Fenner Beau J, Russell Jonathan F, Drack Arlene V, Dumitrescu Alina V, Sohn Elliott H, Russell Stephen R, Boldt H Culver, Affatigato Louisa M, Hoffmann Jeremy M, Andorf Jeaneen L, Stone Edwin M, Han Ian C
Institute for Vision Research, University of Iowa, Iowa City, IA, United States.
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, United States.
Front Med (Lausanne). 2023 Jun 15;10:1204095. doi: 10.3389/fmed.2023.1204095. eCollection 2023.
X-linked retinoschisis (XLRS) is an inherited retinal disease (IRD) caused by pathogenic mutations in the retinoschisin gene, . 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 genotypes to the visual prognosis of affected individuals.
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.
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; = 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 (-squared = 0.03; = 0.08) and CST (-squared = 0.15; = 0.001). Carbonic anhydrase inhibitors (CAIs) improved CST ( = 0.026), but not VA ( = 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; <0.0001). null genotypes had greater odds of at least moderate visual impairment at final follow-up (OR 7.81; 95% CI 2.17, 28.10; = 0.002) which was independent of age at onset, initial CST, initial ORA, or previous RD.
Overall, long-term follow-up of XLRS patients demonstrated relatively stable VA, with presenting CST, development of ORA, and null mutations associated with poorer long-term visual outcomes, indicating a clinically relevant genotype-phenotype correlation in XLRS.
X连锁视网膜劈裂症（XLRS）是一种由视网膜劈裂蛋白基因的致病突变引起的遗传性视网膜疾病（IRD）。受影响的个体出现视网膜层分离，导致视力（VA）丧失。已经尝试了几项XLRS基因治疗试验，但均未达到其主要终点。对XLRS自然病史和临床结果的更好理解可能会为未来的试验提供更好的信息。在此，我们报告了XLRS的长期功能和结构结果以及基因型与受影响个体视觉预后的相关性。
对分子确诊的X连锁视网膜劈裂症患者进行回顾性病历审查。纳入功能和结构结果以及RS1基因型数据进行分析。
该研究纳入了来自33个家庭的52例XLRS患者。症状发作的中位年龄为5岁（范围0 - 49岁），中位随访时间为5.7年（范围0.1 - 56.8年）。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%）发生周边视网膜劈裂，最常发生在下颞象限（40.4%）。初始和最终视力相似（logMAR 0.498对0.521；P = 0.203）。54只眼中有50只（92.6%）在20岁时出现可检测到的外层视网膜丧失，66只眼中有29只（43.9%）在40岁时出现局灶性或弥漫性外层视网膜萎缩（ORA）。ORA而非中心子野厚度（CST）与视力下降相关。双眼视力（P值= 0.03；r = 0.08）和CST（P值= 0.15；r = 0.001）的相关性较弱。碳酸酐酶抑制剂（CAIs）改善了CST（P = 0.026），但未改善视力（P = 0.380）。104只眼中有8只（7.7%）发生XLRS相关的视网膜脱离（RD），与未发生RD的眼睛相比，其预后较差（最终视力中位数0.875对0.487；P <0.0001）。在最终随访时，null基因型至少有中度视力损害的几率更高（OR 7.81；95% CI 2.17，28.10；P = 0.002），这与发病年龄、初始CST、初始ORA或既往RD无关。
总体而言，XLRS患者的长期随访显示视力相对稳定，出现的CST、ORA的发展以及null突变与较差的长期视觉结果相关，表明XLRS存在临床相关的基因型 - 表型相关性。
