Systemic medications may mask high intraocular pressure in glaucoma patients

Issue: September 2000

IOP measurements have long been considered sacrosanct regarding their accuracy and reliability. The perception most clinicians have is that applanation tonometry readings correlate closely to the actual IOP if manometry were performed. Recent studies have shown that a thicker- or thinner-than-normal cornea may cause readings to be higher or lower than in actuality. These artifacts occur even when Goldmann applanation tonometry is used.

In addition to corneal thickness, clinicians must also consider the increasing use of systemic medications, which is another factor that may affect IOP. Internists and family physicians commonly prescribe beta-blockers to treat hypertension. The use of systemic beta-blockers can often reduce IOP, thereby masking elevated readings and making the diagnosis of glaucoma more difficult. While most optometrists recognize that IOP is a risk factor and not diagnostic of glaucoma, an elevated IOP measurement can be an important marker that aids in establishing the diagnosis.

Topical vs. systemic beta-blockers

Topical beta-blockers have long been the mainstay of open-angle glaucoma therapy. When an individual is already using systemic beta-blockers, the response to topical beta-blockers is often not optimal. Also, there is an increased risk of side effects when both topical and systemic beta-blockers are used concurrently. Topical beta-blockers should, thus, no longer be considered the primary agent to prescribe when a patient is already taking systemic beta-blockers.

Consider this question: Does a patient with reduced IOP measurements but with other signs of glaucoma require additional therapy if systemic beta-blockers are being used and the IOP is low at all measurements? In this situation, can we assume that the individual is being treated – coincidentally, with the systemic medication – so additional medications are not required? Will the IOP be reduced on a 24-hour basis with a systemic beta-blocker as well as with its topical counterparts?

Systemic beta-adrenergic blockers are commonly used for treating hypertension as well as other cardiovascular conditions, such as cardiac arrhythmias or angina. They reduce the blood pressure, heart rate and cardiac output. They may reach the anterior segment in great enough quantities to also reduce aqueous formation and lower IOP.

Changing roles of anti-hypertensives

Beta-adrenergic blockers have enjoyed a resurgence in treating hypertension since a report was published in 1993 listing their advantages and disadvantages when compared with other anti-hypertensive medications. This report elevated their status to a primary-level medication — along with thiazide diuretics — because they may reduce morbidity and mortality associated with hypertension. The specific role of other medications — such as angiotensin-converting enzyme (ACE) inhibitors, diuretics and calcium channel blockers — for treating hypertension is now also better understood.

ACE inhibitors are often the primary agent used for treating hypertension if the individual also has a history of heart failure. Systemic calcium-channel blockers, with well-recognized side effects and complications, are more commonly used as second-line agents. The changing roles of these medications in hypertension therapy has led to more patients being placed on systemic beta-blockers than ever before, and their impact on IOP must be kept in mind.

Early days of beta-blockers and IOP

Phillips discussed reducing IOP with intravenous propranolol (Phillips CI, Howitt G, Rowlands DJ. Propranolol as ocular hypotensive agent. Br J Ophthalmol. 1967;51:222-226). A year later, Cote and Drance further discussed the IOP reduction that occurred when propranolol was used systemically in individuals with primary open-angle glaucoma. It was noted that a similar IOP reduction could be achieved when propranolol was given topically, but due to the development of corneal anesthesia, the medication never became a viable commercial drug.

Still, the seeds were planted that beta-blockers could reduce IOP. Several pharmaceutical companies started searching in the early 1970s for a topical beta-blocker that could be useful for treating glaucoma. Timolol became the first such agent.

There are several different classes of systemic beta-blockers, similar to topical agents (nonselective, cardioselective beta-1 blocker and nonselective with intrinsic sympathomimetic activity [ISA]). Each may have a different effect on the IOP, but the nonselective agents — with or without ISA — are the most efficacious. The agents may also come in either a long-acting or standard form. Many of these beta-blockers, such as atenolol, pindolol and nadolol, have been shown through clinical studies to reduce IOP when used systemically. Their mechanism of IOP reduction is similar to topical agents in that aqueous production is reduced.

Alpha-2 agonists

Other systemic medications may also reduce IOP. Clonidine is in a class of medications — alpha-2 agonists or systemic central sympatholytics — that reduce the blood pressure. These medications exert their influence on the alpha-2 receptors by penetrating the blood-brain barrier and mediating a central effect. More than 30 years ago, clonidine was discovered to reduce the IOP when used topically. Systemic absorption of the eye drop led to a significant reduction in blood pressure, which negated its ocular benefits.

Still, individuals using this medication systemically for hypertension may show a reduction in their IOP. Apraclonidine and brimonidine are examples of medications in this class that have been formulated into a topical form for ophthalmic use. Their chemical structures have been altered to reduce their absorption through the blood-brain barrier and their impact on lowering blood pressure.

Calcium channel blockers

Calcium channel blockers are used systemically for managing cardiovascular disease. In particular, they prevent vasospasm and reduce the resistance within blood vessels, thereby enhancing blood flow. Some have advocated their use for treating certain forms of glaucoma because of their ability to improve blood flow to peripheral tissues.

There are several different forms of calcium channel blockers, and their impact on IOP is variable.

Also, topical beta-blockers are contraindicated if the patient is taking systemic calcium channel blockers because of the risk of significant bradycardia. Verapamil has reduced IOP when used topically and was at one time being developed as a commercial preparation.

ACE inhibitors

ACE inhibitors are significant in the treatment of systemic hypertension, though their efficacy in individuals of African descent appears to be reduced. Their effect on IOP has been rarely studied.

Alcohol

Ethyl alcohol in its different forms may have a diuretic effect, which can reduce IOP. It must be used in significant amounts to affect IOP, and it is doubtful that one drink before visiting the optometrist will be substantial enough to lower IOP.

High IOP a warning sign

We have come to recognize that elevated IOP is one of a host of risk factors that contribute to the development of glaucoma; it is still an important warning that the condition is developing. We now recognize that systemic medications may reduce IOP, masking previously elevated readings.

On one hand, for those developing glaucoma, this may provide a positive beneficial effect by reducing previously high readings, but reduce the efficacy of topical beta-blockers if also used to manage the condition. Because a number of systemic medications can affect IOP measurements, it is important that optometrists are aware of what medications their patients are taking.

Suggested Reading:

National High Blood Pressure Education Program Coordinating Committee. The fifth report of the joint national committee on detection, evaluation, and treatment of high blood pressure. Arch Intern Med. 1993;153:154-183.

Neaton JD, Gramm RH, Priners RJ, et al. Treatment of mild hypertension study (TOMHS): final results. JAMA. 1993;270:713-724.

Oglive RI, Burgess ED, Cusson JR, et al. Report of the Canadian hypertension society consensus conference: 3. Pharmacologic treatment of essential hypertension. Can Med Assoc J. 1993;149:575-584.

Zimmerman TJ, Kaufman HE. Timolol: a beta-adrenergic blocking agent for the treatment of glaucoma. Arch Ophthalmol. 1977;95:601-604.

Kennellopoulos AJ, Erickson KA, Netland PA. Systemic calcium channel blockers and glaucoma. J Glaucoma. 1996;5:357-362.

Constad WH, Fiore P, Samson C, Cinotti AA. Use of an angiotensin converting enzyme inhibitor in ocular hypertension and primary open angle glaucoma. Am J Ophthalmol. 1988;105:674-677.