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.

Retinal nerve fiber layer thickness in prematurity is correlated with stage of retinopathy of prematurity

“…Peripapillary RNFL is closely correlated with multiple visual deficits including visual field defect, low-contrast sensitivity, and abnormal electrophysiology results, as well as visual acuity in patients with various disease affecting the optic nerve. [26][27][28][29][30][31] Visual acuity is not the most sensitive marker for optic nerve pathology of various conditions. Because we did not perform tests for visual functions other than visual acuity, we could not determine whether typical features in the peripapillary RNFL distribution observed in preterm patients is related to deficits in other visual functions.…”

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

“…We are familiar with the notion that optic neuritis is more than a demyelination state and that substantial neuroaxonal damage may also occur in the patients, as revealed by recent optical coherence tomography (OCT) studies [15][16][17][18][19] . However, while the functional consequence of this neuroaxonal damage was previously established [20][21][22] , demonstrating reduced visual acuity, contrast acuity and visual quality of life, the functional consequence of demyelination was rarely addressed. Our study was aimed to reveal the functional consequences of demyelination in differentiation from axonal loss and develop clinical tools to quantify these functional changes.…”

Pathophysiological basis of low contrast visual acuity loss in multiple sclerosis

“…The individual relationship between RGC neuroaxonal loss or VEP latency delay with worsening LCVA has been demonstrated previously 14, 15, 24, 27, 38, 39. However, the associations found in our study were generally stronger, possibly due to the use of asymmetry analysis, which eliminates the effect of intersubject variability.…”