Journal article
Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials
Frontiers in medicine, Vol.10, 1204095
06/01/2023
DOI: 10.3389/fmed.2023.1204095
PMCID: PMC10310546
PMID: 37396901
Abstract
Introduction 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. Methods 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. Results 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 .Discussion 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.
Details
- Title: Subtitle
- Long-term functional and structural outcomes in X-linked retinoschisis: implications for clinical trials
- Creators
- Beau J. Fenner - Singapore National Eye CenterJonathan F. Russell - University of IowaArlene V. Drack - University of IowaAlina V. Dumitrescu - University of IowaElliott H. Sohn - University of IowaStephen R. Russell - University of IowaH. Culver Boldt - University of IowaLouisa M. Affatigato - University of IowaJeremy M. Hoffmann - University of IowaJeaneen L. Andorf - University of IowaEdwin M. Stone - University of IowaIan C. Han - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Frontiers in medicine, Vol.10, 1204095
- DOI
- 10.3389/fmed.2023.1204095
- PMID
- 37396901
- PMCID
- PMC10310546
- NLM abbreviation
- Front Med (Lausanne)
- eISSN
- 2296-858X
- Publisher
- Frontiers Media S.A
- Language
- English
- Date published
- 06/01/2023
- Academic Unit
- Stead Family Department of Pediatrics; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Fraternal Order of Eagles Diabetes Research Center; Ophthalmology and Visual Sciences
- Record Identifier
- 9984436284902771
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