Intraocular pressure variations: Causes and clinical significance

doi:10.1016/j.jcjo.2014.07.008

Canadian Journal of Ophthalmology

Volume 49, Issue 6, December 2014, Pages 484-488

https://doi.org/10.1016/j.jcjo.2014.07.008 Get rights and content

Abstract

Reduction of intraocular pressure (IOP) is the only known effective treatment for glaucoma. However, IOP is a highly variable and dynamic parameter, undergoing virtually constant changes from numerous factors, including body position and circadian rhythms. Despite this variability, evidence for the efficacy of IOP reduction in glaucoma is based on studies designed to assess mean IOP and not IOP variations. Post hoc analysis of data from major clinical trials has suggested that IOP variations may be an independent risk factor for the development of glaucoma or glaucomatous progression, at least in some patients, but the evidence is incomplete and further studies are required. In the interim, judicious selection of existing therapies can help to minimize IOP variations. In general, therapies that improve outflow instead of suppressing aqueous humor production result in more stable IOP. However, new technology to allow better monitoring of IOP, ideally in a continuous 24-hour manner, is required to fully understand the role of IOP variations in glaucoma.

Résumé

La réduction de la pression intraoculaire (PIO) est le seul traitement efficace du glaucome actuellement connu. Toutefois, la PIO est un paramètre grandement variable et dynamique, présentant des changements quasi-constants en raison de nombreux facteurs, y compris la position du corps et les rythmes circadiens. Malgré cette variabilité, l’évidence de l’efficacité de la réduction de la PIO dans le traitement du glaucome est basée sur les études d’évaluation de la moyenne de la PIO, et non pas la variabilité de la PIO. L’analyse post-hoc des données des principaux essais cliniques a suggéré que les variations de la PIO pouvaient être un facteur indépendant de risque de développement du glaucome ou de la progression glaucomateuse, au moins chez certains patients, mais l’évidence courante est incomplète et d’autres études sont requises. Entretemps, le choix judicieux des thérapies existantes peut aider à minimiser les variations de la PIO. En général, les thérapies visant à augmenter l’écoulement d’humeur aqueuse plutôt que d’en supprimer sa formation, mènent à des PIO plus stables. Cependant, la nouvelle technologie permettant de mieux suivre la PIO, idéalement de façon constante à travers 24 heures, est requise pour comprendre entièrement le rôle des variations de la PIO dans le glaucome.

Section snippets

Intraocular Pressure Variations in Animals

The intermittent nature of clinical IOP monitoring, involving a single measurement every few months, does not enable the true nature of IOP variability to be detected. To overcome this deficiency, McLaren et al.² used implantable pressure sensors in rabbits to allow continuous telemetric monitoring of IOP. They found that IOP undergoes virtually constant short-term fluctuations, with changes occurring because of systemic pulse pressure, eye position, lid position, breathing patterns, physical

Short-term Intraocular Pressure Fluctuations

Short-term IOP fluctuations in humans can occur for a wide variety of reasons, a few of which are listed in Table 1. In addition to intrinsic fluctuations, measurements of IOP can vary because of numerous sources of error related to measurement technique as well as patient factors.

One source of short-term fluctuations that is of particular interest is the change that occurs with body position. IOP has long been known to vary with body position, increasing from the sitting to supine position.

Clinical Significance of Intraocular Pressure Variations

Evidence for the clinical significance of IOP variations in glaucoma pathogenesis is limited by difficulty in measuring IOP. Current clinical practice involves a brief measurement of IOP for a few seconds every few months while a patient with glaucoma is in the clinic. What happens during the intervening period is largely unknown for most patients. Despite this limitation, existing studies suggest the possibility that IOP variations may be an independent risk factor for glaucoma, at least in

Reducing Intraocular Pressure Variations

Although the evidence supporting the role of IOP variations as an independent risk factor in glaucoma is incomplete, appropriate selection of existing therapies can be used to minimize IOP variability if there is minimal additional risk to the patient.

In particular, medical therapies have markedly differing efficacies during the waking hours compared with the sleeping period. This is likely related to the changes in aqueous humor dynamics that occur at night. Aqueous humor production decreases

Progress Toward Continuous Intraocular Pressure Monitoring in Humans

Although indirect evidence for the significance of IOP variations can be obtained from post hoc analysis of office IOP measurements, better understanding of the role of IOP variations in glaucoma will ultimately require the development and use of continuous IOP monitoring devices in humans. Although this has been a long-standing goal, with efforts spanning over 50 years, recent progress in the field suggests that wide availability of clinical devices may be imminent.⁴⁷

Two basic strategies for

Conclusions

Variations in IOP occur continuously over both short and long time intervals, and with changes in body position and the circadian cycle. Appropriate selection of existing therapies can help to minimize IOP variations. However, the evidence for the role of IOP variation as an independent risk factor in glaucoma is currently mixed, stemming from the inability to measure IOP continuously, the lack of a standard definition for IOP variations, variable patient populations, and the use of

Disclosure

A.J.S. is a consultant and adviser for AcuMEMS Inc, Allergan Inc, Glaukos Corp, and Sensimed AG.

Supported by: This review was supported by the Mayo Foundation for Medical Education and Research in Rochester, Minn., and an unrestricted departmental grant from Research to Prevent Blindness in New York, N.Y. A.J.S. is the recipient of the Robert & Helen Schaub Special Scholar Award from Research to Prevent Blindness.

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To investigate the in vivo effect of scleral buckle surgery on ocular biomechanics and aqueous humor dynamics.
Prospective observational cross-sectional study.
Nine patients with unilateral 360 degree encircling scleral buckles without vitrectomy for rhegmatogenous retinal detachments, between 3 and 39 months postoperative.
All measurements were performed in both eyes of all participants. Intraocular pressure (IOP) was measured in the seated and supine positions using pneumatonometry. Outflow facility was measured using 2-minute weighted pneumatonography. Ocular rigidity coefficient was determined from the Friedenwald equations based on the difference in IOP with and without a weighted tonometer tip. The percentage change in IOP upon transitioning from seated to supine was calculated. Measurements for buckled and nonbuckled eyes were compared using paired Student t test of means.
Sitting and supine IOP and percentage difference between the 2 positions; outflow facility; ocular rigidity coefficient.
Seated IOP was similar between buckled and nonbuckled eyes (16.1 ± 2.5 vs. 16.7 ± 2.7 mmHg; P = 0.5) whereas supine IOP was lower in buckled eyes compared with nonbuckled eyes (18.7 ± 2.6 vs. 21.3 ± 2.5 mmHg; P = 0.008). The percentage increase in IOP upon change in body position from seated to supine was greater in nonbuckled eyes (17.4 ± 9.4% vs. 27.6 ± 9.5%; P = 0.005). Ocular rigidity coefficient was lower in buckled (9.9 × 10^-3 ± 1.4 × 10^-3 μL^-1) vs. nonbuckled eyes (14.4 × 10^-3 ± 3.1 × 10^-3 μL^-1; P = 0.006). Outflow facility was not significantly different in buckled and nonbuckled eyes.
Scleral buckling decreases ocular rigidity but does not affect outflow facility. This change in ocular biomechanics likely results in the attenuated IOP change from seated to supine position. Decreased ocular rigidity may also reduce IOP fluctuations and potentially reduce the risk for glaucoma progression.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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The data showed and confirmed that (1) most of the NTG and healthy control eyes had the peak CLS pattern in the nocturnal period and that the CLS measurements during the acrophase were greater in NTG eyes; (2) 24-hour IOP-related pattern variation was greater in NTG eyes than in healthy controls, and (3) patients with NTG were more likely to assume the decubitus posture during their sleep than were the healthy controls. Intraocular pressure, which reflects the balance between aqueous production and outflow, is known to have a circadian rhythm,12 which is generated by an endogenous clock located in the suprachiasmatic nucleus.13 In healthy eyes, aqueous production is higher during the daytime and lower at night because of the diurnal activity of the sympathetic system.14,15
To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLSs) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma [NTG]) and healthy controls.
Prospective, case-control study.
Thirty eyes of 30 patients with NTG, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects.
Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the 2 groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG.
The IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak), and bathyphase (signal trough) values (millivolt equivalents [mVEq]).
The SDs of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51±26.90 vs. 85.18±29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88±39.96 vs. 106.08±41.49 mVEq, P = 0.004) and acrophase values (277.74±129.80 vs. 190.58±127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. The NTG subjects slept longer in the lateral decubitus posture than the healthy controls (199.1±137.8 vs. 113.2±86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (β = 0.218, P = 0.012) and greater time of decubitus posture during sleep (β = 0.180, P = 0.004) were found to be significantly associated with NTG.
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The results showed an average pressure reduction of 2.3% between the Micro CT and symmetrical cases; also an increment of 3.18% between symmetrical and closed quadrant cases. According to [22,23] an IOP variation of 3% is not significant; however, is not possible to evaluate if this small IOP changes could promote damages in a long period of time and it is important to take into account that patients with glaucoma are sensitive to IOP variations [24]. To the authors’ knowledge, no critical pressure values have been reported in SC.
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: Presented in part at the Glaucoma Management Review Course, 53rd Annual Walter Wright Day, Toronto, Ont., December 6-7, 2013

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Review articleIntraocular pressure variations: Causes and clinical significance

Abstract

Résumé

Section snippets

Intraocular Pressure Variations in Animals

Short-term Intraocular Pressure Fluctuations

Clinical Significance of Intraocular Pressure Variations

Reducing Intraocular Pressure Variations

Progress Toward Continuous Intraocular Pressure Monitoring in Humans

Conclusions

Disclosure

Exp Eye Res

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Surv Ophthalmol

Surv Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Die Spätfolge der Glaukombehandlung bei 76 Privatpatienten von Prof Haab, Zürich

Beitr Augenheilkd

Continuous measurement of intraocular pressure in rabbits by telemetry

Invest Ophthalmol Vis Sci

24-hour IOP telemetry in the nonhuman primate: implant system performance and initial characterization of IOP at multiple timescales

Invest Ophthalmol Vis Sci

Direct-recorded intraocular pressure variations in a human subject

Arch Ophthalmol

The aqueous outflow system as a mechanical pump—evidence from examination of tissue and aqueous movement in human and non-human primates

J Glaucoma

Review article
Intraocular pressure variations: Causes and clinical significance