Retinal Phenotype in Mucopolysaccharidosis Type III

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a group of rare, hereditary, autosomal recessive, lysosomal storage disorders characterized by neurocognitive decline and early mortality. Pronounced visual impairment is frequent and retinal disease is more common in MPS III than in other MPS subtypes. The aim of this study was to characterize the retinal phenotype in MPS III and to provide insights into the disease course.

Retrospective monocenter case series.

In this study, 27 patients with genetically confirmed MPS III (n = 16 MPS IIIA; n = 9 MPS IIIB; n = 2 MPS IIIC) were included. The disease phenotype was classified as rapid or slowly progressive. All patients underwent spectral-domain optical coherence tomography (OCT) imaging to analyze central retinal thickness, peripapillary retinal nerve fiber layer thickness (RNFL), and configuration of retinal layers. Depending on neurocognitive status and compliance, best-corrected visual acuity (BCVA), slitlamp microscopy, and fundoscopy were performed.

The median age at the ophthalmological examination was 6.5 years (range, 1-16 years). Slitlamp examination findings were usually unremarkable. BCVA was assessable in 6 of 27 patients and was within the normal age-adjusted range. Parafoveal degeneration of the outer retinal layers was observed in 59% of patients, whereas foveal thickening of the external limiting membrane was noted in 67%. One MPS IIIA patient showed severe foveal atrophy, and another presented with foveal intraretinal fluid accumulation. Quantitative retinal thickness analysis of all patients showed median values at the lower end of the reference spectrum in the inner perifoveal ring and below the normal range in the outer perifoveal ring, with no distinct pattern that distinguishes the subtypes or phenotypes. RNFL thickness was unremarkable in all patients.

This study reveals a pattern of parafoveal degeneration of outer retinal layers in patients with all 3 MPS III subtypes, of whom MPS IIIA patients, known to have a more rapidly progressive neurocognitive disease, show the most severe retinal involvement. We provide natural history data that may contribute to planning and conducting future clinical trials, and we recommend further systematic ophthalmological examinations of MPS III patients to evaluate ocular involvement.