Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis; a longitudinal OCT study

Abstract

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood.

Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS.Methods In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre.

Results: There was a significant increase in INL volume in eyes with new MSON during the study (N = 61/1562, β = 0.01 mm³, p < .001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β = 0.005, p = .025). INL volume was independent of disease progression (β = 0.002 mm³, p = .474).

Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials.

Keywords: Inflammation; inner nuclear layer; multiple sclerosis; optical coherence tomography.

Figure 1.

Flowchart of study design. Of the 903 individuals in the initial database, 785 patients and 92 healthy controls were included in this study. All participants had at least two visits, and a subset also had a third or fourth visit. Longitudinal data on inner nuclear layer (INL) and ganglion cell-inner plexiform layer (GCIPL) volume (at least two visits, minimum follow-up >6 months) was available for all included individuals and peripapillary retinal nerve fibre layer (pRNFL) for 765 patients and 91 healthy controls. IMSVISUAL: International Multiple Sclerosis Visual System Consortium; MS: multiple sclerosis; MSON: multiple sclerosis optic neuritis.

Figure 2.

Relative change in retinal layer thickness with 95% confidence interval (based on generalised estimation equation model) for (a) all multiple sclerosis (MS) and healthy control (HC) eyes and (b) stratified by multiple sclerosis optic neuritis (MSON). GCIPL: ganglion cell-inner plexiform layer; INL: inner nuclear layer; pRNFL: peripapillary retinal nerve fibre layer.