July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Structural and Functional Abnormalities in Leber Congenital Amaurosis Caused by Mutations in RDH12: A Short-Term Longitudinal Study
Author Affiliations & Notes
  • Katherine E. Uyhazi
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Leona Serrano
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Grace Vergilio
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Denise J Pearson
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Albert M. Maguire
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Jean Bennett
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Tomas S Aleman
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, Center for Advanced Retinal and Ocular Therapeutics, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Katherine Uyhazi, None; Leona Serrano, None; Grace Vergilio, None; Denise Pearson, None; Albert Maguire, Spark Therapeutics (F); Jean Bennett, Biogen (F), Gensight Biologics (S), Limelight (F), Sanofi (C), Spark Therapeutics (P), Spark Therapeutics (S); Tomas Aleman, None
  • Footnotes
    Support  RDH12 Fund for Sight, Hope for Vision, The Foundation Fighting Blindness, Macula Vision Research Foundation, The Paul and Evanina Bell Mackall Foundation Trust, The Brenda and Matthew Shapiro Stewardship, the Robert and Susan Heidenberg Investigative Research Fund for Ocular Gene Therapy, The Pennsylvania Lions Sight Conservation and Research Foundation and Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4509. doi:
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    • Get Citation

      Katherine E. Uyhazi, Leona Serrano, Grace Vergilio, Denise J Pearson, Albert M. Maguire, Jean Bennett, Tomas S Aleman; Structural and Functional Abnormalities in Leber Congenital Amaurosis Caused by Mutations in RDH12: A Short-Term Longitudinal Study. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4509.

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

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Abstract

Purpose : To describe the short-term changes in retinal structure and function in a group of pediatric patients with Leber congenital amaurosis (LCA) caused by mutations in Retinol dehydrogenase 12 (RDH12).

Methods : Eleven patients from six families (ages 3-14 years) with RDH12-LCA underwent a complete ophthalmic exam. Imaging was performed with spectral domain optical coherence tomography (SD-OCT) and near infrared reflectance. Visual thresholds were measured with full-field sensitivity thresholds (FST) and in a subset of patients with two-color dark-adapted perimetry. All patients had evaluations at baseline and approximately one year later (avg = 12.7 months).

Results : Visual acuity ranged from 20/25 to 20/300 and did not change on follow up. All patients showed atrophic maculopathies accompanied by midperipheral pigment migration. SD-OCT revealed foveal thinning in all patients, with detectable but thinned outer nuclear layer (ONL) at greater eccentricities from the fovea into the pericentral and peripapillary retina. ONL thickness at the best-preserved region along the nasal side of the fovea on horizontal SD-OCT profiles was not significantly different after one year. Central sensitivity profiles showed residual rod function in peripapillary retina in 5/8 patients; near normal rod-mediated sensitivity but abnormal cone-mediated sensitivity co-localized with normal peripapillary ONL thickness in two patients. All patients had measurable cone vision near fixation. FST sensitivities were rod-mediated, reduced by about 2 log units, and did not change significantly on follow-up.

Conclusions : RDH12-LCA is a severe, early-onset, retina-wide disease associated with an atrophic maculopathy. Abnormal rod and/or cone-mediated sensitivities were measured within regions of relatively preserved central outer retina. Visual acuity, full-field sensitivity thresholds, and regions of relative ONL preservation but with vision loss remained stable in this one-year longitudinal follow-up study, suggesting that this cone-rod dystrophy is a slowly progressive disease that may have a wide therapeutic window for gene augmentation therapy.

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

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