Parapapillary Retina Is Spared Retinal Degeneration in Human ABCA4 Disease

Abstract

Purpose: : To study regional topography of disease in patients with ABCA4–associated retinal degenerations.

Methods: : Patients with Stargardt disease or cone–rod dystrophy and disease–causing variants in the ABCA4 gene were included. Fixation location was determined under fundus visualization in patients with central scotomas, and central cone–mediated vision was measured using computerized static perimetry in patients with retained foveal vision. Autofluorescence (AF) images were obtained and local heterogeneity was quantified using run–length analysis. Intensity and run–length data in the parapapillary region were transformed into pseudoprofiles using semi–polar integral analysis. Parapapillary retina of an eye donor with ungenotyped Stargardt disease was examined microscopically.

Results: : AF images ranged from normal, to spatially homogenous abnormal increase of intensity, to a spatially heterogenous speckled pattern, to variably sized patches of low intensity. Parafoveal abnormalities in AF intensity and/or heterogeneity appeared to implicate this region as the one with the greatest or earliest vulnerability to ABCA4 disease. In contrast, a parapapillary ring of normal–appearing AF was visible at all disease stages. Quantitative analysis of the intensity and texture properties of AF images showed the preserved region to be an annulus, at least 0.6 mm wide, surrounding the optic nerve head. A similar region of relatively preserved photoreceptor nuclei was apparent in the donor retina. In patients with foveal fixation, there was better cone sensitivity at a parapapillary locus in the nasal retina than at the same eccentricity in the temporal retina. In patients with eccentric fixation, ∼30% had a preferred retinal locus in the parapapillary retina.

Conclusions: : Human retinal degenerations caused by ABCA4 mutations spare the structure of retina and RPE in a circular parapapillary region that commonly serves as the preferred fixation locus when central vision is lost. The retina between fovea and optic nerve head could serve as a convenient, accessible, and informative region for structural and functional studies to determine natural history or outcome of therapy in ABCA4–associated disease.

Keywords: retinal degenerations: hereditary • imaging/image analysis: clinical • optic disc