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.

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.

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.

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.

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.

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.

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.

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.

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.

Real-World Management of Macular Edema Secondary to Retinal Vein Occlusion with Intravitreal Aflibercept: 24-month Results from the AURIGA Observational Study.

INTRODUCTION: AURIGA is the largest real-world study to date to evaluate intravitreal aflibercept (IVT-AFL) treatment of diabetic macular edema or macular edema secondary to retinal vein occlusion (RVO) in routine clinical practice. Here, we report the 24-month outcomes in the RVO cohort from France, Germany, Italy, and Taiwan. METHODS: AURIGA (NCT03161912) was a prospective observational study. Eligible patients with RVO were enrolled for whom the decision to treat with IVT-AFL had already been made by the attending physician. Patients were treated with IVT-AFL for up to 24 months at physician discretion according to local practice. The primary endpoint was mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study [ETDRS] letters) from baseline to month (M) 12. All statistical analyses were descriptive. RESULTS: In 554 treatment-naïve and 65 previously treated patients with RVO, the respective mean (95% confidence interval) change in VA from baseline was + 12.5 (10.8, 14.3) and + 7.9 (3.3, 12.6) letters by M12 and + 11.4 (9.4, 13.3) and + 4.4 (- 0.6, 9.5) letters by M24 (baseline mean ± standard deviation: 51.0 ± 21.9 and 51.9 ± 20.4 letters); 44.0% of treatment-naïve and 27.9% of previously treated patients reported ≥ 15-letter gains by M24. By M24, the mean change in central retinal thickness from baseline was - 247 (- 267, - 227) µm in treatment-naïve patients and - 147 (- 192, - 102) µm in previously treated patients. From baseline to M6, M12, and M24, treatment-naïve patients received a total of 4.0 ± 1.3, 5.5 ± 2.5, and 6.9 ± 4.2 injections, respectively, and previously treated patients received 3.8 ± 1.5, 5.0 ± 2.2, and 6.3 ± 3.7 injections, respectively. The safety profile of IVT-AFL was consistent with that of previous studies. CONCLUSIONS: In AURIGA, patients with RVO experienced clinically relevant functional and anatomic improvements following IVT-AFL treatment in routine clinical practice. These improvements were largely maintained in treatment-naïve patients over the 24-month study despite the decreasing treatment frequency, suggesting long-term durability of IVT-AFL treatment outcomes. Infographic available for this article. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03161912 (May 19, 2017). INFOGRAPHIC.

Non-perfusion severity correlates with central macular thickness and microvascular impairment in branch retinal vein occlusions.

PURPOSE: To study peripheral capillary non-perfusion (PCN-P) in branch retinal vein occlusion (BRVO) by means of ultra wide-field fluorescein angiography (UWFFA), and to correlate its extent and severity with optical coherence tomography (OCT) and OCT-angiography (OCTA) parameters and best corrected visual acuity (BCVA). METHODS: Prospective case series with 2 years of planned follow-up. We recruited patients from June 2019 to December 2019. Ophthalmologic examination included BCVA, UWFFA, OCT and OCTA. Partial (p) and complete (c) ischemic index (ISI) were evaluated on UWFFA images. Vessel density (VD) in both the macular region and the optic nerve head (ONH) was calculated. RESULTS: Twelve BRVO subjects and 12 healthy controls were recruited. Mean age was 63.8 ± 8.74 years. Mean BCVA improved from 0.43 ± 0.25 logMAR to 0.15 ± 0.18 after two years (p < 0.01), while mean central macular thickness (CMT) decreased from 463.83 ± 200.85 µm to 353.17 ± 108.85 µm (p > 0.05). Mean cISI, pISI and total ISI were 25.2 ± 13.0%, 6.3 ± 5.0% and 31.5 ± 12.0%, respectively. Except for VDs of the superficial capillary plexus and choriocapillaris in the macular region, all VDs were lower in the BRVO group (p < 0.01). cISI and tISI negatively correlated with mDCP (p < 0.01), whereas only pISI correlated with CMT at baseline (p < 0.05). Additionally, cISI also negatively correlated with VD at the ONH (p < 0.05). CONCLUSION: The amount of complete and partial ischemia may have different implications in BRVO, with the former being more associated with microvascular impairment and the latter with macular edema.

Comparative study of retinal volume changes in ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion treated with ranib-izumab / 眼科新进展

Objective To compare the clinical outcomes and retinal volume changes in patients with ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion(BRVO-ME)using optical coherence tomography angiography(OCTA).Methods The clinical data of 34 ischemic BRVO-ME patients(34 eyes,ischemic group)and 21 non-ischemic BRVO-ME patients(21 eyes,non-ischemic group)were retrospectively analyzed.Patients in both groups re-ceived intravitreal injections of ranibizumab.The best corrected visual acuity(BCVA)and retinal volume of the macular ar-ea were assessed before,1 day,1 week,1 month,3 months and 6 months after the treatment.Results The BCVA(log-MAR)at 1 day after the treatment was 0.63±0.37 in the ischemic group and 0.44±0.22 in the non-ischemic group,and the difference was statistically significant(P=0.017).The retinal volumes of the outer retina,the full retina,and the Farafovea and Perifovea subdivisions of the full retina before the treatment were(6.42±1.90)mm3,(8.75±1.82)mm3,(3.20±0.87)mm3 and(5.10±0.89)mm3 in the ischemic group and(5.52±1.57)mm3,(7.83±1.56)mm3,(2.80± 0.71)mm3,and(4.66±0.77)mm3 in the non-ischemic group,respectively;1 day after treatment,they were(4.97± 1.18)mm3,(7.46±1.47)mm3,(2.62±0.60)mm3 and(4.53±0.80)mm3 in the ischemic group and(4.25±0.48)mm3,(6.58±0.56)mm3,(2.26±0.26)mm3 and(4.06±0.40)mm3 in the non-ischemic group,respectively;at 1 week after the treatment,they were(4.40±0.82)mm3,(6.90±0.85)mm3,(2.38±0.36)mm3 and(4.24±0.49)mm3 in the ischemic group and(4.04±0.35)mm3,(6.33±0.49)mm3,(2.15±0.19)mm3 and(3.95±0.35)mm3 in the non-ische-mic group,respectively,and the differences between the two groups were statistically significant(all P＜0.05).The a-mount of retinal volume change from baseline in the outer retina and the full retina was(-2.48±2.38)mm3 and(-2.54±2.38)mm3 in the ischemic group,and(-1.31±1.58)mm3 and(-1.38±1.58)mm3 in the non-ischemic group at 1 month after treatment,respectively,and the differences between the two groups were statistically significant(both P＜0.05).Conclusion Ranibizumab is effective in treating both ischemic and non-ischemic BRVO-ME.The short-term visu-al prognosis is better in the non-ischemic group than the ischemic group,and the retinal volume is higher in the ischemic group than the non-ischemic group.However,no significant difference is observed in the visual prognosis or retinal volume between the two groups after long-term treatment.

Relationship between ischemic index, leakage index, and macular edema in branch retinal vein occlusion.

PURPOSE: To investigate the combined association of the ischemic index and leakage index with macular edema on ultra-widefield fluorescein angiography (UWFFA) in patients with branch retinal vein occlusion (BRVO). METHODS: Retrospective image analysis study. The leakage index and ischemic index were calculated using Fiji after aligning early and late UWFFA images. Differences in the ischemic index, leakage index, and central macular thickness (CMT) between ischemic and non-ischemic BRVO were compared. Moreover, the association between the ischemic index, leakage index, and macular edema was analyzed. RESULTS: Eighty-three patients with BRVO were enrolled, including 53 non-ischemic BRVO and 30 ischemic BRVO patients. No significant differences were observed in leakage index and CMT between ischemic BRVO and non-ischemic BRVO (all P > 0.05). In all included patients, CMT correlated with the panretina and all subregion leakage indexes (all P < 0.01), but not with the ischemic index (all P > 0.05). In the ischemic BRVO group, CMT showed a correlation with the leakage index in several regions, but not with the ischemic index. After adjusting for the ischemic index and other clinical features, CMT remained significantly correlated with the leakage index in all regions. CONCLUSION: The leakage index may be a more effective biomarker for monitoring BRVO-associated macular edema compared to the ischemic index. Further follow-up studies are warranted to validate these findings.