Journal of Neurology

, Volume 265, Issue 4, pp 949–953 | Cite as

In vivo assessment of retinal vessel pathology in amyotrophic lateral sclerosis

  • A. Abdelhak
  • A. Hübers
  • K. Böhm
  • A. C. Ludolph
  • J. Kassubek
  • E. H. Pinkhardt
Original Communication



Changes in skin and muscle small blood vessels (SBVs) and microvascular structures of the brain have been reported in patients with amyotrophic lateral sclerosis (ALS). A direct assessment of brain SBVs in vivo is currently not feasible. Retinal vessels are considered a “mirror” of brain SBVs. In this study, we used optic coherence tomography (OCT)-based measurements to detect changes in retinal blood vessels of ALS patients compared to those of healthy controls.


We analysed Spectralis-OCT images of 34 ALS patients and 20 HCs. The inner wall thickness (IWT), outer wall thickness (OWT), and lumen diameter (LD) of retinal vessels were assessed using intensity-based measurements. In addition, the different retinal layers were analysed using automated segmentation software. The correlations between the various retinal layers and clinical parameters [e.g., disease duration and revised ALS functional rating scale (ALS-FRS-R)] were examined.


The OWT of retinal vessels was higher in ALS patients than in HCs (p = 0.04). There were no differences in the IWT, LD. ALS patients showed a thinning of the outer nuclear layer (ONL) compared to HCs (median 1.63 vs. 1.77, p = 0.002). The whole retinal thickness negatively correlated with the ALS-FRS scale (r = 0.3, p = 0.03).


Our study reports retinal vessel pathology in ALS patients. These changes may be related to those observed in SBVs in skin and muscle biopsies. Furthermore, we report a thinning of the ONL in ALS, revealing a possible affection of rods and cones function in ALS.


ALS OCT Retinal vessels 


Compliance with ethical standards

Conflicts of interest

The authors declare that there is no conflict of interest.

Ethical standards

The study was reviewed by the appropriate ethics committee of the University of Ulm (approval number 36/13) and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki.

Informed consent

Written informed consent for the LP was obtained from all patients participating in this study.


  1. 1.
    Brettschneider J, Del Tredici K, Toledo JB, Robinson JL, Irwin DJ, Grossman M, Suh E, Van Deerlin VM, Wood EM, Baek Y, Kwong L, Lee EB, Elman L, McCluskey L, Fang L, Feldengut S, Ludolph AC, Lee VM, Braak H, Trojanowski JQ (2013) Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 74:20–38CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial “Clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(Suppl):96–107CrossRefPubMedGoogle Scholar
  3. 3.
    Brooks BR, Miller RG, Swash M, Munsat TL, World Federation of Neurology Research Group on Motor Neuron Diseases (2000) El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 1:293–299CrossRefPubMedGoogle Scholar
  4. 4.
    Buckley AF, Bossen EH (2013) Skeletal muscle microvasculature in the diagnosis of neuromuscular disease. J Neuropathol Exp Neurol 72:906–918CrossRefPubMedGoogle Scholar
  5. 5.
    Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci 169:13–21CrossRefPubMedGoogle Scholar
  6. 6.
    Garbuzova-Davis S, Sanberg PR (2014) Blood–CNS barrier impairment in ALS patients versus an animal model. Front Cell Neurosci 8:21CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Gorges M, Muller HP, Lule D, Del Tredici K, Brettschneider J, Keller J, Pfandl K, Ludolph AC, Kassubek J, Pinkhardt EH (2015) Eye movement deficits are consistent with a staging model of pTDP-43 pathology in amyotrophic lateral sclerosis. PLoS One 10:e0142546CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Hubers A, Muller HP, Dreyhaupt J, Bohm K, Lauda F, Tumani H, Kassubek J, Ludolph AC, Pinkhardt EH (2016) Retinal involvement in amyotrophic lateral sclerosis: a study with optical coherence tomography and diffusion tensor imaging. J Neural Transm (Vienna) 123:281–287CrossRefGoogle Scholar
  9. 9.
    Kolde G, Bachus R, Ludolph AC (1996) Skin involvement in amyotrophic lateral sclerosis. Lancet 347:1226–1227CrossRefPubMedGoogle Scholar
  10. 10.
    Kromer R, Buhmann C, Hidding U, Keseru M, Keseru D, Hassenstein A, Stemplewitz B (2016) Evaluation of retinal vessel morphology in patients with Parkinson’s disease using optical coherence tomography. PLoS One 11:e0161136CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Lim JK, Li QX, He Z, Vingrys AJ, Wong VH, Currier N, Mullen J, Bui BV, Nguyen CT (2016) The eye as a biomarker for Alzheimer’s disease. Front Neurosci 10:536CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Moss HE, McCluskey L, Elman L, Hoskins K, Talman L, Grossman M, Balcer LJ, Galetta SL, Liu GT (2012) Cross-sectional evaluation of clinical neuro-ophthalmic abnormalities in an amyotrophic lateral sclerosis population. J Neurol Sci 314:97–101CrossRefPubMedGoogle Scholar
  13. 13.
    Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B (2005) Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures. J Anat 206:319–348CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Ratnayaka JA, Serpell LC, Lotery AJ (2015) Dementia of the eye: the role of amyloid beta in retinal degeneration. Eye (Lond) 29:1013–1026CrossRefGoogle Scholar
  15. 15.
    Rim TH, Choi YS, Kim SS, Kang MJ, Oh J, Park S, Byeon SH (2016) Retinal vessel structure measurement using spectral-domain optical coherence tomography. Eye (Lond) 30:111–119CrossRefGoogle Scholar
  16. 16.
    Ringelstein M, Albrecht P, Sudmeyer M, Harmel J, Muller AK, Keser N, Finis D, Ferrea S, Guthoff R, Schnitzler A, Hartung HP, Methner A, Aktas O (2014) Subtle retinal pathology in amyotrophic lateral sclerosis. Ann Clin Transl Neurol 1:290–297CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Schymick JC, Yang Y, Andersen PM, Vonsattel JP, Greenway M, Momeni P, Elder J, Chio A, Restagno G, Robberecht W, Dahlberg C, Mukherjee O, Goate A, Graff-Radford N, Caselli RJ, Hutton M, Gass J, Cannon A, Rademakers R, Singleton AB, Hardiman O, Rothstein J, Hardy J, Traynor BJ (2007) Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes. J Neurol Neurosurg Psychiatry 78:754–756CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Tewarie P, Balk L, Costello F, Green A, Martin R, Schippling S, Petzold A (2012) The OSCAR-IB consensus criteria for retinal OCT quality assessment. PLoS One 7:e34823CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Volpe NJ, Simonett J, Fawzi AA, Siddique T (2015) Ophthalmic manifestations of amyotrophic lateral sclerosis (an American Ophthalmological Society Thesis). Trans Am Ophthalmol Soc 113:T12PubMedPubMedCentralGoogle Scholar
  20. 20.
    Ward ME, Taubes A, Chen R, Miller BL, Sephton CF, Gelfand JM, Minami S, Boscardin J, Martens LH, Seeley WW, Yu G, Herz J, Filiano AJ, Arrant AE, Roberson ED, Kraft TW, Farese RV Jr, Green A, Gan L (2014) Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD. J Exp Med 211:1937–1945CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Zhong Z, Deane R, Ali Z, Parisi M, Shapovalov Y, O’Banion MK, Stojanovic K, Sagare A, Boillee S, Cleveland DW, Zlokovic BV (2008) ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11:420–422CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of UlmUlmGermany

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