Managing Glaucoma in Pregnant Patients

By Ang Li, MD

Intraocular pressure (IOP) in pregnant women is generally lower than in women of similar age who are not pregnant, according to many studies. The decline in IOP starts around 18 weeks of gestation and reaches a low of 1-4 mm Hg below baseline during the third trimester. IOP begins to return to normal about six weeks after childbirth.

It is uncertain why this change occurs. Possible mechanisms include:

• Increased aqueous outflow due to hormonal changes. However, there’s a lack of evidence for how IOP or aqueous outflow are affected by hormonal changes during menstruation.
• Lower episcleral venous pressure in pregnant women compared with nonpregnant women.
• Corneal stromal hydration, as evidenced by increased central corneal thickness in pregnant women and lower measured IOP.

The general decrease in IOP should mean that there is little concern for new glaucoma diagnosis in pregnant women, but what about those with preexisting glaucoma?

In one study of 32 pregnant women with ocular hypertension, IOP was significantly lower starting at 24 weeks of gestation. Pressure dropped an average of 24%, and some patients’ IOP reduced to the normal range. However, another study of 15 patients with preexisting glaucoma showed that nearly half of patients had IOP elevation of at least 5 mm Hg during pregnancy. Another study of patients who were using three or more glaucoma medications before pregnancy reported severe bilateral IOP elevation before the third trimester.

These studies suggest that patients with preexisting glaucoma may have a moderate risk of disease progression during pregnancy that warrants close monitoring. Furthermore, glaucoma that occurs in younger women of childbearing age more likely is of secondary etiology (e.g., uveitic glaucoma, steroid response, pigment dispersion). It is important to manage the underlying condition that can complicate glaucoma progression in this age group.

Treating glaucoma in pregnancy is challenging

Treating glaucoma in pregnant patients is challenging for ophthalmologists because there is a lack of clinical evidence informing treatment. In addition, pregnant patients and their providers have concerns about using medication with any (even a minimal) risk of fetotoxicity.

According to the long-standing five-letter U.S. Food and Drug Administration system labeling medications for pregnant women, most glaucoma drugs are labeled category C: “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.”

It’s important to note that many animal studies use extremely high concentrations of a drug, much higher than would be used clinically. It is, therefore, difficult to extrapolate findings from animal studies.

In addition, there are limited case reports, no prospective studies and no large case series assessing glaucoma medications in pregnant humans. We have very small patient databases — even smaller when considering each trimester.

Available medications

Medications currently available for treating pregnant patients with glaucoma include:

Beta blockers (category C). Timolol is the glaucoma drug with the longest record of use in pregnancy. In a survey of 600 U.K. ophthalmologists, 45% considered timolol a first-line therapy.

Fetal impacts of topical beta blockers are theoretical. Animal studies using 50 mg/kg/day of oral timolol, 7,000 times the human ophthalmic dosing, did not show fetal malformations. There was a single report of bradycardia and arrhythmia in a healthy fetus at 21 weeks when the mother was using timolol eye drops. The condition improved when the dosage of timolol was reduced and completely resolved when timolol was discontinued.

Recommendations are to:

• Avoid beta blockers during the first trimester.
• Use the lowest dose possible.
• Discontinue use two to three days before delivery to limit effect on uterine contractility and prevent potential neonatal complications.

The American Academy of Pediatrics has approved use of beta blockers during breastfeeding. Low levels of the medication have been found in breast milk, so careful monitoring of neonates is recommended.

Carbonic anhydrase inhibitors (category C). When taken orally, these drugs have shown an increase in teratogenicity in preclinical models (i.e., forelimb anomalies in mice). There has been one report of teratoma in the newborn of a patient taking oral acetazolamide and one case of renal tubular acidosis. However, in a series of patients taking oral acetazolamide for idiopathic intracranial hypertension, none reported adverse effects in their newborns.

Topical agents have been linked with teratogenicity in preclinical models, but doses were significantly higher than those used in humans.

It is unclear if these medications are excreted in breast milk. The oral use of acetazolamide has been cleared by the American Academy of Pediatrics.

Alpha adrenergic agents. Brimonidine (category B: “Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.”) is likely the safest glaucoma medication for use in the first trimester. Studies in preclinical models, which used significantly higher doses than those used in humans, have shown no teratogenesis. However, the drug can be transmitted in breast milk, so it should not be used in patients who are breastfeeding.

Apraclonidine (category C) has been shown to be embryocidal in animal studies using extremely high doses. It also should be avoided in patients who are breastfeeding as the drug is secreted in breast milk.

Prostaglandin analogues. Prostaglandins (extrapolated category D: “There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.”) can stimulate contraction in uterine smooth muscle and have been associated with pregnancy termination in humans. Caution is recommended when using these medications in pregnant patients as fetal toxicity has been seen in preclinical models at low doses.

Miotics (category C). Clinical studies of pilocarpine showed no fetal defects when patients used the drug in early pregnancy. A preclinical study showed that minimal amounts of the drug traverse the placenta.

Rho kinase inhibitors. Netarsudil 0.2% (extrapolated category B or C) has not been studied in humans. Preclinical studies have shown no adverse effects on fetuses, even when high doses were administered.

Recommendations for eye drop therapy

For pregnant patients on eye drops for glaucoma, follow these suggestions to help minimize systemic absorption and, therefore, exposure to the fetus:

• Encourage punctal occlusion.
• Prescribe the lowest frequency possible (e.g., timolol monotherapy once daily instead of twice).
• Prescribe the lowest concentration possible (e.g., timolol 0.25% instead of 0.5%).
• Consider alternative formulations (e.g., gel-forming timolol, which may have less systemic absorption).

For patients who are breastfeeding, consider:

• Up to 80% of topical drops are absorbed systemically. Some can be secreted in breast milk.
• Medication levels in breast milk are highest 30-120 minutes after administering eye drops.
• If possible, administer eye drops immediately after nursing to allow the longest time possible before the next feeding.

Alternatives to eye drop therapy

Surgical procedures to treat glaucoma pose other concerns in pregnant patients. For example, glaucoma filtration surgery has a higher risk of failure due to contraindication of antimetabolite usage during pregnancy and breastfeeding. (Mitomycin C and 5 fluorouracil are shown to be teratogenic in animal studies.) There are additional cautions with using anesthesia, supine positioning, and postoperative steroid and antibiotic drops.

As such, it may be best to delay surgical intervention when possible. Instead, selective laser trabeculoplasty is a good alternative, ideally helping to minimize use of glaucoma medications during pregnancy and postponing surgery until after delivery. When surgery is absolutely necessary, a minimally invasive glaucoma procedure under topical anesthesia is advised.

Pregnancy is a high-risk but transient time period. Most glaucoma cases can be monitored closely until more definitive measures can be safely taken after delivery or nursing. Ophthalmologists should work closely with obstetricians and pediatricians to manage glaucoma via a team-based approach to ensure best overall outcome for the mother and child.

Dr. Li is a glaucoma specialist at Cleveland Clinic Cole Eye Institute. This article recaps her presentation at the 2025 American Academy of Ophthalmology annual meeting and was based on the American Glaucoma Society’s Practical Guide to the Pregnant and Breastfeeding Patient With Glaucoma.