Abstract #16: Optical Coherence Tomography As a Clinical Trial Outcome Measure in Multiple Sclerosis: Implications of Treating On-Study Relapses with Intravenous Methylprednisolone

Abstract

Background Optical coherence tomography (OCT) is potentially useful as an outcome measure for clinical trials of neuroprotective therapies in multiple sclerosis (MS). In large-scale clinical trials, it is common for study participants to receive intravenous methylprednisolone (IVMP) as a treatment for relapses while on study. Other anatomic imaging measures such as brain atrophy are subject to transient changes attributed to the anti-inflammatory and water-shifting effects of IVMP, which necessitates delaying imaging studies within a study relative to IVMP dosing. We studied whether IVMP induces short-term changes in OCT metrics including retinal nerve fiber layer thickness (RNFLT) and macular volume (MV). Methods 20 MS patients who received treatment with IVMP for a relapse other than optic neuritis plus 11 controls (patients with MS without relapse or IVMP treatment) were prospectively recruited. Baseline Stratus OCT Fast RNFLT and Fast Macular Volume protocols were performed immediately prior to the first dose of IVMP and repeated 14 days later in steroid-treated patients. Control patients not receiving IVMP underwent follow-up OCT between 14 and 28 days after the baseline scan. A standard protocol of 1000 mg IVMP daily for 3 days followed by a 12-day oral prednisone taper was utilized in all steroid-treated patients. Patients on intermittent pulse IVMP were excluded. Repeated measures mixed statistical models were used to estimate the effect of treatment with IVMP on RNFLT and MV. Results Data from one eye of a control participant were excluded because unilateral primary retinal pathology invalidated the OCT data. All other data were analyzed, including baseline data from one patient in each group who did not complete follow-up. Mean RNFLT at baseline was 87.9 μm in steroid-treated participants and 81.9 μm in control participants. Mean baseline to follow-up change in RNFLT in steroid-treated patients was 2.80 μm (range −4.76 to 17.79 μm). Based on the mixed effects model, the estimated treatment effect of IVMP on baseline to follow-up RNFLT change was 2.14 μm (95% CI = −1.63 to 5.92; p = 0.25). For MV change, the estimated treatment effect was 0.11 mm 3 (95% CI = −0.05 to 0.28; p = 0.17). Conclusions The observed trends suggest any treatment effect of a single course of IVMP on RNFLT and MV is small, and that altering the timing of OCT following treatment of MS relapses within clinical trials may not be necessary. Additional data are needed to confirm this.