Purpose

To describe the natural course, phenotype, and genotype of patients with X-linked retinoschisis (XLRS).

Design

Retrospective cohort study.

Participants

Three hundred forty patients with XLRS from 178 presumably unrelated families.

Methods

This multicenter, retrospective cohort study reviewed medical records of patients with XLRS for medical history, symptoms, visual acuity (VA), ophthalmoscopy, full-field electroretinography, and retinal imaging (fundus photography, spectral-domain [SD] OCT, fundus autofluorescence).

Main Outcome Measures

Age at onset, age at diagnosis, severity of visual impairment, annual visual decline, and electroretinography and imaging findings.

Results

Three hundred forty patients were included with a mean follow-up time of 13.2 years (range, 0.1–50.1 years). The median ages to reach mild visual impairment and low vision were 12 and 25 years, respectively. Severe visual impairment and blindness were observed predominantly in patients older than 40 years, with a predicted prevalence of 35% and 25%, respectively, at 60 years of age. The VA increased slightly during the first 2 decades of life and subsequently transitioned into an average annual decline of 0.44% (P < 0.001). No significant difference was found in decline of VA between variants that were predicted to be severe and mild (P = 0.239). The integrity of the ellipsoid zone (EZ) as well as the photoreceptor outer segment (PROS) length in the fovea on SD OCT correlated significantly with VA (Spearman’s ρ = –0.759 [P < 0.001] and –0.592 [P = 0.012], respectively). Fifty-three different RS1 variants were found. The most common variants were the founder variant c.214G→A (p.(Glu72Lys)) (101 patients [38.7%]) and a deletion of exon 3 (38 patients [14.6%]).

Conclusions

Large variabilities in phenotype and natural course of XLRS were seen in this study. In most patients, XLRS showed a slow deterioration starting in the second decade of life, suggesting an optimal window of opportunity for treatment within the first 3 decades of life. The integrity of EZ as well as the PROS length on SD OCT may be important in choosing optimal candidates for treatment and as potential structural end points in future therapeutic studies. No clear genotype–phenotype correlation was found.

中文翻译：

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X连锁视网膜劈裂症

目的

描述 X 连锁视网膜劈裂 (XLRS) 患者的自然病程、表型和基因型。

设计

回顾性队列研究。

参与者

来自 178 个可能无关的家庭的 340 名 XLRS 患者。

方法

这项多中心、回顾性队列研究回顾了 XLRS 患者的病史、症状、视力 (VA)、检眼镜检查、全视野视网膜电图和视网膜成像（眼底摄影、光谱域 [SD] OCT、眼底自发荧光） .

主要观察指标

发病年龄、诊断年龄、视力损害严重程度、年度视力下降、视网膜电图和影像学检查结果。

结果

包括 340 名患者，平均随访时间为 13.2 年（范围，0.1-50.1 年）。达到轻度视力障碍和低视力的中位年龄分别为 12 岁和 25 岁。严重视力障碍和失明主要发生在 40 岁以上的患者中，预计 60 岁时的患病率分别为 35% 和 25%。VA 在生命的前 20 年略有增加，随后转变为年均下降 0.44%（P < 0.001）。预测为重度和轻度的变体之间的 VA 下降没有显着差异（P = 0.239）。SD OCT 上椭圆体区 (EZ) 的完整性以及中央凹中的感光器外段 (PROS) 长度与 VA 显着相关（Spearman 的 ρ = –0.759 [ P < 0.001] 和 –0.592 [ P = 0.012]，分别）。发现了 53 种不同的RS1变体。最常见的变体是创始变体 c.214G→A (p.(Glu72Lys))（101 名患者 [38.7%]）和外显子 3 缺失（38 名患者 [14.6%]）。

结论

在这项研究中观察到 XLRS 的表型和自然过程存在很大差异。在大多数患者中，XLRS 显示在生命的第二个十年开始缓慢恶化，这表明在生命的前 3 个十年内治疗的最佳机会窗口。EZ 的完整性以及 SD OCT 上的 PROS 长度对于选择治疗的最佳候选者和作为未来治疗研究的潜在结构终点可能很重要。没有发现明确的基因型-表型相关性。