September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
High symmetry of visual field loss in X-linked retinitis pigmentosa
Author Affiliations & Notes
  • Julia-Sophia Bellingrath
    University Eye Hospital , University Hospital Tübingen, Tübingen, Germany
    Nuffield Laboratory of Ophthalmology, Nuffield Laboratory of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom
  • Immanuel Philip Seitz
    University Eye Hospital , University Hospital Tübingen, Tübingen, Germany
    Institute for Ophthalmic Research, University Hospital Tübingen, Tübingen, Germany
  • Susanne Kohl
    Institute for Ophthalmic Research, University Hospital Tübingen, Tübingen, Germany
  • Eberhart Zrenner
    University Eye Hospital , University Hospital Tübingen, Tübingen, Germany
    Institute for Ophthalmic Research, University Hospital Tübingen, Tübingen, Germany
  • Nicola Gloeckle
    Centre for Genomics and Transcriptomics , Tübingen, Germany
  • Holger Prokisch
    Institute of Human Genetics, Helmholtz Centre Munich, Munich, Germany
  • Susan Downes
    Oxford Eye Hospital, Oxford University Hospitals , Oxford, United Kingdom
    Nuffield Laboratory of Ophthalmology, Nuffield Laboratory of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom
  • Simon Ramsden
    Manchester Centre for Genomic Medicine, Central Manchester University Hospitals, Manchester, United Kingdom
  • Robert E MacLaren
    Nuffield Laboratory of Ophthalmology, Nuffield Laboratory of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom
    Oxford Eye Hospital, Oxford University Hospitals , Oxford, United Kingdom
  • Dominik M Fischer
    University Eye Hospital , University Hospital Tübingen, Tübingen, Germany
    Nuffield Laboratory of Ophthalmology, Nuffield Laboratory of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom
  • Footnotes
    Commercial Relationships   Julia-Sophia Bellingrath, None; Immanuel Philip Seitz, None; Susanne Kohl, None; Eberhart Zrenner, None; Nicola Gloeckle, None; Holger Prokisch, None; Susan Downes, None; Simon Ramsden, None; Robert MacLaren, None; Dominik Fischer, None
  • Footnotes
    Support  Studienstiftung des deutschen Volkes, Claussen Simon Stiftung
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 132. doi:
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    • Get Citation

      Julia-Sophia Bellingrath, Immanuel Philip Seitz, Susanne Kohl, Eberhart Zrenner, Nicola Gloeckle, Holger Prokisch, Susan Downes, Simon Ramsden, Robert E MacLaren, Dominik M Fischer; High symmetry of visual field loss in X-linked retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2016;57(12):132.

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

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Abstract

Purpose : Mutations in RPGRORF15 cause 70 to 90% of X-linked retinitis pigmentosa (XLRP), making this gene a high-yield target for therapeutic intervention. By analyzing pre-treatment characteristics in a cohort of 50 XLRP-RPGR patients, this study aims to assist future interventional trials by analyzing symmetry of disease, rate of progression and suitability of outcome measures.

Methods : A retrospective, cross-sectional analysis of 50 patients extracted visual acuity, visual fields (I4e and III4e targets), foveal thickness and ERG data points (ISCEV standard protocol) alongside molecular genetic data. Symmetry and progression were assessed using linear regression and cross-sectional analysis, respectively. Kaplan-Meyer Curves were used to estimate cumulative ‘survival’ of 6/6 vision, reading ability and legal blindness at different ages.

Results : Of the observed phenotypes, 96% followed rod-cone and 4% a cone-rod phenotype. 73% of exonic mutations occurred in ORF15. 80% of missense mutations clustered in exons 1-14, whereas 85% of nonsense mutations were present in ORF15. No clear genotype-phenotype relationship could be established between mutations located in exons 1-14 or ORF15. Patients with ORF15 mutations did not have a significantly different visual acuity (p = 0.9) or visual field (III4e; p = 0.6) than those with mutations in exons 1-14. Comparison of both eyes revealed a strong symmetry of degeneration in all outcome measures, with visual fields (I4e R2 = 0.99; III4e R2 = 0.9) and ERG (30 Hz flicker R2 = 0.9) exhibiting the highest symmetry. Disease progression eluded description by a simple function. Kaplan-Meier curve (KMC) estimates predicted a loss of 6/6 vision at a mean of 34 years (± 2.9; Confidence Interval), with a loss of reading ability occurring at 39 years (± 2.6) and a complete loss of vision at 48 (± 1.6) years.

Conclusions : High symmetry in all outcome measures confirms that the contralateral eye can be used as an internal control in an RPGR-XLRP gene therapy trial. The variability between patients makes an intra-individual control preferable to an inter-individual control. According to these findings, the most sensitive parameter to measure disease progression and treatment success in an interventional RPGR-XLRP trial seems to be kinetic visual field using the III4e target. KMC analysis predicts the most severe decline in vision between the third and fourth decade of life.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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