Defining inclusion criteria and endpoints for clinical trials

Autor: Alberta A H J Thiadens, Nicoline E. Schalij-Delfos, Arthur A.B. Bergen, Carel B. Hoyng, Magda A. Meester-Smoor, L. Ingeborgh van den Born, Mary J. van Schooneveld, Camiel J. F. Boon, Jacoline B. ten Brink, Maria M. van Genderen, Ralph J. Florijn, Jan Wijnholds, Herman E Talsma, Frans P.M. Cremers, Mays Talib
Přispěvatelé: Netherlands Institute for Neuroscience (NIN), Human Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Ophthalmology
Jazyk: angličtina
Rok vydání: 2021
Předmět:
retina
Visual acuity
genetic structures
Visual Acuity
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
chemistry.chemical_compound
0302 clinical medicine
Prospective Studies
Child
Clinical Trials as Topic
medicine.diagnostic_test
General Medicine
Macular dystrophy
Middle Aged
gene therapy
Phenotype
Disease Progression
Original Article
medicine.symptom
Retinal Dystrophies
Adult
medicine.medical_specialty
Adolescent
Endpoint Determination
Nerve Tissue Proteins
03 medical and health sciences
Young Adult
Ophthalmology
retinitis pigmentosa
Retinitis pigmentosa
medicine
Humans
retinal dystrophy
Eye Proteins
Aged
business.industry
Patient Selection
Membrane Proteins
Retinal
Original Articles
medicine.disease
eye diseases
Cross-Sectional Studies
chemistry
030221 ophthalmology & optometry
Maculopathy
sense organs
business
Microperimetry
030217 neurology & neurosurgery
Electroretinography
Zdroj: Acta Ophthalmologica (2008), 99, e402-e414
Acta Ophthalmologica, 99, e402-e414. Wiley-Blackwell
Acta Ophthalmologica
Acta Ophthalmologica, 99(3), E402-E414. WILEY
Acta Ophthalmologica (2008), 99, 3, pp. e402-e414
Acta ophthalmologica, 99(3), e402-e414. Copenhagen Scriptor
Acta Ophthalmologica, 99(3), e402-e414. Wiley-Blackwell Publishing Ltd
ISSN: 1755-375X
Popis: Contains fulltext : 234995.pdf (Publisher’s version ) (Open Access) 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.
Databáze: OpenAIRE
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