Longitudinal Multimodal Assessment of Structure and Function in INPP5E-Related Retinopathy

<b>Background</b>: <i>INPP5E</i>-related retinopathy (<i>INPP5E</i>-RR) is a rare genetic disorder caused by biallelic pathogenic variants in the <i>INPP5E</i> 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 <i>INPP5E</i>-RR. <b>Methods</b>: A 42-year-old female proband with compound heterozygous pathogenic missense variants in <i>INPP5E</i> (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. <b>Results</b>: 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. <b>Conclusions</b>: In this genotypically confirmed case, the longitudinal data identify EZ width, INL thickness, and cone flicker ERG as robust biomarkers of disease progression in <i>INPP5E</i>-RR. These parameters are ideal candidates for monitoring therapeutic outcomes in future clinical trials.