Use of new imaging technology to assess the ocular phenotype of patients with Mucopolysaccharidosis (MPS) receiving different treatment modalities

Abstract

The mucopolysaccharidoses (MPSs) are a group of rare heterogeneous inherited lysosomal storage disorders. Eye features include corneal clouding, retinopathy, and optic neuropathies, which can be sight threatening and impact quality of life. Over the past few decades systemic treatments have improved systemic outcomes and life span. Therefore, understanding the ocular phenotype and effects of systemic treatments on MPS eye features, is now of greater importance. The majority of studies in this area are small, retrospective or utilise subjective measures of the ocular features in MPS, making findings difficult to interpret. This prospective observational study aims to better understand the ocular phenotype in MPS and provide insights into the effects of systemic treatments. Participants were recruited from paediatric ophthalmology clinics at Manchester Royal Eye Hospital. Those over 3-years of age with any type of MPS were eligible. Follow-up was planned for 4-12 month intervals and at each review where possible participants underwent clinical assessment (including visual acuity, intraocular pressure measurement, and slit lamp examination) and ocular imaging (iris camera, Pentacam, Optos wide-field fundus imaging and optical coherence tomography (OCT)). Participants with MPSI, II, IV and VI were recruited. Corneal clouding was observed in MPSI, IV and VI, and retinopathy and optic nerve abnormality in MPSI, II and VI. Visual acuity did not correlate with grade of corneal clouding. Over a median 22 month follow-up, on average stability of corneal clouding was detected using clinical grading and when measured with the iris camera (COM) score, in all types of MPS studied. Pentacam average change in densitometry scores were higher in MPSI (7.7) and MPSVI (7.2), which may suggest overall progression of corneal clouding in these groups. Retinal and optic nerve changes also appear to be stable clinically and on widefield fundus imaging and OCT in the majority of participants with MPSI, II, IV and VI. Variability in the ocular phenotype has been observed. This variation may be due to genetic and environmental factors. This may also in part be due to small numbers of participants with certain types of MPS in this cohort. There is also variation in findings with different measures of the ocular phenotype utilised, which may be due to subjective nature of some assessments and the different areas of tissues assessed with different imaging modalities. Continuing to follow up the participants in this cohort and further large prospective studies with longer follow-up, utilising objective measures of the ocular phenotype, and studying a range of types of MPS, will provide useful insights into the progression of the eye features of MPS over time and the effects of systemic treatments.

Date of Award	1 Aug 2022
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Jane Ashworth (Supervisor) & Tariq Aslam (Supervisor)