July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
The disease course of rhodopsin (RHO)-associated retinitis pigmentosa (RP): a follow-up study
Author Affiliations & Notes
  • Xuan-Thanh-An Nguyen
    Ophthalmology, Leiden University Medical Centre, Leiden, South-Holland, Netherlands
  • Mays Talib
    Ophthalmology, Leiden University Medical Centre, Leiden, South-Holland, Netherlands
  • Mary J van Schooneveld
    Ophthalmology, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
  • Caroline Van Cauwenbergh
    Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
    Center for Medical Genetics, Ghent, Belgium
  • Jacoline B ten Brink
    Clinical Genetics, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
  • Ralph J Florijn
    Clinical Genetics, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
  • Nicoline Schalij-Delfos
    Ophthalmology, Leiden University Medical Centre, Leiden, South-Holland, Netherlands
  • Maria M. van Genderen
    Bartimeus, Diagnostic Center for complex visual disorders, Zeist, Netherlands
  • Frans P Cremers
    Human Genetics and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands
  • L. Ingeborgh van den Born
    Rotterdam Eye Hospital, Rotterdam, Netherlands
  • Alberta A H J Thiadens
    Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands
  • Carel C B Hoyng
    Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands
  • Caroline C W Klaver
    Rotterdam Eye Hospital, Rotterdam, Netherlands
    Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands
  • Arthur A Bergen
    Clinical Genetics, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
    The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, Netherlands
  • Bart P Leroy
    Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium
    Center for Medical Genetics, Ghent, Belgium
  • Camiel Boon
    Ophthalmology, Leiden University Medical Centre, Leiden, South-Holland, Netherlands
    Ophthalmology, Amsterdam UMC, Academic Medical Center, Amsterdam, Netherlands
  • Footnotes
    Commercial Relationships   Xuan-Thanh-An Nguyen, None; Mays Talib, None; Mary van Schooneveld, None; Caroline Van Cauwenbergh, None; Jacoline ten Brink, None; Ralph Florijn, None; Nicoline Schalij-Delfos, None; Maria van Genderen, None; Frans Cremers, None; L. van den Born, None; Alberta Thiadens, None; Carel Hoyng, None; Caroline Klaver, None; Arthur Bergen, None; Bart Leroy, None; Camiel Boon, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4505. doi:https://doi.org/
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      Xuan-Thanh-An Nguyen, Mays Talib, Mary J van Schooneveld, Caroline Van Cauwenbergh, Jacoline B ten Brink, Ralph J Florijn, Nicoline Schalij-Delfos, Maria M. van Genderen, Frans P Cremers, L. Ingeborgh van den Born, Alberta A H J Thiadens, Carel C B Hoyng, Caroline C W Klaver, Arthur A Bergen, Bart P Leroy, Camiel Boon; The disease course of rhodopsin (RHO)-associated retinitis pigmentosa (RP): a follow-up study. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4505. doi: https://doi.org/.

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

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Abstract

Purpose : In view of upcoming gene therapy trials, more insight into the natural disease progression in RHO-associated RP is required. A more detailed clinical disease profile will aid in the selection of eligible candidates, and the establishment of appropriate clinical endpoints for future gene therapy trials. In this retrospective cohort study, we provide a description of the clinical variability and the natural disease course in patients with RHO-associated RP in a longitudinal cohort.

Methods : We reviewed the medical records of patients with RHO-associated retinitis pigmentosa for symptoms, best-corrected visual acuity (BCVA), fundus photography, Goldmann kinetic perimetry (V4e and I4e isopters), full-field electroretinography, spectral-domain optical coherence tomography and fundus autofluorescence imaging.

Results : Ninety-nine patients with RHO mutations were included for analysis. Mutations were located in the extracellular (n=63; 63%), transmembrane (n=20; 21%), or cytoplasmic (n=16; 16%) domains. The median age at which patients reached mild visual impairment (0.3 ≤ BCVA < 0.5) was 72 years. First occurrences of low vision (0.1 ≤ BCVA < 0.3) were observed from the 3rd decade onwards, whereas severe visual impairment (0.05 ≤ BCVA < 0.1) and blindness (BCVA < 0.05) were seen from the 6th decade onwards. Mutations in the cytoplasmic domain were associated with a worse age-adjusted BCVA (p=0.033), but did not alter the BCVA decline rate of 2% per year (p<0.001). Mutations in the extracellular domain were associated with a larger age-adjusted seeing retinal area (I4e) than those in the cytoplasmic (p=0.006) or transmembrane domains (p=0.006), but did not affect the yearly decline rate of the I4e seeing retinal area (5%; p<0.001). Visual function parameters correlated robustly with the thickness of the foveal photoreceptor-retinal pigment epithelium complex (p<0.001). Cystoid maculopathy (CME) was reported in 34/56 patients (61%).

Conclusions : RHO mutations result in a relatively mild form of retinitis pigmentosa. Mutations in the cytoplasmic domain are associated with worse visual function. The relatively late occurrence of blindness and slow rates of BCVA decline indicate a broad therapeutic window, but also warrants further exploration of alternative functional and structural parameters to assess treatment efficacy in upcoming clinical trials.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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