Pregnancy provides a unique challenge within the management of glaucoma, as topical eye drops can have systemic effects which may affect the patient and child.
A prospective study from Germany found glaucoma prevalence in adults aged 18 to <40 years to be 0.16% (of which 46% were female).1 Although the German population is largely Caucasian, which limits generalizability, the data illustrates how it is a small subset of patients who are being treated for glaucoma while pregnant.
This decreased prevalence creates a challenge for physicians who may not be familiar with which eye drops and treatments are safe and which are contraindicated during pregnancy. This article will aim to discuss the management of glaucoma during pregnancy and during the time of breastfeeding.
Epidemiology and progression of glaucoma in pregnancy
A decrease in intraocular pressure (IOP) during pregnancy has been previously noted; furthermore, it has been shown there is a statistically significant decrease in IOP during the third trimester compared to the first trimester.2-4
A few studies have shown glaucoma progression with associated visual field loss during pregnancy.5,6
The progression of glaucoma can occur with associated fluctuations in eye pressure in patients who are on few medications during pregnancy. One study found that there was an increase in IOP or a progression of visual field in 10 of 28 eyes, which was later confirmed on subsequent testing.5 Because of this potential, it is recommended to monitor a pregnant patient with glaucoma at least once each trimester.
Medical treatment options for glaucoma during pregnancy
Different IOP-lowering drops are recommended during different trimesters of pregnancy. So when prescribing glaucoma drops, it is important to discuss if a patient is planning on becoming pregnant; if so, the physician should make an adjusted medication regimen. Preferably, prior to conception, a plan and conversation can take place regarding future therapeutic options during pregnancy.
To limit the systemic effects of drops on pregnant and breastfeeding patients, nasolacrimal occlusion during eyedrop installation can be recommended. Alternatively, one could consider punctal plugs to limit systemic absorption.
Of note, no glaucoma medications have a Category A rating. This means it is important to have a discussion of risks versus benefits with the patient regarding the potential risks of glaucoma medications during pregnancy. When managing glaucoma during periods of pregnancy and breastfeeding, it is important to collaborate with the patient's neonatologist and/or obstetrician.
Table 1 shows which drops are first-, second-, or third-line treatments and which ones are to be avoided during the individual trimesters of a full-term pregnancy.7
| Rating | 0 to 12 weeks | 13 to 37 weeks | 37 to 40 weeks | Lactation | |
|---|---|---|---|---|---|
| Brimonidine (alpha 2 agonist) | Class B | First line | First line | Discontinue | Avoid |
| Beta-blockers | Class C | First and second line | Second line | Continue, monitor infant growth and heart rate | First line, avoid in children with heart disease |
| Prostaglandin analogs | Class C | Third line | Third line | Second line | First line |
| Topical CAI | Class C | Third line | Second line | Continue, monitor for neonatal acidosis | First line |
| Systemic CAI | Avoid during pregnancy, unless acutely needed | N/A | Pro re nata (PRN) if uncontrolled on topical therapy, discuss with obstetrician prior to starting | PRN if uncontrolled on topical therapy, discuss with obstetrician prior to starting | PRN if uncontrolled on topical therapy, discuss with obstetrician prior to starting |
Brimonidine (alpha 2 agonist)
Throughout weeks 0 to 37 of pregnancy, brimonidine is an acceptable first-line treatment. It is considered an alpha 2 agonist and is recommended as a Class B medication during pregnancy.
Of importance, it is recommended brimonidine be stopped at 37 weeks, given the risk of apnea in infants. Furthermore, brimonidine should be avoided in breastfeeding mothers due to the potential for transmission through breast milk and the resultant risk for apnea in infants.
Beta-blockers
Beta-blockers (such as timolol) are recommended as a Class C medication during pregnancy. They are recommended as a first- or second-line agent in weeks 0 to 12 of pregnancy and are recommended as a second-line treatment during weeks 13 to 37 of pregnancy. While it can be used during weeks 37 to 40 of pregnancy, it is important to monitor the fetal heart rate (HR) during this time period.
Beta-blockers can be used during the breastfeeding period; however, they should be avoided in children with heart disease.
Risks reported with beta-blockers include growth impediments, arrhythmia, bradycardia, and lethargy, which has been reported in fetuses or newborns exposed to systemically or topically administered B adrenergic antagonists.2 Agents can be concentrated in breast milk; thus, monitoring the infant's HR and growth is important.7 As a reminder, beta-blockers are used to treat systemic hypertension (HTN) in pregnancy.
Prostaglandin analogs
Prostaglandin analogs (such as latanoprost) are a Class C medication. They are recommended as a third-line treatment during weeks 0 to 37 of pregnancy and can be used as a second-line treatment starting at 37 weeks. After birth, prostaglandin analogs can be used as first-line agents to lower IOP.
Prostaglandin analogs are recommended as third-line given the concern for placental growth factor (PGF) to increase uterine contractility and potentially induce labor (although this requires a much higher dose than topical therapy).7
One small study followed 11 pregnant patients on latanoprost. One was lost to follow-up, one had a miscarriage, and nine had normal deliveries without pregnancy or neonatal abnormalities, or congenital anomalies.8
Topical carbonic anhydrase inhibitor
Topical carbonic anhydrase inhibitors (CAI), such as dorzolamide, are recommended as a Class C medication during pregnancy. They are prescribed as a third-line agent during weeks 0 to 12 and are considered a second-line medication during weeks 13 to 37. Starting at 37 weeks, it is important to monitor for neonatal acidosis. After the birth of the child, topical CAI can be considered a first-line treatment.
In one study, systemic high dose carbonic anhydrase inhibitors were teratogenic in rodents.9 A brinzolamide study in lactating rats showed at an oral medication dose of 15mg/kg per day, there was decreased body weight gain in offspring (312 times ophthalmic dosage); however, no teratogenic defects were seen in rodents.
This is compared to dorzolamide, where this association has been previously noted, thus potentially favoring dorzolamide compared to brinzolamide in pregnancy.10
Systemic CAI
Systemic carbonic anhydrase inhibitors should be avoided in pregnant women during weeks 0 to 12. After 13 weeks, it can be considered acutely if needed for pressure control; however, it should be discussed with the patient’s obstetrician prior to starting.
One study of patients using oral acetazolamide for idiopathic intracranial hypertension (IIH) showed no adverse effects during pregnancy in 50 patients who started acetazolamide prior to 13 weeks gestation (13 weeks was used as the cutoff, given it is considered the teratogenic period).
The risk of spontaneous abortion was similar to the control group, and although anomalies were noted in five of the offspring, there was not a statistically significant difference when compared to the control group. In the control group, there were 16 patients with abnormalities of similar severity. Limitations of this study include observational study performed through patient and physician surveys, small sample size, and it occurred within a single institution.11
Rho kinase inhibitors
At this time, rho kinase inhibitors have not been studied and are not recommended during pregnancy.
Authorized laser treatments for glaucoma during pregnancy
Ocular laser treatments that are safe during pregnancy:
- Select laser trabeculoplasty (SLT)
- Laser peripheral iridotomy (LPI)
- Argon laser trabeculoplasty (ALT), less effective in young patients12
- Endo- and cyclophotocoagulation (ECP and CPC)
Selective laser trabeculoplasty
SLT is indicated in open-angle glaucomas and is considered safe to perform during pregnancy. Thus, SLT may be a good option for a provider who is attempting to take a pregnant patient off an IOP-lowering drop during pregnancy.
Laser peripheral iridotomy
LPIs are safe and indicated for the treatment of prophylaxis in acute angle closure in pregnant women.
Endocyclophotocoagulation
Endocylcophotocoagulation is safe to perform during pregnancy. It is an alternative to traditional incisional glaucoma surgery. Micropulse versus cyclophotocoagulation can be performed in-clinic or in the operating room and can be considered as clinically indicated.
Ocular surgical options for pregnant patients
Surgery during pregnancy provides unique risks. There are risks with local and general anesthesia being absorbed systemically, which should be considered. There is also an increased risk of gastroesophageal reflux disease (GERD) in pregnant patients, which has been shown to increase the risk of pulmonary aspiration with general anesthesia.13 Pregnant women typically are of a younger age, which puts patients at an increased risk of failure.14
If one were to perform surgery, the second trimester is the optimal balance between risk to the child (during the first trimester with sedation and anesthesia) and risk to the mother (heightened during the third trimester as gestation advances).7
Patient positioning is important during the second and third trimesters due to the risk of systemic hypotension from aortic and venal caval compression, which limits fetal circulation. Ideally, the patient is positioned on their left side in a lateral decubitus position.7
Antimetabolites, such as mitomycin C and 5-Fluorouracil, are often used during surgery but are Category X and therefore contraindicated during pregnancy. Not using these agents can lead to an increased rate of failure in filtering surgery. Regarding postoperative drops, atropine is a muscarinic receptor antagonist and is recommended as a Class C medication during pregnancy.
In the literature, there is a concern for fetal bradycardia with the use of atropine; however, it is thought less likely with the ophthalmic dose. Standard postoperative medications, including ocular steroids (Class C) and topical erythromycin (Class B), are considered safe for use in pregnancy.15
FDA pregnancy categories (per the US Department of Health and Human Services)
- Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy
- 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
- Category C: Animal reproduction studies have shown an adverse effect on the fetus, and there are no adequate well-controlled studies in humans; however, despite possible risks, the potential benefits may warrant the use of the drug in pregnant women
- 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 the use of drugs in pregnant women despite potential risks
- Category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in the use of the drug in pregnant women clearly outweigh potential benefits16
Descriptions courtesy of the US Department of Health and Human Services.
Final thoughts
In summary, the management of glaucoma during pregnancy can be difficult as patients may be on fewer agents than prior. A good option for patients with primary open angle glaucoma who also will be on fewer medications during pregnancy may be a good candidate for an SLT procedure.
The management of glaucoma during pregnancy requires follow-up visits at each trimester in an effort to monitor IOP fluctuations and limit the potential for irreversible glaucomatous damage. The importance of clear communication and a partnership between the patient’s obstetrician and physician is very important in helping provide the best care for pregnant patients with glaucoma.
