RT Journal Article
T1 Using Acute Optic Neuritis Trials to Assess Neuroprotective and Remyelinating Therapies in Multiple Sclerosis.
A1 Andorrà, Magí
A1 Alba-Arbalat, Salut
A1 Camos-Carreras, Anna
A1 Gabilondo, Iñigo
A1 Fraga-Pumar, Elena
A1 Torres-Torres, Ruben
A1 Pulido-Valdeolivas, Irene
A1 Tercero-Uribe, Ana I
A1 Guerrero-Zamora, Ana M
A1 Ortiz-Perez, Santiago
A1 Zubizarreta, Irati
A1 Sola-Valls, Nuria
A1 Llufriu, Sara
A1 Sepulveda, Maria
A1 Martinez-Hernandez, Eugenia
A1 Armangue, Thais
A1 Blanco, Yolanda
A1 Villoslada, Pablo
A1 Sanchez-Dalmau, Bernardo
A1 Saiz, Albert
A1 Martinez-Lapiscina, Elena H
AB Neuroprotective and remyelinating therapies are required for multiple sclerosis (MS), and acute optic neuritis (AON) is a potential condition to evaluate such treatments. To comprehensively assess key biological and methodological aspects of AON trials for testing neuroprotection and remyelination in MS. The AON-VisualPath prospective cohort study was conducted from February 2011 to November 2018 at the Hospital Clinic of University of Barcelona, Barcelona, Spain. Consecutive patients with AON were prospectively enrolled in the cohort and followed up for 18 months. Data analyses occurred from November 2018 to February 2019. Participants were followed up for 18 months using optical coherence tomography, visual acuity tests, and in a subset of 25 participants, multifocal visual evoked potentials. Dynamic models of retinal changes and nerve conduction and their associations with visual end points; and eligibility criteria, stratification, and sample-size estimation for future trials. A total of 60 patients (50 women [83%]; median age, 34 years) with AON were included. The patients studied displayed early and intense inner retinal thinning, with a thinning rate of approximately 2.38 μm per week in the ganglion cell plus inner plexiform layer (GCIPL) during the first 4 weeks. Eyes with AON displayed a 6-month change in latency of about 20 milliseconds, while the expected change in the eyes of healthy participants by random variability was 0.13 (95% CI, -0.80 to 1.06) milliseconds. The strongest associations with visual end points were for the 6-month intereye difference in 2.5% low-contrast letter acuity, which was correlated with the peripapillary retinal nerve fiber layer thinning (adjusted R2, 0.57), GCIPL thinning (adjusted R2, 0.50), and changes in mfVEP latency (adjusted R2, 0.26). A 5-letter increment in high-contrast visual acuity at presentation (but not sex or age) was associated with 6-month retinal thinning (1.41 [95% CI, 0.60-2.23] μm less peripapillary retinal nerve fiber layer thinning thinning; P = .001; adjusted R2, 0.20; 0.86 [95% CI, 0.35-1.37] μm less GCIPL thinning; P = .001; adjusted R2, 0.19) but not any change in multifocal visual evoked potential latency. To demonstrate 50% efficacy in GCIPL thinning or change in multifocal visual evoked potential latency, a 6-month, 2-arm, parallel-group trial would need 37 or 50 participants per group to test a neuroprotective or remyelinating drug, respectively (power, 80%; α, .05). Acute optic neuritis is a suitable condition to test neuroprotective and remyelinating therapies after acute inflammation, providing sensitive markers to assess the effects on both processes and prospective visual recovery within a manageable timeframe and with a relatively small sample size.
YR 2020
FD 2020
LK https://hdl.handle.net/10668/25323
UL https://hdl.handle.net/10668/25323
LA en
DS RISalud
RD Apr 6, 2025