Effects of Phenytoin on the Retinal Ganglion Cell-Inner Plexiform Layer in Acute Optic Neuritis
Year: 2025
Type: article
Abstract: BACKGROUND AND OBJECTIVES: Acute demyelinating optic neuritis (AON) can lead to irreversible neuroaxonal loss. We investigated the neuroprotective effects of phenytoin on macular ganglion cell-inner plexiform layer (mGCIPL) thickness. METHODS: We reanalyzed Spectralis optical coherence tomography scans from the phenytoin AON trial (NCT01451593), a randomized, placebo-controlled, double-blind phase 2 trial. Participants attended 2 trial centers in London or Sheffield, United Kingdom. Patients with unilateral AON, age 18-60 years, within 2 weeks of onset, with visual acuities 6/9 or worse, were randomly assigned (1:1) to oral phenytoin (4-6 mg/kg/d) or placebo for 3 months, stratified by onset time, center, previous multiple sclerosis diagnosis, disease-modifying treatment, and corticosteroid use. Macular ganglion cell-inner plexiform layer thicknesses were extracted at baseline and 6 months. Linear regression models evaluated treatment effects on 6-month affected eye mGCIPL, adjusting for 6-month full-field visual evoked potential (VEP) latency and amplitude and baseline variables including mGCIPL thicknesses, steroid use, baseline acuity, and time interval to treatment. We also compared neuroprotective effects between peripapillary retinal nerve fiber layer (pRNFL) and mGCIPL outcomes. RESULTS: = 0.013). Neuroprotective effects on mGCIPL outcomes were more robust than for pRNFL outcomes. DISCUSSION: This study supports superiority of the mGCIPL over the pRNFL as a neuroprotective marker after AON and demonstrates strong associations with myelination, providing additional mechanistic insights. TRIAL REGISTRATION INFORMATION: This trial is registered with ClinicalTrials.gov, number NCT01451593; submitted for registration on October 11, 2011; first patient enrollment was on February 2, 2012. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that compared with placebo, phenytoin is associated with greater preservation of the mGCIPL thickness in patients with acute demyelinating optic neuropathy.
Source: Neurology
Institutions: National Hospital for Neurology and Neurosurgery, UCL Queen Square Institute of Neurology, University College London, University of Palermo, King's College Hospital NHS Foundation Trust, Federico II University Hospital, University of Naples Federico II, Universitat Oberta de Catalunya, Sheffield Teaching Hospitals NHS Foundation Trust
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Funders: Bristol-Myers Squibb, Sanofi, Biogen, Celgene, Cleveland Clinic, European Committee for Treatment and Research in Multiple Sclerosis, National Brain Appeal, National Institute for Health and Care Research, Ataxia UK, Multiple Sclerosis Society, University College London, European Commission, Rosetrees Trust, Ipsen, MedDay Pharmaceuticals, Ministero dell'Università e della Ricerca, Medical Research Council
OpenAlex ID: W4414497769