Three-year outcomes of vascular endothelial growth factor inhibitors in naïve branch retinal vein occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of vascular endothelial growth factor (VEGF) inhibitors in the treatment of cystoid macular oedema (CME) 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 (logMAR) 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 (VA) gain at 3 years in LogMAR 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% CI 9,13), mean adjusted change in CST was -176µm (-193, -159). Median number of injections/visits was 16/24 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 -114µm; 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 amongst the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 µm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

Central Retinal Vein Occlusion 36-Month Outcomes with Anti-VEGF: The Fight Retinal Blindness! Registry.

PURPOSE: To analyze the 3-year outcomes in a broad population of patients starting VEGF inhibitors for central retinal vein occlusion (CRVO) in routine clinical practice. DESIGN: Observational database study. PARTICIPANTS: Overall, 527 treatment-naïve CRVO eyes that commenced VEGF inhibitors between December 1, 2010 and 2018 were tracked in the Fight Retinal Blindness! registry. METHODS: Longitudinal models were used to plot changes in visual acuity (VA) and central subfield thickness (CST). MAIN OUTCOME MEASURES: Mean change in VA from baseline to 36 months, injections, visits, completion, switching, and suspensions of therapy > 180 days at the final review. RESULTS: Overall (527 eyes) mean VA change (95% confidence interval [CI]) was + 10 (7, 12) letters, 37% had final VA ≥ 70 and 30% ≤ 35 letters, mean CST changed -306 µm. Completers (257/527, 49%) had mean 36-month changes in VA and CST of + 12 letters and -324 µm with a median of 18 injections at 26 visits. The adjusted mean VA change was similar to each VEGF inhibitor (mean, + 11.4 letters) despite a greater reduction in CST with aflibercept (-310 µm) versus ranibizumab (-258 µm) versus bevacizumab (-216 µm; P < 0.001). Eyes with baseline VA that was trial-eligible (19-73 letters; 356/527, 68%) gained 7 letters, very poor (< 19 letters; 129/527, 24%) gained 22 letters, or very good (> 73 letters; 42/527, 8%) lost 7 letters. Switching (160/527, 30%) was most often to aflibercept (79 eyes). By using suspensions and discontinuation reasons, we identified similar proportions had ceased therapy (154/527, 29%) and were still receiving it at 36 months (165/527, 31%). Only 62/527 eyes (12%) had resolution of macular edema without treatment for > 6 months. CONCLUSIONS: Patients with CRVO that commenced VEGF inhibitors in routine care for whom follow-up was available had VA improvements of around 12 letters at 3 years, but with > 50% lost to follow-up, the VA outcome for the entire group was likely worse. The choice of VEGF inhibitor influenced CST but not VA outcomes. We estimated that around half of the eyes were still receiving injections after 36 months. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Hemiretinal vein occlusion 12-month outcomes are unique with vascular endothelial growth factor inhibitors: data from the Fight Retinal Blindness! Registry.

BACKGROUND/AIMS: To describe baseline characteristics and 12-month outcomes with vascular endothelial growth factor (VEGF) inhibitors of treatment-naïve hemiretinal vein occlusion (HRVO) compared with branch (BRVO) and central (CRVO) variants in routine clinical care. METHODS: A database observational study recruited 79 HRVO eyes, 590 BRVO eyes and 344 CRVO eyes that initiated therapy over 10 years. The primary outcome was mean change in visual acuity (VA-letters read on a logarithm of minimal angle of resolution chart) at 12 months. Secondary outcomes included mean change in central subfield thickness (CST), injections and visits. RESULTS: At baseline, mean VA in HRVO (53.8) was similar to CRVO (51.9; p=0.40) but lower than BRVO (59.4; p=0.009). HRVO eyes improved to match BRVO eyes from soon after treatment started through 12 months. Mean change in VA was greater in HRVO (+16.4) than both BRVO (+11.4; p=0.006) and CRVO (+8.5; p<0.001). Mean change in CST in HRVO (-231 µm) was similar to CRVO (-259 µm; p=0.33) but greater than BRVO eyes (-151 µm; p=0.003). The groups had similar median burdens of eight injections and nine visits. CONCLUSIONS: HRVO generally experienced the greatest mean change in VA of the three types of RVO when treated with VEGF inhibitors, ending with similar 12-month VA and CST to BRVO despite starting closer to CRVO. Inclusion of HRVO in BRVO or CRVO cohorts of clinical trials would be expected to proportionally inflate and skew the visual and anatomic outcomes.

Changes in 12-month outcomes over time for age-related macular degeneration, diabetic macular oedema and retinal vein occlusion.

OBJECTIVES: To identify whether the outcomes of neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in routine clinical practice have changed over time. METHODS: We analysed 12-month outcomes in treatment-naïve eyes that started aflibercept or ranibizumab for nAMD (3802 eyes), DMO (975 eyes), Branch RVO (BRVO, 357 eyes), Central RVO (CRVO, 371 eyes) and Hemi-RVO (HRVO, 54 eyes) from 2015 and 2019 tracked in the prospectively designed observational Fight Retinal Blindness! Registry. RESULTS: The mean VA change at 12-month for each year between 2015 and 2019 remained stable or otherwise showed no discernible trends over time in eyes with nAMD (+3.3 to +6 letters), DMO (+3.6 to +6.7 letters) and RVO (+10.3 to +11.7 letters for BRVO, +5.9 to +17.7 letters for CRVO and 10.2 to 20.7 letters for HRVO). The median number of VEGF-inhibitor injections in eyes that completed 12-month follow-up also remained stable at 8-9 for nAMD, 6-7 for DMO, 7-9 for RVO. Fewer eyes (

One-year real-world outcomes of bevacizumab for the treatment of macular oedema secondary to retinal vein occlusion.

BACKGROUND: Bevacizumab is the only agent that many people can afford, yet there are only limited data on whether it improves macular oedema (MO) secondary to retinal vein occlusion (RVO) in real-world clinical practice. Here we studied 12-month real-world treatment outcomes of bevacizumab for RVO-related MO. METHODS: This was a multicentre, observational study analysing 12-month data from the Fight Retinal Blindness! (FRB) database. We studied treatment-naïve eyes with MO secondary to RVO commencing bevacizumab therapy between June 2009 and June 2019. Visual acuity (VA) and central subfield thickness (CST) were measured at baseline, 6 and 12 months. The primary outcome was a change in VA from baseline to 12 months. RESULTS: Two hundred and twenty treatment naive eyes were analyzed. The baseline VA for BRVO was better than CRVO (55.8 vs. 42.6 LogMAR letters) and this gap widened over the 12-month period, with a 12-month VA change of +14.0 (95% CI 11.1, 16.8) letters for BRVO and + 11.9 (95% CI 6.4, 17.4) for CRVO. The mean CST at baseline was 511 µm for BRVO and 627 µm for CRVO, falling at 12 months by -155 µm (-190, -121) in BRVO and -198 µm (-252, -145) in CRVO. The median number of injections for BRVO and CRVO completers was 7 (5, 9). CONCLUSIONS: Bevacizumab can be an effective treatment of RVO-MO in a real-world setting with outcomes approaching those reported by the seminal clinical trials. The functional and anatomical outcomes of intravitreal therapy were better for BRVO than CRVO.

Characterization of Poor Visual Outcomes of Diabetic Macular Edema: The Fight Retinal Blindness! Project.

PURPOSE: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice. DESIGN: Observational study. PARTICIPANTS: Treatment-naïve eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined 2 groups with poor visual outcomes: (1) those with sustained vision loss of > 10 letters from baseline without recovery of visual acuity (VA); and (2) those with a VA of < 55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes. METHODS: Kaplan-Meier curves analyzed the proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated the potential baseline predictors of poor outcomes. MAIN OUTCOME MEASURES: The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors. RESULTS: The proportion of eyes with sustained VA of ≥ 10 letter loss was 14% at 2 years; 16% of eyes had VA of ≤ 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with a higher incidence of ≥ 10 letter loss (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P < 0.01). No improvement in the VA at 3 months after starting treatment was associated with ≥ 10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P < 0.01) and VA of ≤ 55 letters at 2 years (HR, 4.28; 95% CI, 2.66-6.89; P < 0.01). The other factors related to higher risk of VA of ≤ 55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65-0.72, P < 0.001). CONCLUSIONS: Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced ≥ 10 letter loss and 16% had VA of ≤55 letters 2 years after starting the treatment for DME. The identification of the incidence and predictors of poor outcomes provides a more accurate assessment of the potential benefit from intravitreal therapy.

12-month outcomes of ranibizumab versus aflibercept for macular oedema in central retinal vein occlusion: data from the FRB! registry.

PURPOSE: To compare 12-month treatment outcomes of eyes receiving aflibercept or ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) in routine clinical practice. METHODS: 296 treatment-naïve eyes receiving either aflibercept (171 eyes, 2 mg) or ranibizumab (125 eyes, 0.5 mg) for macular oedema secondary to CRVO were recruited retrospectively from centres using the prospectively designed FRB! registry. The primary outcome measure was the mean change in LogMAR letter scores of visual acuity (VA). Secondary outcomes included change in central subfield thickness (CST), injections and visits, time to first grading of inactivity, switching and non-completion from baseline to 12 months. RESULTS: Baseline VA (SD) was somewhat better in aflibercept- versus ranibizumab-treated eyes (42.5 ± 25.5 letters versus 36.9 ± 26 letters; p = 0.07) with similar CST (614 (240) µm versus 616 (234) µm: p = 0.95). The 12-month adjusted mean (95%CI) VA change was +16.6 (12.9, 20.4) letters for aflibercept versus +9.8 (5.5, 14.1) letters for ranibizumab (p = 0.001). The mean (95%CI) adjusted change in CST was significantly greater in aflibercept- versus ranibizumab-treated eyes: -304 (-276, -333) µm versus -252 (-220, -282) µm (p < 0.001). Both groups had a median (Q1, Q3) of 7 (5, 9) injections and 10 (8,13) visits. Aflibercept-treated eyes became inactive sooner than ranibizumab (p = 0.02). Switching occurred more commonly from ranibizumab (26 eyes, 21%) than from aflibercept (9 eyes, 5%) (p < 0.001). CONCLUSION: Both aflibercept and ranibizumab improved VA and reduced CST in eyes with CRVO in routine clinical practice, with aflibercept showing significantly greater improvements in this comparative analysis.

Twelve-month outcomes of ranibizumab versus aflibercept for macular oedema in branch retinal vein occlusion: data from the FRB! registry.

BACKGROUND/AIMS: To compare the efficacy of ranibizumab (0.5 mg) with aflibercept (2 mg) in the treatment of cystoid macular oedema due to branch retinal vein occlusion (BRVO) over 12 months. METHODS: A multicentre, international, database observational study recruited 322 eyes initiating therapy in real-world practice over 5 years. The main outcome measure was mean change in EDTRS letter scores of visual acuity (VA). Secondary outcomes included anatomic outcomes, percentage of eyes with VA >6/12 (70 letters), number of injections and visits, time to first inactivity, switching or non-completion. RESULTS: Generalised mixed effect models demonstrated that mean (95% CI) adjusted 12-month VA changes for ranibizumab and aflibercept were similar (+10.8 (8.2 to 13.4) vs +10.9 (8.3 to 13.5) letters, respectively, p=0.59). The mean adjusted change in central subfield thickness (CST) was greater for aflibercept than ranibizumab (-170 (-153 to -187) µm vs -147 (-130 to -164) µm, respectively, p=0.001). The overall median (Q1, Q3) of 7 (4, 8) injections and 9 (7, 11) visits was similar between treatment groups. First grading of inactivity occurred sooner with aflibercept (p=0.01). Switching was more common from ranibizumab (37 eyes, 23%) than from aflibercept (17 eyes, 11%; p=0.002). CONCLUSION: Visual outcomes at 12 months in this direct comparison of ranibizumab and aflibercept for BRVO in real-world practice were generally good and similar for the 2 drugs, despite a greater effect of aflibercept on CST and time to first grading of inactivity.

Intraocular Pressure Changes and Vascular Endothelial Growth Factor Inhibitor Use in Various Retinal Diseases: Long-Term Outcomes in Routine Clinical Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To report long-term changes in intraocular pressure (IOP) in eyes receiving vascular endothelial growth factor (VEGF) inhibitors for various retinal conditions over 12 and 24 months in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! PARTICIPANTS: Treatment-naïve eyes receiving monotherapy with VEGF inhibitors (ranibizumab [0.5 mg], aflibercept [2 mg], or bevacizumab [1 mg]) with at least 3 injections from December 2013 through December 31, 2018, and at least 12 months of follow-up. METHODS: Intraocular pressure was measured at each clinical visit for all eyes as part of routine practice. MAIN OUTCOME MEASURES: The primary outcome was the mean change in IOP (in millimeters of mercury) at 12 months. The following secondary IOP outcome measures were investigated at 12 and 24 months: (1) mean change in IOP from baseline and (2) proportion of clinically significant IOP increase defined as an elevation of at least 6 mmHg to an IOP of more than 21 mmHg at any point during the follow-up. RESULTS: We identified 3429 treatment-naïve eyes (395 receiving bevacizumab, 1138 receiving aflibercept, and 1896 receiving ranibizumab) with complete IOP data from 3032 patients with 12 months of follow-up data, of which 2125 (62%) had 24 months of follow-up data. The overall mean IOP change was -0.5 mmHg (95% confidence interval CI, -0.6 to -0.3 mmHg) at 12 months and -0.4 mmHg (95% CI, -0.6 to -0.3 mmHg) at 24 months, whereas the proportions of clinically significant IOP increases were 5.6% and 8.8%, respectively. A lower mean IOP change and fewer IOP elevations at 12 and 24 months was observed in eyes receiving aflibercept than in those receiving bevacizumab and ranibizumab (P ≤ 0.01 for both comparisons at each time point and outcome). Eyes with pre-existing glaucoma demonstrated more IOP increases over 12 and 24 months (odds ratio [OR], 2.2 [95% CI, 1.2-3.8; P = 0.012] and 2.1 [95% CI, 1.1-3.8; P = 0.025], respectively). CONCLUSIONS: Mean IOP did not change significantly from baseline to 12 and 24 months in eyes receiving VEGF inhibitors, whereas clinically significant IOP elevations occurred in a small proportion of eyes. Aflibercept was associated with fewer clinically significant IOP elevations, whereas eyes with pre-existing glaucoma were at a higher risk.

A systematic review of real-world evidence of the management of macular oedema secondary to branch retinal vein occlusion.

This review assessed the real-world evidence of the management of macular oedema secondary to branch retinal vein occlusion (BRVO). A meta-analysis of 2530 eyes from 48 real-world studies of therapies for macular oedema secondary to BRVO was conducted. Baseline characteristics, visual, anatomical and safety outcomes were recorded. The weighted mean and weighted estimates from random-effects models were calculated for visual acuity (VA) and central subfield thickness (CST) changes at 6, 12 and 24 months. Primary outcome was change in VA (logMAR letters) at 12 months. Study quality was assessed using the quality appraisal checklist for case series developed by Institute of Health Economics. The mean baseline VA for the pooled data was 54.0 (51.5, 56.5) letters and the mean baseline CST was 501.3 (483.5, 519.1) µm. The random-effects estimate for mean (95% CI) change in VA was 14.6 (12.5, 16.7) letters at 12 months (n = 1727). The random-effects estimate for mean (95% CI) change in CST was -181.7 (-230.7, -132.7) µm at 12 months (n = 1325). The quality of studies varied considerably. Ocular and systemic adverse events were discussed in 79% and 42% of treatment arms respectively, with possible under-reporting. Visual and anatomical gains achieved in the real-world for anti-VEGF therapy were not as impressive as seminal RCTs, possibly due to reduced injection frequency in the real world and differences in baseline characteristics. There is an urgent need for consensus on the minimum efficacy, treatment burden and safety data to collect to strengthen the real-world evidence base.

Projection of Long-Term Visual Acuity Outcomes Based on Initial Treatment Response in Neovascular Age-Related Macular Degeneration.

PURPOSE: To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3-year visual acuity (VA) outcomes. DESIGN: Database study, prospectively designed. PARTICIPANTS: Treatment-naïve eyes in the Fight Retinal Blindness! registry that commenced anti-VEGF therapy between January 1, 2007, and March 1, 2014, that received 3 anti-VEGF injections within the first 3 months. METHODS: The early response was defined as occurring up until the fourth injection. Various early response metrics were explored: (1) achieving good VA (≥70 letters; Snellen equivalent, 20/40), (2) absolute change in VA from baseline, (3) time to first grading of the choroidal neovascular lesion as inactive, and (4) maximum rate of VA change between successive injections. MAIN OUTCOME MEASURES: Proportion of eyes achieving ≥70 letters 3 years. RESULTS: This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was associated significantly with (1) having good vision by the fourth injection (VA ≥70 vs. VA <70 letters: odds ratio [OR], 9.8; 95% confidence interval [CI], 6.5-14.7), (2) small (1-5 letters) or large (>5 letters) early VA gains (vs. early VA loss: OR, 1.8; 95% CI, 1.2-2.6; P = 0.002; and OR, 1.8; 95% CI, 1.3-2.5; P < 0.001), (3) fewer injections until first grading of lesion inactivity (≤3 vs. >3 injections: OR, 1.6; 95% CI, 1.2-2.1; P < 0.001), (4) gradual change (between -4 and 4 letters) or rapid gains (≥5 letters) between successive injections (vs. rapid loss: OR, 1.7; 95% CI, 1.1-2.6; P = 0.015; and OR, 1.6; 95% CI, 1.1-2.3; P = 0.018). Eyes that achieved small or large early gains had similar vision at 3 years (65.0 and 64.7 letters, respectively) and had better vision than eyes with early VA loss (57.2 letters). CONCLUSIONS: Attainment of good vision by the fourth injection was associated strongly with 3-year visual outcomes, whereas other early response parameters showed a moderate association. The early response during the initial 3 monthly injections can be a useful guide for subsequent treatment decisions.