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Published in: Journal of Neurology 7/2010

01-07-2010 | Original Communication

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

Authors: Andrew P. D. Henderson, S. A. Trip, P. G. Schlottmann, D. R. Altmann, D. F. Garway-Heath, G. T. Plant, D. H. Miller

Published in: Journal of Neurology | Issue 7/2010

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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.
Literature
1.
go back to reference Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5:256–266CrossRefPubMed Barkhof F, Calabresi PA, Miller DH, Reingold SC (2009) Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol 5:256–266CrossRefPubMed
2.
go back to reference 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 114:1046–1052CrossRefPubMed 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 114:1046–1052CrossRefPubMed
3.
go back to reference 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 48:5798–5805CrossRefPubMed 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 48:5798–5805CrossRefPubMed
4.
go back to reference 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 59:963–969CrossRefPubMed 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 59:963–969CrossRefPubMed
5.
go back to reference 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 14:893–905CrossRefPubMed 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 14:893–905CrossRefPubMed
6.
go back to reference 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 281:74–79CrossRefPubMed 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 281:74–79CrossRefPubMed
7.
go back to reference Drexler W, Fujimoto JG (2008) State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 27:45–88CrossRefPubMed Drexler W, Fujimoto JG (2008) State-of-the-art retinal optical coherence tomography. Prog Retin Eye Res 27:45–88CrossRefPubMed
8.
go back to reference 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 93:1448–1452CrossRefPubMed 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 93:1448–1452CrossRefPubMed
9.
go back to reference Ferris FL III, Kassoff A, Bresnick GH, Bailey I (1982) New visual acuity charts for clinical research. Am J Ophthalmol 94:91–96PubMed Ferris FL III, Kassoff A, Bresnick GH, Bailey I (1982) New visual acuity charts for clinical research. Am J Ophthalmol 94:91–96PubMed
10.
go back to reference 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 113:324–332CrossRefPubMed 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 113:324–332CrossRefPubMed
11.
go back to reference 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 92:91–97PubMed 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 92:91–97PubMed
12.
go back to reference 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):103–113CrossRefPubMed 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):103–113CrossRefPubMed
13.
go back to reference 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 69:1603–1609CrossRefPubMed 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 69:1603–1609CrossRefPubMed
14.
go back to reference Harwerth RS, Wheat JL, Rangaswamy NV (2008) Age-related losses of retinal ganglion cells and axons. Invest Ophthalmol Vis Sci 49:4437–4443CrossRefPubMed Harwerth RS, Wheat JL, Rangaswamy NV (2008) Age-related losses of retinal ganglion cells and axons. Invest Ophthalmol Vis Sci 49:4437–4443CrossRefPubMed
15.
go back to reference 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 131:277–287PubMed 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 131:277–287PubMed
16.
go back to reference 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 251:996–1005CrossRefPubMed 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 251:996–1005CrossRefPubMed
17.
go back to reference 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 254:1178–1181CrossRefPubMed 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 254:1178–1181CrossRefPubMed
18.
go back to reference Ingle GT, Sastre-Garriga J, Miller DH, Thompson AJ (2005) Is inflammation important in early PPMS? A longitudinal MRI study. J Neurol Neurosurg Psychiatry 76:1255–1258CrossRefPubMed Ingle GT, Sastre-Garriga J, Miller DH, Thompson AJ (2005) Is inflammation important in early PPMS? A longitudinal MRI study. J Neurol Neurosurg Psychiatry 76:1255–1258CrossRefPubMed
19.
go back to reference Jindahra P, Petrie A, Plant GT (2009) Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. Brain 132:628–634CrossRefPubMed Jindahra P, Petrie A, Plant GT (2009) Retrograde trans-synaptic retinal ganglion cell loss identified by optical coherence tomography. Brain 132:628–634CrossRefPubMed
20.
go back to reference 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 217:273–278CrossRefPubMed 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 217:273–278CrossRefPubMed
21.
go back to reference 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 64:325–331CrossRefPubMed 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 64:325–331CrossRefPubMed
22.
go back to reference Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed Kurtzke JF (1983) Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 33:1444–1452PubMed
23.
go back to reference 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):701–708CrossRefPubMed 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):701–708CrossRefPubMed
24.
go back to reference 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 46:907–911PubMed 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 46:907–911PubMed
25.
go back to reference Ormerod IE, McDonald WI (1984) Multiple sclerosis presenting with progressive visual failure. J Neurol Neurosurg Psychiatry 47:943–946CrossRefPubMed Ormerod IE, McDonald WI (1984) Multiple sclerosis presenting with progressive visual failure. J Neurol Neurosurg Psychiatry 47:943–946CrossRefPubMed
26.
go back to reference 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 40:2520–2527PubMed 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 40:2520–2527PubMed
27.
go back to reference 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 58:840–846CrossRefPubMed 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 58:840–846CrossRefPubMed
28.
go back to reference Pulicken M, Gordon-Lipkin E, Balcer LJ, Frohman E, Cutter G, Calabresi PA (2007) Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 69:2085–2092CrossRefPubMed Pulicken M, Gordon-Lipkin E, Balcer LJ, Frohman E, Cutter G, Calabresi PA (2007) Optical coherence tomography and disease subtype in multiple sclerosis. Neurology 69:2085–2092CrossRefPubMed
29.
go back to reference 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 85:212–218PubMedCrossRef 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 85:212–218PubMedCrossRef
30.
go back to reference 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 68:1488–1494CrossRefPubMed 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 68:1488–1494CrossRefPubMed
31.
go back to reference 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 300:631–634CrossRefPubMed 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 300:631–634CrossRefPubMed
32.
go back to reference 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 29:53–62CrossRefPubMed 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 29:53–62CrossRefPubMed
33.
go back to reference 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 14:906–912CrossRefPubMed 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 14:906–912CrossRefPubMed
34.
go back to reference 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 58:383–391CrossRefPubMed 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 58:383–391CrossRefPubMed
Metadata
Title
A preliminary longitudinal study of the retinal nerve fiber layer in progressive multiple sclerosis
Authors
Andrew P. D. Henderson
S. A. Trip
P. G. Schlottmann
D. R. Altmann
D. F. Garway-Heath
G. T. Plant
D. H. Miller
Publication date
01-07-2010
Publisher
Springer-Verlag
Published in
Journal of Neurology / Issue 7/2010
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-010-5467-x

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