Session Title: AMD II
Session Date/Time: Friday 18/09/2015 | 14:30-16:00
Paper Time: 15:02
First Author: : I.Stoilov UNITED STATES
Co Author(s): : H. Shapiro R. Frenkel
PURPOSE:To evaluate whether low luminance visual acuity (LLVA) assessment at baseline may have utility in estimating patients’ potential for vision improvement with anti-VEGF monotherapy.
HARBOR (ClinicalTrials.gov: NCT00891735) was a 24-month, phase 3, randomized, multicenter, double-masked, active treatment-controlled study that evaluated the efficacy/safety of ranibizumab in treatment-naïve patients with neovascular AMD. Patients were randomized 1:1:1:1 to receive intravitreal ranibizumab 0.5 mg or 2.0 mg, monthly or as-needed (PRN), after 3 monthly loading doses.
To replicate low luminance conditions, patients read a normally illuminated Early Treatment Diabetic Retinopathy Study (ETDRS) chart with a transparent, gray film (a 2.0-log-unit neutral density filter) in front of the study eye. All HARBOR patients (N=1084) were pooled and divided into quartiles based on the magnitude of the difference between best-corrected visual acuity (BCVA) and LLVA at baseline (BCVA-LLVA gap). Analysis of variance (ANOVA) was used for baseline comparisons of continuous outcomes among treatment groups. The relationship between BCVA and LLVA at baseline was analyzed by linear regression. The association between BCVA-LLVA gap and BCVA gains was analyzed using a linear model.
Mean BCVA and LLVA at baseline were similar across treatment groups, and patients with better BCVA at baseline generally had better LLVA at baseline (P less than 0.0001). For all treatment groups pooled, LLVA improved nearly twice as much as BCVA from baseline at Month 24 (15.4 vs 8.7 letters, respectively). There was no significant correlation between the absolute value of LLVA at baseline and vision improvement. However, the baseline BCVA-LLVA gap was negatively correlated with BCVA gain at Month 24 (P less than 0.0001); the significant association remained after controlling for baseline BCVA and after stratifying by ranibizumab treatment group (0.5 mg or 2.0 mg; monthly or PRN). Patients in the quartile with the narrowest BCVA-LLVA gap (≤17 letters) gained, on average, 13.4 letters in BCVA at Month 24, whereas patients in the quartile with the widest BCVA-LLVA gap (≥33 letters) gained only 2.4 letters from baseline.
Low luminance vision improved nearly twice as much as normal luminance vision with ranibizumab for neovascular AMD. The BCVA-LLVA gap at baseline was prognostic for treatment response in patients with neovascular AMD. Patients experiencing the smallest drop in vision under low luminance conditions gained significantly more vision from baseline compared with patients who experienced a greater drop in vision under low luminance conditions. A narrower BCVA-LLVA gap may be a manifestation of milder retinal impairment and a predictor of greater capacity for visual function recovery with ranibizumab. These data demonstrate that, in a large representative neovascular AMD population, a relatively simple, inexpensive and straightforward functional test – the measurement of the baseline BCVA-LLVA gap – yields specific subgroup predictive capability with a high degree of statistical significance.