TY - JOUR
T1 - CRB1-Associated Retinal Dystrophies
T2 - A Prospective Natural History Study in Anticipation of Future Clinical Trials
AU - Nguyen, Xuan Thanh An
AU - Talib, Mays
AU - van Schooneveld, Mary J.
AU - Wijnholds, Jan
AU - van Genderen, Maria M.
AU - Schalij-Delfos, Nicoline E.
AU - Klaver, Caroline C.W.
AU - Talsma, Herman E.
AU - Fiocco, Marta
AU - Florijn, Ralph J.
AU - ten Brink, Jacoline B.
AU - Cremers, Frans P.M.
AU - Meester-Smoor, Magda A.
AU - van den Born, L. Ingeborgh
AU - Hoyng, Carel B.
AU - Thiadens, Alberta A.H.J.
AU - Bergen, Arthur A.
AU - Boon, Camiel J.F.
N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Electroretinography
KW - Eye Proteins/genetics
KW - Humans
KW - Membrane Proteins/genetics
KW - Nerve Tissue Proteins/genetics
KW - Retina
KW - Retinal Dystrophies/diagnosis
KW - Retinitis Pigmentosa/diagnosis
KW - Tomography, Optical Coherence/methods
KW - Visual Field Tests
KW - Visual Fields
UR - https://www.scopus.com/pages/publications/85118889813
UR - https://www.mendeley.com/catalogue/52a54462-5222-33b2-a86d-c9b5bb66ee78/
U2 - 10.1016/j.ajo.2021.07.021
DO - 10.1016/j.ajo.2021.07.021
M3 - Article
C2 - 34320374
AN - SCOPUS:85118889813
SN - 0002-9394
VL - 234
SP - 37
EP - 48
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
ER -