International Classification System for Ocular Complications of Anti-Vascular Endothelial Growth Factor Agents in Clinical Trials.

OBJECTIVE: Complications associated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies are inconsistently reported 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: 25 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 that voted on inclusion, exclusion, rephrasing, and addition of complications. As well, surveys determined specifiers for the selected complications. This iterative process helped 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 initially categorized from 145 included RCTs. Participant consensus via the Delphi method resulted in the inclusion of 91 (70%) complications after three 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 (52%) complications in the final list. A total of 14 (11%) complications met exclusion thresholds and were eliminated by participants across both rounds. All other remaining complications not meeting inclusion or exclusion thresholds were also excluded from the final classification system after the Delphi process terminated. In addition, 47 out of 75 (63%) proposed complication specifiers were included based on participant agreement. CONCLUSION: 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.

OCTess: AN OPTICAL CHARACTER RECOGNITION ALGORITHM FOR AUTOMATED DATA EXTRACTION OF SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY REPORTS.

PURPOSE: Manual extraction of spectral domain optical coherence tomography (SD-OCT) reports is time and resource intensive. This study aimed to develop an optical character recognition (OCR) algorithm for automated data extraction from Cirrus SD-OCT macular cube reports. METHODS: SD-OCT monocular macular cube reports (n = 675) were randomly selected from a single-center database of patients from 2020 to 2023. Image processing and bounding box operations were performed, and Tesseract (an OCR library) was used to develop the algorithm, OCTess. The algorithm was validated using a separate test data set. RESULTS: The long short-term memory deep learning version of Tesseract achieved the best performance. After reverifying all discrepancies between human and algorithmic data extractions, OCTess achieved accuracies of 100.00% and 99.98% in the training (n = 125) and testing (n = 550) datasets, while the human error rate was 1.11% (98.89% accuracy) and 0.49% (99.51% accuracy) in each, respectively. OCTess extracted data in 3.1 seconds, compared with 94.3 seconds per report for human evaluators. CONCLUSION: We developed an OCR and machine learning algorithm that extracted SD-OCT data with near-perfect accuracy, outperforming humans in both accuracy and efficiency. This algorithm can be used for efficient construction of large-scale SD-OCT data sets for researchers and clinicians.

POSTOPERATIVE PHOTORECEPTOR INTEGRITY AND ANATOMICAL OUTCOMES BASED ON PRESENTING MORPHOLOGIC STAGE OF RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate outer retinal recovery on postoperative optical coherence tomography (OCT) based on presenting morphologic stage of rhegmatogenous retinal detachment (RRD). METHODS: Retrospective cohort of consecutive primary fovea-involving RRDs, referred from January 2012 to September 2022. Baseline OCTs were assessed for morphologic stage of RRD. Postoperative OCT scans were graded at 3, 6, and 12 months for external limiting membrane, ellipsoid zone and interdigitation zone discontinuity, epiretinal membrane formation and severity, and residual subfoveal fluid. RESULTS: Three hundred and fifty-one patients were included. Increasing baseline morphologic stage of RRD was significantly associated with external limiting membrane, ellipsoid zone, and interdigitation zone discontinuity at all time points postoperatively ( P < 0.001) and was shown to be an independent predictor of foveal photoreceptor integrity after adjusting for height of detachment, time to surgery, and duration of fovea involvement ( P < 0.001). Earlier stages were associated with residual subfoveal fluid ( P < 0.001). There was no association between the stages of RRD and epiretinal membrane severity. However, late stages presented with earlier development of epiretinal membrane ( P = 0.012). CONCLUSION: Increasing morphologic stage of RRD is associated with delayed recovery of outer retinal bands in the first year and faster development of epiretinal membrane after RRD repair. The results of this study suggest that the stages may serve as a prognostic biomarker for postoperative photoreceptor recovery.

PARS PLANA VITRECTOMY WITH OR WITHOUT INTERNAL LIMITING MEMBRANE PEEL FOR MACULAR HOLE: A Systematic Review and Meta-Analysis.

PURPOSE: To compare the efficacy and safety of pars plana vitrectomy with and without internal limiting membrane (ILM) peeling for macular hole (MH). METHODS: A systematic literature search on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar was performed from January 2000 to 2023. The primary outcome was the final best-corrected visual acuity (BCVA). Secondary outcomes included MH closure rates and the need for repeat surgery. The authors performed a random-effects meta-analysis on Review Manager 5.4. RESULTS: Fourteen studies on 880 eyes were included. Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA ( P = 0.66). However, pars plana vitrectomy without ILM peeling achieved a significantly better final BCVA in eyes with closed MHs (WMD = 0.05 logMAR, 95% CI, 0.01-0.10, P = 0.02). Pars plana vitrectomy with ILM peeling achieved a significantly higher primary MH closure rate (RR = 1.21, 95% CI, 1.04-1.42, P = 0.02) and lower incidence of MH reoperation (RR = 0.19, 95% CI, 0.11-0.33, P < 0.001). The final MH closure rate ( P = 0.12) and incidence of MH recurrence ( P = 0.25) were similar between groups. CONCLUSION: Pars plana vitrectomy with and without ILM peel achieved a similar final BCVA. However, pars plana vitrectomy without ILM peeling achieved a better final BCVA in eyes with closed MHs. ILM peeling achieved a greater primary MH closure rate and reduced need for reoperation.

SURGICAL DRAINAGE METHODS DURING PARS PLANA VITRECTOMY FOR RHEGMATOGENOUS RETINAL DETACHMENT: A Systematic Review and Meta-Analysis.

PURPOSE: To assess efficacy and safety outcomes of subretinal fluid drainage methods during pars plana vitrectomy for rhegmatogenous retinal detachment. METHODS: A systematic search strategy was conducted for studies published between January 2000 and October 2022. Included studies reported on either the safety or efficacy of two or more drainage methods during pars plana vitrectomy for patients with rhegmatogenous retinal detachment. RESULTS: Two randomized and five observational studies consisting of 1,524 eyes were included. Best-corrected visual acuity at the last study observation and primary reattachment rates were similar across groups. A significantly lower risk of epiretinal membrane formation was associated with draining subretinal fluid through preexisting retinal breaks (risk ratio = 0.70, 95% confidence interval = [0.60, 0.83], P = <0.01, I 2 = 0%) or with perfluorocarbon liquid (risk ratios = 0.70, 95% confidence interval = [0.59, 0.83], P = <0.01, I 2 = 0%) compared with posterior retinotomy. The risk of an abnormal foveal contour was significantly greater in perfluorocarbon liquid-treated eyes relative to posterior retinotomy (risk ratios = 1.56, 95% confidence interval = [1.13, 2.17], P = <0.01, I 2 = 0%). CONCLUSION: No significant differences were observed in the final best-corrected visual acuity at the last study observation and primary reattachment rates across different drainage methods. There remains limited information on the topic, so future research is warranted.

ASSOCIATION OF INTRAVENOUS FLUORESCEIN ANGIOGRAPHY AND ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Case Series.

PURPOSE: To our knowledge, we present the first case series investigating the relationship between adaptive optics (AO) imaging and intravenous fluorescein angiography (IVFA) parameters in patients with diabetic retinopathy. METHODS: Consecutive patients with diabetic retinopathy older than age 18 years presenting to a single center in Toronto, Canada, from 2020 to 2021 were recruited. Adaptive optics was performed with the RTX1 camera (Imagine Eyes, Orsay, France) at retinal eccentricities of 2° and 4°. Intravenous fluorescein angiography was assessed with the artificial intelligence-based RETICAD system to extract blood flow, perfusion, and blood-retinal-barrier (BRB) permeability at the same retinal locations. Correlations between AO and IVFA parameters were calculated using Pearson's correlation coefficient. RESULTS: Across nine cases, a significant positive correlation existed between photoreceptor spacing on AO and BRB permeability (r = 0.303, P = 0.027), as well as perfusion (r = 0.272, P = 0.049) on IVFA. When stratified by location, a significant positive correlation between photoreceptor dispersion and both BRB permeability and perfusion (r = 0.770, P = 0.043; r = 0.846, P = 0.034, respectively) was observed. Cone density was also negatively correlated with BRB permeability (r = -0.819, P = 0.046). CONCLUSION: Photoreceptor spacing on AO was significantly correlated with BRB permeability and perfusion on IVFA in patients with diabetic retinopathy. Future studies with larger sample sizes are needed to understand the relationship between AO and IVFA parameters in diverse patient populations.

VALIDATION OF M-CHARTS FOR QUANTITATIVE ASSESSMENT OF METAMORPHOPSIA FOLLOWING RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To validate the quantitative assessment of metamorphopsia in rhegmatogenous retinal detachment (RRD) using M-CHARTS by determining its correlation with subjective reporting of metamorphopsia with a validated metamorphopsia questionnaire (modified MeMoQ). METHODS: The Research Ethics Board approved a prospective observational study carried out at St. Michael's Hospital, Toronto, Canada. Patients with primary, unilateral RRD and healthy controls were included. Metamorphopsia at 3 months was assessed with modified MeMoQ and M-CHARTS. RESULTS: One hundred patients (50 with RRD, 50 controls) were included. Seventy percent (35/50) of the RRD group had metamorphopsia with M-CHARTS and 80% (40/50) with MeMoQ. The modified MeMoQ and total M-CHARTS scores were significantly higher in patients with RRD compared with controls ( P < 0.0001). Cronbach's alpha reliability coefficient was 0.934 in the RRD group. Horizontal, vertical, and total M-CHARTS scores were significantly correlated with MeMoQ scores (r s  = 0.465, P = 0.0007; r s  = 0.405, P = 0.004; r s  = 0.475, P = 0.0005, respectively). M-CHARTS was 72.7% sensitive and 94.6% specific for detection of metamorphopsia (positive score ≥ 0.2), with an area under the receiver operating characteristic curve = 0.801. A stronger correlation was found in patients who scored ≥0.2 on the M-CHARTS and reported metamorphopsia with the MeMoQ (r s  = 0.454, P = 0.001). CONCLUSION: The authors have validated M-CHARTS as a tool to quantitatively assess metamorphopsia in patients with RRD, which is significantly correlated with patient-reported outcomes using the MeMoQ. A total score of ≥0.2 with M-CHARTS was more strongly correlated with MeMoQ.

ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Cohort Study.

PURPOSE: To investigate the correlation between diabetic retinopathy (DR) severity and microscopic retinal and vascular alterations using adaptive optics imaging. METHODS: In this single-center, prospective cohort study, adult participants with healthy eyes or DR underwent adaptive optics imaging. Participants were classified into control/mild nonproliferative DR, moderate/severe nonproliferative DR, and proliferative DR. Adaptive optics imaging using the RTX1 camera was obtained from 48 participants (87 eyes) for photoreceptor data and from 36 participants (62 eyes) for vascular data. RESULTS: Photoreceptor parameters significantly differed between DR groups at 2° and 4° of retinal eccentricity. Wall-to-lumen ratio varied significantly at 2° eccentricity, while other vascular parameters remained nonsignificant. Cone density and dispersion were the strongest predictors for DR severity ( P < 0.001) in multivariable generalized estimating equation modeling, while other vascular parameters remained nonsignificant between DR severity groups. All photoreceptor parameters showed significant correlations with visual acuity overall and across most DR severity groups. CONCLUSION: To date, this is one of the largest studies evaluating the use of adaptive optics imaging in DR. Adaptive optics imaging was demonstrated to differentiate between various levels of disease severity in DR. These results support the potential role in diagnostic and therapeutic microstructural evaluation in research and clinical practice.

THE ABILITY OF ARTIFICIAL INTELLIGENCE CHATBOTS ChatGPT AND GOOGLE BARD TO ACCURATELY CONVEY PREOPERATIVE INFORMATION FOR PATIENTS UNDERGOING OPHTHALMIC SURGERIES.

INTRODUCTION: To determine whether the two popular artificial intelligence chatbots, ChatGPT and Bard, can provide high-quality information concerning procedure description, risks, benefits, and alternatives of various ophthalmic surgeries. METHODS: ChatGPT and Bard were prompted with questions pertaining to the description, potential risks, benefits, alternatives, and implications of not proceeding with various surgeries in different subspecialties of ophthalmology. Six common ophthalmic procedures were included in the authors' analysis. Two comprehensive ophthalmologists and one subspecialist graded each response independently using a 5-point Likert scale. RESULTS: Likert grading for accuracy was significantly higher for ChatGPT in comparison with Bard (4.5 ± 0.6 vs. 3.8 ± 0.8, P < 0.0001). Generally, ChatGPT performed better than Bard even when questions were stratified by the type of ophthalmic surgery. There was no significant difference between ChatGPT and Bard for response length (2,104.7 ± 271.4 characters vs. 2,441.0 ± 633.9 characters, P = 0.12). ChatGPT responded significantly slower than Bard (46.0 ± 3.0 vs. 6.6 ± 1.2 seconds, P < 0.0001). CONCLUSION: Both ChatGPT and Bard may offer accessible and high-quality information relevant to the informed consent process for various ophthalmic procedures. Nonetheless, both artificial intelligence chatbots overlooked the probability of adverse events, hence limiting their potential and introducing patients to information that may be difficult to interpret.

Intravitreal Triamcinolone Acetonide for Diabetic Macular Edema and Macular Edema Secondary to Retinal Vein Occlusion: A Meta-Analysis.

BACKGROUND: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. OBJECTIVES: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. METHODS: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE, and EMBASE from January 2005 to May 2022. Studies that reported on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA were included. A random-effects meta-analysis was performed. Cochrane's Risk of Bias Tool 2 was used to assess the risk of bias, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) guidelines were used to assess certainty of evidence. RESULTS: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high-dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD = -4.75 ETDRS letters, 95% CI = [-7.73, -1.78], p = 0.002) and reduction in retinal thickness (WMD = -93.02 µm, 95% CI = [-153.23, -32.82], p = 0.002) at months 4-6 compared to low-dose (1-2 mg) IVTA. However, high-dose IVTA had a higher risk of intraocular pressure-related adverse events (RR = 2.99, 95% CI = [1.05, 8.50], p = 0.04) and cataract surgery (RR = 5.67, 95% CI = [3.09, 10.41], p < 0.00001) than low-dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high-dose and low-dose IVTA were not observed in DME eyes. CONCLUSIONS: The RCT evidence in this setting is limited. High-dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low-dose IVTA at months 4-6. However, high-dose IVTA had a less favorable safety profile than low-dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

Pars Plana Vitrectomy with or without Internal Limiting Membrane Peel for Epiretinal Membrane: A Systematic Review and Meta-Analysis.

BACKGROUND: The safety and effectiveness of pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling remains poorly understood for the treatment of epiretinal membrane (ERM). OBJECTIVES: Our study aims to compare the safety and effectiveness of PPV with and without ILM peeling for ERM. METHODS: A systematic literature search was conducted on Ovid MEDLINE, Embase, Cochrane Library, and Google Scholar from January 2000 to January 2023 for comparative studies reporting visual and anatomical outcomes for patients with ERM that received PPV with or without ILM peeling. Primary outcomes included best-corrected visual acuity (BCVA) at last study observation and change in BCVA from baseline. Secondary outcomes included retinal thickness (RT) at last study observation, change in RT from baseline, risk of ERM recurrence, and adverse events. A random-effects meta-analysis was performed. Risk of bias of randomized controlled trials was assessed using the Risk of Bias 2 tool of observational studies using the Risk of Bias in Non-randomized Studies of Interventions-I tool. The certainty of evidence of outcomes was evaluated using Grading of Recommendations, Assessment, Development and Evaluation criteria. RESULTS: Nineteen studies reporting on 1,291 eyes at baseline were included. PPV with and without ILM peel achieved a similar BCVA at last study observation (p = 0.68) and change in BCVA from baseline (p = 0.79). These findings remained consistent irrespective of whether simultaneous phacoemulsification was performed. PPV with ILM peel achieved a significantly lower incidence of ERM recurrence (risk ratio [RR] = 0.26, 95% CI = [0.13, 0.51], p < 0.0001) and additional surgery (RR = 0.17, 95% CI = [0.04, 0.74], p = 0.02) compared to PPV without ILM peel. CONCLUSION: PPV with and without ILM peel achieved a similar BCVA at last study observation in ERM patients. Patients treated with PPV and ILM peel also had a reduced risk of ERM recurrence and lower reoperation risk. These conclusions are associated with a moderate certainty of evidence and potential for bias from multiple non-randomized studies.

ChatGPT-4: An assessment of an upgraded artificial intelligence chatbot in the United States Medical Licensing Examination.

PURPOSE: ChatGPT-4 is an upgraded version of an artificial intelligence chatbot. The performance of ChatGPT-4 on the United States Medical Licensing Examination (USMLE) has not been independently characterized. We aimed to assess the performance of ChatGPT-4 at responding to USMLE Step 1, Step 2CK, and Step 3 practice questions. METHOD: Practice multiple-choice questions for the USMLE Step 1, Step 2CK, and Step 3 were compiled. Of 376 available questions, 319 (85%) were analyzed by ChatGPT-4 on March 21st, 2023. Our primary outcome was the performance of ChatGPT-4 for the practice USMLE Step 1, Step 2CK, and Step 3 examinations, measured as the proportion of multiple-choice questions answered correctly. Our secondary outcomes were the mean length of questions and responses provided by ChatGPT-4. RESULTS: ChatGPT-4 responded to 319 text-based multiple-choice questions from USMLE practice test material. ChatGPT-4 answered 82 of 93 (88%) questions correctly on USMLE Step 1, 91 of 106 (86%) on Step 2CK, and 108 of 120 (90%) on Step 3. ChatGPT-4 provided explanations for all questions. ChatGPT-4 spent 30.8 ± 11.8 s on average responding to practice questions for USMLE Step 1, 23.0 ± 9.4 s per question for Step 2CK, and 23.1 ± 8.3 s per question for Step 3. The mean length of practice USMLE multiple-choice questions that were answered correctly and incorrectly by ChatGPT-4 was similar (difference = 17.48 characters, SE = 59.75, 95%CI = [-100.09,135.04], t = 0.29, p = 0.77). The mean length of ChatGPT-4's correct responses to practice questions was significantly shorter than the mean length of incorrect responses (difference = 79.58 characters, SE = 35.42, 95%CI = [9.89,149.28], t = 2.25, p = 0.03). CONCLUSIONS: ChatGPT-4 answered a remarkably high proportion of practice questions correctly for USMLE examinations. ChatGPT-4 performed substantially better at USMLE practice questions than previous models of the same AI chatbot.

BACILLARY LAYER DETACHMENT AND ASSOCIATED ABNORMALITIES IN RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To describe bacillary layer detachment and related abnormalities of the foveal bouquet in rhegmatogenous retinal detachment and assess their impact on photoreceptor recovery and full-thickness macular hole formation, using optical coherence tomography. METHODS: Prospective cohort of 93 consecutive patients with fovea-off rhegmatogenous retinal detachment presenting to St. Michael's Hospital from January 2020 to April 2022, with gradable preoperative foveal optical coherence tomography. RESULTS: 23.7% (22/93) of patients had evidence of bacillary layer detachment and associated abnormalities. The mean fovea-off duration was 6.4 days (±5.6 SD). 86.4% (19/22) had foveal bacillary layer detachment, 15.8% (3/19) of which had cleavage planes extending from the outer nuclear layer into the myoid zone, and 14% (3/22) had an inner lamellar hole with a residual bridge of photoreceptor remnants (all of which progressed to full-thickness macular hole). Among patients with gradable optical coherence tomography at 3 months post-operatively, 80% (12/15) had ellipsoid zone discontinuity, which persisted in 41% (5/12) at 1 year. CONCLUSION: Bacillary layer detachment was described for the first time in the setting of rhegmatogenous retinal detachment. This is hypothesized to occur from horizontal traction secondary to hydration/lateral expansion of the outer retina in the presence of the Müller cell cone scaffold. Bacillary layer detachment may render the fovea susceptible to further injury, possibly representing a pathophysiological basis for full-thickness macular hole formation in rhegmatogenous retinal detachment.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY MORPHOLOGY AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR: ALIGN Post Hoc Analysis.

PURPOSE: To compare foveal avascular zone (FAZ) geometric indices using optical coherence tomography angiography (OCTA) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). FAZ morphology was assessed as a possible imaging feature of retinal displacement. METHODS: This ALIGN post hoc analysis included primary fovea-off RRDs that underwent successful PnR or PPV, and performed OCTA, and fundus autofluorescence at (FAF) 3 months postoperatively at St. Michael's Hospital, Toronto, Canada. FAZ area (mm 2 ), axial ratio, circularity, and roundness were measured, and FAF images were assessed for retinal displacement. RESULTS: Seventy-two patients were included, 78% (56/72) were male mean age was 60 ± 9 years, and 60% (43/72) were phakic. Sixty-five percent (47/72) and 35% (25/72) underwent PnR and PPV, respectively. The mean baseline logarithm of the minimum angle of resolution visual acuity was 1.49 ± 0.76. FAZ circularity was lower after PPV (0.629 ± 0.120) versus PnR (0.703 ± 0.122); P = 0.016. Sixty-six patients had gradable FAF images. Retinal displacement was present in 29% (19/66), 84.2% (16/19) of which had displacement in the macula. FAZ circularity was lower in eyes with displacement in the macula (0.613 ± 0.110) versus those without displacement (0.700 ± 0.124); P = 0.015. There was a moderate negative correlation between 12-month aniseikonia and FAZ circularity(r = -0.262; P = 0.041). CONCLUSION: FAZ circularity was lower after PPV and in eyes with retinal displacement in the macula. Circularity was negatively correlated with 12-month aniseikonia scores. FAZ circularity may be another imaging feature to consider postoperatively after RRD repair.

Anti-Vascular Endothelial Growth Factor Therapy Regimens for Polypoidal Choroidal Vasculopathy: A Systematic Review.

INTRODUCTION: There are no guidelines on the optimal anti-vascular endothelial growth factor (anti-VEGF) monotherapy regimen for patients with polypoidal choroidal vasculopathy (PCV). In this study, we aimed to assess the comparative safety and efficacy of different treatment regimens of anti-VEGF monotherapy for PCV. METHODS: We conducted a systematic literature search on Ovid MEDLINE, Embase, and Cochrane Library from January 2000 to May 2023 for comparative articles reporting on different treatment regimens of anti-VEGF agents in PCV. Our primary outcomes were the final best-corrected visual acuity (BCVA) and the change in BCVA from baseline. Secondary outcomes were the final retinal thickness (RT), the change in RT from baseline, the rate of polyp closure, and the incidence of adverse events. RESULTS: A total of 10,440 studies were screened, and seven studies reporting on 636 eyes with PCV at baseline were included in this systematic review. One RCT of 53 eyes found a similar final BCVA, change in BCVA from baseline, final RT, and complete polyp closure rate between a treat-and-extend (T&E) regimen and a bimonthly fixed-dosing regimen of aflibercept. This trial also found superiority of T&E for change in RT from baseline. One observational study of 33 eyes found a similar BCVA at last study observation between a pro re nata (PRN) regimen and bimonthly fixed-dosing regimen of aflibercept. One observational study of 42 eyes found a similar change in BCVA from baseline and complete polyp closure rate between a PRN regimen and bimonthly fixed-dosing regimen of aflibercept. One RCT of 249 eyes found a similar change in BCVA and RT from baseline, as well as polyp closure, between a T&E regimen and fixed 12-week dosing regimen of conbercept. One observational study of 30 eyes found a superiority of T&E aflibercept for change in BCVA and risk of polyp recurrence, compared to a PRN regimen. CONCLUSION: Overall, there is a paucity of evidence comparing various treatment regimens of anti-VEGF therapy in patients with PCV. This limited evidence suggests that current treatment regimens are similarly efficacious, though T&E aflibercept achieved superior outcomes when compared to bimonthly dosing or PRN in some individual studies. Further trials are needed to confirm or refute these findings.

STATIN USE AND THE INCIDENCE OF AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.

PURPOSE: Age-related macular degeneration (AMD) shares many of the same risk factors with atherosclerosis. There is a postulated role of lipid-lowering agents in preventing AMD. This meta-analysis investigates the possible role of statins in the prevention of AMD onset and progression. METHODS: MEDLINE, EMBASE, Cochrane CENTRAL, and the reference lists of included studies were systematically searched from inception to September 2020. Studies were included if they measured the risk of AMD development or progression with statin use. The primary outcomes assessed were AMD incidence and progression. Secondary outcomes were the incidence of early AMD, late AMD, choroidal neovascularization, and geographic atrophy. RESULTS: Twenty-one articles (1 randomized control trial and 20 observational studies) collectively reporting on 1,460,989 participants were included. The pooled risk ratios (95% confidence interval) for statin use on any, early, and late AMD incidence were 1.05 (0.85-1.29) (P = 0.44), 0.99 (0.88-1.11) (P = 0.86), and 1.15 (0.90-1.47) (P = 0.27), respectively. In patients with existing AMD, the respective risk ratios for statin use on incidence of AMD progression, choroidal neovascularization, and geographic atrophy were 1.04 (0.70-1.53) (P = 0.85), 0.99 (0.66-1.48) (P = 0.95), and 0.84 (0.58-1.22) (P = 0.36). CONCLUSION: This meta-analysis found that there was no significant difference in the incidence or progression of AMD based on statin use.

A MULTICENTER REVIEW EVALUATING THE RISK OF RHEGMATOGENOUS RETINAL DETACHMENT POST ENDOPHTHALMITIS: A Canadian Retina Research Network Investigation.

PURPOSE: To describe the characteristics of rhegmatogenous retinal detachments (RDs) that developed after endophthalmitis and to provide insight regarding incidence, management, and outcomes. METHODS: Retrospective chart review of consecutive patients diagnosed with endophthalmitis at two Canadian institutions and from one surgeon at a third center over a 10-year period. RESULTS: Three hundred sixteen eyes presented with endophthalmitis of which 32 (10%) were complicated by subsequent RD. The mean age (SD) of patients was 72.0 (13.77) years. Intravitreal injections (33%) and cataract surgery (31%) were the most common inciting events for the endophthalmitis. Cases were managed with tap and inject (16%), vitrectomy (30%), or both (47%). There were no differences in the rate of RD when comparing the inciting events, microbial growth, or management approaches. Baseline visual acuity was the only predictor of RD ( P = 0.009). There was an improvement in visual acuity following management of the RD (logarithm of the minimum angle of resolution 2.33 vs. 1.69 or Snellen hand motion vs. 20/980, P = 0.009), but final visual acuity in these patients was worse than in those who did not develop RD (logarithm of the minimum angle of resolution 1.69 vs. 1.27 or Snellen 20/980 vs. 20/372, P = 0.029). CONCLUSION: All patients with RD post endophthalmitis required additional surgery, and functional outcomes remained poor. Nevertheless, repair of these RDs can preserve some vision and be globe saving.

RISK OF INTRAOCULAR INFLAMMATION AFTER INJECTION OF ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS: A Meta-analysis.

PURPOSE: This meta-analysis investigates the incidence of intraocular inflammation (IOI) after intravitreal antivascular endothelial growth factor injections in neovascular age-related macular degeneration. METHODS: A systematic search was performed on Ovid MEDLINE, Embase, and Cochrane Central from January 2005 to April 2021. Randomized controlled trials comparing IOI after intravitreal bevacizumab, ranibizumab, brolucizumab, or aflibercept in neovascular age-related macular degeneration were included. Primary outcomes were sight-threatening IOI, final best-corrected visual acuity, and change in best-corrected visual acuity from baseline. Secondary outcomes included the incidence of other IOI events. Meta-analysis was performed using a random-effects model. RESULTS: Overall, 11,460 unique studies were screened, of which 14 randomized controlled trials and 6,759 eyes at baseline were included. There was no difference between agents for the risk of endophthalmitis and retinal vascular occlusion. Compared with aflibercept, brolucizumab had a higher incidence of generalized IOI (risk ratio = 6.24, 95% confidence interval = [1.40-27.90]) and vitreous haze/floaters (risk ratio = 1.64, 95% confidence interval = [1.00-2.67]). There were no significant differences between comparators for other secondary end points. CONCLUSION: There was no difference in the risk of severe sight-threatening IOI outcomes between intravitreal antivascular endothelial growth factor agents. There was a significantly higher risk of generalized IOI after brolucizumab relative to aflibercept. Our results alongside other recent safety findings suggest the need for further investigation in the risk-benefit profile of brolucizumab for the treatment of neovascular age-related macular degeneration.

Anti-Vascular Endothelial Growth Factor Treatment Compared with Steroid Treatment for Retinal Vein Occlusion: A Meta-Analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) and steroid treatment are both used for macular edema (ME) secondary to retinal vein occlusion (RVO), however a continual reevaluation of their comparative efficacy is required. OBJECTIVES: This meta-analysis aimed to compare the efficacy and safety of intravitreal anti-VEGF agents and intravitreal steroids for the treatment of ME secondary to RVO. METHODS: A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and the Cochrane Controlled Register of Trials for studies published between January 2005 and November 2021. Randomized controlled trials (RCTs) reporting on patients with ME secondary to RVO who were treated with intravitreal steroids or anti-VEGF agents were included. A random effects meta-analysis was performed. RESULTS: 879 eyes from 11 RCTs were included. At the last study observation, intravitreal anti-VEGF agents were associated with a significantly better best corrected visual acuity (WMD = -0.14 logMAR, 95% CI = [-0.19, -0.09], p < 0.00001) and lower retinal thickness (WMD = -38.01 µm, 95% CI = [-56.17, -19.85], p < 0.0001) relative to intravitreal steroids. Similar findings were found at 3-12 month time points. Intravitreal anti-VEGF agents were associated with a significantly lower incidence of IOP-related adverse events (RR = 0.28, 95% CI = [0.15, 0.51], p < 0.0001), cataract development/progression (RR = 0.22, 95% CI = [0.09, 0.49], p = 0.0003), and conjunctival hemorrhage (RR = 0.52, 95% CI = [0.32, 0.86], p = 0.01). CONCLUSIONS: Our meta-analysis found superiority of intravitreal anti-VEGF agents relative to intravitreal steroids for the treatment of ME secondary to RVO with regards to visual acuity, anatomic outcomes, and safety endpoints.

Scleral Buckling Alone or in Combination with Pars Plana Vitrectomy for Rhegmatogenous Retinal Detachment Repair: A Meta-Analysis of 7,212 Eyes.

PURPOSE: The efficacy and safety of scleral buckling (SB) versus combination SB and pars plana vitrectomy (SB + PPV) for rhegmatogenous retinal detachment (RRD) repair remains unclear. METHODS: A systematic review and meta-analysis was conducted to identify comparative studies published from Jan 2000-Jun 2021 that reported on the efficacy and/or safety following SB and SB + PPV for RRD repair. Final best-corrected visual acuity (BCVA) represented the primary endpoint, while reattachment rates and ocular adverse events were secondary endpoints. A random-effects meta-analysis was performed, and 95% confidence intervals were calculated. RESULTS: Across 18 studies, 3912 SB and 3300 SB + PPV eyes were included. Final BCVA was nonsignificantly different between SB and SB + PPV (20/38 vs. 20/66 Snellen; WMD = -0.11 LogMAR; 95% CI: [-0.29, 0.07]; p = 0.23). Primary reattachment rate was similar between procedures (p = 0.74); however, SB alone achieved a significantly higher final reattachment rate (97.40% vs. 93.86%; RR = 1.03; 95% CI: [1.00, 1.06]; p = 0.04). Compared to SB + PPV, SB alone had a significantly lower risk of postoperative macular edema (RR = 0.69; 95% CI: [0.47, 1.00]; p = 0.05) and cataract formation (RR = 0.34; 95% CI: [0.12, 0.96]; p = 0.04). The incidence of macular hole, epiretinal membrane, residual subretinal fluid, proliferative vitreoretinopathy, elevated intraocular pressure, and extraocular muscle dysfunction were similar between SB and SB + PPV. CONCLUSIONS: There was no significant difference in final BCVA between SB + PPV and SB alone in RRD. SB alone offers a slightly higher final reattachment rate along with a reduced risk of macular edema and cataract. Primary reattachment rate and the incidence of other complications were similar between the two procedures.