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WGC-2021

Editors Selection IGR 21-2

Basic Science: Beyond OCT-A: imaging the deep eye vasculature

Ningli Wang
Diya Yang

Comment by Ningli Wang & Diya Yang on:

86280 Diurnal Cycle of Translaminar Pressure in Nonhuman Primates Quantified With Continuous Wireless Telemetry, Jasien JV; Samuels BC; Johnston JM et al., Investigative Ophthalmology and Visual Science, 2020; 61: 37

See also comment(s) by Joel R. Palko


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It has been a decade since the first prospective and retrospective clinical studies1,2 have suggested that glaucoma patients with normal intraocular pressure have significantly lower CSF pressure (CSFp) and a higher trans-lamina cribrosa pressure difference (TLPD) in comparison with normal subjects. More interestingly, with the chronic lowering of CSFp (resulting in increased TLPD) in non-human primates, a glaucoma-like optic neuropathy was induced in those monkeys.3 Assuming that an elevated TLPD is important for glaucomatous optic nerve damage, attempts have been made to quantify the TLPD in human (non-invasively) or in animal studies.4,5

Jasien, Downs and coworkers quantified the TLPD in real time with an implantable wireless telemetry pressure transducer and analyzed the diurnal cycle of TLPD in four rhesus monkeys. Results show that CSFp is significantly higher by an average of 4.8 ± 0.8 mmHg during sleeping hours (P < 0.01). IOP showed a small but significant nocturnal elevation (0.7-1.9 mmHg) in two of the four animals despite the monkeys slept in upright position (P < 0.05). TLPD was significantly lower during sleep (7.1 ± 0.6 mmHg; P < 0.01) than when the animals were awake and active (11.0 ± 0.9 mmHg), driven primarily by the large increase in ICP during sleep.

Given the fact that monkeys slept in a standing position, it is interesting and unexpected to find more significant elevation of CSFp than IOP, thus a significant lowering of TLPD during sleeping hours. The result matches the increase of CSFp reported in humans who slept in the supine position.

This study is important because it showed us a continuous recording of TLPD dynamics in diurnal cycles. Given the fact that monkeys slept in a standing position, it is interesting and unexpected to find more significant elevation of CSFp than IOP, thus a significant lowering of TLPD during sleeping hours. The result matches the increase of CSFp reported in humans who slept in the supine position. As a nocturnal elevation of IOP has been proven in healthy human subjects,6 it may give a plausible hypothesis that CSFp elevation may act as a counter pressure to alleviate the optic nerve head (reduce TLPD) from increased IOP while sleeping. Hence, for glaucoma patients, a deficient CSFp elevation during sleep may also contribute to the pathogenesis of glaucomatous optic neuropathy.

For glaucoma patients, a deficient CSFp elevation during sleep may also contribute to the pathogenesis of glaucomatous optic neuropathy.

Overall, this study given us insights to the physiology of 24-hour IOP, CSFp and TLPD rhythm patterns. In order to improve current glaucoma management, further continuous non-invasive measurement of human TLPD would be taken into exploration.

References

  1. Ren R, Jonas JB, Tian G, et al. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology. 2010;117:259-266.
  2. Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal Fluid Pressure Is Decreased in Primary Open-angle Glaucoma. Ophthalmology. 2008;115:763-768.
  3. 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): 3067-3073.
  4. 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):2065-2073.e1.
  5. Hou R, Zhang Z, Yang D, et al. Intracranial pressure (ICP) and optic nerve subarachnoid space pressure (ONSP) corre- lation in the optic nerve chamber: the Beijing Intracra- nial and Intraocular Pressure (iCOP) study. Brain Res. 2016;1635:201-208.
  6. Liu JH, Bouligny RP, Kripke DF, Weinreb RN. Nocturnal elevation of intraocular pressure is detectable in the sitting position. Invest Ophthalmol Vis Sci. 2003;44(10):4439-4442.


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