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Frank G Holz, Lisa Tuomi, Beiying Ding, J Jill Hopkins; Development of atrophy in neovascular AMD treated with ranibizumab in the HARBOR study. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):890.
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To evaluate macular atrophy (MA) incidence in ranibizumab (RBZ)-treated eyes with subfoveal neovascular age-related macular degeneration (nAMD).
This retrospective, posthoc study analyzed MA incidence in the phase 3 HARBOR trial (N=1095), which evaluated intravitreal RBZ 0.5-mg or 2.0-mg administered monthly or as-needed (PRN) for nAMD. Atrophy was assessed on fluorescein angiograms (FA) and color fundus photographs at baseline (BL), month (M) 3, M12, and M24, defined as: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter ≥250 µm, corresponding to flat areas of well-demarcated staining on FA; excluding atrophy associated with retinal pigment epithelium tears. All atrophy immediately within, adjacent to and nonadjacent to choroidal neovascular (CNV) lesions was included. Outcomes included MA incidence, BCVA, and factors associated with MA development.
At BL, 11.2% of study eyes had MA. Among eyes with no BL MA, MA developed in 29% at M24. Eyes with vs without BL MA gained on average +6.7 vs +9.1 letters from BL at M24, respectively. Development of MA was associated with BL presence of intraretinal cysts (hazard ratio [HR] 2.45; 95% confidence interval [CI], 1.76-3.42) and BL fellow eye MA (HR, 2.02; 95% CI, 1.42-2.87). BL subretinal fluid (SRF) presence was inversely associated with MA (HR, 0.50; 95% CI, 0.33-0.74). At M24, MA was detected in 8.1% vs 32.9% of eyes with vs without concurrent SRF, respectively. RBZ dose was not associated with MA development (2.0-mg vs 0.5-mg: HR, 1.09; 95% CI, 0.84-1.41); monthly treatment trended toward a greater association with MA vs PRN (HR, 1.29; 95% CI, 0.99-1.68). In the PRN arms, MA incidence did not appear to be associated with injection frequency.
BCVA gains were achieved in the presence of atrophy over 24 months. SRF absence, fellow eye MA presence, and intraretinal cyst presence at BL were associated with MA development. Study limitations include the lack of a control/natural history cohort or methodology consensus for MA diagnosis/evaluation. At this time, it is unclear whether MA in treated nAMD is caused by the natural progression of underlying dry AMD, CNV lesion-related collateral damage, or interference with local vascular endothelial growth factor levels. Based on existing data, MA development does not appear to outweigh the benefits of RBZ therapy for nAMD over a 2 year period.
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