Characterization of the Subclinical Perilesional Zone in the Macula of Early-Stage ABCA4 Disease

To characterize photoreceptor layer thinning in clinically unremarkable regions adjacent to the atrophic lesion in early-stage ABCA4 disease eyes.

Twenty-seven patients with confined atrophic lesions (≤3.5 mm in diameter) were included. Two pathogenic alleles were confirmed by sequencing of the ABCA4 locus. Multimodal imaging included fundus photography, short-wavelength autofluorescence, and near-infrared autofluorescence imaging (NIR-AF). Total receptor+ (TREC+) thickness was segmented in spectral-domain optical coherence tomography (SD-OCT) scans in patient eyes (n = 27) along with age-matched healthy control eyes (n = 20).

Mean age of the study cohort was 24.1 years, and 15 of 27 (55.6%) patients harbored genotypes consisting of the p.(Gly1961Glu) variant of the ABCA4 gene. Atrophic lesions ranged from 0.61 to 3.13 mm in diameter (μ = 1.73, σ = 0.70). Six patients had mild RPE mottling adjacent to the lesion on NIR-AF. The atrophic lesion corresponded to a disruption of photoreceptor-attributable bands on SD-OCT, while all layers were visibly intact outside the lesion. TREC+ thickness in patient eyes was <0.15 mm (below 4σ) of healthy control thickness immediately adjacent to the lesion edge and gradually normalized to within ±2σ at ≈1.2 mm eccentricity from the fovea.

A uniform subclinical perilesional zone of photoreceptor thinning extends around the perimeter of early-stage atrophic lesions in ABCA4 disease. This region spatially maps to known regions of vision loss and more accurately approximates the extent of photoreceptor abnormality compared to disease changes visible on standard fundus imaging.

Semi-automated segmentation of SD-OCT scans identifies a consistent subclinical biomarker relevant to early photoreceptor degeneration in ABCA4 disease.