Article Date: 8/1/2011

Pressure Points
intraocular pressure

Pressure Points

A look at recent concepts in IOP measurement and their implications for practice

Deepak Gupta, O.D., F.A.A.O.,
Stamford, Conn.

RL was a 76-year-old male patient who I'd been monitoring for glaucoma for several years. His risk factors: a positive family history (mother), elevated intraocular pressure (IOP) (27mmHg OD, 26mmHg OS with average thickness corneas) and an increased cup-to-disk ratio (OD .50 H, .60 V, OS .50 H, .70 V). Subsequent nerve fiber layer analysis and visual field (VF) testing revealed a definitive diagnosis of open-angle glaucoma.

Based on this diagnosis, I prescribed a prostaglandin OU, q.h.s. The patient responded well, as his IOP decreased to 16mmHG OU. In fact, his IOP remained at or below target IOP for almost all his follow-up visits, including those early in the morning and during evening hours. Yet despite his compliance with both treatment and follow-up visits, two years later this patients' glaucoma progressed, as evident on VF testing. As a result, I was forced to supplement his prostaglandin with a beta-blocker (to be used once in the morning) to preserve his visual function.

So, why did this patient and why do others like him progress? One of the answers lies in recent research regarding IOP — a risk factor that no longer defines glaucoma, though nevertheless plays a major role in the disease.

Here, I discuss this research and its implications for glaucoma management.

Fundus photos (OD, OS) of the 76-year-old male patient showed increased cup-to-disc ratio.

Fluctuation 24/7

We, as eyecare practitioners, have been taught that if a patient's IOP measurement is outside the target range or remains elevated for long periods of time, he's at risk for both glaucoma development and progression. Recent studies, however, reveal that IOP fluctuation throughout the day in the socalled “normal” range may be a significant risk factor for progression.

In fact, one study showed that open-angle glaucoma patients who had a large IOP fluctuation range (5.4mmHg) even after adjusting for office IOP measurement, age, race, gender and VF damage at baseline, had an almost six times greater risk of glaucoma progression through an eight-year period than those who had a small IOP range fluctuation (3.1mmHg).1 This study included 64 patients (104 eyes) who used a home tonometry device at periodic intervals of the day through a five-day period. The purpose of the study was to study the risk associated with diurnal IOP variations in patients who had open-angle glaucoma.

In addition, a prospective, multicenter, randomized study showed that greater IOP fluctuation was an independent risk factor for glaucoma progression.2 Specifically, the researchers of this study showed that for every 1mmHg increase in IOP fluctuation, the risk of progression of VF damage increased 30% through a seven-year period. This study assessed data from 401 patients in the Advanced Glaucoma Intervention Study. The purpose of the study was to identify VF loss progression risk factors.

Night moves

Most of us learned in optometry school that IOP is highest first thing in the morning for most patients. This makes sense, intuitively, as aqueous production decreases during the nocturnal hours. Therefore, less aqueous humor is produced at night, which, in turn, decreases inflow, which then lowers IOP. In fact for many decades, this was the basis for the use of topical beta-blockers during early morning hours.

Recent studies, however, reveal that nocturnal IOP is actually higher in glaucoma patients than was previously recognized. Specifically, these studies suggest that the dynamics of aqueous humor change when a patient is supine. So, IOP for many patients may be elevated during nocturnal hours.

One study revealed IOP was higher at night than during the day for both non-glaucomatous patients and glaucoma patients.3 In this study, researchers measured IOP, blood pressure and heart rate every two hours during a 24-hour period. The study was comprised of 24 untreated patients (ages 40 to 78) who had newly diagnosed abnormal optic discs and/or abnormal VFs. During the 16-hour diurnal awake period, IOP was obtained while patients were sitting and supine, and blood pressure and heart rate were acquired while patients were supine. During the eighthour nocturnal sleep period, all measurements were obtained while patients were supine. The mean diurnal and nocturnal IOP, blood pressure and heart rate in the glaucoma group were then compared with data acquired from an age-matched control group of 24 individuals who had non-glaucomatous eyes. The purpose of the study was to characterize the 24-hour pattern of IOP in untreated patients who had newly diagnosed early glaucomatous changes.

Another study showed that in two-thirds of healthy patients, the peak IOP occurred outside normal office hours.4 In this study, researchers reviewed 24-hour data of IOP collected from 33 young, healthy subjects (ages 18 to 25), 35 older, healthy subjects (ages 40 to 74) and 35 untreated, older glaucoma patients (ages 40 to 79), all of whom were housed in a sleep laboratory. Measurements of IOP were obtained every two hours via a pneumatonometer, with subjects in the sitting and supine positions during the diurnal/wake period (7:00am to 11:00pm) and in the supine position during the nocturnal/sleep period. Correlations between average sitting or supine IOP in the right eye between 9:30am and 3:30pm (office hours) and peak right eye IOP during nocturnal hours were assessed. The purpose of the study was to evaluate the correlations between office-hour IOP and peak nocturnal IOP in both healthy and glaucomatous eyes.

Further, in a retrospective study comprised of progressive glaucoma patients, researchers found that the peak 24-hour IOP measurements were 5mmHG higher, and in some cases as much as 12mmHg higher than IOP measurements obtained during office visits.5 And, the researchers discovered that in the majority of patients, peak IOP measurements occurred outside office hours. As a result, 24-hour IOP monitoring resulted in a change of clinical management in a majority of these patients, including 13, who were offered trabeculectomy. The study was comprised of 29 subjects who were sequentially admitted for 24-hour IOP monitoring while taking their established anti-glaucoma therapy. The purpose of the study was to determine the value of 24-hour IOP monitoring in routine clinical practice.

The nerve fiber analysis of the 76-year-old male demonstrated decreased retinal nerve fiber layer OU.

Management implications

So given this research, should we alter our glaucoma management to include 24-hour IOP monitoring, sleep studies and midnight office hours? The truth is none of these methods is practical. It's currently impossible for our patients or us to obtain 24-hour measurements. In addition, many patients are unable to undergo sleep studies, due to claustrophobia, among other issues, and having midnight office hours invites a slew of logistical challenges, such as staffing — not to mention the fact that you're likely not as sharp in the middle of the night as you are during normal office hours. The answer then is to do the following until technology becomes available to provide us with a clear picture of what happens to a patient's IOP throughout the day and night (see “IOP Monitoring Technology in the Pipeline,” below):

Obtain several IOP measurements. Because elevated IOP is one of the risk factors for glaucoma development and progression and the aforementioned studies reveal IOP measurements fluctuate throughout a 24-hour period and those patients with the greatest fluctuations, regardless of measurement, are at greatest risk of development and progression, make it a point to assess IOP at different points throughout the day. You can easily accomplish this in one of two ways: As you will typically have the patient return for ocular coherence tomography, nerve fiber layer analysis and VF testing, you can check his IOP along with these tests. Or, you can have your patient present for serial tonometry, at which you can check his IOP at various points during the course of the day.

Don't be satisfied. Given the fact that recent studies have shown IOP measurements are highest at night, realize that the IOP measurements obtained during office hours don't tell the whole story. Significant damage is often occurring outside office hours due to increased IOP. As a result, seek to flatten the circadian curve as much as possible via careful drug selection. Many studies have demonstrated that certain classes of ocular hypotensive drugs control IOP at night better than others. To review these studies, visit www.pubmed.com, and type “lowering nocturnal IOP.” (A caveat: Whenever making the decision to treat glaucoma for a new diagnosis or for glaucomatous progression, be sure the look at all factors — optic nerve, nerve fiber layer, corneal thickness, diagnostic testing, family history, VF testing and gonioscopy before deciding on the correct course of action for your patient. In other words, remember glaucoma isn't solely about IOP.)

Send the patient to a sleep study center or hospital for overnight IOP monitoring. If the patient is willing and his glaucoma is in the advanced stages, this makes sense. To locate such centers, search on the Internet for local hospitals that have ophthalmology departments, and call those hospitals to see whether they offer such a service, or whether anyone in the ophthalmology department would know of other hospitals or sleep centers that do.

Elevated IOP is only one risk factor for the development and progression of glaucoma, yet it is the only risk factor we have the power to modify at this time. Therefore, in order to give ourselves an excellent chance of preventing more outcomes like the one illustrated above, it's essential we stay abreast of the latest IOP research and IOP measurement technology. OM

IOP Monitoring Technology in the Pipeline
Researchers have been refining microfabrication design techniques in order to devise implantable telemetry systems to provide extended IOP-monitoring for patients. Approaches have included tonometers incorporated into intraocular lenses, inserted into the suprachoroidal space, attached to the iris or built into contact lenses. As of today, none have been approved for use in the United States.
That said, the Sensimed Triggerfish (Sensimed AG, Lausanne, Switzerland) recently received approval for use in Europe and is currently under FDA review. Sensimed Triggerfish is a soft, hydrophilic single use contact lens that contains passive and active strain gauges embedded in the silicone to monitor fluctuations in diameter of the corneoscleral junction, the company says. The output signal sent wirelessly to the Sensimed Triggerfish antenna is directly correlated to fluctuations in IOP. This antenna, which is adhesive, is worn around the eye and is connected to a portable recorder through a thin, flexible data cable. The patient wears the lens up to 24 hours and can participate in normal activities, such as sleeping. When the patient presents to his eyecare practitioner, the data is transferred from the recorder to the practitioner's computer via Bluetooth technology for immediate analysis. A recent study on this device revealed it provided usable data, its surface wetting ability was good, best-corrected visual acuity was significantly reduced during Sensor wear and upon immediate removal, and three out of 10 subjects reported mild, transientcorneal abrasion.6
In addition, the PASCAL Dynamic Contour Tonometer, from Ziemer Group AG in Port, Switzerland, has proven to provide highly reliable values regarding true IOP. Specifically, Measurements with the DCT showed good concordance with intracameral IOP. (For more information, visit www.ncbi.nlm.nih.gov/pubmed?term=boehm%20dct.) For this reason, a prototype of a pressure-sensitive contact lens incorporating the PASCAL technology was developed for continuous IOP monitoring. The purpose was to assess the clinical applicability of this concept, and the achieved results were very promising, the company says. (For more information, visit www.ncbi.nlm.nih.gov/pubmed? term=19756646, and www.ncbi.nlm.nih.gov/pubmed?term= 20051894). However, further research and development is required before a decision about a potential design and finally about the marketing of such a solution can be taken.

1. Asrani S, Zeimer R, Wilensky J, Gieser D, et al. Large fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000 Apr;9(2):134-142.
2. Nouri-Mahdavi K. Hoffman D, Coleman AL, et al. Predictive factors for glaucomatous visual field progression in the Advanced Glaucoma Intervention Study. Ophthalmology. 2004 Sep;111(9): 1627-35.
3. Liu JK, Zhang X, Kripke, Weinreb RN. Twenty-four-hour intraocular pressure pattern associated with early glaucomatous changes. Invest Ophthalmol Vis Sci. 2003 Apr;44(4); 1586-90.
4. Mosaed S, Liu JH, Weinreb RN. Correlation between office and peak nocturnal intraocular pressures in healthy subjects and glaucoma patients. Am J Ophthalmol. 2005 Feb;139(2):320-24.
5. Hughes E, Spry P, Diamond J. 24-hour monitoring of intraocular pressure in glaucoma management: A retrospective review. J Glaucoma 2003 Jun;12(3): 232-6.
6. De Smedt S, Mermoud A, Schnyder C. 24-hour intraocular pressure fluctuation monitoring using an ocular telemetry sensor: tolerability and functionality in healthy subjects. J Glaucoma. 2011 May 19 [Epub ahead of print.]

Dr. Gupta is a partner at Stamford Vision Care in Stamford, Conn., where he manages a large glaucoma practice. In addition, he's a member of the Optometric Glaucoma Society, and he speaks extensively on the topic. E-mail him at deegup4919@hotmail.com, or send comments to optometricmanagement@gmail.com.


Optometric Management, Issue: August 2011