New Insights into Ocular Hypertension

Translaminar Pressure Gradient Hypothesis and Pressure-Independent Viewpoint
  • Xiaobin Xie
  • Ningli WangEmail author
Part of the Advances in Visual Science and Eye Diseases book series (AVSED, volume 1)


Ocular hypertension (OHT), the same as “normal-tension glaucoma,” is not a clinical entity [1]. This term usually refers to a situation in which intraocular pressure (IOP) is consistently elevated, usually an IOP of 22 mmHg or higher on two or more occasions without glaucomatous discs or visual field abnormality [2]. This would distinguish them from patients with “elevated” pressure and clear evidence of glaucomatous optic nerve damage [1]. OHT is often considered the opposite end of the glaucoma spectrum to normal-tension glaucoma. OHT is a condition requiring closer observation for the potential development of glaucomatous damage. The 5-year cumulative incidence of primary open-angle glaucoma (POAG) was 9.5% in the observational ocular hypertensive group without treatment intervention [3].


  1. 1.
    Sommer A. Ocular hypertension and normal-tension glaucoma: time for banishment and burial. Arch Ophthalmol. 2011;129(6):785–7.CrossRefGoogle Scholar
  2. 2.
    Perkins ES. The Bedford glaucoma survey. I. Long-term follow-up of borderline cases. Br J Ophthalmol. 1973;57(3):179–85.CrossRefGoogle Scholar
  3. 3.
    Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701–13. discussion 829-730CrossRefGoogle Scholar
  4. 4.
    Morgan WH, Yu DY, Cooper RL, Alder VA, Cringle SJ, Constable IJ. The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient. Invest Ophthalmol Vis Sci. 1995;36(6):1163–72.PubMedGoogle Scholar
  5. 5.
    Jonas JB, Berenshtein E, Holbach L. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci. 2003;44(12):5189–95.CrossRefGoogle Scholar
  6. 6.
    Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology. 2008;115(5):763–8.CrossRefGoogle Scholar
  7. 7.
    Berdahl JP, Fautsch MP, Stinnett SS, Allingham RR. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Invest Ophthalmol Vis Sci. 2008;49(12):5412–8.CrossRefGoogle Scholar
  8. 8.
    Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117(2):259–66.CrossRefGoogle Scholar
  9. 9.
    Ren R, Wang N, Zhang X, Cui T, Jonas JB. Trans-lamina cribrosa pressure difference correlated with neuroretinal rim area in glaucoma. Graefes Arch Clin Exp Ophthalmol. 2011;249(7):1057–63.CrossRefGoogle Scholar
  10. 10.
    Wang N, Xie X, Yang D, et al. Orbital cerebrospinal fluid space in glaucoma: The Beijing Intracranial and Intraocular Pressure (iCOP) Study. Ophthalmology. 2012;119(10):2065–73. e2061CrossRefGoogle Scholar
  11. 11.
    Yang D, Fu J, Hou R, et al. Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys. Invest Ophthalmol Vis Sci. 2014;55(5):3067–73.CrossRefGoogle Scholar
  12. 12.
    Quigley HA, Enger C, Katz J, Sommer A, Scott R, Gilbert D. Risk factors for the development of glaucomatous visual field loss in ocular hypertension. Arch Ophthalmol. 1994;112(5):644–9.CrossRefGoogle Scholar
  13. 13.
    Guy AH, Wiggs JL, Turalba A, Pasquale LR. Translating the low translaminar Cribrosa pressure gradient hypothesis into the clinical Care of Glaucoma. Semin Ophthalmol. 2016;31(1–2):131–9.CrossRefGoogle Scholar
  14. 14.
    Fleischman D, Berdahl JP, Zaydlarova J, Stinnett S, Fautsch MP, Allingham RR. Cerebrospinal fluid pressure decreases with older age. PLoS One. 2012;7(12):e52664.CrossRefGoogle Scholar
  15. 15.
    Xie X, Zhang X, Fu J, et al. Noninvasive intracranial pressure estimation by orbital subarachnoid space measurement: the Beijing intracranial and intraocular pressure (iCOP) study. Crit Care. 2013;17(4):R162.CrossRefGoogle Scholar
  16. 16.
    Smit M, Werner MJ, Lansink-Hartgring AO, Dieperink W, Zijlstra JG, van Meurs M. How central obesity influences intra-abdominal pressure: a prospective, observational study in cardiothoracic surgical patients. Ann Intensive Care. 2016;6(1):99.CrossRefGoogle Scholar
  17. 17.
    Pasquale LR, Willett WC, Rosner BA, Kang JH. Anthropometric measures and their relation to incident primary open-angle glaucoma. Ophthalmology. 2010;117(8):1521–9.CrossRefGoogle Scholar
  18. 18.
    Ramdas WD, Wolfs RC, Hofman A, de Jong PT, Vingerling JR, Jansonius NM. Lifestyle and risk of developing open-angle glaucoma: the Rotterdam study. Arch Ophthalmol. 2011;129(6):767–72.CrossRefGoogle Scholar
  19. 19.
    Berdahl JP, Fleischman D, Zaydlarova J, Stinnett S, Allingham RR, Fautsch MP. Body mass index has a linear relationship with cerebrospinal fluid pressure. Invest Ophthalmol Vis Sci. 2012;53(3):1422–7.CrossRefGoogle Scholar
  20. 20.
    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.CrossRefGoogle Scholar
  21. 21.
    Killer HE, Jaggi GP, Flammer J, Miller NR, Huber AR, Mironov A. Cerebrospinal fluid dynamics between the intracranial and the subarachnoid space of the optic nerve. Is it always bidirectional? Brain. 2007;130(Pt 2):514–20.CrossRefGoogle Scholar
  22. 22.
    Wostyn P, Audenaert K, De Deyn PP. More advanced Alzheimer’s disease may be associated with a decrease in cerebrospinal fluid pressure. Cerebrospinal Fluid Res. 2009;6:14.Google Scholar
  23. 23.
    Guo L, Salt TE, Luong V, et al. Targeting amyloid-beta in glaucoma treatment. Proc Natl Acad Sci U S A. 2007;104(33):13444–9.CrossRefGoogle Scholar
  24. 24.
    Nucci C, Martucci A, Martorana A, Sancesario GM, Cerulli L. Glaucoma progression associated with altered cerebral spinal fluid levels of amyloid beta and tau proteins. Clin Exp Ophthalmol. 2011;39(3):279–81.CrossRefGoogle Scholar
  25. 25.
    Wostyn P, De Groot V, Van Dam D, Audenaert K, De Deyn PP. Senescent changes in cerebrospinal fluid circulatory physiology and their role in the pathogenesis of normal-tension glaucoma. Am J Ophthalmol. 2013;156(1):5–14. e12CrossRefGoogle Scholar
  26. 26.
    Wostyn P, De Groot V, Van Dam D, Audenaert K, Killer HE, De Deyn PP. Fast circulation of cerebrospinal fluid: an alternative perspective on the protective role of high intracranial pressure in ocular hypertension. Clin Exp Optom. 2016;99(3):213–8.CrossRefGoogle Scholar
  27. 27.
    Furlanetto RL, De Moraes CG, Teng CC, et al. Risk factors for optic disc hemorrhage in the low-pressure glaucoma treatment study. Am J Ophthalmol. 2014;157(5):945–52.CrossRefGoogle Scholar
  28. 28.
    Charlson ME, de Moraes CG, Link A, et al. Nocturnal systemic hypotension increases the risk of glaucoma progression. Ophthalmology. 2014;121(10):2004–12.CrossRefGoogle Scholar
  29. 29.
    Leske MC, Wu SY, Hennis A, Honkanen R, Nemesure B, Group BES. Risk factors for incident open-angle glaucoma: the Barbados eye studies. Ophthalmology. 2008;115(1):85–93.CrossRefGoogle Scholar
  30. 30.
    Leske MC, Heijl A, Hyman L, et al. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11):1965–72.CrossRefGoogle Scholar
  31. 31.
    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;113(2):216–21.CrossRefGoogle Scholar
  32. 32.
    Topouzis F, Wilson MR, Harris A, et al. Association of open-angle glaucoma with perfusion pressure status in the Thessaloniki eye study. Am J Ophthalmol. 2013;155(5):843–51.CrossRefGoogle Scholar
  33. 33.
    Jonas JB, Wang N, Wang YX, You QS, Yang D, Xu L. Ocular hypertension: general characteristics and estimated cerebrospinal fluid pressure. The Beijing Eye Study 2011. PLoS One. 2014;9(7):e100533.CrossRefGoogle Scholar
  34. 34.
    Caprioli J, Coleman AL. Blood pressure, perfusion pressure, and glaucoma. Am J Ophthalmol. 2010;149(5):704–12.CrossRefGoogle Scholar
  35. 35.
    Bonomi L, Marchini G, Marraffa M, Bernardi P, Morbio R, Varotto A. Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt study. Ophthalmology. 2000;107(7):1287–93.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Eye Hospital, China Academy of Chinese Medical SciencesBeijingChina
  2. 2.Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
  3. 3.Beijing Ophthalmology & Visual Sciences Key LaboratoryBeijingChina

Personalised recommendations