Retinopathy in Mucopolysaccharidoses.

Purpose: To determine the pattern(s) of onset, variation, and progression of retinopathy in patients with mucopolysaccharidoses (MPS).

Design: Prospective, longitudinal, observational study.

Participants: Between November 2015 and March 2023, individuals with MPS were recruited from ophthalmology clinics at the Manchester Royal Eye Hospital, United Kingdom.

Methods: Participants underwent assessment of visual acuity, corneal clouding, and intraocular pressure, along with fundoscopy, ultrawidefield (UWF) color fundus photography, fundus autofluorescence (FAF) imaging, OCT, and electroretinography (ERG), where feasible.

Main outcome measures: Evaluation of findings from clinical examination, retinal imaging, and ERG studies to ascertain the presence and patterns of retinopathy.

Results: Data were collected for 75 patients, including 45 with MPS I, 9 with MPS II, 13 with MPS IVA, and 8 with MPS VI, aged 3 to 53 years. Fundus photography was conducted in 65 patients, FAF in 61 patients, OCT in 58 patients, and electrodiagnostic studies in 36 patients. Retinopathy was defined as signs of retinal disease evident through retinal examination or fundus photography, such as depigmentation, bone-spicule pigmentation, vascular tortuosity, retinal pigment epithelium (RPE) mottling/other changes, macular atrophy/puckering/epiretinal membranes, FAF findings such as a central hyperautofluorescent dot, hyperautofluorescent parafoveal ring, hypoautofluorescent lesions around fovea (double bull's eye), areas of hyper/hypoautofluorescence, and extrafoveal changes, OCT imaging features such as central external limiting membrane (ELM) thickening, RPE disturbance, photoreceptor layer loss, parafoveal retinal atrophy, and outer retinal/intrachoroidal cavities, or ERG studies revealing rod-mediated retinopathy or rod-cone dystrophy. Retinopathy was confirmed in 32 patients, including 25 with MPS I, 4 with MPS II, 1 with MPS IVA, and 2 with MPS VI. Five participants were first diagnosed with retinopathy with clinical examination, and 31 participants were identified on UWF color fundus photography supported by FAF and OCT. A total of 21 patients exhibited ERG abnormalities consistent with retinopathy. Fifteen of the total 32 participants described symptoms of nyctalopia. The onset of retinopathy varied substantially, with initial detection between 2 and 53 years of age.

Conclusions: Patients with MPS as young as 2 years may develop retinopathy, diagnosed through fundus examination, ophthalmic imaging, or ERG. Emerging treatments, including gene therapy, may prevent or stabilize retinopathy. Phenotypic data and natural history of MPS-related retinopathy are thus of paramount importance.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.