Measuring effects of disease-modifying therapies
What about the effects of disease-modifying therapies? According to Dr. Saidha, there has been a paucity of studies assessing the effects of DMTs on retinal layer thickness, and they are limited by small patient numbers, cross-sectional design, and/or short periods of observation. In a retrospective analysis, he and his associates examined the effects of treatments in relapsing-remitting MS patients at his center who underwent OCT (Neurology. 2017;88[6]:525-32). Over a mean 3 years of follow-up, they examined the effects of glatiramer acetate (Copaxone), natalizumab (Tysabri), and interferon beta-1a subcutaneously (Rebif) and intramuscularly (Avonex). They adjusted for gap time, which is the interval between when a patient started a treatment and when they started to undergo retinal observation with OCT. “This is to try to account for some of the biological changes that might have occurred during that period of time,” he explained. The researchers observed that rates of GCIP atrophy as well as other retinal measures were significantly lower in people treated with natalizumab, relative to all other DMTs. “What I found fascinating was the rate of GCIP atrophy of those on natalizumab was basically the same as healthy controls,” Dr. Saidha said. “It didn’t differ.”
Retinal inflammation and treatment’s impact
Significant inflammation in the unmyelinated retina may inform clinicians about other aspects of MS, he continued. For example, retinal periphlebitis occurs in about 20% of MS patients and may be a marker of CNS inflammation. In addition, intermediate uveitis occurs in about 16% of MS patients, and postmortem studies reveal retinal inflammation with microglia. Specifically, macular microcystoid changes occur in the eyes of about 5% of MS patients and may represent a breakdown of the blood-retinal barrier and inflammation. “Since it’s a dynamic process, increased thickness of the INL in the absence of visible microcystoid changes might occur,” Dr. Saidha said. “We found that baseline INL thickness is predictive of clinico-radiologic disease activity.”
In a separate analysis of 108 MS patients and 40 healthy controls, German researchers evaluated the impact of DMTs on INL volume (Brain. 2016;11[1]:2855-63). They found that higher baseline INL volume correlated with new T2 and GAD lesions over 1 year. The reduction in INL volume was significantly associated with reduced activity, and overall, DMTs reduced INL volume over 6 months. Patients who were not treated, or who were treated and did not achieve NEDA-3 (no evidence of disease activity) did not show reductions in INL volume. They concluded that INL volume might be a novel outcome of DMT treatment.