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Tanya Glaser, E Lauren Doss, Elvira Agrón, Divya Nigam, Emily Chew, Wai Wong; Significance of Drusen Regression in Intermediate Age-Related Macular Degeneration (AMD) in Progression to Advanced Disease. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4151.
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To investigate the prognostic implications of drusen regression (DrR) in eyes with intermediate AMD for progression to advanced AMD.
Participants at the NEI site of the Age-Related Eye Disease Study 2 (AREDS2) who met enrollment criteria (aged 50 years and older, and with large drusen (≥125 µm) in both eyes or large drusen in one eye and advanced disease in the fellow eye) were prospectively followed with annual color and monochromatic fundus photography and fundus autofluorescence (FAF) imaging for five years. Eyes not progressing to advanced disease by year 2 were identified and analyzed, with each participant contributing at most one eye. Annual multimodal images were spatially aligned using i2k Retina Software (DualAlign LLC, Clifton Park). The occurrence and location of significant DrR (area >125 µm) between baseline and year 2 were detected and outlined using computer-assisted image analysis. For eyes progressing to advanced AMD, areas of CGA on mFC FAF imaging and areas of late fluorescein angiography leakage were manually delineated by planimetry.
Out of fifty-eight eyes from 58 patients with intermediate AMD and large drusen, 31 (53%) demonstrated significant DrR between baseline and year 2. Annual follow up showed that rates of progression to advanced AMD (CGA or nvAMD) for eyes with DrR vs. without DrR were: 23% (7/30) vs. 7% (2/27) by year 3; 32% (9/28) vs. 11% (4/28) by year 4; and 38% (9/24) vs. 17% (4/24) by year 5. Progression to CGA by year 5 was 17% (4/24) vs. 0% (0/23), while progression to nvAMD by year 5 was 21% (5/24) vs. 17% (4/23). Hazard ratios for progression to advanced AMD (CGA or CNV), and to nvAMD were 2.47 (p = 0.15) and 1.23 (p = 0.75) respectively. The mean percentage of DrR areas that developed subsequent GA was 59±33% and the mean probability of colocalization relative to chance was 10.4 (0.9 - 31).
Significant DrR is a common occurrence in eyes with intermediate AMD. Eyes demonstrating significant DrR may be at increased risk for short-term progression to GA, relative to eyes without DrR. The high probability of overlap between areas of GA and DrR suggests that areas of DrR may be locally predisposed to the formation of GA, and that DrR constitutes an early step in local events leading to AMD advancement.
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