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TOPIC: To evaluate the efficacy and safety of anti-vascular endothelial growth factor (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 (PRISMA) 1. 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, Copenhagen, Denmark). 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 GRADE (Grading Recommendations Assessment, Development and Evaluation) approach. RESULTS: Nineteen studies were included, with 1,361 patients (n eyes=1,788) 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 to PRP at 3 months (MD=2.35 letters, 95% CI: 1.18, 3.52, I2=0%) and 12 months follow-up (MD=3.39 letters, 95% CI: 0.63, 6.14, I2=26%). Combination treatment showed better BCVA outcomes compared to PRP at 12 months (MD=4.06 letters, 95% CI: 0.26, 7.86, I2=0%). Combination showed lower CMT at 3 months (MD=-33.10 µm, 95% CI: -40.12, -26.08, I2=25%) and 6 months (MD=-34.28 µm, 95% CI: -55.59, -12.97, I2=85%) compared to PRP, but CMT results were similar at 12 months. Complete regression of Total Neovascularization (NVT) was more likely with anti-VEGF compared to PRP (OR=6.15, 95% CI: 1.39, 27.15, I2=80%). Post-treatment vitreous hemorrhage, vitrectomy, and increased intraocular pressure (IOP) events were similar between the anti-VEGF and combination groups compared to 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, while 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 (DME) 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.
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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.
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Inhibidores de la Angiogénesis , Axitinib , Células Endoteliales de la Vena Umbilical Humana , Imidazoles , Indazoles , Indoles , Inhibidores de Proteínas Quinasas , Pirroles , Receptores de Factores de Crecimiento Endotelial Vascular , Sunitinib , Axitinib/farmacología , Humanos , Sunitinib/farmacología , Inhibidores de la Angiogénesis/farmacología , Imidazoles/farmacología , Pirroles/farmacología , Indoles/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Indazoles/farmacología , Animales , Inhibidores de Proteínas Quinasas/farmacología , Receptor TIE-2/metabolismo , Receptor TIE-2/antagonistas & inhibidores , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismoRESUMEN
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.
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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.
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Atrofia Geográfica , Presión Intraocular , Inyecciones Intravítreas , Humanos , Presión Intraocular/efectos de los fármacos , Presión Intraocular/fisiología , Femenino , Masculino , Atrofia Geográfica/tratamiento farmacológico , Atrofia Geográfica/fisiopatología , Atrofia Geográfica/diagnóstico , Anciano , Persona de Mediana Edad , Tonometría Ocular , Agudeza Visual/fisiología , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Resultado del Tratamiento , Método Doble Ciego , Estudios de Seguimiento , Fragmentos Fab de InmunoglobulinasRESUMEN
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.
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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.
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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.
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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.
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Correo Electrónico , Oftalmología , Publicaciones Periódicas como Asunto , Estudios Transversales , Humanos , Publicaciones Periódicas como Asunto/normas , EdiciónRESUMEN
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.
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Presión Intraocular , Curvatura de la Esclerótica , Humanos , Fenómenos Biomecánicos , Estudios Transversales , Tonometría Ocular , Lactante , PreescolarRESUMEN
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.
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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.
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Diabetes Mellitus , Retinopatía Diabética , Edema Macular , Perforaciones de la Retina , Masculino , Humanos , Persona de Mediana Edad , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Edema Macular/tratamiento farmacológico , Edema Macular/etiología , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/tratamiento farmacológico , Perforaciones de la Retina/etiología , Retina , Fluocinolona AcetonidaRESUMEN
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.
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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.
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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.
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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.
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Desprendimiento de Retina , Vitreorretinopatía Proliferativa , Humanos , Vitreorretinopatía Proliferativa/tratamiento farmacológico , Vitreorretinopatía Proliferativa/metabolismo , RetinaRESUMEN
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.
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Atrofia Geográfica , Degeneración Macular Húmeda , Humanos , Atrofia Geográfica/diagnóstico , Atrofia Geográfica/tratamiento farmacológico , Atrofia Geográfica/etiología , Inhibidores de la Angiogénesis/uso terapéutico , Actividades Cotidianas , Calidad de Vida , Degeneración Macular Húmeda/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular , Agudeza Visual , Proteínas del Sistema Complemento/uso terapéutico , Preparaciones FarmacéuticasRESUMEN
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, I2 = 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, I2 = 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.
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Perforaciones de la Retina , Humanos , Perforaciones de la Retina/diagnóstico , Perforaciones de la Retina/cirugía , Agudeza Visual , Ojo , Vitrectomía , Posición PronaRESUMEN
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.
Asunto(s)
Inhibidores de la Angiogénesis , Degeneración Macular Húmeda , Humanos , Inhibidores de la Angiogénesis/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Protocolos Clínicos , Inyecciones Intravítreas , Resultado del Tratamiento , Proteínas Recombinantes de Fusión/uso terapéutico , Degeneración Macular Húmeda/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Oftalmopatías , Atrofia Geográfica , Degeneración Macular , Humanos , Incidencia , Minnesota/epidemiología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/epidemiología , Estudios RetrospectivosRESUMEN
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.