Longitudinal Changes in Vision and Retinal Morphology in Wolfram Syndrome

Area of Science:

• Ophthalmology
• Genetics
• Neuro-ophthalmology

Background:

• Wolfram syndrome is a rare genetic disorder characterized by diabetes insipidus, diabetes mellitus, optic atrophy, and hearing loss.
• Understanding the long-term ophthalmic progression is crucial for managing patients with Wolfram syndrome.

Purpose of the Study:

• To document long-term ophthalmic findings in Wolfram syndrome.
• To quantify rates of visual decline, macular thinning, retinal nerve fiber layer (RNFL) thinning, and outer plexiform layer (OPL) changes.

Main Methods:

• A single-center, cohort study involving 38 participants with Wolfram syndrome.
• Annual comprehensive ophthalmic examinations and optical coherence tomography (OCT) imaging.
• Longitudinal data analysis using linear mixed-effects models to assess changes in visual acuity and retinal morphometry.

Main Results:

• Mean follow-up of 6.44 years (range 2-10 years).
• All participants experienced visual acuity decline (mean slope of 0.059 logMAR/y), with nearly 25% showing more rapid progression.
• Retinal nerve fiber layer (RNFL) thickness decreased in superior, inferior, and nasal quadrants.
• Outer plexiform layer (OPL) lamination was observed in 3 participants, two with autosomal dominant mutations.

Conclusions:

• This is the longest and largest natural history study of visual decline and retinal morphometry in Wolfram syndrome.
• The findings suggest the existence of distinct slower and faster progressing subgroups within Wolfram syndrome.
• Outer plexiform layer (OPL) lamination is a newly identified feature in some individuals with Wolfram syndrome.