# Peripapillary retinal nerve fibre layer thinning in patients with X-linked retinoschisis

## TL;DR

This study found that most patients with X-linked retinoschisis have thinning in the retinal nerve fiber layer, which could affect outcomes in gene therapy trials.

## Contribution

The study identifies patterns of peripapillary retinal nerve fibre layer thinning in XLRS patients and links it to retinoschisis and macular volume.

## Key findings

- 72% of right eyes and 79% of left eyes showed pRNFL thinning in at least one sector.
- Temporal pRNFL thinning was strongly correlated with macular volume.
- Thinning was linked to peripheral retinoschisis and occurred after macular cystoid cavities collapsed.

## Abstract

To assess peripapillary retinal nerve fibre layer (pRNFL) thickness in patients with X-linked retinoschisis (XLRS), as pRNFL thinning may limit functional improvements in gene therapy trials.

This retrospective multicentre study included 49 eyes from 25 patients diagnosed with XLRS. Data collected with multimodal imaging at baseline and last follow-up (when available) included age, best-recorded visual acuity (BRVA), central retinal thickness (CRT), macular volume (MV), presence and location of peripheral retinoschisis and pRNFL thickness in the global (G), superotemporal (TS), superonasal (NS), inferotemporal (TI), inferonasal (NI), nasal (N) and temporal (T) sectors. Retinal sensitivity, assessed by microperimetry, was also recorded for seven patients at baseline.

pRNFL was thinner (below the fifth percentile) in at least one sector in 72% of the right eyes and 79% of the left eyes, with thinning across three or more sectors in 20% of the right and 17% of the left eyes. In 44% of cases, thinning occurred in the temporal sectors of both eyes, with no nasal sectoral thinning. Peripheral retinoschisis quadrants topographically matched the corresponding thinned pRNFL sectors. A strong positive correlation was found between MV and temporal pRNFL thickness (r=0.71, p<0.01), while weak negative correlation trends were noted with age (p=0.05) and BRVA (logMAR; p=0.12) related to temporal thickness of pRNFL sectors.

pRNFL thinning, predominantly sectoral and linked to macular or peripheral retinoschisis, occurs in about three-quarters of patients with XLRS, while diffuse thinning occurs in one-fifth. Temporal pRNFL thinning might occur only after the collapse of intraretinal cystoid cavities in the macula.