Retinal nerve fiber layer evaluation in multiple sclerosis with spectral domain optical coherence tomography

Abstract

Purpose: Histopathologic studies have reported retinal nerve fiber layer (RNFL) thinning in various neurodegenerative diseases. Attempts to quantify this loss in vivo have relied on time-domain optical coherence tomography (TDOCT), which has low resolution and requires substantial interpolation of data for volume measurements. We hypothesized that the significantly higher resolution of spectral-domain optical coherence tomography (SDOCT) would better detect RNFL changes in patients with multiple sclerosis, and that RNFL thickness differences between eyes with and without optic neuritis might be identified more accurately.

Methods: In this retrospective case series, patients with multiple sclerosis were recruited from the Judith Jaffe Multiple Sclerosis Center at Weill Cornell Medical College in New York. Patients with a recent clinical diagnosis of optic neuritis (less than three months) were excluded. Eyes with a history of glaucoma, optic neuropathy (other than multiple sclerosis-related optic neuritis), age-related macular degeneration, or other relevant retinal and/or optic nerve disease were excluded. Both eyes of each patient were imaged with the Heidelberg Spectralis(®) HRA + OCT. RNFL and macular thickness were measured for each eye using the Heidelberg OCT software. These measurements were compared with validated published normal values, and were modeled as linear functions of duration of disease. The odds of an optic neuritis diagnosis as a function of RNFL and macular thickness were calculated.

Results: Ninety-four eyes were prospectively evaluated using OCT. Ages of patients ranged from 26 to 69 years, with an average age of 39 years. Peripapillary RNFL thinning was demonstrated in multiple sclerosis patients; mean RNFL thickness was 88.5 μm for individuals with multiple sclerosis compared with a reported normal value of 97 μm (P < 0.001). Eyes with a history of optic neuritis had more thinning compared with those without optic neuritis (83.0 μm versus 90.5 μm, respectively, P = 0.02). No significant differences were observed in macular thickness measurements between eyes with and without optic neuritis, nor were macular thickness measurements significantly different from normal values. As a function of multiple sclerosis duration and controlling for age, RNFL thickness was decreased in patients with a duration of multiple sclerosis greater than five years compared with those with a duration less than or equal to one year (P = 0.008).

Conclusions: Patients with a history of multiple sclerosis had RNFL thinning that was detectable on SDOCT. Decreasing RNFL thickness in eyes with optic neuritis was found, and the odds of having optic neuritis were increased significantly with decreasing RNFL thickness. Average RNFL thinning with increasing duration of disease was an excellent predictor of a reported history of optic neuritis. SDOCT retinal imaging may represent a high-resolution, objective, noninvasive, and easily quantifiable in vivo biomarker of the presence of optic neuritis and severity of multiple sclerosis.

Keywords: multiple sclerosis; nerve fiber layer; nerve fiber layer thickness; optic neuritis; optical coherence tomography; spectral-domain optical coherence tomography.

Figure 1

Comparative time-domain and spectral-domain OCT scans of peripapillary RNFL and macula in subjects with multiple sclerosis. In all four panels, OCT B-scans are accompanied by the corresponding fundus images indicating B-scan locations. Upper left: Heidelberg Spectralis^® HRA + OCT Circular B-Scan. Red lines represent inner and outer boundaries of the RNFL. Upper right: Heidelberg Spectralis^® HRA + OCT macular thickness scan composed of 73 horizontal B-scans within the green box area. Top red line represents the vitreoretinal interface (ie, inner boundary of macular thickness measurement). Bottom red line represents retinal pigment epithelium-choroid interface (ie, outer boundary of macular thickness measurement). Lower left: Stratus OCT Circular B-Scan. White lines represent inner and outer boundaries of RNFL. Lower right: Stratus OCT macular thickness scan composed of six radial B-scans. Top white line represents the vitreoretinal interface, and bottom white line represents the inner segment-outer segment interface. Abbreviations: OCT, optical coherence tomography; RNFL, retinal nerve fiber layer.