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Sophie J Bakri,1 Winfried MK Amoaku,2 Danielle Altman,3 Stéphane Quéré,4 Jaclyn Quilantan,5 Julia Carpenter-Conlin,5 Sujata P Sarda,5 Daniel L Jones,5 Jared S Nielsen6, † 1Department of Ophthalmology, Mayo Clinic, Rochester, MN, USA; 2Faculty of Medicine & Health Sciences, University of Nottingham, Queens Medical Centre, Nottingham, England, UK; 3Modus Outcomes, a THREAD Company, Cary, NC, USA; 4Modus Outcomes, a THREAD Company, Lyon, France; 5Apellis Pharmaceuticals, Inc, Waltham, MA, USA; 6Wolfe Eye Clinic PC, West Des Moines, IA, USA†Dr Jared S Nielsen passed away on June 14, 2024Correspondence: Sophie J Bakri, Department of Ophthalmology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA, Tel +1 507-284-3614, Email bakri.sophie@mayo.eduPurpose: Geographic atrophy (GA) impacts both patients and caregivers, yet little is understood about their respective burdens. The MOSAIC study aimed to identify the clinical, emotional, and financial burden among patients with GA and caregivers.Methods: A total of 28 patients with GA and 17 caregivers from the United States (US), the United Kingdom, and Australia participated in individualized qualitative interviews followed by a cross-sectional quantitative survey of 102 patients and 102 caregivers in the US. Interview transcripts were analyzed to develop conceptual models, which were then used to guide the design of quantitative surveys. Data were described at the item level and score level when appropriate (National Eye Institute Visual Function Questionnaire [NEI VFQ]-39 and Zarit Burden Interview [ZBI]). For the patient/caregiver dyad sample, the association between the NEI VFQ-39 scores and ZBI score was explored through correlation coefficients and scatterplots.Results: GA had a substantial impact on patients’ vision-related quality of life, activities of daily living, and instrumental activities of daily living. There was considerable overlap between perspectives and key concerns identified by patients and caregivers. Eighty-three percent of caregivers reported having to drive patients to appointments due to limited patient mobility, for example, and 41% reported a change in their employment status after becoming a caregiver, with 50% of them unable to work due to caregiving. The burden of patients and caregivers had a correlation ranging from − 0.63 to − 0.21 between NEI VFQ-39 subscale and composite scores and ZBI score.Conclusion: This study confirms the paucity of support for both patients with GA and caregivers. Both groups require expanded access to financial, social, and mental health resources.Plain Language Summary: What is this summary about?People with geographic atrophy, also called GA, can lose their eyesight and have a hard time driving, reading, and recognizing faces. This can worsen their quality of life. Often, people with GA need someone to care for them. The MOSAIC study was done to find out how GA affects health, happiness, and finances of people with GA and their caregivers.What were the results?One hundred and two people with GA and 102 caregivers in the United States were interviewed. The average age of people with GA was 68 years and of caregivers was 46 years. The findings showed that most people with GA did not drive because of their poor eyesight and instead counted on their caregivers to drive them to doctor appointments and other places. They also had a reading and doing things around their home because of their worsened eyesight.Both people with GA and caregivers said they felt stressed. They both worried about spending money on things they need to make living with GA easier. They also felt stressed about their finances because they could not work as much. People with GA worried most about losing their independence and caregivers worried most about the future of their loved one with GA.What do the results mean?This study showed that GA has a serious effect on people’s health and quality of life while also having a major impact on their caregivers.Keywords: age-related macular degeneration, functional vision, geographic atrophy, health-related quality of life, caregiver burden, disease burden

Vaidehi S Dedania,1 Sophie J Bakri21Department of Ophthalmology, Albany Medical Center, Lions Eye Institute, Albany, NY, USA; 2Department of Ophthalmology, Mayo Clinic, Rochester, MN, USABackground: This review summarizes the Phase III studies addressing intravitreal ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD), macular edema (ME) from retinal vein occlusion (RVO), and diabetic ME (DME).Results: The data from 12 major Phase III studies: six studies in patients with neovascular AMD, two studies in patients with ME from RVO, and four studies in patients with DME demonstrate significant improvement in vision in patients undergoing treatment with intravitreal ranibizumab over patients receiving no treatment or receiving only grid laser. These effects are achieved with low incidences of ocular and nonocular adverse events.Conclusion: Intravitreal ranibizumab is a highly effective and safe therapy for improving vision and reducing vision loss in patients with neovascular AMD, ME from RVO, and DME. Patients generally require long-term treatment although some data show that frequency of treatment necessary to maintain visual outcomes decreases over time.Keywords: age-related macular degeneration, branch retinal vein occlusion, central retinal vein occlusion, diabetic macular edema, intravitreal, macular edema

Purpose: To report patient acceptance and safety of repeated intravitreal injections of anti-VEGF agents for exudative AMD, by retina specialists, without an eye examination before every injection. Methods: Retrospective chart review. 115 eyes (110 patients) with exudative AMD underwent repeated intravitreal anti-VEGF injections with limited interval examination and diagnostic testing. Medication, laterality, number of injection cycles started and completed, number of injections per injection cycle, subjective visual changes, pre- and post-injection visual acuity (VA), pre- and post-injection intraocular pressure (IOP), nurse- and patient-initiated phone calls, emergency (non-scheduled) clinic visits, complications, new diagnoses, and patient complaints after each injection were recorded. The main outcome measures were complications and patient complaints. Results: 396 injections were administered in the injection clinic to 110 patients in 175 injection cycles (range: 0 to 5 injections per cycle). Of 175 injection cycles, there were 134 uninterrupted cycles and 41 interrupted cycles where an eye exam was performed. Fourteen new diagnoses were made: six during emergency visits, three at injection clinic appointments, and five at the next full examination after completion of a prescribed injection clinic cycle. Conclusions: Administration of anti-VEGF injections in a designated injection clinic, by retina specialists, according to a prescribed schedule, and with limited pre-injection testing, for patients with wet AMD, is well-tolerated. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the potency and efficacy of a library of dopamine receptor D2 (D2R) antagonists in the mitigation of fibrotic activation in retinal pigment epithelial (RPE) cells. Methods: ARPE-19 cells were cultured and treated with methotrexate or 27 district D2R antagonists using a fibronectin deposition assay. The most potent compounds were then further assessed in assays measuring cellular proliferation, cellular migration, and profibrotic gene expression. Results: The previously established antifibrotic D2R antagonist loxapine exerted a robust and dose-dependent inhibition of fibronectin deposition, whereas methotrexate exerted minimal inhibition. The most potent D2R antagonist identified, fluphenazine, effectively blocked in vitro models of fibrosis at 300-1,000 nM concentrations. Conclusions: Here we found multiple FDA-approved D2R antagonists that potently block RPE cell fibrogenesis. These findings further support the potential of D2R antagonism as a potential therapeutic for retinal fibrotic disease.

Topic: To evaluate the efficacy and safety of anti-VEGF and panretinal photocoagulation (PRP) for the treatment of proliferative diabetic retinopathy (PDR). The outcomes examined are changes in best-corrected visual acuity (BCVA), neovascularization (NV), central macular thickness (CMT), and adverse outcomes., Clinical Relevance: Diabetic retinopathy is the leading cause of blindness in working-aged adults globally. At present, no consensus has been reached on the optimal choice for the treatment of PDR., Methods: Cochrane, Embase, PubMed, Scopus, Web of Science, and CiNAHL were searched for articles from their inception to June 2023 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis. The review was registered prospectively with PROSPERO (CRD42023437778). Tool data analysis was performed using RevMan software version 5.4 (Review Manager [RevMan] [computer program], The Cochrane Collaboration, 2020). Randomized control trials (RCTs) of PDR patients treated with anti-VEGF, PRP, or a combination were included. Risk of bias was assessed using the Rob2 assessment tool (revised tool for risk of bias in randomized trials), and certainty of evidence was assessed with the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach., Results: Nineteen studies were included, with 1361 patients (n = 1788 eyes) treated for PDR with either anti-VEGF (n = 274), PRP (n = 482), or combination (n = 320). Our results show more favorable BCVA outcomes with anti-VEGF compared with PRP at 3 months (mean difference [MD] = 2.35 letters; 95% confidence interval [CI], 1.18-3.52; I 2  = 0%) and 12 months follow-up (MD = 3.39 letters; 95% CI, 0.63-6.14; I 2  = 26%). Combination treatment showed better BCVA outcomes compared with PRP at 12 months (MD = 4.06 letters; 95% CI, 0.26-7.86; I 2  = 0%). Combination showed lower CMT at 3 months (MD = -33.10 μm; 95% CI, -40.12 to -26.08; I 2  = 25%) and 6 months (MD = -34.28 μm; 95% CI, -55.59 to -12.97; I 2  = 85%) compared with PRP, but CMT results were similar at 12 months. Complete regression of total NV (NVT) was more likely with anti-VEGF compared with PRP (odds ratio = 6.15; 95% CI, 1.39-27.15; I 2  = 80%). Posttreatment vitreous hemorrhage, vitrectomy, and increased intraocular pressure events were similar between the anti-VEGF and combination groups compared with PRP; however, macular edema results favored the anti-VEGF over the PRP group. Using the GRADE assessment, BCVA evidence was rated to be of moderate certainty, whereas CMT and NVT evidence certainty was rated as very low., Conclusion: Anti-VEGF and combination treatments could be regarded as alternative approaches to PRP alone in the management of PDR after engaging in a shared decision-making process based on patients' adherence, diabetic macular edema status, and preference. Limitations of this meta-analysis include the heterogeneity in participants' characteristics, treatment regimens, and outcome reporting between studies. Further RCTs should be conducted to compare the effectiveness of these treatments in the long term., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate trends associated with email communication from potentially predatory publishers to faculty in ophthalmology., Design: Cross-sectional study METHODS: Ophthalmologists (n = 14) from various subspecialties and institutions were recruited to participate. Participants identified unsolicited emails that they had received originating from publishers in May 2021. Information collected included details on email contents and publisher organizations. Trends in communications from predatory publishers were evaluated., Results: Over a 30-day study period, a total of 1813 emails were received from 383 unique publishers and 696 unique journals, with a mean (SD) of 4.73 (2.46) emails received per day per participant. Of the 1813 emails identified, 242 (13%) emails were invitations to conferences, whereas 1440 (80%) were solicitations for article submissions to open-access, pay-to-publish journals. A total of 522 (29.0%) emails were related to ophthalmology, and reference to a prior publication of the participant occurred in 262 emails (14%). Of the 696 unique journals identified, 174 (25%) journals were indexed on PubMed and 426 (61%) were listed on Beall's list. When comparing journals that were listed on PubMed vs those that were not, PubMed indexed journals had a higher impact factor (2.1 vs 1.5, P = .002), were less likely to use "greetings" (76% vs 91%, P < .001), had fewer spelling/grammar errors (40% vs 51%, P = .01), and were less likely to offer rapid publication (16% vs 25%, P = .02)., Conclusions: Unsolicited requests to publish occur frequently and may diminish the quality of the scientific literature. We encourage individuals in ophthalmology to be aware of these trends in predatory publishing., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Surgical repair of complex tractional retinal detachments (TRDs) can be challenging due to the difficulty in delineating the fibroglial membranes from the underlying retinal surface. We describe the visual and retinal reattachment rate with the intraoperative use of trypan blue (TB) to visualize proliferative fibrous membranes in patients with TRDs., Design: Retrospective study., Participants: Seventeen patients who underwent a pars plana vitrectomy for surgical TRD repair with TB use between January 1, 2005, and December 31, 2020., Methods: Patient charts were retrospectively evaluated for surgical details, preoperative and postoperative logMAR best-corrected visual acuity (BCVA) and status of retinal attachment om days 30 and 90 and at the most recent follow-up visit., Results: In the cohort of 17 patients, TRDs were found to be secondary to proliferative diabetic retinopathy, complications from endophthalmitis, open globe injury, and neovascularization secondary to a retinal vein occlusion. Mean ± SD preoperative BCVA was 1.7 ± 1.7 logMAR (Snellen, 20/1000), whereas postoperative BCVA at the most recent follow-up visit was 1.4 ± 1.2 logMAR (Snellen, 20/500). The use of TB was successful in delineating the proliferative preretinal membranes in 100% of patients, with no residual staining of posterior segment tissues or adverse reactions related to the dye noted at postoperative visits. Eighty-eight percent (15 of 17) and 76% of retinas (13 of 17) were attached at postoperative month 3 and 6 visits, respectively., Conclusion: TB can be a useful adjunct tool to visualize and allow for a thorough removal of tractional fibrous proliferative epiretinal membranes in patients with complex TRDs, possibly yielding better surgical and long-term reattachment outcomes., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Importance: Intraocular pressure (IOP) elevations of clinical relevance have been observed after the commonly used 0.05-mL volume for intravitreous injections. However, more recently approved intravitreous agents involve volumes from 0.07 to 0.1 mL. It is not well established whether repeated 0.1-mL intravitreous injections may result in IOP-related complications., Objective: To investigate the effect of 1 year of repeated 0.1-mL intravitreous injections on IOP outcomes., Design, Setting, and Participants: This study was a post hoc analysis of 2 clinical trials investigating the IOP safety of intravitreous lampalizumab on geographic atrophy secondary to age-related macular degeneration. Both trials were conducted between 2014 and 2018 and recruited participants who were 50 years or older and had bilateral geographic atrophy. This post hoc analysis was performed between 2018 and 2022., Interventions: Intravitreous lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks., Main Outcomes and Measures: IOP changes in the 4-week-frequency study arms and ocular adverse events to week 48 in all arms. The hypothesis for this analysis was formulated after data collection., Results: Among a total of 1851 participants, there was no change in mean pre-injection IOP values through 48 weeks in either arm. The adverse events glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm., Conclusions and Relevance: Over 1 year, IOP increases were rare and did not affect treated participants more frequently than sham arm participants. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL., Trial Registration: ClinicalTrials.gov Identifiers: NCT02247479 and NCT02247531.

Purpose: Complications associated with intravitreal anti-VEGF therapies are reported inconsistently in the literature, thus limiting an accurate evaluation and comparison of safety between studies. This study aimed to develop a standardized classification system for anti-VEGF ocular complications using the Delphi consensus process., Design: Systematic review and Delphi consensus process., Participants: Twenty-five international retinal specialists participated in the Delphi consensus survey., Methods: A systematic literature search was conducted to identify complications of intravitreal anti-VEGF agent administration based on randomized controlled trials (RCTs) of anti-VEGF therapy. A comprehensive list of complications was derived from these studies, and this list was subjected to iterative Delphi consensus surveys involving international retinal specialists who voted on inclusion, exclusion, rephrasing, and addition of complications. Furthermore, surveys determined specifiers for the selected complications. This iterative process helped to refine the final classification system., Main Outcome Measures: The proportion of retinal specialists who choose to include or exclude complications associated with anti-VEGF administration., Results: After screening 18 229 articles, 130 complications were categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 complications (70%) after 3 rounds. After incorporating further modifications made based on participant suggestions, such as rewording certain phrases and combining similar terms, 24 redundant complications were removed, leaving a total of 67 complications (52%) in the final list. A total of 14 complications (11%) met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds also were excluded from the final classification system after the Delphi process terminated. In addition, 47 of 75 proposed complication specifiers (63%) were included based on participant agreement., Conclusions: Using the Delphi consensus process, a comprehensive, standardized classification system consisting of 67 ocular complications and 47 unique specifiers was established for intravitreal anti-VEGF agents in clinical trials. The adoption of this system in future trials could improve consistency and quality of adverse event reporting, potentially facilitating more accurate risk-benefit analyses., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Pathological angiogenesis and vascular instability are observed in diabetic retinopathy (DR), diabetic macular edema (DME), and wet age-related macular degeneration (wAMD). Many receptor tyrosine kinases (RTKs) including vascular endothelial growth factor receptors (VEGFRs) contribute to angiogenesis, whereas the RTK TIE2 is important for vascular stability. Pan-VEGFR tyrosine kinase inhibitors (TKIs) such as vorolanib, sunitinib, and axitinib are of therapeutic interest over current antibody treatments that target only one or two ligands. This study compared the anti-angiogenic potential of these TKIs., Methods: A kinase HotSpot™ assay was conducted to identify TKIs inhibiting RTKs associated with angiogenesis and vascular stability. Half-maximal inhibitory concentration (IC50) for VEGFRs and TIE2 was determined for each TKI. In vitro angiogenesis inhibition was investigated using a human umbilical vein endothelial cell sprouting assay, and in vivo angiogenesis was studied using the chorioallantoic membrane assay. Melanin binding was assessed using a melanin-binding assay. Computer modeling was conducted to understand the TIE2-axitinib complex as well as interactions between vorolanib and VEGFRs., Results: Vorolanib, sunitinib, and axitinib inhibited RTKs of interest in angiogenesis and exhibited pan-VEGFR inhibition. HotSpot™ assay and TIE2 IC50 values showed that only axitinib potently inhibited TIE2 (up to 89%). All three TKIs effectively inhibited angiogenesis in vitro. In vivo, TKIs were more effective at inhibiting VEGF-induced angiogenesis than the anti-VEGF antibody bevacizumab. Of the three TKIs, only sunitinib bound melanin. TKIs differ in their classification and binding to VEGFRs, which is important because type II inhibitors have greater selectivity than type I TKIs., Conclusions: Vorolanib, sunitinib, and axitinib exhibited pan-VEGFR inhibition and inhibited RTKs associated with pathological angiogenesis. Of the three TKIs, only axitinib potently inhibited TIE2 which is an undesired trait as TIE2 is essential for vascular stability. The findings support the use of vorolanib for therapeutic inhibition of angiogenesis observed in DR, DME, and wAMD., Competing Interests: Sophie J Bakri is a consultant for Abbvie, Adverum, Apellis, Aviceda, Eyepoint, ilumen, Iveric Bio, Genentech, Neurotech, Novartis, Outlook Therapeutics, Pixium, Revana, Regenxbio, Regeneron, Rejuvitas, Roche, Voxel, and Zeiss; and has received research funding from Regenxbio and Lowy Medical Foundation. Jeffrey Lynch, Michelle Howard-Sparks, Stephan Saint-Juste, and Said Saim are employees of EyePoint Pharmaceuticals, Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Bakri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To evaluate safety and tolerability of EYP-1901, an intravitreal insert containing vorolanib, a pan-VEGF receptor inhibitor packaged in a bioerodible delivery technology (Durasert E™) for sustained delivery, in patients with wet age-related macular degeneration (wAMD) previously treated with anti-VEGF therapy., Design: Phase I, multicenter, prospective, open-label, dose-escalation trial., Participants: Patients with wAMD and evidence of prior anti-VEGF therapy response., Methods: Patients received a single intravitreal injection of EYP-1901., Main Outcome Measures: The primary objective was to evaluate safety and tolerability of EYP-1901. Secondary objectives assessed biologic activity of EYP-1901 including best-corrected visual acuity (BCVA) and central subfield thickness (CST). Exploratory analyses included reduction in anti-VEGF treatment burden and supplemental injection-free rates., Results: Seventeen patients enrolled in the 440 μg (3 patients), 1030 μg (1 patient), 2060 μg (8 patients), and 3090 μg (5 patients) dose cohorts. No dose-limiting toxicity, ocular serious adverse events (AEs), or systemic AEs related to EYP-1901 were observed. There was no evidence of ocular or systemic toxicity related to vorolanib or the delivery technology. Moderate ocular treatment-emergent AEs (TEAEs) included reduced visual acuity (2/17) and retinal exudates (3/17). One patient with reduced BCVA had 3 separate reductions of 17, 18, and 16 letters, and another had a single drop of 25 letters. One severe TEAE, neovascular AMD (i.e., worsening/progressive disease activity), was reported in 1 of 17 study eyes but deemed unrelated to treatment. Mean change from baseline in BCVA was -1.8 letters and -5.4 letters at 6 and 12 months. Mean change from baseline in CST was +1.7 μm and +2.4 μm at 6 and 12 months. Reduction in treatment burden was 74% and 71% at 6 and 12 months. Of 16 study eyes, 13, 8, and 5 were injection-free up to 3, 6, and 12 months., Conclusion: In the DAVIO trial (ClinicalTrials.gov identifier, NCT04747197), EYP-1901 had a favorable safety profile and was well tolerated in previously treated eyes with wAMD. Measures of biologic activity remained relatively stable following a single EYP-1901 injection. These preliminary data support ongoing phase II and planned phase III trials to assess efficacy and safety., Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article., (© 2024 by the American Academy of Ophthalmology.)

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions., Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty., Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts., Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use., Competing Interests: POTENTIAL COMPETING INTERESTS The authors report no competing interests.

Objective: To assess the quality, empathy, and safety of expert edited large language model (LLM), human expert created, and LLM responses to common retina patient questions., Design: Randomized, masked multicenter study., Participants: Twenty-one common retina patient questions were randomly assigned among 13 retina specialists., Methods: Each expert created a response (Expert) and then edited a LLM (ChatGPT-4)-generated response to that question (Expert + artificial intelligence [AI]), timing themselves for both tasks. Five LLMs (ChatGPT-3.5, ChatGPT-4, Claude 2, Bing, and Bard) also generated responses to each question. The original question along with anonymized and randomized Expert + AI, Expert, and LLM responses were evaluated by the other experts who did not write an expert response to the question. Evaluators judged quality and empathy (very poor, poor, acceptable, good, or very good) along with safety metrics (incorrect information, likelihood to cause harm, extent of harm, and missing content)., Main Outcome: Mean quality and empathy score, proportion of responses with incorrect information, likelihood to cause harm, extent of harm, and missing content for each response type., Results: There were 4008 total grades collected (2608 for quality and empathy; 1400 for safety metrics), with significant differences in both quality and empathy ( P  < 0.001, P  < 0.001) between LLM, Expert and Expert + AI groups. For quality, Expert + AI (3.86 ± 0.85) performed the best overall while GPT-3.5 (3.75 ± 0.79) was the top performing LLM. For empathy, GPT-3.5 (3.75 ± 0.69) had the highest mean score followed by Expert + AI (3.73 ± 0.63). By mean score, Expert placed 4 out of 7 for quality and 6 out of 7 for empathy. For both quality ( P  < 0.001) and empathy ( P  < 0.001), expert-edited LLM responses performed better than expert-created responses. There were time savings for an expert-edited LLM response versus expert-created response ( P  = 0.02). ChatGPT-4 performed similar to Expert for inappropriate content ( P  = 0.35), missing content ( P  = 0.001), extent of possible harm ( P  = 0.356), and likelihood of possible harm ( P  = 0.129)., Conclusions: In this randomized, masked, multicenter study, LLM responses were comparable with experts in terms of quality, empathy, and safety metrics, warranting further exploration of their potential benefits in clinical settings., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of the article., (© 2024 by the American Academy of Ophthalmology.)

Objective: To study the prevalence of intraocular tumours detected by screening ultrasonography in eyes with opaque media., Methods: Retrospective review of B-scan ultrasonography in eyes with opaque media and diagnosis of blindness or phthisis between January 1, 1994, and December 31, 2013. Ultrasounds for diagnostic purposes in acute endophthalmitis, retinal detachment, or vitreous hemorrhage were excluded., Results: There were 119 blind eyes with opaque media examined with B-scan ultrasonography. Mean patient age was 59 years, with visual acuity of hand motions or worse in 89 eyes (74.8%), elevated intraocular pressure in 23 eyes (19.3%), and pain in 30 eyes (25.4%). Follow-up was ≥1 year in 69 eyes (58%) with a mean 64 months (median, 56 months; range, 12-129 months). Of these 69 eyes, ultrasound frequency was more often than annual in 2 eyes (2.9%), annual in 2 eyes (2.9%), every 13-60 months in 43 eyes (62%), every 61-120 months in 19 eyes (27.5%), and less often than every 120 months in 3 eyes (4.3%). Sixteen eyes with opaque media only received ultrasound at presentation, and 6 eyes had screening ultrasonography only prior to evisceration or enucleation. No intraocular tumours were detected in any eye during the study period., Conclusions: In this series, no intraocular tumours were detected by screening ultrasonography in eyes with opaque media. Larger studies with long-term follow-up are required to determine the utility and cost-effectiveness of serial ultrasonography monitoring. Ultrasound may have its highest utility in the setting of initial evaluation, clinical change, and preoperative work-up to avoid evisceration in the setting of occult malignancy., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To investigate the in vivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics., Design: Prospective observational cross-sectional study., Participants: Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative., Methods: All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means., Main Outcome Measures: Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient., Results: Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P = 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P = 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P = 0.005). Ocular rigidity coefficient was lower in buckled (9.9 × 10 -3 ± 1.4 × 10 -3 μL -1 ) vs. nonbuckled eyes (14.4 × 10 -3 ± 3.1 × 10 -3 μL -1 ; P = 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes., Conclusions: Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: We discuss a case of macular edema and retinal hemorrhage associated with scleromyxedema., Methods: A case report is presented., Results: A 64-year-old male with history of deep vein thrombosis and pulmonary embolism presented with new onset rash in the setting of switching anticoagulation treatments. He developed blurred vision was found to have macular edema and dot blot retinal hemorrhages which improved with systemic and topical corticosteroids., Conclusions: Systemic autoimmune conditions including scleromyxedema should be considered in the workup of occult cystoid macular edema.

Introduction: There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24 months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA., Methods: This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan ® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6 months prior to their first anti-VEGF treatment and for a duration of at least 24 months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24 months of treatment. Discontinuation rate beyond 24 months and its association with treatment intervals at 24 months was estimated using the Kaplan-Meier method and Cox proportional hazards models., Results: The overall discontinuation rate among the 1702 eligible patients from 24 to 60 months after treatment initiation was 30%. At 60 months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95% CI 1.43, 2.82], p < 0.001)., Conclusion: Patients with DME on longer anti-VEGF treatment intervals at 24 months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals., (© 2023. The Author(s).)

Proliferative vitreoretinopathy (PVR), the most common cause of recurrent retinal detachment, is characterized by the formation and contraction of fibrotic membranes on the surface of the retina. There are no Food and Drug Administration (FDA)-approved drugs to prevent or treat PVR. Therefore, it is necessary to develop accurate in vitro models of the disease that will enable researchers to screen drug candidates and prioritize the most promising candidates for clinical studies. We provide a summary of recent in vitro PVR models, as well as avenues for model improvement. Several in vitro PVR models were identified, including various types of cell cultures. Additionally, novel techniques that have not been used to model PVR were identified, including organoids, hydrogels, and organ-on-a-chip models. Novel ideas for improving in vitro PVR models are highlighted. Researchers may consult this review to help design in vitro models of PVR, which will aid in the development of therapies to treat the disease., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to report a case of spontaneous formation and resolution of a lamellar macular hole in a patient with diabetic macular edema treated with steroid implants., Methods: This study is a case report., Results: A 53-year-old man presented with blurry vision and was found to have diabetic macular edema that remained refractory to treatment despite multiple short-term intravitreal steroid implants. He was eventually treated with an intravitreal fluocinolone acetonide implant and was subsequently noted to have developed a lamellar macular hole that then resolved spontaneously without any additional therapy., Conclusion: There can be spontaneous formation and resolution of lamellar holes in the treatment of diabetic macular edema because of reorganization of the inner retinal layers, without significant impact on visual acuity. To the best of our knowledge, this finding has not been previously reported.

Purpose: The purpose of this study is to compare the use of metformin in patients with both exudative and non-exudative age-related macular degeneration (AMD) versus control populations., Design: Retrospective review of three age- and sex-matched cohorts from 1/1/2004 to 12/31/2013: patients with exudative AMD, a cohort of dry AMD patients, and a cohort of patients without AMD. The primary endpoint was the incidence of metformin use in all of the cohorts., Results: There were 1512 patients, with 504 in each of the three cohorts. There was no difference in the prevalence of diabetes between cohorts. Compared to patients with dry AMD, patients with no AMD had increased likelihood of metformin use (p = 0.0168, OR 1.66 (1.09-2.51). There was no difference in the likelihood of metformin use between exudative AMD patients and non-AMD controls., Conclusions: There appears to be an increased incidence of metformin use in patients without AMD compared to patients with dry AMD. Metformin's current role in the treatment of anti-aging diseases makes it a plausible target for use in the treatment of AMD, particularly dry AMD., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD), characterized by atrophic lesions that first start in the outer retina and progressively expand to cover the macula and the fovea, the center of the macula, leading to irreversible loss of vision over time. GA is distinct from wet or neovascular AMD (nAMD), the other form of advanced AMD. Neovascular AMD is characterized by new invading leaky blood vessels in the macula that can lead to acute vision loss. GA and nAMD may coexist in the same eye. The underlying pathophysiology of GA is complex and thought to involve chronic inflammation due to overactivation of the complement system that leads to the loss of photoreceptors, retinal pigment epithelium (RPE), and the underlying choriocapillaris. The disappearance of these structures appears as sharply demarcated atrophic lesions that are typical of GA. Researchers have reported about 1 million reported cases of GA in the United States, and about 160,000 cases occur per year. The most important risk factors for GA are increasing age and family history. Diagnosis of GA is usually made by using multimodal imaging techniques. Lesions associated with GA are highly heterogeneous, and the growth rate may differ from patient to patient. Despite the progressive nature of GA, the fovea may be spared until much later in the disease, thereby retaining central vision in patients. With time, atrophic lesions may progressively grow to involve the fovea, thereby severely impairing central vision. Vision loss can happen rapidly once the lesions reach the fovea. However, even without the involvement of the fovea, ongoing vision impairment impacting daily life may be present. Median time from GA not involving the center of the fovea (without subfoveal involvement) to GA with lesion boundary affecting the foveal center (subfoveal involvement) ranges from 1.4 to 2.5 years. GA can greatly impact patients' functioning and quality of life and limit their independence by interfering with activities of daily living, including difficulties with reading, driving, watching television, recognizing faces, and being unable to do household chores. No treatments have been available until intravitreal pegcetacoplan was recently approved by the US Food and Drug Administration for GA secondary to AMD. DISCLOSURES: Dr Bakri serves as a consultant to Apellis Pharmaceuticals, as well as AbbVie, Adverum, Eyepoint, iLumen, Iveric Bio, Genentech, Novartis, Outlook Therapeutics, Pixium, Regeneron, Roche, and Regenxbio. Drs Sharp, Luo, and Sarda are employees of Apellis Pharmaceuticals. Dr Bektas and Ms Khan are employees of RTI Health Solutions. Apellis developed and led the concept design of this publication, review and interpretation, approval, and decision to publish. This research was developed under a research contract between RTI Health Solutions and Apellis Pharmaceuticals and was funded by Apellis Pharmaceuticals. This supplement is to describe the disease of geographic atrophy and was funded by Apellis. Apellis Pharmaceuticals has developed Syfovre (pegcetacoplan), the first and only treatment for geographic atrophy.

Diabetic retinopathy (DR) is a microvascular disease caused by poorly controlled blood glucose, and it is a leading cause of vision loss in people with diabetes. In this review we discuss the current management of DR with particular focus on the use of intraocular anti-vascular endothelial growth factor (anti-VEGF) agents. Intraocular anti-VEGF agents were first studied in the 1990s, and now several of these agents are either FDA approved or used off-label as first-line treatments for DR. Recent evidence shows that anti-VEGF agents can halt the progression of markers of DR severity, reduce the risk of DR worsening, and reduce the onset of new macular edema. These significant benefits have been demonstrated in patients with proliferative DR and the milder nonproliferative DR (NPDR). A wealth of evidence from recent trials and meta-analyses has detailed the intraoperative and postoperative benefits of adjunctive anti-VEGF therapy prior to pars plana vitrectomy (PPV) for proliferative DR with vitreous hemorrhage. In this review, we also discuss literature comparing various anti-VEGF injection regimens including monthly, quarterly, as-needed, and treat and extend protocols. Combination protocols with panretinal photocoagulation (PRP) or PPV are also discussed. Current evidence suggests that anti-VEGF therapies are effective therapy for NPDR and PDR and may also provide significant benefits when used adjunctively with other DR treatment modalities such as PRP or PPV.

This study aimed to compare efficacy and treatment burden of treat-and-extend (T&E) anti-VEGF against fixed and pro re nata (PRN) regimens for neovascular age-related macular degeneration (nAMD). MEDLINE, CENTRAL, and EMBASE were searched. Randomized-controlled trials and observational studies comparing T&E to PRN or fixed dosing for treatment-naïve AMD patients were included. Mean difference (MD) for visual acuity (VA) and number of injections are presented. Risk of bias was assessed according to Cochrane guidelines. Methodology was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). VA improvement was similar with T&E and fixed dosing at one (MD -0.08 letters, p = 0.95) and two years (MD 0.58 letters, p = 0.62). In contrast, VA improvements were significantly greater for T&E when compared against a PRN regimen at one (MD 3.95 letters, p < 0.0001) and two years (MD 4.08 letters, p < 0.001). Significantly fewer ranibizumab injections were administered in the T&E arm at one (MD -2.42 injections, p < 0.0001) and two years (MD -6.06 injections, p < 0.00001) relative to fixed dosing. Fewer aflibercept injections were likewise administered to patients on a T&E regimen versus fixed dosing at one year (MD -0.78 injections, p < 0.0001). Low-certainty evidence from the present synthesis implies that T&E preserves VA similar to fixed schedules with significantly fewer injections at one and two years. Also, patients with T&E dosing achieved better VA outcomes than those on PRN regimen but T&E dosing was associated with more injections., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Topic: The importance of postoperative face-down positioning (FDP) to achieve anatomic and functional success after full-thickness macular hole (FTMH) surgery is explored in this meta-analysis of randomized controlled trials (RCTs)., Clinical Relevance: There is considerable variability in clinical practices regarding the need and length of FDP recommended to patients after FTMH surgery. There is also a lack of robust clinical guidelines on the topic. As such, an updated estimate of the effect size of FDP on clinically important outcomes is critical to inform practice., Methods: Ovid MEDLINE, EMBASE, CENTRAL, and SCOPUS databases were searched from inception to October 3, 2021, for RCTs evaluating FDP versus non-FDP (nFDP). Data were collected for 7 clinically important outcomes after macular hole surgery: closure rate, visual acuity (VA) improvement, recurrence of FTMH, visual function, quality of life, patient satisfaction, and complication rates. We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias and followed the Grade of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty in the evidence across outcomes. We conducted meta-analyses using random-effects modeling. Subgroup analyses were carried out based on hole size, type of gas, and duration of FDP., Results: Eight RCTs of 709 eyes were included. The relative risk (RR) of FTMH closure rate comparing FDP versus nFDP was RR 1.05 (95% confidence interval [CI]: 0.99, 1.12, P = 0.09, I 2  = 44%, GRADE rating: LOW). The mean difference (MD) regarding VA improvement comparing FDP and nFDP was MD -0.07 (95% CI: -0.12 to 0.01, P = 0.03, I 2  = 16%, GRADE rating: LOW)., Conclusion: The current review did not demonstrate a difference between FDP and nFDP with respect to FTMH closure, although the CIs were wide. There was a visual benefit to FDP; however, the CIs included values of trivial clinical significance. Subgroup analyses demonstrated that the VA benefit observed was driven by large holes. Limited data precluded analysis regarding the rate of FTMH recurrence, measures of visual function, quality of life measures, and patient satisfaction metrics. Further prospective trials are required to assess the gaps in the literature and improve the certainty of evidence for the outcomes examined., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the impact of physician face mask use on the rates and outcomes of postinjection endophthalmitis., Methods: A multicenter retrospective, comparative cohort study comparing endophthalmitis rate and visual acuity of eyes that developed endophthalmitis after antivascular endothelial growth factor injections at Mayo Clinic Rochester (MCR) and at Mayo Clinic Health System sites depending on physician masking., Results: A total of 164,824 injections were performed at MCR and Mayo Clinic Health System sites. Of these, 66,098 injections were in the no mask group and 98,726 injections were in the mask group. Overall, there were no differences in the rates of infectious endophthalmitis in the no mask versus mask cohorts (overall: no mask: 20 cases [0.0303%] vs. mask: 41 cases (0.0415%); P = 0.24; infectious: no mask: 12 cases [0.018%] versus mask: 13 cases [0.0132%]; P = 0.42). At MCR alone, there was a significant reduction in infectious endophthalmitis between the no mask versus mask groups (no mask: 9 cases [0.0297%] versus mask: 2 cases [0.003%]; P < 0.001). Only 2 cases of infectious endophthalmitis occurred at MCR after the face mask policy was implemented (1 in 30,000 injections). At presentation and at 6 months, the average visual acuity was similar for patients who developed endophthalmitis between the no mask versus mask groups., Conclusion: Physician face mask use did not affect the rate or outcome of postinjection endophthalmitis. However, there was a significant reduction at MCR after masking along with other quality improvement measures, including performance of injections in a dedicated procedure room and preparation of patients by nurses, that led to a low rate of endophthalmitis.

Purpose: To examine the risk, prevalence, and progression of glaucoma development in age-related macular degeneration (AMD) eyes receiving intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections compared to controls., Design: Retrospective clinical cohort study., Methods: Retrospective review of eyes receiving intravitreal anti-VEGF injections from January 1, 2004, to December 31, 2013, for exudative AMD. Age- and sex-matched control groups of eyes included eyes with nonexudative AMD (NEAMD) and no AMD. Eyes with a diagnosis of glaucoma or glaucoma suspect were reviewed for injection details, type and date of glaucoma diagnosis, glaucoma treatments, standard automated perimetry (SAP), and spectral domain optical coherence tomography (SD-OCT). Qualitative progression was determined by indication of glaucoma progression in provider notes. Quantitative progression was assessed based on change in mean deviation (MD) on SAP, retinal nerve fiber layer thickness on SD-OCT, and intraocular pressure (IOP)., Results: There were 707 eyes of 504 patients treated with anti-VEGF injections and 1008 eyes in the NEAMD and no-AMD cohorts. There was no difference in glaucoma or suspect prevalence at initial presentation between eyes treated with injections and NEAMD (6.9% vs 9.7%, P = .22) or no-AMD controls (vs 8.5%, P = .55). There was no difference in cumulative 5-year probability of new glaucoma diagnosis after anti-VEGF injections compared to NEAMD (1.9% vs 1.0%, P = .69) or no-AMD controls (vs 1.6%, P = .88). There was no difference in qualitative progression of glaucoma in the injection cohort vs NEAMD (P = .19) or no-AMD controls (P = .61). The rate of MD change in injection eyes was similar to NEAMD eyes (P = .74) but greater than no-AMD eyes (P = .02). Eyes receiving injections required more topical glaucoma medications compared with NEAMD (P = .03) and more glaucoma laser treatments compared with no-AMD controls (P = .009). Eyes receiving injections did not require more frequent incisional glaucoma surgery compared with NEAMD (21.0% vs 15.0%, P = .95) or no-AMD controls (vs 10.0%, P = .10)., Conclusion: Eyes treated with intravitreal anti-VEGF injections for exudative AMD did not have increased risk of developing glaucoma compared with controls. Of those with a glaucoma diagnosis, exudative AMD eyes receiving injections required a greater number of topical glaucoma medications compared with NEAMD eyes and had a greater rate of MD loss than no-AMD controls., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: To assess the association between treatment interval and likelihood of anti-vascular endothelial growth factor (anti-VEGF) discontinuation among patients with neovascular age-related macular degeneration (nAMD) in a real-world setting in the United States., Design: Retrospective clinical cohort study., Methods: Health insurance claims data from the IBM MarketScan Commercial and Medicare Supplemental databases were retrospectively reviewed to identify adults with nAMD who received anti-VEGF for the first time between July 1, 2011, and June 30, 2017. The proportion of discontinued patients was analyzed using Kaplan-Meier curves. Cox proportional hazards models were used to examine the association between treatment intervals at 24 months and anti-VEGF discontinuation., Results: The analysis included 8167 patients on continuous, unilateral anti-VEGF treatment for at least 24 months. Baseline demographics and clinical characteristics were well balanced between treatment interval groups. The overall rate of discontinuation from 24 months until 60 months after treatment initiation was 30.4%. At 60 months, patients on shorter treatment intervals were more likely to remain on treatment than those on longer intervals, ranging from 76.8% (4-week interval group) to 60.6% (>12-week interval group) and corresponding to a 28% lower likelihood (HR [SE] 0.72 [0.12], P < .01) and 55% higher likelihood of discontinuing treatment (HR [SE] 1.55 [0.07], P < .01), respectively, compared with the 8-week group., Conclusions: nAMD patients on longer anti-VEGF treatment intervals at 24 months had consistently higher discontinuation rates than patients on shorter intervals in the following years. This highlights the need to support and educate patients on long treatment intervals to continue with their treatment., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objectives: This study's objective was to describe long-term visual outcomes of patients with age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor injections who were lost to follow-up and then resumed treatment with anti-vascular endothelial growth factor injections., Materials and Methods: This was a retrospective cohort study of eyes with at least 7 years of follow-up following the initiation of treatment for wet AMD with and without gaps in therapy., Results: The baseline mean logMAR visual acuity was 0.65 ± 0.5 (Snellen acuity 20/89) in eyes with gaps in therapy and 0.53 ± 0.3 (20/68) in eyes without gaps. In the initial 7-year follow-up period, the eyes with gaps in therapy had significantly worse visual acuity ( P < .001) and this remained significant when accounting for baseline visual acuity ( P < .001)., Conclusions: Gaps in intravitreal injection therapy for exudative AMD were negatively associated with visual acuity. Adherence to therapy is important to address in the care of patients with exudative AMD. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:481-489.] .

Retinal pigmented epithelial (RPE) cells play an important role in retinal fibrotic diseases such as proliferative vitreoretinopathy (PVR). The purpose of this study was to elucidate the involvement of dopamine receptor signaling in regulating the fibrotic activation of RPE cells. Dopamine receptor expression, the effect of dopamine on fibrotic activity, and dopamine production were measured in the human RPE cell line ARPE-19. The fibrotic activation of RPE cells was evaluated in response to treatments with selective dopamine receptor agonists and antagonists by measuring gene expression, migration, proliferation, and fibronectin deposition. DRD2 and DRD5 are the dominant dopaminergic receptors expressed in ARPE-19 cells and TGF-β stimulation enhances the autocrine release of dopamine, which we show further exasperates fibrotic activation. Finally, treatment with D2 dopamine receptor antagonists or D5 dopamine receptor agonists inhibits profibrotic gene expression, migration, proliferation, and fibronectin deposition and thus may serve as effective mechanisms for treating retinal fibrosis including PVR.

Topic: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on intraocular pressure (IOP) 12 and 24 months after initiation., Clinical Relevance: It is unclear whether serial anti-VEGF injections result in sustained IOP increases., Methods: Randomized controlled trials (RCTs) comparing anti-VEGF agents with each other or with controls for the treatment of neovascular age-related macular degeneration, retinal vein occlusions, or diabetic macular edema were included. Pairwise meta-analysis and Bayesian network meta-analysis examined the proportion of patients whose IOP (1) increased 5 mmHg or more from baseline on consecutive visits, (2) increased 10 mmHg or more from baseline at any visit, (3) was 21 mmHg or more on consecutive visits, (4) was 25 mmHg or more at any visit, (5) was 30 mmHg or more at any visit, (6) prompted initiation of IOP-lowering medications, or (7) increased as per the clinicians' discretion. Grading of Recommendations Assessments, Development, and Evaluations methodology informed the certainty of evidence., Results: Twenty-six RCTs of 12 522 eyes were included. Aflibercept, bevacizumab, ranibizumab (0.3 mg and 0.5 mg), and noninjection controls were analyzed. Eighty-three of 84 network estimates for comparisons between anti-VEGF agents demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates than bevacizumab of IOP measurements of 30 mmHg or more at 12 months (low certainty of evidence). Fifty-three of 56 network estimates for comparisons between anti-VEGF agents and controls demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates of consecutive IOP increases of 5 mmHg or more at 24 months (low certainty of evidence) and higher rates of IOP increases as per the clinicians' discretion at 12 and 24 months (low and very low certainty of evidence, respectively). The 95% credible intervals in comparisons without statistically significant effects did not rule out important clinical effects. The certainty of evidence in these comparisons is limited by imprecision., Conclusion: This network meta-analysis does not show any clear difference in IOP increases 12 and 24 months after treatment initiation between anti-VEGF agents and controls. Imprecision precludes definitive conclusions., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Myeloproliferative neoplasms (MPNs) have been associated with increased systemic levels of vascular endothelial growth factor (VEGF). This study investigated an association between systemic busulfan for treatment of MPN and the requirement for intravitreal anti-VEGF injections for treatment of retinal pathology., Methods: Retrospective chart review of patients receiving systemic busulfan for myeloproliferative neoplasm and intravitreal anti-VEGF injections for macular and retinal vascular diseases from 2007 to 2021., Results: Of seven patients receiving oral busulfan for a hematological neoplasm and having concomitant retinal pathology requiring intravitreal anti-VEGF, all were white females >60 years old with MPN and exudative age-related macular degeneration. Of these, two patients had a reduced anti-VEGF requirement while on systemic busulfan, two took busulfan for fewer than 5 months, one developed retinal pathology over one year after stopping busulfan, one developed new retinal pathology while taking busulfan, and one had limited follow-up. Of the two patients with reduced anti-VEGF requirement while taking systemic busulfan, both had JAK2 V617F mutated MPN, and subsequent busulfan discontinuation was associated with an increased requirement for intravitreal anti-VEGF injections., Conclusions and Importance: Systemic busulfan for treatment of MPN was associated with a reduced requirement for intravitreal anti-VEGF injections for retinal vascular disease in two patients. This association could be a result of inhibition of proliferative angiogenesis or reduced systemic VEGF levels with effective systemic treatment for MPN. Further study is required to confirm this association and determine whether this relationship is specific to busulfan or extends to other systemic medications used to treat MPN., (© 2022 The Authors.)

Background and Objective: To characterize diabetic retinopathy (DR) progression without therapy., Patients and Methods: This post hoc analysis of the phase 3 RIDE and RISE trials examined the association between baseline DR severity on rates of ≥ 2-step DR progression and improvement in untreated fellow eyes (n = 530) and ranibizumab-treated study eyes (n = 369). Kaplan-Meier analyses estimated progression to proliferative DR (PDR) over 2 years in eyes with nonproliferative DR (NPDR) at baseline., Results: At month 24, 28.8% of untreated fellow eyes with moderately severe to severe NPDR at baseline experienced ≥ 2-step DR progression, versus 10.3% of eyes with absent to moderate NPDR and 0 eyes with mild- to high-risk proliferative DR. Of the untreated fellow eyes with moderately severe to severe NPDR, 18.9% achieved ≥ 2-step DR improvement, compared with 88.4% of ranibizumab-treated eyes., Conclusion: Without treatment, patients with moderately severe to severe NPDR are at risk of rapid disease progression and vision loss. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53(4):202-207.] .

Purpose: To report the representation of female ophthalmologists receiving private industry funding from 2015 through 2018, and to compare to previously observed trends., Design: Retrospective, comparative trend study METHODS: The study population consisted of US ophthalmologists listed in CMS Open Payments Database. Data were reviewed for payments for research, consulting, honoraria, industry grants, faculty and speakers, royalties, and services other than consulting. The primary outcome measure was percentage of female representation compared to male in each sub-category of payment., Results: The percentage of female, board-certified ophthalmologists who practiced in the United States ranged from 21.3% to 24.1%. The total number of reported ophthalmologists with industry ties ranged from 1629 to 1873, of whom between 17.2% and 19.4% were women. Women received significantly less industry compensation by than men in 2015 (median average $3273 vs $4825, P = .003), 2016 ($3600 vs $4750, P = .023), 2017 ($2493 vs $3500, P = .013), and 2018 ($2000 vs $3000, P = .011). Women remained underrepresented in receiving payments for research (ranging from 5.4% of total paid for research to 8.0%), consulting (11%-17.4%), honoraria (6%-14.9%), industry grants (4%-41.2%), royalties and licenses (0.1%-10.2%), faculty and speakers (11.6%-16.4%), and services other than consulting (8.4%-28.9%). Compared to 2013-2014, an increasing proportion of women received industry payments for consulting (P = .012), honoraria (P = .007), royalties and licenses (P = .019), faculty and speakers (P = .007), and services other than consulting (P = .007)., Conclusions: Female ophthalmologists remain underrepresented in terms of the percentage of women who receive private industry funding and dollar value of the funding., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To describe the newer predatory movement within academia: predatory conferences and its associated characteristics., Design: Perspective METHODS: Literature review of currently published literature regarding the topic RESULTS: Although ophthalmology and vision science are often spared from falling prey to predatory organizations, it is important for scientists of all levels, from trainees to senior faculty, to be aware of the existence of for-profit conferences and their characteristics., Conclusion: We discuss the details of predatory conferences and provide resources to help identify such meetings for all scientists and professionals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To assess the incidence of unplanned return to the operating room (ROR) at ≤45 days or ≥46 days after primary retinal detachment (RD) surgery and correlate ROR with preoperative risk factors and visual outcomes., Design: Retrospective cohort study., Methods: This was a retrospective review of patients with primary RD surgery to assess for unplanned ROR between January 1, 2012 and June 30, 2014, with follow-up of 90 days to 8 years (mean, 1.5 years). We assessed 268 patients receiving 270 primary rhegmatogenous RD surgeries between January 1, 2012 and June 30, 2014 in an academic tertiary referral center., Results: Of the 270 RD surgeries, 82 were complicated (history of proliferative vitreoretinopathy or trauma-related RDs at presentation) and 188 were uncomplicated (RD unrelated to trauma or proliferative vitreoretinopathy at presentation). The ROR rate for all surgeries was 12.2% (33/270) over the follow-up period, with 51.5% (17/33) having reoperations within 45 days. The complicated detachment group had a ROR rate of 14.6% (12/82) over the follow-up period, and 50% of those (6/12) had reoperations within 45 days. The uncomplicated detachment group had a ROR rate of 11.2% (21/188) over the follow-up period. Of those, 52.4% (11/21) had reoperations within 45 days., Conclusions: Given that only 51.5% of all RORs occurred within 45 days, a 45-day ROR surgical quality metric that has been previously used may be of limited value for RD surgery. Factors such as age at presentation, number of retinal breaks, number of detached clock hours, use of silicone oil tamponade for pars plana vitrectomy, history of choroidal detachment, high myopia, ocular trauma, and open globe were associated with increasing risk of ROR. Implementing risk-adjusted metrics may provide a more accurate and useful quality improvement metric for evaluating quality of surgical care in vitreoretinal surgery. Am J Ophthalmol 2021;221:•••-•••. © 2021 Elsevier Inc. All rights reserved., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: To investigate the outcomes of cataract surgery in patients with active diabetic macular edema (DME) who are receiving active treatment with intravitreal anti-vascular endothelial growth factor (VEGF) injections in the perioperative period., Design: Retrospective clinical cohort study., Methods: We reviewed all patients who underwent cataract surgery and were receiving intravitreal anti-VEGF injections from January 1, 2012 through December 31, 2017. Thirty-seven eyes underwent cataract surgery and received ≥1 intravitreal anti-VEGF injection for a diagnosis of DME within 6 months before surgery. Outcome measures included the development of subretinal or intraretinal fluid in the 6 months after surgery, timing of injections, number of injections, best-corrected visual acuity, and central subfield thickness., Results: There was a significant improvement between pre- and postoperative best-corrected visual acuity when comparing all eyes (Ps < .0001) and no significant difference in central subfield thickness before and after surgery (P > .05). There were 30 eyes (81.1%) that had fluid on the preoperative optical coherence tomography scan. Seventeen eyes (45.9%) developed new or worsening postoperative DME. Comparing the eyes that did or did not develop worsening DME, there were no differences in postoperative visual acuities (P > .05). Eyes that did develop new fluid had significant increases in postoperative central subfield thickness at both 1 month (350 vs 320 μm, P = .036) and 6 months (342 vs 305 μm, P = .013)., Conclusion: In a real-world setting, patients with cataracts and actively treated DME may undergo cataract surgery but may see a worsening of DME not immediately affecting the best-corrected visual acuity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Extremely thin sclera often necessitates abortion of scleral buckle procedures. In patients in whom a scleral buckle is desired, previous techniques have included the use of cyanoacrylate glue and continuing with surgery or placing donor tissue over the areas of thin sclera, but this can delay surgery. This was a retrospective review of three patients with thin sclera encountered during scleral buckling procedures. All patients had Tutoplast Pericardial Graft placed over the areas of thin sclera which allowed the scleral buckle to be sutured onto the Tutoplast rather than the thin sclera. Tutoplast Pericardial Graft is a useful adjunct in scleral buckle procedures with extremely thin sclera, and a scleral buckle can be safely placed over it and lead to successful retinal reattachment., Competing Interests: There are no conflicts of interest. Ethics approval: IRB approval waived. Consent to participate: Consent to publish these findings and images were gathered from the patients., (Copyright © 2021 Mathew and Bakri.)

Purpose: To analyze the frequency of systemic corticosteroid prescriptions before and after central serous chorioretinopathy (CSC) diagnosis., Design: Retrospective claims-based analysis., Participants: A nationally representative sample of commercial insurance beneficiaries who received care between 2007 and 2015., Methods: We limited the study population to beneficiaries with incident CSC diagnosed by an eye care provider, excluding those with other major ophthalmologic comorbidities. We developed a non-CSC comparison cohort matched to CSC patients by age, sex, general health (Charlson Comorbidity Index), and geographic region. We compared systemic corticosteroid prescriptions before and after CSC diagnosis and by diagnosing provider (optometrist vs. ophthalmologist) and evaluated likelihood of steroids treatment among CSC versus matched control patients using logistic and Cox proportional hazard regression models., Main Outcome Measures: Systemic corticosteroid prescription frequency among CSC patients within 12 months pre-diagnosis and at 6, 12, and 24 months post-diagnosis, median time to steroid initiation and discontinuation, and odds of receiving steroids post-diagnosis among CSC and control patients., Results: We identified 3418 CSC patients. Nearly 39% (n = 1326) were prescribed systemic steroids at some point during the analysis period, versus 23% of controls (4033 of 17 178 patients). Over 12% of CSC patients (n = 430) within 1 year pre-diagnosis, and nearly 12% (n = 404) within 1 year post-diagnosis. Most patients who received steroids after diagnosis were steroid naive (n = 231). Among those receiving steroids, CSC patients demonstrated longer median time to first post-diagnosis steroid prescription (1.82 years vs. 0.50 years for non-CSC patients) and longer time to last steroid prescription (1.62 years vs. 0.35 years for non-CSC patients). Although CSC patients were significantly less likely to receive steroids within 6 months post-diagnosis compared with non-CSC patients (odds ratio, 0.72; 95% confidence interval, 0.59-0.89), they were significantly more likely to receive steroids by 2 years post-diagnosis. Prescribing patterns were similar for patients diagnosed by an ophthalmologist versus optometrist., Conclusions: Despite evidence showing that steroids contribute to CSC development, many patients continue to be prescribed systemic corticosteroids after CSC diagnosis. Our results suggest a need for greater communication and collaboration among providers to ensure that clinical practice reflects evidence-based recommendations., (Published by Elsevier Inc.)