June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Preliminary Baseline Characteristics of Patients with Leber Hereditary Optic Neuropathy (LHON) Enrolled in the RESCUE and REVERSE Clinical Gene Therapy Trials
Author Affiliations & Notes
  • Patrick Yu-Wai-Man
    Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, ENGLAND, United Kingdom
    NIHR Biomedical Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom
  • Nancy J Newman
    Departments of Ophthalmology, Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia, United States
  • Robert Sergott
    Neuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
    Optic Nerve Research Center, Philadelphia, Pennsylvania, United States
  • Molly Scannell Bryan
    Optic Nerve Research Center, University of Illinois at Chicago , Chicago, Illinois, United States
  • Valerio Carelli
    IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy
    Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy
  • Thomas Klopstock
    Department of Neurology, Friedrich-Baur-Institute, Munich, Germany
    University Hospital of LMU, Munich, Germany
  • Mark Moster
    Neuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, United States
    Departments of Neurology and Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, United States
  • Alfredo A. Sadun
    Doheny Eye Institute, Los Angeles, California, United States
    Department of Ophthalmology, UCLA, Los Angeles, California, United States
  • Jose Alain Sahel
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Catherine Vignal
    Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
    Fondation Ophtalmologique Rothschild, Paris, France
  • Scott Uretsky
    GenSight Biologics, Paris, France
  • Footnotes
    Commercial Relationships   Patrick Yu-Wai-Man, GenSight Biologics (C); Nancy Newman, GenSight Biologics (C), Santhera Pharmaceuticals (C); Robert Sergott, None; Molly Scannell Bryan, None; Valerio Carelli, GenSight Biologics (C); Thomas Klopstock, GenSight Biologics (C), Santhera Pharmaceuticals (C); Mark Moster, GenSight Biologics (F); Alfredo Sadun, Edison (F), GenSight Biologics (F), Stealth BioTherapeutics (F); Jose Sahel, Chronocam (I), Chronolife (I), Genesignal (C), GenSight Biologics (C), GenSight Biologics (I), Pixium Vision (C), Pixium Vision (I); Catherine Vignal, GenSight Biologics (C); Scott Uretsky, GenSight Biologics (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3865. doi:
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      Patrick Yu-Wai-Man, Nancy J Newman, Robert Sergott, Molly Scannell Bryan, Valerio Carelli, Thomas Klopstock, Mark Moster, Alfredo A. Sadun, Jose Alain Sahel, Catherine Vignal, Scott Uretsky; Preliminary Baseline Characteristics of Patients with Leber Hereditary Optic Neuropathy (LHON) Enrolled in the RESCUE and REVERSE Clinical Gene Therapy Trials. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3865.

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

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Abstract

Purpose : RESCUE (NCT02652767) and REVERSE (NCT02652780) are Phase III, randomized, double-masked, sham-controlled trials of rAAV2/2-ND4, an intravitreally-injected gene therapy vector for the treatment of ND4 LHON. RESCUE patients have vision loss for ≤6 months and REVERSE patients from >6 months to 1-year.

Methods : Inclusion criteria included age ≥15-years, presence of the G11778A-ND4 mutation and at least CF vision. Concurrent idebenone use was prohibited. We compared baseline characteristics of the first consecutively-recruited 10 RESCUE and 11 REVERSE patients.

Results : 16/21 were men (RESCUE 8/10, REVERSE 8/11). Mean (range) age (years): RESCUE 39.4 (20-69); REVERSE 36.2 (20-64); (p=0.7312). Mean (range) vision loss duration (days) for all eyes: RESCUE 128 (0-179); REVERSE 294.9 (184-364); p<0.0001. 5/21 patients had simultaneous onset. Two eyes had >20/20 vision at baseline in RESCUE; all eyes were <20/400 in REVERSE. Mean (range) LogMAR at baseline for all eyes: RESCUE 1.109 (-0.2-2.11); REVERSE 1.696 (1-2.26). For best-/worst-seeing eyes: RESCUE: best 0.78 (-0.2-1.5), worst 1.438 (0.6-2.11); REVERSE best 1.586 (1-2.16), worst 1.806 (1.5-2.26). Combining all eyes of RESCUE/REVERSE patients revealed a significant positive correlation (squarerootR2=0.571) between vision loss duration and baseline LogMAR (p<0.0001). Of 82 baseline HVF, 34% were reliable; mean MD was -12.2 (RESCUE) and -27.8 (REVERSE); p=0.0002. Mean (SD) total macular volume (mm3) was smaller in REVERSE (7.7 (0.3) vs. 8.5 (0.4); p< 0.0001) driven by thinning of the RNFL and GCL. A statistically significant relationship existed between retinal metrics and vision, with decreases in RNFL and GCL associated with worse vision (RNFL: p=0.0005; GCL: p=0.0004).

Conclusions : In these preliminary analyses, no age/gender differences were seen between the studies, but there were clinically significant differences in baseline LogMAR for all and best-/worst-seeing eyes, with the expected positive correlation between vision loss duration and worse baseline visual acuities. REVERSE patients demonstrated thinner RNFL, GCL and macular volumes and worse acuity at baseline.

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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