June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
A two-year prospective natural history study in patients with CRB1-associated retinal dystrophies: establishing clinical endpoints for future gene therapy trials
Author Affiliations & Notes
  • Xuan-Thanh-An Nguyen
    Department of Ophthalmology, Leiden University Medical Centre, Netherlands
  • Mays Talib
    Department of Ophthalmology, Leiden University Medical Centre, Netherlands
  • Mary J. van Schooneveld
    Department of Ophthalmology, Amsterdam University Medical Center, Netherlands
  • Jan Wijnholds
    Department of Ophthalmology, Leiden University Medical Centre, Netherlands
    The Netherlands Institute for Neuroscience, Netherlands
  • Maria M. van Genderen
    Department of Ophthalmology, University Medical Centre Utrecht, Netherlands
    Bartiméus, Diagnostic Centre for complex visual disorders, Netherlands
  • Ralph J. Florijn
    Department of Clinical Genetics, Amsterdam University Medical Center, Netherlands
  • Jacoline ten Brink
    Department of Clinical Genetics, Amsterdam University Medical Center, Netherlands
  • Frans P Cremers
    Department of Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Netherlands
  • Magda A. Meester
    Department of Ophthalmology, Erasmus Medical Center, Netherlands
  • Caroline Klaver
    Department of Ophthalmology, Radboud University Medical Center, Netherlands
    Department of Ophthalmology, Erasmus Medical Center, Netherlands
  • L. Ingeborgh van den Born
    Rotterdam Eye Hospital, Netherlands
  • Carel C B Hoyng
    Department of Ophthalmology, Radboud University Medical Center, Netherlands
  • Alberta Thiadens
    Department of Ophthalmology, Erasmus Medical Center, Netherlands
  • Arthur Bergen
    Department of Clinical Genetics, Amsterdam University Medical Center, Netherlands
    The Netherlands Institute for Neuroscience, Netherlands
  • Camiel Boon
    Department of Ophthalmology, Leiden University Medical Centre, Netherlands
    Department of Ophthalmology, Amsterdam University Medical Center, Netherlands
  • Footnotes
    Commercial Relationships   Xuan-Thanh-An Nguyen, None; Mays Talib, None; Mary J. van Schooneveld, None; Jan Wijnholds, Leiden University Medical Center (P); Maria M. van Genderen, None; Ralph J. Florijn, None; Jacoline ten Brink, None; Frans Cremers, None; Magda Meester, None; Caroline Klaver, None; L. Ingeborgh van den Born, None; Carel Hoyng, None; Alberta Thiadens, None; Arthur Bergen, None; Camiel Boon, None
  • Footnotes
    Support  Supported by the Stichting Blindenhulp and Uitzicht Grant No. 2019–11.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3051. doi:
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      Xuan-Thanh-An Nguyen, Mays Talib, Mary J. van Schooneveld, Jan Wijnholds, Maria M. van Genderen, Ralph J. Florijn, Jacoline ten Brink, Frans P Cremers, Magda A. Meester, Caroline Klaver, L. Ingeborgh van den Born, Carel C B Hoyng, Alberta Thiadens, Arthur Bergen, Camiel Boon; A two-year prospective natural history study in patients with CRB1-associated retinal dystrophies: establishing clinical endpoints for future gene therapy trials. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3051.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : No curative treatment is available for CRB1-associated retinal dystrophies (RDs), but promising results have been shown using gene therapy in rodent models. In view of future clinical trials, we assessed the natural course and investigated potential clinical endpoints in patients with CRB1-associated retinal dystrophies.

Methods : Seventeen patients underwent comprehensive ophthalmologic assessment at baseline and at 2-year follow-up, including best-corrected visual acuity (BCVA; ETDRS), slit-lamp examination, fundus photography, spectral-domain optical coherence tomography and fundus autofluorescence imaging, Goldmann kinetic perimetry (V4e and I4e isopters), microperimetry, full-field electroretinography and full-field stimulus testing.

Results : Patients had a mean age of 23.7 years (standard deviation [SD]: 10.7), with a diagnosis of retinitis pigmentosa (n = 15), cone-rod dystrophy (n = 1), or macular dystrophy (n = 1). Nanophthalmos (axial length < 20.5 mm) was seen in 7/17 (41%) patients. Cystoid macular edema was observed in 8/17 patients (47%). Thickening of inner retinal layers was seen in all patients (100%), and mild to moderate laminar disorganization was seen in 13/17 (76%) patients. A significant decrease in mean retinal sensitivity (p = 0.005) on microperimetry was seen between time points, which was not observed for BCVA (p = 0.408), V4e retinal seeing areas (p = 0.136), or I4e retinal seeing areas (p = 0.781).

Conclusions : BCVA and retinal seeing areas on visual fields remain relatively stable over the course of 2 years, and may not be optimal as clinical endpoints to assess efficacy of gene therapy. Of the assessed parameters, macular sensitivity measurement on microperimetry appears to be most sensitive in detecting disease progression over a 2-year period in patients with CRB1-associated RDs, and should be considered as a potential outcome measure in future therapeutic trials.

This is a 2020 ARVO Annual Meeting abstract.

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