CRB1-associated retinal dystrophies: a prospective natural history study in anticipation of future clinical trials

Xuan-Thanh-An Nguyen, Mays Talib, Mary J van Schooneveld, Jan Wijnholds, Maria M van Genderen, Nicoline E Schalij-Delfos, Caroline C W Klaver, Herman E Talsma, Marta Fiocco, Ralph J Florijn, Jacoline B Ten Brink, Frans P M Cremers, Magda A Meester-Smoor, L Ingeborgh van den Born, Carel B Hoyng, Alberta A H J Thiadens, Arthur A Bergen, Camiel J F Boon

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

PURPOSE: To describe the natural disease course of CRB1-associated retinal dystrophies, and to identify clinical endpoints for future clinical trials.

DESIGN: Single center, prospective case series.

METHODS: An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using ETDRS charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography (ERG), full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography and fundus autofluorescence imaging.

RESULTS: Based on genetic, clinical and electrophysiological data, patients were diagnosed with retinitis pigmentosa (n = 19; 86%), cone-rod dystrophy (n = 2; 9%) or isolated macular dystrophy (n = 1; 5%). Two-year analysis of the entire cohort showed no significant changes in BCVA (p = 0.069) or V4e isopter seeing retinal areas (p = 0.616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at 2-year follow-up (p < 0.001). FST responses were measurable in patients with non-recordable ERGs. On average, FST responses remained stable during follow-up.

CONCLUSION: In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up, and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical endpoint in future human treatment trials for CRB1-associated retinal dystrophies.

Original languageEnglish
JournalAmerican Journal of Ophthalmology
DOIs
Publication statusE-pub ahead of print - Jul 2021

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