Tracking changes over time in retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in multiple sclerosis

Abstract

Background: Neurodegeneration plays an important role in permanent disability in multiple sclerosis (MS).

Objective: The objective of this paper is to determine whether progressive neurodegeneration occurs in MS eyes without clinically evident inflammation.

Methods: Retinal nerve fiver layer thickness (RNFLT) and ganglion cell-inner plexiform layer thickness (GCIPT) were measured using Cirrus optical coherence tomography (OCT) in 133 relapsing-remitting MS (RRMS) patients (149 non-optic neuritis (ON), 97 ON eyes, last ON ≥6 months). Ninety-three patients were scanned at two visits. Percentages of abnormal GCIPT vs RNFLT (<5% of machine norms) in cross-sectional data were compared. Relations between RNFLT/GCIPT and MS duration (cross-sectional) and follow-up time (longitudinal) were assessed.

Results: GCIPT was abnormal in more eyes than RNFLT (27% vs 16% p = 0.004 in non-ON, 82% vs 72% p = 0.007 in ON). RNFLT and GCIPT decreased with MS duration by -0.49 µm/yr (p = 0.0001) and -0.36 (p = 0.005) for non-ON; -0.52 (p = 0.003) and -0.41 (p = 0.007) for ON. RNFLT and GCIPT decreased with follow-up time by -1.49 µm/yr (p < 0.0001) and -0.53 (p = 0.004) for non-ON, -1.27 (p = 0.002) and -0.49 (p = 0.04) for ON.

Conclusions: In RRMS eyes without clinically evident inflammation, progressive loss of RNFLT and GCIPT occurred, supporting the need for neuroprotection in addition to suppression of autoimmune responses and inflammation.

Keywords: Multiple sclerosis; ganglion cell inner plexiform layer; neurodegeneration; optic neuritis; optical coherence tomography; retinal nerve fiber layer.

Figure 1

Scatter plot showing RNFLT vs MS duration (A and B) and GCIPT vs MS duration (C and D) for individual no-ON and ON eyes. Each symbol (circles for RNFLT and squares for GCIPT) represents an individual eye of a patient. Open symbols represent no-ON and filled symbols represent ON eyes. The solid lines are the fitted linear regression lines (GEE models). The dashed lines are the average reported normative values for a cohort between 18 and 84 years of age.

Figure 2

Logistic regression analysis showing increase in the probability of abnormalities with MS duration for GCIPT no-ON (A), RNFLT ON (B) and GCIPT ON (C). Circles represent the raw data (0 for normal, 1 for abnormal). The line is the fitted logistic regression curve (GEE model).

Figure 3

Scatter plot showing relationship between the RNFLT change (A and B) and GCIPT change (C and D) with follow-up time for no-ON and ON eyes. Each symbol (circles for RNFLT and squares for GCIPT) represents an individual eye of a patient. Open symbols represent no-ON eyes and filled symbols represent ON eyes. The solid lines are the fitted linear regression lines (GEE models). The dashed lines are the testretest variability limits reported for Cirrus OCT.^,

Figure 4

Scatter plot of MD vs MS duration (A and B) and MD change vs follow-up time (C and D) for no-ON and ON eyes. Each symbol represents an individual eye of a patient. Open symbols represent no-ON eyes and filled symbols represent ON eyes. The solid lines are the fitted linear regression lines (GEE models).