Researchers Propose Two New Metrics to Quantify GA’s Visual Impact

Reduction in the rate of geographic atrophy (GA) enlargement is a well-established outcome measure used in clinical trials of medical therapies for the condition. However, this metric does not characterize central macular involvement or any effects on structure-function relationships—specifically, preservation of visual acuity—leading a team of researchers to propose a new treatment endpoint they believe would be more clinically meaningful.In a recent study, the researchers evaluated how retinal tissue and photoreceptor integrity within central 1mm and 3mm circles centered on the fovea correlate with visual function. Baseline and one-year fundus autofluorescence (FAF) and OCT scans from 43 GA clinical trial participants were analyzed. The percentages of non-GA area within 1mm and 3mm circles centered on the fovea were quantified using FAF images to calculate a new metric this group proposed, which they call the macular tissue integrity index (MTII). The percentages of intact ellipsoid zone within the same circles were used to define another metric, the ellipsoid zone integrity index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity. In these FAF images from the study, green represents intact retinal tissue (top) and ellipsoid zone (bottom), while red represents areas of geographic atrophy. The researchers found correlations between such anatomical findings and BCVA and low-light VA. Photo: Erb BM, et al. Ophthalmol Sci. June 20, 2025. Click image to enlarge. They found that MTII and EZII within the central 1mm correlated significantly with best-corrected visual acuity (BCVA) while EZII in the 3mm zone correlated with both BCVA and low-luminance visual acuity (LLVA). The findings were reported in Ophthalmology Science.Changes in MTII or EZII over time were not associated with GA area growth, nor were they associated with baseline integrity indices. “These findings suggest that macular tissue loss is independent of both baseline integrity and GA area growth, emphasizing the heterogeneous nature of disease progression and the complexities of structure-function correlations,” the authors wrote in their paper on the work.This aligns with previous studies showing that GA grows at an annual rate of approximately 2mm² and neither baseline GA area nor changes in GA area correlated with visual acuity, underscoring the limitation of using GA area alone as a functional endpoint, according to the authors. “Slowing the progression of GA toward the fovea may offer a more patient-centered and functionally meaningful outcome, preserve central vision and maintain quality of life,” the authors wrote in their paper.The differences in correlations between BCVA and LLVA with the ring size may be attributed to the distribution of photoreceptors. “Cones, concentrated in the central macula (1mm circle), are critical for fine detail vision, and structural loss in this region is closely associated with BCVA decline. Conversely, rods, which are more prevalent in the parafoveal region (3mm circle), primarily mediate night vision, explaining the stronger association between 3mm metrics and LLVA,” the authors explained in their article. “In fact, LLVA has been shown to have better correlation with fovea-sparing GA.”These findings, the authors argue, highlight that MTII and EZII capture functionally relevant macular changes, with location-dependent associations. Despite strong cross-sectional correlations, longitudinal associations between changes in MTII and visual acuity were weaker, which may reflect the complex nature of GA progression and correlation with vision, the authors found in their study. Small peripheral MTII losses within the central 1mm ring may not significantly impact BCVA if the fovea remains intact, and functional decline may lag behind structural damage.Previous studies have shown that GA expands faster peripherally than centrally, which can be the reason for the lack of correlation between GA growth and MTII/EZII loss. Macular integrity appears to depend on the type of GA growth, which could be macula-sparing, macula-centric or a mixed pattern of peripheral and central enlargement, the authors wrote.“Additionally, fragmented growth, where small multifocal lesions coalesce, or the de novo appearance of multifocal lesions within the central 1mm disrupting macular metrics, add further complexity,” the authors noted in their paper. “These variations illustrate that GA growth does not follow a straightforward narrative, and its relationship with MTII/EZII is multifaceted.”They added that these heterogeneous progression patterns may reflect underlying biological differences in lesion behavior. “For example, rapid GA growth with minimal central loss could result from centrifugal spread that initially spares central photoreceptors, perhaps due to junctional zone activity or choroidal perfusion,” the researchers argued in their paper. “In contrast, slow GA growth with substantial central tissue loss may involve early centripetal progression or central multifocal atrophy, potentially linked to or subfoveal vulnerability.”These observations show the heterogeneity of GA progression, and that GA growth alone is insufficient to predict macular tissue loss, the authors concluded.“Despite over a decade of data on GA area enlargement and associated risk factors, no meaningful correlations with visual outcomes have been established,” the researchers summed up. “ It is time to investigate these promising new metrics, which have potential to redefine how we monitor and understand GA,” they argued.Click here for the journal source. Erb BM, Botros E, Saunders TF, et al. Investigating macular tissue integrity index as a novel biomarker in geographic atrophy. Ophthalmol Sci. June 20, 2025. [Epub ahead of print.]