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.

27 patients with confined atrophic lesions (≤ 3.5mm in diameter) were included. Two pathogenic alleles were confirmed by sequencing of the ABCA4 locus. Multimodal imaging included color fundus photography, short wavelength-autofluorescence (SW-AF) and near infrared-autofluorescence (NIR-AF) imaging. 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).

μ _age of the study cohort was 24.1 years and 15/27 (55.6%) patients harbored genotypes consisting of the p.(Gly1961Glu) variant in ABCA4. Atrophic lesions in the central macula 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 were <0.15 mm or below 4σ of normal control eyes 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 (SPZ) 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 the 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.