X-linked retinoschisis: Long-term follow-up and genetic spectrum in 340 patients

Abstract

Purpose : Detailed knowledge regarding genetic and clinical characteristics of X-linked retinoschisis (XLRS) is necessary to provide patients with a more accurate prognosis, but also to identify clinical endpoints and optimal patient selection for (gene) therapy. This study aims to improve clinical counseling and acquire crucial information for the development process of treatment by evaluating the largest cohort of XLRS patients to this date.

Methods : This multicenter retrospective study reviewed medical records for medical history, symptoms, best-corrected visual acuity (BCVA), ophthalmoscopy, full-field electroretinography and retinal imaging (fundus photography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence).

Results : In total, 340 patients from presumably 178 different families were included with a mean age of 28.6±19.3 years at last visit. The median BCVA of the better-seeing eye at last examination was 0.52 logarithm of the minimum angle of resolution (logMAR) (Interquartile range, Q1: 0.30, Q3: 0.70 logMAR). Severe visual impairment below 1.0 logMAR was predominantly present in patients above 40 years old, with a prevalence of 13.5% in that age group. Linear mixed models revealed a slow annual decline of 0.39% in BCVA (P < 0.001), with a relatively stable visual acuity until the age of 20 years. The integrity of the ellipsoid zone (EZ) as well as the photoreceptor outer segment (PROS) length on SD-OCT were significantly correlated with visual acuity (Spearman’s r = -0.604, P < 0.001; r = -0.759, P < 0.001; respectively). Fifty-three different RS1 gene mutations were found. The most common variants were two founder mutations: c.214G>A (p.Glu72Lys; 102 subjects, 38.2%) and a deletion of exon 3 (38 subjects, 14.6%). There was no significant difference in decline of BCVA between mutations that were predicted to be severe and mild (p=0.852).

Conclusions : In general, XLRS showed a slow progression starting around the age of 20, suggesting an optimal window of opportunity for treatment within the first two decades of life. The integrity of EZ as well as the PROS length on SD-OCT may be important potential clinical endpoints in future therapeutic studies. No clear genotype-phenotype correlations were found.

This is a 2021 ARVO Annual Meeting abstract.