Pregnancy Special Considerations

Numerous physiologic effects occur within the body during pregnancy, and the eye is no exception. This article outlines both normal physiologic changes and pathological changes in the eye that can occur from pregnancy. ^{[1, 2, 3, 4, 5]} Moreover, a brief discussion of ocular medications and their potential effects on the fetus are reviewed.

Cornea

Corneal sensitivity has been found to be decreased in most pregnant women, where a majority of changes occur in the third trimester and then reverse in postpartum. ^{[2, 6]} One potential mechanism may be related to the slight increase in corneal thickness that may develop from corneal edema. ^[7]

Furthermore, an increase in corneal curvature and steepening may also occur. These changes have been reported to develop even in the postpartum period during breastfeeding. However, corneal curvature is reversible upon cessation of breastfeeding.

Contact lens intolerance may occur during pregnancy as a result of a change in corneal curvature, increased corneal thickness/edema, or an altered tear film. In any case, it is recommended that one should wait several weeks postpartum before prescribing to a new refraction. Additionally, decreased or transient loss of accommodation may occur during pregnancy or within the postpartum period.

Newly developed Krukenberg spindles have been observed early in pregnancy. The mechanism presumably is related to hormonal changes (eg, low progesterone levels). However, by the third trimester, an increase in progesterone and aqueous outflow often result in decreased or absence of Krukenberg spindles.

Intraocular pressure

A decrease in intraocular pressure has been shown to occur during pregnancy and often persists for several months postpartum. ^[8] Various mechanisms have been described for this observation: an increase in aqueous outflow; a decrease in systemic vascular resistance, leading to decreased episcleral venous pressure; generalized increased tissue elasticity, leading to decreased scleral rigidity; and generalized acidemia during pregnancy.

This decrease in intraocular pressure may have implications for pregnant women with preexisting glaucoma, since improvement of the disease during pregnancy has been reported in a few cases. ^[9]

Visual field changes

Wide speculation exists about the degree and mechanism of visual field changes that may occur in pregnant women. Types of field loss may include bitemporal loss, concentric constriction, and enlarged blind spots. ^[8] Proposed mechanisms are equally diverse and include changes to the pituitary gland that may affect the optic chiasm. These asymptomatic visual field changes were shown to be completely reversible postpartum. However, pregnant women with symptomatic visual field loss warrant further investigations.

External changes

A decrease in conjunctival capillaries and an increase in the granularity of conjunctival venules have been reported to occur; each being reversible during the postpartum period.

Another common external result of pregnancy is changes to the skin called chloasma. Due to increased hormone levels (ie, progesterone), some pregnant women experience increased pigmentation around the eyes and cheeks. The pigmentation changes tend to fade slowly postpartum.

Pregnancy-induced hypertension (preeclampsia)

The onset of hypertension (>140/90 after 20 wk) in an otherwise normotensive pregnant woman with proteinemia (>300 mg/24 h) is the minimal criteria needed to diagnose a patient with preeclampsia. ^{[6, 10, 11]} Furthermore, if these changes are associated with seizures, which are not attributed to any other cause, then the disorder is classified as eclampsia. The incidence of preeclampsia is approximately 5%, and it is more common in primigravids, in younger and older women, and in those patients with maternal systemic diseases. The onset of this disorder is usually after the 20th week of gestation.

Preeclampsia has various maternal and fetal consequences. In up to one third of cases, ocular sequelae have been reported. The most common ocular complaint is visual blurriness; however, other symptoms have also been noted, including photopsias, scotomas, and diplopia. The protean ocular manifestations include retinopathy, optic neuropathy, serous detachments, and occipital cortical changes.

The changes that occur in retinopathy due to preeclampsia are similar to changes from hypertensive retinopathy. ^[12] The most common finding is focal retinal arteriole narrowing, which also may be diffuse. Other changes may include retinal hemorrhages, edema, exudates, nerve fiber layer infarcts, and vitreous hemorrhage secondary to neovascularization. A positive correlation exists between the severity of preeclampsia and the degree of retinopathy; however, most changes are reversible once preeclampsia resolves. Preeclampsia retinopathy may be more severe with underlying diabetes, chronic hypertension, and renal disease.

Optic nerve changes that have been reported include papilledema, acute ischemic optic neuropathy, and optic atrophy.

Serous exudative retinal detachments may occur in severe preeclampsia or eclampsia. They tend to be bilateral, bullous, and with preeclampsia retinopathy changes. The underlying mechanism is thought to be related to choroidal nonperfusion and resultant subretinal leakage. Most patients with serous detachments have resolution of symptoms a few weeks within postpartum.

Cortical blindness, although a rare complication, has been a reported cause of vision loss in patients with preeclampsia. Cerebral edema is believed to be the mechanism of vision loss. Two proposed theories may account for the cerebral edema. One theory suggests that vasospasm causes transient ischemia and produces cytotoxic edema. The other theory explains that preeclampsia causes increased permeability from circulatory dysregulation, thus providing vasogenic edema. Treatment or resolution of preeclampsia and the resultant cerebral edema usually parallels visual recovery.

Preeclampsia may cause certain non–vision-threatening changes in the eye, including conjunctival vascular spasm or tortuosity, papillary mydriasis, ptosis, and nystagmus.

Central serous retinopathy

Although not typical, central serous retinopathy (CSR) has been reported to occur during pregnancy. ^[2] Although more common in the third trimester, it may also occur during the first or second trimesters. The condition resolves spontaneously in the first few months postpartum and has been known to recur in future pregnancies, usually in the same eye. The underlying mechanism remains unclear.

Benign intracranial hypertension

Benign intracranial hypertension (BIH), also known as pseudotumor cerebri, is defined as increased intracranial hypertension and its possible sequelae, with normal cerebrospinal fluid composition and normal neuro-imaging. ^[2] It typically occurs in obese females in their third decade of life. Interestingly, pregnancy does not increase the risk of developing BIH. If BIH does occur, it usually presents in the first trimester but may occur later.

BIH does not carry any fetal consequences and carries the same visual outcome in nonpregnant patients. Treatment for BIH in pregnancy is similar to that in nonpregnant patients with a few considerations. First, intense weight loss is not recommended because of risk to fetal viability. Second, carbonic anhydrase inhibitors are contraindicated during pregnancy due to the potential fetal teratogenic effects. Thirdly, the use of diuretics poses the risk of electrolyte and placental blood flow changes. Reports exist of spontaneous improvement with no treatment and very close follow-up care of optic nerve function. However, with visual compromise, interventions, such as bed rest, lumbar puncture, optic nerve sheath decompression, and lumboperitoneal shunting, have been reported.

Occlusive vascular disorders

It is well appreciated that pregnancy represents a hypercoagulable state, through various changes that occur with platelets, clotting factors, and arteriovenous flow dynamics. Such changes may be related to the development of retinal artery and vein occlusions, disseminated intravascular coagulopathy (DIC), thrombotic thrombocytopenic purpura (TTP), amniotic fluid embolism, and cerebral venous thrombosis. ^[2]

Both branch and central retinal artery occlusions have been reported to occur in pregnancy. Although a hypercoagulable workup may detect an abnormality, routine hematological workup may be unremarkable. A case report exists of bilateral central retinal artery occlusion from amniotic fluid embolism, which in and of itself is a potentially fatal condition. Retinal vein occlusions are less common than arterial occlusions.

DIC is characterized by widespread small vessel thrombosis often associated with hemorrhage and tissue necrosis. It may occur with complications in pregnancy, such as abruptio placentae, severe preeclampsia, complicated abortion, and intrauterine death. The choroid is the most common location in the eye for DIC to manifest. Patients often complain of visual loss from choroidal infarction or hemorrhage, retinal pigment epithelial, or serous detachments usually located in the posterior pole. Visual recovery usually occurs once the DIC resolves; however, mild pigmentary changes may persist.

TTP is a rare disorder characterized by small vessel thrombosis, thrombocytopenia, microangiopathic hemolytic anemia, neurologic and renal dysfunction, and fever. Visual symptoms may occur due to serous retinal detachment, retinal artery narrowing, retinal hemorrhage, and optic nerve head edema. The central nervous system may be involved, and the most common visual complaint is a homonymous hemianopia.

Antiphospholipid antibody syndrome is another condition that warrants consideration. In this syndrome, patients are in a thrombophilic state and are prone to recurrent arterial and/or venous thrombosis. Diagnostic criteria include clinical evidence of recurrent pregnancy loss or thrombosis in any organ or tissue as well as laboratory evidence of circulating antiphospholipid antibodies or lupus anticoagulant. Ophthalmic manifestations may present in the form of vascular thrombosis of the retina, the choroid, the optic nerve and visual pathway, and ocular motor nerves.

Miscellaneous disorders

Ptosis has been reported to occur during and after normal pregnancy and usually is unilateral. The mechanism is thought to be due to defects that develop in the levator aponeurosis from fluid, hormonal, and other changes due to the stress of labor and delivery.

Endogenous candidal endophthalmitis, although rare, has been associated with pregnant or postpartum women with indwelling intravenous catheters, systemic antibiotic use, and surgery. However, postpartum candidal endophthalmitis has also been reported in an otherwise uncomplicated labor and delivery.

Diabetic Retinopathy

Pregnancy can have an adverse outcome on the state of preexisting diabetic retinopathy. ^{[2, 8, 13]}  The worsening of disease depends on a multitude of factors, as follows: the severity of retinopathy at conception, duration of diabetes, glycemic control, and presence of coexisting hypertension. Gestational diabetes poses a very low risk for the development of retinopathy.

Studies on patients who have had no initial diabetic retinopathy show that approximately 10% of pregnant women with diabetes progress to some background retinopathy changes. However, less than 0.2% of pregnant women with diabetes progressed to the proliferative disease. A single baseline ophthalmologic examination may be adequate in the first trimester unless visual symptoms occur.

Additionally, studies in patients who had nonproliferative diabetic retinopathy demonstrated that as many as 50% of them may show an increase in their nonproliferative retinopathy, which often improves by the third trimester and postpartum. Approximately 5-20% of patients develop proliferative changes, where the risk being higher in those patients who had severe nonproliferative retinopathy at the beginning of their pregnancy. An ophthalmologic examination at least once every trimester is recommended for patients with nonproliferative diabetic retinopathy.

In terms of patients with proliferative diabetic retinopathy, studies have shown that a progression of disease may occur in as many as 45% of them. However, in those patients who had laser treatment before pregnancy, the risk of progression was reduced by 50%. Moreover, no cases of recurrence during pregnancy have been reported, if total regression of proliferative changes occurred prior to onset of pregnancy. Hence, initiation of laser photocoagulation is recommended prior to pregnancy if not during the early trimester once severe nonproliferative or proliferative changes occur. Proliferative retinopathy may regress at the end of the third trimester or postpartum without treatment. In patients with proliferative diabetic retinopathy, monthly ophthalmologic examinations are warranted.

Macular edema may develop or worsen during pregnancy. It has been shown that macular edema is often linked to pregnant women who have diabetes along with proteinuria and hypertension. No studies have been conducted examining the initiation of treatment during pregnancy. It may not be unreasonable to observe such patients until they reach postpartum, especially given that studies have shown that most cases have resolved spontaneously after delivery.

Intrapartum glycemic control has been demonstrated to be a better indicator of potential fetal well-being than the grade of diabetic retinopathy at the onset of pregnancy. Hence, obstetrical and endocrinological follow-up care is critical to the future well-being of the mother and fetus.

Intracerebral and Other Tumors

Pituitary adenomas

With pregnancy, previously asymptomatic pituitary adenomas or microadenomas may enlarge and result in various ophthalmic symptoms, such as headache, visual field change, and/or visual acuity loss. ^[14] For this reason, patients with amenorrhea are often screened to rule out pathological causes (ie, pituitary mass) prior to initiating pro-ovulation medications. Although most pituitary adenomas remain asymptomatic during their pregnancy, a small proportion may require radiation or surgical intervention if vision becomes threatened. Both radiation and surgical therapy is effective and has no perinatal implications.

In patients with a prolactinoma, an alternative treatment is bromocriptine, which has been shown not to have any increased risk to the fetus. Corticosteroid therapy has been reported as a treatment option. After pregnancy, pituitary adenomas regress in size and usually have no visual sequelae. It is recommended that pregnant patients with pituitary adenomas and microadenomas have monthly ophthalmic follow-up care with visual field assessment to rule out enlargement. Symptomatic pituitary adenomas may require the combined efforts of an ophthalmologist, obstetrician, neurosurgeon, and endocrinologist to decide upon the appropriate medical, surgical, or radiation treatment.

One potentially visual-threatening complication of pituitary adenomas is the sudden increase in pituitary size from infarction or hemorrhage referred to as pituitary apoplexy. This condition may present as a sudden onset of headache, visual loss, and/or ophthalmoplegia. Pregnancy is one of several potential risk factors for its occurrence. The management of such patients includes a neurosurgical opinion for potential surgical decompression. Endocrinological coverage also is warranted because of the risk of hypopituitarism (Sheehan syndrome).

Meningiomas

Meningiomas are benign, slow-growing tumors that typically occur in older females. However, they may present in pregnancy due to their usually rapid increase in size. ^[15] Often ophthalmic symptoms of decreased vision or visual field loss are the first manifestations. Since most of these tumors regress in size postpartum, those patients who are asymptomatic or with mild symptoms can be observed and left untreated. For those patients who require treatment, it is usually surgical since these tumors are not radiation or chemotherapy sensitive. Indications for timing and type of intervention require individual case analysis.

Uveal melanoma

Uveal melanoma is a rare occurrence among pregnant patients, as they usually occur in the older population. ^[16] From the limited case reports that exist, it appears that uveal melanomas behave no differently in pregnancy, and those that have been treated show similar 5-year survival rates to the nonpregnant treated population. No increased risk of metastases is apparent with pregnancy, and no case reports of placental or fetal metastases exist.

Miscellaneous

Case reports exist of other intracranial tumors occurring during pregnancy, such as lymphocytic hypophysitis, which may mimic a pituitary adenoma. Other uncommon intracranial masses include choroidal hemangiomas, craniopharyngiomas, and orbital hemangiomas.

Uveitis and Inflammatory Conditions

Vogt-Koyanagi-Harada syndrome

Vogt-Koyanagi-Harada syndrome is a bilateral panuveitis with central nervous system and cutaneous involvement. Reports exist of improvement and even complete remission during pregnancy and postpartum.

Sarcoidosis, ankylosing spondylitis, and juvenile rheumatoid arthritis

Ample case reports exist of improvement in both ocular and systemic manifestations of the above diseases during pregnancy. This improvement may perhaps be due to the increased amount of endogenous corticosteroids during pregnancy. Postpartum recurrence or flare-ups are not uncommon.

Toxoplasmosis

Toxoplasma gondii is a parasite that can be acquired congenitally via an acutely infected mother or ingestion of infected meat. Congenital infection occurs through transplacental transmission from a mother infected just before or during pregnancy to the developing fetus. The severity of congenital infection is highest when acquired during the first trimester of pregnancy, although the frequency of transmission to the fetus is greatest during the third trimester when contact of the maternal and fetal circulations is more likely to occur. Once maternal immunity has developed, it is believed that all future fetuses are protected from the development of congenital toxoplasmosis.

Latent ocular toxoplasmosis may reactivate during pregnancy in the mother. These patients usually are treated in a similar fashion to patients who are not pregnant. However, since pyrimethamine is potentially teratogenic, spiramycin has been recommended as a safer and equally effective alternative. The risk to the fetus of acquiring congenital toxoplasmosis in these cases is almost negligible.

Miscellaneous Conditions

Graves disease

An exacerbation of Graves disease may occur during the first trimester of pregnancy or even postpartum. ^{[17, 18]} The disease usually is quiescent during the latter portion of the pregnancy. Patients with Graves orbitopathy are treated in a similar fashion to patients who are not pregnant. The ophthalmologist should be aware of the symptoms of thyrotoxicosis (ie, tachycardic, weight loss, labile emotions, tremor, diaphoretic) because it represents an endocrinological emergency to both the mother and the fetus. ^[19]

Retinitis pigmentosa

A few case reports of progression of retinitis pigmentosa during pregnancy exist. These reports are anecdotal and do not suggest a clear mechanism.

Multiple sclerosis

Much like the inflammatory conditions, multiple sclerosis has been known to stabilize or even improve during pregnancy. However, an increased risk of relapse postpartum exists. Pregnancy does not appear to affect the overall course of multiple sclerosis and vice versa.

High myopia

In the past, there has been concern of retinal tears and detachments in patients with high myopia undergoing spontaneous vaginal delivery. However, one study of women with -4.5 D to -15 D and various preexisting retinal pathology (eg, lattice degeneration, treated retinal tears or detachments) has demonstrated no deleterious effects on the retina with spontaneous vaginal delivery. ^[20]

Little is known of the effect of ophthalmic medications on pregnancy, fetal well-being, and breast milk contamination. ^{[21, 22, 23, 24]} However, the National Registry of Drug-Induced Ocular Side Effects published a comprehensive review of their findings. Their findings and recommendations are summarized below.

Glaucoma medications

Beta-blockers (eg, timolol, levobunolol, betaxolol, carteolol) should be avoided or used in the lowest possible dose in the first trimester of pregnancy and be discontinued 2-3 days prior to delivery to avoid beta-blockade in the infant. Due to case reports of beta-blockers being concentrated in breast milk, they should be avoided in mothers who are breastfeeding. ^[25] However, timolol has been reported to be compatible with lactation according to the American Academy of Pediatrics.

Topical and systemic carbonic anhydrase inhibitors (eg, acetazolamide, dorzolamide, brinzolamide) are contraindicated during pregnancy because of potential teratogenic effects. They should be avoided in mothers who are breastfeeding because of the potential hepatic and renal effects to the infant. However, acetazolamide has been reported to be compatible with lactation according to the American Academy of Pediatrics.

Miotics (eg, pilocarpine, echothiophate, carbachol) appear to be safe during pregnancy. The toxicity during lactation is unknown. One exception is demecarium, which is toxic and is contraindicated in pregnancy and mothers who are breastfeeding.

Prostaglandin analogs (eg, latanoprost) are not well studied, and the reports that do exist are conflicting. Prostaglandins are used systemically for labor induction and termination, and as such, the topical use for glaucoma during pregnancy raises natural concern. Therefore, caution should be exercised when latanoprost is administered in women who are pregnant or breastfeeding.

In animal studies, adrenergic agonists (eg, brimonidine) have not demonstrated any fetal risk. Although no studies were conducted in pregnant patients, it may be used if necessary. Whether brimonidine is excreted in human milk is not known. Therefore, caution should be exercised since topical brimonidine given to human infants aged younger than 2 months has been reported to cause bradycardia, hypertension, hypothermia, and apnea.

Mydriatics

Use of occasional dilating drops during pregnancy for the purposes of ocular examination is safe. However, repeated use is contraindicated because of potential teratogenic effects of both parasympatholytics (eg, atropine) and sympathomimetics (eg, epinephrine). Due to either the anticholinergic or hypertensive effects on the fetus, use of mydriatics is contraindicated in mothers who are breastfeeding.

Corticosteroids

Although systemic corticosteroids are contraindicated in pregnancy, there are no known teratogenic effects of topical steroids. Because little is known about the risk of topical corticosteroids during lactation, it should be avoided in mothers who are breastfeeding.

Antibiotics

Antibiotics that are known to be safe during pregnancy include erythromycin, ophthalmic tobramycin, ophthalmic gentamicin, polymyxin B, and the quinolones. During lactation, polymyxin B and sulfonamides have been shown to be safe. Known antibiotics that should be avoided during pregnancy include the following:

• Chloramphenicol

• Systemic gentamicin

• Neomycin

• Rifampin

• Tetracycline

• Systemic tobramycin

Antivirals

All antivirals should be avoided during pregnancy because of teratogenic effects. Moreover, they should be avoided in mothers who are breastfeeding because of tumorigenicity. However, acyclovir has been reported to be compatible with lactation according to the American Academy of Pediatrics.

Fluorescein

No known teratogenic effects of fluorescein during pregnancy exist. However, the effect of fluorescein in mothers who are breastfeeding is unknown.

Topical anesthetic

No known contraindications exist to the use of topical anesthetic drops in pregnancy or in mothers who are breastfeeding.

Medication use

As described above, patients who are pregnant may require the use of medication to supplement their treatment. However, to ensure a decreased incidence of systemic absorption and toxicity two simple measures have been used. First, prescribing the patient the lowest recommended dose reduces the total amount of available drug. Secondly, patients are instructed when using topical medications to provide nasolacrimal duct and punctual occlusion thus reducing the amount of medication absorbed by the nasal mucosa.