Investigators Quantify Geographic Atrophy in Age-Related Macular Degeneration

Maximillian Pfau, MD

Sensitive outcome measures for disease progression are needed for treatment trials in geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

A team, led by Maximillian Pfau, MD, Department of Biomedical Data Science, Stanford University, quantified photoreceptor degeneration outside of regions of geographic atrophy in eyes with nonexudative age-related macular degeneration to evaluate its association with future geographic atrophy progression and characterize its spatio-temporal progression.

In the monocenter cohort study dubbed the Directional Spread in Geographic Atrophy trial, the investigators analyzed data from a normative data study at a tertiary referral center. The team examined 158 eyes from 89 patients with a mean age of 77.7 years, a median area of GA of 8.87 mm² (IQR, 4.09-15.60), and median follow-up of 1.1 years (IQR, 0.52-1.7 years). They also examined 93 normal eyes from 93 control group participants.

The investigators segmented longitudinal spectral-domain optical coherence tomography (SD-OCT) volume scans (121 B-scans across 30° × 25°) with a deep-learning pipeline that were standardized in a pointwise manner with age-adjusted normal data (z scores).

They also quantified outer nuclear layer (ONL), photoreceptor inner segment (IS), and outer segment (OS) thickness along evenly spaced contour lines surrounding geographic atrophy lesions.

The investigators also applied linear mixed models to assess the association between photoreceptor-related imaging features and GA progression rates. This allowed them to characterize the pattern of photoreceptor degeneration over time.

The researchers sought main outcomes and measures of the association of ONL thinning with follow-up time, after adjusting for age, retinal topography [z score], and distance to the GA boundary.

The fully automated B-scan segmentation was accurate (dice coefficient, 0.82; 95% CI, 0.80-0.85; compared with manual markings), revealing a marked interpatient variability in photoreceptor degeneration.

The ellipsoid zone (EZ) loss-to-GA boundary distance and outer segment thickness were prognostic for future progression rates and outer nuclear layer and photoreceptor inner segment thinning over time was significant, even after the researchers adjusted for age and proximity to the GA boundary (estimates of −0.16 μm/y; 95% CI, −0.30 to −0.02; and −0.17 μm/y; 95% CI, −0.26 to −0.09).

“Distinct and progressive alterations of photoreceptor laminae (exceeding GA spatially) were detectable and quantifiable,” the authors wrote. “The degree of photoreceptor degeneration outside of regions of retinal pigment epithelium atrophy varied markedly between eyes and was associated with future GA progression. Macula-wide photoreceptor laminae thinning represents a potential candidate end point to monitor treatment effects beyond mere GA lesion size progression.”

AMD is currently the leading cause of legal blindness in industrialized countries and while anti-VEGF therapies have halted or substantially delayed exudation-related vision loss in eyes with neovascular age-related macular degeneration, there is no treatment available to slow the progression of geographic atrophy.

The study, “Progression of Photoreceptor Degeneration in Geographic Atrophy Secondary to Age-related Macular Degeneration,” was published online in JAMA Ophthalmology.