72

Twenty-Four–Hour Intraocular Pressure Monitoring in Glaucoma

Gene Kim, MD; Brian J. Song, MD, MPH; and Lama A. Al-Aswad, MD, MPH

Glaucoma is classically defined as an optic neuropathy leading to progressive visual field loss. Historically, glaucoma was often described as high pressure in the eye leading to blindness if left untreated.^1–3 However, it is now well established that glaucoma is not simply a condition of elevated intraocular pressure (IOP). Multiple risk factors (eg, age, race, family history) have been associated with glaucoma, but of these, only IOP is currently modifiable. Though elevated IOP is a significant risk factor associated with glaucoma development, it is now known that glaucoma can occur at any level of IOP. Furthermore, fluctuations in IOP have been identified as a potentially greater risk factor for visual field loss than an elevated mean IOP itself.⁴ Until the development of direct neuroprotective or neuroregenerative treatments, IOP remains the only modifiable and effective target for glaucoma therapy.^5–9 Consequently, the accurate assessment and understanding of IOP and its diurnal fluctuations are essential for both diagnosis and monitoring when evaluating the efficacy of treatment in patients with glaucoma.¹⁰ Recent advances in technology have allowed for novel approaches to monitor IOP over time in glaucoma patients, and more advanced methods that are currently under development can be expected in the near future.

CIRCADIAN VARIATIONS IN INTRAOCULAR PRESSURE

Twenty-four-hour measurements of IOP have shown that IOP tends to fluctuate throughout the course of the day in all persons.^11–15 However, it is believed that patients with ocular hypertension and glaucomatous disease experience greater fluctuations in IOP than those with normal eyes.¹⁶ Both short-term and long-term factors can affect the variability of the diurnal IOP curve. Short-term factors such as eating and drinking can not only increase one’s overall fluid volume, but the change in osmolarity that occurs (depending on what is consumed) can also cause a rise in IOP.¹⁷ In addition, changes in blood pressure and posture have also been shown to affect IOP.^17–19 As body position changes, shifts in body fluids can alter ocular hemodynamics and perfusion pressure.¹⁸ Furthermore, maneuvers that increase intrathoracic pressure (eg, Valsalva) can also cause elevations in IOP.²⁰ Over the long term, IOP seems to be correlated with diurnal cortisol levels, as aqueous production is highest in the morning and trends downward throughout the day.²¹ There is also limited evidence that IOP may undergo seasonal fluctuations as well.²²

Previous studies have shown that IOP tends to be highest in the morning hours in both normal and glaucoma patients.²³ This peak appears to be followed by a steady decline throughout the day. IOP then peaks again during the nocturnal period, possibly because of the change in body position from upright to supine, despite the decreased production of aqueous humor during this time period.^19,24 Figure 72-1 depicts the 24-hour IOP curves in the sitting and supine positions in healthy, young individuals. In a study utilizing self-tonometry in both normal participants and patients with glaucoma, Wilensky and colleagues²⁵ found that the highest pressures were recorded outside of normal clinic hours (ie, between 5:00 PM and 8:00 AM) in approximately half of all cases. One possible explanation for this finding may be the increase in episcleral venous pressure that occurs while in the supine sleeping position.²⁶ As a result, decreasing episcleral venous pressure has been proposed as a potential target for developing new therapies for these patients.18 However, 2 studies^27,28 examining supine IOPs found that nocturnal IOPs were higher than diurnal IOPs in healthy young individuals, implying that the nocturnal pressure spike cannot be completely explained by body positioning. Conversely, these same studies also showed that diurnal IOP may actually be higher than the nocturnal IOP in patients with glaucoma. It should be noted, however, that all such studies²⁹ that examine 24-hour diurnal fluctuations in IOP assume that awakening the patient from sleep to measure IOP does not otherwise alter the normal physiologic fluctuations in IOP.

CORNEAL BIOMECHANICS AND INTRAOCULAR PRESSURE

Central corneal thickness (CCT) is a well-established confounding factor that can impact the accuracy of applanation tonometry.³⁰ While thinner corneas tend to lead to an underestimation of true IOP, eyes with anatomically thicker corneas lead to an overestimation in IOP measurements. The Ocular Hypertension Treatment Study¹⁰ highlighted the importance of CCT of corneal thickness by demonstrating an inverse relationship between CCT and the risk of developing glaucoma. Interestingly, it has been found that CCT also follows a diurnal pattern.³¹ Like IOP, CCT is highest in the morning upon awakening and tends to decrease throughout the day. As a result, it is unclear what degree of measured diurnal IOP fluctuations are due to true variations in IOP vs variations in CCT. In addition to CCT, however, corneal biomechanics encompass other properties, such as viscosity, elasticity, and hydration, that can influence IOP measurement and evaluation.³²

The concept of corneal hysteresis (CH), which can be likened to corneal stiffness, has been postulated as a potentially more important biomechanical property than CCT with regard to its effect on IOP measurements during applanation tonometry.^33–36 CH is the difference between the force-in and force-out applanation pressures using a metered air pulse from a device called an Ocular Response Analyzer (ORA; Reichert Technologies).^37,38 While thicker corneas tend to be more rigid, there are exceptions, such as in Fuchs’ dystrophy where the cornea is thicker than normal but biomechanically less rigid.^38,39 As a result, CH may be a more useful measure of corneal resistance than CCT.³⁷ A second property, corneal resistance factor, is defined as a linear function of the 2 peak pressures measured by the ORA and reflects corneal elasticity, whereas CH is more comparable to corneal viscosity.³⁸ As with CCT, there is a significant inverse relationship between IOP and CH.⁴⁰ Though it is still unclear whether people with thinner and/or less rigid corneas have a corresponding defect in structural integrity that predisposes them to glaucomatous optic nerve damage, increasing evidence shows a correlation between decreased CCT and CH with glaucoma⁴¹ with multiple reports^42–45 in the literature now demonstrating an association between CH and visual field severity and progression.

IMPLICATIONS OF DIURNAL VARIATIONS IN INTRAOCULAR PRESSURE

In other organ systems, including the eye, the human body demonstrates a remarkable ability to adapt to chronic changes to varying degrees. For example, chronic systemic hypertension is associated with the development of atherosclerosis and other changes, such as left ventricular hypertrophy, but the majority of these patients tend to be asymptomatic for long periods of time. Over the course of many years, these alterations eventually lead to end-organ dysfunction, such as heart failure, renal failure, or retinopathy. In the setting of acute hypertensive crisis, however, patients are often symptomatic with complaints of blurry vision, headaches, and mental status changes, in part due to the body’s inability to adapt to such an acute elevation in pressure.

In this regard, the concept of IOP and its role in glaucoma is analogous. The vast majority of chronic glaucoma patients do not experience pain or other symptoms as the eye trends to a higher IOP over a prolonged period of time. Most patients are unaware of their peripheral vision loss as elevated IOP causes apoptosis of retinal ganglion cells over time, and many patients with glaucoma retain good central vision even with moderate or advanced disease. It is usually during the acute glaucomas (eg, acute angle closure, neovascular) that patients may actually complain of symptoms such as pain and photophobia, in part because the eye has not had time to adapt to the sudden and dramatic increase in IOP that occurs in these conditions. Consequently, the body (and, in this case, the eye) does not appear to tolerate abrupt loading and unloading changes in pressure well. For these reasons, it is not surprising that fluctuations in IOP have been identified as a significant independent risk factor for glaucomatous vision loss compared to elevated mean IOP alone in some studies.4,46–49

While the evidence to suggest that fluctuations in IOP are truly an independent risk factor for visual field progression is somewhat debatable, a growing number of studies seem to suggest that this is the case. In a review by Singh and Shrivastava,²⁴ the authors indicate that the severity of disease or the level of IOP may actually determine the magnitude of fluctuations as opposed to the fluctuations being the cause of worsening disease.²⁴ While studies have demonstrated that patients with glaucoma tend to experience larger fluctuations in IOP than healthy individuals, it is unclear whether larger variations in IOP are a cause or a consequence of glaucomatous disease.^16,24 Prospective studies and the development of better tools to measure IOP fluctuations are needed to understand the implications of diurnal IOP variations in the development and progression of glaucoma.

The challenges of measuring and managing IOP variations are largely 2-fold. The first is to detect the magnitude of diurnal variation that occurs in patients with glaucoma. While increasing the frequency of and staggering office visits at different times of the day can be helpful to detect such fluctuations, this strategy is ineffective in detecting the changes that occur when changing positions or during the nocturnal period. As a result, a single IOP measurement during a routine office visit may not accurately represent the actual state of a patient’s diurnal IOP curve as a whole. However, in the absence of validated and reproducible methods for continuous IOP measurement that are amenable to clinical use, true 24-hour IOP and its associated fluctuations cannot be measured using current techniques.²⁴

The second and perhaps more challenging aspect of managing IOP variations is to develop methods to not only lower IOP but to decrease the enlarged fluctuations that occur in glaucoma patients to a more physiologic range. The ideal treatment modality would cause a uniform reduction in both diurnal and nocturnal IOP.²⁹ In general, antiglaucoma medications increase outflow and have a longer half-life, such as the prostaglandin analogs, and seem to be more effective at restricting IOP fluctuations than shorter-acting agents, such as pilocarpine and alpha-adrenergics.^50–54 However, pharmacokinetic properties of a drug may not be the only factor that determines its ability to regulate fluctuations in IOP. Two studies^55,56 measuring diurnal IOP demonstrated that the carbonic anhydrase inhibitors were more effective than the beta-blockers at decreasing nocturnal IOP despite the fact that the primary mechanism of action of both classes of medications is aqueous suppression.

Lastly, it should also be noted that there is a direct correlation between mean IOP and the range of diurnal fluctuations, with the largest fluctuations occurring in those with the highest mean IOP.^17,53 As a result, the most effective antiglaucoma medications at lowering IOP may also be the most effective at narrowing the degree of diurnal variations. The same effect is seen in patients who undergo laser trabeculoplasty, as the mean IOP is lowered due to the effect of the procedure, but there is also a corresponding reduction in the diurnal range.⁵⁷ In a study comparing glaucoma patients on medical therapy with those who underwent trabeculectomy, it was found that those patients who underwent trabeculectomy had a smaller diurnal range than those who were being managed by medications alone (2.2 mm Hg vs 3.2 mm Hg, respectively).⁵⁸ However, the mean IOP of the surgical patients (10.5 mm Hg) was also lower than that of the medically managed patients (11.2 mm Hg), thus reinforcing the notion that mean IOP and diurnal range are directly related.^58,59

METHODS FOR TWENTY-FOUR–HOUR INTRAOCULAR PRESSURE MONITORING

Goldmann applanation tonometry (GAT; Haag-Streit) is currently considered the gold standard for measuring IOP. The basis of GAT is the Imbert-Fick law, which states that the pressure inside a sphere surrounded by an infinitely thin membrane can be measured by a counterpressure that just flattens the membrane.⁶⁰ By applying a force to an applanated area of the central cornea, IOP is then calculated by using this principle.⁶¹ However, GAT is limited by the fact that it is a static measurement that records IOP at a single point in time while the patient is in a sitting position, which does not account for habitual changes in body position.

A more recent and dynamic method of measuring IOP is with the Pascal Dynamic Contour Tonometer (DCT; Ziemer Ophthalmic Solutions). This instrument is able to record 100 IOP measurements per second while measuring IOP fluctuations throughout the cardiac cycle, providing a dynamic measurement over a 5- to 8-second period. Unlike GAT, which flattens an area of the central cornea, the contact surface of the DCT is concave to better match the curved contour of the corneal surface. As a result, DCT reduces some of the potential confounding effects of corneal biomechanics on IOP measurement. Consequently, studies have shown CCT affects IOP measurements in DCT to a much lesser degree than in GAT and may be especially useful for patients who have had corneal or refractive surgery.^62–65

Another promising method of IOP measurement is rebound tonometry (Icare Finland Oy). The Icare tonometer utilizes a magnetized rod probe with a 1.8-mm plastic tip, which momentarily impacts the surface of the cornea and rebounds back. The deceleration movement of the probe is measured by a solenoid in the device and converted into an IOP measurement. No anesthetic agent is required, and patients typically do not experience pain or discomfort. Similar to GAT, rebound tonometry is influenced by CCT and other corneal biomechanical properties. Given its simplicity of use, rebound tonometry has gained popularity as a means of measuring IOP for population screening as well as in pediatric or uncooperative adult patients.

Stay updated, free articles. Join our Telegram channel

Join