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Cross-Sectional Analysis of Baseline Visual Parameters in Subjects Recruited Into the RESCUE and REVERSE ND4-LHON
Mark L Moster1, Robert C Sergott, Nancy J Newman
1Departments of Neurology and Ophthalmology (MLM, RCS, AAD), Wills Eye Hospital and Thomas Jefferson University, Philadelphia, Pennsylvania; Departments of Ophthalmology (NJN, VB), Neurology and Neurological Surgery, Emory University School of Medicine, Atlanta, Georgia; Cambridge Centre for Brain Repair and MRC Mitochondrial Biology Unit (PY-W-M), Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom; Cambridge Eye Unit (PY-W-M), Addenbrooke's Hospital, Cambridge University Hospitals, Cambridge, United Kingdom; Moorfields Eye Hospital (PY-W-M), London, United Kingdom; UCL Institute of Ophthalmology (PY-W-M), University College London, London, United Kingdom; IRCCS Istituto Delle Scienze Neurologiche di Bologna (VC, MC), UOC Clinica Neurologica, Bologna, Italy; Unit of Neurology (VC), Department of Biomedical and Neuromotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; Institute of Health Research and Policy (MSB), University of Illinois, Chicago, Chicago, Illinois; Statistics Consultant (GS), GenSight Biologics, CaliforniaDepartment of Neuro Ophthalmology and Emergencies (CV-C, RH), Rothschild Foundation Hospital, Paris, France; Centre Hospitalier National D'Ophtalmologie des Quinze Vingts (CV-C, RH), Paris, France; Department of Neurology (TK), Friedrich-Baur-Institute, University Hospital, LMU Munich, Munich, Germany; German Center for Neurodegenerative Diseases (DZNE) (TK), Munich, Germany; Munich Cluster for Systems Neurology (SyNergy) (TK), Munich, Germany; Doheny Eye Center UCLA (AAS, RK), Department of Ophthalmology David Geffen School of Medicine at UCLA, Doheny Eye Institute, Los Angeles, CaliforniaDepartment of Ophthalmology (SP), University Hospital, LMU Munich, Munich, Germany ; Department of Ophthalmology (RK), University of Ottawa Eye Institute, Ottawa Canada ; GenSight Biologics (LB, MT), Paris, France; Medical Consultant (BK), GenSight Biologics; Sorbonne Université (JAS), INSERM, CNRS, Institut de La Vision, 75012 Paris, France ; Fondation Ophtalmologique A. de Rothschild (JAS), 25-29 Rue Manin, Paris; Department of Ophthalmology (JAS), the University of Pittsburgh School of Medicine, PittsburghCHNO des Quinze-Vingts (JAS), Institut Hospitalo-Universitaire FOReSIGHT, INSERM-DGOS CIC 1423, Paris, France.
Objective:
This report presents a cross-sectional analysis of the baseline characteristics of subjects with Leber hereditary optic neuropathy enrolled in the gene therapy trials RESCUE and REVERSE, to illustrate the evolution of visual parameters over the first year after vision loss.
Methods:
RESCUE and REVERSE were 2 phase III clinical trials designed to assess the efficacy of rAAV2/2-ND4 gene therapy in ND4-LHON subjects. At enrollment, subjects had vision loss for ≤6 months in RESCUE, and between 6 and 12 months in REVERSE. Functional visual parameters (best-corrected visual acuity [BCVA], contrast sensitivity [CS], and Humphrey Visual Field [HVF]) and structural parameters assessed by spectral-domain optical coherence tomography were analyzed in both cohorts before treatment. The cross-sectional analysis of functional and anatomic parameters included the baseline values collected in all eyes at 2 different visits (Screening and Inclusion).
Results:
Seventy-six subjects were included in total, 39 in RESCUE and 37 in REVERSE. Mean BCVA was significantly worse in RESCUE subjects compared with REVERSE subjects (1.29 and 1.61 LogMAR respectively, P = 0.0029). Similarly, mean CS and HVF were significantly more impaired in REVERSE vs RESCUE subjects (P < 0.005). The cross-sectional analysis showed that the monthly decrease in BCVA, ganglion cell layer macular volume, and retinal nerve fiber layer thickness was much more pronounced in the first 6 months after onset (+0.24 LogMAR, -0.06 mm3, and -6.00 microm respectively) than between 6 and 12 months after onset (+0.02 LogMAR, -0.01 mm3, and -0.43 microm respectively).
Conclusion:
LHON progresses rapidly in the first months following onset during the subacute phase, followed by relative stabilization during the dynamic phase.
