Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis

Abstract

Objective-Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON).Methods-Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at three centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed.Results-Among 299 patients (593 eyes) with ≥6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p<0.001; VA: p=0.005). RNFL thinning increased over time, with average losses of 2.9 μm at 2-3 years and 6.1 μm at 3-4.5 years (p<0.001 vs. 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (≥6.6 μm) increased from 11% at 0-1 year to 44% at 3-4.5 years (p<0.001).Interpretation-Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with sub-clinical axonal loss in the anterior visual pathway in MS and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.Address all correspondence to: Dr. Laura J. Balcer, Department of Neurology, 3 E. Gates, 3400 Spruce Street, Philadelphia, PA 19104, 215-349-8072, Fax 215-349-5579, lbalcer@mail.med.upenn.edu. NIH Public Access Author ManuscriptAnn Neurol. Author manuscript; available in PMC 2011 June 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptVisual dysfunction is a common cause of disability and reduced quality of life in multiple sclerosis (MS). 1 The anterior visual pathway is a frequent site for inflammation and demyelination, and axonal degeneration is likely to be a final common pathway to permanent visual loss. [2][3][4][5] Recognized by MS experts as a critical dimension for outcomes assessment, 6 vision has been an important area of investigation. The findings of many studies have supported low-contrast letter acuity as a candidate clinical trial outcome measure. It can capture subtle visual impairment, treatment effects, MRI lesion burden, prolonged visual evoked potential latencies, and quality of life. 1,[7][8][9][10][11][12][13] Many ongoing MS trials have incorporated low-contrast acuity as a tertiary outcome.The emergence of optical coherence tomography (OCT) in MS has brought the anterior visual pathway to the forefront as a model for measuring therapeutic efficacy, particularly for trials involving neuroprotection. 14-32 A reliable marker for axonal loss in MS, 24 retina...

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.…”

“…OCT measurement of inner retinal layers (including the retinal nerve fiber layer (RNFL) has been validated as an accurate measure on axonal loss in anterior visual pathway and has been extensively applied to the investigation of MS 14, 15, 16, 17, 18. Thinning of the RNFL identifies retrograde axonal degeneration following damage to the optic nerve or the optic tract, providing an opportunity to quantitatively assess axonal damage associated with ON.…”

Optical Coherence Tomography in Patients with Relapsing-Remitting Multiple Sclerosis without Optic Neuritis: A 20-Month Longitudinal Study

“…Even so, the MS patients in our cohort had a mean annual rate of average RNFL change of À1.17 (95% CI: À2.27 to 4.74) similar to the results reported in previous studies. 10,11 In conclusion, ON might be present in subclinical (occult) form without typical symptoms or complains. 32,33 Our patients did not have any complaints, especially visual, during the follow-up period and had not been examined by OCT or another technique for early detection of subclinical optic neuritis in the inter-observational period.…”

“…10,16 Talman et al reported progressive RNFL thinning in some patients with MS, even in the absence of ON, during a mean follow-up of 18 months in 299 patients. 10 Another study, which investigated a large cohort of MS patients and healthy controls during a 2-year follow-up, reported greater decreases of RNFL thickness in the MS patients, but statistical differences were found only for the average RNFL thickness and not for other measures such as superior and inferior RNFL. 16 Different studies have reported progressive, agerelated decline of RNFL and macular thicknesses in healthy subjects determined by OCT or other non-invasive imaging in cross-sectional and longitudinal studies during short-term follow-up.…”

“…7 The current OCT technology uses the spectral domain (SD-OCT), which offers improved accuracy and a simple-to-use and cost-effective tool over the previous time-domain OCT. 8 In recent years, OCT has been widely used for visualisation of axonal loss in some neurodegenerative diseases, especially in MS. Several studies demonstrated axonal loss measured by OCT in patients with MS, even in the absence of any reported optic neuritis (ON). [8][9][10] On the other hand, some longitudinal studies found that RNFL thickness measured by OCT did not decrease significantly in MS patients during the follow-up period. 11,12 It is known that RNFL thickness of healthy individuals without any history of neurological or ocular disorders decrease over time.…”