Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study

Liang Wang; Hongmei Tan; Jian Yu; Jingzi ZhangBao; Wenjuan Huang; Xuechun Chang; Lei Zhou; Chuanzhen Lu; Yiqin Xiao; Jiahong Lu; Chongbo Zhao; Min Wang; Xue Wu; Mengyun Wu; Qiang Dong; Kok Yew Ngew; Chao Quan

doi:10.1111/ene.15612

Baseline retinal nerve fiber layer thickness as a predictor of multiple sclerosis progression: New insights from the FREEDOMS II study

Eur J Neurol. 2023 Feb;30(2):443-452. doi: 10.1111/ene.15612. Epub 2022 Nov 15.

Authors

Liang Wang^{1

2}, Hongmei Tan^{1

2}, Jian Yu³, Jingzi ZhangBao^{1

2}, Wenjuan Huang^{1

2}, Xuechun Chang^{1

2}, Lei Zhou^{1

2}, Chuanzhen Lu^{1

2

4}, Yiqin Xiao⁵, Jiahong Lu^{1

2

4}, Chongbo Zhao^{1

2

4}, Min Wang³, Xue Wu⁶, Mengyun Wu⁶, Qiang Dong^{1

2

4}, Kok Yew Ngew⁷, Chao Quan^{1

2

4}

Affiliations

¹ Department of Neurology and Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
² National Center for Neurological Disorders, Shanghai, China.
³ Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁵ Department of Ophthalmology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁶ Novartis Pharmaceuticals, Shanghai, China.
⁷ Novartis Corporation (Malaysia) Sdn. Bhd., Petaling Jaya, Malaysia.

PMID: 36286605
DOI: 10.1111/ene.15612

Abstract

Background and purpose: The aim was to evaluate the potential of retinal nerve fiber layer thickness (RNFLT) measured with optical coherence tomography in predicting disease progression in relapsing-remitting multiple sclerosis (RRMS).

Methods: Analyses were conducted post hoc of this 24-month, phase III, double-blind study, in which RRMS patients were randomized (1:1:1) to once daily oral fingolimod 0.5 mg, 1.25 mg or placebo. The key outcomes were the association between baseline RNFLT and baseline clinical characteristics and clinical/imaging outcomes up to 24 months. Change of RNFLT with fingolimod versus placebo within 24 months and time to retinal nerve fiber layer (RNFL) thinning were evaluated.

Results: Altogether 885 patients were included. At baseline, lower RNFLT was correlated with higher Expanded Disability Status Scale score (r = -1.085, p = 0.018), lower brain volume (r = 0.025, p = 0.006) and deep gray matter volume (r = 0.731, p < 0.0001), worse visual acuity (r = -19.846, p < 0.0001) and longer duration since diagnosis (r = -0.258, p = 0.018). At month 12, low baseline RNFLT (<86 μm) versus high baseline RNFLT (≥99 μm) was associated with a greater brain volume loss (percentage change -0.605% vs. -0.315%, p = 0.035) in patients without optic neuritis history. At month 24, low baseline RNFLT versus high baseline RNFLT was associated with a higher number of new or newly enlarged T2 lesions (mean number 4.0 vs. 2.8, p = 0.014) and a higher risk of subsequent RNFL thinning (hazard ratio 2.55; 95% confidence interval 1.84-3.53; p < 0.001). The atrophy of the RNFL in the inferior quadrant was alleviated with fingolimod 0.5 mg versus placebo at month 24 (Δ(least squares mean) = 1.8, p = 0.047).

Conclusion: Retinal nerve fiber layer thickness could predict disease progression in RRMS.

Trial registration: Clinicaltrials.gov identifier: NCT00355134, https://clinicaltrials.gov/ct2/show/NCT00355134.

Keywords: disease progression; optical coherence tomography; predictor; relapsing-remitting multiple sclerosis; retinal nerve fiber layer thickness.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Disease Progression
Fingolimod Hydrochloride / therapeutic use
Humans
Multiple Sclerosis* / complications
Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting* / drug therapy
Nerve Fibers / pathology
Retina / diagnostic imaging
Retina / pathology
Tomography, Optical Coherence / methods

Substances

Fingolimod Hydrochloride

Associated data

ClinicalTrials.gov/NCT00355134