistry]; Travoprost/pd [Pharmacology]

Diabetic Macular Edema Management in Asian Population: Expert Panel Consensus Guidelines. - Chhablani, Jay; Wong, Kelvin; Tan, Gavin S; Sudhalkar, Aditya; Laude, Augustinus; Cheung, Chui Ming Gemmy; Zhao, Paul; Uy, Harvey; Lim, Jeffrey; Valero, Sherman; Ngah, Nor Fariza; Koh, Adrian (Asia-Pacific journal of ophthalmology (Philadelphia, Pa.), 2020)
PURPOSE: The aim of this consensus article was to provide comprehensive recommendations in the management of diabetic macular edema (DME) by reviewing recent clinical evidence., DESIGN: A questionnaire containing 47 questions was developed which encompassed clinical scenarios such as treatment response to anti-vascular endothelial growth factor and steroid, treatment side effects, as well as cost and compliance/reimbursement in the management of DME using a Dephi questionnaire as guide., METHODS: An expert panel of 12 retinal specialists from Singapore, Malaysia, Philippines, India and Vietnam responded to this questionnaire on two separate occasions. The first round responses were compiled, analyzed and discussed in a round table discussion where a consensus was sought through voting. Consensus was considered achieved, when 9 of the 12 panellists (75%) agreed on a recommendation., RESULTS: The DME patients were initially profiled based on their response to treatment, and the terms target response, adequate response, nonresponse, and inadequate response were defined. The panellists arrived at a consensus on various aspects of DME treatment such as need for classification of patients before treatment, first-line treatment options, appropriate time to switch between treatment modalities, and steroid-related side effects based on which recommendations were derived, and a treatment algorithm was developed., CONCLUSIONS: This consensus article provides comprehensive, evidence-based treatment guidelines in the management of DME in Asian population. In addition, it also provides recommendations on other aspects of DME management such as steroid treatment for stable glaucoma patients, management of intraocular pressure rise, and recommendations for cataract development.
Keywords: *Angiogenesis Inhibitors/ad [Administration & Dosage]; *Consensus; Diabetic Retinopathy/co [Complications]; Diabetic Retinopathy/di [Diagnosis]; *Diabetic Retinopathy/dt [Drug Therapy]; Follow-Up Studies; *Glucocorticoids/ad [Administration & Dosage]; Humans; Intravitreal Injections; Macular Edema/di [Diagnosis]; *Macular Edema/dt [Drug Therapy]; Macular Edema/et [Etiology]; Retrospective Studies; Surveys and Questionnaires; Treatment Outcome; Vascular Endothelial Growth Factor A/ai [Antagonists & Inhibitors]; *Visual Acuity

Compliance behaviour change in contact lens wearers: a randomised controlled trial. - Arshad, Memoona; Carnt, Nicole; Tan, Jacqueline; Stapleton, Fiona (Eye (London, England), 2021)
BACKGROUND: Water exposure during contact lens wear has been associated with contact lens disease including microbial keratitis and sterile corneal infiltrates. Despite the documented risks, water exposure is common amongst lens wearers. This study aimed to determine the effect of water education in the form of "no-water" lens case stickers on water-contact behaviours and storage case contamination., METHODS: In a prospective, masked, randomised controlled trial, 200 daily lens wearers were randomised to either receive a storage case with a "no-water" sticker (test) or without a "no-water" sticker (control). Both groups received written compliance information. Participants completed a self-administered lens hygiene questionnaire at baseline and after 6 weeks. Microbial analysis of used storage cases, collected at both study visits, was conducted using ATP and limulus amebocyte lysate (LAL) assays for overall microbial contamination and endotoxin levels, respectively. A one-way ANCOVA and multiple logistic regression determined the change in water-contact behaviours and storage case contamination over time., RESULTS: A total of 188 lens wearers completed both study visits; 128 females and 60 males; average age 29 +/- 13 (range 18-78 years); 95 test and 93 control participants. After 6 weeks, the overall water exposure score and endotoxin levels reduced significantly in the test group compared with the control group (p < 0.05). There were no significant changes in individual water-contact behaviours or overall storage case contamination., CONCLUSION: A no-water infographic on the contact lens case improved overall water-contact behaviours and reduced storage case endotoxin. Refining the messaging may be beneficial in future to improve other aspects of compliance.
Keywords: Adolescent; Adult; Aged; *Contact Lens Solutions; *Contact Lenses; Female; Humans; Hygiene; Male; Middle Aged; Prospective Studies; Surveys and Questionnaires; Young Adult

Patient satisfaction with the virtual glaucoma clinic. - Spackman, William; Waqar, Salman; Booth, Adam (Eye (London, England), 2021)
Comment on (CON)
Keywords: Ambulatory Care Facilities; *Glaucoma; Humans; *Patient Satisfaction

Increasing Engagement of African American Patients with Glaucoma during Medical Encounters: Creation of a Pre-visit Video. - Sleath, Betsy; Davis, Scott A; Carpenter, Delesha M; Robin, Alan L; Muir, Kelly W; Lee, Charles; Garcia, Nacire; Budenz, Donald L (Optometry and vision science : official publication of the American Academy of Optometry, 2020)
SIGNIFICANCE: The developed video can be accessed by African American patients with glaucoma from across the United States on YouTube to learn why it is important to ask eye care providers any questions they might have about glaucoma and/or its treatment., PURPOSE: Our objective was to develop an educational video for African Americans with glaucoma to watch before their ophthalmology office visits to help motivate them to be actively involved in their care., METHODS: The Social Cognitive Theory guided the development of the video. We conducted three focus groups with African American patients with glaucoma and three focus groups with providers who care for African American patients with glaucoma. The research team reviewed the transcripts of the focus groups and then developed a plan for video production., RESULTS: The themes that both patients and providers felt should be covered in the video to motivate patient question-asking included the following: what is glaucoma, glaucoma treatment, glaucoma testing, and treatment adherence. Based on focus group results, the resulting video had one male African American physician and four African American patients covering the themes that emerged., CONCLUSIONS: Ophthalmologists and African Americans with glaucoma gave us excellent insight into developing videos to increase patient involvement during their visits.
Keywords: *African Americans/eh [Ethnology]; Aged; Communication; Female; Focus Groups; *Glaucoma/eh [Ethnology]; Humans; Male; Middle Aged; Office Visits; Ophthalmologists; *Patient Education as Topic/mt [Methods]; *Patient Participation; Physician-Patient Relations; United States; *Video Recording

Preserved Versus Preservative-Free Latanoprost for the Treatment of Glaucoma and Ocular Hypertension: A Post Hoc Pooled Analysis. - Harasymowycz, Paul; Hutnik, Cindy; Rouland, Jean-Francois; Negrete, Francisco J Munoz; Economou, Mario A; Denis, Philippe; Baudouin, Christophe (Advances in therapy, 2021)
INTRODUCTION: To compare the tolerability and efficacy of a preservative-containing latanoprost (PCL) to a preservative-free formulation of latanoprost (PFL) in patients with open-angle glaucoma or ocular hypertension., METHODS: A pooled analysis was performed of data from five published studies. The primary outcome was tolerability as evaluated by the severity of hyperemia. The secondary objectives were patient tolerance based on a composite ocular surface disease (OSD) score arising from ocular signs and symptoms, patient and investigator satisfaction, and a comparison of IOP-lowering efficacy., RESULTS: There were three randomized controlled trials and two observational studies included in the analysis. Conjunctival hyperemia improved significantly in 25.6% (388) of patients switched to the PFL group versus 11.7% (117) of patients switched to the PCL group (p < 0.001). PFL was two times superior to PCL in reducing ocular hyperemia (odds ratio = 1.96; p < 0.001). The mean OSD composite score decreased by 32.2% in patients switched to the PFL group and 14.1% in the PCL group (p < 0.001). At 3 months, the mean IOP was similar between groups (p = 0.312)., CONCLUSION: This post hoc pooled analysis confirmed the findings of the individual studies that PFL is as efficacious at reducing IOP as PCL but better tolerated. After switching to PFL, there was twice the improvement in the OSD composite score. PFL was twice as effective at reducing ocular hyperemia and other ocular signs. These findings suggest that PFL has features that may improve patient compliance, thereby potentially improving the IOP-lowering efficacy on a long-term basis.
Keywords: Antihypertensive Agents/tu [Therapeutic Use]; Glaucoma/dt [Drug Therapy]; *Glaucoma; Glaucoma, Open-Angle/dt [Drug Therapy]; *Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension/dt [Drug Therapy]; *Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic/tu [Therapeutic Use]; *Prostaglandins F, Synthetic; Treatment Outcome

Glaucoma in Developing Countries. - Thapa, Suman Shumshere; Paudyal, Indira; Joshi, Pratibha Lama; Singh, Kalpana; Parajuli, Anil (Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPH, 2021)
Glaucoma is a leading cause of blindness worldwide. The diagnosis and management of glaucoma is especially difficult in the developing countries. Lack of cost effective screening strategies, low income, low rates of literacy and inadequate infrastructures and human resources for eye care services are the obstacles for delivering glaucoma service. Majority of people with glaucoma in developing countries usually present at an advanced stage at the time of diagnosis; which negatively affects their quality of life. Further research, proper allocation of resources and collaborative effort by blindness prevention programs will hopefully provide new evidences on cost effective ways to screen and manage glaucoma in the future. This article aims to highlight the burden of glaucoma and ways to address the challenges in developing countries. Copyright © NEPjOPH.
Keywords: Blindness/di [Diagnosis]; Blindness/ep [Epidemiology]; Blindness/et [Etiology]; *Developing Countries; Glaucoma/di [Diagnosis]; Glaucoma/ep [Epidemiology]; *Glaucoma; Humans; Mass Screening; Quality of Life

Return of phacoemulsification after emergency status related to COVID-19: experience of a tertiary referral center. - Vieira, Rita; Baptista, Pedro; Castro, Catarina; Leite, Joao; Meneres, Maria Joao; Meneres, Pedro (Journal of cataract and refractive surgery, 2021)
PURPOSE: To present a protocol of priority criteria for phacoemulsification after the backlog due to severe acute respiratory syndrome coronavirus (SARS-CoV)-2 pandemic status., SETTING: Ophthalmology department of Centro Hospitalar e Universitario do Porto (CHUP), Oporto, Portugal., DESIGN: Cross-sectional, nonrandomized, retrospective study., METHODOLOGY: Data of all patients waiting for cataract surgery were analyzed at the beginning of May 2020, after 2 months without performing elective surgery. The waiting time since surgical inscription was considered an independent and overriding factor. In addition, higher priority was given to patients with white or brunescent cataracts and patients with low visual acuity: corrected distance visual acuity (CDVA) of 20/200 or less in binocular patients or CDVA of 20/63 or less in monocular patients. Criteria of medium priority included patients who remained with anisometropia and patients with glaucoma or low to moderate risk for chronic angle closure. Data of scheduled surgeries in the following months were then analyzed., RESULTS: A total of 717 patients were waiting for phacoemulsification. One hundred ninety-one patients (26.64%) were on the waiting list more than 4.5 months; the medium waiting time was 3.51 +/- 1.57 months. According to both priority criteria and waiting time, 348 (48.6%) were categorized as priority cases. A total of 158 patients (22.0%) met the highest priority; 61 patients (8.5%) met the medium priority criteria. In 129 patients (18.0%), priority was considered based solely on higher waiting time. This algorithm allowed surgeons to operate on all priority cases within the first 3 months., CONCLUSIONS: The presented protocol showed to be effective, providing a timely surgical opportunity for priority cases. Copyright © 2021 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.
Keywords: *COVID-19; *Cataract; Cross-Sectional Studies; Humans; *Lens Implantation, Intraocular/mt [Methods]; *Phacoemulsification/mt [Methods]; Retrospective Studies; SARS-CoV-2; Tertiary Care Centers; *Waiting Lists

Patients' satisfaction with ophthalmic counselling services in a tertiary hospital in Calabar, South-South Nigeria. - Etim, Bassey A; Ibanga, Affiong A; Udoh, Martha-Mary E; Nkanga, Elizabeth D; Utam, Utam A; Okwejie, John A (Ghana medical journal, 2020)
Objective: To assess the level of satisfaction of patients who access the Ophthalmic counselling services anchored by trained social workers of the University of Calabar Teaching Hospital, Calabar, Nigeria., Methods: A cross-sectional study of serial consenting participants was done. Ethical approval was obtained from the University of Calabar Teaching hospitals' ethics committee. Data was obtained using a semi-structured interviewer-administered questionnaire. Data were collated and analyzed using the SPSS for Windows (version 20, SPSS inc. Chicago, IL, USA). Modified Likert scale (very satisfied, satisfied and not satisfied) was used to rate the satisfaction level., Results: A total of 120 respondents met the inclusion criteria and were enrolled into the study. Majority of the respondents (60%) were male with an overall mean age of 45.32+/- 1.82. Over a quarter (28.3%) of the respondents were in the age bracket of 41-50. Glaucoma (48.3%) was the most common eye condition of the respondents. Seventy-five percent of the respondents were satisfied with the average time spent for the counselling services while 76.7% were satisfied with the overall ophthalmic counselling services they received with 46.7% believing that the service was provided by a social worker., Conclusion: Majority of the Patients were satisfied with the Ophthalmic counselling services mainly anchored by social workers. Training and retraining of allied support staff to render ophthalmic counselling services in order to ease the workload of the Ophthalmologist should be encouraged in resource-limited settings., Funding: None declared. Copyright © The Author(s).
Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Child; *Counseling/sn [Statistics & Numerical Data]; Cross-Sectional Studies; Female; Hospitals, Teaching; Humans; Male; Middle Aged; Nigeria; *Ophthalmology; Patient Satisfaction/sn [Statistics & Numerical Data]; Surveys and Questionnaires; Young Adult

Single Administration of a Biodegradable, Separable Microneedle Can Substitute for Repeated Application of Eyedrops in the Treatment of Infectious Keratitis. - Park, SeungHyun; Lee, KangJu; Kang, Heekyoung; Lee, YeJin; Lee, JiYong; Kim, Jeong Hun; Song, Hyun Beom; Ryu, WonHyoung (Advanced healthcare materials, 2021)
Infectious keratitis is mainly treated with topical antibiotics. To achieve and maintain the required therapeutic concentration in the cornea where the tear fluid continuously rinses the surface, the antibiotics must be frequently applied, even while the patient is sleeping, and oral medication is sometimes required. However, the inevitably poor compliance and avascular nature of the cornea decrease drug bioavailability. In this study, a single microneedle (MN) is injected into the cornea to substitute for the repeated application of eyedrops in the treatment of infectious keratitis. After comparing the mechanical integrity and drug release profiles of three different drug-tips, the drug-tip with the "high" drug concentration that releases 12.5 ng drug within 3 days is applied to a cornea to evaluate the transferability and in vivo drug release. In the treatment of infectious keratitis with repeated application of eyedrops for six consecutive days, a single MN injection is substituted for the initial 3 days of eyedrop applications. The progression remains similarly attenuated after 3 days without eyedrops, and comparable efficacy is achieved on day 6 when combined with delayed eyedrop treatment from day 3. Thus, the single administration of a biodegradable MN can substitute for the repeated application of eyedrops in the treatment of infectious keratitis. Copyright © 2021 Wiley-VCH GmbH.
Keywords: Administration, Topical; Cornea; Humans; Keratitis/dt [Drug Therapy]; *Keratitis; Needles; Ophthalmic Solutions/tu [Therapeutic Use]; Tears

Novel water soluble sterile natamycin formulation (Natasol) for fungal keratitis. - Velpandian, Thirumurthy; Nirmal, Jayabalan; Sharma, Hanuman P; Sharma, Sanjay; Sharma, Namrata; Halder, Nabanita (European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2021)
The purpose of this study was to develop, characterize and evaluate novel water soluble formulation for its topical and intrastromal application. Natamycin complexed with cyclodextrin was characterized by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The complexed powder was used to formulate 1% w/v aqueous natamycin formulation (Natasol 1%) for topical use. The developed formulation was subjected to stability testing at various conditions. Single and multi-dose trans-corneal permeation of Natasol 1% was evaluated in New Zealand Albino rabbits in comparison with marketed 5% natamycin suspension. Sterile unpreserved Natasol (0.01% w/v natamycin) formulation was also developed for intrastromal injection. Both formulations were evaluated for the ocular toxicity. FTIR and DSC studies revealed successful complexation of natamycin that further protected the degradation at various stability conditions. Single dose trans-corneal permeation studies revealed that Natasol 1% attained Cmax at one hr and maintain its intraocular concentration 5 and 2.5 times higher at 4th and 6th hr compared to 5% natamycin suspension. Multi-dose kinetics revealed the steady state pharmacokinetics after hourly and two hourly dosing schedules. Topical Natasol 1% and sterile unpreserved Natasol 0.01% intrastromal injection, did not show any ocular toxicity in the animals. To conclude, the newly developed topical 1% w/v natamycin formulation was found to be non-inferior to 5% natamycin topical suspension. It is expected to increase patient compliance for the treatment of fungal keratitis. Copyright © 2021 Elsevier B.V. All rights reserved.
Keywords: Animals; Antifungal Agents/tu [Therapeutic Use]; Eye Infections, Fungal/dt [Drug Therapy]; *Eye Infections, Fungal; Humans; Keratitis/dt [Drug Therapy]; *Keratitis; Natamycin; Rabbits; Water

Recent progress on wearable point-of-care devices for ocular systems. - Shin, Haein; Seo, Hunkyu; Chung, Won Gi; Joo, Byung Jun; Jang, Jiuk; Park, Jang-Ung (Lab on a chip, 2021)
The eye is a complex sensory organ that contains abundant information for specific diseases and pathological responses. It has emerged as a facile biological interface for wearable healthcare platforms because of its excellent accessibility. Recent advances in electronic devices have led to the extensive research of point-of-care (POC) systems for diagnosing and monitoring diseases by detecting the biomarkers within the eye. Among these systems, contact lenses, which make direct contact with the ocular surfaces, have been utilized as one of the promising candidates for non-invasive POC testing of various diseases. The continuous and long-term measurement from the sensor allows the patients to manage their symptoms in an effective and convenient way. Herein, we review the progress of contact lens sensors in terms of the materials, methodologies, device designs, and target biomarkers. The anatomical structure and biological mechanisms of the eye are also discussed to provide a comprehensive understanding of the principles of contact lens sensors. Intraocular pressure and glucose, which are the representative biomarkers found in the eyes, can be measured with the biosensors integrated with contact lenses for the diagnosis of glaucoma and diabetes. Furthermore, contact lens sensors for various general pathologies as well as other ocular diseases are also considered, thereby providing the prospects for further developments of smart contact lenses as a future POC system.
Keywords: *Biosensing Techniques; *Contact Lenses; Humans; Intraocular Pressure; Point-of-Care Systems; *Wearable Electronic Devices

Glaucoma: Management and Future Perspectives for Nanotechnology-Based Treatment Modalities. - El Hoffy, Nada M; Abdel Azim, Engy A; Hathout, Rania M; Fouly, Marwa A; Elkheshen, Seham A (European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2021)
Glaucoma, being asymptomatic for relatively late stage, is recognized as a worldwide cause of irreversible vision loss. The eye is an impervious organ that exhibits natural anatomical and physiological barriers which renders the design of an efficient ocular delivery system a formidable task and challenge scientists to find alternative formulation approaches. In the field of glaucoma treatment, smart delivery systems for targeting have aroused interest in the topical ocular delivery field owing to its potentiality to oppress many treatment challenges associated with many of glaucoma types. The current momentum of nano-pharmaceuticals, in the development of advanced drug delivery systems, hold promises for much improved therapies for glaucoma to reduce its impact on vision loss. In this review, a brief about glaucoma; its etiology, predisposing factors and different treatment modalities has been reviewed. The diverse ocular drug delivery systems currently available or under investigations have been presented. Additionally, future foreseeing of new drug delivery systems that may represent potential means for more efficient glaucoma management are overviewed. Finally, a gab-analysis for the required investigation to pave the road for commercialization of ocular novel-delivery systems based on the nano-technology are discussed. Copyright © 2020. Published by Elsevier B.V.
Keywords: Drug Delivery Systems; Eye; Glaucoma/dt [Drug Therapy]; *Glaucoma; Humans; Nanotechnology

Health care cost and benefits of artificial intelligence-assisted population-based glaucoma screening for the elderly in remote areas of China: a cost-offset analysis. - Xiao, Xuan; Xue, Long; Ye, Lin; Li, Hongzheng; He, Yunzhen (BMC public health, 2021)
BACKGROUND: Population-based screening was essential for glaucoma management. Although various studies have investigated the cost-effectiveness of glaucoma screening, policymakers facing with uncontrollably growing total health expenses were deeply concerned about the potential financial consequences of glaucoma screening. This present study was aimed to explore the impact of glaucoma screening with artificial intelligence (AI) automated diagnosis from a budgetary standpoint in Changjiang county, China., METHODS: A Markov model based on health care system's perspective was adapted from previously published studies to predict disease progression and healthcare costs. A cohort of 19,395 individuals aged 65 and above were simulated over a 15-year timeframe. Fur illustrative purpose, we only considered primary angle-closure glaucoma (PACG) in this study. Prevalence, disease progression risks between stages, compliance rates were obtained from publish studies. We did a meta-analysis to estimate diagnostic performance of AI automated diagnosis system from fundus image. Screening costs were provided by the Changjiang screening programme, whereas treatment costs were derived from electronic medical records from two county hospitals. Main outcomes included the number of PACG patients and health care costs. Cost-offset analysis was employed to compare projected health outcomes and medical care costs under the screening with what they would have been without screening. One-way sensitivity analysis was conducted to quantify uncertainties around model results., RESULTS: Among people aged 65 and above in Changjiang county, it was predicted that there were 1940 PACG patients under the AI-assisted screening scenario, compared with 2104 patients without screening in 15 years' time. Specifically, the screening would reduce patients with primary angle closure suspect by 7.7%, primary angle closure by 8.8%, PACG by 16.7%, and visual blindness by 33.3%. Due to early diagnosis and treatment under the screening, healthcare costs surged dramatically to $107,761.4 dollar in the first year and then were constantly declining over time, while without screening costs grew from $14,759.8 in the second year until peaking at $17,900.9 in the 9th year. However, cost-offset analysis revealed that additional healthcare costs resulted from the screening could not be offset by decreased disease progression. The 5-, 10-, and 15-year accumulated incremental costs of screening versus no screening were estimated to be $396,362.8, $424,907.9, and $434,903.2, respectively. As a result, the incremental cost per PACG of any stages prevented was $1464.3., CONCLUSIONS: This study represented the first attempt to address decision-maker's budgetary concerns when adopting glaucoma screening by developing a Markov prediction model to project health outcomes and costs. Population screening combined with AI automated diagnosis for PACG in China were able to reduce disease progression risks. However, the excess costs of screening could never be offset by reduction in disease progression. Further studies examining the cost-effectiveness or cost-utility of AI-assisted glaucoma screening were needed.
Keywords: Aged; Artificial Intelligence; China/ep [Epidemiology]; Cost-Benefit Analysis; Glaucoma/di [Diagnosis]; *Glaucoma; *Glaucoma, Angle-Closure; Health Care Costs; Humans

Low-carbohydrate-diet scores and the risk of primary open-angle glaucoma: data from three US cohorts. - Hanyuda, Akiko; Rosner, Bernard A; Wiggs, Janey L; Willett, Walter C; Tsubota, Kazuo; Pasquale, Louis R; Kang, Jae H (Eye (London, England), 2020)
BACKGROUND/OBJECTIVES: To assess the long-term association between low-carbohydrate dietary patterns and incident primary open-angle glaucoma (POAG), and POAG subtypes defined by highest untreated intraocular pressure (IOP) and by pattern of visual field (VF) loss at diagnosis., SUBJECTS/METHODS: We followed 185,638 participants of three large US prospective cohorts biennially (1976-2016, 1986-2016 and 1991-2017). Deciles of three low-carbohydrate-diet scores were calculated to represent adherence to diets lower in carbohydrate and higher in protein and fat from any source, animal sources or plant sources. We confirmed POAG cases (n = 2112) by medical record review and used Cox proportional hazards models to estimate multivariable-adjusted relative risks (MVRRs) and 95% confidence intervals (CIs)., RESULTS: There was no association between the three types of low-carbohydrate-diet scores and POAG: the MVRR for POAG in the highest vs. lowest deciles was 1.13 (95% CI, 0.91-1.39; Ptrend = 0.40) for the overall score; 1.10 (95% CI, 0.89-1.35; Ptrend = 0.38) for the animal score and 0.96 (95% CI, 0.79-1.18; Ptrend = 0.88) for the vegetable score. No differential associations by IOP level was found (Pheterogeneity >= 0.06). However, the vegetable score showed a suggestive inverse association with early paracentral VF loss (highest vs. lowest decile MVRR = 0.78 [95% CI, 0.55-1.10]; Ptrend = 0.12) but not with peripheral VF loss only (MVRR = 1.09 [95% CI, 0.83-1.44]; Ptrend = 0.14; Pheterogeneity = 0.03)., CONCLUSIONS: Low-carbohydrate diets were not associated with risk of POAG. Our data suggested that higher consumption of fat and protein from vegetable sources substituting for carbohydrates was associated with lower risk of the POAG subtype with initial paracentral VF loss.
Keywords: Carbohydrates; Diet, Carbohydrate-Restricted; Follow-Up Studies; Glaucoma, Open-Angle/ep [Epidemiology]; Glaucoma, Open-Angle/et [Etiology]; *Glaucoma, Open-Angle; Humans; Intraocular Pressure; Prospective Studies; Risk Factors; Surveys and Questionnaires

Adherence to glaucoma medication, illness perceptions, and beliefs about glaucoma: Attitudinal perspectives among Turkish population. - Guven, Soner; Koylu, Mehmet Talay; Mumcuoglu, Tarkan (European journal of ophthalmology, 2021)
PURPOSE: To evaluate the topical glaucoma eye drops adherence prevalence and its association with beliefs and illness perceptions about glaucoma in Turkey. We also aimed to explore the factors linked to patients' total, voluntary, and involuntary non-adherence to medication in different patient attitudes., MATERIAL AND METHODS: A prospective study with cross-sectional design which included a total of 317 glaucoma patients who completed questionnaires. We assessed the adherence to medication, illness perceptions, and the beliefs about the glaucoma treatment by the "Reported Adherence to Medication scale," "the Brief Illness Perception Questionnaire," and "the Beliefs about Medicine-Specific Questionnaire," respectively. According to the RAM scale, voluntary and involuntary non-adherence scores were also distinguished. Different adherence categories in RAM scale were compared with perception and belief measures. Patient attitudes were assessed from the BMQ. We also performed attitudinal type comparisons with different adherence groups., RESULTS: The full adherence prevelance to glaucoma medication was 40%. The proportion of voluntary and involuntary non-adherence was 26% and 57%, respectively. The adherence groups were similar in terms of belief measures but statistically different according to illness perceptions (consequences (p = 0.002), timeline (p = 0.008), personal control (p = 0.001), identity (p = 0.019), concerns (p = 0.003)), and attitude types (ambivalent (p = 0.030) and accepting (p = 0.029))., CONCLUSION: New strategies are required to improve patient adherence to glaucoma medication in Turkey. The beliefs about the glaucoma treatment and illness perceptions are also needed to be enhanced.
Keywords: Adult; Aged; Aged, 80 and over; Antihypertensive Agents/ad [Administration & Dosage]; Cross-Sectional Studies; Female; *Glaucoma/dt [Drug Therapy]; Glaucoma/eh [Ethnology]; *Glaucoma/px [Psychology]; Health Knowledge, Attitudes, Practice/eh [Ethnology]; *Health Knowledge, Attitudes, Practice; Humans; *Illness Behavior/ph [Physiology]; Male; Medication Adherence/px [Psychology]; *Medication Adherence/sn [Statistics & Numerical Data]; Middle Aged; Ophthalmic Solutions/ad [Administration & Dosage]; Perception; Prospective Studies; Surveys and Questionnaires; Turkey/ep [Epidemiology]; Young Adult

Patient-reported outcomes measures and patient preferences for minimally invasive glaucoma surgical devices. - Li, Tianjing; Le, Jimmy T; Hays, Ronald D; Cui, Qi N; Eydelman, Malvina; Spaeth, George; Tarver, Michelle E; Singh, Kuldev (Eye (London, England), 2020)
BACKGROUND: Many therapeutic options are available to glaucoma patients. One recent therapeutic option is minimally invasive glaucoma surgical (MIGS) devices. It is unclear how patients view different treatments and which patient-reported outcomes would be most relevant in patients with mild to moderate glaucoma. We developed a questionnaire for patients eligible for MIGS devices and a patient preference study to examine the value patients place on certain outcomes associated with glaucoma and its therapies., OBJECTIVES: To summarize the progress to date., METHODS: Questionnaire development: We drafted the questionnaire items based on input from one physician and four patient focus groups, and a review of the literature. We tested item clarity with six cognitive interviews. These items were further refined. Patient preference study: We identified important benefit and risk outcomes qualitatively using semi-structured, one-on-one interviews with patients who were eligible for MIGS devices. We then prioritized these outcomes quantitatively using best-worst scaling methods., RESULTS: Questionnaire testing: Three concepts were deemed relevant for the questionnaire: functional limitations, symptoms, and psychosocial factors. We will evaluate the reliability and validity of the 52-item draft questionnaire in an upcoming field test. Patient preference study: We identified 13 outcomes that participants perceived as important. Outcomes with the largest relative importance weights were "adequate IOP control" and "drive a car during the day.", CONCLUSIONS: Patients have the potential to steer clinical research towards outcomes that are important to them. Incorporating patients' perspectives into the MIGS device development and evaluation process may expedite innovation and availability of these devices.
Keywords: Glaucoma/su [Surgery]; *Glaucoma; Humans; Intraocular Pressure; *Patient Preference; Patient Reported Outcome Measures; Reproducibility of Results

Comparison of Goldmann applanation and Ocular Response Analyser tonometry: intraocular pressure agreement and patient preference. - McCann, Paul; Hogg, Ruth E; Wright, David M; McGuinness, Bernadette; Young, Ian S; Kee, Frank; Azuara-Blanco, Augusto (Eye (London, England), 2020)
OBJECTIVES: To evaluate the agreement between Goldmann applanation tonometry (GAT) and Ocular Response Analyser (ORA) intraocular pressure (IOP) measurements, and patients' preferences., METHODS: Both eyes of participants in the 'Glaucoma within the Northern Ireland Cohort for the Longitudinal Study of Ageing' (GwNICOLA) were included. Participants underwent GAT by a glaucoma expert and ORA tonometry in a random order. Investigators were masked to measurements between devices. Participants were asked which tonometer, if any, they would prefer. We estimated the 95% limits of agreement (95% LoA) and the variables that influence agreement between tonometers., RESULTS: There were 228 eyes of 120 participants included in this study. Mean age of participants was 68.0 years (SD 8.79) and 52.5% were female. For GAT-ORA IOPcc the mean difference with GAT (95% CI) was -0.23 mmHg (-0.57 mmHg, 0.11 mmHg) and the 95% LoA (95% CIs) were from 4.82 mmHg (5.15 mmHg, 4.48 mmHg) to -5.28 mmHg (-5.61 mmHg, -4.94 mmHg). 40.8% of eyes had an IOP difference of 2 mmHg or more between GAT and ORA IOPcc. Corneal resistance factor (CRF) as estimated by ORA influenced the agreement between GAT and ORA IOPcc. There were no differences in preference for method of tonometry., CONCLUSIONS: Although ORA IOPcc measurements with ORA did not show significant bias compared with GAT, the relatively large proportion of measurement differences between ORA IOPcc and GAT that were >2 mmHg indicates that GAT and ORA IOP measurements may not be interchangeable. There were no differences in preference for method of tonometry.
Keywords: Aged; Cornea; Female; Humans; *Intraocular Pressure; Longitudinal Studies; Male; Manometry; Northern Ireland; *Patient Preference; Tonometry, Ocular

Micro-interaction of mucin tear film interface with particles: The inconsistency of pharmacodynamics and precorneal retention of ion-exchange, functionalized, Mt-embedded nano- and microparticles. - Han, Xinyue; Zhao, Yawen; Liu, Hanyu; Li, Huamei; Liu, Shuo; Rupenthal, Ilva D; Yang, Fan; Lv, Zhufen; Chen, Yanzhong; Zang, Linquan; Li, Wei; Ping, Qineng; et al. (Colloids and surfaces. B, Biointerfaces, 2021)
Physiological reflexes and anatomical barriers render traditional eye drop delivery inefficient. We previously reported that drug-loaded nanoparticles and microspheres prepared from montmorillonite and Eudragit polymers exhibited good sustained-release and lowered intraocular pressure. Here, we compared the performance of optimized formulations to select the most suitable formulation for glaucoma therapy. We found that the microspheres had much higher encapsulation efficiency and drug loading than nanoparticles. Moreover, cytocompatibility experiments demonstrated that nanoparticles showed more severe cytotoxicity than microspheres, probably due to their smaller particles, enhanced cell uptake, and intracellular solubility. Interestingly, the pre-corneal retention time of nanoparticles reflected a clear advantage over microspheres, while the duration of the pharmacological effect of nanoparticles was not as good as that of microspheres: compared with the nanoparticle depressurization duration of only 8 h, the microspheres continuously depressurized for 12 h. The slower release of the microspheres and its micro-interaction mechanism with the discontinuous mucin layer of the tear film led to the inconsistency between duration of pharmacodynamics and fluorescence ocular retention time. In summary, the lower cytotoxicity and longer pharmacological effect of microspheres indicate their potential advantages for glaucoma applications. Copyright © 2020 Elsevier B.V. All rights reserved.
Keywords: Delayed-Action Preparations; Ion Exchange; Microspheres; *Mucins; *Nanoparticles; Particle Size

Low-cost, smartphone-based frequency doubling technology visual field testing using a head-mounted display. - Alawa, Karam AlRahman; Nolan, Ryan P; Han, Elaine; Arboleda, Alejandro; Durkee, Heather; Sayed, Mohamed S; Aguilar, Mariela C; Lee, Richard K (The British journal of ophthalmology, 2021)
BACKGROUND: Current visual field screening machines are bulky and expensive, limiting their accessibility, affordability and use. We report the design and evaluation of a novel, portable, cost-effective system for glaucoma screening using smartphone-based visual field screening using frequency doubling technology (FDT) and a head-mounted display., METHODS: Nineteen eyes of 10 subjects with new-onset or chronic primary open angle glaucoma were tested and compared with the Humphrey Zeiss FDT and the newly developed Mobile Virtual Perimetry (MVP) FDT with the C-20 testing pattern. Mann-Whitney, Bland-Altman and linear regression analyses were performed to assess statistical difference, agreement and correlation, respectively, between the two devices., RESULTS: The average age of the participants was 58+/-15 years. No statistically significant difference was found between the MVP FDT and the Humphrey Zeiss FDT (p>0.05). Bland-Altman and linear regression analyses demonstrated good agreement and correlation between the two devices., CONCLUSION: The MVP FDT is a low-cost, portable visual field screening device that produces comparable results to the Humphrey Zeiss FDT and may be used as an easily accessible screening tool for glaucoma. Copyright © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: Equipment Design; Female; *Glaucoma, Open-Angle/di [Diagnosis]; Glaucoma, Open-Angle/pp [Physiopathology]; Humans; *Intraocular Pressure/ph [Physiology]; Male; Middle Aged; *Smartphone; *Visual Field Tests/is [Instrumentation]; *Visual Fields/ph [Physiology]

Impact of COVID-19 on follow-up and medication adherence in patients with glaucoma in a tertiary eye care centre in south India. - Subathra, G N; Rajendrababu, Sharmila R; Senthilkumar, Vijayalakshmi A; Mani, Iswarya; Udayakumar, B (Indian journal of ophthalmology, 2021)
Purpose: COVID-19 pandemic has affected the healthcare system worldwide hindering the continuum of treatment of chronic disease patients. The objective of the study is to analyze the barriers encountered by the glaucoma patients for the follow-up visit and medication adherence during the pandemic., Methods: This cross-sectional study included glaucoma patients who did not attend the scheduled appointment from April 1, 2020 to July 31, 2020 in a tertiary eye care center (88.21%). Eligible patients of age >18 years and advised antiglaucoma medication in Madurai Zone were interviewed with validated questionnaire through telephonic call., Results: 363 patients answered the questionnaire through telephonic interview. 57.3% of the patients were found to be non-adherent to medication. The main barriers for glaucoma follow-up visit during the pandemic were lockdown restriction, transport problem, and financial difficulties. The top barriers for medication adherence were non availability of medication (54.81%), financial difficulties (30.29%), did not feel much improvement with eye drops (20.19%). On multiple regression analysis, longer distance to hospital, low socioeconomic status, more than one antiglaucoma medication use, lack of awareness of glaucoma, non-complaint before COVID-19 and stress due to the pandemic were found to be significant factors for medication non adherence., Conclusion: COVID-19 pandemic has emphasized the need for reformation in health care system for accessibility of medical care to patients in rural areas. Decentralization of health system to primary care level and utilization of teleophthalmology should be considered by health care planners in future.
Keywords: Adolescent; *COVID-19; Communicable Disease Control; Cross-Sectional Studies; Follow-Up Studies; Glaucoma/dt [Drug Therapy]; Glaucoma/ep [Epidemiology]; *Glaucoma; Humans; India/ep [Epidemiology]; Medication Adherence; *Ophthalmology; Pandemics; SARS-CoV-2; *Telemedicine

The role of Visual Evoked Potential (VEP) in monitoring the progression and in guiding the treatment of glaucoma patients with poor compliance. - Firan, Anne Marie; Iancu, Raluca Claudia; Bujor, Inna Adriana; Ciuluvica, Radu Constantin; Tudosescu, Ruxandra; Ungureanu, Emil; Pasca, Irena Gabriela; Voinea, Liliana; Istrate, Sinziana (Romanian journal of ophthalmology, 2020)
Objectives: The objectives of the present study were to analyze the possibility of using pattern VEPs (VEP of pattern type) in glaucoma patients and their role in the follow-up and coordination/ management of anti-glaucoma treatment. Patients and Methods: This is a prospective study on 54 eyes of 30 consecutive glaucoma patients, whose compliance capacity did not allow automatic perimetry and OCT scan to be carried out. The patients were divided into two groups: group A - the study group and group B - the control group. All patients underwent FO exam and pachymetry, plus VEP exam for group A patients. Patients were analyzed at the initial visit and at 1 month, 3, 6, 12 months. Statistical analysis was made using t-test, ANOVA, Fisher test and Pearson correlation coefficient. Results: These participants presented a positive correlation between C/ D ratio and the latency of the P100 wave at 1 degree and a negative correlation between C/ D ratio and the amplitude of the P100 wave both at 1 degree (60 arc minutes) and at 0.25 degrees (15 arc minutes). During the study, the values of the latent P100 changed statistically at 6 months and at 1 year. Using all the data, the authors of the study considered it necessary to modify the treatment for 2 patients out of 13 in group B and for 9 patients out of 16 in group A (p = 0,02892). Conclusions: VEP supplies additional/ further data that significantly help guiding the treatment and monitoring the progression, therefore, it should be part of the routine examination for these patients. Further studies are necessary to deepen our understanding of the visual evoked potentials utility. Copyright ©Romanian Society of Ophthalmology.
Keywords: Aged; Aged, 80 and over; *Antihypertensive Agents/tu [Therapeutic Use]; Disease Progression; *Evoked Potentials, Visual/ph [Physiology]; Female; Follow-Up Studies; Glaucoma/dt [Drug Therapy]; *Glaucoma/pp [Physiopathology]; *Guideline Adherence; Humans; *Intraocular Pressure/ph [Physiology]; Male; Middle Aged; *Monitoring, Physiologic/mt [Methods]; *Patient Compliance; Prospective Studies

Bacterial keratitis due to Moraxella nonliquefaciens. - Diaz Barron, A; Sanz Gallen, L; Hervas Hernandis, J M; Tarrago Simon, E; Duch-Samper, A M (Archivos de la Sociedad Espanola de Oftalmologia, 2020)
Moraxella keratitis can lead to important complications. Moraxella nonliquefaciens(M. nonliquefaciens) has the worst prognosis. Only three cases of corneal infections due to M. nonliquefaciens have been published. The case is presented of a 79-year-old man with bullous keratopathy, recently affected with severe infectious keratitis. Dense, deep, and central stromal infiltrates and hyphaema were detected. After the identification of M. nonliquefaciens in the culture, and given the progression of the condition, the initial empirical treatment was modified to topical ciprofloxacin and ceftazidime in accordance with the antibiogram, combining oral ciprofloxacin and amoxicillin-clavulanate. After 27 days, there was total resolution of the lesion, with central residual leucoma. Keratitis caused by M. nonliquefaciens is rare and must be suspected in elderly patients with local predisposing factors, such as corneal damage or previous eye surgery. Early antibiogram-guided treatment and close monitoring are important to avoid complications and poor compliance. Copyright © 2020. Publicado por Elsevier Espana, S.L.U.
Keywords: Aged; Amoxicillin-Potassium Clavulanate Combination/tu [Therapeutic Use]; Anti-Bacterial Agents/tu [Therapeutic Use]; Ceftazidime/tu [Therapeutic Use]; Ciprofloxacin/tu [Therapeutic Use]; Corneal Opacity/et [Etiology]; Corneal Ulcer/dt [Drug Therapy]; *Corneal Ulcer/mi [Microbiology]; Drug Substitution; Eye Infections, Bacterial/dt [Drug Therapy]; *Eye Infections, Bacterial/mi [Microbiology]; Humans; Hyphema/et [Etiology]; Male; *Moraxella/ip [Isolation & Purification]; Moraxellaceae Infections/dt [Drug Therapy]; *Moraxellaceae Infections/mi [Microbiology]; Vancomycin/tu [Therapeutic Use]

The differences between patient and optometrist experiences of contact lens hygiene education from the perspective of a Scottish university teaching hospital. - Hind, Jennifer; Williams, Olayinka; Oladiwura, Dilys; Macdonald, Elisabeth (Contact lens & anterior eye : the journal of the British Contact Lens Association, 2020)
BACKGROUND: Contact lens related keratitis is a frequent presentation to acute ophthalmology services. Patients often do not recall being counselled regarding the safe use of contact lenses therefore fail to comply with guidance. This study aimed to identify the content and format of advice given to patients with contact lens keratitis concerning appropriate hygiene practices, determine their compliance with this and finally characterise optometrist practices regarding contact lens advice provided to patients., METHODS: All adult patients presenting with contact lens related keratitis to the acute ophthalmology clinic were asked to complete a survey. Information was collected on lens type, format of advice received and compliance. Community optometrists were asked to complete an electronic survey on their contact lens review practices and routine patient education., RESULTS: All patients surveyed recalled counselling on initiation of contact lenses; however 12% (6/50) were given no advice on return visits. This advice was in written format for 20% (10/50) of patients on initiation increasing to 32% (16/50) on renewal. Many patients slept (22%), showered (44%) or swam (36%) in lenses. 92% cleaned their contact lenses appropriately, but cases were washed infrequently (19% of cases cleaned<monthly) or with tap water (27%). All optometrists surveyed claimed to provide advice to patients in either written or verbal format for new and returning contact lens users. 49% (16/33) of optometrists gave written advice to patients on initial contact lens fitting, but only 1/33 continued with written advice for repeat customers., CONCLUSION: This study identified that although most patients were informed of appropriate hygiene requirements, compliance was poor. Optometrists regularly provide verbal advice but do not routinely offer written support and there is a mismatch between patient recollection and self-reported optometrist practice. It is suggested that patient education needs greater emphasis and both verbal and written information should be regularly provided on initial review and follow up assessments. Copyright © 2019 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
Keywords: *Contact Lenses; *Education, Medical; *Hospitals, Teaching; Humans; *Hygiene/ed [Education]; *Optometrists/ed [Education]; Patient Compliance/sn [Statistics & Numerical Data]; Prospective Studies; Scotland; *Self Report; Surveys and Questionnaires

An exploratory study of compliance to anti-glaucoma medications among literate primary glaucoma patients at an urban tertiary eye care center in South India. - Ramesh, Prasanna Venkatesh; Parthasarathi, Sathyan; John, Rajesh Kumar (Indian journal of ophthalmology, 2021)
Purpose: To understand the factors that explain compliance to anti-glaucoma medication (AGM) in terms of application,purchase, stocking and compliance behaviour., Methods: This was a cross-sectional study conducted in the outpatient department of an urban tertiary eye care center in South India. Interviews were completed with consenting, consecutive, literate primary glaucoma patients. The components of the questionnaire included duration, application, purchase, stocking and caregiver's role. Self-reported compliance in medication taking was tested for association with rest of the components by Chi-square test and discriminant analysis., Results: A total of 101 patients, aged 34-87 years, were interviewed. Majority (64.4%) were on AGM for more than two years. Early purchase was reported among 44.3% and stocking among 41.2%. Cost was high for income among 28.7%. Majority (91.1%) of them were not aware of side-effects. Fear of blindness was the major factor (68.1%) encouraging regular usage. Half (50.5%) of the patients though, still reported missing medication in the past month. Major reasons cited were relative priority (45.1%) and forgetfulness (35.3%). Self-reported compliance was not different by demographic variables or with responses to questions regarding duration (P = 0.070), application (0.825), time of purchase (0.272), stocking (0.598), and cost perception (0.415)., Conclusion: Self-reporting of AGM compliance behaviour did not reflect with responses regarding application, purchase, stocking behaviour or cost perception. Awareness and knowledge of the above factors, with an aim of improving compliance by regulating counselling for even literate patients using AGM is called for.
Keywords: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Glaucoma/dt [Drug Therapy]; Glaucoma/ep [Epidemiology]; *Glaucoma; Humans; India/ep [Epidemiology]; Medication Adherence; Middle Aged; Surveys and Questionnaires

Visual demand, visual ability and vision standards for hairdressers - An observational study from Chennai, Tamil Nadu. - Janani, Suresh; Dhanalakshmi, Sankar; Rashima, Asokan; Krishnakumar, Ramani; Santanam, P P (Indian journal of ophthalmology, 2021)
Purpose: The aim of this study was to create vision standards for various tasks performed by hairdressers and to assess the spectacle compliance and its impact at work., Methods: The observational cross-sectional study enrolled hairdressers in and around Chennai, Tamil Nadu. It was done in three phases: (i) Job profiling from visual task analysis, creating vision standards for various hairdressing tasks and arriving at test protocols; (ii) Comprehensive eye examination, and (iii) Assessment of spectacle compliance and its impact on work. Descriptive analysis using Microsoft Excel and SPSS (IBM SPSS Statistics Version 21.0) was performed., Results: There were 305 participants with a mean age of 48 (SD +/- 12) years. The visual acuity demand was found to be 6/18 and N15, for distance and near, respectively. Appropriate spectacles were prescribed for 203 (67%) hairdressers. Even with the best possible refractive correction, a few hairdressers did not meet the distance (13) and near (11) visual acuity standard. In all, 54 hairdressers were referred for further examination to a tertiary eye care center for lenticular changes, retinal abnormalities, and glaucoma screening. Among the subjects who were dispensed with spectacles, 181 (86%) were available for telephonic spectacle compliance assessment, and 164 (90%) were compliant with spectacle usage at work. Improved visual ability was reported by 133 (81%) hairdressers at work., Conclusion: This study provides vision standards for hairdressers. From the visual task analysis, hairdressing tasks were found to be visually demanding and hazardous. The study emphasizes that providing appropriate spectacle correction showed a clinically evident positive impact at work.
Comment in (CIN)
Keywords: Cross-Sectional Studies; Eyeglasses; Humans; India/ep [Epidemiology]; Middle Aged; Refractive Errors/di [Diagnosis]; Refractive Errors/ep [Epidemiology]; Refractive Errors/th [Therapy]; *Refractive Errors; Visual Acuity

Medication Adherence and Persistence of Open-Angle Glaucoma Patients in Korea: A Retrospective Study Using National Health Insurance Claims Data. - Jang, Yunjeong; Jee, Donghyun; Lee, Donghwan; Choi, Nam-Kyong; Bae, SeungJin (International journal of environmental research and public health, 2021)
This study aimed to analyze medication adherence and persistence among open-angle glaucoma patients in Korea. A retrospective study was conducted using the Korean National Health Insurance (NHI) claims database from 2016 to 2019. Newly diagnosed open-angle glaucoma patients who were prescribed with the intraocular pressure (IOP)-lowering eyedrops were included. Adherence was measured using the medication possession ratio (MPR), and persistence was measured using the duration of therapy during the 24 month follow-up period. During the study period, 14,648 open-angle glaucoma patients were identified, and 3118 (21.3%) and 4481 patients (30.6%) were adherent to and persistent with their glaucoma treatment, respectively. The mean MPR was 48.8%, and the mean duration of therapy was 357.2 days. Logistic regression analysis showed that patients who are older, female, using prostaglandins as the index medication, and visiting secondary or tertiary hospitals were significantly associated with greater rates of adherence (odds ratio (OR) = 1.21, 1.12, 1.27, and 1.73, respectively) and persistence (OR = 1.11, 1.17, 1.16, 1.17, and 1.36, respectively) during the study period. Patients with open-angle glaucoma in Korea had substandard medication adherence and discontinued their treatment. Ophthalmologists should pay more attention to younger, male patients to improve adherence.
Keywords: Antihypertensive Agents/tu [Therapeutic Use]; *Antihypertensive Agents; Female; Glaucoma, Open-Angle/dt [Drug Therapy]; Glaucoma, Open-Angle/ep [Epidemiology]; *Glaucoma, Open-Angle; Humans; Male; Medication Adherence; National Health Programs; Republic of Korea; Retrospective Studies

Patients' perception of glaucoma diagnosis practice: Results from a survey of glaucoma patients in North India. - Sood, Devindra; Sood, Ishaana; Sood, Shivam; Kumar, Dinesh; Sood, Rajeev; Sood, Narender N (International ophthalmology, 2020)
PURPOSE: This study assesses the practice patterns of diagnosing ophthalmologists, as reported by glaucoma patients attending specialty glaucoma clinics in urban and rural areas of North India, for a second opinion., METHODS: Prospective cross-sectional study using a structured interview-based survey was conducted from 1 November 2011 to 31 October 2012 on patients attending two specialty glaucoma care facilities in North India. Both clinics were in North India; however, one was rural (Kaithal) and one was urban (Delhi). Patients were asked through descriptions of machines and processes, regarding practice patterns of their glaucoma diagnosing ophthalmologists. The interview was conducted by ophthalmic assistants in tune with the vernacular of the region, in a language understood by the interviewee., RESULTS: A total of 1506 patients consented to participate in the survey. The majority of patients reported undergoing tests for intraocular pressure measurement; however, 56-60% of these tests were carried out by the non-contact tonometer. More than 90% of patients reported no knowledge regarding the type and severity of the glaucoma they suffered from, and even less reported undergoing gonioscopy (3.6% Karnal and 16% Delhi). 84-86% patients who underwent perimetry reported undergoing at least some digital imaging of the optic disc., CONCLUSIONS: Better counselling of, and communication with, the patient would help increase their awareness regarding their condition and the care required. This has the potential to enable better compliance with and adherence to treatment. Standardized training of ophthalmologists to improve clinical diagnosis of glaucoma would also go a long way.
Keywords: Communication; Cross-Sectional Studies; Glaucoma/di [Diagnosis]; Glaucoma/ep [Epidemiology]; *Glaucoma; Humans; India/ep [Epidemiology]; *Intraocular Pressure; Physician-Patient Relations; Prospective Studies

Nanomedicines for the treatment of glaucoma: Current status and future perspectives. - Zhai, Zimeng; Cheng, Yiyun; Hong, Jiaxu (Acta biomaterialia, 2021)
Glaucoma is the global leading cause of irreversible blindness. It is a chronic progressive disorder and, therefore, often requires long-term management with drugs on patients' discretion. However, there is a shortage of antiglaucoma drugs in the current market due to their low bioavailability. This is because there are multiple biological barriers of the human eyes, thereby leading to increased demands for frequent dosage regimen per day of these drugs, which could result in concomitant side effects and eventually reduced patient compliance. Recently, nanomedicines have become optimized alternatives to conventional ophthalmic formulations due to advantages of improved barrier permeability, sustained drug release, tissue targeting, and lowered systemic absorption of instilled medications. These merits provide the active ingredients in these nanomedicines an effective manner to reach the ideal concentrations at sites of damaged nerves, offering a promising platform for neuroprotective treatment of these conditions. In this study, nanomedicines and nanomedicine-based novel strategies for pharmacotherapy of glaucoma were reviewed, including liposomes, niosomes, nanoparticles, and dendrimers. This article intends to offer a comprehensive review of frontier progresses as well as hotspots and issues that appeared in the field of nanomedicines, which may enable a practical flourish in the future. STATEMENT OF SIGNIFICANCE: Recent novel pharmaceutical strategies toward glaucoma, a chronic blinding ocular disease that currently requires frequent daily dosage regimen, based on nanomedicines and nanomaterials have been comprehensively reviewed in this manuscript. The collection of field hotspots and issues in the late years should offer a quick grasp of the general concept and up-to-date threads upon the refinement of existing treatment patterns for glaucoma. Meanwhile, the Conclusion and Future Perspective section given at the end of the text brings out the possible shortages and opinions in terms of ideal research direction, which hopefully could facilitate a future practical flourish in the area. Copyright © 2021 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Keywords: Drug Delivery Systems; Glaucoma/dt [Drug Therapy]; *Glaucoma; Humans; Liposomes; Nanomedicine; *Nanoparticles

Investigation of Approval Trends and Benefits of New Fixed-Dose Combination Drugs in Japan. - Kikuchi, Chikara; Ohno, Mifuyu; Izumo, Takafumi; Takahashi, Satoru; Aoki, Masayuki; Shimomura, Hitoshi; Kawano, Yohei; Shimada, Shuji; Aoyama, Takao (Therapeutic innovation & regulatory science, 2020)
BACKGROUND: New fixed-dose combination drugs (FDCs) had been developed in limited numbers in Japan. Since regulatory requirements were relaxed in 2005, 73 new FDCs have been approved by PMDA since 2006. In this study, we investigate trends in new FDCs and their benefits through a questionnaire survey provided to patients and pharmacists., METHODS: The new FDCs were analyzed by therapeutic categories, first approval country and drug lag (DL). Questionnaire surveys were conducted on hypertension, bronchial asthma, and glaucoma in approximately 300 patients and 700 pharmacists in 66 hospitals to investigate the benefits of new FDCs., RESULTS: The highest number of FDCs approved by the therapeutic category was 15 cardiovascular agents. The DL (median) was less than 1 year in several therapeutic categories including cardiovascular agents. The survey results showed that patient compliance improved in 30.8% of the bronchial asthma. Regarding the time and effort required to prescribe these drugs, 32.5% of pharmacists reported "slightly decreased" in bronchial asthma, while 32.0% reported "slightly increased" in hypertension. More than one-third (70.6%) responded "recommend" in bronchial asthma., CONCLUSION: The number of new FDCs markedly increased since 2006, and this presented new opportunities for the Japanese pharmaceutical industry. FDCs not only increase convenience to the patient but also improve patient compliance and the efficiency of pharmacist prescription processes. However, the rapid increase in new FDCs may cause confusion in the medical field, and new FDCs should be developed not only to improve convenience but also to consider the benefits they provide to patients, pharmacists, and physicians.
Keywords: *Drug Approval; *Drug Combinations; *Drug Industry; Humans; Japan; Surveys and Questionnaires

AMNIOTIC MEMBRANE TRANSPLANTATION AT THE DEPARTMENT OF OPHTHALMOLOGY OF THE UNIVERSITY HOSPITAL BRNO. - Zemanova, M; Pacasova, R; Sustackova, J; Vlkova, E (Ceska a slovenska oftalmologie : casopis Ceske oftalmologicke spolecnosti a Slovenske oftalmologicke spolecnosti, 2021)
BACKGROUND: The aim of the work is a discussion of amniotic membrane transplantation at the Eye Clinic of the University Hospital Brno and a retrospective evaluation of a group of patients for the period 2014-2019 who were treated for various indications., METHODS: Retrospective evaluation of the number and effectiveness of individual types of amniotic membrane in a group of patients after amniotic membrane transplantation (AMT) for various indications. A total of 134 patients were included in the study group, of which 68 were men and 66 were women. The median age was 70 years. The total number of amniotic membrane transplants performed during the selected six years was 139, with half the distribution using frozen (69 eyes) and lyophilized amniotic membrane (70 eyes). The AMT technique was chosen based on the initial finding and diagnosis. The type of amniotic membrane used (lyophilized vs. frozen) depended on the urgency of the procedure., RESULTS: The number of amniotic membrane transplantations was evaluated in a group of 134 patients (139 eyes) and their effectiveness in individual diagnoses was demonstrated. During the follow-up period, more transplantations of amniotic membranes were performed during hospitalization than in the outpatient department, both types of membranes (frozen and lyophilized). Amniotic membrane transplantation during hospitalization was performed in 89 eyes, in the outpatient mode in 50 eyes. Indications for amniotic membrane transplantation included microperforation and corneal perforation (30 eyes), non-healing corneal defects (21 eyes), descemetocele (19 eyes), neurotrophic defects (16 eyes), ablation of pterygium (12 eyes) and corneal lysis (11 eyes). eyes). Other conditions (conjunctival lesions, fornix reconstruction, burns, peripheral ulcerative keratitis, ocular cicatricial pemphigoid and keratectomy) were represented in smaller numbers. Despite the very diverse group of indications and the advanced age of the patients, a very good efficacy of the performed amniotic membrane transplantations was found. Some patients died during the follow-up period, so the limitation of work is short and unequal follow-up period., CONCLUSION: The success of the procedure depends not only on the correct timing, indication and technique of transplantation, but also on patient compliance and well-functioning cooperation of regional ophthalmologists.
Keywords: Aged; Amnion/tr [Transplantation]; *Conjunctival Diseases; Corneal Diseases/su [Surgery]; *Corneal Diseases; *Eye Diseases; Female; Hospitals; Humans; Male; Retrospective Studies

Assessing patient cosmetic satisfaction after glaucoma drainage device surgery for different patch grafts. - Milibari, Doaa S; Fatani, Dalal; Ahmad, Abeer; Owaidhah, Ohoud; AlObeidan, Saleh A; Almobarak, Faisal A; Malik, Rizwan (BMC ophthalmology, 2021)
BACKGROUND: The use of a tissue patch graft is common practice with a glaucoma drainage device (GDD). Patch grafts can be visible in the palpebral fissure and may be cosmetically displeasing for some patients. The aim of this study was to report the cosmetic satisfaction of pericardial, scleral, and corneal patch grafts related to superior GDD surgery., METHODS: Baseline clinical data were collected for consecutive patients with glaucoma operated between 2014 and 2019 at two tertiary eye care institutions (for superiorly-placed) Ahmad glaucoma valve implant using sclera, cornea and pericardium patch graft. A patient questionnaire that contained 4 concise questions, with a Likert-scale grading relating to cosmetic satisfaction was administered by a telephone-based interview. Responses and scores for each question were compared across patients who received the three different types of graft. A binominal logistic regression analysis was used to assess the effects of age, gender, type of graft, number of previous ocular surgeries, and final visual acuity to explain differences., RESULTS: We included 92 patients who met our inclusion criteria (24 patients received a corneal patch graft, 30 who received sclera and 38 who received pericardium). The mean (+/-SD) age was 50 (+/-17.5) years, and the average follow up was 20.7 (+/- 18.6) months. Regardless of the type of patch graft, most (67-84%) of patients were satisfied with the appearance of their eyes. Patients who received cornea or sclera were more likely to report that their eye looked 'abnormal' by others. Younger age was significantly associated with the response to this question., CONCLUSION: Patients are generally satisfied with the appearance of their eye following GDD surgery with each of the patch grafts for superiorly-placed GDDs. Younger patients with cornea or sclera were more likely to report that their eyes looked abnormal.
Keywords: Adult; Aged; *Glaucoma Drainage Implants; Humans; Intraocular Pressure; Middle Aged; Patient Satisfaction; *Personal Satisfaction; Prosthesis Implantation; Retrospective Studies

Evaluation of early medication persistence with omidenepag isopropyl, a topical selective prostaglandin EP2 agonist, in patients with glaucoma: a retrospective two-institute study. - Nakakura, Shunsuke; Kanamori, Akiyasu; Fukuma, Yasuko; Wakabayashi, Seita; Nagata, Yuki; Adachi, Miku (BMJ open, 2021)
OBJECTIVES: We evaluated early medication persistence with new topical antiglaucoma eyedrops, omidenepag isopropyl 0.002% (a selective prostaglandin EP2 agonist)., DESIGN AND SETTING: Retrospective two-institute study in Himeji and Akashi in Japan., PARTICIPANTS: We analysed patients with glaucoma who were prescribed topical omidenepag isopropyl from November 2018 to December 2019. From the last outpatient visit of patients until February 2020, 235 patients were prescribed a new solution of omidenepag isopropyl (129 patients in the initial monotherapy group, 85 in the switching group (switched from another topical antiglaucoma eyedrops), 19 added to another topical antiglaucoma eyedrops group, and 2 were lost to follow-up)). Additionally, we recruited 98 patients (3 were lost to follow-up) who received initial latanoprost 0.005% monotherapy during the same period as a control group., OUTCOMES: Medication persistence failure was defined as drug discontinuation due to any adverse effects or change of therapy. Kaplan-Meier survival analysis was performed with a Cox regression analysis., RESULTS: Among 233 patients, 48 (20%) showed failure of treatment; the median persistence time of all patients was 165 days, and the median time until discontinuation of omidenepag isopropyl was 45 days. The total persistence rates were 85%, 80% and 70% at 3, 6 and 12 months, respectively. Risk factors for failure were male gender (HR: 1.45, p=0.023) and monotherapy/switching (HR: 1.715, p=0.002). Comparison between latanoprost and omidenepag isopropyl monotherapy, only male gender (HR: 1.43, p=0.016) was a significant risk factor. Failures associated with omidenepag isopropyl were due to insufficient intraocular pressure-lowering efficiency (n=26, observed during all the period), followed by conjunctival hyperaemia (n=10) and visual acuity disturbance (n=5) in patients who were observed until 3 months., CONCLUSION: Medication persistence with omidenepag isopropyl is mostly positive; however, clinicians should also be cautious of early failure. Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: Antihypertensive Agents/tu [Therapeutic Use]; Female; Glaucoma/dt [Drug Therapy]; *Glaucoma; Glycine/aa [Analogs & Derivatives]; Humans; Intraocular Pressure; Japan; Male; Medication Adherence; Ophthalmic Solutions; *Prostaglandins; Pyrazoles; Pyridines; Retrospective Studies

Comparison of adherence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: a retrospective non-interventional cohort study. - Shirai, Chikako; Matsuoka, Nobushige; Nakazawa, Toru (BMC ophthalmology, 2021)
BACKGROUND: Adherence to chronic therapies is crucial to prevent the progression of disease, such as glaucoma. However, only a limited number of studies have investigated them using real-world data in Japan. This study aimed to evaluate Japanese patients' adherence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice., METHODS: This retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate., RESULTS: A total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/beta-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and alpha2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed-combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC >= 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9-53.0] vs. 24.9% [95% CI: 20.4-29.7], P < 0.0001)., CONCLUSIONS: Japanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.
Keywords: Antihypertensive Agents/tu [Therapeutic Use]; Cohort Studies; Glaucoma/dt [Drug Therapy]; *Glaucoma; Humans; Japan; Medication Adherence; *Pharmacy; Retrospective Studies

Medication adherence, self-efficacy and health literacy among patients with glaucoma: a mixed-methods study protocol. - Achilleos, Maria; Merkouris, Anastasios; Charalambous, Andreas; Papastavrou, Evridiki (BMJ open, 2021)
INTRODUCTION: As the world population ages, glaucoma is becoming an increasingly significant cause of blindness. A key component in the management of glaucoma is the use of prescribed medications and the adherence to treatment. However, there is evidence of low adherence to prescribed medication in chronic diseases, such as glaucoma. This study aims to explore the level of medication adherence, self-efficacy, social support and health literacy among the patients with glaucoma and to determine if there are any correlations between them. The ultimate aim is to use the information to develop an educational programme for patients with glaucoma at a later stage., METHODS AND ANALYSIS: This is a mixed-methods study which includes two stages: a descriptive study (stage 1) and focus group discussions (stage 2)., SAMPLE: Patients with glaucoma or ocular hypertension, using at least one kind of drops, from two ophthalmology clinics. Selected measures include: The Glaucoma Treatment Compliance Assessment Tool, The European Health Literacy Survey Questionnaire, The Glaucoma Medication Self-Efficacy Questionnaire and The Multidimensional Scale of Perceived Social Support. Two focus groups will be used for the collection of qualitative data, aiming to enrich the study with the patients' experiences. The data will be analysed with SPSS, using descriptive and inferential statistics for stage 1 whereas content analysis will be used for the data from the focus group discussions (stage 2)., ETHICS AND DISSEMINATION: Permission to conduct the study was received from the National Bioethics Committee and the board of management of the two ophthalmology clinics. All participants will be informed fully on the purpose and methods of the study. Consent forms will be signed and at any time participants will have the right to withdraw. Confidentiality and the protection of data will be respected at all times. Copyright © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Keywords: Glaucoma/dt [Drug Therapy]; *Glaucoma; *Health Literacy; Humans; Medication Adherence; *Ocular Hypertension; Self Efficacy

Evaluation of His6-Metal Assemblies as a Drug Delivery Vehicle in the Treatment of Anterior Segment Disease Using a Corneal Inflammation Model. - Wang, Liwen; Luo, Shan; Xu, Hongyan; Wu, Xiaoxiao; Hao, Pengyan; Zhang, Yagang; Huang, Wenjuan; Zan, Xingjie (ACS biomaterials science & engineering, 2020)
Keratitis is a common ophthalmological disease and also a common cause of blindness (second only to cataracts). This disease is routinely treated by topical administration of dexamethasone sodium phosphate (Dexp). However, due to the presence of anatomical and physiological barriers, frequent administration is needed, often resulting in poor patient compliance and diverse side effects. In this work, Dexp was in situ encapsulated into a His6-metal assembly (HmA) to generate Dexp@HmA, which was utilized in the ocular delivery of Dexp. The physicochemical properties of HmA and Dexp@HmA particles were characterized in detail using various techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), and UV-vis spectroscopy. Compared to commercial Eudragi and reported PLGA nanoparticles, HmA showed higher encapsulation efficiency (EE%) and higher loading capacity (LC wt %) of Dexp. Dexp@HmA displayed pH-dependent release; after 33 days at pH 5.8, 6.5, and 7.2, 100%, 65%, and 42% of Dexp, respectively, had been released. In addition, HmA and Dexp@HmA showed low cytotoxicity to macrophages and to all common ocular cell types tested. The effect of Dexp@HmA on corneal inflammation was evaluated using in vitro and in vivo models. Our results demonstrate that Dexp@HmA is much superior to free Dexp in both in vitro and in vivo models. These positive results suggest that HmA may represent a promising candidate nanocarrier for the treatment of various diseases of the anterior segment of the eye.
Keywords: Dexamethasone; Drug Delivery Systems; Humans; Inflammation/ci [Chemically Induced]; Keratitis/dt [Drug Therapy]; *Keratitis; *Nanoparticles

A Service Coverage Analysis of Primary Congenital Glaucoma Care Across the United States. - Vu, Daniel M; Stoler, Justin; Rothman, Adam L; Chang, Ta Chen (American journal of ophthalmology, 2021)
PURPOSE: To assess the number of infants at risk of delayed primary congenital glaucoma (PCG) evaluation due to long travel times to specialists., DESIGN: Cross-sectional geospatial service coverage analysis., METHODS: All American Glaucoma Society (AGS) and American Association for Pediatric Ophthalmology and Strabismus (AAPOS) provider locations were geocoded using each organization's member directory. Sixty-minute drive time regions to providers were generated using ArcGIS Pro (Esri). The geographic intersection of AGS and AAPOS service areas was computed because patients typically require visits to both types of specialists. American Community Survey data were then overlaid to estimate the number of infants within and beyond the AGS/AAPOS service areas., RESULTS: One thousand twenty-nine AGS and 1,040 AAPOS provider locations were geocoded. The analysis yielded 944,047 infants age 0-1 year (23.6%) who live beyond the AGS/AAPOS service areas. Therefore, approximately 14-94 new PCG cases/year may be at risk of delayed diagnosis as a result of living in a potential service desert. Compared with children living within the AGS/AAPOS service areas, children aged <6 years in these potential service deserts were more likely to live in households earning below the US federal poverty level, lack health insurance, and live in a single-parent home. These communities are disproportionately likely to experience other rural health disparities and are more prevalent across the Great Plains., CONCLUSION: Service coverage analysis is a useful tool for identifying underserved regions for PCG referrals and evaluation. These data may assist in targeting screening programs in low access areas for pediatric glaucoma care. Copyright © 2020 Elsevier Inc. All rights reserved.
Keywords: Child; Child, Preschool; Cross-Sectional Studies; Female; Geographic Information Systems; *Health Personnel/sn [Statistics & Numerical Data]; *Health Services Accessibility/sn [Statistics & Numerical Data]; Humans; *Hydrophthalmos/di [Diagnosis]; *Hydrophthalmos/th [Therapy]; Infant; Infant, Newborn; Male; *Medically Underserved Area; *Ophthalmologists/sn [Statistics & Numerical Data]; Ophthalmology/og [Organization & Administration]; Societies, Medical; United States

Biomechanical Modulation Therapy-A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns. - Gouveia, Ricardo M; Connon, Che J (Translational vision science & technology, 2020)
Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed. Copyright 2020 The Authors.
Keywords: *Burns, Chemical; Corneal Diseases/th [Therapy]; *Corneal Diseases; Humans; *Limbus Corneae; Stem Cell Transplantation

The Human Touch: Using a Webcam to Autonomously Monitor Compliance During Visual Field Assessments. - Jones, Pete R; Demaria, Giorgia; Tigchelaar, Iris; Asfaw, Daniel S; Edgar, David F; Campbell, Peter; Callaghan, Tamsin; Crabb, David P (Translational vision science & technology, 2020)
Purpose: To explore the feasibility of using various easy-to-obtain biomarkers to monitor non-compliance (measurement error) during visual field assessments., Methods: Forty-two healthy adults (42 eyes) and seven glaucoma patients (14 eyes) underwent two same-day visual field assessments. An ordinary webcam was used to compute seven potential biomarkers of task compliance, based primarily on eye gaze, head pose, and facial expression. We quantified the association between each biomarker and measurement error, as defined by (1) test-retest differences in overall test scores (mean sensitivity), and (2) failures to respond to visible stimuli on individual trials (stimuli -3 dB or more brighter than threshold)., Results: In healthy eyes, three of the seven biomarkers were significantly associated with overall (test-retest) measurement error (P = 0.003-0.007), and at least two others exhibited possible trends (P = 0.052-0.060). The weighted linear sum of all seven biomarkers was associated with overall measurement error, in both healthy eyes (r = 0.51, P < 0.001) and patients (r = 0.65, P < 0.001). Five biomarkers were each associated with failures to respond to visible stimuli on individual trials (all P < 0.001)., Conclusions: Inexpensive, autonomous measures of task compliance are associated with measurement error in visual field assessments, in terms of both the overall reliability of a test and failures to respond on particular trials ("lapses"). This could be helpful for identifying low-quality assessments and for improving assessment techniques (e.g., by discounting suspect responses or by automatically triggering comfort breaks or encouragement)., Translational Relevance: This study explores a potential way of improving the reliability of visual field assessments, a crucial but notoriously unreliable clinical measure. Copyright 2020 The Authors.
Keywords: Adult; Glaucoma/di [Diagnosis]; *Glaucoma; Humans; Reproducibility of Results; Touch; Visual Field Tests; *Visual Fields

Steroid-eluting contact lenses for corneal and intraocular inflammation. - Bengani, Lokendrakumar C; Kobashi, Hidenaga; Ross, Amy E; Zhai, Hualei; Salvador-Culla, Borja; Tulsan, Rekha; Kolovou, Paraskevi E; Mittal, Sharad K; Chauhan, Sunil K; Kohane, Daniel S; Ciolino, Joseph B (Acta biomaterialia, 2020)
Ocular inflammation is one of the leading causes of blindness worldwide, and steroids in topical ophthalmic solutions (e.g. dexamethasone eye drops) are the mainstay of therapy for ocular inflammation. For many non-infectious ocular inflammatory diseases, such as uveitis, eye drops are administered as often as once every hour. The high frequency of administration coupled with the side effects of eye drops leads to poor adherence for patients. Drug-eluting contact lenses have long been sought as a potentially superior alternative for sustained ocular drug delivery; but loading sufficient drug into contact lenses and control the release of the drug is still a challenge. A dexamethasone releasing contact lens (Dex-Lens) was previously developed by encapsulating a dexamethasone-polymer film within the periphery of a hydrogel-based contact lens. Here, we demonstrate safety and efficacy of the Dex-Lens in rabbit models in the treatment of anterior ocular inflammation. The Dex-Lens delivered drug for 7 days in vivo (rabbit model). In an ocular irritation study (Draize test) with Dex-Lens extracts, no adverse events were observed in normal rabbit eyes. Dex-Lenses effectively inhibited suture-induced corneal neovascularization and inflammation for 7 days and lipopolysaccharide-induced anterior uveitis for 5 days. The efficacy of Dex-Lenses was similar to that of hourly-administered dexamethasone eye drops. In the corneal neovascularization study, substantial corneal edema was observed in rabbit eyes that received no treatment and those that wore a vehicle lens as compared to rabbit eyes that wore the Dex-Lens. Throughout these studies, Dex-Lenses were well tolerated and did not exhibit signs of toxicity. Dexamethasone-eluting contact lenses may be an option for the treatment of ocular inflammation and a platform for ocular drug delivery. STATEMENT OF SIGNIFICANCE: Inflammation of the eye can happen either on the ocular surface (i.e. the cornea) or inside the eye, both of which can result in loss of vision or even blindness. Ocular inflammation is normally treated by steroid eye drops. Depending on the type and severity of inflammation, patients may have to take drops every hour for days at a time. Such severe dosing regimen can lead to patients missing doses. Also, more than 95% drug in an eye drop never goes inside the eye. Here we present a contact lens that release a steroid (dexamethasone) for seven days at a time. It is much more efficient than eye drops and a significant improvement since once worn, the patient will avoid missing doses. Copyright © 2020. Published by Elsevier Ltd.
Keywords: Animals; *Contact Lenses; Cornea; Humans; Inflammation/dt [Drug Therapy]; Rabbits; Steroids; Uveitis/dt [Drug Therapy]; *Uveitis

Dually functional hollow ceria nanoparticle platform for intraocular drug delivery: A push beyond the limits of static and dynamic ocular barriers toward glaucoma therapy. - Luo, Li-Jyuan; Nguyen, Duc Dung; Lai, Jui-Yang (Biomaterials, 2020)
Delivery of ophthalmic drugs to the interior parts of the eye for effective treatment of glaucoma (i.e., a chronic disease) remains a huge challenge because of the well-known static and dynamic ocular barriers. Herein, we present a new antiglaucoma formulation based on the development of a dual-functional therapeutic nanocarrier platform for intraocular targeted and sustained delivery of pilocarpine. Specifically, chitosan and ZM241385 are functionalized onto surfaces of hollow ceria nanoparticles (hCe NPs), thereby endowing the nanocarriers with a strong capability to open corneal epithelial tight junctions and deliver drug molecules to the targeted intraocular tissue (i.e., ciliary body). Moreover, the nanocarriers are demonstrated in vitro and in vivo to possess potent anti-oxidant and anti-inflammatory properties, which are beneficial to simultaneously alleviate glaucomatous damage. Single topical instillation of the pilocarpine-loaded dual-functional therapeutic nanocarriers with optimized delivery performance onto experimentally glaucomatous eyes can effectively mitigate disease progression for 7 days while that employing the traditional commercial eye drops only provides a moderate treatment efficacy for 4 h, possibly due to improved intraocular drug delivery (~250-fold greater bioavailability in the ciliary body) and intrinsic therapeutic activity of the ophthalmic formulation. These findings show great promise for the development of advanced nano eye drops toward efficient management of ocular diseases occurred in the inner segments of the eye. Copyright © 2020 Elsevier Ltd. All rights reserved.
Keywords: Chitosan/tu [Therapeutic Use]; *Chitosan; Drug Delivery Systems; Glaucoma/dt [Drug Therapy]; *Glaucoma; Humans; *Nanoparticles; Ophthalmic Solutions

Modeling a new dynamic approach to measure intraocular pressure with solitary waves. - Nasrollahi, Amir; Rizzo, Piervincenzo (Journal of the mechanical behavior of biomedical materials, 2020)
Glaucoma is an age-related disease and the second cause of blindness in the world. The measurement of intraocular pressure (IOP) is the cornerstone of glaucoma treatment because elevated IOP is the only risk factor that can be modified. Clinical evidences proved that single measurements obtained during office visits are neither sufficient to capture the circadian rhythm of IOP nor valid to demonstrate the effect of medication or patients' compliance to a given therapy. As such, patients would benefit from a device that they can self-administer to gage the IOP multiple times a day. In this paper, we present a numerical study on a new approach to measure IOP noninvasively using engineering principles never explored in ophthalmology. The method relies on the dynamical interaction between the solitary waves propagating within a chain of particles and the eye to be evaluated that is in contact with the end of the chain. In the study presented in this paper, a numerical model of such interaction was implemented to demonstrate the sensitivity of the proposed approach to the variation of IOP. The findings show that some features of the waves are monotonically dependent on the IOP. These findings may pave the way to the development of a new kind of tonometer that will enable millions of glaucoma patients to perform routine self-measurements of the eye pressure without clinical visits. Copyright © 2019 Elsevier Ltd. All rights reserved.
Keywords: Circadian Rhythm; Glaucoma/di [Diagnosis]; *Glaucoma; Humans; *Intraocular Pressure; Risk Factors; Tonometry, Ocular

[The role of citicoline in glaucoma]. - Junemann, Anselm G M; Grieb, P; Rejdak, R (Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft, 2021)
BACKGROUND: In recent years, many experimental and clinical studies have shown that in glaucoma, neuronal degeneration occurs not only at the level of the retina and optic nerve, but also along the entire visual pathway and the brain., OBJECTIVE: This article presents the neuroprotective effects of citicoline and their mechanisms in glaucoma disease., MATERIALS AND METHODS: The relevance of citicoline is explained against the background of neuroanatomy, neuroimaging, and the pathogenesis of glaucoma. Data from experimental and clinical studies are presented and a conclusion is drawn for clinical application., RESULTS: Citicoline has a neuroprotective effect via mechanisms relevant to glaucoma. The neuroprotective effect of citicoline in open-angle glaucoma can be demonstrated functionally and morphologically. It is independent of the glaucoma damage and intraocular pressure, and usually occurs only after 1 year. The effects of oral citicoline occur at a daily dose of 500-1000mg. Citicoline can be taken permanently or in cycles. No side effects occurred in the studies when taking citicoline. Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients., CONCLUSION: This relatively old nootropic drug, which is now marketed as a food supplement, seems to be a valuable addition to conventional treatment and also a rational option for prophylaxis of open-angle glaucoma.
Keywords: Cytidine Diphosphate Choline/tu [Therapeutic Use]; Glaucoma/dt [Drug Therapy]; *Glaucoma; Humans; Intraocular Pressure; Neuroprotective Agents/tu [Therapeutic Use]; *Neuroprotective Agents; Quality of Life; Tonometry, Ocular

Perspectives and impediment to eye care in caregivers of children with childhood glaucoma. - Rao, Aparna; Raj, Niranjan; Padhy, Debananda; Sarangi, Sarada Prasanna (Indian journal of ophthalmology, 2020)
Purpose: To study the perceptions, attitude, knowledge of the disease, and impediments to seeking early eye care in caregivers of children with childhood glaucoma., Methods: The study included new and old children diagnosed with childhood glaucoma (which included congenital glaucoma and developmental glaucoma) at a tertiary hospital of east India. The caregivers were administered a video-based questionnaire through open-ended questions intended to collect demographic and other personal details such as caregiver's socioeconomic status, knowledge, attitude towards eye health, and other social barriers. The responses were analyzed using thematic analysis technique into different buckets such as social status, knowledge/attitude, and sociocultural beliefs while individual responses in each bucket were analyzed., Results: Of a total of 43 patients included,> 75% of patients came from places> 200 km from the eye care centre with> 50% coming from> 300 km. Most patients presented either <1 year (42%, n = 18) or> 3 years (52%, n = 22) with only 2% (n = 3) presenting between 1-3 years of age. The mother was the first person of contact to diagnose the eye abnormality in> 45% of patients. Comparing differences among children who presented within 1 year of first diagnosis and those that presented later, caregivers hailing from long-distance> 200 km from an eye care center, monthly income <5000 INR, and those with social/cultural taboos (like children's eyes should not be operated) were more likely to seek delayed eye care for congenital glaucoma, P < 0.001., Conclusion: Impediments in seeking early eye care for blinding diseases in children (including distance from the nearest hospital, low socioeconomic constraints, and sociocultural beliefs/taboos) mandate serious policies towards improving education about eye disease and eye health among caregivers.
Keywords: Caregivers; Child; *Eye Diseases; Female; *Health Knowledge, Attitudes, Practice; Health Services Accessibility; Humans; *Hydrophthalmos; Mothers; Surveys and Questionnaires

A Geodemographic Service Coverage Analysis of Travel Time to Glaucoma Specialists in Florida. - Rothman, Adam L; Stoler, Justin B; Vu, Daniel M; Chang, Ta C (Journal of glaucoma, 2020)
PRECIS: Approximately 1 in 9 Florida residents over the age of 65 years (438,642 people) live more than an hour away from a glaucoma specialist, which represents a significant barrier to care., PURPOSE: To describe access to glaucoma care for Florida's elderly population using travel time to American Glaucoma Society (AGS) member offices., METHODS: For this cross-sectional service coverage analysis, a list of AGS member locations was extracted from the AGS website, and addresses were geocoded using ArcGIS Online. Driving time regions were created using the service area tool in ArcGIS Pro 2.4 and overlaid with 2010 United States Census and 2016 American Community Survey data for all Florida residents age 65 or older., RESULTS: Fifty-eight AGS member providers with 65 locations were identified and geocoded. There were 3,797,625 individuals aged over 65 years in Florida, of which 1,153,320 (30.4%) lived within 15 minutes of driving time from an AGS provider's office, 2,586,825 (68.1%) within 30 minutes, 3,358,983 (88.4%) within 60 minutes, and 3,491,815 (91.9%) within 120 minutes. The areas with the lowest access include rural areas near Lake Okeechobee and the Florida Panhandle. The population living beyond a 60-minute drive was more likely to be White, non-Hispanic and older, but less likely to be living below the federal poverty level or receiving public assistance than the population living within a 60-minute drive., CONCLUSIONS: There is a significant travel burden for the elderly community of Florida to reach AGS providers. Additional studies could help identify other social barriers to accessing glaucoma providers in Florida and beyond in an effort to improve patient compliance and, ultimately, vision outcomes.
Keywords: Aged; Cross-Sectional Studies; Female; Florida/ep [Epidemiology]; Geographic Information Systems; Geographic Mapping; *Glaucoma; Health Personnel/sn [Statistics & Numerical Data]; *Health Services Accessibility/sn [Statistics & Numerical Data]; Hispanic Americans; Humans; Intraocular Pressure/ph [Physiology]; Male; *Specialization; Surveys and Questionnaires; Time Factors; *Travel/sn [Statistics & Numerical Data]

Validation of a More Reliable Method of Eye Drop Self-Administration. - Freddo, Thomas F; Ho, Derek Y; Steenbakkers, Michelle; Furtado, Nadine (Optometry and vision science : official publication of the American Academy of Optometry, 2020)
SIGNIFICANCE: We propose an alternative method for eye drop self-administration. Similar IOP reductions were found with this method compared with clinician instillation. The alternative method of self-administration potentially benefits patients who have trouble successfully instilling drops., PURPOSE: The purpose of this study was to validate the efficacy of an alternative method of drop instillation., METHODS: This study is a randomized controlled crossover clinical trial. Thirty participants were recruited. A drop of 0.5% timolol maleate was instilled into subject's eye on two separate visits. On one visit, eye drop instillation was by a trained clinician, and on the other, self-instillation using an alternative method was used. The order was randomly chosen. Intraocular pressure was measured before drop instillation and 2 hours after drop instillation. The investigator was masked during measurement, and an observer recorded the IOP measurements., RESULTS: Mean +/- SD IOP measurement before 0.5% timolol maleate instillation measured 13.89 +/- 2.29 mmHg. An average reduction 3.75 +/- 2.36 mmHg was found with clinician administration, and an average reduction of 3.32 +/- 2.31 mmHg was recorded with the new method. No significance was found in IOP reduction between two groups P < .45. Percent reduction was 25.17 +/- 16.21% and 24.38 +/- 16.31% in clinician instillation and alternative instillation method group, respectively. No significant difference was found. This percentage reduction was similar to previously reported studies. No reported cases of eye infection or irritation were found in any case, within a 3-month follow-up period., CONCLUSIONS: We have proposed a more reliable method for instillation that provides a larger area for instillation and lessen the risk of contamination and patient's fear for eye drops. Similar efficacy was found compared with that of having a clinician directly administer the drop. This alternative method could potentially benefit patients who require topical eye drop therapy and result in increased compliance.
Keywords: *Administration, Ophthalmic; Adult; *Antihypertensive Agents/ad [Administration & Dosage]; Cross-Over Studies; Double-Blind Method; Female; Humans; *Intraocular Pressure/de [Drug Effects]; Male; Middle Aged; *Ocular Hypertension/dt [Drug Therapy]; Ophthalmic Solutions/ad [Administration & Dosage]; Reproducibility of Results; Self Administration; *Timolol/ad [Administration & Dosage]; Tonometry, Ocular; Young Adult

Low Vision Care - Out of Site. Out of Mind. - Goldstein, Judith E; Guo, Xinxing; Boland, Michael V; Swenor, Bonnielin K (Ophthalmic epidemiology, 2020)
PURPOSE: To estimate the number of patients accessing eye care with low vision (LV) at a large multi-site ophthalmology institute who utilize low vision rehabilitation (LVR) services and compare their characteristics to individuals who do not utilize LVR services., METHODS: This is an electronic health record-based retrospective chart analysis. Patients with LV were identified as having at least one encounter in 2014 where the best visual acuity (VA) in the better-seeing eye was worse than 20/40. Utilization of LVR services across 9 clinic locations was evaluated. Logistic regression analyses were used to examine patient characteristics associated with service utilization., RESULTS: Of the 7,752 LV patients, 1,585 (20%) utilized LVR services over the 17-month period. Those utilizing LVR were more likely to have VA between 20/60 and 20/200 or between 20/200 and 20/500 than non-users (P < .001). The highest LVR utilization rates were in patients evaluated in retina (23%), glaucoma (22%), and neuro-ophthalmology (18%) subspecialties. Patients seen at clinic locations with onsite LVR services available were more likely to utilize services (odds ratio [OR] ranged from 2.69 [95% confidence interval, 95% CI: 1.63-4.44] to 4.94 [95% CI: 2.12-11.48] across location categories), as were patients who had evidence of fluctuations in VA measurements (OR = 3.33, 95% CI: 2.89-3.84)., CONCLUSIONS: Patients are more likely to utilize services when VA is moderately to severely impaired, VA fluctuations are present, or when LVR services are provided at the same location where other ophthalmic services are obtained. These estimates are important for developing interventions aimed at improving LVR utilization.
Keywords: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Electronic Health Records/sn [Statistics & Numerical Data]; Female; Glaucoma/pp [Physiopathology]; Humans; Male; Middle Aged; *Patient Acceptance of Health Care/sn [Statistics & Numerical Data]; Retina/pp [Physiopathology]; Retrospective Studies; *Vision Disorders/rh [Rehabilitation]; Vision, Low/di [Diagnosis]; *Vision, Low/rh [Rehabilitation]; *Visual Acuity/ph [Physiology]; Young Adult

The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability. - Konstas, Anastasios G; Labbe, Antoine; Katsanos, Andreas; Meier-Gibbons, Frances; Irkec, Murat; Boboridis, Konstadinos G; Hollo, Gabor; Garcia-Feijoo, Julian; Dutton, Gordon N; Baudouin, Christophe (Expert opinion on drug safety, 2021)
Introduction: Preservative-free (PF) medications represent a valuable treatment strategy in the lifelong management of glaucoma. By removing preservative toxicity, PF formulations provide tangible clinical benefits to glaucoma patients worldwide. They improve tolerability and adherence, leading to a positive impact in long-term intraocular pressure (IOP) control. Areas covered: A critical review of the subject is provided, including selected evidence on the safety and tolerability of currently available topical PF formulations. Cumulative evidence confirms that topical PF medications are at least equally efficacious to their preserved equivalents. There is convincing short-term evidence for superior tolerability and safety of PF formulations compared to preserved medications. The long-term benefits and success of PF therapy requires further elucidation. Expert opinion: Successful stepwise administration of medical therapy for glaucoma remains elusive. There is a greater risk for ocular toxicity and therapy failure with preserved topical glaucoma therapy. Currently available and emerging PF therapy options potentially optimize lifelong stepwise glaucoma therapy and may enhance outcome. To avert complications from preservatives leading to poor adherence, ideally, future antiglaucoma therapy should become 100% PF. There are still key aspects of PF therapy that warrant further investigation.
Keywords: Administration, Ophthalmic; Animals; *Glaucoma/dt [Drug Therapy]; Humans; *Intraocular Pressure/de [Drug Effects]; Medication Adherence; *Preservatives, Pharmaceutical/ae [Adverse Effects]; Preservatives, Pharmaceutical/ch [Chemistry]

Understanding Barriers to Glaucoma Treatment Adherence among Participants in South India. - Killeen, Olivia J; Pillai, Manju R; Udayakumar, B; Shroff, Sujani; Vimalanathan, Menaka; Cho, Juno; Newman-Casey, Paula Anne (Ophthalmic epidemiology, 2020)
Purpose: Data on glaucoma treatment barriers in South India is limited; improved knowledge of barriers could advance disease self-management. We aimed to understand glaucoma treatment barriers in South India. Methods: Glaucoma patients >=18 taking >=1 medication at the Aravind Eye Hospital were screened with a validated medication adherence tool. Patients who self-reported poor adherence and/or were >3 months late for follow-up completed semi-structured interviews on treatment barriers. Interviews were audio-recorded, transcribed, translated and back-translated to ensure accuracy. Researchers used grounded theory to code the transcripts and identify themes using NVivo 11.0. Demographic and clinical characteristics were abstracted from the medical record. Results: 70/167 (42%) had poor self-reported adherence to drops. The 45 interviewed were 62 +/- 12 years and took 1.6 +/- 0.7 drops. Forty-two (93%) were non-adherent to medication and 21 (47%) were late for follow-up. Top barriers to medication adherence were difficulty obtaining drops (20, 44%), being busy (18, 40%), and the expense (17, 38%). Top barriers to appointment follow-up were distance to the hospital (21, 47%), expense (20, 44%), and no escort (15, 33%). Other important barriers included mistrust in the health system, poor knowledge of glaucoma and family needs. Conclusions: Previously, 6% of glaucoma patients in South India self-reported poor medication adherence; the 42% identified in this study is in line with glaucoma medication adherence rates globally. Complex factors caused high rates of non-adherence. Societal-level interventions that address systemic barriers and counselling that supports patients' and families' motivation for behaviour change should be implemented.
Keywords: Aged; Attitude to Health; Female; Glaucoma/di [Diagnosis]; *Glaucoma/dt [Drug Therapy]; Humans; India/ep [Epidemiology]; Interviews as Topic; Male; Medication Adherence/px [Psychology]; *Medication Adherence/sn [Statistics & Numerical Data]; Middle Aged; Ophthalmic Solutions/tu [Therapeutic Use]; Qualitative Research; Treatment Adherence and Compliance/px [Psychology]; *Treatment Adherence and Compliance/sn [Statistics & Numerical Data]

Uptake, Persistence, and Performance of Weekly Home Monitoring of Visual Field in a Large Cohort of Patients With Glaucoma. - Prea, Selwyn M; Kong, George Y X; Guymer, Robyn H; Vingrys, Algis J (American journal of ophthalmology, 2021)
PURPOSE: This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients., DESIGN: Single-center, observational, longitudinal, compliance study., METHODS: Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean +/- [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap., RESULTS: We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing >=1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85)., CONCLUSIONS: VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Keywords: Adult; Aged; Aged, 80 and over; *Algorithms; Female; *Glaucoma/di [Diagnosis]; Glaucoma/pp [Physiopathology]; Humans; Intraocular Pressure/ph [Physiology]; Male; Middle Aged; *Monitoring, Physiologic/mt [Methods]; *Patient Compliance; Reproducibility of Results; Visual Field Tests/mt [Methods]; *Visual Fields/ph [Physiology]; Young Adult

Development, Implementation, and Evaluation of Treatment Guidelines for Herpes Simplex Keratitis in Sydney, Australia. - Cabrera-Aguas, Maria; Kerdraon, Yves; Symes, Richard J; McCluskey, Peter; Samarawickrama, Chameen; Rawlinson, William; Watson, Stephanie L (Cornea, 2020)
PURPOSE: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia., METHODS: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline., RESULTS: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources., CONCLUSIONS: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.
Keywords: *Disease Management; *Eye Infections, Viral/th [Therapy]; Humans; *Keratitis, Herpetic/th [Therapy]; New South Wales; *Practice Guidelines as Topic