This study explored the relationship between geographic atrophy lesion characteristics, growth rates, and visual acuity loss in patients with advanced age-related macular degeneration over 24 months.
“The pathophysiology of geographic atrophy (GA) is complex, multifactorial, and not fully understood,” the investigators wrote in their recent article in Ophthalmology. “Inflammation is proposed to play a key role and several pro-inflammatory factors, including complement pathway components, have been identified as leading contributors to the development of GA lesions.” They noted that the differences between morphological functional outcomes and the absence of functional benefit from complement inhibition therapies from past clinical trials need further exploration.
To begin further investigation into these elements, the researchers conducted a retrospective analysis of 2,006 eyes from the lampalizumab clinical trial program—Chroma, Spectri (randomized phase 3 trials), and Proxima A (prospective observational study). These studies followed a consistent protocol for best-corrected visual acuity (BCVA) and lesion measurement. Patients with bilateral GA secondary to age-related macular degeneration (AMD), no prior choroidal neovascularization, and lesion sizes ranging from 2.54 to 17.78 mm² were included. Baseline BCVA was 49 ETDRS letters or more (Snellen equivalent ~20/100 or better), with a mean of 66 ETDRS letters (~20/50). The baseline mean GA lesion size was 8.07 mm², and the mean GA growth rate was 1.89 mm²/year. The researchers analyzed GA growth rates with fundus autofluorescence every six months during the 2-year follow-up period.
The researchers found faster GA growth rates were weakly correlated with more significant BCVA loss. This correlation strengthened over time: Approximately 75% of eyes lost 5 or more ETDRS letters, 50% lost 10 or more letters, and 25% lost 15 or more letters over 2 years. Eyes in the fastest quartile of GA growth exhibited an average BCVA decline of 17.75 ETDRS letters (~4 lines) over two years, compared to 1.69 letters in the slowest quartile. Faster GA growth rates correlated with earlier and more severe BCVA losses.
Subfoveal lesions were associated with worse baseline BCVA compared to nonsubfoveal lesions, but showed no significant differences in BCVA decline rates. Unifocal lesions exhibited faster BCVA loss than multifocal lesions, particularly in subfoveal regions. These lesions in the fastest growth quartile represented the highest-risk group for rapid vision loss. GA lesion area at baseline was not significantly associated with BCVA changes over time.
The researchers wrote this finding was unsurprising: “Prior studies support an absence of correlation between the size of the GA lesion and VA changes because regions of the fovea can remain uninvolved for many years.” They “also observed that adjusting for the distance from the posterior edge of the lesion to the foveal center did not alter the rate of BCVA loss.”
While generalizability of the findings may be limited and not wholly representative of GA in clinical settings because this analysis was focused on the participants from the lampalizumab trials, the researchers sought to “highlight the discord between BCVA and GA lesion size at a single point in time (cross sectional) and also when examined longitudinally.” They concluded: “The present analysis suggests that, although faster GA growth is associated with faster BCVA loss, this relationship is modified by GA lesion characteristics. Our analyses demonstrate that eyes with moderate to good VA, despite some degree of central macular involvement, are at highest risk of visual loss. In such eyes, even a modest reduction in GA growth rate might lead to slower vision loss, which may demonstrate a functional treatment benefit in future clinical trials.”
A full list of author disclosures can be found in the published research.
