Predictive Factors for Functional and Anatomical Outcomes After Anti-VEGF Treatment for Macular Edema in Patients with Branch Retinal Vein Occlusion.

Purpose: This study aimed to identify predictive factors for the improvement of best-corrected visual acuity (BCVA) and reduction of central macular thickness (CMT) after treatment of macular edema (ME) due to branch retinal vein occlusion (BRVO) in a real-world setting. Methods: This retrospective study included patients with ME secondary to BRVO who were treated with intravitreal injection of bevacizumab as the first-line therapy and were followed up for 12 months. Demographic and clinical data, in addition to baseline spectral domain optical coherence tomography (SD-OCT) features, were considered as possible biomarkers of final BCVA and CMT. We also collected the data concerning the need for additional treatment including sectorial laser photocoagulation, change to another anti-VEGF agent, or intravitreal corticosteroid injection. Results: A total of 161 eyes were analyzed. BCVA significantly improved from baseline to 12-month follow-up (0.6 and 0.4 logMAR, respectively; P < 0.01). CMT decreased significantly during the follow-up period (from 498.0 to 325.0 µ m; P < 0.01). Final BCVA correlated positively with baseline BCVA (P < 0.01, r = 0.57). Older age at diagnosis and baseline SD-OCT findings including CMT, disruption of the retinal inner layers, retinal pigment epithelium (RPE) damage, and impairment of the ellipsoid zone and external limiting membrane negatively affected final BCVA (P < 0.01). Multiple regression analysis identified age and BCVA at baseline as the only independent predictors of final BCVA (P = 0.001 and P < 0.01, respectively). No association was found between clinical data, SD-OCT parameters, and final CMT. Conclusion: Various clinical and SD-OCT parameters are prognostically relevant for visual improvement in ME secondary to BRVO. Age at diagnosis and baseline BCVA were found to be independent predictors of visual outcome.

Grad-CAM-Based Investigation into Acute-Stage Fluorescein Angiography Images to Predict Long-Term Visual Prognosis of Branch Retinal Vein Occlusion.

Background/Objectives: The purpose of this study was to analyze relevant areas in acute-stage fluorescein angiography (FA) images, predicting the long-term visual prognosis of branch retinal vein occlusion (BRVO) based on gradient-weighted class activation mapping (Grad-CAM). Methods: This retrospective observational study included 136 eyes with BRVO that were followed up for more than a year post-FA. Cropped grayscale images centered on the fovea (200 × 200 pixels) were manually pre-processed from early-phase FA at the acute phase. Pairs of the cropped FA images and the best-corrected visual acuity (BCVA) in remission at least one year post-FA were used to train a 38-layer ResNet with five-fold cross-validation. Correlations between the ResNet-predicted and true (actually measured) logMAR BCVAs in remission, and between the foveal avascular zone (FAZ) area measured by ImageJ (version 1.52r) from FA images and true logMAR BCVA in remission were evaluated. The heat maps generated by Grad-CAM were evaluated to determine which areas were consumed as computational resources for BCVA prediction. Results: The correlation coefficient between the predicted and true logMAR BCVAs in remission was 0.47, and that between the acute-stage FAZ area and true logMAR BCVA in remission was 0.42 (p < 0.0001 for both). The Grad-CAM-generated heat maps showed that retinal vessels adjacent to the FAZ and the FAZ per se had high selectivity (95.7% and 62.2%, respectively). Conclusions: The Grad-CAM-based analysis demonstrated FAZ-neighboring vessels as the most relevant predictor for the long-term visual prognosis of BRVO.

Factors Affecting Compliance and Visual Outcomes in Patients Receiving Intravitreal Bevacizumab Injections.

Background Vascular endothelial growth factor (VEGF) is a powerful mitogen for endothelial cells that promotes migration, proliferation, and tube formation necessary for the angiogenic development of new blood vessels. When VEGF increases significantly, it causes pathological angiogenesis and increased vascular permeability in eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO). These disorders have become important global sources of morbidity and have a substantial financial impact not only on the medical community but also on the patients. Therefore, this study aims to determine the success rates of intravitreal bevacizumab therapy and the visual outcomes which may be increased by determining the factors affecting patient compliance and raising awareness about DR, neovascular AMD, and RVO among patients and studying the factors responsible for non-compliance to treatment. Methodology This experimental pre-post study was conducted in the ophthalmology department at a tertiary care hospital and research center in western Maharashtra from September 2022 to June 2024. A total of 150 eyes of 150 patients who were diagnosed cases of DR, neovascular AMD, and non-ischemic RVO were included in the study. Written informed consent was obtained from each patient. Data were entered in Microsoft Excel (Microsoft Corp., Redmond, WA, USA) and statistical analysis was done using SPSS 27.0 software (IBM Corp., Armonk, NY, USA). The chi-square test was employed to check the association between categorical variables. Pearson's correlation test was used, and p-values <0.05 were considered significant. Results The compliance rate in our study was 79.3% (113 individuals). In our study, 58% (87 individuals) were male while 42% (63 individuals) were females. Most patients were from urban areas 74.7% (112 individuals). Among the study participants, DR patients constituted 48.6% (73 individuals), while neovascular AMD and RVO were seen in 32% (48 individuals) and 19.4% (29 individuals), with 62% (93 individuals) being diabetic and 64.7% (97 individuals) being hypertensive. In our study, 92% (138 individuals) were willing to take treatment, with 88.7% (133 individuals) worried about their visual outcomes and 66% (99 individuals) afraid of getting injected. Appointments posed a financial burden to 30.7% (46 individuals) of patients, with 55.3% (83 individuals) having transportation issues. Overall, 18.7% (28 individuals) of patients had missed appointments between 14 and 90 days while 30.7% (46 individuals) had missed their appointments by 90 and 365 days. Younger patients with a shorter duration of diabetes had higher compliance rates. Post-injection, there was an overall significant improvement in vision as well as a reduction in the central subfield macular thickness, volume cube, and thickness average cube. Conclusions In the present study, four-fifths of the patients were compliant with treatment, and visual improvement was significant. In addition, there was a significant reduction in the macular thickness after the treatment. One of the factors for non-compliance included in our study was the need for follow-up. Younger patients and those with a shorter duration of diabetes had significantly higher compliance. We recommend further studies should be conducted to compare the effectiveness with the control group in randomized control trials.

Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies.

Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME.

Association Between Serum Vitamin D Levels and Retinal Vascular Occlusion: A Systematic Review and Meta-Analysis.

Previous studies found seasonal variations in the incidence of retinal vascular occlusion (RVO), with more occurrence in winter. There is increasing evidence linking vitamin D deficiency and RVO. Therefore, we conducted a meta-analysis to evaluate the association between vitamin D levels and RVO. From inception to February 2024, MEDLINE and EMBASE databases were comprehensively searched. Observational studies comparing 25-hydroxyvitamin D (25(OH)D) levels between adult patients with RVO and non-RVO controls were included. We calculated pooled mean difference (MD) and pooled odds ratio (OR) with 95% confidence intervals (CI) of our data using a random-effects model and generic inverse variance method. Five studies involving 528 patients (228 patients with RVO and 300 controls were included in the meta-analysis. 25(OH)D was significantly lower in patients with RVO (pooled MD of -9.65 (95%CI -13.72 to -5.59, I2 = 92.2%). Vitamin D deficiency (serum 25(OH)D < 20) was significantly associated with RVO with the pooled OR of 14.52 (95%CI 1.72 to 122.59, I2 = 90.5). There was no difference in 25(OH)D levels between patients with central RVO and branched RVO (pooled MD of -0.94 (95%CI -3.91 to 2.03, I2 = 59.1%). In conclusion, our meta-analysis demonstrates that serum vitamin D levels were lower in patients with RVO than non-RVO controls. Clinicians could consider screening for vitamin D deficiency in patients with RVO. Further studies are warranted to determine the correlation between vitamin D levels and disease severity and the role of vitamin D supplements in these populations.

Relationship between retinal volume changes and the prognosis of BRVO-ME treated with ranibizumab.

Background: This study aimed to evaluate the efficacy of ranibizumab for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO-ME), changes in retinal volume and central retinal thickness (CRT) before and after therapy, and the connection between visual prognosis and changes in retinal volume. Methods: The 120 patients(121 eyes) of BRVO-ME were recruited from July 2020 to October 2022 at the Affiliated Hospital of Weifang Medical University. The clinical data of patients were retrospectively examined for changes in best-corrected visual acuity (BCVA), retinal volume, and CRT at 1 day, 1 week, 1 month, 3 months, 6 months and 1year after treatment. Findings: Visual acuity improved gradually and became steady approximately 1 months after treatment, whereas retinal volume decreased gradually in both the outer and full layers and stabilized around 6 month after treatment. The decline in retinal volume and CRT was more visible in the deeper layers than in the inner levels. A higher correlation was observed between retinal volume and BCVA than between CRT and BCVA. BCVA after one year of treatment had a high correlation with baseline outer retinal volume. Interpretation: Treatment of BRVO-ME with ranibizumab is highly effective, and the recovery of visual function was depends more on early treatment. The outer retina is the major site of edema. Changes in retinal volume may serve as a better predictor of visual prognosis than changes in CRT. Baseline ourter retinal volume is correlated with long-term visual prognosis.

Association between time to treatment and outcome in branch retinal vein occlusion.

PURPOSE: To investigate the association between the time from onset to initial treatment and changes in visual acuity or the number of treatments in patients with branch retinal vein occlusion (BVO). DESIGN: Retrospective. METHODS: Thirty-nine eyes of 39 consecutive patients with untreated acute-phase BVO who visited the University of Tokyo Hospital and were followed up for at least one year were included. The patients were initially treated with anti-vascular endothelial growth factor (VEGF) therapy and additional pro re nata therapy within six months of onset. The patients were classified according to the time from disease onset to the first treatment (group A: 28 days or less, group B: over 28 days). RESULTS: The mean (SD) age was 73 ± 8 years, and 19 patients were male. The mean (SD) time to the first treatment was 31.6 ± 17.9 days. The mean (SD) logMAR visual acuity at first treatment was 0.37 ± 0.30. After 12 months of treatment, the mean (SD) logMAR change was - 0.15 ± 0.23, and the mean number (SD) of treatments was 3.1 ± 1.7. No significant association was observed between the timing of treatment initiation and changes in logMAR visual acuity. Patients in group A and central macular thickness at the initial visit were independently associated with the greater number of treatments at one year (p = 0.03 and p = 0.01, respectively). CONCLUSIONS: At one year, the time between onset and the start of anti-VEGF therapy for BVO was not associated with subsequent visual acuity changes. Meanwhile, it may have significant association with the number of treatments.

Prediction of treatment outcome for branch retinal vein occlusion using convolutional neural network-based retinal fluorescein angiography.

Deep learning techniques were used in ophthalmology to develop artificial intelligence (AI) models for predicting the short-term effectiveness of anti-VEGF therapy in patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME). 180 BRVO-ME patients underwent pre-treatment FFA scans. After 3 months of ranibizumab injections, CMT measurements were taken at baseline and 1-month intervals. Patients were categorized into good and poor prognosis groups based on macular edema at the 4th month follow-up. FFA-Net, a VGG-based classification network, was trained using FFA images from both groups. Class activation heat maps highlighted important locations. Benchmark models (DesNet-201, MobileNet-V3, ResNet-152, MansNet-75) were compared for training results. Performance metrics included accuracy, sensitivity, specificity, F1 score, and ROC curves. FFA-Net predicted BRVO-ME treatment effect with an accuracy of 88.63% and an F1 score of 0.89, with a sensitivity and specificity of 79.40% and 71.34%, respectively.The AUC of the ROC curve for the FFA-Net model was 0.71. The use of FFA based on deep learning technology has feasibility in predicting the treatment effect of BRVO-ME. The FFA-Net model constructed with the VGG model as the main body has good results in predicting the treatment effect of BRVO-ME. The typing of BRVO in FFA may be an important factor affecting the prognosis.

Demographic profile, prevalence, pattern, and risk factors for retinal vein occlusion in Liberia: A retrospective study.

PURPOSE: This study aims to describe the demographic profile, prevalence, pattern, and risk factors for retinal vein occlusion (RVO) in patients over 40 years of age presenting to the Liberia Eye Centre, John F Kennedy Memorial Medical Centre, Monrovia, Liberia. SUBJECTS AND METHODS: A retrospective study was conducted on patients presenting to Liberia Eye Centre from July 2017 to February 2021. A total of 17506 new patients were examined during this period out of which 10813 patients were over 40 years of age. Data were collected from the electronic medical record system database. The variables in the collected data included age, gender, location, laterality of eye affected, uncorrected visual acuity, best-corrected visual acuity, intraocular pressure, ocular diagnosis, systemic risk factors, and associated complications. RESULTS: Of the 10813 patients, RVO was found in 111 patients with an overall prevalence rate of 1.03% (95% confidence interval 0.80-1.2). Central RVO (CRVO) was more common than branch RVO (BRVO) in the defined population with similar proportions of both genders. The mean age for any RVO was 64.45 ± 12.27 standard deviation (SD) years (P = 0.734). Majority of the cases of RVO were from Lofa (n = 20; 18%). Fifty-five (61.1%) patients had hypertension, 5 (5.6%) had diabetes mellitus, and 6 (6.7%) had dyslipidemia. More than one systemic risk factor was present in 24 (26.7%) patients. However, none of the systemic risk factors were statistically significant. Visual acuity was most affected in patients with CRVO, with a visual acuity of <3/60 in 45 (63.4%) patients compared to 12 (30.0%) in BRVO patients. Glaucoma was present in 34 (30.6%) patients. The most common ocular complication was macular edema (n = 62, 55.8%) followed by vitreous hemorrhage (n = 8, 7.2%). CONCLUSIONS: RVO was detected in 1.03% of the study population over the age of 40 years in Liberia, CRVO being more common than BRVO. The clinical presentation of RVO in the Liberian population for the first time provides insight into the burden of the disease and opportunity for further research.

Risk of stroke development following retinal vein occlusion: A systematic review and meta-analysis.

Retinal vein occlusion (RVO) and cerebrovascular disease share common risk factors and may be independently associated; however, the strength and nature of this association remain unclear. We conducted a systematic review and meta-analysis, informed by studies from PubMed, Scopus, EMBASE, Web of Science, and Google Scholar until January 6, 2024, aimed to clarify this relationship. Eligible studies included cohorts observing stroke incidence in RVO patients for over a year. Pooled effect estimates were calculated using random-effects models, with subgroup analyses evaluating associations between RVO types (central and branch) and stroke subtypes (ischemic and hemorrhagic). Ten cohort studies with a total of 428,650 participants (86,299 RVO patients) were included. Compared to controls, RVO patients exhibited a significantly increased risk of stroke (pooled risk ratio [RR]=1.38, 95 % confidence interval (95 %CI)=1.34-1.41). Subgroup analyses indicated elevated risk for both ischemic (RR=1.37, 95 %CI=1.32-1.42) and hemorrhagic (RR=1.55, 95 %CI=1.08-2.22) strokes in RVO patients. Additionally, both central (RR=1.50, 95 %CI=1.27-1.78) and branch (RR=1.41, 95 %CI=1.32-1.50) RVO were associated with stroke risk. Sensitivity analyses confirmed consistent results across various criteria, and funnel plots indicated no publication bias. RVO significantly increases the risk of both ischemic and hemorrhagic stroke, regardless of RVO type, suggesting a strong independent association between these conditions.

Comparing ranibizumab, dexamethasone implant, and combined therapy for macular edema secondary to branch retinal vein occlusion: a clinical trial.

BACKGROUND: Macular edema (ME) is a common complication following branch retinal vein occlusion (BRVO) and is also the main reason for visual impairment. This study aimed to compare the efficacy and safety of intravitreal ranibizumab (IVR) or dexamethasone implant (IDI) monotherapy, as well as the combination of IVR and IDI injections, in patients with ME secondary to branch retinal vein occlusion (BRVO). METHODS: This multicenter, prospective, and comparative study included 292 patients with unilateral ME involvement (total of 292 eyes) secondary to BRVO. The patients were randomly assigned to three groups and followed up for 12 months. Patients in group 1 (n = 96) were treated with 3-dose loading IVR injections followed by a pro re nata (PRN) regimen. Patients in group 2 (n = 98) received IVR combined with IDI injection, followed by IVR PRN regimen. Patients in group 3 (n = 98) were treated with IDI injection, followed by repeated IDI injection based on clinical necessity. Best corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and frequency of injections were recorded and compared between the three groups. RESULTS: At baseline, the three groups did not differ in age, gender, duration of ME, BCVA, IOP, and CRT (P > 0.05). Mean number of total injections per eye within 12 months were 7.1 ± 2.3 (range 4-9) in group 1, 3.7 ± 1.5 (range 2-6) in group 2, and 1.8 ± 0.4 (range 1-3) in group 3. There was a statistical difference in the number of injections between group 1 and group 2 (P = 0.037). Eyes in group 3 received fewer injections than those in group 2, but the difference was not statistically significant (P = 0.052). BCVA improvement and CRT reduction were achieved in all groups and there was no significant difference between the three groups at the end of the 12th month. However, IOP elevation and cataract progression were more frequent in group 3, especially in those patients who received repeated IDI injections. CONCLUSION: Three therapeutic regimens had comparable efficacy in treating ME secondary to BRVO. Combination therapy had an advantage in maintaining good effect with fewer re-injections and complications. TRIAL REGISTRATION INFORMATION: The study complied with the principles of the Declaration of Helsinki and was approved by Xi'an Aier Ancient City Eye Hospital, Xi'an Aier Eye Hospital, and Xianyang Aier Eye Hospital ethics committees (2022SF-367).

The measurement and correlation analysis of scleral and choroid thickness in branch retinal vein occlusion.

To use Optical Coherence Tomography (OCT) to measure scleral thickness (ST) and subfoveal choroid thickness (SFCT) in patients with Branch Retinal Vein Occlusion (BRVO) and to conduct a correlation analysis. A cross-sectional study was conducted. From May 2022 to December 2022, a total of 34 cases (68 eyes) of untreated unilateral Branch Retinal Vein Occlusion (BRVO) patients were recruited at the Affiliated Eye Hospital of Nanchang University. Among these cases, 31 were temporal branch vein occlusions, 2 were nasal branch occlusions, and 1 was a superior branch occlusion. Additionally, 39 cases (39 eyes) of gender- and age-matched control eyes were included in the study. Anterior Segment Optical Coherence Tomography (AS-OCT) was used to measure ST at 6 mm superior, inferior, nasal, and temporal to the limbus, while Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) was used to measure SFCT. The differences in ST and SFCT between the affected eye, contralateral eye, and control eye of BRVO patients were compared and analyzed for correlation. The axial lengths of the BRVO-affected eye, contralateral eye, and control group were (22.92 ± 0.30) mm, (22.89 ± 0.32) mm and (22.90 ± 0.28) mm respectively, with no significant difference in axial length between the affected eye and contralateral eye (P > 0.05). The SFCT and ST measurements in different areas showed significant differences between the BRVO-affected eye, contralateral eye in BRVO patients (P < 0.05). The CRT of BRVO-affected eyes was significantly higher than that of the contralateral eyes and the control eyes (P < 0.001). In comparison between BRVO-affected eyes and control eyes, there were no statistically significant differences in age and axial length between the two groups (P > 0.05). However, significant differences were observed in SFCT and temporal, nasal, superior, and inferior ST between the two groups (P < 0.05). The difference in temporal ST between the contralateral eyes and the control eyes was not statistically significant (t = - 0.35, P = 0.73). However, the contralateral group showed statistically significant increases in SFCT, nasal, superior and inferior ST compared to control eyes (t = - 3.153, 3.27, 4.21, 4.79, P = 0.002, 0.002, < 0.001, < 0.001). However, the difference between the CRT of the contralateral and control eyes was not statistically significant (P = 0.421). When comparing SFCT and ST between BRVO-affected eyes with and without macular edema, no statistically significant differences were found (t = - 1.10, 0.45, - 1.30, - 0.30, 1.00; P = 0.28, 0.66, 0.21, 0.77, 0.33). The thickness of SFCT and temporal ST in major BRVO group is higher than the macular BRVO group and the difference was statistically significant (t = 6.39, 7.17, P < 0.001 for all). Pearson correlation analysis revealed that in BRVO patients, there was a significant positive correlation between SFCT/CRT and temporal ST (r = 0.288, 0.355, P = 0.049, 0.04). However, there was no correlation between SFCT/CRT and nasal ST, superior ST, and inferior ST (P > 0.05). In BRVO patients, both SFCT/CRT and ST increase, and there is a significant correlation between SFCT/CRT and the ST at the site of vascular occlusion.

Visual Acuity and Retinal Thickness and Sensitivity after Intravitreal Ranibizumab Injection for Macular Edema in Branch Retinal Vein Occlusion.

Background/Objectives: To investigate changes in visual acuity and retinal sensitivity and thickness after intravitreal ranibizumab injection (IRI) for macular edema in branch retinal vein occlusion (BRVO) patients. Methods: This study evaluated 34 patients with treatment-naïve BRVO and at least 6 months' follow-up after pro re nata IRI. Best-corrected visual acuity (BCVA) was determined as the logarithm of the minimum angle of resolution (logMAR). In nine retinal regions, retinal sensitivity was calculated by MP-3 microperimetry; and in nine macular subfields, retinal thickness was measured by optical coherence tomography (OCT); evaluations were performed before IRI and then monthly for 6 months. Results: IRI significantly improved visual acuity and retinal sensitivity and thickness. In patients with good improvement in BCVA (change in logMAR > 0.2), IRI significantly improved retinal sensitivity in eight of nine regions, i.e., in all except the outer non-occluded region, and in patients with poor improvement in BCVA (change in logMAR < 0.2), in six of nine regions, i.e., not in the inner, outer non-occluded, and outer temporal regions. We found significant differences in the trend profile in the foveal, outer occluded, and inner nasal regions between patients with good and poor improvement in BCVA. Conclusions: The findings suggest that IRI improves visual acuity and retinal sensitivity and thickness and that retinal effects may vary between patients with good and poor visual improvement.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. DESIGN: Multicenter, international, BRVO database study. SUBJECTS: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. MAIN OUTCOME MEASURES: Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. RESULTS: Mean adjusted VA change was +11 letters (95% confidence interval 9-13), mean adjusted change in CST was -176 µm (-193, -159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n = 677) and as a monotherapy in 71% (n = 538). Few eyes were switched to steroids (11%, n = 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs. -128 vs. -114 µm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. CONCLUSIONS: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy, Safety, and Treatment Burden of Aflibercept 2 mg and Ranibizumab in Retinal Vein Occlusion: A Systematic Review and Meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to provide an updated evidence base for clinical decision-making by comparing the efficacy and safety of aflibercept 2 mg and ranibizumab in treating retinal vein occlusion (RVO). METHODS: A systematic search was conducted using eight databases up to December 2021. Randomized controlled trials (RCTs) and real-world studies (RWSs) comparing aflibercept and ranibizumab in patients with RVO were evaluated. The primary outcomes assessed were efficacy, number of injections administered, and adverse events. RESULTS: Three RCTs (424 patients) and 11 RWSs (1415 patients) were included. For central RVO (CRVO), RCTs demonstrated a comparable efficacy, whereas RWSs showed that mean changes from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were significantly greater with aflibercept compared to ranibizumab; the number of injections of aflibercept was fewer than that of ranibizumab in RCTs, but similar in RWSs. For branch RVO (BRVO), no statistically significant difference in efficacy between the two drugs in RCTs/RWSs was observed, with fewer injections of aflibercept at 12 months in RWSs. The safety profiles of both drugs were similar for both CRVO and BRVO. CONCLUSIONS: For CRVO, aflibercept had similar efficacy and safety profile but with fewer injections versus ranibizumab in RCTs; RWSs showed greater BCVA improvement and CRT reduction with aflibercept than ranibizumab. For BRVO, RCTs showed similar in efficacy, safety, and injection numbers for both drugs, while RWSs demonstrated that aflibercept required fewer injections at 12 months of follow-up. Overall, this study provides updated evidence for clinical decision-making in the treatment of RVO.

Frosted branch angiitis in a patient with systemic juvenile idiopathic arthritis: a case report.

BACKGROUND: Frosted branch angiitis is a retinal vascular condition that is associated with a viral infection or autoimmune disorders like Crohn's disease, systemic lupus erythematosus, and Behcet's disease. Frosted branch angiitis presents with vascular inflammation, retinal edema, and severe retinal vascular sheathing. We present a case of systemic juvenile idiopathic arthritis, an autoinflammatory disease, presenting with frosted branch angiitis. REPORT OF CASE: A 14-year-old female with systemic juvenile idiopathic arthritis and a history of bilateral anterior uveitis developed acute unilateral vision loss and was found to have frosted branch angiitis complicated by branch retinal vein occlusion. She underwent an extensive serology workup and aqueous viral PCR to rule out other possible autoimmune and viral etiologies for forested branch angiitis. She received systemic and intravitreal antiviral treatment due to positive CMV IgM initially. However, the clinical picture improved following the use of a higher dose of oral steroids and the switch of the immunosuppressive agent to a TNF-a inhibitor. CONCLUSION: To our knowledge, this would be the first case in the literature demonstrating a systemic juvenile idiopathic arthritis patient presenting with frosted branch angiitis. Infectious causes still must be ruled out, especially CMV, as it is the most common cause of secondary frosted branch angiitis.

Changes in Neurodegeneration and Visual Prognosis in Branch Retinal Vein Occlusion after Resolution of Macular Edema.

This study aimed to examine the thicknesses of the ganglion cell layer (GCL) and peripapillary retinal nerve fiber layer (RNFL) in eyes with resolved macular edema (ME) in branch retinal vein occlusion (BRVO) and determine their relationship with visual acuity (VA). This retrospective observational case-control study included 57 eyes of BRVO patients with resolved ME after treatment. The macular GCL thickness, peripapillary RNFL thickness, and central macular thickness (CMT) measured on swept-source optical coherence tomography scans with the contralateral eyes used as controls were evaluated. The mean CMT was 270.48 ± 32.7 µm; the mean RNFL thickness was 105.46 ± 25.94 µm in BRVO eyes. Although the average RNFL thickness was decreased in BRVO eyes compared to unaffected eyes, there was no significant difference between the groups. However, the temporal and nasal RNFL thicknesses were significantly different between the groups. The mean affected quadrant had a significantly thinner GCL compared to the corresponding opposite unaffected quadrant (p = 0.02). Final VA was significantly correlated with nasal and middle GCL thicknesses in the affected area (r = -0.512, p = 0.003 and r = -0.537, p = 0.001, respectively); no correlation was found between the average RNFL thickness and mean CMT. The peripapillary RNFL and GCL thicknesses of the affected area were reduced in BRVO eyes compared to unaffected eyes. VA significantly correlated with nasal and middle GCL thicknesses in the affected area. Inner retinal damage occurring in patients with ME secondary to BRVO may be related to the visual prognosis.

Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study.

BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Association of triglyceride­glucose index in branch retinal vein occlusion.

BACKGROUND: To investigate the association between the triglyceride-glucose (TyG) index and newly diagnosed branch retinal vein occlusion (BRVO) in patients. METHODS: The study included 57 individuals with BRVO and a control group comprising 50 healthy volunteers matched for age and gender. Detailed eye examinations were conducted, and various blood biochemistry and hematological parameters were recorded. The TyG index was calculated using fasting plasma glucose and triglyceride values. RESULTS: The mean age was 61.4 ± 9.6 years for the BRVO group and 60.6 ± 10.3 years for the control group. The TyG values were significantly higher in the BRVO group when compared to the control group (8.84 ± 0.41 vs. 8.52 ± 0.29, p < 0.001). Multivariate analysis revealed that the TyG index independently predicted BRVO (odds ratio = 2.58, 95% confidence interval = 1.69-3.93; p < 0.001). In receiver operating characteristics analysis, the TyG index had an area under the curve of 0.749, and a TyG index higher than 8.52 predicted BRVO with 83% sensitivity and 70% specificity. CONCLUSIONS: This study establishes a significant association between an elevated TyG index and BRVO. Consequently, the TyG index could serve as a valuable predictive tool for identifying individuals at risk for BRVO.

Anatomical and Functional Results of Early or Late Switching from Anti-VEGF to Dexamethasone Implant in Case of Poor Anatomical Response in Naïve Patients with Macular Edema Secondary to Branch Retinal Vein Occlusion.

PURPOSE: To compare the outcomes of early or late switching from intravitreal (IV) anti-vascular endothelial growth factor (anti-VEGF) injection to IV Dexamethasone (DEX) implant injection in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion. METHODS: This study included 68 eyes of 68 treatment-naïve BRVO patients who started anti-VEGF treatment. After the loading dose, the patients were divided into two groups: Early DEX group (n:34) (DEX implant treatment started after 3 loading doses) and Late DEX group (n:34) (DEX implant treatment started after 6 months). Visual acuity and examination findings were recorded at baseline, 3rd, 6th, and 12th month follow-ups. Optical coherence tomography data were recorded for central macular subfield thickness assessment. RESULTS: A total of 30 (44.1%) women and 38 (55.9%) men participated, and the average age was 67.6 ± 6.4 years. The mean letter gains at week 52 was 15.1 and 20.9 in the Early DEX and Late DEX groups, respectively. The group with the highest gain of ≥15 letters was the Late DEX group (26/34 patients) and the gain of ≥15 letters was 14/34 in the Early DEX group (p: 0.006). At week 52, the anatomical gain was 115.3 µm and 136.9 µm in the Early DEX and Late DEX groups, respectively. CONCLUSIONS: A gain of 15 or more letters was demonstrated to be higher in patients who switched to DEX implant late after anti-VEGF treatment. If it is necessary to switch, the late switch may be more effective for more visual gain at the end of the first year.