Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies

Talib, M.; Schooneveld, M.J. van; Wijnholds, J.; Genderen, M.M. van; Schalij-Delfos, N.E.; Talsma, H.E.; ... ; Boon, C.J.F. (2021)

Article / Letter to editor

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.

• retina
• retinal dystrophy
• retinitis pigmentosa
• gene therapy

• All authors: Talib, M.; Schooneveld, M.J. van; Wijnholds, J.; Genderen, M.M. van; Schalij-Delfos, N.E.; Talsma, H.E.; Florijn, R.J.; Brink, J.B. ten; Cremers, F.P.M.; Thiadens, A.A.H.J.; Born, L.I. van den; Hoyng, C.B.; Meester-Smoor, M.A.; Bergen, A.A.; Boon, C.J.F.
• Date: 2021-02-02
• Journal: Acta Ophthalmologica
• Volume: 99
• Issue: 3
• Pages: E402 - E414
• DOI: doi:10.1111/aos.14597
• Link: https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/aos.14597