Further Characterization of Autosomal Dominant North Carolina Macular Dystrophy

Abstract

Purpose: To report the retinal phenotype and genetic results in a large autosomal dominant kindred with North Carolina macular dystrophy (NCMD) like disease

Methods: Six affected members of a Caucasian family (age range: 12 - 47 years) underwent detailed ophthalmological evaluation that included best corrected visual acuity (BCVA) measurement, color vision testing and fundus evaluation. Fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ERG) and electro-oculography (EOG) were performed in 5 cases. The proband (IV-4) had genetic testing, specifically a 25 gene maculopathy/cone-rod dystrophy panel. The proband’s son (V-1) was tested a large sequencing panel of 131 retinal dystrophy genes.

Results: Grade-1 NCMD defined as fine drusen or mild retinal pigment epithelial (RPE) changes confined to the central macula was noted in III-4, IV-5 and the right eye (RE) of V-2. Grade-2 NCMD characterized by confluent elevated subretinal material with or without pigmentary changes was noted in the left eyes of V-2 and III-2. Grade-3 NCMD described as central macular chorioretinal atrophy with fibrous tissue and pigmentation along the rim of the atrophy was noted in IV-4, V-1 and the RE of III-2. The BCVA ranged between 0.3 and 3.0 logMAR in grade-3 eyes; and between 0.0 and 0.86 logMAR in grade-1 and 2 eyes. Color vision was normal or showed mild deficits. Radial, peripheral-retinal yellowish deposits that hyper-fluoresced on FAF were noted in 2 cases. Grade-1 and 2 eyes showed hyper-fluorescent macular lesions. The atrophic lesions in grade-3 eyes hypo-fluoresced on FAF, but its rim demonstrated hyper-fluorescence. On SD-OCT, grade-1 eyes showed subtle drusenoid deposition at the RPE with minimal disruption of photoreceptor layer. Grade-2 eyes showed large hyper/iso-reflective lesions at the RPE with moderate disruption of overlying retina. Grade-3 lesions show thinned retina with marked disruption of all retinal layers; the rim of the lesion showed large areas of deposition and pigment hyperplasia. ERG and EOG were normal in all tested. No disease causing variants were observed in any genes associated with macular/cone-rod dystrophy.

Conclusions: This kindred establishes the OCT features in NCMD. The disease demonstrates good retinal function and BCVA is well preserved until grade-3 disease. The causative gene for NCMD remains unknown