Ganglion cell loss in relation to visual disability in multiple sclerosis

Abstract

Purpose: We used high-resolution spectral-domain optical coherence tomography (SD-OCT) with retinal segmentation to determine how ganglion cell loss relates to history of acute optic neuritis (ON), retinal nerve fiber layer (RNFL) thinning, visual function, and vision-related quality of life (QOL) in multiple sclerosis (MS).

Design: Cross-sectional study.

Participants: A convenience sample of patients with MS (n = 122; 239 eyes) and disease-free controls (n = 31; 61 eyes). Among MS eyes, 87 had a history of ON before enrollment.

Methods: The SD-OCT images were captured using Macular Cube (200×200 or 512×128) and ONH Cube 200×200 protocols. Retinal layer segmentation was performed using algorithms established for glaucoma studies. Thicknesses of the ganglion cell layer/inner plexiform layer (GCL+IPL), RNFL, outer plexiform/inner nuclear layers (OPL+INL), and outer nuclear/photoreceptor layers (ONL+PRL) were measured and compared in MS versus control eyes and MS ON versus non-ON eyes. The relation between changes in macular thickness and visual disability was also examined.

Main outcome measures: The OCT measurements of GCL+IPL and RNFL thickness; high contrast visual acuity (VA); low-contrast letter acuity (LCLA) at 2.5% and 1.25% contrast; on the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement composite score.

Results: Macular RNFL and GCL+IPL were significantly decreased in MS versus control eyes (P<0.001 and P = 0.001) and in MS ON versus non-ON eyes (P<0.001 for both measures). Peripapillary RNFL, macular RNFL, GCL+IPL, and the combination of macular RNFL+GCL+IPL were significantly correlated with VA (P≤0.001), 2.5% LCLA (P<0.001), and 1.25% LCLA (P≤0.001). Among OCT measurements, reductions in GCL+IPL (P<0.001), macular RNFL (P = 0.006), and the combination (macular RNFL+GCL+IPL; P<0.001) were most strongly associated with lower (worse) NEI-VFQ-25 and 10-Item Supplement QOL scores; GCL+IPL thinning was significant even accounting for macular RNFL thickness (P = 0.03 for GCL+IPL, P = 0.39 for macular RNFL).

Conclusions: We demonstrated that GCL+IPL thinning is most significantly correlated with both visual function and vision-specific QOL in MS, and may serve as a useful structural marker of disease. Our findings parallel those of magnetic resonance imaging studies that show gray matter disease is a marker of neurologic disability in MS.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Figure 1

Vertical spectral-domain optical coherence tomography (OCT) section of right eye macula illustrating retinal segmentation techniques. The software algorithm delineates 4 macular layers: (1) Macular retinal nerve fiber layer (RNFL); (2) ganglion cell layer and inner plexiform layer (GCL+IPL); (3) outer plexiform layer and inner nuclear layer (OPL+INL); and (4) outer nuclear layer and photoreceptor layer (ONL+PRL). The software also calculates segmental thickness in 3 concentric circles with diameters of 1, 3, and 6 mm divided into equal quadrants in a diagonal orientation, similar to the pattern provided in commercial OCT.

Figure 2

Spectral-domain optical coherence tomography thicknesses (in μm) for eyes of patients with multiple sclerosis (MS) versus disease-free controls. Mean values for peripapillary retinal nerve fiber layer (RNFL), macular RNFL, ganglion cell layer, and inner plexiform layer (GCL+IPL), and the combination of macular RNFL+GCL+IPL were significantly lower for MS eyes versus controls (P values are from generalized estimating equation models, accounting for age and within-patient, intereye correlations). INL = inner nuclear layer; ONL = outer nuclear layer; OPL = outer plexiform layer; PRL = photoreceptor layer.

Figure 3

Spectral-domain optical coherence tomography thicknesses (in μm) for eyes of patients with multiple sclerosis (MS) with a history of acute optic neuritis (ON) before study enrollment (MS ON eyes) versus MS eyes without an ON history (MS non-ON eyes). Mean values for peripapillary retinal nerve fiber layer (RNFL), macular RNFL, ganglion cell layer plus inner plexiform layer (GCL+IPL), and the combination of macular RNFL+GCL+IPL were significantly lower for MS ON eyes versus MS non-ON eyes (P values are from generalized estimating equation models, accounting for age and within-patient, intereye correlations). INL = inner nuclear layer; ONL = outer nuclear layer; OPL = outer plexiform layer; PRL = photoreceptor layer.

Figure 4

Scatter plot and fitted linear regression line showing relation of ganglion cell layer plus inner plexiform layer (GCL + IPL) thickness to 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) composite scores and low-contrast acuity at 2.5% level. The regression lines represent fitted values for mean GCL + IPL thickness for each value of NEI-VFQ-25 or low-contrast acuity; the gray shaded areas show the 95% confidence intervals from the standard errors of the predictions for the fitted lines. This graph for all multiple sclerosis eyes illustrates that there are very few outliers with respect to quality of life (QOL) or low-contrast acuity. Linear correlations were significant. Accounting for age and adjusting for within-patient, intereye correlations, the relation of QOL and low-contrast acuity to GCL + IPL thickness was significant (P<0.001, generalized estimating equation models).