Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis
Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, et al.;
Commented by , 22 Mar 2006
Optic coherence tomography (OCT) allows evaluation of the retinal nerve fiber layer (RNFL) thickness, which recently have been shown to correlate with axonal loss in the optic nerve (ref. 1). In this way the method may provide direct quantitative information of the neurodegenerative processes in multiple sclerosis (MS).
To relate visual function to nerve RNFL thickness as a surrogate measure of axonal loss in MS. To compare RNFL thickness in MS eyes with a history of optic neuritis (ON), MS eyes without ON history and normal controls.
The authors studied 90 MS patients (180 eyes) and 36 normal controls (72 eyes). RNFL thickness was measured using OCT and vision was tested using sensitive tests for MS related dysfunction: Low contrast letter acuity (Sloan charts) and contrast sensitivity (Pelli-Robson chart) as well as visual acuity (retroilluminated Early Treatment Diabetic Retinopaty charts). Main outcome measures were RNFL thickness measured by OCT and visual tests.
RNFL thickness was significantly reduced in eyes of MS patients (92 mm) compared with controls (105mm) (p<0.001) and reduction was most pronounced in MS ON eyes (85mm) (p<0.001; n=63). Lower visual function scores were associated with reduced overall RNFL thickness in MS eyes (p<0.001).
For each 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mm. RNFL thickness was associated with EDSS score (P=0.02) as well as the MS functional composite score (P=0.001) and furthermore declined with increasing disease duration (P=0.003)
Dr Blinkenberg's comments
The authors show that low-contrast letter acuity and contrast sensitivity measurements are associated with RNFL thickness, and it is recommended that these tests are used as secondary clinical outcome measures in clinical trials.
Furthermore it is recommended that OCT is used for studies of neuroprotective and disease modifying drugs. The authors find no difference between fellow eyes of patients with ON history compared with eyes of patients with no ON history, which support the notion that RNFL reductions in non ON eyes reflect the general neurodegenerative process in MS.
OCT measurements provide a unique opportunity to study naked axons directly within the CNS. The technique seems robust, quick, has low cost, and can be performed by nonphysician personnel.
Conventional MRI techniques (T2, PD and T1 black holes and gadolinium enhancement) provide quantitative information of MS related inflammation and demyelination. Evaluation of neuronal and axonal deterioration have been measured using MRI spectroscopy and diffusion tensor imaging, although these approaches still need refinement in order to provide reliable quantitative data. MRI atrophy measures reflect the final consequence of these processes, but are most relevant in prospective studies with duration of more than two years.
In this way OCT may prove to be a highly relevant surrogate marker of disease progression and neurodegeneration in MS, to be used in trials as well as in clinical routine. The current study actually demonstrates an association with disability scores, which is encouraging with regard to future clinical use, although we still need to see how RNFL reductions is related to cerebral atrophy and other measures of neurodegeneration in different stages of the disease.
1. Trip SA, Schlottmann PG, Jones SJ, Li WY, Garway-Heath DF, Thompson AJ, et al. Optic nerve atrophy and retinal nerve fibre layer thinning following optic neuritis: Evidence that axonal loss is a substrate of MRI-detected atrophy. Neuroimage 2006 Jan 26 (Epub ahead of print)