PDF(Pubmed)
Abstract：
UNASSIGNED: X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, RS1. Affected individuals develop retinal layer separation, leading to loss of visual acuity (VA). Several XLRS gene therapy trials have been attempted but none have met their primary endpoints. An improved understanding of XLRS natural history and clinical outcomes may better inform future trials. Here, we report the long-term functional and structural outcomes of XLRS and the relevance of RS1 genotypes to the visual prognosis of affected individuals.
UNASSIGNED: A retrospective chart review of patients with molecularly confirmed X-linked retinoschisis was performed. Functional and structural outcomes, and RS1 genotype data, were included for analysis.
UNASSIGNED: Fifty-two patients with XLRS from 33 families were included in the study. Median age at symptom onset was 5 years (range 0-49) and median follow-up was 5.7 years (range 0.1-56.8). Macular retinoschisis occurred in 103 of 104 eyes (99.0%), while peripheral retinoschisis occurred in 48 of 104 eyes (46.2%), most often in the inferotemporal quadrant (40.4%). Initial and final VA were similar (logMAR 0.498 vs. 0.521; p = 0.203). Fifty of 54 eyes (92.6%) developed detectable outer retinal loss by age 20, and 29 of 66 eyes (43.9%) had focal or diffuse outer retinal atrophy (ORA) by age 40. ORA but not central subfield thickness (CST) was associated with reduced VA. Inter-eye correlation was modest for VA (r-squared = 0.03; p = 0.08) and CST (r-squared = 0.15; p = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST (p = 0.026), but not VA (p = 0.380). Eight of 104 eyes (7.7%) had XLRS-related retinal detachment (RD), which was associated with poorer outcomes compared to eyes without RD (median final VA 0.875 vs. 0.487; p <0.0001). RS1 null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; p = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD.
UNASSIGNED: Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null RS1 mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.
UNASSIGNED: A retrospective chart review of patients with molecularly confirmed X-linked retinoschisis was performed. Functional and structural outcomes, and RS1 genotype data, were included for analysis.
UNASSIGNED: Fifty-two patients with XLRS from 33 families were included in the study. Median age at symptom onset was 5 years (range 0-49) and median follow-up was 5.7 years (range 0.1-56.8). Macular retinoschisis occurred in 103 of 104 eyes (99.0%), while peripheral retinoschisis occurred in 48 of 104 eyes (46.2%), most often in the inferotemporal quadrant (40.4%). Initial and final VA were similar (logMAR 0.498 vs. 0.521; p = 0.203). Fifty of 54 eyes (92.6%) developed detectable outer retinal loss by age 20, and 29 of 66 eyes (43.9%) had focal or diffuse outer retinal atrophy (ORA) by age 40. ORA but not central subfield thickness (CST) was associated with reduced VA. Inter-eye correlation was modest for VA (r-squared = 0.03; p = 0.08) and CST (r-squared = 0.15; p = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST (p = 0.026), but not VA (p = 0.380). Eight of 104 eyes (7.7%) had XLRS-related retinal detachment (RD), which was associated with poorer outcomes compared to eyes without RD (median final VA 0.875 vs. 0.487; p <0.0001). RS1 null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; p = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD.
UNASSIGNED: Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null RS1 mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.
摘要：
■X连锁视网膜裂孔（XLRS）是由视网膜裂孔素基因的致病性突变引起的遗传性视网膜疾病（IRD），RS1.受影响的个体发生视网膜层分离，导致视力丧失（VA）。已经尝试了一些XLRS基因治疗试验，但没有达到其主要终点。对XLRS自然史和临床结果的更好理解可能会更好地为未来的试验提供信息。这里,我们报告了XLRS的长期功能和结构结局,以及RS1基因型与受影响个体视觉预后的相关性.
■对分子证实为X-连锁视网膜裂孔的患者进行回顾性图表回顾。功能和结构成果，和RS1基因型数据，被纳入分析。
■来自33个家庭的52例XLRS患者被纳入研究。症状发作的中位年龄为5岁（范围0-49），中位随访为5.7年（范围0.1-56.8）。104只眼中有103只（99.0％）发生黄斑视网膜劈裂，而104只眼中有48只(46.2%)发生外周视网膜裂孔,最常见的是下颞叶象限（40.4%）。初始和最终VA相似（logMAR0.498vs.0.521；p=0.203）。到20岁时，54只眼中的50只眼（92.6％）出现了可检测的外部视网膜丧失，到40岁时，66只眼中的29只眼（43.9％）出现了局灶性或弥漫性外部视网膜萎缩（ORA）。ORA而不是中心子场厚度（CST）与VA降低有关。VA（r平方=0.03；p=0.08）和CST（r平方=0.15；p=0.001）的眼间相关性适中。碳酸酐酶抑制剂（CAIs）改善CST（p=0.026），但不是VA（p=0.380）。104只眼中有8只（7.7％）患有XLRS相关性视网膜脱离（RD），与没有RD的眼睛相比，这与较差的结局相关(中位数最终VA0.875vs.0.487；p<0.0001)。RS1无效基因型在最终随访时至少有中度视力损害的可能性更大（OR7.81;95％CI2.17，28.10;p=0.002），这与发病年龄无关，初始CST，最初的ORA,或以前的RD。
■总的来说，XLRS患者的长期随访显示相对稳定的VA，介绍CST，ORA的发展，和与较差的长期视力结果相关的无效RS1突变，表明XLRS中临床相关的基因型-表型相关性。
■对分子证实为X-连锁视网膜裂孔的患者进行回顾性图表回顾。功能和结构成果，和RS1基因型数据，被纳入分析。
■来自33个家庭的52例XLRS患者被纳入研究。症状发作的中位年龄为5岁（范围0-49），中位随访为5.7年（范围0.1-56.8）。104只眼中有103只（99.0％）发生黄斑视网膜劈裂，而104只眼中有48只(46.2%)发生外周视网膜裂孔,最常见的是下颞叶象限（40.4%）。初始和最终VA相似（logMAR0.498vs.0.521；p=0.203）。到20岁时，54只眼中的50只眼（92.6％）出现了可检测的外部视网膜丧失，到40岁时，66只眼中的29只眼（43.9％）出现了局灶性或弥漫性外部视网膜萎缩（ORA）。ORA而不是中心子场厚度（CST）与VA降低有关。VA（r平方=0.03；p=0.08）和CST（r平方=0.15；p=0.001）的眼间相关性适中。碳酸酐酶抑制剂（CAIs）改善CST（p=0.026），但不是VA（p=0.380）。104只眼中有8只（7.7％）患有XLRS相关性视网膜脱离（RD），与没有RD的眼睛相比，这与较差的结局相关(中位数最终VA0.875vs.0.487；p<0.0001)。RS1无效基因型在最终随访时至少有中度视力损害的可能性更大（OR7.81;95％CI2.17，28.10;p=0.002），这与发病年龄无关，初始CST，最初的ORA,或以前的RD。
■总的来说，XLRS患者的长期随访显示相对稳定的VA，介绍CST，ORA的发展，和与较差的长期视力结果相关的无效RS1突变，表明XLRS中临床相关的基因型-表型相关性。
