Q&A: Shiv Saidha, MBBCh, Discusses the Impact of BMI on Retinal Atrophy in MS


New findings published in Multiple Sclerosis Journal indicate that elevated body mass index (BMI) may be associated with accelerated ganglion cell + inner plexiform layer (GCIPL) atrophy in the absence of overt metabolic comorbidities among patients with multiple sclerosis (MS).

“Obesity, a modifiable risk factor, may be associated with accelerated neurodegeneration in MS,” the authors of the study wrote.

They arrived at their conclusion after performing an observational study of 513 participants with MS. Over a median of 4.4 years, patients were followed using serial spectral-domain optical coherence tomography (OCT). Individuals with diabetes, uncontrolled hypertension, eyes with optic neuritis (ON) 6 or fewer months prior to baseline OCT or during follow-up were excluded from the final analysis. Patients were placed into categories of normal weight (BMI: 18.5 kg/m2 to 24.9 kg/m2), overweight (BMI: 25 kg/m2 to 29.9 kg/m2), or obese (BMI: 30 kg/m2).

The results of the study indicated that patients with obesity (n = 146) had accelerated rates of GCIPL atrophy (-0.57% per year) compared with patients with normal weight (n = 214; -0.42% per year). No differences in rates of GCIPL atrophy were observed between patients with overweight (n = 153; -0.47% per year) compared with those with normal weight (-0.42% per year).

Each additional 1 kg/m2 increase in BMI was found to be associated with accelerated GCIPL atrophy (-0.011% per year). The study findings did not change after consideration of age, sex, race, MS subtype, and ON history in multivariable analyses, the researchers noted.

Neurology Learning Network discussed these findings further with study author Shiv Saidha, MBBCh, associate professor of neurology at the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Neurology Learning Network: What prompted you and your colleagues to assess the association between BMI and longitudinal rates of retinal atrophy in multiple sclerosis?

Dr Saidha: Several recent studies have demonstrated that elevated BMI is associated with accelerated brain atrophy and worse disability outcomes in people with MS. Reduction in GCIPL thickness, as quantified by OCT, has been shown to mirror whole brain atrophy, and especially gray matter atrophy, over time in MS. Moreover, GCIPL thickness correlates with, as well as predicts, future global disability in MS. Longitudinal GCIPL thickness evaluation therefore represented an attractive biomarker to further evaluate the relationship between BMI and neurodegeneration in MS, due in part to the excellent reliability and reproducibility of this OCT measure, as well as the rapid and non-invasive nature of OCT as an office-based tool for quantifying neurodegeneration in MS.

NLN: Did you anticipate these findings, or were any of them surprising?

Dr Saidha: Our study findings were in accordance with previous studies demonstrating more rapid disease progression in MS patients with elevated BMI. Most significantly, we demonstrated that patients categorized as obese (BMI ≥30kg/m2) demonstrated faster rates of GCIPL thinning, or in other words, faster rates of retinal neurodegeneration. Our findings are similar to those described by Mowry et al, who observed greater rates of brain atrophy among MS patients on the higher extreme of the BMI spectrum.

While we did not observe similar associations between BMI and other retinal layers assessed, this was unsurprising given the previously demonstrated superiority of GCIPL thickness as compared with other retinal layers in monitoring overall neurodegeneration in MS, as well as the superior reliability and reproducibility of this particular OCT measure.

NLN: Do these findings yet have implications for the impact of weight loss on the management and treatment of MS?

Dr Saidha: Our study was a retrospective observational study, and by limitation our findings are therefore not definitive. Our study neither proves causality nor provides support for weight loss as a definitive therapeutic contribution in MS. Although our findings are suggestive of a relationship between BMI and retinal neuro-axonal atrophy in MS, further studies are needed to investigate whether weight loss would alter clinical outcomes in MS. This being said, there is mounting evidence that vascular health may have an overall impact on the MS disease course, based on associations of worse outcomes in those people with MS who not only have an elevated BMI, but who smoke, have poorly controlled hypertension, diabetes, or dyslipidemia, for example.

NLN: What key takeaways do you hope to leave with neurologists on this topic?

Dr Saidha: In this study, we demonstrated that higher BMI is associated with an accelerated rate of GCIPL atrophy in MS. Since GCIPL atrophy mirrors brain atrophy and disability accumulation in MS, our findings should serve as a reminder that obesity (BMI ≥30 kg/m2), a potentially modifiable factor, among other vascular risk factors, might be associated with more rapid disease progression and worse outcomes in MS.

NLN: What is the next step in terms of future research in this area?

Dr Saidha: A key unanswered question in this area pertains to the biological mechanisms underlying our findings. It is currently unclear whether the observed association between BMI and retinal neuro-axonal loss is due to promotion of processes that are specific to the pathobiology of MS, or whether the mechanisms at play are consequences of general processes related to either overt or occult metabolic syndrome, independent of MS. Nevertheless, since weight is modifiable, an important next step would be to determine whether the management of obesity, and indeed of metabolic comorbidities, improves imaging and clinical outcomes in MS. If our findings are validated in independent prospective studies, weight optimization may be viewed as a complementary strategy in the management of MS.

—Christina Vogt

Filippatou AG, Lambe J, Sotirchos ES, et al. Association of body mass index with longitudinal rates of retinal atrophy in multiple sclerosis. Mult Scler J. Published online April 16, 2020. doi:10.1177/1352458519900942