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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.