The clinical relevance of ultra-widefield angiography findings in patients with central retinal vein occlusion and macular oedema receiving anti-VEGF therapy

AIMS: To report, using ultra-widefield angiography (UWFA) the area, distribution, and change in retinal capillary nonperfusion (RCNP) at baseline and 100 weeks in eyes with central retinal vein occlusion (CRVO) receiving anti-VEGF for macula oedema. METHODS: Prospective longitudinal multi-centre cohort study. Adults with CRVO treated with anti-VEGF therapy for macular oedema underwent UWFA at baseline and week-100. The area, distribution, and change in total, peripheral and posterior pole RCNP were determined. RESULTS: Of 153 eyes at baseline, mean area of RCNP was 34.3DA and 12 (7.8%) had ≥75DA RCNP. More than 10DA RCNP was present in the temporal periphery in 75.8% of eyes vs. 10.5% in the nasal periphery. At week-100, mean RCNP was 42.1DA with a median change from baseline of 3.3DA 95% CI [0.4, 7.3]; p 10DA at week-100. These eyes had a median increase in total RCNP of 69.7DA [95% CI 27.2–85.4] vs 0DA [0.0–1.4]; p 10DA posterior pole RCNP is a marker for widespread RCNP and in such cases the risk of anterior segment neovascularisation is not abolished by concomitant anti-VEGF therapy

Efficacy and Safety of Ranibizumab 0.5 mg for the Treatment of Macular Edema Resulting from Uncommon Causes: Twelve-Month Findings from PROMETHEUS.

PURPOSE To evaluate the efficacy and safety of ranibizumab 0.5 mg in adult patients with macular edema (ME) resulting from any cause other than diabetes, retinal vein occlusion, or neovascular age-related macular degeneration. DESIGN A phase 3, 12-month, double-masked, randomized, sham-controlled, multicenter study. PARTICIPANTS One hundred seventy-eight eligible patients aged ≥18 years. METHODS Patients were randomized 2:1 to receive either ranibizumab 0.5 mg (n = 118) or sham (n = 60) at baseline and month 1. From month 2, patients in both arms received open-label individualized ranibizumab treatment based on disease activity. A preplanned subgroup analysis was conducted on the primary end point on 5 predefined baseline ME etiologies (inflammatory/post-uveitis, pseudophakic or aphakic, central serous chorioretinopathy, idiopathic, and miscellaneous). MAIN OUTCOME MEASURES Changes in best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study letters) from baseline to month 2 (primary end point) and month 12 and safety over 12 months. RESULTS Overall, 156 patients (87.6%) completed the study. The baseline characteristics were well balanced between the treatment arms. Overall, ranibizumab showed superior efficacy versus sham from baseline to month 2 (least squares mean BCVA, +5.7 letters vs. +2.9 letters; 1-sided P = 0.0111), that is, a treatment effect (TE) of +2.8 letters. The mean BCVA gain from baseline to month 12 was 9.6 letters with ranibizumab. The TE at month 2 was variable in the 5 predefined etiology subgroups, ranging from >5-letter gain to 0.5-letter loss. The safety findings were consistent with the well-established safety profile of ranibizumab. CONCLUSIONS The primary end point was met and ranibizumab showed superiority in BCVA gain over sham in treating ME due to uncommon causes, with a TE of +2.8 letters versus sham at month 2. At month 12, the mean BCVA gain was high (9.6 letters) in the ranibizumab arm; however, the TE was observed to be variable across the different etiology subgroups, reaching a >1-line TE in BCVA in patients with ME resulting from inflammatory conditions/post-uveitis or after cataract surgery. Overall, ranibizumab was well tolerated with no new safety findings up to month 12

Efficacy and safety of intravitreal aflibercept using a treat-and-extend regimen for neovascular age-related macular degeneration: the ARIES study

PURPOSE Treating neovascular age-related macular degeneration (nAMD) with intravitreal aflibercept (IVT-AFL) treat-and-extend (T&E) can reduce treatment burden. ARIES assessed whether IVT-AFL early-start T&E was noninferior (NI) to late-start T&E. METHODS A randomized, open-label, Phase 3b/4 study that included treatment-naïve patients aged ≥50 years with best-corrected visual acuity (BCVA) 73-25 Early Treatment Diabetic Retinopathy Study letters and active choroidal neovascularization secondary to AMD. Patients received 2mg IVT-AFL at Week (W)0, W4, W8, and W16. At W16 patients were randomized 1:1 to early-start (2W interval adjustments) or late-start T&E (8W intervals until W48 then 2W interval adjustments). Primary endpoint: BCVA change from randomization to W104. RESULTS 271 patients were randomized. Mean (standard deviation [SD]) BCVA at baseline was 60.2 (12.1; early-T&E) and 61.3 (10.8; late-T&E) letters. Mean (SD) BCVA change (W16-104) was -2.1 (11.4) vs -0.4 (8.4) letters (early- vs late-T&E; least-squares mean difference: -2.0; 95% CI: -4.75 to 0.71; P=0.0162 for NI); +4.3 (13.4) vs +7.9 (11.9) letters (W0-104). Mean (SD) number of injections was 12.0 (2.3) vs 13.0 (1.8). From baseline to W104, 93.4% and 96.2% maintained BCVA; mean (SD) central retinal thickness change was -161.6 (135.6) µm and -158.6 (125.1) µm. Last injection interval (W104) was ≥12W for 47.2% and 51.9% of patients. CONCLUSION Outcomes were similar between patients with nAMD treated with an IVT-AFL early- or late-T&E regimen following initial dosing, with one injection difference over 2 years

A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study) 12-month data:report 2

Purpose: To report the findings at 1 year of a study comparing repeated intravitreal bevacizumab (ivB) and modified Early Treatment of Diabetic Retinopathy Study (ETDRS) macular laser therapy (MLT) in patients with persistent clinically significant diabetic macular edema (CSME).Design: Prospective, randomized, masked, single-center, 2-year, 2-arm clinical trial.Participants: A total of 80 eyes of 80 patients with center-involving CSME and at least 1 prior MLT.Methods: Subjects were randomized to either ivB (6 weekly; minimum of 3 injections and maximum of 9 injections in the first 12 months) or MLT (4 monthly; minimum of 1 treatment and maximum of 4 treatments in the first 12 months).Main Outcome Measures: The primary end point was the difference in ETDRS best-corrected visual acuity (BCVA) at 12 months between the bevacizumab and laser arms.Results: The baseline mean ETDRS BCVA was 55.7 +/- 9.7 (range 34-69) in the bevacizumab group and 54.6 +/- 8.6 (range 36-68) in the laser arm. The mean ETDRS BCVA at 12 months was 61.3 +/- 10.4 (range 34-79) in the bevacizumab group and 50.0 +/- 16.6 (range 8-76) in the laser arm (P = 0.0006). Furthermore, the bevacizumab group gained a median of 8 ETDRS letters, whereas the laser group lost a median of 0.5 ETDRS letters (P = 0.0002). The odds of gaining >= 10 ETDRS letters over 12 months were 5.1 times greater in the bevacizumab group than in the laser group (adjusted odds ratio, 5.1; 95% confidence interval, 1.3-19.7; P = 0.019). At 12 months, central macular thickness decreased from 507 +/- 145 mu m (range 281-900 mu m) at baseline to 378 +/- 134 mu m (range 167-699 mu m) (P<0.001) in the ivB group, whereas it decreased to a lesser extent in the laser group, from 481 +/- 121 mu m (range 279-844 mu m) to 413 +/- 135 mu m (range 170-708 mu m) (P = 0.02). The median number of injections was 9 (interquartile range [IQR] 8-9) in the ivB group, and the median number of laser treatments was 3 (IQR 2-4) in the MLT group.Conclusions: The study provides evidence to support the use of bevacizumab in patients with center-involving CSME without advanced macular ischemia