Skip to main content
SpringerLink
Log in

How to Define a Glaucomatous Optic Neuropathy

  • Chapter
  • First Online:
Book cover Intraocular and Intracranial Pressure Gradient in Glaucoma

Part of the book series: Advances in Visual Science and Eye Diseases ((AVSED,volume 1))

  • 492 Accesses

Abstract

While RGC axonal insult within the ONH is central to glaucomatous vision loss and its manifestations are the source of all current forms of clinical staging (visual field, retinal nerve fiber layer (RNFL) thickness, etc.), we propose that RGC axonal insult is not the pathophysiology that defines the optic neuropathy of glaucoma. In making this statement, we acknowledge the essential need to preserve RGC axons, soma, and their peripheral connections in all glaucoma patients, because preservation of vision is the goal of all glaucoma therapy. However, we also emphasize that, to date, selectively killing RGC soma or axons alone, by whatever mechanism, has not been shown to create a glaucomatous optic neuropathy (i.e., glaucomatous ONH cupping) [1–6]. We propose that the defining pathophysiology of a glaucomatous optic neuropathy is the deformation, remodeling, and mechanical failure of the ONH connective tissues [7]. The primary goal of this report is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Brooks DE, Kallberg ME, Cannon RL, Komaromy AM, Ollivier FJ, Malakhova OE, Dawson WW, Sherwood MB, Kuekuerichkina EE, Lambrou GN. Functional and structural analysis of the visual system in the rhesus monkey model of optic nerve head ischemia. Invest Ophthalmol Vis Sci. 2004;45:1830–40.

    Article  Google Scholar 

  2. Chauhan BC, LeVatte TL, Jollimore CA, Yu PK, Reitsamer HA, Kelly ME, Yu DY, Tremblay F, Archibald ML. Model of endothelin-1-induced chronic optic neuropathy in rat. Invest Ophthalmol Vis Sci. 2004;45:144–52.

    Article  Google Scholar 

  3. Ing E, Ivers KM, Yang H, Gardiner SK, Reynaud J, Cull G, Wang L, Burgoyne CF. Cupping in the monkey optic nerve transection model consists of prelaminar tissue thinning in the absence of posterior laminar deformation. Invest Ophthalmol Vis Sci. 2016;57:2598–611.

    Article  Google Scholar 

  4. Joachim SC, Reinehr S, Kuehn S, Laspas P, Gramlich OW, Kuehn M, Tischoff I, von Pein HD, Dick HB, Grus FH. Immune response against ocular tissues after immunization with optic nerve antigens in a model of autoimmune glaucoma. Mol Vis. 2013;19:1804–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Wax MB, Tezel G, Yang J, Peng G, Patil RV, Agarwal N, Sappington RM, Calkins DJ. Induced autoimmunity to heat shock proteins elicits glaucomatous loss of retinal ganglion cell neurons via activated T-cell-derived fas-ligand. J Neurosci. 2008;28:12085–96.

    Article  CAS  Google Scholar 

  6. Yang D, Fu J, Hou R, Liu K, Jonas JB, Wang H, Chen W, Li Z, Sang J, Zhang Z, Liu S, Cao Y, Xie X, Ren R, Lu Q, Weinreb RN, Wang N. Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys. Invest Ophthalmol Vis Sci. 2014;55:3067–73.

    Article  Google Scholar 

  7. Yang H, Reynaud J, Lockwood H, Williams G, Hardin C, Reyes L, Stowell C, Gardiner SK, Burgoyne CF. The connective tissue phenotype of glaucomatous cupping in the monkey eye -clinical and research implications. Prog Retin Eye Res. 2017;59:1–52.

    Article  CAS  Google Scholar 

  8. Burgoyne CF, Downs JC. Premise and prediction-how optic nerve head biomechanics underlies the susceptibility and clinical behavior of the aged optic nerve head. J Glaucoma. 2008;17:318–28.

    Article  Google Scholar 

  9. Jonas JB, Mardin CY, Schlötzer-Schrehardt U, Naumann GO. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci. 1991;32(2):401–5.

    CAS  PubMed  Google Scholar 

  10. Shaarawy T, Sherwood MB, Hitchings RA, Crowston JG, editors. Glaucoma. 1st ed. London: W.B. Saunders; 2009.

    Google Scholar 

  11. Downs JC, Roberts MD, Burgoyne CF. Mechanical strain and restructuring of the optic nerve head. In: Shaarawy T, Sherwood MB, Hitchings RA, Crowston JG, editors. Glaucoma. 1st ed. London: Saunders; 2009.

    Google Scholar 

  12. Burgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma. Exp Eye Res. 2011;93:120–32.

    Article  CAS  Google Scholar 

  13. Bellezza AJ, Rintalan CJ, Thompson HW, Downs JC, Hart RT, Burgoyne CF. Anterior scleral canal geometry in pressurised (IOP 10) and non-pressurised (IOP 0) normal monkey eyes. Br J Ophthalmol. 2003a;87:1284–90.

    Article  CAS  Google Scholar 

  14. Bellezza AJ, Hart RT, Burgoyne CF. The optic nerve head as a biomechanical structure: initial finite element modeling. Invest Ophthalmol Vis Sci. 2000;41:2991–3000.

    CAS  PubMed  Google Scholar 

  15. Burgoyne C. The morphological difference between glaucoma and other optic neuropathies. J Neuroophthalmol. 2015;35(Suppl 1):S8–S21.

    Article  Google Scholar 

  16. Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res. 2005;24:39–73.

    Article  Google Scholar 

  17. Morgan WH, Yu DY, Alder VA, Cringle SJ, Cooper RL, House PH, Constable IJ. The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure. Invest Ophthalmol Vis Sci. 1998;39:1419–28.

    CAS  PubMed  Google Scholar 

  18. Clark AF. The cell and molecular biology of glaucoma: biomechanical factors in glaucoma. Invest Ophthalmol Vis Sci. 2012;53:2473–5.

    Article  CAS  Google Scholar 

  19. Downs JC. Optic nerve head biomechanics in aging and disease. Exp Eye Res. 2015;133:19–29.

    Article  CAS  Google Scholar 

  20. Eilaghi A, Flanagan JG, Simmons CA, Ethier CR. Effects of scleral stiffness properties on optic nerve head biomechanics. Ann Biomed Eng. 2010;38:1586–92.

    Article  Google Scholar 

  21. Girard MJ, Beotra MR, Chin KS, Sandhu A, Clemo M, Nikita E, Kamal DS, Papadopoulos M, Mari JM, Aung T, Strouthidis NG. In vivo 3-dimensional strain mapping of the optic nerve head following intraocular pressure lowering by trabeculectomy. Ophthalmology. 2016;123(6):1190–200.

    Article  Google Scholar 

  22. Girard MJ, Dahlmann-Noor A, Rayapureddi S, Bechara JA, Bertin BM, Jones H, Albon J, Khaw PT, Ethier CR. Quantitative mapping of scleral fiber orientation in normal rat eyes. Invest Ophthalmol Vis Sci. 2011;52:9684–93.

    Article  Google Scholar 

  23. Girard MJ, Strouthidis NG, Desjardins A, Mari JM, Ethier CR. In vivo optic nerve head biomechanics: performance testing of a three-dimensional tracking algorithm. J R Soc Interface. 2013;10:20130459.

    Article  Google Scholar 

  24. Grytz R, Girkin CA, Libertiaux V, Downs JC. Perspectives on biomechanical growth and remodeling mechanisms in glaucoma. Mech Res Commun. 2012;42:92–106.

    Article  Google Scholar 

  25. Lei Y, Rajabi S, Pedrigi RM, Overby DR, Read AT, Ethier CR. In vitro models for glaucoma research: effects of hydrostatic pressure. Invest Ophthalmol Vis Sci. 2011;52:6329–39.

    Article  Google Scholar 

  26. Sigal IA, Bilonick RA, Kagemann L, Wollstein G, Ishikawa H, Schuman JS, Grimm JL. The optic nerve head as a robust biomechanical system. Invest Ophthalmol Vis Sci. 2012;53:2658–67.

    Article  Google Scholar 

  27. Sigal IA, Ethier CR. Biomechanics of the optic nerve head. Exp Eye Res. 2009;88:799–807.

    Article  CAS  Google Scholar 

  28. Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. Reconstruction of human optic nerve heads for finite element modeling. Technol Health Care. 2005;13:313–29.

    PubMed  Google Scholar 

  29. Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. Modeling individual-specific human optic nerve head biomechanics. Part I: lOP-induced deformations and influence of geometry. Biomech Model Mechanobiol. 2009a;8:85–98.

    Article  Google Scholar 

  30. Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. Modeling individual-specific human optic nerve head biomechanics. Part II: influence of material properties. Biomech Model Mechanobiol. 2009b;8:99–109.

    Article  Google Scholar 

  31. Sigal IA, Grimm JL. A few good responses: which mechanical effects of IOP on the ONH to study? Invest Ophthalmol Vis Sci. 2012;53:4270–8.

    Article  Google Scholar 

  32. Sigal IA, Grimm JL, Schuman JS, Kagemann L, Ishikawa H, Wollstein G. A method to estimate biomechanics and mechanical properties of optic nerve head tissues from parameters measurable using optical coherence tomography. IEEE Trans Med Imaging. 2014;33:1381–9.

    Article  CAS  Google Scholar 

  33. Stewart PS, Jensen OE, Foss AJ. A theoretical model to allow prediction of the CSF pressure from observations of the retinal venous pulse. Invest Ophthalmol Vis Sci. 2014;55:6319–23.

    Article  Google Scholar 

  34. Wang X, Rumpel H, Lim WE, Baskaran M, Perera SA, Nongpiur ME, Aung T, Milea D, Girard MJ. Finite element analysis predicts large optic nerve head strains during horizontal eye movements. Invest Ophthalmol Vis Sci. 2016;57:2452–62.

    Article  Google Scholar 

  35. Zhang L, Albon J, Jones H, Gouget CL, Ethier CR, Goh JC, Girard MJ. Collagen microstructural factors influencing optic nerve head biomechanics. Invest Ophthalmol Vis Sci. 2015;56:2031–42.

    Article  CAS  Google Scholar 

  36. Yang H, Downs JC, Bellezza A, Thompson H, Burgoyne CF. 3-D histomorphometry of the normal and early glaucomatous monkey optic nerve head: prelaminar neural tissues and cupping. Invest Ophthalmol Vis Sci. 2007a;48:5068–84.

    Article  Google Scholar 

  37. Bellezza AJ, Rintalan CJ, Thompson HW, Downs JC, Hart RT, Burgoyne CF. Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma. Invest Ophthalmol Vis Sci. 2003b;44:623–37.

    Article  Google Scholar 

  38. Burgoyne CF, Downs JC, Bellezza AJ, Hart RT. Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve head connective tissues. Invest Ophthalmol Vis Sci. 2004;45:4388–99.

    Article  Google Scholar 

  39. Downs JC, Suh JK, Thomas KA, Bellezza AJ, Hart RT, Burgoyne CF. Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes. Invest Ophthalmol Vis Sci. 2005;46:540–6.

    Article  Google Scholar 

  40. Downs JC, Yang H, Girkin C, Sakata L, Bellezza A, Thompson H, Burgoyne CF. Three-dimensional histomorphometry of the normal and early glaucomatous monkey optic nerve head: neural canal and subarachnoid space architecture. Invest Ophthalmol Vis Sci. 2007;48:3195–208.

    Article  Google Scholar 

  41. Yang H, Downs JC, Girkin C, Sakata L, Bellezza A, Thompson H, Burgoyne CF. 3-D histomorphometry of the normal and early glaucomatous monkey optic nerve head: lamina cribrosa and peripapillary scleral position and thickness. Invest Ophthalmol Vis Sci. 2007b;48:4597–607.

    Article  Google Scholar 

  42. Fortune B, Reynaud J, Hardin C, Wang L, Sigal IA, Burgoyne CF. Experimental glaucoma causes optic nerve head neural rim tissue compression: a potentially important mechanism of axon injury. Invest Ophthalmol Vis Sci. 2016;57:4403–11.

    Article  Google Scholar 

  43. Yang H, Ren R, Lockwood H, Williams G, Libertiaux V, Downs C, Gardiner SK, Burgoyne CF. The connective tissue components of optic nerve head cupping in monkey experimental glaucoma part 1: global change. Invest Ophthalmol Vis Sci. 2015;56:7661–78.

    Article  CAS  Google Scholar 

  44. He L, Yang H, Gardiner SK, Williams G, Hardin C, Strouthidis NG, Fortune B, Burgoyne CF. Longitudinal detection of optic nerve head changes by spectral domain optical coherence tomography in early experimental glaucoma. Invest Ophthalmol Vis Sci. 2014;55:574–86.

    Article  Google Scholar 

  45. Strouthidis NG, Fortune B, Yang H, Sigal IA, Burgoyne CF. Longitudinal change detected by spectral domain optical coherence tomography in the optic nerve head and peripapillary retina in experimental glaucoma. Invest Ophthalmol Vis Sci. 2011;52:1206–19.

    Article  Google Scholar 

  46. Chen CS, Johnson MA, Flower RA, Slater BJ, Miller NR, Bernstein SL. A primate model of nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2008;49:2985–92.

    Article  Google Scholar 

  47. Miller NR, Johnson MA, Nolan T, Guo Y, Bernstein AM, Bernstein SL. Sustained neuroprotection from a single intravitreal injection of PGJ(2) in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2014;55:7047–56.

    Article  CAS  Google Scholar 

  48. Burgoyne CF, Quigley HA, Thompson HW, Vitale S, Varma R. Early changes in optic disc compliance and surface position in experimental glaucoma. Ophthalmology. 1995;102:1800–9.

    Article  CAS  Google Scholar 

  49. Morrison JC, Dorman-Pease ME, Dunkelberger GR, Quigley HA. Optic nerve head extracellular matrix in primary optic atrophy and experimental glaucoma. Arch Ophthalmol. 1990;108:1020–4.

    Article  CAS  Google Scholar 

  50. Quigley HA, Anderson DR. The histologic basis of optic disk pallor in experimental optic atrophy. Am J Ophthalmol. 1977;83:709–17.

    Article  CAS  Google Scholar 

  51. Cioffi GA, Sullivan P. The effect of chronic ischemia on the primate optic nerve. Eur J Ophthalmol. 1999;9(Suppl 1):S34–6.

    Article  Google Scholar 

  52. Cioffi GA, Wang L, Fortune B, Cull G, Dong J, Bui B, Van Buskirk EM. Chronic ischemia induces regional axonal damage in experimental primate optic neuropathy. Arch Ophthalmol. 2004;122:1517–25.

    Article  Google Scholar 

  53. Orgul S, Cioffi GA, Bacon DR, Van Buskirk EM. An endothelin-1-induced model of chronic optic nerve ischemia in rhesus monkeys. J Glaucoma. 1996a;5:135–8.

    CAS  PubMed  Google Scholar 

  54. Cioffi GA, Orgul S, Onda E, Bacon DR, Van Buskirk EM. An in vivo model of chronic optic nerve ischemia: the dose-dependent effects of endothelin-1 on the optic nerve microvasculature. Curr Eye Res. 1995;14:1147–53.

    Article  CAS  Google Scholar 

  55. Orgul S, Cioffi GA, Wilson DJ, Bacon DR, Van Buskirk EM. An endothelin-1 induced model of optic nerve ischemia in the rabbit. Invest Ophthalmol Vis Sci. 1996b;37:1860–9.

    CAS  PubMed  Google Scholar 

  56. Tezel G, Wax MB. The immune system and glaucoma. Curr Opin Ophthalmol. 2004;15:80–4.

    Article  Google Scholar 

  57. Tezel G, Yang X, Luo C, Cai J, Powell DW. An astrocyte-specific proteomic approach to inflammatory responses in experimental rat glaucoma. Invest Ophthalmol Vis Sci. 2012;53:4220–33.

    Article  CAS  Google Scholar 

  58. Grus FH, Joachim SC, Wuenschig D, Rieck J, Pfeiffer N. Autoimmunity and glaucoma. J Glaucoma. 2008;17:79–84.

    Article  Google Scholar 

Download references

Acknowledgments

The text and figures of this manuscript have appeared previously in a Progress in Retinal and Eye Research review of our work: Yang, H., Reynaud, J., Lockwood, H., Williams, G., Hardin, C., Reyes, L., Stowell, C., Gardiner, S.K., Burgoyne, C.F., 2017. The Connective Tissue Phenotype of Glaucomatous Cupping in the Monkey Eye—Clinical and Research Implications. Prog Retin Eye Re.s Accepted for Publication March, 2017 [7]. They have been used with permission and edited for this chapter. The work reported herein has been supported in part by USPHS grants R01EY011610 (CFB) and R01EY021281 (CFB) from the National Eye Institute, National Institutes of Health, Bethesda, Maryland; a grant from the American Health Assistance Foundation, Rockville, Maryland (CFB); a grant from The Whitaker Foundation, Arlington, Virginia (CFB); a Career Development Award (CFB); The Legacy Good Samaritan Foundation, Portland, Oregon; and the Sears Trust for Biomedical Research, Mexico, Missouri.

Author information

Authors and Affiliations

  1. Devers Eye Institute, Optic Nerve Head Research Laboratory, Legacy Research Institute, Portland, OR, USA

    Claude F. Burgoyne

Authors
  1. Claude F. Burgoyne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Claude F. Burgoyne .

Editor information

Editors and Affiliations

  1. Beijing Tongren Hospital, Capital Medical University, Beijing, China

    Ningli Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Burgoyne, C.F. (2019). How to Define a Glaucomatous Optic Neuropathy. In: Wang, N. (eds) Intraocular and Intracranial Pressure Gradient in Glaucoma. Advances in Visual Science and Eye Diseases, vol 1. Springer, Singapore. https://doi.org/10.1007/978-981-13-2137-5_37

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-2137-5_37

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-2136-8

  • Online ISBN: 978-981-13-2137-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation