Macular atrophy incidence and rate of progression over 5 years among ranibizumab-treated subjects in the ANCHOR, MARINA and HORIZON trials (SEVEN-UP Study)

Abstract

Purpose: To access macular atrophy incidence, progression rate and vision outcomes in patients with exudative age-related macular degeneration treated with anti-VEGF therapy from ANCHOR, MARINA, HORIZON: (SEVEN-UP Study).

Methods: Cross-sectional, cohort study of 65 subjects who were previous participants at fourteen US sites in the ranibizumab arms of ANCHOR/MARINA and HORIZON trials.To perform the analysis of macular atrophy progression, fluorescein angiography (FA) and autofluorescence (FAF) images at year 2 (ANCHOR or MARINA month 24 exit) and year 7 were assessed.Macular atrophy area, disc area (DA) and great linear diameter (GLD) were measured in a masked and independent fashion. For statistical analysis, paired student t-test was used to compare data means using Stata 10.1. Macular atrophy was defined as an area of window defect on FA and decreased autofluorescence on FAF. Subjects with images not available or with poor quality at measurement were excluded.

Results: From 65 subjects, 40 patients had available imaging data to meet study criteria. Macular atrophy was present in all study eyes by year 7. After 1 year of MARINA/ANCHOR exit, patients had a mean number of 4.2 injections in the first year of the HORIZON, and mean of 1.6 injections per year from years 4 to SEVEN-UP visit. Mean visual acuity was 66.5± 14.75 (SE 20/100) and 44.92± 26.06 (SE 20/250) ETDRS letters at year 2 and year 7, respectively. Measurements of macular atrophy showed that the mean area of atrophy at year 2 was 0.85 ± 0.96mm2, increased to 5.55± 4.57mm2 at year 7 (p <0.001). Foveal center was involved in and 77.5% at year 2 and 95% of eyes at year 7. The mean area of macular atrophy at year 2 was 0.48± 0.55 DA and 3.73± 2.60 DA at year 7, with a mean increase of 2.65±2.33 (p value <0.001). At year 2, only 15% eyes had macular atrophy >1DA and 75.1% eyes at year 7 presented macular atrophy >1DA. At year 2, the GLD was 1,289.70μm ±668.81 and at year 7 was 3,191.80μm ±1415.86, with a mean increase of 2,002.10μm (p value <0.001). The mean increase in macular atrophy area over these approximate 5 years was 0.95mm2/year (range 0.02-15.22) and 400.10μm/year in GLD (range 98.5-4,593).

Conclusions: Ranibizumab-treated subjects from ANCHOR or MARINA and HORIZON demonstrated significant increases in macular atrophy area and foveal center involvement over 5 years since.

Keywords: 412 age-related macular degeneration • 748 vascular endothelial growth factor • 466 clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials