Quantitative Fundus Autofluorescence in PROM1-Macular Dystrophy

Abstract

Purpose : Mutations in PROMININ 1 (PROM1), a transmembrane glycoprotein, alter photoreceptor outer segment disk morphogenesis and can cause Stargardt-like macular dystrophy (STGD4; MIM603786) with fundus features similar to ABCA4-disease (recessive Stargardt disease, STGD1). As short wavelength fundus autofluorescence (SW-AF) is elevated in STGD1 we sought to quantify the levels of autofluorescence in STGD4 to seek a better understanding of the disease process.

Methods : Ten eyes of 7 patients (33-66 years, mean age = 49,4 years) were prospectively studied by clinical exam and multimodal imaging. Autofluorescence (AF) images were acquired with the Spectralis SLO-OCT (Heidelberg Eng.) modified by insertion of an internal AF reference to account for variable laser power and detector sensitivity for quantitative autofluorescence (qAF). Further clinical testing also included near-infrared autofluorescence (NIR-AF), spectral domain-optical coherence tomography (SD-OCT) and full-field electroretinography (ffERG). The genetic cause of the disease was confirmed by direct sequencing of the PROM1 gene (23 exons) in all patients.

Results : All patients presented with isolated lesions of macular atrophy, however one family with individuals affected across two generations exhibited granular fleck-like deposits across the posterior pole. Areas of granular deposition corresponded to intermittent loss of the EZ band while discrete regions of hypoautofluorescence corresponded to complete loss of outer retinal layers on SD-OCT. Four patients presented with foveal sparing. Autofluorescence levels within the macula (qAF₈) the macula of all patients were found to be within the 95% confidence intervals of healthy age-matched individuals.

Conclusions : Although PROM1-macular dystrophy (STGD4) can exhibit phenotypic overlap with STGD1, significantly increased autofluorescence levels are not detected. As such, lipofuscin accumulation may not be a significant event in the pathophysiology of PROM1-disease. The qAF approach could serve as a method of early differential diagnosis when considering different types of macular dystrophy. qAF will help to identify appropriate disease targets as therapeutics become available to treat retinal disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.