Compared to low-efficacy disease-modifying therapies (DMTs), high-efficacy medications are more effective at slowing the loss of nerve cells making up different layers of the retina — the region at the back of the eye that enables one to see — in patients with relapsing-remitting multiple sclerosis (RRMS).
The retina is made up of several layers of nerve cells that are connected to the brain through the optic nerve. Like the rest of the central nervous system (CNS, comprised of the brain and spinal cord), the retina also can start showing signs of neurodegeneration over the course of multiple sclerosis (MS).
“Optic neuritis, or inflammation of the optic nerve, is the initial manifestation of MS in approximately 25% of people,” according to Saidha, and “roughly up to 50% of people with MS will experience an episode of optic neuritis at some point during their disease course.”
Unlike the rest of the CNS, the retina can be examined easily for signs of nerve degeneration; for this reason it is being used more frequently to monitor disease progression in MS patients.
“Almost all aspects of MS pathobiology are well represented in the retina of people with MS, with the exception of demyelination” Saidha said. This is because the retina, as a CNS structure, is devoid of myelin under normal circumstances.
Recent studies have shown that certain measures of retinal neurodegeneration assessed by optical coherence tomography (OCT) — a non-invasive imaging test that uses light to take pictures of the retina — reflect the overall progression of MS. As such, results can be used to assess the therapeutic effects of different types of MS therapies.
The team analyzed the use of high-efficacy DMTs, including Tysabri (natalizumab, marketed by Biogen) and rituximab (a therapy used off-label in MS), and also of DMTs considered of low-efficacy or potency, such as interferons and Copaxone (glatiramer acetate, by Teva Pharmaceuticals).
Their analyses revealed that in RRMS patients, treatment with high-efficacy DMTs was associated with a slower rate of nerve cell loss in the ganglion cell–inner plexiform layer (GCIPL) of the retina, compared to low-efficacy DMTs.
According to Saidha, one particularly relevant observation was that “the rate of retinal GCIPL atrophy in RRMS patients treated with natalizumab [Tysabri] was 0.16, which was actually not different from healthy controls [0.14].”
Of note, the slower rates of retinal atrophy (shrinkage or loss) seen with high-efficacy DMTs resembled their effects on reducing the rate of brain atrophy in RRMS patients as reported in previous studies.
The team also assessed the modulation of retinal atrophy in MS patients treated with rituximab in a study with a median duration of follow-up of about three years. Researchers saw differences in the rates of GCIPL change over time following the start of DMT treatment, suggesting a faster rate of atrophy in the first 12 months of treatment compared to the period afterward.
This was valid for both rituximab (GCIPL loss of 0.69 micrometers in thickness in the first 12 months, and 0.14 in the 12-months post-treatment) and Tysabri (GCIPL loss of 0.45 micrometers in thickness in the first 12 months, and 0.13 in the 12-months post-treatment).
These results suggested that the therapeutic optimization of the effects of these DMTs in retinal atrophy in RRMS patients could potentially take up to 6-12 months.
Researchers also discovered that loss of nerve cells making up two other layers of the retina, the inner nuclear layer (INL) and the outer nuclear layer (ONL), seemed to be more specific to those with progressive forms of MS, including primary and secondary progressive MS.
In a recently published study, the team showed that “progressive MS is independently associated with accelerated rates of INL and ONL thinning that we didn’t see in relapsing MS,” Saidha said.
Interestingly, the team also found that INL and ONL measures in progressive MS patients seem to be unaffected by DMTs.
In fact, no significant differences in the rate of retinal atrophy in any of the three layers analyzed were found between patients with progressive MS who were being treated with either low- or high-efficacy DMTs.
“Low and high potency DMTs do not affect retinal atrophy in progressive MS to the same extent as in RRMS,” Saidha said, noting however that further long-term studies are required to confirm these results in larger progressive MS groups.
Overall, the team concluded that the “rates of GCIPL atrophy are slower in RRMS patients treated with high potency [high-efficacy], as compared to low potency DMTs,” and that “current, conventional, and primarily anti-inflammatory DMTs (whether high or low potency) have not been shown to significantly reduce retinal atrophy in [progressive] MS, unlike RRMS.”
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