Low luminance visual dysfunction as a predictor of subsequent visual acuity loss from geographic atrophy in age-related macular degeneration

Abstract

Objective: To show that low luminance visual dysfunction is predictive of subsequent visual acuity (VA) loss in eyes with geographic atrophy (GA) resulting from age-related macular degeneration (AMD).

Design: Cohort study examining the prospective natural history study of GA from 1992 through 2000 at the Wilmer Eye Institute.

Participants: Ninety-one participants with GA resulting from AMD without choroidal neovascularization in at least 1 eye who completed a 2-year study examination.

Methods: Annual examinations included measurement of best-corrected VA, low luminance VA, Pelli-Robson contrast sensitivity, reading speed, examination, and fundus photography. The total GA area was quantified, as was the GA within a 10.2-mm(2) circle centered on the fovea.

Main outcome measures: Visual acuity loss at 2 years and risk factors for visual loss.

Results: Participants with baseline VA of 20/50 or more had a 40% 2-year rate of VA loss of 3 lines or more, compared with 13% for the participants with worse baseline acuities. The baseline low-luminance deficit (LLD) in VA was a strong predictor of subsequent VA loss for all levels of baseline VA. Within the good baseline VA group, the relative risk (RR) of 3-line loss for the worse LLD group compared with the better LLD group was 2.88 (95% confidence interval [CI], 1.13-7.35). The LLD is a stable and reproducible measure. Other significant visual function predictors of subsequent VA loss in eyes with good baseline VA included foveal dark-adapted sensitivity (RR, 4.20; 95% CI, 1.39-12.71) and reduced reading rate (RR, 2.43; 95% CI, 1.11-5.31). The rate of VA loss within the good acuity group was higher when the GA included 25% to 75% of the central 10.2 mm(2) than in eyes with GA including less than 25% or more than 75% of the central 10.2 mm(2). The following were not significant predictors of subsequent VA loss among these participants: age, gender, fellow eye diagnosis, fellow eye VA, baseline GA area, and GA enlargement rate.

Conclusions: Visual function measures can predict the risk of future VA loss in subjects with GA and good baseline VA. They may allow identification of the highest risk group for VA loss, enabling more efficient design of clinical trials. They also may be appropriate surrogate measures of foveal health in short-term treatment trials.

Figure 1

Visual acuity loss at two years as a function of baseline visual acuity for all 91 subjects with a two-year follow-up examination after baseline. Those points above the horizontal dashed line indicate at least moderate visual loss, and those points above the upper horizontal dotted line indicate severe visual loss. The solid line shows the univariate linear regression analysis (slope −0.28, p=0.0015). Visual acuities are graphed in logMAR (logarithm of the minimum angle of resolution) notation, with some Snellen equivalents written below.

Figure 2

Visual acuity loss at two years as a function of baseline visual acuity for all 91 subjects with a two-year follow-up visit after baseline, stratified by baseline low luminance deficit (LLD). Those points above the horizontal dashed line indicate at least moderate visual loss, and those points above the upper horizontal dotted line indicate severe visual loss. The open squares indicate eyes with a lesser baseline deficit under reduced luminance conditions (better LLD), while the solid diamonds indicate eyes with a greater deficit under reduced luminance conditions (worse LLD). Visual acuities are graphed in logMAR (logarithm of the minimum angle of resolution) notation, with some Snellen equivalents written below.

Figure 3

(online only supplement). Two-year visual acuity (VA) loss in logMAR (logarithm of the minimum angle of resolution) units, as a function of baseline low luminance deficit (LLD) for all 91 subjects. Two-year VA loss increases with worsening LLD (slope 0.42, p=0.0001), but this dependence levels off for very high LLD. A spline (bilinear) model, with a negative term for LLD above 0.7 (bilinear regression lines shown), provides a better fit to the data than does a single linear regression line. Table 3 (online only) provides further details.

Figure 4

(online only supplement). Stability of low luminance deficit (LLD) over a one-year period. For eyes that had stable visual acuity over the one-year period, the LLD measure remained stable as well. Open symbols indicate eyes that lost no more than one line of ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity over one year; closed symbols indicate eyes that lost more than one line of ETDRS visual acuity over one year. The graph is divided into quadrants by lines dividing the LLD measures into worse LLD and better LLD groups.

Figure 5

(online only supplement). The relationship between baseline foveal dark-adapted sensitivity and low luminance deficit (LLD) at baseline. There is a strong correlation between foveal dark-adapted sensitivity and the LLD measure (Pearson correlation coefficient=0.55, p=0.0001). The solid symbols indicate those eyes with >=3-line of ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity (VA) loss at two years.