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Updated: Jun 27, 2026
Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients
Published on: April 14, 2014
Multiple sclerosis: structural and functional integrity of the visual system following alemtuzumab therapy
Chenyu Wang1,2, Joshua Barton2, Kain Kyle1,2
1Sydney Neuroimaging Analysis Centre, Camperdown, New South Wales, Australia.
Objective:
To investigate potential neuroprotective and pro-remyelinating effects of alemtuzumab in multiple sclerosis (MS), using the visual pathway as a model.
Methods:
We monitored clinical, multifocal visual evoked potential (mfVEP) and MRI outcomes in 30 patients commencing alemtuzumab for relapsing MS, and a reference group of 20 healthy controls (HCs), over 24 months. Change in mfVEP latency was the primary endpoint; change in optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity over the course of the study were secondary endpoints.
Results:
In patients, we observed a mean shortening of mfVEP latency of 1.21 ms over the course of the study (95% CI 0.21 to 2.21, p=0.013), not altered by correction for age, gender, disease duration or change in OR T2 lesion volume. Mean mfVEP latency in the HC group increased over the course of the study by 0.72 ms (not significant). Analysis of chronic OR T2 lesions (patients) showed an increase in normalised fractional anisotropy and axial diffusivity between baseline and 24 months (both p<0.01). Mean Mars letter contrast sensitivity was improved at 24 months vs baseline (p<0.001), and driven by an early improvement, in both patients and HC.
Conclusion:
We found evidence of partial lesion remyelination after alemtuzumab therapy, indicating either natural restoration in the context of a 'permissive' local milieu; or potentially an independent, pro-reparative mechanism of action. The visual system presents a unique opportunity to study function-structure specific effects of therapy and inform the design of future phase 2 MS remyelination trials.
Insights
Alemtuzumab may promote remyelination in multiple sclerosis (MS) patients, evidenced by improved visual pathway function and optic radiation lesions. This suggests potential pro-reparative effects beyond immune modulation in MS.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system.
- Alemtuzumab is an effective disease-modifying therapy for relapsing MS, targeting B and T lymphocytes.
- The visual pathway offers a unique model to study neuroprotection and remyelination in MS.
Purpose of the Study:
- To investigate the neuroprotective and pro-remyelinating effects of alemtuzumab in MS.
- To utilize the visual pathway as a model system to assess these effects.
- To evaluate changes in visual evoked potentials, MRI metrics, and contrast sensitivity.
Main Methods:
- A 24-month prospective study of 30 relapsing MS patients treated with alemtuzumab and 20 healthy controls (HCs).
- Primary endpoint: change in multifocal visual evoked potential (mfVEP) latency.
- Secondary endpoints: optic radiation (OR) lesion diffusion metrics and Mars letter contrast sensitivity.
Main Results:
- Patients showed a significant mean shortening of mfVEP latency (1.21 ms, p=0.013).
- Analysis of chronic OR lesions revealed increased fractional anisotropy and axial diffusivity, indicating partial remyelination.
- Mars letter contrast sensitivity improved significantly in patients and HCs by 24 months.
Conclusions:
- Evidence suggests partial lesion remyelination following alemtuzumab therapy in MS.
- This may indicate a pro-reparative mechanism of action or natural repair in a permissive environment.
- The visual system is a valuable model for studying therapy-induced repair in MS and designing future remyelination trials.
