Retinal inner nuclear layer thinning is decreased and associates with the clinical outcome in ocrelizumab-treated primary progressive multiple sclerosis

Abstract

Background Ocrelizumab was found to decrease brain atrophy rate in primary progressive multiple sclerosis (PPMS), but no data are currently available on the effect of ocrelizumab on retinal layer thicknesses in the PPMS population. Objective To assess retinal layer changes in ocrelizumab-treated PPMS and test their possible application as biomarkers of therapy response. Methods 36 PPMS patients, treated with ocrelizumab for at least 6 months, and 39 sex- and age-matched healthy controls (HC) were included in a blind, longitudinal study. Spectrum-domain optical coherence tomography (SD-OCT) was performed at study entry (T0) and after 6 (T6) and 12 months (T12). At month 24 (T24), patients were divided into responders (no evidence of 1-year confirmed disability progression, 1y-CDP) and non-responders (evidence of 1y-CDP). Results At T24, 23/36 (64%) patients were considered responders and 13/36 (36%) non-responders. At T0, peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell–inner plexiform layer (GCIPL) and inner retinal layer (IRL) volume were significantly lower in PPMS compared to HC (p = 0.001 for all comparisons). At T6 and T12, non-responders significantly differed in the inner nuclear layer (INL) thinning rate compared to responders (p = 0.005 at both time-points). Conclusions Ocrelizumab significantly slows down INL thinning rate in PPMS responders. The longitudinal analysis of retina layer changes by means of OCT may be a promising prognostic test, and merits further investigations.

Inner Retinal Layer Changes Reflect Changes in Ambulation Score in Patients with Primary Progressive Multiple Sclerosis

“…Additionally, we detected a significant difference in the relative annual change rate of INL volume between PwMS and HC. We emphasize that several authors reported influencing factors on the INL analysis, including physiological variations [ 22 ], clinical MS activity during the observation period [ 23 ], and immunotherapy effects [ 24 ]. In addition, there is an ongoing debate about the INL change rate in relation to age and MS disease duration [ 13 , 25 , 26 , 27 ].…”

Ocrelizumab in Patients with Active Primary Progressive Multiple Sclerosis: Clinical Outcomes and Immune Markers of Treatment Response

“…The clinically meaningful threshold for the reduction in the disability progression rate, regarded as treatment response in the context of active progressive MS, should be explored in future studies that also take into consideration the rate of disability progression before treatment initiation. Other structural biomarkers, such as the rate of retinal inner nuclear layer thinning, assessed with optical coherence tomography (OCT) techniques, are also under evaluation and may collectively contribute to an effective assessment of the neurodegenerative component in progressive MS [ 85 ].…”

Update on recent advances in amyotrophic lateral sclerosis

“…The increasing interest on retinal involvement in neurodegenerative diseases in recent years also includes ALS with evidence that the retinal nerve fiber layer (RNFL) may be reduced, with an asymmetric involvement and correlating with disease progression [210]. However, these results need to be confirmed, since other reports while confirming the presence of retinal involvement, have not found that they correlate with disease duration or severity [211][212][213]. More recent studies have focused also on the autonomic nervous system and skin nerve fibers in ALS patients.…”