Endpoints and Design for Clinical Trials in USH2A-Related Retinal Degeneration: Results and Recommendations From the RUSH2A Natural History Study.

Autor:	Maguire MG; Jaeb Center for Health Research, Tampa, FL, USA., Birch DG; Retina Foundation of the Southwest, Dallas, TX, USA., Duncan JL; University of California, San Francisco, San Francisco, CA, USA., Ayala AR; Jaeb Center for Health Research, Tampa, FL, USA., Ayton LN; University of Melbourne, and Centre for Eye Research Australia, East Melbourne, VIC, Australia., Cheetham JK; Foundation Fighting Blindness, Columbia, MD, USA., Cheng P; Jaeb Center for Health Research, Tampa, FL, USA., Durham TA; Foundation Fighting Blindness, Columbia, MD, USA., Ferris FL 3rd; Ophthalmic Research Consultants, Waxhaw, NC, USA., Hoyng CB; Radboud University Medical Center, Nijmegen, Netherlands., Huckfeldt RM; Massachusetts Eye and Ear, Boston, MA, USA., Jaffe GJ; Duke Department of Ophthalmology, Duke University, Durham, NC, USA., Kay C; Vitreoretinal Associates, Gainesville, FL, USA., Lad EM; Duke Department of Ophthalmology, Duke University, Durham, NC, USA., Leroy BP; Ghent University Hospital, Ghent University, Ghent, Belgium., Liang W; Jaeb Center for Health Research, Tampa, FL, USA., McDaniel LS; Jaeb Center for Health Research, Tampa, FL, USA., Melia M; Jaeb Center for Health Research, Tampa, FL, USA., Michaelides M; Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK., Pennesi ME; Retina Foundation of the Southwest, Dallas, TX, USA.; Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA., Sahel JA; Institut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France.; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France.; Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Samarakoon L; Jaeb Center for Health Research, Tampa, FL, USA.
Jazyk:	angličtina
Zdroj:	Translational vision science & technology [Transl Vis Sci Technol] 2024 Oct 01; Vol. 13 (10), pp. 15.
DOI:	10.1167/tvst.13.10.15
Abstrakt:	Purpose: To evaluate functional and structural assessments as endpoints for clinical trials for USH2A-related retinal degeneration. Methods: People with biallelic disease-causing variants in USH2A, visual acuity ≥ 20/80, and visual field ≥ 10° diameter were enrolled in a 4-year, natural history study. Participants underwent static perimetry, microperimetry, visual acuity, fullfield stimulus testing (FST), and optical coherence tomography annually. Rates of change estimated from mixed-effects linear models and percentages of eyes with changes exceeding the coefficient of repeatability (CoR) or thresholds conforming with U.S. Food and Drug Administration (FDA) guidelines were evaluated. Results: Rates of change were generally more sensitive to change than proportions of eyes exceeding a threshold such as the CoR. Baseline ellipsoid zone area ≥ 3 mm2 was necessary to detect change. Mean sensitivity and volumetric hill of vision measures on static perimetry had similar properties and were the most sensitive to changes of the continuous measures. The highest 4-year proportions of eyes exceeding the CoR were from FST testing (47%) and microperimetry (32%). Specification of loci as functional transition points (FTPs) resulted in 45% (static perimetry) and 46% (microperimetry) at 4 years, meeting FDA guidelines for progression. Conclusions: Rate of change of mean sensitivity on static perimetry was a sensitive perimetric continuous measure. Percentages of within-eye change were largest with FST testing and microperimetry. FTPs appear to be particularly sensitive to change. These results affect clinical trial design for USH2A-related retinal degeneration. Translational Relevance: Analyses of natural history data from the Rate of Progression in USH2A-Related Retinal Degeneration (RUSH2A) study can inform eligibility criteria and endpoints for clinical trials.
Databáze:	MEDLINE
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