Characteristics of incident geographic atrophy in the complications of age-related macular degeneration prevention trial

Abstract

Objective: To characterize the size, location, conformation, and features of incident geographic atrophy (GA) as detected by annual stereoscopic color photographs and fluorescein angiograms (FAs).

Design: Retrospective cohort study within a larger clinical trial.

Participants: Patients with bilateral large drusen in whom GA developed during the course of the Complications of Age-related Macular Degeneration Prevention Trial (CAPT).

Methods: Annual stereoscopic color photographs and FAs were reviewed from 114 CAPT patients in whom GA developed in the untreated eye during 5 to 6 years of follow-up. Geographic atrophy was defined according to the Revised GA Criteria for identifying early GA.(23) Color-optimized fundus photographs were viewed concurrently with the FAs during grading.

Main outcome measures: Size and distance from the fovea of individual GA lesions, number of areas of atrophy, and change in visual acuity (VA) when GA first developed in an eye.

Results: At presentation, the median total GA area was 0.26 mm(2) (0.1 disc area). Geographic atrophy presented as a single lesion in 89 (78%) eyes. The median distance from the fovea was 395 μm. Twenty percent of incident GA lesions were subfoveal and an additional 18% were within 250 μm of the foveal center. Development of GA was associated with a mean decrease of 7 letters from the baseline VA level compared with 1 letter among matched early age-related macular degeneration eyes without GA. Geographic atrophy that formed in areas previously occupied by drusenoid pigment epithelial detachments on average were larger (0.53 vs. 0.20 mm(2); P = 0.0001), were more central (50 vs. 500 μm from the center of the fovea; P<0.0001), and were associated with significantly worse visual outcome (20/50 vs. 20/25; P = 0.0003) than GA with other drusen types as precursors.

Conclusions: Incident GA most often appears on color fundus photographs and FAs as a small, singular, parafoveal lesion, although a large minority of lesions are subfoveal or multifocal at initial detection. The characteristics of incident GA vary with precursor drusen types. These data can facilitate design of future clinical trials of therapies for GA.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Figure 1

Color fundus photographs (CFP) and corresponding fluorescein angiograms (FA) over time from a subject who developed geographic atrophy during the course of the Complications of Age-related macular degeneration Prevention Trial( CAPT). The subject’s visual acuity remained ≥20/32 at all visits. (A) Initial CAPT study visit (Year 0). On CFP, there were soft confluent drusen. Corresponding FA demonstrated a staining pattern consistent with drusen. (B) One year before geographic atrophy developed (Year 1), the appearance of the drusen on CFP has become more confluent and an area of depigmentation/incipient atrophy develops just temporal to the fovea. The FA shows a corresponding area of hyperfluorescence in a staining pattern consistent with drusen. (C) Incident geographic atrophy was detected at Year 2 using the revised grading criteria. The CFP again shows a focal area of depigmentation with well-defined borders just temporal to the fovea in same location occupied by confluent drusen the previous year. This lesion would not have met the standard grading criteria for geographic atrophy using CFP alone. In this case, the sharp borders of the window defect on fluorescein angiography confirm the presence of geographic atrophy. (Area=0.16 mm²). (D) One year after detection using the revised criteria (Year 3), the area of geographic atrophy becomes larger and more apparent on CFP alone, meeting the standard CFP criteria used in previous studies (i.e. depigmentation, circular, sharp borders). The fluorescein angiogram again confirms the presence of geographic atrophy. (Area=0.2mm²).

Figure 3

Change in visual acuity (VA) from baseline by incident geographic atrophy (GA) location. Boxplots of the number of letters lost from the Complications of Age-related macular degeneration Prevention Trial (CAPT) baseline to first detection of geographic atrophy in eyes with GA that was subfoveal, within the foveal avascular zone but not subfoveal, or more than 250 microns from the foveal center. Top, middle and bottom horizontal lines of the boxes represent the 75^th percentile, median, and 25^th percentile; horizontal lines on the whiskers represent the most extreme values within 1.5 interquartile range of the box. The dots outside the 1.5 interquartile range of the box were outliers.