Cross-sectional baseline analysis of 87 eyes with early atrophic AMD (iRORA or cRORA, total lesion size ≤1.27 mm²) examining how structural metrics — FAF-defined GA lesion size, swept-source OCT hypertransmission defect (HyperTD) size, and distance to fovea (DTF) — relate to a broad set of functional outcomes including mesopic and dark-adapted fundus-controlled perimetry (FCP), BCVA, LLVA, Moorfields Acuity Test, and reading performance.
Lesion size was most strongly linked to FCP sensitivity loss: each doubling of targeted GA size reduced targeted mesopic sensitivity by 3.55 dB and targeted dark-adapted sensitivity by 3.65 dB (both P<0.001; correlations up to ρ=−0.66). Central visual acuity and reading outcomes were instead driven by lesion proximity to the fovea — each 1 mm increase in DTF improved BCVA by ~4.6 letters, LLVA by ~4.2 letters, MAT by ~4.6 letters, and reading acuity by 0.11 logRAD (all adjusted P≤0.046).
Cross-sectional design precludes conclusions about longitudinal responsiveness or predictive validity of any endpoint. Not all structural metrics were available for all 87 eyes (FAF-GA only in 38, HyperTDs in 81), limiting comparability. The cohort was predominantly white (94.7%), restricting generalizability.
In early atrophic AMD, lesion-targeted FCP best captures structural disease burden, while standard acuity and reading tests mainly reflect how close the lesion is to the fovea. Clinicians and trialists should select functional endpoints based on the specific question — FCP for lesion-related sensitivity loss, acuity/reading measures for patient-relevant visual impact.
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