Can retinal thinning predict disability in MS?

Retinal thinning predicts disability in patients newly diagnosed with relapsing multiple sclerosis (MS), an immune-mediated disease affecting the brain and spinal cord, in a new study presented at EAN 2023.

Retinal thinning was associated with a more than fourfold increased risk of an Expanded Disability Status Scale (EDSS) score of ≥3.0, said study investigator Dr Gabriel Bsteh from the Medical University of Vienna in Vienna, Austria. A score of 5 to 9.5 signifies a loss of ambulatory ability.

Using spectral-domain optical coherence tomography (OCT), Bsteh and team assessed the retinal thickness of 230 patients with MS within 3 months of diagnosis and within 9 months of symptom onset. [EAN 2023, abstract OPR-008]

Relevance of OCT

“The OCT tells us how much nerve layer is left,” he said. “The peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell and inner plexiform layer (GCL) are associated with future physical and cognitive disability and brain atrophy and are reliable biomarkers of axonal damage.”

However, it is unknown whether the thickness of the two layers could independently predict disability progression in MS patients. In the study, patients were selected for inclusion based on the 2017 McDonal criteria – they must have evidence of CNS damage that is disseminating in space, or appearing in multiple regions of the nervous system, or evidence of damage disseminating in time or occurring at different points in time.

The mean age of the patients was 30.3 years; 74 percent were female. Follow-up was at least 12 months. The median number of T2 lesions on magnetic resonance imaging was 11. About 59.3 percent of the patients had at least 10 lesions.

At baseline, 27.3 percent were treated with highly effective disease-modifying treatments (DMTs),  59.7 percent with moderately effective DMTs, and 13 percent were not receiving any drug therapy.

“After 8 years of follow-up, a pRNFL thickness of ≤88 µm at baseline was associated with a hazard ratio for EDSS of ≥3.0 vs a thickness of >88 µm of 4.0 (p<0.001),” said Bsteh. “Similarly, a GCL thickness of <77 µm at baseline was associated with a hazard ratio for EDSS ≥3.0 of 5.1 (p<0.001).

There was an association between the risk of EDSS ≥3 and patient age, so with incomplete remission and more lesions on MRI. The use of high-efficacy DMT was associated with a reduced risk of EDSS ≥3.0.

As for progression independent of relapse activity (PIRA), both pRNFL ≤88 µm and GCL <77 µm were significantly associated with PIRA (hazard ratios [HR], 3.1 and 4.1, respectively; p<0.001 for both) compared with greater thickness.

No association with the second clinical attack

“Interestingly, both pRNFL ≤88 µm and GCL <77 µm were not associated with time to second clinical attack which suggests that inflammatory activity may not be relevant to the degree of damage seen on OCT,” said Bsteh.

Dr  Giancarlo Comi, founder and director of the Institute of Experimental Neurology at the Scientific Institute San Raffaele in Milan, Italy said this was surprising as his own research found “an association between OCT measures and second clinical attack.”

As for the limitations, Bsteh said the changes measured on OCT were not specific to multiple sclerosis. Another caveat is that the thickness of the layers can be influenced by a lot of factors, including glaucoma and diabetes, for example. Another limitation is the availability of OCT in practice.