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Published on: May 26, 2023
Longitudinal Analysis of a Resolving Foveomacular Vitelliform Lesion in ABCA4 Disease
Winston Lee1, Pei-Yin Su2, Jana Zernant2
1Department of Genetics & Development, Columbia University, New York, New York; Department of Ophthalmology, Columbia University, New York, New York.
Purpose:
To describe the longitudinal progression and phenotypic association of bilateral foveomacular vitelliform lesions in the setting of ABCA4 disease.
Design:
Case report and cross-sectional cohort study.
Participants:
Nineteen patients with confirmed ABCA4 disease exhibiting an optical gap phenotype.
Methods:
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.
Main Outcome Measures:
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.
Results:
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.
Conclusions:
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.
