TY - JOUR
T1 - Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies
AU - Talib, Mays
AU - van Schooneveld, Mary J.
AU - Wijnholds, Jan
AU - van Genderen, Maria M.
AU - Schalij-Delfos, Nicoline E.
AU - Talsma, Herman E.
AU - Florijn, Ralph J.
AU - ten Brink, Jacoline B.
AU - Cremers, Frans P. M.
AU - Thiadens, Alberta A. H. J.
AU - van den Born, L. Ingeborgh
AU - Hoyng, Carel B.
AU - Meester-Smoor, Magda A.
AU - Bergen, Arthur A.
AU - Boon, Camiel J. F.
N1 - Publisher Copyright: © 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.
PY - 2021/5
Y1 - 2021/5
N2 - Purpose: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints. Methods: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6–74 years), and who had a decimal best-corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI). Results: Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes. Conclusions: Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.
AB - Purpose: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints. Methods: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6–74 years), and who had a decimal best-corrected visual acuity (BCVA) ≥ 0.05 at the last visit, were studied clinically with ETDRS BCVA, corneal topography, spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, Goldmann visual field (VF), microperimetry, full-field electroretinography (ERG) and full-field stimulus testing (FST). Ten patients were from a genetic isolate (GI). Results: Patients had retinitis pigmentosa (n = 19; GI and non-GI), cone-rod dystrophy (n = 2; GI) or macular dystrophy (n = 1; non-GI). Median age at first symptom onset was 3 years (range 0.8–49). Median decimal BCVA in the better and worse-seeing eye was 0.18 (range 0.05–0.83) and 0.08 (range light perception-0.72), respectively. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid maculopathy in 8 subjects; inner retinal thickening (n = 20), a well-preserved (para)foveal outer retina (n = 7) or severe (para)foveal outer retinal atrophy (n = 14). All retinal layers were discernible in 13/21 patients (62%), with mild to moderate laminar disorganization in the others. Nanophthalmos was observed in 8 patients (36%). Full-field stimulus testing (FST) provided a subjective outcome measure for retinal sensitivity in eyes with (nearly) extinguished ERG amplitudes. Conclusions: Despite the generally severe course of CRB1-RDs, symptom onset and central visual function are variable, even at advanced ages. Phenotypes may vary within the same family. Imaging and functional studies in a prospective longitudinal setting should clarify which endpoints may be most appropriate in a clinical trial.
KW - gene therapy
KW - retina
KW - retinal dystrophy
KW - retinitis pigmentosa
UR - http://www.scopus.com/inward/record.url?scp=85100167569&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/aos.14597
DO - https://doi.org/10.1111/aos.14597
M3 - Article
C2 - 33528094
SN - 1755-375X
VL - 99
SP - e402-e414
JO - Acta ophthalmologica
JF - Acta ophthalmologica
IS - 3
ER -