June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Natural History of Inherited Retinal Disease (IRD) in Patients with Mutations in the Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Genes
Author Affiliations & Notes
  • Robert K Koenekoop
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Robert Koenekoop, Novelion Therapeutics (C)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2010. doi:
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      Robert K Koenekoop; Natural History of Inherited Retinal Disease (IRD) in Patients with Mutations in the Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT) Genes. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2010.

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

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Purpose : Studies over the past several decades have reported on the natural history of visual function in IRD subjects but were not always inclusive or limited to patients with particular genetic defects. This retrospective, multicenter, case history study was designed to expand this knowledge in subjects with LCA or RP due to RPE65 or LRAT gene mutations, including treatment naïve patients and those previously treated with oral synthetic retinoid, Zuretinol acetate (QLT091001) therapy (ZA-treated) in order to assess the extent to which ZA treatment may improve or prolong visual function.

Methods : Study subjects with IRD were divided into two cohorts, treatment naïve and previously ZA-treated. Inclusion criteria for the treatment naïve cohort 1 included at least two documented kinetic visual fields (KVFs) of the same isopter(s) in at least one eye at least 2 years apart between ages of 6 and 65 years. Inclusion criteria for the treated cohort 2 included at least one documented KVF and/or visual acuity (VA) assessment prior to or following participation in the ZA trials. The natural history slopes of KVF and VA over time were generated using a random coefficient regression model.

Results : Data of 54 subjects at 9 study centers are reported, including 29 subjects in cohort 1 and 25 in cohort 2. Overall there were equal numbers of males and females with a mean age of first assessment of 11.1 years for cohort 1 and 15.2 years for cohort 2. Forty six subjects (85%) were diagnosed with LCA and 8 subjects (15%) with RP. The majority of cohort 1 subjects showed loss in KVF area over time. The rate of decline in KVF area appeared to be faster for the larger target sizes and slower for the smaller target sizes. VA also declined but showed periods of relative stability. For cohort 2, ZA-treatment resulted in improvement in visual function for a majority of subjects. Most subjects lost KVF area prior to ZA-treatment and continued to lose function after ZA-treatment effects ceased.

Conclusions : The study demonstrated a progressive deterioration over time in both VF area and VA in subjects with LCA or RP associated with RPE65 or LRAT gene mutations. A majority of cohort 2 subjects demonstrated improvements in VF and/or VA with ZA-treatment, which cannot be explained by the natural history of the disease.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.


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