Disease-modifying therapies modulate retinal atrophy in multiple sclerosis

Abstract

Objective: To retrospectively investigate whether disease-modifying therapies (DMTs) exert differential effects on rates of retinal atrophy in relapsing-remitting multiple sclerosis (RRMS), as assessed using optical coherence tomography (OCT).Methods: A total of 402 patients with RRMS followed at the Johns Hopkins MS Center who underwent Cirrus-HD OCT were assessed for eligibility. Inclusion criteria included at least 1 year of OCT follow-up and adherence to a single DMT during the period of follow-up. Combined thickness of the ganglion cell 1 inner plexiform (GCIP) and other retinal layers was computed utilizing automated macular segmentation. Retinal thickness changes were analyzed using mixed-effects linear regression.Results: The effects of glatiramer acetate (GA; n 5 48), natalizumab (NAT; n 5 46), and interferonb-1a subcutaneously (IFN SC ; n 5 35) and intramuscularly (IFN IM ; n 5 28) were assessed. Baseline analyses revealed no significant differences between groups in terms of age, sex, optic neuritis history, or follow-up duration. During follow-up, relative to NAT-treated patients, IFN SC -and GAtreated patients exhibited 0.37 mm/y (p , 0.001) and 0.14 mm/y (p 5 0.035) faster rates of GCIP thinning, respectively, adjusting for the interval between initiation of DMT and OCT monitoring (gap time), age, sex, relapses, and disease duration. In the IFN SC group, GCIP thinning was 1.53 mm/y faster during the first year of therapy vs during the time interval afterwards (p , 0.001).Conclusions: Rates of GCIP atrophy in patients with RRMS vary according to DMT utilization. Our findings support OCT for monitoring neurodegenerative treatment effects in the retina, an easily accessible tissue, and as a practical outcome measure in RRMS clinical trials. Neurology ® 2017;88:525-532 GLOSSARY AMT 5 average macular thickness; DMT 5 disease-modifying therapy; GA 5 glatiramer acetate; GCIP 5 ganglion cell 1 inner plexiform layer; HC 5 healthy control; IFN 5 interferon; IFN IM 5 intramuscular interferon-b-1a; IFN SC 5 subcutaneous interferon-b-1a; INL 5 inner nuclear layer; MME 5 microcystic macular edema; MS 5 multiple sclerosis; NAT 5 natalizumab; OCT 5 optical coherence tomography; ON 5 optic neuritis; ONL 5 outer nuclear layer; pRNFL 5 peripapillary retinal nerve fiber layer thickness; RRMS 5 relapsing-remitting multiple sclerosis.Although multiple sclerosis (MS) is conventionally regarded as an autoimmune, inflammatory, demyelinating disorder of the CNS, neurodegeneration resulting from these processes is recognized as the principal substrate of long-term disability.1,2 Currently available disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS) modulate or suppress the immune system, reducing the risk for future inflammation and associated neurodegeneration.3 Accordingly, the effect of DMTs on MRI-derived estimates of brain atrophy is a common outcome in MS trials. [4][5][6][7] Recent studies reveal that retinal atrophy mirrors brain atrophy over time in MS. 8 However, it remains unclear wh...

Optical Coherence Tomography in Multiple Sclerosis

“…For example, patients treated with natalizumab exhibit lower rates of GCL/IPL thinning compared with those on platform injectable therapies. 48…”

Assessing Repair in Multiple Sclerosis: Outcomes for Phase II Clinical Trials

“…This again reinforced the hypothesis that there is ongoing axonal degeneration in MS independent of acute inflammatory demyelinating disease. Recently effect of treatments emerged on OCT measures in patients with MS [84]: the effects of glatiramer acetate, natalizumab interferon-β1a subcutaneously and intramuscularly were assessed retrospectively on 402 patients. Rates of GCIP atrophy in this cohort of patients with RRMS vary according to DMT utilization, with lower GCIP thinning in patients treated with natalizumab.…”

Focal Thickness Reduction of the Ganglion Cell-Inner Plexiform Layer Best Discriminates Prior Optic Neuritis in Patients With Multiple Sclerosis

“…Thinning of the peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) as measured in vivo using spectraldomain optical coherence tomography (SD-OCT) represent optic nerve damage and correlate with neurodegeneration, therapeutic efficacy, and disease progression. [6][7][8][9][10] Recent studies suggested that intereye pRNFL and GCIPL thickness differences [11][12][13] identified a history of unilateral ON, which may demonstrate optic nerve lesions in patients with MS and facilitate the diagnosis. However, intereye thickness differences only provide moderate discrimination power and identify approximately 70% of ON from healthy controls (HC).…”