Skip to main content

The Relationship Between Cerebrospinal Fluid Pressure and Blood Flow in the Retina and Optic Nerve

  • Chapter
  • First Online:

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

Abstract

Advancements in imaging technologies over the past several decades have allowed for the identification of non-intraocular pressure (IOP) processes involved in glaucomatous optic neuropathy. Perhaps the most commonly cited non-IOP risk factors are impaired ocular circulation and/or faulty vascular regulation and vasospasm [1, 2]. Other important considerations include the possible synergistic interaction between IOP and intracranial pressure (ICP) and their effects on ocular structure and circulation [3]. The ability to assess ICP in glaucoma has been significantly limited by the highly invasive nature of ICP measurements. Recently, the ability to quantify ICP noninvasively has significantly improved, with pilot data suggesting a link between low ICP and glaucoma [4]. Even though the limited data on the topic prevents us from drawing definitive conclusions, the emergence of noninvasive assessment protocols holds great promise to define the pathway of ICP’s involvement in glaucoma. In this article, new data and analysis on cerebrospinal fluid pressure (CSFp) and its impact on optic nerve and retinal microcirculation will be explored alongside the broader implications of ICP in glaucoma. One difficulty in interpreting ICP as a risk factor for the onset and progression of glaucoma is the interplay and possible synergies among IOP, ICP, and the ocular circulation. Advances in physically based mathematical modeling have recently allowed for the exploration of glaucoma risk factor interconnectivity [5–9], providing further insight into glaucoma pathophysiology, and eventually may allow for individualized screening and improved patient-specific treatment options [10]. The concepts of ICP, pilot data, and future paradigms in glaucoma management are presented herein, with a focus on comprehensively understanding the role and impact that ICP may have on glaucomatous optic neuropathy.

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

Buying options

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

Learn about institutional subscriptions

References

  1. Moore D, Harris A, WuDunn D, Kheradiya N, Siesky B. Dysfunctional regulation of ocular blood flow: a risk factor for glaucoma? Clin Ophthalmol. 2008;2(4):849–61.

    PubMed  PubMed Central  Google Scholar 

  2. Moore NA, Harris A, Wentz S, Verticchio Vercellin AC, Parekh P, Gross J, Hussain RM, Thieme C, Siesky B. Baseline retrobulbar blood flow is associated with both functional and structural glaucomatous progression after 4 years. Br J Ophthalmology. 2016; https://doi.org/10.1136/bjophthalmol-2016-308460.

  3. Siaudvytvte L, Janulevicience I, Daveckaite A, Ragauskas A, Bartusis L, Kucinoviene J, Siesky B, Harris A. Literateure review and meta-analysis of translaminar pressure difference in open-angle glaucoma. Eye (Lond). 2015a;29(10):1242–50.

    Article  Google Scholar 

  4. Siaudvytyte L, Januleviciene I, Ragauskas A, Bartusis L, Meiliuniene I, Siesky B, Harris A. The difference in translaminar pressure gradient and neuroretinal rim area in glaucoma and healthy subjects. J Ophthalmol. 2014;2014:937360.

    Article  Google Scholar 

  5. Arciero J, Harris A, Siesky B, Amireskandari A, Gershuny V, Pickrell A, Guidoboni G. Theoretical analysis of vascular regulatory mechanisms contributing to retinal blood flow autoregulation. Invest Ophthalmol Vis Sci. 2013;54(8):5584–93.

    Article  Google Scholar 

  6. Carichino L, Harris A, Guidoboni G, Siesky BA, Abegão Pinto L, Vandewalle E, Olafsdottir OB, Hardarson SH, van Keer K, Stalmans I, Stefánsson E, Arciero JC. A theoretical investigation of the increase in venous oxygen saturation levels in advanced glaucoma patients. J Model Ophthalmol. 2016;1(1):64–87.

    Google Scholar 

  7. Cassani S, Guidoboni G, Janulviciene I, Carichino L, Siesky BA, Tobe LA, Amireskandari A, Baikstiene DP, Harris A. Effect of trabeculectomy on retinal hemodynamics: mathematical modeling of clinical data. In: Causin P, Guidoboni G, Sacco R, Harris A, editors. Integrated Multidisciplinary Approaches in the Study and Care of the Human Eye. Amsterdam: Kugler Publications; 2014. p. 29–36.

    Google Scholar 

  8. Dziubek A, Guidoboni G, Harris A, Hirani AH, Rusjan E, Thistleton W. Effect of ocular shape and vascular geometry on retinal hemodynamics: a computational model. Biomech Model Mechanobiol. 2016;15(4):893–907. [Epub 2015 Oct 7]

    Article  Google Scholar 

  9. Guidoboni G, Harris A, Cassani S, Arciero J, Siesky B, Amireskandari A, Tobe L, Egan P, Januleviciene I, Park J. Intraocular pressure, blood pressure and retinal blood flow autoregulation: a mathematical model to clarify their relationship and clinical relevance. Invest Ophthalmol Vis Sci. 2014a;55(7):4105–18.

    Article  Google Scholar 

  10. Gross JC, Harris A, Siesky BA, Sacco R, Shah A, Guidoboni G. Mathematical modeling for novel treatment approaches to open-angle glaucoma. Expert Rev Ophthalmol. 2017;12:443–55.

    Article  CAS  Google Scholar 

  11. Sadler TW. Langman’s medical embryology. 12th ed: Lipincott Williams & Wilkins; 2012. p. 330–1.

    Google Scholar 

  12. Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016;20(1):129.

    Article  Google Scholar 

  13. Prada D, Harris A, Guidoboni G, Siesky B, Huang AM, Arciero JC. Autoregulation and neurovascular coupling in the optic nerve head. Surv Ophthalmol. 2016a;61(2):164–86.

    Article  Google Scholar 

  14. Harris A, Arend O, Wolf S, Cantor LB, Martin BJ. CO2 dependence of retinal arterial and capillary blood velocity. Acta Ophthalmol Scand. 1995;73(5):421–4.

    Article  CAS  Google Scholar 

  15. Harris A, Zarfati D, Zalish M, Biller J, Sheets CW, Rechtman E, Migliardi R, Garzoli HT. Reduced cerebrovascular blood flow velocities and vasoreactivity in open angle glaucoma. Am J Ophthalmol. 2003;135(2):144–7.

    Article  Google Scholar 

  16. Siesky B, Harris A, Brizendine E, Marques C, Loh J, Mackey J, Overton J, Netland P. Literature review and meta-analysis of topical carbonic anhydrase inhibitors and ocular blood flow. Surv Ophthalmol. 2009;54(1):33–46.

    Article  Google Scholar 

  17. Martinez A, Gonzalez F, Capeans C, Perez R, Sanchez-Salorio M. Dorzolamide effect on ocular blood flow. Invest Ophthalmol Vis Sci. 1999;40(6):1270–5.

    CAS  PubMed  Google Scholar 

  18. Siesky B, Harris A, Kagemann L, Stefansson E, McCranon L, Miller B, Bwatwa J, Regen G, Ehrlich R. Ocular blood flow and oxygen delivery to the retina in primary open-angle glaucoma patients: the addition of dorzolamide to timolol monotherapy. Acta Ophthalmol. 2010;88(1):142–9.

    Article  Google Scholar 

  19. Hosking SL, Harris A, Chung HS, Jonescu-Cuypers CD, Kagemann L, Roff Hilton EJ, Garzozi H. Ocular haemodynamic responses to induced hypercapnia and hyperoxia in glaucoma. Br J Ophthalmol. 2004;88(3):406–11.

    Article  CAS  Google Scholar 

  20. Ho JD, Hu CC, Lin CC. Open angle glaucoma and the risk of stroke development: a 5-yr populaiton-based follow up study. Stroke. 2009;40(8):2685–90.

    Article  Google Scholar 

  21. Doucette LP, Rasnitsyn A, Seifi M, Walter MA. The interactions of genes, age, and environment in glaucoma pathogenesis. Surv Ophthalmol. 2015;60(4):310–26.

    Article  Google Scholar 

  22. Yang D, Cabral D, Gaspard EN, Lipton RB, Rundek T, Derby CA. Cerebral hemodynamics in the elderly: a transcranial doppler study in the Einstein aging study cohort. J Ultrasound Med. 2016;35(9):1907–14.

    Article  Google Scholar 

  23. Krejza J, Mariak Z, Walecki J, Szydlik P, Lewko J, Ustymowicz A. Transcranial color Doppler sonography of basal cerebral arteries in 182 healthy subjects: age and sex variability and normal reference values for blood flow parameters. Am J Roetgenol. 1999;172(1):213–8.

    Article  CAS  Google Scholar 

  24. Harris A, Harris M, Biller J, Garzozi H, Zarfty D, Ciulla TA, Martin B. Aging affects the retrobulbar circulation differently in women and men. Arch Ophthalmol. 2000;118(8):1076–80.

    Article  CAS  Google Scholar 

  25. Ehrlich R, Kheradiya NS, Winston DM, Moore DB, Wirostko B, Harris A. Age-related ocular vascular changes. Graefes Arch Clin Exp Ophthalmol. 2009;247(5):583–91.

    Article  Google Scholar 

  26. Fleischman D, Berdahl P, Zaydlarova J, Stinnett S, Fautsch MP, Allingham RR. Cerebrospinal fluid pressure decreases with older age. PLoS One. 2012;7(12):e52664. Epub 2012 Dec 26

    Article  CAS  Google Scholar 

  27. Harris et al. Association for Research in Vision and Ophthalmology (ARVO). Presentation entitled, ‘Fourier domain optical coherence tomography blood flow assessment in patients with glaucoma: A new blood flow method’. Fort Lauderdale, FL. May 2–6, 2010.

    Google Scholar 

  28. Tielsch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995 Feb;113(2):216–21.

    Google Scholar 

  29. Koustenis A, Harris A, Gross J, Januleviciene I, Shah A, Siesky B. Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research. Br J Ophthalmol. 2017;101(1):16–20. Epub ahead of print

    Article  Google Scholar 

  30. Bonomi L, Marchini G, Marraffa M, Morbio R. The relationship between intraocular pressure and glaucoma in a defined population. Data from the Egna-Neumarkt Glaucoma study. Ophthalmology. 2000;107(7):1287–93.

    Article  CAS  Google Scholar 

  31. Hulsman CA, Vingerling JR, Hofman A, Witteman JC, de Jong PT. Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol. 2007;125(6):805–12.

    Article  Google Scholar 

  32. Leske MC, Connell AM, Wu SY, Hyman LG, Schachat AP. Risk factors for open-angle glaucoma The Barbados Eye Study. Arch Ophthalmol. 1995;113(7):918–24.

    Article  CAS  Google Scholar 

  33. Quigley HA, West SK, Rodriquez J, Munoz B, Klein R, Snyder R. The prevalence of glaucoma in a population-based study of Hispanic subject: Proyecto VER. Arch Ophthalmol. 2001;119(12):1819–26.

    Article  CAS  Google Scholar 

  34. Memarzadeh F, Ying-Lai M, Chung J, Azen SP, Varma R, Los Angeles Latino Eye Study Group. Blood pressure, perfusion pressure, and open-angle glaucoma: the Los Angeles Latino Eye Study. Invest Ophthalmol Vis Sci. 2010;51(6):2872–7.

    Article  Google Scholar 

  35. Zheng Y, Wong TY, Mitchell P, Friedman DS, He M, Aung T. Distribution of ocular perfusion pressure and its relationships with open-angle glaucoma: the Singapore Malay Eye Study. Invest Ophthalmol Vis Sci. 2010;51(7):3399–404.

    Article  Google Scholar 

  36. Deb AK, Kaliaperumal S, Rao VA, Sengupta S. Relationship between systemic hypertension, perfusion pressure, and glaucoma: a comparative study in an adult Indian population. Indian J Ophthalmol. 2014;62(9):917–22.

    Article  Google Scholar 

  37. Tieisch JM, Katz J, Sommer A, Quigley HA, Javitt JC. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113(2):216–21.

    Article  Google Scholar 

  38. De Moraes CG, Liebman JM, Greenfield DS, Gardiner SK, Ritch R, Krupin J, Low-pressure Glaucoma Treatment Study Group. Risk factors for visual field progression in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2012;154(4):702–11.

    Article  Google Scholar 

  39. Leske MC, Heijl A, Hyman L, Bengtsson B, Dong L, Yang Z, EMGT Group. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11):1965–72.

    Article  Google Scholar 

  40. Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B, BEBs Study Group. Risk factors for incident open-angle glaucoma: the Barbados eye studies. Ophthalmology. 2008;115(1):85–93.

    Article  Google Scholar 

  41. Ramdas WD, Wolfs RC, Hofman A, de Jong PT, Vingerling JR, Jansonius NM. Ocular perfusion pressure and the incidence of glaucoma: real effect or artifact? The Rotterdam study. Invest Ophthalmol Vis Sci. 2011;52(9):6875–81.

    Article  Google Scholar 

  42. Topouzis F, Coleman AL, Harris A, Jonescu-Cuypers C, Yu F, Marvoudis L, Anastasopoulos E, Pappas T, Koskosas A, Wilson MR. Association of blood pressure status with the optic disk structure in non-glaucoma subjects: the Thessaloniki Eye Study. Am J Ophthalmol. 2006;142(11):60–7.

    Article  Google Scholar 

  43. Topouzis F, Wilson MR, Harris A, Founti P, Yu F, Anastasopoulos E, Pappas T, Koskosas A, Salonikiou A, Coleman AL. Association of open-angle glaucoma with perfusion pressure status in the Thessaloniki Eye Study. Am J Ophthalmol. 2013;155(5):843–51.

    Article  Google Scholar 

  44. Ren R, Jonas JB, Tian G, Zhen Y, Ma K, Li S, Wang H, Li B, Zhang X, Wang N. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117(2):259–66.

    Article  Google Scholar 

  45. Harris A, Evans D, Martin B, Zalish M, Kagemann L, McCranor L, Garzozi H. Nocturnal blood pressure reduction: effect on retrobulbar hemodynamics in glaucoma. Graefes Arch Clin Exp Ophthalmol. 2002;240(5):372–8. Epub 2002 Apr 16

    Article  Google Scholar 

  46. Raboel PH, Bartek J, Andresen M, Bellander BM, Romner B. Intracranial pressure monitoring: invasive versus non-invasive methods—a review. Crit Care Res Pract. 2012;2012:950393.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Siaudvytvte L, Janulevicience I, Daveckaite A, Ragauskas A, Siesky B, Harris A. Neuroretinal rim area and ocular haemodynamic parameters in patients with normal-tension glaucoma with differing intracranial pressures. Br J Ophthalmol. 2015b;100(8):1134–8.

    Article  Google Scholar 

  48. Jóhannesson G, Eklund A, Lindén C. Intracranial and Intraocular Pressure at the Lamina Cribrosa: Gradient Effects Curr Neurol Neurosci Rep. 2018;18(5):25.

    Google Scholar 

  49. Boltz A, Schmidl D, Werkmeister RM, Lasta M, Kaya S, Palkovits S, Told R, Napora KJ, Popa-Cherecheanu A, Garhöfer G, Schmetterer L. Regulation of optic nerve head blood flow during combined changes in intraocular pressure and arterial blood pressure. J Cereb Blood Flow Metab. 2013;33(12):1850–6. https://doi.org/10.1038/jcbfm.2013.137. Epub 2013 Aug 7

    Article  PubMed  PubMed Central  Google Scholar 

  50. Harris A, Guidoboni G, Arciero JC, Ameriskandari A, Tobe LA, Siesky BA. Ocular hemodynamics and glaucoma: the role of mathematical modeling. Eur J Ophthalmol. 2013;23(2):139–46.

    Article  Google Scholar 

  51. Guidoboni G, Harris A, Carichino L, Arieli Y, Siesky BA. Effect of intraocular pressure on the hemodynamics of the central retinal artery: a mathematical model. Math Biosci Eng. 2014b;11(3):523–46.

    Article  Google Scholar 

  52. Carichino L, Guidoboni G, Siesky BA, Amireskandari A, Januleviciene I, Harris A. Effect of intraocular pressure and cerebrospinal fluid pressure on the blood flow in the central retinal vessels. In: Causin P, Guidoboni G, Sacco R, Harris A, editors. Integrated multidisciplinary approaches in the study and care of the human eye. Amsterdam: Kugler Publications; 2014. p. 59–66.

    Google Scholar 

  53. 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(8):1419–28.

    CAS  PubMed  Google Scholar 

  54. Burgoyne CF. A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma. Exp Eye Res. 2011;93(2):120–32.

    Article  CAS  Google Scholar 

  55. D. Prada, R. Sacco, B. Cockburn, L. Bociu, J. Webster, B. A. Siesky, A. Harris. Influence of tissue viscoelasticity on the optic nerve head perfusion: a mathematical model. In: ARVO 2016 Annual Meeting, Program Number 3558, Poster Board Number A0256, 2016b.

    Google Scholar 

  56. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol. 1983;95(5):673–91.

    Article  CAS  Google Scholar 

  57. Jonas JJ, Mardin CY, Schrehardt US, Naumann GOH. Morphometry of the human lamina cribrosa surface. Invest Ophthalmol Vis Sci. 1991;32(2):401–5.

    CAS  PubMed  Google Scholar 

  58. Crawford Downs J, Roberts MD, Sigal IA. Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism. Exp Eye Res. 2011;93(2):133–40.

    Article  CAS  Google Scholar 

  59. Yong Woo Kim, Byeong Wook Yoo, Jin Wook Jeoung, Hee Chan Kim, Ki Ho Park. Lamina cribrosa pore characteristics in eyes with primary open-angle glaucoma: A swept-source optical coherence tomography study. In ARVO Annual Meeting Abstract, June 2015.

    Google Scholar 

  60. M. J. Girard, E. Birgersson, H. L. Leo, A. Thiery, T. Chuangsuwanich. Factors Influencing Lamina Cribrosa Microcapillary Hemodynamics and Oxygen Concentrations. ARVO 2016 Annual Meeting, Program Number: 4711.

    Google Scholar 

  61. Bociu L, Guidoboni G, Sacco R, Webster JT. Analysis of nonlinear poro-elastic and poro-visco-elastic models. Arch Ration Mech Anal. 2016;222(3):1445–519. [Epub 2016 Jul 14]

    Article  Google Scholar 

  62. Causin P, Guidoboni G, Harris A, Prada D, Sacco R, Terragni S. A poroelastic model for the perfusion of the lamina cribrosa in the optic nerve head. Math Biosci. 2014;257:33–41.

    Article  Google Scholar 

  63. 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(2):540–6.

    Article  Google Scholar 

  64. Palko JR, Iwabe S, Pan X, Agarwal G, Komáromy AM, Liu J. Biomechanical properties and correlation with collagen solubility profile in the posterior sclera of canine eyes with an ADAMTS10 mutation. Invest Ophthalmol Vis Sci. 2013;54(4):2685–95.

    Article  CAS  Google Scholar 

Download references

Disclosures

Dr. Alon Harris would like to disclose that he receives remuneration from CIPLA, AdOM and Shire for serving as a consultant. Dr. Harris also holds an ownership interest in AdOM and Oxymap. All relationships listed above are pursuant to Indiana University’s policy on outside activities. None of the other authors listed have any financial disclosures.

Funding

This work has been partially supported by the NSF DMS-1224195, NIH 1R21EY022101-01A1, a grant from Research to Prevent Blindness (RPB, New York, NY, USA), an Indiana University Collaborative Research Grant of the Office of the Vice President for Research, the Chair Gutenberg funds of the Cercle Gutenberg (France), and the Labex IRMIA (University of Strasbourg, France). The funding parties did not have any role in the study design, collection of data, analysis of data, writing of the manuscript, or decision to submit the manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alon Harris .

Editor information

Editors and Affiliations

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

Harris, A. et al. (2019). The Relationship Between Cerebrospinal Fluid Pressure and Blood Flow in the Retina and Optic Nerve. 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_33

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-2137-5_33

  • 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