Neuro-ophthalmology and Pregnancy

Abstract

Purpose of Review:

This article summarizes the impact of pregnancy on neuro-ophthalmic pathways and presents an approach to the evaluation of pregnant women who have neuro-ophthalmic symptoms or signs.

Recent Findings:

Advances in noninvasive ophthalmic imaging have increased knowledge of the impact of pregnancy on ocular blood flow, which may have relevance for understanding the impact of preeclampsia and eclampsia on the eye.

Summary:

The framework for approaching neuro-ophthalmic symptoms and signs in pregnant women is similar to the general approach for people who are not pregnant. Visual symptoms are common in preeclampsia and eclampsia. Some diseases that impact the neuro-ophthalmic pathways are more common in pregnant women. Pregnancy should be considered when recommending the workup and treatment for neuro-ophthalmic symptoms and signs.

INTRODUCTION

Pregnancy induces changes throughout the body, including in the eyes and brain. This article begins with a discussion of pregnancy-associated changes in visual pathway structures that occur physiologically and pathophysiologically in states of preeclampsia and eclampsia. The remainder of the article provides a clinical approach to pregnant women who present with neuro-ophthalmic symptoms (eg, blurry vision, double vision) or signs (eg, papilledema, ptosis). Although the focus is on neuro-ophthalmic pathways, including the optic nerve, central visual pathways, and eye movements, common ophthalmic conditions with increased prevalence during pregnancy are also reviewed.

For the most part, the approach to pregnant patients with visual symptoms or signs is similar to the approach to nonpregnant patients, including comanagement with an eye care provider for conditions necessitating monitoring of vision or ophthalmic structures. The treating neurologist should be aware of mechanisms and etiologies of visual pathway disease that are more common in pregnant women and consider the risk to both the patient and fetus when recommending testing or treatment.

THE EYE IN PREGNANCY

Pregnancy induces physiologic changes in many, if not all, maternal organ systems, including in the eye. Although many of these changes are benign, they can cause visual symptoms and patients accordingly present for medical assessment. Other pregnancy-associated changes in the eyes and visual pathway are pathologic.

Physiologic Changes in the Eye

Pregnancy can be associated with shifts in refraction, which may cause blur at near or distance because of the need for new glasses or contact lenses.^1,2 This can be attributed to hormonal effects on the lens and cornea that alter their optical properties. Impaired accommodation can lead to blur at near. Dry eye disease related to decreased tear production increases during the third trimester,³ which may contribute to eye discomfort, blur, and contact lens intolerance.⁴ Although intraocular pressure generally decreases in pregnancy,⁵ this is not universal, and some people with glaucoma experience worsening during the course of pregnancy. Thus, close ophthalmologic monitoring of any pregnant woman with glaucoma is important.⁶

Blood flow to the retina is altered during normal pregnancy. Optical coherence tomography (OCT) is a noninvasive ophthalmic imaging technology with which cross-sectional images of the retina can be obtained with 5-micron resolution without dilating the pupils. OCT angiography obtains noncontrast images of the retinal microvasculature by detecting movement, similar to time-of-flight MRI. Multiple studies using OCT angiography have shown that the outer retina vascular density (a measure of perfusion) in the macula increases during pregnancy.^7–9 One study also showed an increase in perfusion of and around the optic nerve.⁹ Reports of vascular density changes in the inner retina have been conflicting. No differences in perfusion or thickness of the choroid, a high-flow vascular bed between the retina and the sclera, were seen in subjects with uncomplicated pregnancy compared with control subjects in a single study.¹⁰

Pathophysiologic Changes in the Eye

Central serous chorioretinopathy is an idiopathic local detachment of the retinal pigment epithelium that is typically more common in men but can cause focal vision disturbance in pregnant women.¹¹ The same mechanisms responsible for cerebral infarct in pregnant women (eg, amniotic fluid emboli, hematologic emboli, vasculitis) can cause central retinal artery and branch retinal arterial occlusion presenting as sudden (partial) vision loss in one eye. Central and branch retinal vein occlusions also occur in association with hypercoagulable states in pregnancy and also present with sudden (partial) vision loss in one eye. Purtscher-like retinopathy is a rare cause of vision loss in the immediate postpartum setting because of patchy retinal infarction postulated to be due to amniotic fluid activation of complement causing leukocyte aggregates blocking arterioles.¹²

Diabetic retinopathy can worsen in pregnant women with risk factors such as longer duration of diabetes prepregnancy, higher baseline level of diabetic retinopathy during pregnancy, and worse glycemic control.¹³ Diabetic retinopathy is generally not an issue in those with solely gestational diabetes. Vision-impacting retinal disease is typically apparent via examination by a qualified eye care provider, with the exception of central serous chorioretinopathy, for which OCT can aid in diagnosis (Figure 7-1). For a comprehensive review of ophthalmic changes during pregnancy, refer to excellent reviews by Grant¹⁴ and Kalogeropoulos.¹⁵

Figure 1.

Retinal causes of acute vision loss in pregnancy. Inferior temporal branch retinal artery occlusion of the right eye (A, arrows) causing temporal visual field loss (B). Lack of retinal whitening is consistent with either a hyperacute or chronic state. Central retinal vein occlusion of the right eye shows optic nerve head swelling, enlarged tortuous venules, and retinal hemorrhages (C) compared to baseline (D). Optical coherence tomography of central serous chorioretinopathy shows retinal pigment epithelial detachment pushing up the fovea (E, arrow) compared to the normal foveal contour (F).

Panels A and B courtesy of Kathleen Digre, MD. Panels C and D courtesy of Huy Nguyen, MD. Panels E and F courtesy of Ted Leng, MD.

THE VISUAL SYSTEM IN PREECLAMPSIA AND ECLAMPSIA

Visual symptoms are common in people with preeclampsia and eclampsia, with one study reporting prevalence of almost 30% in preeclampsia and almost 70% in eclampsia among patients who reported neurologic symptoms.¹⁶ This is likely an overestimate as patients without neurologic symptoms were not included in this study. In another study, 45% of patients reported visual disturbance before an eclampsia-defining seizure.¹⁷ The most common symptoms are “spots” (in approximately 35% of patients with preeclampsia/eclampsia) and color vision disturbances (in approximately 25%), with blurred vision and reduced visual acuity seen in a minority of patients with severe preeclampsia/eclampsia.¹⁸ Blindness can rarely occur.¹⁹

The etiologies of visual symptoms are myriad and include changes to the retina and brain as well as sporadic involvement of the optic nerve and cranial nerves. Retinal changes are similar to those seen in non–pregnancy-related hypertension, including arteriolar narrowing, focal retinal ischemia (cotton wool spots), hemorrhages, and, in severe cases, optic disc edema. Preeclampsia can cause focal occlusion of the choroidal circulation leading to changes in the overlying retina, including color changes (Elschnig spots) and serous retinal detachments (Figure 7-2).²⁰ Retinal and choroidal thickness measured using OCT have been reported to be increased in severe preeclampsia²¹ and may be a marker for this given that choroid thickness is not generally increased in pregnancy.¹⁰

Figure 2.

Retinal findings in preeclampsia/eclampsia. Cotton wool spots (A, arrows), indicating retinal ischemia; retinal hemorrhages (B, arrows); hypopigmented areas caused by choroidal infarction underneath the neurosensory retina (C, arrows); serous retinal detachment (D, arrows).

Figure courtesy of Kathleen Digre, MD.

Although not common, cranial nerve involvement can occur in association with preeclampsia/eclampsia and contribute to visual symptoms. Optic nerve swelling and dysfunction can occur in association with hypertensive retinopathy, elevated intracranial pressure (ICP), or ischemic optic neuropathy.²² Both single and multiple cranial nerve palsies impacting extraocular motility have been described in association with preeclampsia.²³

Posterior reversible encephalopathy syndrome (PRES) associated with preeclampsia/eclampsia can cause visual disturbance on a cerebral basis (Figure 7-3). Visual symptoms are more common in patients with PRES, occurring in 50% compared to in 25% of those without PRES in one study.¹⁶ The same study found visual disturbances to be more common in patients with cytotoxic edema than in patients with vasogenic edema on MRI. Blindness from any cause has been estimated to occur in 15% of patients with eclampsia, with over 80% of these attributable to PRES¹⁹ Other symptoms of PRES include visual processing disturbances (eg, simultagnosia, optic ataxia, alexia).¹²

Figure 3.

MRI changes characteristic of posterior reversible encephalopathy syndrome (PRES) associated with preeclampsia/eclampsia. Axial fluid-attenuated inversion recovery (FLAIR) images show hyperintensity of parietal and occipital white matter, which can be associated with vision loss and visual processing disturbances.

Figure courtesy of Nancy Fischbein, MD.

Magnesium, which is used to treat preeclampsia, can impair accommodation and cause blur.²⁴ This can be diagnosed using a pinhole occluder. Although recovery of visual deficits from preeclampsia/eclampsia is typically excellent, permanent visual impairment can persist. Interestingly, reduced vision-specific quality of life was reported in patients with eclampsia an average of 10 years postpartum despite normal visual field testing.²⁵

APPROACH TO VISUAL SYMPTOMS IN PREGNANCY

As in nonpregnant patients, localization of the cause of blur is the first step in evaluation of pregnant patients with blurry vision. Asking if the symptoms are present when using both eyes, the right eye alone, or the left eye alone guides localization. If the patient does not know, they can be talked through the exercise in the office or during a telehealth visit. A symptom that is present only when both eyes are open but not with either eye alone suggests ocular misalignment as the cause of the symptom. A symptom present when using one eye in isolation but not when using the other suggests a problem anterior to the chiasm on the affected side. A symptom that is similar with each eye used in isolation and with both eyes used together suggests a retrochiasmal cause. Dysfunction of the chiasm or structures anterior to the chiasm on both sides will typically cause dissimilar symptoms when comparing each eye used in isolation.

Examination should include visual acuity with each eye at the distance at which the patient is symptomatic (ie, near or far). If visual acuity is abnormal despite the patient’s usual corrective lenses, acuity should be rechecked using a pinhole occluder, which will correct for most refractive and ocular surface causes of blur. Confrontation visual fields are sensitive and specific for severe vision loss. Formal perimetry, available in most ophthalmology offices, should be obtained if concern exists for peripheral vision loss and confrontation visual field testing is normal. Pupil examination should assess for anisocoria in light versus dark and relative afferent pupillary defect(rAPD). Anisocoria worse in light suggests that the large pupil has trouble constricting (e.g. due to parasympathetic impairment). Anisocoria worse in light suggests that the small pupil has trouble dilating (e.g. due to sympathetic impairment. rAPD demonstrates lower direct than indirect pupillary response and suggests impaired perception of light in that eye (e.g. due to optic neuropathy). Extraocular motility examination should be complemented by assessment of ocular alignment using techniques such as Maddox rod or alternating cover testing.

Funduscopic examination is necessary to assess the optic nerve head and vascular changes in the retina. If visualization is difficult, options include dilating the pupils with topical mydriatic medications, which is regarded to be safe during pregnancy,²⁶ and the use of nonmydriatric funduscopic photography. OCT, which is nonmydriatic, can also be helpful to visualize the shape of the retina and optic nerve head. Referral to an eye care provider may be necessary to obtain a dilated funduscopic examination, fundus photography, or OCT imaging.

BLURRY VISION IN ONE EYE (CAN IMPACT BOTH EYES)

Central serous chorioretinopathy in the retina can cause local loss of vision or metamorphopsia (Figure 7-1), seen as focal waviness of straight lines when viewing an Amsler grid, which is a grid of horizontal and vertical lines used to test the central 20 degrees of vision. Although this can be challenging to observe on funduscopic examination, it is readily visible using OCT. Acute vision loss in one eye is concerning for ischemia (arterial or venous) to the retina (Figure 7-1) or optic nerve. Ischemia of the retina is the equivalent of cerebral stroke and should be managed similarly. For more information on stroke in pregnancy, refer to the article “Maternal Stroke” by Eliza C. Miller, MD, MS, in this issue of Continuum.

A common consideration for unilateral vision loss in women of childbearing age regardless of pregnancy status is optic neuritis. A typical history is progressive loss of vision in one eye over days associated with pain on eye movements. Examination findings include loss of visual acuity, visual field loss, and relative afferent pupillary defect. The optic nerve head can appear normal or mildly swollen in the acute setting. Women with multiple sclerosis generally experience fewer attacks of optic neuritis during pregnancy, thought to relate to a relative immunosuppressed state during pregnancy; however this relative remission is less pronounced in patients with neuromyelitis optica (NMO). Both multiple sclerosis and NMO often have more activity in the postpartum period.²⁷ Two case series examined relapses of anti–myelin oligodendrocyte glycoprotein (MOG)–associated disorder during pregnancy, reporting 10% to 20% of patients with attacks (mostly optic neuritis) during pregnancy, 40% with postpartum attacks, and 50% to 70% with no attacks during gestation or postpartum.^27,28 See demyelinating disease chapter in this issue of continuum for more information.

Meningiomas, particularly of the skull base or optic nerve sheath, can grow during pregnancy to cause accelerated visual symptoms due to optic nerve compression. This accelerated growth is thought to be related to increased estrogen, progesterone, prolactin, and possibly vascular endothelial growth factor (VEGF).²⁹ In a large case series of pregnancy-related meningiomas, skull base location and presentation with visual symptoms were more common than in non–pregnancy-related meningiomas.³⁰ See neuro-oncology chapter in this issue of continuum for more information.

BLURRY VISION IN BOTH EYES

If pregnant patients have blurry vision in both eyes, consideration should be given to refractive error or accommodation impairment (which both generally differ in near versus distance viewing and improve with pinhole) and ocular surface dryness; the symptoms of ocular surface dryness are usually variable and respond to topical artificial tears, which can be obtained without prescription.

In addition to bilateral presentation of the unilateral conditions discussed above, symptoms in both eyes should prompt consideration of chiasmal or retrochiasmal disease. Chiasm-impacting diseases with increased incidence in pregnant women include enlargement of pituitary tumors, Sheehan syndrome due to hemorrhage into an infarcted pituitary tumor (see neuro-oncology chapter in this issue of continuum), lymphocytic hypophysitis, and, rarely, physiologic pituitary enlargement.³¹ All of these can cause classic bitemporal visual field loss, but also unilateral vision loss as well as cranial nerve III, IV, V, or VI palsy due to cavernous sinus extension. Lymphocytic hypophysitis is an inflammatory condition of the pituitary thought to be autoimmune in etiology that is clinically and radiologically heterogeneous. The most common symptoms are hypopituitarism, headaches, and vision loss. Half of all cases of lymphocytic hypophysitis occur in association with pregnancy (Case 7-1).³² For pregnant women with known pituitary adenomas, monitoring with formal visual fields during pregnancy can be helpful to detect chiasmal dysfunction. Acute onset of symptoms localizing to the chiasm suggests Sheehan syndrome or pituitary apoplexy. Acute-onset vision loss localizing to retrochiasmal dysfunction suggests stroke or PRES associated with preeclampsia/eclampsia.

Case 7–1.

A 29-year-old woman at 35 weeks’ gestation presented with headaches and blurry vision worsening over 2 weeks. Her visual acuity was 20/20 with each eye, and confrontation visual fields were normal. Ophthalmoscopic examination was normal. Humphrey visual field testing showed mild temporal visual field constriction in both eyes. This prompted MRI of the sellar region, which showed an enlarged pituitary gland abutting the optic chiasm (Figure 7-4). Shortly after completion of the MRI, she spontaneously delivered a healthy baby boy. Transsphenoidal biopsy of the lesion performed postpartum showed inflammatory infiltrates of B cells and T cells without abnormal morphology diagnostic of lymphocytic hypophysitis. She was treated with corticosteroids, and her vision normalized. Endocrine evaluation was unrevealing.

Comment

This case exemplifies one of the suprasellar pathologies that can grow during pregnancy to compress the chiasm and cause peripheral vision loss.

Figure 4.

Imaging of the patient in Case 7-1. Coronal noncontrast T1-weighted MRI shows enlargement and enhancement of the pituitary gland abutting the optic chiasm.

Figure courtesy of Nancy Fischbein, MD.

Migraine with aura is less likely to remit during pregnancy than migraine without aura, and migraine with aura can also occur de novo during pregnancy.³³ For more information on migraine and pregnancy, refer to the article “Headache in Pregnancy and Lactation” by Melissa Rayhill, MD, FAHS, in this issue of Continuum. Migraine with aura may also worsen during the postpartum period because of interrupted sleep. Typical symptoms of auras are positive visual phenomena that evolve over 10 to 20 minutes and feature movement of the image that occurs prior to or without headache. Sudden onset of visual symptoms suggests ischemia.

PAPILLEDEMA

Although papilledema due to elevated ICP does cause visual symptoms, including peripheral vision loss, general blur, and transient visual obscurations, up to 50% of individuals with papilledema do not have visual symptoms.³⁴ [KP 7] Evaluation for papilledema in pregnant patients with headache or other symptoms suggestive of high ICP, such as pulsatile tinnitus, is imperative to prompt evaluation for both primary and secondary causes of high ICP. Some secondary causes of ICP, such as cerebral venous sinus thrombosis (diagnosed using neuroimaging) may be more common in the third trimester and postpartum because of the associated hypercoagulable state. If no secondary cause is found on MRI of the brain and magnetic resonance venography (MRV) of the brain, lumbar puncture is important to measure opening pressure and evaluate CSF for secondary causes of high ICP. Even if a secondary cause is found on neuroimaging, lumbar puncture may provide temporary lowering of pressure to provide symptom relief and mitigate the short-term risk of vision loss.

Regardless of the cause of high ICP, any patient with papilledema due to high ICP must be monitored regularly by an ophthalmologist or neuro-ophthalmologist to assess the optic nerve appearance and peripheral visual function so that the risk of vision loss can be appropriately managed. Because vision loss from papilledema can be difficult to detect on bedside examination, formal visual field testing with automated perimetry is preferred.

Idiopathic Intracranial Hypertension

Although some people develop idiopathic intracranial hypertension (IIH) during pregnancy, it is perhaps more common that women with preexisting IIH become pregnant (Case 7-2). Despite the well-established association between IIH and weight gain, pregnancy does not typically exacerbate IIH, nor are outcomes different than in nonpregnant women with IIH.³⁵ IIH in pregnancy was recently reviewed by Park and colleagues.³⁶

Case 7–2.

A 35-year-old woman with a 1 year history of idiopathic intracranial hypertension managed on acetazolamide sought prenatal consultation regarding medication management. She had no visual symptoms and no headaches. Visual acuity was 20/20 with each eye, and Humphrey visual field testing was normal. She had mild fullness of both optic nerves. Optical coherence tomography showed mild optic nerve elevation without ganglion cell injury.

Given her lack of symptoms, she was weaned off acetazolamide over 2 months without development of symptoms or change in optic nerve appearance. Following conception, she was monitored by her neuro-ophthalmologist every 6 to 8 weeks. In the second trimester, her optic nerves became more elevated, but she did not develop headaches, visual field loss, or ganglion cell injury; therefore, no medication was started. This remained stable throughout the remainder of her pregnancy. She had consultations with maternal-fetal medicine and anesthesia regarding her delivery plan. Given the lack of vision loss or signs of optic nerve injury on examination and ophthalmic imaging, plans were made to proceed with a vaginal delivery. This occurred spontaneously at 37 weeks with no complications.

Comment

This case exemplifies the medication, monitoring, and delivery planning considerations in a pregnant woman with preexisting idiopathic intracranial hypertension.

The goals of treatment of IIH in a pregnant woman are to prevent permanent vision loss due to optic nerve damage and manage symptoms. Accordingly, it may be appropriate not to treat IIH in a patient with mild papilledema, without vision loss and no or minimal headaches. Weight loss, which is effective for treatment of IIH in nonpregnant people, should be undertaken with caution in those who are pregnant. Restricted weight gain (eg, with a salt-restricted diet) has been reported to reduce visual dysfunction.³⁷ Oral acetazolamide, which has Level I evidence for IIH treatment in the nonpregnant population, is classified as Category C by the US Food and Drug Administration (FDA) using the pre-2015 classifications. Although case reports exist of fetal malformations born to people exposed to acetazolamide, studies of 113 pregnant women who were exposed to acetazolamide, including 59 in the first trimester, did not identify adverse outcomes as a result of acetazolamide use.^38,39 Topiramate, classified as Category D by the FDA using the pre-2015 classifications, is associated with oral clefts.⁴⁰ In patients with no evidence of vision loss or ganglion cell injury, symptomatic management of headache is an option. For more information about symptomatic management of headaches in pregnant women, refer to the article “Headache in Pregnancy and Lactation” by Melissa Rayhill, MD, FAHS, in this issue of Continuum.

Lumbar puncture transiently lowers ICP and can provide longer than expected relief in some patients. In pregnant patients with severe vision loss associated with papilledema, surgical intervention with optic nerve sheath fenestration or CSF diversion can be considered if the risk of vision loss outweighs the risks of surgery and anesthesia.

Uterine contractions are associated with a rise in ICP of 3.4 cm H₂O, whereas Valsalva during delivery caused an increase of 10.8 cm H₂O in a study of pregnant women without IIH.⁴¹ Another study estimated higher increases to 70 cm H₂O during labor. Furthermore, lumbar epidural anesthesia may elevate ICP, and this elevation may be more pronounced when baseline ICP is elevated, based on an animal model.⁴² Although this increase could theoretically put additional stress on an optic nerve with dysfunction, many people with IIH have had successful vaginal deliveries with the aid of obstetrical anesthesia without maternal or fetal morbidity.⁴³ Ultimately, the decision is best made by the patient’s multidisciplinary care team.

DIPLOPIA

If a person presents with diplopia, the first thing to check is whether it resolves with covering either eye. Resolution with covering either eye suggests that the person is experiencing binocular diplopia (one image coming from each eye) due to ocular misalignment. If the diplopia persists when one eye is covered, it is monocular diplopia attributable to an optical cause in the eye (refer to the discussion on refractive error and dry eye above). Lack of diplopia does not exclude ocular misalignment (eg, in people with poor vision in one eye or poor binocularity).

Careful examination of eye movements and ocular alignment in different directions of gaze is helpful to localize the underlying cause of binocular diplopia or ocular misalignment. Other clues can be gathered from the symptoms: vertical or oblique diplopia suggests involvement of the superior oblique or vertical rectus muscles, horizontal diplopia worse at distance suggests esotropia, and horizontal diplopia worse at near suggests exotropia. For example, horizontal diplopia worse at distance that resolves when looking to the left suggests a right sixth nerve palsy Symptom patterns and measurable misalignment may be apparent before obvious extraocular motility deficits manifest.

Idiopathic cranial nerve palsies can occur during pregnancy but are diagnoses of exclusion. Sixth nerve palsies are associated with gestational hypertension and preeclampsia. They can also result from intracranial hypertension and may be a presenting sign of cerebral venous sinus thrombosis. Intracranial hypotension (eg, after lumbar puncture or inadvertent dural puncture during obstetrical anesthesia) can also cause sixth nerve palsy.⁴⁴

Cavernous sinus invasion because of pituitary tumor growth, pituitary apoplexy, Sheehan syndrome, or lymphocytic hypophysitis can cause diplopia through dysfunction of cranial nerves III, IV, and VI, with cranial nerve VI being the most commonly affected. Numbness in the forehead and cheek suggestive of involvement of the V1 and V2 divisions of the trigeminal nerve and Horner syndrome can also occur in cavernous sinus disease. Skull base meningiomas can grow during pregnancy to impact cranial nerves and have been reported to recoverafter delivery.⁴⁵

As in nonpregnant people, an expanding posterior communicating artery aneurysm in pregnant women is a cause of cranial nerve III palsy, necessitating emergent treatment. Parenchymal disease due to multiple sclerosis, strokes, or tumors can cause diplopia because of internuclear ophthalmoplegia and skew deviation.

Diplopia, ophthalmoplegia, and/or nystagmus can occur because of thiamine deficiency as part of Wernicke encephalopathy (Case 7-3). Other symptoms include ataxia and confusion. The funduscopic examination can show hemorrhages. Wernicke encephalopathy can can be provoked by hyperemesis gravidarum, and urgent repletion with IV thiamine should be instituted.⁴⁶

Case 7–3.

A 27-year-old woman at 15 weeks’ gestation presented with blurry vision and fatigue. She described excessive vomiting for the past 7 weeks, with a weight loss of 12 kg (26.5 lb), for which she had not received care. On examination, she had upbeat nystagmus, and her extraocular movements were full without diplopia. Her gait was unsteady. Thiamine deficiency causing partial Wernicke encephalopathy was suspected, and she was empirically treated with IV thiamine and IV fluids while blood test results were pending. Over the ensuing days, her fatigue and blurry vision resolved. Following treatment with antiemetics, she was able to tolerate an oral diet.

Comment

This case exemplifies the clinical presentation of thiamine deficiency induced by malnutrition due to hyperemesis gravidarum. Maintaining a high clinical suspicion for malnutrition in patients with hyperemesis gravidarum is critically important to allow for prompt diagnosis and treatment as delayed treatment is associated with permanent sequelae including Korsakoff syndrome characterized by memory loss.

Ocular myasthenia gravis and thyroid eye disease are autoimmune diseases impacting the neuromuscular junction and extraocular muscles that can cause diplopia. Ocular myasthenia gravis can improve, worsen, or stabilize during pregnancy. Because ptosis and diplopia are not life-threatening symptoms, conservative management with patching one eye (applying translucent tape to glasses is often effective) and cosmetic lid tape can be offered if medications are being avoided. For more information on myasthenia gravis and pregnancy, refer to the article “Neuromuscular Disorders and Pregnancy” by Janice M. Massey, MD, FAAN, and Karissa Gable, MD, in this issue of Continuum. Preexisting thyroid eye disease has a variable course during pregnancy and can cause worsening of orbital signs, diplopia, and lid retraction in some people.⁴⁷ Although conservative management is generally appropriate, severe cases may need orbital decompression to reverse compressive optic neuropathy.⁴⁸ Detection and treatment of associated thyroid hormone dysregulation is important for the health of the pregnancy.

OTHER EYE AND FACIAL SYMPTOMS

Symptoms involving the eyelids, facial muscles and pupils as well as pain in the eyes and face can occur in association with pregnancy.

Eyelid and Facial Abnormalities

The palpebral fissure can appear smaller because of ptosis and larger because of lid retraction or proptosis. Isolated Horner syndrome causing a small pupil and mild ipsilateral ptosis can occur because of migration of spinal anesthetic,⁴⁹ but carotid dissection should also be considered (Case 7-4). Myasthenia gravis can cause fluctuating ptosis, often with variable diplopia. Ptosis in association with extraocular motility limitations suggests third cranial nerve palsy. Aponeurotic ptosis due to hormonal effects on the levator palpebrae muscle can manifest during pregnancy.⁵⁰ The eye can appear prominent, with sclera visible superior or inferior to the iris in the relaxed state because of orbicularis oculi weakness from cranial nerve VII palsy, lid retraction from thyroid eye disease, or proptosis because of increased orbital volume due to mass or inflammation.

Case 7–4.

A 30-year-old woman was noted to have left ptosis following vaginal delivery of a healthy baby. She had no other symptoms. During delivery, she had received epidural analgesia with a T8 sensory level. On examination, she had 1 mm of relative ptosis of the left eye with symmetric levator function. In dark, the right pupil was 4 mm and the left pupil was 1 mm. In light, the right pupil was 2 mm and the left pupil was 1 mm. A diagnosis of a left Horner syndrome was made. Magnetic resonance angiography (MRA) of the neck with fat saturation did not show carotid dissection, and her symptoms were presumed to be due to upward spread of anesthetic in the epidural space to impact the sympathetic fibers at their site of origination in the lower cervical and upper thoracic spinal cord (see anesthesia chapter in this issue of Continuum). The ptosis and miosis resolved within 24 hours.

Comment

This case demonstrates Horner syndrome developing from anesthetic migration. As this is a diagnosis of exclusion, neuroimaging was performed to exclude alternative causes.

Cranial nerve VII palsy is approximately 3 times more common in pregnant women than in nonpregnant women of similar age, typically developing during the third trimester, and may be associated with worse long-term outcomes.⁵¹ Perineural edema causing compression, hypercoagulability, and viral reactivation may contribute.⁵² Some experts advocate for treatment with steroids, as in non–pregnancy-associated cranial nerve VII palsy, citing safe use of steroids for other conditions in pregnancy along with the association with better outcomes in nonpregnant people.⁵² Cranial nerve VII palsy has been reported in association with spinal and epidural anesthesia⁴⁴ If the eyelid does not close completely, protection of the ocular surface with frequent application of ocular lubricant and taping the lid shut overnight is important. Surgical tarsorrhaphy can be performed if patients have ocular surface damage.

An enlarged palpebral fissue due to mild proptosis can appear similar cranial nerve VII palsy. One cause of this is orbital varices, which can become symptomatic in pregnancy because of changes in hemodynamics to cause orbital fullness that is worse with bending over or Valsalva.⁵³

Pupil Abnormalities

The pupil can be large because of impaired parasympathetic response or small because of impaired sympathetic response. Comparison of pupil asymmetry in light and dark environments helps to determine which is the abnormal pupil. As in nonpregnant people, the most concerning cause of a large pupil with anisocoria more pronounced in light is a posterior communicating artery aneurysm, and careful examination should be pursued to detect ipsilateral ptosis and ocular motility limitations to suggest third nerve palsy. A small pupil with anisocoria worse in dark is concerning for Horner syndrome, as discussed above. Impaired accommodation can occur in association with migraine or idiopathically to cause bilateral large pupils with blurry vision at near that resolves with pinhole or reading glasses. A relative afferent pupillary defect suggests optic nerve dysfunction.

Eye Pain

If patients have localized eye pain, an ophthalmologic examination is advised to exclude eye disease (eg, uveitis, corneal abrasion) as a cause of the pain. Dry eye, which increases during pregnancy, can cause eye pain that may worsen at the end of the day or after screen use. Initial treatment is with nonprescription artificial tears 3 to 4 times daily to improve the ocular surface and prevent dryness from developing. Primary headache syndromes are commonly associated with eye pain that is not necessarily temporally coincident with the headache. This can be managed together with the eye pain.

CONCLUSION

The approach to neuro-ophthalmic symptoms and signs in a pregnant woman is similar to that for people who are not pregnant, including obtaining a thorough history and careful examination. The differential diagnosis should consider any preexisting disease; the physiologic changes of pregnancy; the pathophysiologic changes of pregnancy, particularly eclampsia; and disease processes that are more prevalent during pregnancy. Evaluation and management should consider risks and benefits to both the parent and the fetus.

KEY POINTS.

• [KP 1]Ocular surface and cornea changes in pregnancy can cause blur, eye pain, refractive shift, and contact lens discomfort.
• [KP 2]Branch retinal vein occlusions, branch retinal artery occlusions, and central serous chorioretinopathy are retinal causes of acute partial vision loss in pregnancy.
• [KP 3]Visual symptoms occur in more than one-fourth of patients with preeclampsia and almost half of patients with eclampsia.
• [KP 4]The approach to visual symptoms in pregnancy is similar to the approach to visual symptoms in other patients.
• [KP 5]Dilating the pupils with eye drops is regarded to be safe during pregnancy.
• [KP 6]Optic neuritis related to multiple sclerosis, neuromyelitis optica, and myelin oligodendrocyte glycoprotein–associated disorder is less common during pregnancy and has increased frequency postpartum.
• [KP 7]Bilateral optic disc edema from increased intracranial pressure does not cause visual symptoms in up to half of affected patients.
• [KP 8]Regular formal perimetry to monitor visual fields of patients with papilledema from primary or secondary high intracranial pressure is important to detect vision loss so that ICP lowering therapy can be advanced to prevent further worsening.
• [KP 9]Sixth nerve palsies in pregnancy can result from intracranial hypertension (eg, due to cerebral venous sinus thrombosis) and hypotension (eg, due to dural puncture during anesthesia).
• [KP 10]

  Growth of sellar and suprasellar structures during pregnancy can cause vision loss, diplopia, facial numbness, and Horner syndrome.

• [KP 11]

  Eye movement abnormalities can be caused by thiamine deficiency provoked by hyperemesis gravidarum, which requires urgent treatment.

• [KP 12]

  Facial nerve palsy is the most common cranial nerve palsy in pregnancy.

• [KP 13]

  Artificial tears are the first-line treatment for management of eye pain and blur due to dry eye.

ABBREVIATIONS

CSF

Cerebrospinal fluid

FDA

US Food and Drug Administration

ICP

Intracranial pressure

IIH

Idiopathic intracranial hypertension

IV

Intravenous

MOG

Myelin oligodendrocyte glycoprotein

MRA

Magnetic resonance angiography

MRI

Magnetic resonance imaging

MRV

Magnetic resonance venography

NMO

Neuromyelitis optica

OCT

Optical coherence tomography

PRES

Posterior reversible encephalopathy syndrome

VEGF

Vascular endothelial growth factor