TY - JOUR
T1 - X-Linked Retinoschisis
T2 - Novel Clinical Observations and Genetic Spectrum in 340 Patients
AU - Hahn, Leo C.
AU - van Schooneveld, Mary J.
AU - Wesseling, Nieneke L.
AU - Florijn, Ralph J.
AU - ten Brink, Jacoline B.
AU - Lissenberg-Witte, Birgit I.
AU - Strubbe, Ine
AU - Meester-Smoor, Magda A.
AU - Thiadens, Alberta A.
AU - Diederen, Roselie M.
AU - van Cauwenbergh, Caroline
AU - de Zaeytijd, Julie
AU - Walraedt, Sophie
AU - de Baere, Elfride
AU - Klaver, Caroline C. W.
AU - Ossewaarde-van Norel, Jeannette
AU - Ingeborgh van den Born, L.
AU - Hoyng, Carel B.
AU - van Genderen, Maria M.
AU - Sieving, Paul A.
AU - Leroy, Bart P.
AU - Bergen, Arthur A.
AU - Boon, Camiel J. F.
N1 - Funding Information: This research was supported by the ODAS Foundation (grant no: 2018-2) and the European Society of Retina Specialists (EURETINA Clinical Research Award 2019, grant no: 2019-1974 [L.C.H., C.J.F.B.]); the Ghent University Special Research Fund (grant nos.: BOF15/GOA/011 [E.D.B.] and BOF20/GOA/023 [E.D.B. and B.P.L.]); Ghent University Hospital Innovation Fund (grant NucleUZ [E.D.B.]); and Research Foundation - Flanders (senior clinical investigator grant nos.: 1802220N [E.D.B.] and 1803821N [B.P.L.]). The RD5000 consortium was supported by Uitzicht (grant 2015-30 financed by ODAS, Oogfonds, Retinafonds, and Bartim?us Sonneheerdt [C.C.W.K.]). The sponsors or funding organizations had no role in the design or conduct of this research. This study was performed as part of a collaboration within the European Reference Network for Rare Eye Diseases, of which E.D.B., C.C.W.K., L.I.v.d.B., C.B.H, B.P.L., A.A.B., and C.J.F.B. are members and which is co-funded by the Health Program of the European Union (Framework Partnership Agreement no.: 739534 ?ERN-EYE?). Obtained funding: Study was performed as part of the authors' regular employment duties. No additional funding was provided.' Funding Information: This research was supported by the ODAS Foundation (grant no: 2018-2) and the European Society of Retina Specialists (EURETINA Clinical Research Award 2019, grant no: 2019-1974 [L.C.H., C.J.F.B.]); the Ghent University Special Research Fund (grant nos.: BOF15/GOA/011 [E.D.B.] and BOF20/GOA/023 [E.D.B. and B.P.L.]); Ghent University Hospital Innovation Fund (grant NucleUZ [E.D.B.]); and Research Foundation - Flanders (senior clinical investigator grant nos.: 1802220N [E.D.B.] and 1803821N [B.P.L.]). The RD5000 consortium was supported by Uitzicht (grant 2015-30 financed by ODAS, Oogfonds, Retinafonds, and Bartiméus Sonneheerdt [C.C.W.K.]). The sponsors or funding organizations had no role in the design or conduct of this research. This study was performed as part of a collaboration within the European Reference Network for Rare Eye Diseases, of which E.D.B., C.C.W.K., L.I.v.d.B., C.B.H, B.P.L., A.A.B., and C.J.F.B. are members and which is co-funded by the Health Program of the European Union (Framework Partnership Agreement no.: 739534 ‘ERN-EYE’). Publisher Copyright: © 2021 American Academy of Ophthalmology
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Genotype
KW - Natural history
KW - Phenotype
KW - Surrogate end points
KW - X-linked retinoschisis
UR - http://www.scopus.com/inward/record.url?scp=85120181275&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ophtha.2021.09.021
DO - https://doi.org/10.1016/j.ophtha.2021.09.021
M3 - Article
C2 - 34624300
SN - 0161-6420
VL - 129
SP - 191
EP - 202
JO - Ophthalmology
JF - Ophthalmology
IS - 2
ER -