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Consider surgical management of glaucoma in pregnant women
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Studies show that lowering intraocular pressure (IOP) reduces the rate of progression of glaucoma. First-line therapy in the United States usually consists of topical medical therapy, with surgical intervention reserved for advanced cases. However, glaucoma management becomes complicated during pregnancy, secondary to the potential side effects of the medications to the fetus. A surgical approach may delay or eliminate the need for glaucoma medications and minimize the risk of pharmaceutical side effects to the fetus.
Pregnancy usually lowers IOP
During pregnancy, evidence exists of a physiological reduction in IOP possibly secondary to endogenous hormone levels causing an increase in uveoscleral outflow and a generalized reduction in peripheral vascular resistance causing a decrease in the episcleral venous pressure. (Maris and colleagues)
Because of these physiological changes, it is rare for glaucoma to be first diagnosed during pregnancy, and patients who have glaucoma usually show improved IOP control throughout the pregnancy. However, complications arise when the pregnant patient is diagnosed with glaucoma or when the uncontrolled glaucoma patient becomes pregnant.
Glaucoma meds have systemic effects
Despite the lower dosage from ocular use, persistent systemic side effects have been documented with various topical medications. This is partly due to the fact that 80% of the topical medication volume instilled is drained into the nasolacrimal duct and absorbed systemically. Therefore, it passes the hepatic metabolism, which would have inactivated most of the medication (Wagenvoort and colleagues).
The accompanying table shows the U.S. Food and Drug Administration’s categorization of drugs in various classes depending on the safety of use in pregnant patients. Most topical glaucoma medications belong to the pregnancy Class C, which is categorized as uncertain safety because of adverse fetal effects in animals.
No clinical guidelines
Currently, no clinical guidelines exist for managing and treating glaucoma in pregnancy. The knowledge concerning the side effects of topical glaucoma medication is based on information derived from the use of systemic medications of similar drug classes on pregnant and lactating women.
Generally, nonionized, lipid-soluble and low molecular weight (<700 Daltons) drugs have been shown to cross the placenta easily. Most glaucoma medications have molecular weight in the range of 90 to 390 Daltons; therefore, the drugs will cross the placenta to the fetus with little resistence. Furthermore, drugs less than 200 Daltons have been shown to enter the breast milk easily (Kooner and colleagues, Part I). In addition, milk is more acidic than plasma, so drugs that are basic tend to be more concentrated in breast milk.
Studies show that drug levels in breast milk are highest 30 to 120 minutes following drug instillation (Johnson and colleagues), however, “the maximum amount of drug that is secreted to the breast milk will seldom exceed 1% to 2% of the administered maternal dose,” according to Kooner and colleagues (Part I). To further understand the treatment of glaucoma in pregnancy and the potential side effects to mother and fetus, the eye care professional needs to be familiar with the different glaucoma drug classes.
Avoid adrenergics
Alpha-adrenergics decrease IOP by reducing aqueous production and increasing uveoscleral outflow. Based on animal studies, brimonidine and dipivefrin are the only Class B glaucoma medications. Not much is known about topical adrenergics, but systemic adrenergic compounds have been shown to cause “delays in second stage labor and a prolonged period of uterine atony with hemorrhage,” according to Maris and colleagues.
Although topical brimonidine shows no evidence of risk to fetus, its use in pregnant or nursing mothers should be avoided due to the fact that there have been documented cases of bradycardia, hypertension, hypothermia, hypotonia and apnea in infants younger than 2 months of age who were using topical brimonidine (Johnson and colleagues).
Beta-blockers OK during lactation
Beta-blockers reduce aqueous production by blocking beta-receptors in the ciliary body. Because of its action on beta-receptors, a case of bradycardia and arrhythmia in the fetus has been reported secondary to the use of timolol maleate 0.5% in the pregnant mother. However, with discontinuation of the topical beta-blocker, the fetal heart rate returned to normal levels (Wagenvoort and colleagues).
The cause of toxicity in the fetus is possibly due to the smaller blood volume and immature metabolic system, causing plasma levels of timolol in the fetus to exceed therapeutic range. This leads to increased side effects and increased half-life of the drug, which is four to six times longer than in adults (Wagenvoort and colleagues).
In addition, studies have also shown that levels of timolol are six times higher in breast milk than in plasma. However, even with this elevated concentration, only 1/80 of the cardiac-effective dose is present. Therefore, the concern is minimal unless impairment of the infant’s hepatic or renal function is noted (Maris and colleagues). Thus, timolol is approved by the American Academy of Pediatrics for use during lactation (Johnson and colleagues).
CAIs OK during lactation
Acetazolamide, which also reduces IOP by reducing aqueous production, is another medication approved by the American Academy of Pediatrics for use during lactation. While its concentration in breast milk is one-third of maternal plasma levels, plasma levels in infants after nursing have been shown to be very low. Therefore, acetazolamide is compatible with breast-feeding (Johnson and colleagues).
On the other hand, use of topical acetazolamide in the pregnant mother is not without risk. There has been a documented case of metabolic acidosis, hypocalcemia and hypomagnesemia in a newborn infant whose mother had been treated with acetazolamide, pilocarpine and timolol for glaucoma during pregnancy (Chung and colleagues).
Prostaglandin analogs: risky
Prostaglandins increase uveoscleral outflow, which leads to decreased IOP. Interestingly, prostaglandins have been used to induce labor, terminate pregnancy and regulate menstruation. In particular, “travoprost is a prodrug that will hydrolyse in the cornea to become fluprostenol, a type of prostaglandin that is highly selective for F2a receptors, which is used to induce abortion in animals,” according to Chung and colleagues.
Therefore, the use of this drug in pregnant patients has caused much concern. On the other hand, one study showed no side effects from the use of latanoprost in 11 pregnant women. However, this study is too small to make any statistically significant conclusions (De Santis and colleagues).
Surgical management
Other options such as argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT), in lieu of medical management, may be a better alternative because of the reduced side effects with surgical intervention. ALT works by using laser photocoagulation to shrink the collagen in the trabecular meshwork (TM), thereby increasing aqueous outflow.
SLT is similar to ALT except that it uses a “cold” laser to selectively target pigmented cells in the TM. Consequently, less thermal damage occurs to the TM compared to ALT, and the procedure can be repeated, unlike ALT.
For more information:References:
- Mindy C. Nguyen, OD, is an instructor of optometry at the Illinois College of Optometry/Illinois Eye Institute. She can be reached at 3241 South Michigan Ave., Chicago, IL 60616; (312) 949-7189; fax: (312) 949-7558; e-mail: mnguyen@ico.edu.
- Chung CY, Kwok AKH, Chung KL. Use of ophthalmic mediations during pregnancy. Hong Kong Med J. 2004;10(3):191-195.
- De Santis M, Lucchese A, Carducci B, et al. Latanoprost exposure in pregnancy. Am J Ophthalmol. 2004;138(2):305-306.
- Johnson SM, Martinez M, Freedman S. Management of glaucoma in pregnancy and lactation. Surv Ophthalmol. 2001;45(5):449-454.
- Kooner KS, Zimmerman TJ. Antiglaucoma therapy during pregnancy – Part I. Ann Ophthalmol. 1988;20(5):166-169.
- Kooner KS, Zimmerman TJ. Antiglaucoma therapy during pregnancy – Part II. Ann Ophthalmol. 1988;20(6):208-211.
- Maris PJG, Mandal AK, Netland PA. Medical therapy of pediatric glaucoma and glaucoma in pregnancy. Ophthalmol Clin North Am. 2005;19(3):461-488.
- Wagenvoort AM, Van Vugt JMG, Sobotka M, Van Geijn HP. Topical timolol therapy in pregnancy: Is it safe for the fetus? Teratology. 1998;58(6):258-262.