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 journalArticleAcademicpeer-review

Abstract

PURPOSE: To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points 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 Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, 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 (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. 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 end point in future human treatment trials for CRB1-associated retinal dystrophies.

Original languageEnglish
Pages (from-to)37-48
Number of pages12
JournalAmerican journal of ophthalmology
Volume234
DOIs
Publication statusPublished - 1 Feb 2022

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