Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration.

PURPOSE

To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD).

DESIGN

Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial.

PARTICIPANTS

Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN).

METHODS

Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: 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. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included.

MAIN OUTCOME MEASURES

Macular atrophy incidence, best-corrected visual acuity (BCVA).

RESULTS

At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1-9.3]; +9.1 [8.0-10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3-63.7] and 64.7 [63.2-66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76-3.42]) and fellow eye atrophy (HR, 2.02 [1.42-2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33-0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99-1.68]), but was not statistically significant.

CONCLUSIONS

New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24 months. Baseline subretinal fluid absence, intraretinal cyst presence, and fellow eye atrophy presence were associated with month 24 MA presence. With existing data, the benefits of ranibizumab for neovascular AMD outweighed the risk of MA development over 24 months in HARBOR, although outcomes >2 years were not evaluated.