Longitudinal study in autosomal recessive PROM1 inherited retinal disease.

Introduction: PROM1 inherited retinal diseases (IRDs) result in significant phenotypic heterogeneity ranging from macular dystrophy to severe rod-cone dystrophy. This study examined a cohort of patients with autosomal recessive (AR) PROM1-associated IRD to determine important potential biomarkers of disease progression on multimodal imaging.

Methods: Ophthalmic phenotyping included clinical examination, OCT, fundus autofluorescence and electrophysiology.

Results: The cohort included six patients with bi-allelic variants, including two novel variants, and a median of 11.8 years of follow-up. Best-corrected visual acuity (BCVA) was maintained until a steep decline around 15 years of age. This was preceded by contraction of the subfoveal ellipsoid zone length (EZL), measured on OCT. Review of the literature demonstrated that cone or cone-rod dystrophy was the most frequently identified clinical phenotype. Loss of function variants including nonsense, frameshift and splice variants were particularly common.

Discussion: This study provides detailed insights into the natural history of AR PROM1 IRD and current understanding in the published literature. Contraction of the subfoveal EZL appears to be a potential biomarker for disease progression and occurs earlier than reduction in BCVA.