PRESENTATION AND LONG-TERM CLINICAL COURSE OF ITM2B-RELATED RETINAL DYSTROPHY

Abstract

Purpose : Mutations in ITM2B have been associated with Alzheimer-like dementia with cerebral amyloid deposits and, more recently, with an unusual autosomal dominant retinal-restricted dystrophy (RD). The aim of the study was to appraise the presentation and the clinical course of the ITM2B-related RD.

Methods : a retrospective analysis of the charts and clinical exams of 4 patients with a molecular diagnosis of ITM2B-related RD was performed. Best corrected visual acuity (BCVA) with early treatment diabetic retinopathy study charts (ETDRS) and Goldmann visual field (VF), fundus examination, optical coherence tomography (OCT), OCT angiography (OCTA) and fundus autofluorescence (FAF) were evaluated. Full-field electroretinography (ff-ERG) incorporated the minimum standards of the International Society for Clinical Electrophysiology of Vision. If available, neurological and ear-nose-throat data were collected.

Results : the available follow-up was 8 years for 3 subjects and 11 years for the fourth (2 males, median age at baseline: 46.5 years, range: 45-47 years). Median BCVA at baseline was 20/63 Snellen (range: 20/80 – 20/50 Snellen). All subjects showed a mild reduction in BCVA (about 2 ETDRS lines) along with a mild progression of the centrocecal scotoma, while preserving a normal peripheral VF during the years. Peculiar was the presence of hyperreflective material within the inner retina (ganglion cells-inner plexiform layers) and the central outer nuclear layer as well as a thinning of the retinal nerve fiber layer temporally to the optic disc in OCT. All subjects showed mildly progressive inner retinal and cone dysfunction at ff-ERG but subtle changes were noted on the fundus, OCT and FAF over the years. OCTA was available for 3 subjects at the last visit. Compared to age-matched controls, patients had a marked reduction of the superficial and, less importantly, of the deep capillary plexuses. Choriocapillaris showed no pathologic changes. Of note, brain MRI performed on 3 patients was normal. On the other hand, at the last examination, 3/4 had evidence of high frequency hearing loss with no reported history of trauma on the audiogram.

Conclusions : ITM2B-related RD is a peculiar rare slow progressive retinal degeneration, which combines retinal ganglion cell abnormalities and progressive inner retina and cone dysfunctions. Further investigations are needed to better define the natural history of this new pathologic entity.

This is a 2020 ARVO Annual Meeting abstract.