Natural history of central sparing in geographic atrophy secondary to non-exudative age-related macular degeneration

Abstract

Background: The macular central 1 mm diameter zone is crucial to patients' visual acuity, but the long-term natural history of central sparing in eyes with geographic atrophy (GA) is unknown.

Methods: We manually segmented GA in 210 eyes with GA involving central 1 mm diameter zone (mean follow-up=3.8 years) in the Age-Related Eye Disease Study. We measured the residual area in central 1 mm diameter zone and calculated central residual effective radius (CRER) as square root of (residual area/π). A linear mixed-effects model was used to model residual size over time. We added a horizontal translation factor to each data set to account for different durations of GA involving the central zone.

Results: The decline rate of central residual area was associated with baseline residual area (p=0.008), but a transformation from central residual area to CRER eliminated this relationship (p=0.51). After the introduction of horizontal translation factors to each data set, CRER declined linearly over approximately 13 years (r²=0.80). The growth rate of total GA effective radius was 0.14 mm/year (95% CI 0.12 to 0.15), 3.7-fold higher than the decline rate of CRER (0.038 mm/year, 95% CI 0.034 to 0.042). The decline rate of CRER was 53.3% higher in eyes with than without advanced age-related macular degeneration in the fellow eyes at any visit (p=0.007).

Conclusions: CRER in eyes with GA declined linearly over approximately 13 years and may serve as an anatomic endpoint in future clinical trials aiming to preserve the central zone.

Keywords: degeneration; macula; retina; treatment medical.

Figure 1

Measurement of the central residual area on colour fundus photographs of the right eye of a representative patient. The solid white lines represent the borders of geographic atrophy (GA) lesions and the broken black circle represents central 1 mm diameter zone. We defined central residual area as the nonatrophic area in central 1 mm diameter zone. We calculated the central residual effective radius as square root of (central residual area/π). For this eye, central residual area was (A) 0.61 mm2 at year 2, (B) 0.25 mm2 at year 5 and (C) 0.22 mm2 at year 8 after enrollment into the study.

Figure 2

Change of the central residual area and effective radius in eyes with small and large baseline residual area over 4 years (N = 210 eyes). We defined the small baseline residual area (orange) as ≤0.39 mm2 and the large baseline residual area (blue) as>0.39 mm2. We chose 0.39mm2 as the cut-off because it is approximately half of the maximum area of central 1 mm diameter zone (0.785mm2). In each figure, the left y axis is for the small baseline residual area group, and the right y axis is for the large baseline residual area group. The error bar represents the 95% CI. (A) The decline rate of the central residual area was significantly higher in the large residual area group (0.083mm2 /year, 95% CI =0.072 to 0.093; blue) than in the small residual area group (0.045mm2 /year, 95% CI=0.036 to 0.054; orange) (p<0.001). (B) After converting the area to effective radius in the y axis, the two lines became closer to each other. The decline rate of the central residual effective radius was similar for the large residual area group (0.041mm/year, 95% CI=0.034 to 0.047; blue) and the small residual area group (0.037mm/year, 95% CI=0.030 to 0.045; orange) (p=0.28).

Figure 3

Decline of central residual effective radius as a function of time. (A) Decline of the central residual effective radius as a function of time in 210 individual eyes. Each dashed line represents 1 eye, and the solid circles on the dotted line represent the central residual effective radius at baseline and subsequent follow-up(s). At time 0, the central residual sizes varied widely across different eyes, suggesting that these eyes might have different durations of geographic atrophy (GA) in the central zone. Despite the large interindividual variations, the central residual effective radius declined over time (r2 = 0.16). (B) Same data after adding a horizontal translation factors (expressed in years) to each dataset (ie, each dotted line) in (A) to account for different baseline durations of atrophy in the central zone among individual eyes. Horizontal axis now represents the inferred duration of GA in the central zone rather than the follow-up time. After the introduction of the horizontal translation factors, datasets now followed along a straight line with a decline rate of 0.038 mm/year (r2 = 0.80). The decline rate in central residual effective radius appeared to be relatively constant over the elapsed time.