Longitudinal Multimodal Assessment of Structure and Function in INPP5E-Related Retinopathy.
Overview
abstract
Background: INPP5E-related retinopathy (INPP5E-RR) is a rare genetic disorder caused by biallelic pathogenic variants in the INPP5E gene, which encodes an enzyme critical for phosphoinositide signaling. While early-onset rod-cone dystrophy is a hallmark feature, detailed longitudinal data on the phenotype are scarce. This study aims to report a 6-year longitudinal assessment of retinal structure and function in a case of non-syndromic INPP5E-RR. Methods: A 42-year-old female proband with compound heterozygous pathogenic missense variants in INPP5E (p.Arg486Cys and p.Arg378Cys) was monitored from 2019 to 2025. She underwent serial comprehensive ophthalmologic evaluations, including optical coherence tomography (OCT), fundus autofluorescence, adaptive optics transscleral flood illumination, full-field 30Hz flicker electroretinography (ERG), and macular frequency-doubling technology perimetry. Results: Over the 6-year follow-up, OCT imaging revealed a progressive decline in the ellipsoid zone (EZ) width, from 1220 µm to 720 µm (~80 µm/year), and in the inner nuclear layer (INL) thickness. The central outer nuclear layer (ONL) thickness was preserved, but intraretinal cysts developed. Functional testing revealed a progressive decline in cone flicker ERG amplitudes, while visual acuity and macular perimetry remained stable. Conclusions: In this genotypically confirmed case, the longitudinal data identify EZ width, INL thickness, and cone flicker ERG as robust biomarkers of disease progression in INPP5E-RR. These parameters are ideal candidates for monitoring therapeutic outcomes in future clinical trials.
