Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease

Abstract

To describe the longitudinal progression and phenotypic association of bilateral foveomacular vitelliform lesions in the setting of ABCA4 disease. Case report and cross-sectional cohort study. Nineteen patients with confirmed ABCA4 disease exhibiting an optical gap phenotype. Multimodal retinal imaging across multiple visits included autofluorescence imaging, spectral-domain OCT (SD-OCT), and OCT angiography. Electro-oculogram (EOG) and full-field electroretinogram testing results were analyzed. Exome sequencing was performed for diagnostic confirmation and the verification of other variations. Light-peak-to-dark-trough ratio (Arden ratio) on EOG; thickness and en face maps of various retinal layers on SD-OCT; area measurements on 488- and 787-nm autofluorescence images; and the presence of variation in vitelliform-associated genes identified using exome sequencing. A 25-year-old White man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid. The result of EOG testing was inconsistent with bestrophinopathy (Arden ratio= 1.62), and no generalized rod or cone dysfunction was detected on full-field electroretinogram. Exome sequencing identified the pathogenic variants c.5882G>A (p.(Gly1961Glu)) and c.4139C>T (p.(Pro1380Leu)) in ABCA4 and no other vitelliform-associated genes. Significant thinning and abnormal reflectivity of photoreceptor-attributable layers as well as near-infrared autofluorescence abnormalities were found in lesion-adjacent areas. Complete resorption of the vitelliform fluid occurred after 30 months, after which the optical gap lesions exhibited an enlarged and "cavitated" appearance. Phenotypic screening for additional cases from a large ABCA4 disease database (n= 602) identified 18 additional patients at various stages of optical gap lesion formation, most of whom harbored the c.5882G>A (p.(Gly1961Glu)) variant (P < 0.001), although none had apparent vitelliform fluid. At least 5 of the 18 (31.6%) patients exhibited optical gap lesions with the distinct "cavitated" appearance, whereas the lesions remained unperturbed in the other patients over the course of examination. Foveomacular vitelliform deposition is a mechanistically congruent but rare manifestation of ABCA4 disease. Specifically, this disease phenotype may be clinically associated with the c.5882G>A (p.(Gly1961Glu)) allele and optical gap lesions.