Neuro-ophthalmic Disorders in Pregnancy

Abstract

Purpose of Review

This review discusses evaluation and treatment of neuro-ophthalmic disorders in the pregnant patient.

Recent Findings

Any neuro-ophthalmic abnormality seen in nonpregnant women can be seen in pregnant women. Pregnancy-specific complications (preeclampsia and eclampsia) cause visual symptoms and can affect the entire visual axis.

Summary

Appropriate evaluation and examination is important to preserve the health and vision of the mother and prevent complications in the fetus. Evaluation should proceed in the same way for a pregnant patient as it would for a nonpregnant patient, with few exceptions. Treatment decisions may be influenced by stage of pregnancy.

INTRODUCTION

Almost every neurologist will see pregnant women who have visual concerns. Neurologists should be able to evaluate these concerns and determine whether these are neurologically based, and should be aware of common neuro-ophthalmic disorders that occur in pregnancy.

As with all neurologic disorders, a detailed history and neurologic examination contribute the most to accurate diagnosis.

COMMON VISUAL CONCERNS

Decreased visual acuity or blurred vision is a common and nonspecific concern (Table 9-1). To determine the etiology, the neurologist should start by getting visual acuity using a near card and then discuss with the patient how the visual symptoms vary from baseline. Since blurred vision is a nonspecific concern, the examiner must discern whether the blurring is really a refractive error, a scotoma (blind spot), metamorphopsia (visual distortion or waviness), or diplopia (double vision).

Table 9-1.

Etiologies of Common Visual Symptoms

Blurred vision due to a refractive error is a common problem in otherwise healthy pregnant women. The refractive error occurs due to a myopic shift and/or decreased accommodation. Pregnancy-specific hormonal changes, specifically the increase in progesterone, result in edema of the cornea and lens. The increase in corneal thickness can lead to a myopic shift which also causes nyctalopia (difficulty seeing at night). Corneal changes cause problems with contact lenses, since a transient myopic shift occurs, and swelling of the cornea can result in a less than perfect fit of the lenses on the cornea. Fluid shifts in the lens can decrease accommodation, making near vision blurry. These changes are considered normal in pregnancy.1,2,3 A way to determine if the blurred vision is related to a refractive error is to ask the woman to look at a near card through a pinhole and see if the blurred vision is correctable. The remainder of the screening examination should be normal. In addition, pregnancy induces changes in the lacrimal gland that can result in dry eye.4

Migraine is common in women of childbearing age and may first present during pregnancy. A common cause ofvisual blurring in pregnancy is migraine aura. The visual symptoms can include fortification spectra, decreased accommodative ability, or scotoma affecting both eyes. Typically, fortification spectra symptoms start centrally and move outward or vice versa. In contrast, visual blurring related to ischemia or other vascular etiologies are typically abrupt and maximal at onset, and ischemia to the retina can cause a visual symptom described as a shade being pulled down. Migraine often starts in the first trimester and may or may not improve during the second and third trimester.5,6,7 For more on this topic, refer to “Headache in Pregnancy” by Professor E. Anne MacGregor in this issue of CONTINUUM.

More serious causes of decreased visual acuity in pregnancy can include vascular disease (such as diabetic retinopathy), ocular vascular events, cerebral vascular events, and preeclampsia and eclampsia. Pregnancy is a mildly hypercoagulable state, leading to the unmasking of previously unknown clotting disorders. During pregnancy, the clotting factors plasminogen, fibrinogen, and factors I, VII, IX, X are all increased. In addition, fibrinolysis, protein S, and antithrombin levels decrease. Although some controversy about this exists, protein C levels probably remain unchanged, but many women have activated protein C resistance during pregnancy. Smooth muscle hyperplasia occurs as well as fragmentation of reticular fibers in blood vessels. All of these changes are a setup for the Virchow triad of hypercoagulability, hemodynamic changes, and endothelial dysfunction/injury.8,9,10 Consequently, a variety of vascular events can occur, resulting in decreased visual acuity, blurred vision, or visual loss.

Diabetic women are at risk for nonproliferative and proliferative diabetic retinopathy in pregnancy. Progression during pregnancy can occur and then regress after delivery. Rate of change is often dependent on the level of glucose and blood pressure control, amount of retinopathy before conception, and number of years with diabetes mellitus. The most common symptom may be visual blurring. Changes seen in diabetic retinopathy include microaneurysms, nerve fiber layer and intraretinal hemorrhages, macular edema, cotton wool spots, exudates, retinal vascular changes, and disc edema.11,12 Diabetic women with visual symptoms should be assessed by an ophthalmologist for diabetic retinopathy.

If visual loss is abrupt and monocular and not transient, a careful look for a retinal vascular occlusion should ensue. Visual acuity, confrontation visual fields, Amsler grid (Figure 9-1), swinging flashlight test looking for a relative afferent pupillary defect (RAPD), dilated examination, fluorescein angiography, and Humphrey visual fields (HVFs) can be used to detect and monitor these abnormalities. Arteriolar occlusion leads to ischemia and whitening of the retina seen on dilated fundus examination. The majority of arteriolar occlusions in pregnancy are from a cardiac source.13,14,15 However, vascular occlusion can result from a hematologic disorder, inflammatory vasculitic disorder, or emboli from other sources, such as amniotic fluid. Venous occlusions can also cause monocular blindness and may cause hemorrhages of the retina along with mild or severe vision loss, depending on the amount of ischemia present. Central or branch retinal arterial occlusions are usually treated with 81 mg/d aspirin and referred for evaluation and control ofatherosclerosis or possible emboli (Figure 9-2).13,16,17,18,19

Figure 9-1.

Normal Amsler grid. The Amsler grid is a great asset to have in the neurologist’s tool kit for evaluating metamorphopsia and visual loss at the pregnant woman’s bedside.

Figure 9-2.

Retinal vascular occlusion. A, Color fundus photo example of a small branch retinal embolus that was found near the left macula (arrow). A small corresponding central visual field defect was detected on automated visual field testing (B) and an extensive evaluation showed a patent foramen ovale as a possible etiology for the embolus. Reprinted with permission from Digre KB, Corbett JJ. Butterworth-Heinemann.19

See Table 9-220 for a summary of pregnancy-related issues regarding ophthalmic testing for pregnant women with ocular symptoms.

Table 9-2.

Ophthalmic Testing for Pregnant Women With Ocular Symptoms^a

Amniotic fluid embolism is a rare, life-threatening complication of pregnancy that affects multiple systems, including the eye. Breakdown of the maternal-fetal barrier occurs with release of amniotic particulate in the maternal circulation; this can result in coagulopathy and cardiovascular collapse. Two case reports link amniotic fluid embolism with retinal arteriolar occlusions.16

Central serous chorioretinopathy is accumulation of fluid underneath the retinal pigmented epithelium. This condition results in metamorphopsia and mildly decreased visual acuity without a RAPD. Its funduscopic appearance is like a blister under the macula. It is most common in young to middle-aged male patients; however, pregnancy, steroid use, stress, and hypertension are known to increase the risk.21 Patients are typically observed without treatment, and the fluid resolves spontaneously. The patient should be seen by an ophthalmologist or neuro-ophthalmologist to diagnose and follow (see Table 9-1).

Preeclampsia and eclampsia cause a variety of visual symptoms, including blurred or decreased vision, spots in the vision, or color defects. Preeclampsia and eclampsia can affect the visual system from the retina to the occipital lobe. In pregnant women with any visual concern, preeclampsia should be considered as an underlying etiology.

Funduscopic changes in preeclampsia and eclampsia are from acute or chronic systemic hypertension. The funduscopic signs include vascular narrowing, segmental vasospasm, cotton wool spots, hemorrhages, disc edema, or emboli. Rarely, bilateral retinal infarction can occur.22 Occlusions of the choroidal vascular system can lead to asymptomatic overlying retinal pigment epithelial changes known as Elschnig spots, or to effusion and serous retinal detachments. Elschnig spots are red or yellow spots with dark centers that result from microvascular disease and infarction of the choroid (Figure 9-3 shows typical findings in severe preeclampsia and eclampsia). These may be subtle and are often best seen on fluorescein and indocyanine green (ICG) angiography. The examination should focus on visual acuity and visual fields. If retinal changes are suspected, the patient should be referred to an ophthalmologist for further evaluation and a dilated fundus examination. Case 9-1 demonstrates the classical visual symptoms of scotoma, with funduscopy revealing disc and retinal edema with associated visual field abnormalities on automated perimetry.

Figure 9-3.

A color fundus photo of a 28-year-old primigravida with severe preeclampsia and visual blurring. Dilated examination revealed subtle small cream-colored lesions in the choroid—sometimes referred to as Elschnig spots (A, arrows; B). Fluorescein angiogram revealed choroidal infarction and staining (C, arrows).

Reprinted with permission from Digre KB, Corbett JJ. Butterworth-Heinemann.19

Visual blurring or visual loss occurring with eclampsia can also reflect higher-order cerebral visual function disorders, especially of the occipital lobe, causing alexia with or without agraphia and simultanagnosia. Careful evaluation of visual acuity, pupils, and visual fields is helpful in the setting of eclampsia. If cerebral blindness is present, pupillary light reflexes will be intact. The well-known Cookie Theft Picture from the Boston Naming Test can reveal simultanagnosia (affected patients will be unable to integrate the picture). Hoffmann reported that 97% of women with eclampsia could not correctly describe the photo.23 Balint syndrome is characterized by spasm of fixation, optic ataxia, and simultanagnosia and can be seen if ischemia to the bilateral inferior parietal lobes also occurs.24

As part of the evaluation of a patient with preeclampsia or eclampsia, the neurologic examination may reveal hyperreflexia and other focal neurologic abnormalities. MRI findings include disruption of the gray-white junction, especially in the parieto-occipital regions, and other features of the posterior reversible encephalopathy syndrome, as discussed in the articles “Neuroradiology in Women of Childbearing Age” by Drs Riley Bove and Joshua Klein and “Cerebrovascular Disorders Complicating Pregnancy” by Drs Steven Feske and Aneesh Singhal in this issue of CONTINUUM. Neuro-ophthalmic complications of eclampsia include cerebral blindness in 15% of patients.25 Spontaneous recovery from cerebral blindness occurs most commonly, but vision loss can be permanent if progression to ischemic or hemorrhagic stroke occurs. Infarctions of the lateral geniculate have been observed, which lead to permanent homonymous hemianopias.26 Treatment for preeclampsia/eclampsia is discussed in “Cerebrovascular Disorders Complicating Pregnancy” by Drs Steven Feske and Aneesh Singhal in this issue of CONTINUUM. Magnesium, used in treatment of this syndrome, can also cause visual blurring because it causes relaxation of accommodation, decreased convergence, and ptosis of the eyelids. However, the Amsler grid will be normal if magnesium is the reason for visual blurring.27

Case 9-1

A 29-year-old woman at 25 weeks’ gestation was admitted to the hospital with 3 to 4 days of intermittent epigastric pain. She also reported intermittent headache and scotomas. Laboratory results confirmed preeclampsia, and the patient was transferred to another hospital. She was started on IV magnesium and steroids, but cesarean delivery had to be performed because of worsening blood pressure. After delivery, she had an eclamptic seizure and continued to have problems with persistent preeclampsia and scotomas, so she was referred to the neuro-ophthalmology department. Ocular examination was normal except for grade 3 bilateral disc edema with retinal edema on the left. Humphrey visual field testing showed bilaterally enlarged blind spots. MRI and magnetic resonance angiography confirmed thrombosis of the left transverse and sigmoid sinus. Lumbar puncture revealed an opening pressure of 333 mm CSF. She was treated with acetazolamide for the secondarily induced intracranial hypertension and anticoagulation with enoxaparin sodium for her thrombosis. Hypercoagulability workup was negative.

Comment. This case demonstrates three reasons for abnormal vision in the pregnant woman, including initial diagnosis of eclampsia, followed by a complication of sinus thrombosis, and increased intracranial pressure. It is important to consider all complications in pregnancy and explain all of the visual phenomena.

OPTIC NEURITIS

Another cause of visual loss is optic neuritis. Symptoms of optic neuritis include visual loss, eye pain (especially with movement), and central visual field changes. Signs of optic neuritis may include RAPD, abnormal visual field to confrontation, and either a normal disc or an edematous disc. The MRI may show T2 signal in a noncontrasted dedicated orbit study, and periventricular fluid-attenuated inversion recovery (FLAIR) intensities may be evident if this is a presenting sign of multiple sclerosis (MS). Evaluation in the pregnant woman should proceed in a similar way to evaluation of a nonpregnant patient.28 Optic neuritis can be seen in MS and neuromyelitis optica (NMO). During pregnancy, immunoregulatory changes typically lead to a decrease in MS activity, and relapses are lowest during the last trimester. After delivery, relapse risk in MS is increased for 12 weeks. NMO differs in that risk of demyelination is increased during the last trimester.29 Look for the NMO antibody in anyone with optic neuritis, especially in the third trimester. Optic neuritis occurring in lactating women has been reported but is rare, and the exact relationship between demyelination and lactation is not understood.30 Treatment of severe optic neuritis in pregnancy can be with IV steroids, as is the case in the nonpregnant state. There have been no trials of the treatment of optic neuritis in pregnancy; each case should be discussed with the treating obstetrician.29,31 In general, the authors usually wait to treat the associated MS with disease-modifying therapy until after the pregnancy ends. For more on this topic, refer to “Multiple Sclerosis in Pregnancy” by Dr Patricia K. Coyle in this issue of CONTINUUM.

OTHER OPTIC NEUROPATHIES

Optic neuropathy refers to damage ofthe optic nerve for any reason. Damage can be infiltrative, inflammatory, demyelinating, ischemic, or the result of mass effect. The same entities that can cause optic neuropathy in nonpregnant patients, such as such as malignancy, diabetes mellitus, and glaucoma, can occur in pregnant women. Pituitary tumors can enlarge during pregnancy and may manifest as visual loss (Case 9-2). For mass effect, the physician should look carefully at visual acuity, visual fields to confrontation, and funduscopy. A formal visual field is helpful when assessing for visual field dysfunction from a mass lesion such as a pituitary tumor. Imaging, usually MRI, should be directed to the orbit and brain. Tumors such as meningiomas may become symptomatic in pregnancy because some of these tumors have estrogen and progesterone receptors.32,33

Transient vision loss can commonly occur from interrupted blood flow, as discussed above, but can also occur in papilledema. Optic disc edema and papilledema are not synonymous, although papilledema is one of the causes of optic disc edema. Optic disc edema can be seen with diabetes mellitus, infections, infiltration, acute hypertension, optic neuritis, and other entities. Papilledema, by definition, is optic disc edema from increased intracranial pressure, which can be primary or secondary to another lesion, such as venous sinus thrombosis. Symptoms of intracranial hypertension include diplopia, headache, nausea, visual field defects, pulse-synchronous tinnitus, and decreased visual acuity.20,34

Primary intracranial hypertension, now known as idiopathic intracranial hypertension (IIH), is a diagnosis in women of childbearing age, so this disorder is seen in pregnancy. It is the most frequent cause of papilledema in pregnant women and in nonpregnant obese women (Figure 9-5). However, pregnancy does not precipitate or exacerbate IIH.35 Obesity and recent weight gain are the major risk factors for this condition. Criteria for the diagnosis include signs and symptoms of increased intracranial pressure, such as headache, papilledema, diplopia (often from cranial nerve 6 palsy), nausea, vomiting, transient visual obscurations, and pulsatile tinnitus.35,36,37 Patients must have no localizing findings on neurologic examination, as well as normal brain imaging with no evidence of venous thrombosis, an opening CSF pressure of greater than 250 mm CSF while the patient is in the lateral decubitus position with legs straight, normal CSF studies, and no other identified cause of increased intracranial pressure.20,34 Delivery can proceed based on normal obstetric practice. If concern exists for visual loss with Valsalva maneuver induced by labor, low outlet forceps may be used or cesarean delivery may be done.35

Figure 9-5.

A color fundus photo of bilateral optic discs in a woman with idiopathic intracranial hypertension discovered at about 24 weeks‘ gestation. Her discs remained swollen during pregnancy (A, B), with enlarged blind spots on automated visual field testing. She was not treated since her vision remained stable on repeat examinations. She delivered a healthy baby vaginally and uneventfully. Later, after weight loss, her discs became completely normal.

Reprinted with permission from Digre KB, Corbett JJ. Butterworth-Heinemann.19

Causes of secondary intracranial hypertension are numerous. Most importantly, a careful search for cerebral venous sinus thrombosis must be done in any pregnant woman with papilledema. Cerebral/dural venous thrombosis occurs in 1/1000 to 1/10,000 pregnant women.38 Papilledema is seen in cerebral venous sinus thrombosis along with headache. Patients may have seizures and other neurologic findings. While thrombosis is most common in the puerperium, it can occur at any time during pregnancy. Since pregnancy is already a slightly hypercoagulable state, familial clotting disorders such as factor V Leiden and protein C/S deficiencies can manifest. Evaluation of papilledema, whether primary or secondary, includes appropriate imaging of the brain and venous system (see “Neuroradiology in Women of Childbearing Age” by Drs Riley Bove and Joshua Klein in this issue of CONTINUUM). All women with papilledema should also have a dilated examination and a formal visual field examination, since visual acuity is affected later than visual fields in papilledema.20,34 Case 9-1demonstrates classical visual symptoms and examination findings consistent with secondary intracranial hypertension from venous thrombosis during the puerperium.

Underlying causes of secondary intracranial hypertension should be treated directly, when possible. If the diagnosis is primary IIH and there are no, or only mild, vision changes, then limit weight gain to 9.07 kg (20 pounds) and treat with diuretics. Acetazolamide is the medication of choice because it allegedly reduces CSF production by inhibiting carbonic anhydrase. While acetazolamide is a US Food and Drug Administration (FDA) class C drug, it has been used safely in pregnancy. In the largest study, Falardeau and colleagues contacted pediatricians of children whose mothers took acetazolamide in the first trimester, and no major defects or complications were reported.39 Chlorthalidone (FDA class B) or hydrochlorothiazide (FDA class B) can be considered as an alternative for diuretic therapy. No systematic studies of these drugs in pregnancy have been done.20,40

The major threat of papilledema from primary or secondary intracranial pressure is visual loss. All pregnant women with IIH need to be followed with formal visual fields. The neurologist should work closely with an ophthalmologist or a neuro-ophthalmologist to follow the vision. Repeat lumbar punctures with CSF drainage can be used for temporary treatment. If vision is threatened despite medical therapy, optic nerve sheath fenestration can be considered. Headache management includes nonsteroidal anti-inflammatory drugs (class B early in pregnancy and class D later in pregnancy) early on, but this medication must be stopped later in pregnancy because of risk of premature closure of the patent ductus arteriosus. For uncontrolled headaches, a CSF diversion procedure can be considered.35,41 If venous sinus thrombosis is causing secondary intracranial hypertension, anticoagulation is indicated. Heparin and heparinoids are usually chosen because these do not cross the placenta in pregnancy, and warfarin is avoided because it causes fetal malformations.42

Case 9-2

A 34-year-old right-handed woman was first evaluated in the neuro-ophthalmology clinic for decreased vision. Examination showed stage 5 disc edema of the left eye (Figure 9-4A) but was otherwise normal. Clinical testing showed an enlarged blind spot on Humphrey visual field (HVF) testing (Figure 9-4B), and imaging showed a mass of the optic nerve sheath compressing the left optic nerve (Figure 9-4C); it had typical features of an optic nerve sheath meningioma. Because of her episodes of vision loss, she underwent 6 weeks of low-dose orbital radiation. Within a year after radiation therapy, she had stable vision, decreased frequency of episodic vision loss, marked improvement of her left optic nerve edema, and improvement of the enlarged physiologic blind spot on HVF testing. After 6 months of pregnancy, 2 years after the radiation, she had increased frequency of episodic vision loss as well as return of stage 5 disc edema of the left eye. HVF testing continued to show an enlarged physiologic blind spot of the left eye while remaining normal on the right. She was followed carefully during the remainder of her gestation, and her optic neuropathy remained stable. After successful delivery, her vision was stable on follow-up, and no significant changes were seen on her MRI.

Figure 9-4.

Color fundus photo of left optic disc edema from an optic nerve meningioma in the patient in Case 9-2 (A) with a normal visual field on the right and a slightly enlarged physiologic blind spot on the left (B) during pregnancy. MRI shows a meningioma of the left optic nerve (C).

Comment. This case demonstrates the enlargement that can occur with meningiomas during pregnancy. Close observation is the typical course of action unless there is significant progressive loss of vision or spread into the chiasm.

DIPLOPIA

Diplopia (double vision) has many etiologies. When a patient reports diplopia, the examiner first has to determine whether it is binocular or monocular, constant or intermittent, vertical or horizontal, and comitant (the same in all directions) or incomitant (worse in one direction). Monocular diplopia is usually the result of structural ocular abnormality such as dry eye or cataract. Binocular diplopia suggests an orbital, cranial nerve, or brainstem abnormality. In pregnancy, risk of cranial nerve palsies, growth of tumors, and nutritional deficiencies is increased.20,34

The most common cranial neuropathy in pregnancy involves cranial nerve 7, followed by cranial nerves 6 and then 4. Cranial nerve 7 palsy may cause a monocular diplopia secondary to exposure and dry eye. Supportive measures for dry eye include ocular lubrication or tarsorrhaphy (a surgical procedure in which the eyelids are temporarily or permanently partially sutured together to limit corneal exposure). Cranial nerve 6 palsy can be due to increased intracranial pressure or other causes and results in a binocular horizontal diplopia. Diplopia will be worse in the affected direction of gaze. Esotropia, nasal deviation of the affected eye, may be seen on clinical examination. The etiologies of sixth nerve palsy in pregnancy include hypertension (which seems to be the most commonly associated factor and usually resolves with delivery),43 demyelinating disease (eg, MS), and increased intracranial pressure. Sometimes the cause is not found. Cranial nerve 4 palsy causes a vertical or oblique binocular diplopia. Extraocular movement examination will show weakness of the superior oblique muscle (trouble moving the eye in and down). Cover/cross-cover testing will show the affected eye to be higher (hypertropia). Cranial nerve palsies can also be caused by excess interstitial fluid in pregnancy,44 which will resolve with delivery. Other causes of fourth nerve palsy include congenital, inflammatory orbital disease, idiopathic, trauma, and demyelination.20,34

Pituitary microadenomas and asymptomatic macroadenomas may grow during pregnancy and become symptomatic macroadenomas. Presentation is variable from asymptomatic to diplopia, photophobia, ophthalmoplegia, and typically bitemporal visual field defects, but junctional scotomas also occur. Any woman with a known pituitary tumor should have formal visual field testing during pregnancy. Sudden onset of headache and diplopia is concerning for apoplexy, and patients should have immediate imaging. Apoplexy is most frequently seen postpartum after hemorrhage or shock, sometimes known as Sheehan syndrome. Hemorrhagic necrosis of a tumor can also result in apoplexy or infarction into a pituitary tumor. Sometimes the only manifestation of apoplexy is the lack of menstrual periods postpartum.32,45,46 A rare entity known as lymphocytic hypophysitis can occur postpartum and mimics a pituitary tumor.

While an Arnold-Chiari type 1 malformation may become symptomatic during pregnancy, it must be differentiated from the more common acquired tonsillar herniation due to intracranial hypotension. Leakage from a lumbar puncture or inadvertent lumbar puncture during epidural anesthesia can lead to intracranial hypotension. Besides headache, diplopia is a common symptom of intracranial hypotension; it is usually due to subtle bilateral sixth nerve palsies or comitant esotropia. Diagnosis of intracranial hypotension is by imaging that shows low-lying tonsils, flattening of the pons against the clivus, pituitary gland enlargement, low-lying cerebellum, and enhancement of the pachymeninges with gadolinium.20,47 Finding and repairing the source of the leak or doing a blood patch will typically resolve the problem. Asking the patient about a previous epidural for delivery may help to identify the source of the leak.

Wernicke encephalopathy presents with diplopia, ptosis, or nystagmus, with or without retinal hemorrhages, as well as ataxia and confusion (typically memory disturbance). This entity is most typically seen during the first trimester with nausea and vomiting. Demand for thiamine increases during pregnancy; consequently, if hyperemesis gravidarum or poor diet are present, a deficiency may result.48 Clinicians should have a high index of suspicion for Wernicke encephalopathy even if only portions of the clinical syndrome are present, and immediate treatment with IV thiamine is critical in order to prevent devastating complications, including a profound and potentially irreversible amnestic state.

Ocular myasthenia can occur in pregnancy and cause diplopia, ophthalmoparesis, or ptosis just as in a nonpregnant woman. Ocular myasthenia during pregnancy can worsen in some patients but be unchanged or improve in others. If symptom exacerbation occurs, it is more likely to occur in the first trimester or after delivery (see “Pregnancy and Myasthenia Gravis” by Drs Janice Massey and Carolina De Jesus-Acosta in this issue of CONTINUUM for more on this topic).49

OCULAR AND ORBITAL PAIN

Diseases of the orbit will usually cause proptosis, possibly diplopia, and frequently pain. The most common orbital condition causing proptosis is thyroid eye disease. Approximately 5% of pregnant women have thyroid abnormalities. Thyroid-associated eye disease is more common in hyperthyroid than in euthyroid or hypothyroid states. Hypothyroid states must be treated pharmacologically for normal mental development of the fetus. Regardless of the etiology of thyroid-associated orbitopathy, the ocular results are the same.50 Ocular symptoms of thyroid eye disease include diplopia, conjunctival injection, photophobia, gritty sensation, and exophthalmos. Normal pregnancy can result in physiologic thyroid changes that mimic hyperthyroidism. Graves hyperthyroidism and gestational hyperthyroidism are the two most common etiologies for hyperthyroidism seen in pregnancy. Gestational hyperthyroidism can be observed. Graves hyperthyroidism should be treated with propylthiouracil (FDA grade D) during the first trimester and methimazole (FDA grade D) during the second and third trimester, since methimazole has a known teratogenic effect in the first trimester. Additionally, painless thyroiditis is the cause of thyrotoxicosis in 10% of patients overall and can occur in postpartum women, referred to as postpartum thyroiditis.50,51

Spontaneous orbital hemorrhage can occur with the Valsalva maneuver (vomiting or during labor). Symptoms include sudden pain, proptosis, and diplopia. Anticoagulation is a risk factor for this spontaneous event. The diagnosis is made with orbital ultrasound, orbital CT scan, or orbital magnetic resonance scanning. Generally, these orbital hemorrhages resolve without treatment.52,53

Orbital varices are not caused by pregnancy but can become manifest during pregnancy. A varix is an intraorbital mass consisting of abnormally large or dilated veins or a plexus of venous channels. Orbital varices present as a slowly increasing fullness of the orbit that may increase with bending over, sinus pressure, or other Valsalva maneuvers. The reason these manifest in pregnancy is related in part to increased blood volume that occurs in pregnancy. Diagnosis is made by orbital ultrasound, CT, or MRI, and no special management is usually needed for orbital varices because they usually do not cause problems.54

ABNORMAL PUPILS AND EYELIDS

Anisocoria or other pupil abnormalities should be approached in a pregnant woman the same way a nonpregnant patient would be evaluated. The neurologist needs to determine onset and chronicity of the anisocoria. It can be helpful to lookat old photographs, determine whether the patient has had prior ocular trauma or surgeries, and do a detailed review of all medications—even topical medications can inadvertently reach the eye. On examination, the neurologist should evaluate the patient’s direct and consensual constrictive response to light, rate of redilation, and near response. If the anisocoria is greater in dim light, the smaller pupil is the abnormal pupil, and Horner syndrome should be considered. If the anisocoria is greater in bright light, the larger pupil is the abnormal pupil, and Adie syndrome or an iris sphincter problem should be considered. Finally, evaluation should include the position of the eyelids and whether or not any pain or headache is present with the onset of the abnormal pupils, suggesting carotid artery dissection.

A painful Horner syndrome can occur as the presenting finding in carotid dissection, aneurysm, or tumor/mass effect. Self-limited acquired Horner syndrome can occur due to cephalad spread of anesthesia and because of a high epidural block.55 If other findings of a third nerve palsy, including a dilated pupil, are present, magnetic resonance or CT angiographic imaging should be done, because vascular causes, such as expansion and rupture of a posterior communicating artery aneurysm, may occur during pregnancy. The physician should look carefully for other associated signs to direct imaging: proptosis, ptosis, and any neurologic findings.53

Ptosis can be congenital or acquired. Etiologies include neurogenic (Horner syndrome, third nerve palsy), myogenic (myasthenia gravis), aponeurotic/levator dehiscence (most common), or mechanical. Mechanical ptosis is usually caused by an eyelid mass such as chalazion, eyelid edema, or dermatochalasis (excess upper eyelid skin). The neurologist can evaluate by looking at the margin reflex distance, which is the distance between the light reflex on the cornea and the upper and lower eyelids, and measuring palpebral fissure height and distance of upper eyelid crease from upper eyelid margin, as well as levator function (upper eyelid excursion). To evaluate eyelid excursion, the neurologist can place a thumb on the brow to eliminate assistance from the frontalis muscle, then ask the patient to look down toward his or her toes and then all the way up. Measuring the distance of travel is the amount of levator function, which is normally 12 mm or greater. The neurologist should then check for fatigability of eyelid elevation without blinking for 30 or more seconds. Progressive ptosis with upgaze is indicative of myasthenia. Associated miosis suggests Horner syndrome. A dilated pupil and associated adduction and vertical motility defects suggest a third cranial nerve palsy. Pupils are normal in myasthenia gravis.

CONCLUSION AND TRENDS

Pregnancy and the puerperium are a unique time period. However, workup for most eye concerns should proceed as if the patient were not in the pregnant state. Treatment should ensue, following the information available with regard to medication safety during pregnancy. Diagnosis of the problem causing the neuro-ophthalmic symptom is often crucial for the health of the patient and fetus.

KEY POINTS

• Differentiation of visual symptoms can help with diagnosis. The neurologist must determine whether the symptom is mild or severe blurring of vision, diplopia, scotoma (visual loss), or ocular pain.

• Vascular occlusions can occur with more frequency during pregnancy due to the hypercoagulable state of pregnancy.

• Blurred vision can also be migraine aura, which can be first experienced in the first trimester of pregnancy.

• Refractive error and corneal or lens changes are the most common reason for mildly blurred vision in pregnant women.

• Diabetic pregnant women are at risk for development or progression of retinopathy; each diabetic woman should have an eye examination during pregnancy.

• If a retinal artery occlusion is present in pregnancy, consider echocardiogram, since most occlusions are cardiac related.

• Preeclampsia and eclampsia can cause a wide variety of visual abnormalities and must be considered in any pregnant woman with visual concerns.

• Multiple sclerosis has an increased risk of symptom exacerbation during the postpartum period, while neuromyelitis optica has an increased risk of symptom exacerbation during the last trimester of pregnancy.

• The cause of disc edema or papilledema must be found and evaluated.

• When papilledema is present in pregnancy, look carefully for secondary causes including venous sinus thrombosis. Idiopathic intracranial hypertension can first occur in pregnancy in obese women.

• Meningiomas may increase in size during pregnancy; optic nerve meningioma may cause visual field changes.

• All women with papilledema, regardless of its cause, need to be followed with visual fields.

• Sudden onset of a headache in a patient known to have a pituitary tumor calls for imaging to look for apoplexy.

• Thyroid-associated orbitopathy is the most common etiology for proptosis in pregnancy.

• With anisocoria, onset and associated symptoms must be obtained. A careful search of the patient’s recent medications also needs to be evaluated.

ACKNOWLEDGMENTS

This review was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York, USA, to the Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah. Michael Varner, MD, provided suggestions about the content of this article. Susan Schulman assisted with preparation of the manuscript.