Twelve-month Natural History Study of Centrosomal Protein 290 (CEP290)-associated Inherited Retinal Degeneration.

Autor:	Pierce EA; Ocular Genomics Institute, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts., Ashimatey BS; Editas Medicine Inc, Cambridge, Massachusetts., Jayasundera T; Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, Ann Arbor, Michigan., Hoyng C; Department of Ophthalmology, Radboud University, Nijmegen, Netherlands., Lam BL; Department of Ophthalmology, Bascom Palmer Eye Institute, Miami, Florida., Lorenz B; Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany., Kim K; Editas Medicine Inc, Cambridge, Massachusetts., Rashid A; Editas Medicine Inc, Cambridge, Massachusetts., Myers R; Editas Medicine Inc, Cambridge, Massachusetts., Pennesi ME; Casey Eye Institute, Oregon Health & Science University, Portland, Oregon.
Jazyk:	angličtina
Zdroj:	Ophthalmology science [Ophthalmol Sci] 2024 Feb 07; Vol. 4 (5), pp. 100483. Date of Electronic Publication: 2024 Feb 07 (Print Publication: 2024).
DOI:	10.1016/j.xops.2024.100483
Abstrakt:	Purpose: To define the clinical characteristics of centrosomal protein 290 ( CEP290 )-associated inherited retinal degeneration (IRD) and determine which assessments may provide reliable endpoints in future interventional trials. Design: Participants in this natural history study were enrolled into 2 best-corrected visual acuity (BCVA) cohorts: light perception to > 1.0 logarithm of the minimum angle of resolution (logMAR) and 1.0 logMAR to 0.4 logMAR. Each comprised 4 age cohorts (3-5, 6-11, 12-17, and ≥ 18 years). Participants: Patients with CEP290 -associated IRD caused by the intron 26 c.2991+1655A>G mutation and BCVA ranging from light perception to 0.4 logMAR. Methods: Best-corrected visual acuity, full-field stimulus threshold (FST) sensitivity, Ora-Visual Navigation Challenge (Ora-VNC) composite score, and OCT-outer nuclear layer (OCT-ONL) average thickness were assessed at screening, baseline, 3 months, 6 months, and 12 months. Main Outcome Measures: Best-corrected visual acuity, FST sensitivity, Ora-VNC composite score, and OCT-ONL average thickness. Results: Twenty-six participants were included in this analysis. Nineteen were female. All participants were White and 4 reported Hispanic ethnicity. At screening, 13 of 16 adult and 9 of 10 pediatric participants had BCVA > 1.0 logMAR. Baseline BCVA was variable (median [range] = 2.0 [0.5, 3.9] logMAR) and was uncorrelated with age, as were VNC composite score, FST sensitivity, and OCT-ONL average thickness. Mean (95% confidence interval [CI]) test-retest variability was -0.04 (-0.09, 0.01) logMAR for BCVA (n = 25); 0.6 (-0.1, 1.3) for VNC composite score (n = 18); and 0.10 (-0.07, 0.27) log cd.s/m 2 for red FST (n = 14). A greater than expected test-retest variability (5 [0, 10] μm, n = 14) was observed for OCT-ONL average thickness as nystagmus impacted ability to repeat measures at the same retinal location. Functional assessments were stable over 12 months. Mean (95% CI) change from baseline was 0.06 (-0.17, 0.29) logMAR for BCVA (n = 23); -0.1 (-1.2, 1.0) for VNC composite score (n = 21); and -0.15 (-0.43, 0.14) log cd.s/m 2 for red FST (n = 16). Conclusions: Vision was stable over 12 months. Best-corrected visual acuity, FST, and VNC composite score are potentially viable endpoints for future studies in CEP290-associated IRD. Repeatability of OCT measures poses challenges for quantifying anatomical changes in this population. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. (© 2024 by the American Academy of Ophthalmology.)
Databáze:	MEDLINE
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