The Course of Glaucoma During Pregnancy: A Retrospective Case Series

Objective  To better understand the course of glaucoma during pregnancy in women with preexisting disease.

Methods  Retrospective case series of 28 eyes of 15 women with glaucoma followed up during pregnancy. Data were analyzed for age, race/ethnicity, medications, glaucoma type, intraocular pressure (IOP), and visual fields before, during, and after pregnancy.

Results  In 16 (57.1%) of 28 eyes, IOP was stable during pregnancy, with no progression of visual field loss. In 5 eyes (17.9%), visual field loss progressed during pregnancy, while IOP remained stable or increased. In 5 eyes (17.9%), IOP increased during pregnancy, but there was no progression of visual field loss. In 2 eyes (7.1%), data were inconclusive because of medication noncompliance and preexisting severe visual field loss. Glaucoma medications were used by 13 of 15 patients to control glaucoma during pregnancy. The classes of medications used most frequently were β-blockers, α₂-adrenergic agents, cholinergic agents, and topical carbonic anhydrase inhibitors.

Conclusions  The course of glaucoma during pregnancy is variable, and women must be monitored closely during pregnancy. Medications may be necessary to control IOP and to prevent vision loss during pregnancy.

It is recognized that intraocular pressure (IOP) decreases during pregnancy.^1-10 Investigations in healthy subjects have shown a statistically significant decrease in IOP during all trimesters of pregnancy compared with nonpregnant control subjects. Intraocular pressure declines as pregnancy progresses, with a statistically significant decrease in IOP from the first to the third trimesters.^5,7,8 During pregnancy women with ocular hypertension demonstrate a similar decrease in IOP that becomes notable during the second trimester and decreases further with advancing pregnancy.⁵ These findings have been used to support the hypothesis by Imre¹ that preexisting glaucoma improves and that few cases of glaucoma are diagnosed during pregnancy. However, case reports^11,12 describe women with glaucoma whose IOP was difficult to control during pregnancy, despite medical and surgical intervention. To our knowledge, no larger studies are present in the literature regarding the effect of pregnancy on glaucoma. In addition, in a recent survey of ophthalmologists in the United Kingdom, 26% of responders had treated patients with glaucoma during pregnancy.¹³ However, 31% of ophthalmologists in the study were unsure how to treat a patient whose IOP was at a level likely to cause disease progression during pregnancy. We compiled a series of women with glaucoma who were followed up before, during, and after pregnancy. This series of patients should shed light on the natural course of glaucoma during pregnancy.

The medical records of 15 patients with glaucoma who were followed up by us during pregnancy were reviewed retrospectively. Cases were identified by recall of the attending physician. Institutional review board approval was obtained for the study. Data were analyzed for age, race/ethnicity, medications, glaucoma type, IOP, and visual fields before, during, and after pregnancy. Some patients had multiple pregnancies. Data from only 1 pregnancy for each patient were included. Attempts were made to include data from the first pregnancy of each patient. When unavailable, data from the earliest pregnancy available were analyzed. In most patients, both eyes were studied, but each eye was treated independently. Two eyes were excluded from the study, including the right eye of patient 10 because of no light perception visual acuity and insufficient data and the left eye of patient 13 because it was unaffected by glaucoma. Data are expressed as mean ± SD. Attempts were made to examine patients every 3 months during pregnancy or more often as clinically indicated. When multiple IOP readings were recorded in a trimester of pregnancy, the mean IOP is given. Intraocular pressure was measured by applanation tonometry or Tono-Pen tonometer (Medtronic, Jacksonville, Fla) at each visit, except in patients with severe keratopathy, in whom pneumotonometry was performed. Because of the presence of a keratoprosthesis in the right eye of patient 11, tactile tensions were recorded in this patient. Increased IOP during pregnancy was defined as a change of at least 5 mm Hg in prepregnancy vs pregnancy values. The highest IOP measured during all 3 trimesters of pregnancy was used for this analysis. Eyes with a change in IOP of less than 5 mm Hg, or those with an IOP of less than 18 mm Hg throughout the study, were considered stable. Depending on patient cooperation and the extent of visual field loss, visual field tests were performed using Humphrey or Goldmann visual field machines. Visual field progression was defined by the appearance of a new arcuate defect or nasal step, deepening of existing defects, or increased constriction. Progression of visual field loss was confirmed on subsequent examinations and was irreversible. Individual case management was determined by each treating physician.

Demographic data are given in Table 1. Fifteen women (a total of 28 eyes) were included in the study. There were equal numbers of right and left eyes.

Table 2 lists the surgical and laser procedures before pregnancy for each patient in the study. Every attempt was made to include as much historical data as possible; details of some surgical procedures were unavailable because they occurred many years before pregnancy. The patients most likely to have had previous surgery included those with the following types of glaucoma: uveitic, aphakic, primary congenital, aniridic, developmental, and angle closure. One patient with juvenile open-angle glaucoma underwent 2 laser trabeculoplasties in an eye before an anticipated pregnancy. Decisions to perform all other prior procedures listed in the table were made independent of pregnancy.

Table 3 gives study patient data documenting the mean IOP and number of medications before pregnancy, during each trimester, and post partum. Visual field test results before pregnancy were compared with postpartum results (Table 3). Visual field progression was confirmed by repeat tests post partum and was irreversible. In 16 (57.1%) of 28 eyes, IOP remained stable with no change in the visual fields. Many of these eyes were maintained on fewer IOP-lowering medications during pregnancy compared with before pregnancy. In 5 (17.9%) of 28 eyes, visual field loss progressed during pregnancy while IOP remained stable or increased. In 5 (17.9%) of 28 eyes, IOP increased during pregnancy without progression of visual field loss. In the remaining 2 eyes (7.1%), data were inconclusive because of medication noncompliance and preexisting severe visual field loss.

Table 4 lists the medications used during pregnancy by the study patients. The most commonly used medications before pregnancy to control IOP included β-blockers, α₂-adrenergic agents, cholinergic agents, and topical carbonic anhydrase inhibitors. Once the patients became pregnant, there was a general trend to reduce the number of medications, as long as IOP remained under control. Compared with before pregnancy, the number of patients using β-blockers during pregnancy remained stable. There was a slight decrease in the number of patients using topical carbonic anhydrase inhibitors and α₂-adrenergic agents at the beginning of pregnancy, followed by an increase in the number of patients taking these medications by the third trimester. Patient 9 (in Tables 1, 2, and 3), who was taking an oral carbonic anhydrase inhibitor, stopped taking all of her IOP-lowering medications on her own initiative when she learned of her pregnancy. All use of prostaglandin analogue medications was discontinued as early in pregnancy as possible. Before pregnancy, none of the patients in the study were taking cholinergic agents. During the first trimester, 2 patients began taking pilocarpine hydrochloride, and by the third trimester 3 of 14 women were taking it. All patients taking cholinesterase agents were switched to alternative IOP-lowering medications when the ophthalmologist learned of the pregnancy. One patient used the α- and β-adrenergic agonist dipivefrin hydrochloride for a short time during the first trimester of pregnancy.

There were no adverse effects of medication use during pregnancy observed in the patients or their offspring. All women were instructed to perform punctual occlusion following instillation of topical medications to decrease systemic absorption. No surgical interventions were undertaken during pregnancy in the women in our study. Four women in our study had subsequent pregnancies; no major differences were noted in IOP control compared with data from earlier pregnancies.

It is well documented that IOP decreases during pregnancy in healthy women. It has been hypothesized that a similar decrease in IOP should be seen during pregnancy in women with preexisting glaucoma. To our knowledge, this is the first case series of women with glaucoma compiled to better understand the course of disease during pregnancy. In 16 (57.1%) of 28 eyes with glaucoma, there was no increase in IOP and no change in visual fields during pregnancy. Many of these women were maintained on fewer IOP-lowering medications during pregnancy compared with before pregnancy, and no progression of disease was observed. However, in 10 (35.7%) of 28 eyes in our study, there was an increase in IOP or a progression of visual field loss during pregnancy that was confirmed on subsequent testing. Many of these women required additional medication to control their IOP.

Whenever possible, physicians should address glaucoma management options in all women of childbearing age before pregnancy occurs. With proper planning, surgical treatments such as laser trabeculoplasty can be offered in anticipation of decreasing or stopping medication use during pregnancy. It is common for patients to be reluctant to take medication during pregnancy because of potential teratogenic adverse effects. We found an increase in medication noncompliance during pregnancy, with patients 8 and 9 (in Tables 2 and 3) discontinuing all medications when they learned of their pregnancy, that resulted in an increase in IOP. This reinforces the need for good communication between physician and patient to minimize risk to the fetus while preserving vision in the patient.

Thirteen of 15 women in our study required medication during pregnancy to control IOP. All topical ophthalmic medication should be considered to have some level of systemic absorption through the nasolacrimal drainage system.^14,15 We instructed all pregnant women to use punctual occlusion after instillation of drops to decrease systemic absorption of medication. All medications are classified for safety during pregnancy. None of the glaucoma medications meet the criteria of pregnancy category A, indicating that controlled studies in women fail to demonstrate a risk to the fetus in the first trimester and that the medications have a low risk for causing fetal harm. Brimonidine tartrate and dipivefrin are pregnancy category B medications, indicating that animal studies have not demonstrated a risk to the fetus, to our knowledge, but there are no controlled studies in pregnant women, or animal studies that have shown an adverse effect that was not confirmed in pregnant women. Most glaucoma medications, including β-blockers, carbonic anhydrase inhibitors (topical and systemic), prostaglandin analogues, cholinergic agents, anticholinesterases, and apraclonidine hydrochloride, are classified as pregnancy category C medications. This designation indicates that studies in animals have shown adverse effects on the fetus and there are no controlled studies in women, or that studies in women and animals are unavailable. These medications should be given only if the potential benefit to the pregnant woman justifies the potential risk to the fetus.^14-16

When selecting IOP-lowering medications for use during pregnancy, our approach is to consider the pregnancy safety categories already described and to work closely with the patient's obstetrician. In our experience, obstetricians are most comfortable with the use of β-blockers because this class of medications is used to control hypertension during pregnancy.¹⁷ Topical timolol maleate use in a pregnant woman has been associated with fetal bradycardia and arrhythmia.¹⁸ We also use brimonidine for IOP control during pregnancy because of its pregnancy category B designation. Our third alternative for IOP-lowering medication after β-blockers and α₂-adrenergic agents is topical carbonic anhydrase inhibitors. There are reports in the literature of associations between the use of oral carbonic anhydrase inhibitors and sacrococcygeal teratoma and transient renal tubular acidosis in neonates,^19,20 although there are no reported cases of adverse effects during pregnancy from topical carbonic anhydrase inhibitors. Historically, the prostaglandin analogues have been avoided during pregnancy because similar agents are used to induce labor. A recent report of 11 women exposed to latanoprost during pregnancy found that there was no evidence of adverse effects on pregnancy or neonatal outcomes due to medication use.²¹ The use of cholinergic agents has been associated with neonatal hyperthermia, restlessness, seizures, and diaphoresis when given to women who are near term.²² There were no adverse effects from medications used during pregnancy in the patients or their offspring in our study.

There are many mechanisms that have been proposed to explain why IOP decreases during pregnancy in healthy women. Initial theories focused on the hormonal levels that fluctuate during pregnancy, such as estrogen, relaxin, progesterone, and β-human chorionic gonadotrophin.^1,23-25 It has been shown that the aqueous humor formation rate does not change during pregnancy but that outflow facility increases during pregnancy, causing a decrease in IOP.^24-26 In addition, Wilke²⁷ demonstrated a decrease in episcleral venous pressure during pregnancy. Pregnancy also induces a slight metabolic acidosis that contributes to decreased IOP.³ The decrease in IOP during pregnancy is likely multifactorial, involving hormonal mechanisms and second messenger systems that result in increased outflow facility and in decreased episcleral venous pressure.

The limitations of our study are those inherent in a case series performed retrospectively. Attending physician recall was used to select cases for the study, which may introduce bias. In addition, the cases included represent multiple types of glaucoma with varying degrees of severity that are difficult to compare with each other. However, our case series represents the variety of cases encountered when treating women with glaucoma during pregnancy. Our objective was to provide as much data as possible from our collective experience, which can be generalized to guide management of future patients.

Although most women in the study remained stable during pregnancy, 10 (35.7%) of 28 eyes demonstrated an increase in IOP or a progression of visual field loss. This study illustrates that some eyes with preexisting glaucoma behave differently during pregnancy than healthy eyes and must be monitored closely. It also emphasizes the importance of discussing glaucoma treatment options with all women of childbearing age before pregnancy begins. It is often necessary to use medication to control IOP and to prevent vision loss during pregnancy. This should be prescribed in collaboration with obstetricians to ensure the safety of the mother and the fetus. Future research should investigate why some glaucomatous eyes behave differently than healthy eyes and how best to manage these patients' conditions during pregnancy.

Correspondence: Cynthia L. Grosskreutz, MD, PhD, Massachusetts Eye & Ear Infirmary, Harvard Medical School, 243 Charles St, Boston, MA 02114 (cynthia_grosskreutz@meei.harvard.edu).

Submitted for Publication: August 25, 2005; final revision received January 25, 2006; accepted March 5, 2006.

Financial Disclosure: None reported.