Advertisement

Journal of Neurology

, Volume 257, Issue 7, pp 1083–1091 | Cite as

A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis

  • Andrew P. D. HendersonEmail author
  • S. A. Trip
  • P. G. Schlottmann
  • D. R. Altmann
  • D. F. Garway-Heath
  • G. T. Plant
  • D. H. Miller
Original Communication

Abstract

Thinning of the retinal nerve fiber layer (RNFL) of clinically unaffected eyes is seen in patients with multiple sclerosis (MS). It is uncertain when this thinning occurs, and whether ongoing RNFL loss can be measured over time with optical coherence tomography (OCT). Using time-domain OCT, we studied 34 patients with progressive MS (16 primary progressive MS, 18 secondary progressive; 14 male; 20 female; mean age at study entry 51 years; median EDSS 6; mean disease duration at study entry 12 years) on two occasions with a median interval of 575 (range 411–895) days apart. Eighteen healthy controls (10 male; eight female; mean age at study entry 46 years) were also studied twice, with a median interval of 656 days (range 398–890). Compared to controls, the patients had significant decreases in the RNFL thickness and macular volume of their clinically unaffected eyes at study entry. No significant decrease in RNFL thickness was observed between baseline and follow-up in either patients or controls. Macular volume declined significantly in patients and controls, but there was no difference in this change between the two groups. The study findings suggest that time domain OCT detects little disease-related ongoing loss of retinal axons in progressive forms of MS and has limited use for monitoring potential neuroprotective therapies at this stage of disease. Further studies are needed using higher-resolution OCT systems and in larger groups of patients, to elucidate the timing and mechanism of RNFL loss that is observed in clinically unaffected nerves in MS.

Keywords

Multiple sclerosis Retina Optical coherence tomography Axonal loss 

Notes

Acknowledgments

We thank all the subjects who took part in this study. We also thank Prof. Paul Matthews for enabling the acquisition of the OCT machine; the Multiple Sclerosis Society of Great Britain and Northern Ireland (grant support to NMR Research Unit); GlaxoSmithKline (unrestricted grant for OCT machine) and Department of Health’s Comprehensive Biomedical Research Centre at University College Hospitals Trust.

References

  1. 1.
    Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5:256–266CrossRefPubMedGoogle Scholar
  2. 2.
    Budenz DL, Anderson DR, Varma R, Schuman J, Cantor L, Savell J, Greenfield DS, Patella VM, Quigley HA, Tielsch J (2007) Determinants of normal retinal nerve fiber layer thickness measured by Stratus OCT. Ophthalmology 114:1046–1052CrossRefPubMedGoogle Scholar
  3. 3.
    Cheng H, Laron M, Schiffman JS, Tang RA, Frishman LJ (2007) The relationship between visual field and retinal nerve fiber layer measurements in patients with multiple sclerosis. Invest Ophthalmol Vis Sci 48:5798–5805CrossRefPubMedGoogle Scholar
  4. 4.
    Costello F, Coupland S, Hodge W, Lorello GR, Koroluk J, Pan YI, Freedman MS, Zackon DH, Kardon RH (2006) Quantifying axonal loss after optic neuritis with optical coherence tomography. Ann Neurol 59:963–969CrossRefPubMedGoogle Scholar
  5. 5.
    Costello F, Hodge W, Pan YI, Eggenberger E, Coupland S, Kardon RH (2008) Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography. Mult Scler 14:893–905CrossRefPubMedGoogle Scholar
  6. 6.
    Costello F, Hodge W, Pan YI, Freedman M, Demeulemeester C (2009) Differences in retinal nerve fiber layer atrophy between multiple sclerosis subtypes. J Neurol Sci 281:74–79CrossRefPubMedGoogle Scholar
  7. 7.
    Drexler W, Fujimoto JG (2008) State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 27:45–88CrossRefPubMedGoogle Scholar
  8. 8.
    Eriksson U, Alm A (2008) Macular thickness decreases with age in normal eyes. A study on the macular thickness map protocol in the Stratus OCT. Br J Ophthalmol 93:1448–1452CrossRefPubMedGoogle Scholar
  9. 9.
    Ferris FL III, Kassoff A, Bresnick GH, Bailey I (1982) New visual acuity charts for clinical research. Am J Ophthalmol 94:91–96PubMedGoogle Scholar
  10. 10.
    Fisher JB, Jacobs DA, Markowitz CE, Galetta SL, Volpe NJ, Nano-Schiavi ML, Baier ML, Frohman EM, Winslow H, Frohman TC, Calabresi PA, Maguire MG, Cutter GR, Balcer LJ (2006) Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology 113:324–332CrossRefPubMedGoogle Scholar
  11. 11.
    Frisén L, Hoyt WF (1974) Insidious atrophy of retinal nerve fibers in multiple sclerosis. Funduscopic identification in patients with and without visual complaints. Arch Ophthalmol 92:91–97PubMedGoogle Scholar
  12. 12.
    Fu L, Matthews PM, De Stefano N, Worsley KJ, Narayanan S, Francis GS, Antel JP, Wolfson C, Arnold DL (1998) Imaging axonal damage of normal-appearing white matter in multiple sclerosis. Brain 121(Pt 1):103–113CrossRefPubMedGoogle Scholar
  13. 13.
    Gordon-Lipkin E, Chodkowski B, Reich DS, Smith SA, Pulicken M, Balcer LJ, Frohman EM, Cutter G, Calabresi PA (2007) Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis. Neurology 69:1603–1609CrossRefPubMedGoogle Scholar
  14. 14.
    Harwerth RS, Wheat JL, Rangaswamy NV (2008) Age-related losses of retinal ganglion cells and axons. Invest Ophthalmol Vis Sci 49:4437–4443CrossRefPubMedGoogle Scholar
  15. 15.
    Henderson AP, Trip SA, Schlottmann PG, Altmann DR, Garway-Heath DF, Plant GT, Miller DH (2008) An investigation of the retinal nerve fibre layer in progressive multiple sclerosis using optical coherence tomography. Brain 131:277–287PubMedGoogle Scholar
  16. 16.
    Hickman SJ, Toosy AT, Miszkiel KA, Jones SJ, Altmann DR, MacManus DG, Plant GT, Thompson AJ, Miller DH (2004) Visual recovery following acute optic neuritis—a clinical, electrophysiological and magnetic resonance imaging study. J Neurol 251:996–1005CrossRefPubMedGoogle Scholar
  17. 17.
    Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA et al (1991) Optical coherence tomography. Science 254:1178–1181CrossRefPubMedGoogle Scholar
  18. 18.
    Ingle GT, Sastre-Garriga J, Miller DH, Thompson AJ (2005) Is inflammation important in early PPMS? A longitudinal MRI study. J Neurol Neurosurg Psychiatry 76:1255–1258CrossRefPubMedGoogle Scholar
  19. 19.
    Jindahra P, Petrie A, Plant GT (2009) Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. Brain 132:628–634CrossRefPubMedGoogle Scholar
  20. 20.
    Kanamori A, Escano MF, Eno A, Nakamura M, Maeda H, Seya R, Ishibashi K, Negi A (2003) Evaluation of the effect of aging on retinal nerve fiber layer thickness measured by optical coherence tomography. Ophthalmologica 217:273–278CrossRefPubMedGoogle Scholar
  21. 21.
    Klistorner A, Arvind H, Nguyen T, Garrick R, Paine M, Graham S, O’Day J, Grigg J, Billson F, Yiannikas C (2008) Axonal loss and myelin in early ON loss in postacute optic neuritis. Ann Neurol 64:325–331CrossRefPubMedGoogle Scholar
  22. 22.
    Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMedGoogle Scholar
  23. 23.
    Losseff NA, Webb SL, O’Riordan JI, Page R, Wang L, Barker GJ, Tofts PS, McDonald WI, Miller DH, Thompson AJ (1996) Spinal cord atrophy and disability in multiple sclerosis. A new reproducible and sensitive MRI method with potential to monitor disease progression. Brain 119(Pt 3):701–708CrossRefPubMedGoogle Scholar
  24. 24.
    Lublin FD, Reingold SC (1996) Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology 46:907–911PubMedGoogle Scholar
  25. 25.
    Ormerod IE, McDonald WI (1984) Multiple sclerosis presenting with progressive visual failure. J Neurol Neurosurg Psychiatry 47:943–946CrossRefPubMedGoogle Scholar
  26. 26.
    Parisi V, Manni G, Spadaro M, Colacino G, Restuccia R, Marchi S, Bucci MG, Pierelli F (1999) Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest Ophthalmol Vis Sci 40:2520–2527PubMedGoogle Scholar
  27. 27.
    Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, Lublin FD, Metz LM, McFarland HF, O’Connor PW, Sandberg-Wollheim M, Thompson AJ, Weinshenker BG, Wolinsky JS (2005) Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Ann Neurol 58:840–846CrossRefPubMedGoogle Scholar
  28. 28.
    Pulicken M, Gordon-Lipkin E, Balcer LJ, Frohman E, Cutter G, Calabresi PA (2007) Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 69:2085–2092CrossRefPubMedGoogle Scholar
  29. 29.
    Riise T, Gronning M, Fernandez O, Lauer K, Midgard R, Minderhoud JM, Nyland H, Palffy G, Poser S, Aarli JA (1992) Early prognostic factors for disability in multiple sclerosis, a European multicenter study. Acta Neurol Scand 85:212–218PubMedCrossRefGoogle Scholar
  30. 30.
    Sepulcre J, Murie-Fernandez M, Salinas-Alaman A, Garcia-Layana A, Bejarano B, Villoslada P (2007) Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS. Neurology 68:1488–1494CrossRefPubMedGoogle Scholar
  31. 31.
    Thompson AJ, Kermode AG, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, McDonald WI (1990) Patterns of disease activity in multiple sclerosis: clinical and magnetic resonance imaging study. BMJ 300:631–634CrossRefPubMedGoogle Scholar
  32. 32.
    Thompson AJ, Kermode AG, Wicks D, MacManus DG, Kendall BE, Kingsley DP, McDonald WI (1991) Major differences in the dynamics of primary and secondary progressive multiple sclerosis. Ann Neurol 29:53–62CrossRefPubMedGoogle Scholar
  33. 33.
    Toledo J, Sepulcre J, Salinas-Alaman A, Garcia-Layana A, Murie-Fernandez M, Bejarano B, Villoslada P (2008) Retinal nerve fiber layer atrophy is associated with physical and cognitive disability in multiple sclerosis. Mult Scler 14:906–912CrossRefPubMedGoogle Scholar
  34. 34.
    Trip SA, Schlottmann PG, Jones SJ, Altmann DR, Garway-Heath DF, Thompson AJ, Plant GT, Miller DH (2005) Retinal nerve fiber layer axonal loss and visual dysfunction in optic neuritis. Ann Neurol 58:383–391CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Andrew P. D. Henderson
    • 1
    • 2
    Email author
  • S. A. Trip
    • 1
    • 2
  • P. G. Schlottmann
    • 4
  • D. R. Altmann
    • 1
    • 3
  • D. F. Garway-Heath
    • 4
  • G. T. Plant
    • 2
  • D. H. Miller
    • 1
  1. 1.NMR Research Unit, Institute of NeurologyUniversity College LondonLondonUK
  2. 2.Department of NeurologyThe National Hospital for Neurology and NeurosurgeryLondonUK
  3. 3.Medical Statistics UnitLondon School of Hygiene and Tropical MedicineLondonUK
  4. 4.Glaucoma Research UnitMoorfields Eye HospitalLondonUK

Personalised recommendations