Treatment of Geographic Atrophy with Intravitreal Sirolimus: The Age-Related Eye Disease Study 2 Ancillary Study

Purpose To evaluate the efficacy and safety of sirolimus, an immunosuppressive drug, for the treatment of age-related macular degeneration (AMD)–associated geographic atrophy (GA). Design Randomized, controlled, single-masked multicenter phase II clinical trial of intravitreal sirolimus versus sham therapy in Age-Related Eye Disease Study 2 (AREDS2) clinical centers. Participants Patients with GA. Methods Participants were assigned randomly to a monthly intravitreal injection of sirolimus (20 μL [440 μg]) or sham treatment. Best-corrected visual acuity (BVCA), spectral-domain OCT, fundus color photography, and fundus autofluorescence (FAF) images were obtained at baseline and every 6 months until visit month 24. Main Outcome Measures Rate of progression of GA (square millimeters per year) measured on color fundus photographs from baseline to 24 months. Secondary outcome measures include change in BVCA, worsening of vision by 3 lines or more, and changes in area of GA measured on FAF and OCT. Results Fifty-two participants (mean age, 79 years) were enrolled, with 27 study eyes assigned to sirolimus from May 2012 through March 2014. The baseline median area of GA was 4.73 disc areas (DA; 12.01 mm 2 ). The mean growth rates of GA detected on color fundus photographs were 2.27 mm 2 (standard deviation [SD], 2.17 mm 2 ) and 1.91 mm 2 (SD, 2.27 mm 2 ) at month 12 and 4.94 mm 2 (SD, 2.96 mm 2 ) and 5.72 mm 2 (SD, 3.97 mm 2 ) at month 24 for the sirolimus and sham groups, respectively. There was no statistically significant difference in the GA growth rates between the 2 treatment groups ( P  = 0.33). Median visual acuity changes and incidence of 15-letter loss from baseline were not different between the 2 treatment groups ( P  = 0.19). The intervention was stopped early because of sterile endophthalmitis that occurred in 3 participants in the sirolimus group. Participants were followed up for safety until the study was closed in May 2015 because of lack of efficacy. Conclusions Sirolimus did not result in different rates of GA growth in this phase II study. Immunosuppression may be important for some stages of the AMD process, but may not necessarily be the main pathway for the development of GA.