Clinical characteristics of Finnish patients with X-linked Retinoschisis

Abstract

Purpose: To study the clinical characteristics of the eyes including retinal morphology in patients with X-linked retinoschisis (XLRS) and to investigate genotype-phenotype correlations. Methods: Retrospective assessment of medical records of patients diagnosed with or treated for XLRS at Helsinki University Hospital. Patients' demographic data ophthalmic and optometric examination results were collected from electronic and paper records. A detailed analysis of the retinal structure was performed on available SD-OCT images and Topcon fundus photographs. Results: The study included 74 male patients, average follow-up years (±SD) was 13 (±12). XLRS manifested at the mean age of 11 (±14) years. Cystic macular changes and spoke-wheel patterned retinal abnormality were present in 78% and 75%, respectively, and peripheral schisis in 28% of eyes. Macular atrophy was present in 27% of eyes and was associated with older age (p=<0.001). The most common pathogenic variants in the retinoschisin 1 (RS1) gene (n=45) were three founder mutations in exon 4, 214G>A (49%), 221G>T (22%), and 325G>C (11%). Three patients were detected with the pathogenic variant c.554C>A (7%). No association was found between the genotypes and phenotypes. Initial age of onset of vitreous haemorrhage (VH, n=11) was 9.2 (±6.9) years. VH appeared more frequently when peripheral schisis was present (p=<0.001). There was no significant difference in central macular thickness during follow up (-7.2 μm (±100.2), p=0.5442). The mean photoreceptor outer segment length was 26.29 (±6.95) μm. Qualitative defects of photoreceptor layers appeared frequently. Ellipsoid zone (EZ) disruption was present in 54% of eyes. Best-corrected visual acuity (BCVA) was stable from childhood to young adult age but appeared to decline in the third decade of life (R=-0.396 p=<0.01). Mean BCVA was 0.35 (±0.21) at baseline and 0.32 (±0.21) at the last visit. An association was observed between BCVA and macular atrophy (p=0.003) and peripheral schisis (p=0.001). Half of the patients were classified as visually impaired. The mean autorefraction was more hypermetropic (2.31 (±2.30) D) at baseline than at the last visit (1.63 (±2.33) D). As a whole, 89% of the patients remained emmetropic or hypermetropic until the end of the follow-up period, whereas myopic patients only accounted for 11%. Conclusion: This study established a large variety of phenotypes in XLRS. The study confirmed macular alterations and defects on photoreceptor microstructure appear frequently. Macular atrophy was associated with older age and decreased visual acuity. Vitreous haemorrhage was more frequent among patients who presented with peripheral schisis. We found a much faster decline of visual acuity as early as in the third decade of life than previously reported and confirmed previously noticed prevalence of hypermetropic refraction in population throughout the follow-up period.