Shared Features in Retinal Diseases with Primary Involvement of Retinal Pigment Epithelium

Abstract

Purpose : We compared fundus features in patients carrying mutations in ABCA4 (16 patients) and peripherin-2/RDS (PRPH2/RDS) (7), both of which are associated with fundus flecks; retinol dehydrogenase 5 (RDH5) (1) and retinaldehyde-binding protein 1 (RLBP1) (2) that display white-dot lesions and patients (9) manifesting reticular pseudodrusen (RPD) in association with age-related macular degeneration (AMD).

Methods : This retrospective study included spectral domain optical coherence tomography (SD-OCT); near infrared fundus autofluorescence (NIR-AF) that originates from melanin; short-wavelength fundus autofluorescence (SW-AF) originating in bisretinoid lipofuscin; and ultrawide-field pseudocolor fundus images.

Results : At positions of flecks, dots and RPD in en face images, hyperreflective lesions were detected in SD-OCT scans. These lesions presented as corrugated thickenings of interdigitation zone (IZ) and ellipsoid zone (EZ) or in later stages as rectangular or pyramidal shaped foci that extended radially through photoreceptor cell-attributable bands interrupting the IZ, EZ in association with a thinned outer nuclear layer (ONL). Hypertransmission of OCT signal, a sign of non-intact retinal pigment epithelium (RPE) was observed with dot-lesions and RPD. Dots, flecks and RPD were typically (but not always) hypoautofluorescent in NIR-AF images, and hyperautofluorescent (flecks, dots) or hypoautofluorescent (RPD) relative to the surround in SW-AF images. Flecks profiles were larger in NIR-AF than in SW-AF images. In wide-field pseudocolor images acquired from an RLBP1-patient, depigmented dot-like foci were organized into peripheral radial arrays resembling patterns in ocular albinism indicative of RPE clones. Target configurations were observed in NIR-AF images associated with dots (RDH5, RLBP1) and RPD.

Conclusions : Common to these disorders are hyperreflective lesions that extend anteriorly and progressively incorporate photoreceptor-attributable OCT bands. We suggest that these deposits may be left by degenerative processes in groups of photoreceptor cells, the degeneration beginning in inner and outer segments and being preceded by RPE dysfunctioning, thinning or atrophy. Differences in en face appearances of these lesions may be accounted for by disease-associated levels of retinoids and bisretinoid, melanin, sensitivity settings and image normalization.

This is a 2021 ARVO Annual Meeting abstract.