Axonal loss in the retinal nerve fiber layer in patients with multiple sclerosis

Abstract

Objective

To quantify axonal loss in the retinal nerve fiber layer (RNFL) in patients with multiple sclerosis (MS), with and without a history of optic neuritis, by means of ocular imaging technologies.

Methods

This cross-sectional study enrolled 50 patients with MS and 25 age- and sex-matched healthy controls. All patients underwent neurologic assessment and a complete ophthalmic examination that included visual acuity, visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (GDx) and visual evoked potentials (VEPs). Visual parameters and RNFL measurements were evaluated in MS eyes with a prior optic neuritis episode (MS-ON), with no prior episode (MS-NON) and control subjects.

Results

There were significant differences (p < 0.05, analysis of variance) between MS-ON (n = 25 eyes) and healthy eyes (n = 25 eyes) for all RNFL parameters measured by OCT and GDx. Significant differences between MS-NON (n = 75 eyes) and healthy eyes were also found for most of these parameters. RNFL thickness in the temporal quadrant was the parameter with the greatest differences between groups (71.79 μm in healthy eyes, 60.29 μm in MS-NON and 53.92 μm in MS-ON, p < 0.0005). Although there was a highly significant but moderate correlation between RNFL thickness and duration of the disease, no correlation was observed between RNFL thickness and neurologic impairment (Expanded Disability Status Scale).

Conclusions

Axonal loss was detected not only in MS eyes with a previous acute optic neuritis, but also in MS eyes with no known optic neuritis episode. Structural abnormalities correlate with functional assessments of the optic nerve.

Keywords

axonal loss multiple sclerosis relapsing–remitting

Get full access to this article

View all access options for this article.

References

1 Hauser SL Oksenberg JR . The neurobiology of multiple sclerosis: genes, inflammation, and neurodegeneration. Neuron 2006; 52: 61 – 76 .

2 Imitola J Chitnis T Khoury SJ . Insights into the molecular pathogenesis of progression in multiple sclerosis: potential implications for future therapies. Arch Neurol 2006; 63: 25 – 33 .

3 Smith KJ Kapoor R Hall SM Davies M . Electrically active axons degenerate when exposed to nitric oxide. Ann Neurol 2001; 49: 470 – 476 .

4 Brosnan CF Battistini L Raine CS Dickson DW Casadevall A Lee SC . Reactive nitrogen intermediates in human neuropathology: an overview. Dev Neurosci 1994; 16: 152 – 161 .

5 McDonald WI Barnes D . The ocular manifestations of multiple sclerosis. 1. Abnormalities of the afferent visual system. J Neurol Neurosurg Psychiatry 1992; 55: 747 – 752 .

6 Jaffe GJ Caprioli J . Optical coherence tomography to detect and manage retinal disease and glaucoma. Am J Ophthalmol 2004; 137: 156 – 169 .

7 Paunescu LA Schuman JS Price LL Stark PC Beaton S Ishikawa H . Reproducibility of nerve fiber thickness, macular thickness, and optic nerve head measurements using StratusOCT. Invest Ophthalmol Vis Sci 2004; 45: 1716 – 1724 .

8 Weinreb RN Shakiba S Zangwill L . Scanning laser polarimetry to measure the nerve fiber layer of normal and glaucomatous eyes. Am J Ophthalmol 1995; 119: 627 – 636 .

9 Costello F Coupland S Hodge W Lorello GR Koroluk J Pan YI . Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 2006; 59: 963 – 969 .

10.

10 Danesh-Meyer HV Carroll SC Ku JY Hsiang J Gaskin B Gamble GG . Correlation of retinal nerve fiber layer measured by scanning laser polarimeter to visual field in ischemic optic neuropathy. Arch Ophthalmol 2006; 124: 1720 – 1726 .

11.

11 Steel DH Waldock A . Measurement of the retinal nerve fibre layer with scanning laser polarimetry in patients with previous demyelinating optic neuritis. J Neurol Neurosurg Psychiatry 1998; 64: 505 – 509 .

12.

12 Poser CM Paty DW Scheinberg L McDonald WI Davis FA Ebers GC . New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13: 227 – 231 .

13.

13 Huang D Swanson EA Lin CP Schuman JS Stinson WG Chang W . Optical coherence tomography. Science 1991; 254: 1178 – 1181 .

14.

14 Celesia GG Bodis-Wollner I Chatrian GE Harding GF Sokol S Spekreijse H . Recommended standards for electroretinograms and visual evoked potentials. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol 1993; 87: 421 – 436 .

15.

15 Kalkers NF Bergers E Castelijns JA van Walderveen MA Bot JC Ader HJ . Optimizing the association between disability and biological markers in MS. Neurology 2001; 57: 1253 – 1258 .

16.

16 Trapp BD Peterson J Ransohoff RM Rudick R Mork S Bo L . Axonal transection in the lesions of multiple sclerosis. New Engl J Med 1998; 338: 278 – 285 .

17.

17 Frohman E Costello F Zivadinov R Stuve O Conger A Winslow H . Optical coherence tomography in multiple sclerosis. Lancet Neurol 2006; 5: 853 – 863 .

18.

18 Frisen L Hoyt WF . Insidious atrophy of retinal nerve fibers in multiple sclerosis. Funduscopic identification in patients with and without visual complaints. Arch Ophthalmol 1974; 92: 91 – 97 .

19.

19 Elbol P Work K . Retinal nerve fiber layer in multiple sclerosis. Acta Ophthalmol (Copenh) 1990; 68: 481 – 486 .

20.

20 Honrubia F Calonge B . Evaluation of the nerve fiber layer and peripapillary atrophy in ocular hypertension. Int Ophthalmol 1989; 13: 57 – 62 .

21.

21 Quigley HA Addicks EM . Quantitative studies of retinal nerve fiber layer defects. Arch Ophthalmol 1982; 100: 807 – 814 .

22.

22 Funaki S Shirakashi M Funaki H Yaoeda K Abe H . Relationship between age and the thickness of the retinal nerve fiber layer in normal subjects. Jpn J Ophthalmol 1999; 43: 180 – 185 .

23.

23 Budenz DL Anderson DR Varma R Schuman J Cantor L Savell J . Determinants of normal retinal nerve fiber layer thickness measured by stratus OCT. Ophthalmology 2007; 114: 1046 – 1052 .

24.

24 Jones SJ . Visual evoked potentials after optic neuritis. Effect of time interval, age and disease dissemination. J Neurol 1993; 240: 489 – 494 .

25.

25 Trip SA Schlottmann PG Jones SJ Garway-Heath DF Thompson AJ Plant GT . Quantification of optic nerve head topography in optic neuritis: a pilot study. Br J Ophthalmol 2006; 90: 1128 – 1131 .

26.

26 Trip SA Schlottmann PG Jones SJ Altmann DR Garway-Heath DF Thompson AJ . Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 2005; 58: 383 – 391 .

27.

27 Monteiro ML Medeiros FA Ostroscki MR . Quantitative analysis of axonal loss in band atrophy of the optic nerve using scanning laser polarimetry. Br J Ophthalmol 2003; 87: 32 – 37 .

28.

28 Della MG Bacchetti S Zeppieri M Brusini P Cutuli D Gigli GL . Nerve fibre layer analysis with GDx with a variable corneal compensator in patients with multiple sclerosis. Ophthalmologica 2007; 22: 186 – 189 .

29.

29 Banks MC Robe-Collignon NJ Rizzo JF Pasquale LR . Scanning laser polarimetry of edematous and atrophic optic nerve heads. Arch Ophthalmol 2003; 121: 484 – 490 .

30.

30 Halliday AM . Visual evoked potentials in demyelinating disease. Adv Neurol 1981; 31: 201 – 215 .

31.

31 Weinstock-Guttman B Baier M Stockton R Weinstock A Justinger T Munschauer F . Pattern reversal visual evoked potentials as a measure of visual pathway pathology in multiple sclerosis. Mult Scler 2003; 9: 529 – 534 .

32.

32 Parisi V Manni G Spadaro M Colacino G Restuccia R Marchi S . Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 1999; 40: 2520 – 2527 .

33.

33 Ferguson B Matyszak MK Esiri MM Perry VH . Axonal damage in acute multiple sclerosis lesions. Brain 1997; 120: 393 – 399 .

34.

34 Losseff NA Wang L Lai HM Yoo DS Gawne-Cain ML McDonald WI . Progressive cerebral atrophy in multiple sclerosis. A serial MRI study. Brain 1996; 119: 2009 – 2019 .

35.

35 Sepulcre J Murie-Fernandez M Salinas-Alaman A Garcia-Layana A Bejarano B Villoslada P . Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 2007; 68: 1488 – 1494 .

36.

36 Fisher JB Jacobs DA Markowitz CE Galetta SL Volpe NJ Nano-Schiavi ML . Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 113; 324 – 332 .