The Reliability of Intraocular Pressure Measurements
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Glaucoma is disease defined by characteristic optic nerve findings and associated visual field dysfunction. While elevated intraocular pressure (IOP) is not pathognomonic for the disease, it remains critical in disease detection and management. To date, IOP is the only directly modifiable risk factor for glaucoma and the target for all therapeutic treatments, whether medication, laser, or surgery. This article aims to discuss the reliability of various techniques available to measure IOP.
Physiologic and Pathologic variation in IOP
Physiological and pathological variations in IOP have been extensively studied in the past few decades. For example, studies have shown that static measurements of IOP during regular clinic hours may not be sufficient to accurately depict the degree of fluctuation of IOP, as two-thirds of glaucoma patients exhibit their highest IOP values outside regular clinic hours, particularly during the nocturnal/sleep period and may vary considerably, by 10 mmHg or more, over a 24-hour period (1). Furthermore, seasonal variations in IOP have also been observed, with distinct seasonal variation of IOP in patients with normal-tension glaucoma over a 20-year study period (2). In another study, the difference in mean winter IOP was significantly higher than summer (3).
Other factors can also cause physiological and pathological variations in IOP. For instance, physical activity, body position, and changes in atmospheric pressure can all affect IOP readings. One study reported differences in IOP measurement when sitting, supine, and standing (4). Physical activity can also increase IOP which could lead to reduced ocular perfusion pressure (5).
Certain medical conditions can also cause variations in IOP. For example, patients with diabetes with elevated HbA1c levels have higher IOP readings compared to healthy individuals (6). Long term corticosteroid use has also been associated with increased IOP, with 2.8% of steroid users converting glaucoma (7). Additionally the use of antidepressants and stimulants also affect IOP. A single dose of fluoxetine, a popular antidepressant, was shown to increase IOP measurement (8). Both current and past smoking history also leads to an increase in IOP (9).
Palpation
Palpation is the earliest method for measuring IOP, only surpassed by instrumentation in the 20th century. It remains a simple and quick method for estimating IOP by directly pressing against the globe. Palpation is still used in situations where mechanical measurements are not possible, such as in patients who have had an artificial cornea. For example, the use of a pneumotonometer or handheld tonometer on the sclera in patients with a keratoprosthesis has been shown to overestimate IOP, while digital palpation may be more accurate (10). However, the reliability of this method is questionable because digital palpation has been demonstrated to only make crude assessments and distinguish whether the IOP is less or greater than 30mmHg. There is also little correlation between digital palpation and Goldmann tonometry readings (11). Furthermore, a study that compared palpation and Tono-Pen measurements after cataract surgery showed a mean difference between IOP readings of 10 mmHg. (12).
Applanation
Applanation tonometry is the most prolific method for measuring IOP. Its direct contact with the cornea and determines IOP by utilizing the Imbert-Fick principle to measure the force applied by the device when a predetermined area of the cornea is flattened. (13)
The Goldmann and Perkins tonometers are the most widely used applanators and are considered the gold standard for IOP measurement. The Goldmann tonometer was introduced in 1954 and measures the force necessary to flatten a corneal area of 3.06mm diameter. The IOP equals the flattening force multiplied by 10. The Perkins tonometer is handheld and can be used without a slit lamp, making it more portable. However, the reliability of any applanation tonometer can be affected by various factors such as central corneal thickness (CCT) and corneal curvature.
Studies have shown that there is significant physician and technician variability in measurements, with two expert glaucoma physicians obtaining consecutive IOP measurements that differed greater than 2mmHg in 17% of eyes and even greater disagreement with consecutive technician measurements at 25% (14). Intraobserver and interobserver reliability in measurements have been reported to be 1.5 +/- 1.96 mmHg and 1.79 +/- 2.41 mmHg, respectively (14). In other words, the accuracy of any individual IOP measurement may vary by 3 or more mmHg simply based on the reliability limitations of the instrument.
Several corneal parameters have importance when measuring IOP. Central Corneal Thickness (CCT) is also a significant factor in the accuracy of applanation tonometry, as the instrument was designed for an average corneal thickness of 520 microns. Patients classified as glaucoma suspects have been reported to have a higher CCT than individuals with open-angle glaucoma or healthy individuals, with 42% of glaucoma suspects having a CCT of greater than 585 microns. It has been estimated that 30-57% of elevated IOPs in glaucoma suspects are actually artifacts of measurement, and there is no universally accepted formula to "correct" IOP measurements for any given CCT. Based on a review of various correction-factor approaches, the range probably falls between 2.5 and 3.5 mmHg per 50 microns of difference from normal. The Ocular Hypertension Treatment Study (OHTS) showed that for those with a mean baseline IOP greater than 25.75 mmHg, the risk for glaucomatous damage at 5 years was 36% if the patient had a thin or average (555 micron) cornea and 13% with a CCT of 565 to 588 (15). A recent publication by Khawaja et al suggests that the association between CCT and glaucoma may be due to collider bias rather than a biological association. The findings suggest that CCT alone should not be used as a factor to identify people at high risk of glaucoma and using CCT in combination with IOP may be more effective (16).
There is evidence to suggest that corneal curvature may influence the accuracy of Goldmann applanation tonometry (GAT) in certain patient populations. For example, a study found GAT measurements were significantly influenced by corneal astigmatism (17). Similarly, another study reported GAT measurements were less reliable in eyes with moderate to high levels of astigmatism and recommended performing two separate measurements at 90 degrees apart to obtain a more accurate estimate of IOP (18). In contrast, some studies have suggested that corneal curvature may not have a significant influence on GAT or other tonometry methods, such as dynamic contour tonometry (DCT). For example, a study found corneal curvature affected IOP with DCT but not GAT measurements (19).
Corneal thickness also causes deviations in IOP with physiologically thick corneas overestimating and pathologically thick corneas underestimating the actual IOP (20). However, contact lens-induced corneal edema caused a small underestimation error in IOP measurements by the Pascal DCT and an overestimation error in Goldmann tonometry measurements (21). In post-surgical central corneal edema, no significant difference was found in IOP measurements using GAT and DCT before and 1 day after surgery (22).
Non-contact tonometry
The Ocular Response Analyzer (ORA) measures corneal hysteresis (CH) and IOP through a pneumatic mechanism with a column of air. After sufficient pressure is applied to applanate the cornea, the additional pressure needed to indent the cornea is used to calculate corneal elasticity and therefore CH. Algorithms are then used to adjust the measured IOP to compensate for the degree of measured CH. The ORA's reliability in measuring IOP was reported in a study to not be significantly associated with CCT, corneal curvature, or axial length (22). In another study comparing the reliability of ORA and GAT, the ORA was found to overestimate IOP in comparison to Goldmann applanation, with the degree of overestimation increasing at higher IOPs. (23).
Air-puff non-contact tonometry utilizes a column of air to applanate the cornea without need for topical anesthesia. It has been shown to overestimate IOPs in the lower range and underestimate IOPs in the higher range when compared to GAT.
Indention tonometry
Indentation tonometry involves creating a corneal deformation with a truncated cone. There are two types of indentation tonometry - Schiotz and Tonopen. The Schiotz indentation tonometer, introduced in 1905, was found to have better correlation to IOP obtained by Perkins applanation tonometer, especially when CCT was in the range of 501-550 μm (24). It is largely of historical reference, as it is rarely utilized in current practice.
The tonopen, however, is a very common instrument utilized in measuring IOP. Tonopen measurements were found to be affected by CCT, with reported errors of 0.29 mmHg per 10 microns in men and 0.12 mmHg per 10 microns in women. In addition, Tonopen readings may mask a third of eyes with elevated IOP and two-thirds of eyes with potentially above goal IOP, and it may not be interchangeable with GAT or sufficiently reliable for patient management or screening (25,26).
There are some studies that suggest that tonometry with Tonopen may be more reliable in patients who have had corneal surgery. One study found that Tonopen readings have greater reliability than GAT after LASIK surgery (27). Some studies have also suggested that Tonopen may underestimate IOP at low pressures and overestimate IOP at high pressures. One study found that Tonopen measurements were less reliable than Perkins tonometer in pressures greater than 16mmHg (28). Another study found that Tonopen measurements were lower in IOP less than 11mmHg and higher when IOP was greater than 11mmHg (29).
Rebound tonometry
A study on 141 eyes with glaucoma showed good correlation between rebound tonometry (RT) and GAT, although RT gave higher IOP measurements that increased as the IOP values correspondingly increased (30).
The iCare ic100 rebound tonometer showed excellent clinical reliability in terms of repeatability, interobserver reproducibility, and concordance after intravenous anesthesia in both control and LASIK groups. The reliability was independent of corneal parameters and axial length in both groups (31). However in another study, ICare and Tono-Pen XL significantly overestimated IOP compared to Perkins applanation tonometry. The mean difference between Perkins and ICare and Perkins and Tono-Pen XL was -3.35 +/- 2.28 mm Hg and -2.78 +/- 2.53 mm Hg, respectively (32). A study showed that iCare has correlation with GAT with 73% concordance within 5 mmHg (33). The iCare tonometer has also been studied as an effective and accurate method for measuring IOP at home, which allows for continuous IOP monitoring (33,34). A survey conducted by iCare home users showed that 73.7% of patients found it easy to use and 100% found it useful (34).
Pascal Dynamic Contour Tonometer
Although not widely used today, studies suggested this device can measure IOP with minimal impact from corneal characteristics (35,36).
Continuous IOP monitoring
New devices such as the SENSIMED Triggerfish® and Eyemate are designed to continuously measure the IOP. Studies have found weak correlation between the SENSIMED Triggerfish® CLS data output and IOP measurements taken using the Tono-pen® XL applanation tonometer. This suggests that the Triggerfish CLS may only provide data on relative changes in the IOP rather than absolute IOP. Additionally, the validity of Triggerfish CLS at estimating IOP compared to other methods is still controversial. (37, 38)
Eyemate is a micro-sensor embedded in a soft, biocompatible material in long-term medical implants to measure IOP. The device is found to be reliable, with a mean difference of -0.2 mmHg from GAT measurements and 100% of measurements within ±5 mmHg of GAT (39).
Interdevice variability of CCT
A study comparing CCT measurements using Scheimpflug, ultrasound, and optical coherence tomography found deviations within each device ranged from 5 to 15 microns, while differences between devices ranged up to 120 microns, with OCT measurements having the least deviation (40). Another study found a significant correlation between GAT and CCT, but not between DCT and CCT (41).
Conclusion
IOP measurements are crucial in the diagnosis and management of glaucoma, and there are significant limitations to the reliability of these measurements. While there are various methods for measuring IOP, conflicting evidence exists on the reliability of each. Physicians should be cognizant of this when utilizing their IOP measurements, and should consider compiling data when making clinical and surgical decisions.
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