Abstract Body:

Purpose: To describe the clinical, full-field electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT) findings in mucopolysaccharidosis (MPS) type I.

Study Design: Retrospective cohort study.

Methods: This study was approved by the SickKids Research Ethics Board. Fourteen children (50% female) with MPS I Hurler (I-H, n=11) and Hurler-Scheie (I-H/S, n=3) who had ERG and SD-OCT were identified. Clinical features, genetic analysis, ERG and fundus photography were retrospectively reviewed. Segmentation analysis was performed using Iowa reference algorithms on both macular cube scans and high definition 5-line raster scans of Cirrus SD-OCT. The external limiting membrane (ELM) thickness at the foveal centre was measured manually by drawing a line perpendicular to the retinal pigment epithelium (RPE) that passed through the central fovea.

Results: Diagnosis was confirmed by IDUA mutational analysis (n=9) or alpha-L-iduronidase deficiency (n=5). Children with MPS I-H had hematopoietic stem cell transplant (mean age 1.22 years) and I-H/S received enzyme replacement (mean age 4.69 years). All children had diffuse ground glass stromal opacities, 9 requiring deep anterior lamellar keratoplasty. At the initial ERG (mean 10.10 years, range: 1.58 - 17.92), mean visual acuity was 0.70 logMAR (range: 0.3 - 1.6) and mean cycloplegic spherical equivalent was +1.79 D (range: -25.00 to +8.75). Mean initial standard flash b/a ratio was 1.13 (range: 0.37-3.58). Eleven cases (79%) had at least one electronegative ERG. Four children had maculopathy, but none showed peripheral pigmentary retinopathy. SD-OCT demonstrated central macular ELM thickening in all cases. Mean foveal ELM thickness was 34.41 μm (range: 14.20-53.11).

Conclusions: Despite systemic therapy, micro-structural and functional retinal changes are uniformly seen in MPS I prior to clinically apparent retinal changes. Central macular ELM thickening may reflect glycosaminoglycan deposition detected histopathologically or be due to secondary changes in Müller cells in MPS. The presence of an electronegative ERG represents a post-transductional abnormality, which could be explained by ELM thickening.