The eye and visual system in pregnancy, what to expect? An in-depth review

Abstract

Pregnancy represents a real challenge to all body systems. Physiological changes can involve any of the body organs including the eye and visual system. The ocular effect of pregnancy involves a wide spectrum of physiologic and pathologic changes. The latter might be presenting for the first time during pregnancy such as corneal melting and corneal ectasia, or an already existing ocular pathologies that are modified by pregnancy such as diabetic retinopathy and glaucoma. In addition, pregnancy can affect vision through systemic disease that are either specific to the pregnant state itself such as the pre-eclampsia/eclampsia and Sheehan's syndrome, or systemic diseases that occur more frequently in relation to pregnancy such as Graves’ disease, idiopathic intracranial hypertension, anti-phospholipid syndrome, and disseminated intravascular coagulation.

Introduction

Pregnancy represents a serious challenge to all body systems. The progressive physiological changes that occur are essential to support and protect the developing fetus in addition to prepare the mother for parturition.[1] These physiologic changes involve cardiovascular, renal, pulmonary, hormonal, metabolic, hematologic, immunologic, and visual systems.[1] In the presence of clinical or sub-clinical pathology, the normal physiologic changes of pregnancy can place significant strain on already compromised systems.[1,2]

Ocular complications are common during pregnancy.[3] In general, the ocular effect of pregnancy can be divided in to physiologic and pathologic changes. The pathologic changes are further divided in to the following:

• Ocular changes occurring for the first time during pregnancy

• An already existing ocular pathology that is modified by pregnancy

• Ocular complications of systemic diseases. These are either pregnancy specific diseases such as pre-eclampsia/eclampsia syndrome and Sheehan syndrome, or diseases that occur more frequently during pregnancy such as idiopathic intracranial hypertension (IIH), Graves’ disease, Antiphospholipid syndrome (APS) and disseminated intravascular coagulation (DIC).[3]

Although, most of pregnancy ocular complications are mild, transient and require no treatment, some are occasionally serious, permanent and require prompt ophthalmic referral. In addition, some ocular complications occurring during pregnancy may provide a direct insight in to the pathophysiology of many systemic diseases.

This article provides a review of the physiologic changes of pregnancy, the effect of pregnancy on pre-existing ocular disease and the ocular manifestations of systemic diseases in pregnant women. The ocular complications of pre-eclampsia/eclampsia syndrome will be discussed in part 2 of this review.

Physiologic Changes

Eyelids

One of the most common ocular physiologic changes includes increased pigmentations around the eye.[4] These pigmentations, known as melasma or chloasma, are reversible and fade slowly after pregnancy. It is postulated that hormonal variations of pregnancy increase melanin as a result of an increase in both melanogenesis and melanocytosis.[4]

Tear

Pregnancy affects the physiology of the tear film resulting in dry eye syndrome.[5] This may occur as a result of the direct disruption of lacrimal acinar cells through pregnancy enhanced immune-reactivity of prolactin, transforming growth factor beta 1, and epidermal growth factor in ductal cells.[5,6]

Cornea

Cornea may show changes in sensitivity, thickness or curvature. Corneal sensitivity tends to decrease, with most changes occur late in pregnancy.[7] A measurable increase in corneal thickness due to edema has been reported to occur during pregnancy.[8] An increase in corneal curvature also has been reported.[9] Park et al. showed that there was a statistically significant increase in corneal curvature during the second and third trimesters which resolved completely after delivery or after the cessation of breast feeding.[9]

Changes in thickness may alter the refractive index of the cornea; thereby changing refraction.[10] Many women develop contact lens intolerance while pregnant despite a previous success. This intolerance may be due to the increase in either corneal curvature or thickness.[10,11] It is advisable that pregnant women wait until at least several weeks postpartum before obtaining a new spectacle prescription or new contact lens fitting.[10,11]

Lens

Transient loss of accommodation has been reported previously both with pregnancy and lactation.[3] The timing for refractive surgery in a pregnant woman or in a woman planning to become pregnant can be a difficult decision. It is better to delay refractive surgery during pregnancy and wait until stability of refraction is clear postpartum.[11]

Intraocular pressure

IOP decreases during pregnancy.[12,13] Studies in healthy women have shown a statistically significant decrease in IOP during all trimesters of pregnancy compared with non-pregnant women.[14] IOP declines as pregnancy advances, with statistically significant decrease in IOP from the first to the third trimesters.[13]

Immunity

Pregnancy is associated with immune suppression, an essential physiologic element for the implantation of the embryo.[15] It is associated with lower rates of flare-ups of non-infectious uveitis compared to the non-pregnant state.[14] Pregnancy has a beneficial effect on number of uveitis syndromes including Vogt-Koyanagi-harada syndrome, Behcet disease and the idiopathic uveitis syndrome.[14,16]

Visual field

VF changes have been reported in pregnant women.[17] Wide speculation exists about the degree and mechanism of these changes. In one study that was conducted in healthy pregnant women, Akar et al.[17] found that the VF mean threshold sensitivity increased significantly in the third trimester. These asymptomatic VF changes were shown to be completely reversible postpartum.[17]

Ocular Diseases Modified by Pregnancy

Diabetic retinopathy

The number of women with diabetes in pregnancy is increasing, partly as a reflection of increasing obesity in women of child-bearing age.[18] DR is the most common ocular condition modified by pregnancy and pregnancy is associated with an increased risk of development and progression of DR.[18,19,20,21]

DR developing during pregnancy may show a high-rate of spontaneous regression after delivery. In a study of patients with no DR at onset who then developed mild non-proliferative DR (NPDR) during pregnancy, 50% had complete regression, and 30% had partial regression of DR after delivery.[22]

Factors that have been shown to influence the progression of DR in pregnancy include, the pregnant state itself, duration of diabetes, degree of retinopathy at time of conception, metabolic control of diabetes, and the presence of co-existing hypertension.[23]

The exact pathogenesis for the progression of DR during pregnancy remains controversial. Some studies demonstrated a decrease in retinal venous diameter and volumetric blood flow in diabetic patients during pregnancy and hypothesized that this may exacerbate retinal ischemia and hypoxia.[24,25] On the other hand, several studies have reported an increase in retinal blood flow in diabetic patients during pregnancy and suggested that this hyper-perfusion causes an added stress to an already compromised retinal circulation leading to the progression of Diabetic retinopathy (DR).[26]

Several studies have shown that higher glycosylated hemoglobin (HbA1C) levels at conception and the rapid tightening of glycemic control during pregnancy have been associated with a higher risk of DR progression. The diabetes in early pregnancy study showed that elevated HbA1C at baseline was associated with a higher risk of retinopathy progression and the rates of progression almost doubled in women with HbA1C levels greater than 6 standard deviation above the control mean.[19,26]

Diabetic women in child-bearing age should be counseled regarding the risk of development and progression of DR. The risk of retinopathy progression during pregnancy is higher in patients with inadequate glycemic control, thus, whenever possible, tight glycemic control should be attained before conception.[27]

Patients with severe NPDR or proliferative DR (PDR) are at a higher risk of progression during pregnancy thus, it is advisable to postpone conception until stabilization of their ocular disease.[27]

Diabetic patients with PDR during pregnancy should be managed the same way as non-pregnant patient. However, retinopathy level should be monitored closely and treatment initiated early once indicated. Guidelines for screening of diabetic women include, an ophthalmic evaluation before conception and then again in the first trimester. Subsequent examination depends on the level of retinopathy. Women with gestational diabetes are not at an increased risk of DR and thus, don’t need to be examined under these guidelines.[19,25,26,27]

Glaucoma

It was mentioned earlier that IOP decreases during pregnancy as part of normal physiologic changes.[12,13] During pregnancy women with ocular hypertension demonstrate a similar decrease in IOP that becomes notable during the second trimester and decreases further with advancing pregnancy.[28] The decrease in IOP during pregnancy is likely multifactorial. Theories to explain the mechanisms of IOP drop include, special consideration to hormonal levels that fluctuate during pregnancy such as estrogen, relaxin, progesterone, and human chorionic gonadotrophin- and second messenger systems that result in increased outflow facility and in decreased episcleral venous pressure.[29]

In general, pre-existing glaucoma improves and few cases of glaucoma are diagnosed during pregnancy.[30] However, there are few case reports described women with glaucoma whose IOP was difficult to control during pregnancy, despite medical and surgical intervention.[31,32]

It is common for patients to be hesitant to take medication during pregnancy because of the potential teratogenic adverse effects. Whenever possible, physicians should address glaucoma management options in all women of child-bearing age before conception. With proper planning, surgical treatments such as laser trabeculoplasty can be offered in anticipation of decreasing or stopping medication use during pregnancy when choosing IOP-lowering medications for use during pregnancy, it is wise to consider the pregnancy safety categories and to work closely with the patient's obstetrician.[31,32]

Systemic Disease with Ocular Complications

Systemic diseases with ocular complications occurring during pregnancy are either specific to the pregnancy itself such as the eclampsia/pre-eclampsia complex, and Sheehan syndrome, or occur more in relation to pregnancy such as Graves’ disease, IIH, APS, and DIC.

Sheehan syndrome

One of the most common causes of hypopituitarism in the developing countries is an ischemic necrosis of the pituitary gland due to severe postpartum hemorrhage.[33] It is considered a potentially visually-threatening disorder as a result of sudden increase in pituitary size from infarction or hemorrhage. It may present as a sudden onset of headache, visual loss, and/or ophthalmoplegia.[34]

The symptomatology of pituitary apoplexy is dependent on compression of the neighboring structures by the expanding infarcted or hemorrhagic pituitary adenoma.[34] VF defect presents in 64% of cases and visual acuity (VA) abnormalities present in 52% of cases. VF defect results from upward expansion of the tumor, which compresses the optic chiasm, optic tracts, or optic nerve. The classic VF defect is a bitemporal superior quadrantic defect.[3,34]

Ophthalmoplegia occurs in 78% of cases. It results from compression of the cavernous sinus, which makes cranial nerves III, IV, and VI vulnerable to injury. Oculomotor nerve is involved the most commonly, resulting in a unilateral dilated pupil, ptosis, with inferiorly and laterally deviated globe.[33,34]

Cranial nerve IV is also involved resulting in vertical diplopia. The sixth cranial nerve is least commonly involved, perhaps because of its sheltered position in the cavernous sinus. Its involvement produces horizontal diplopia. Horner syndrome may develop from damage to the sympathetic fibers.

Following pituitary apoplexy, resolution of ophthalmoplegia is more likely to occur than recovery of vision.[34]

Graves's disease

Thyroid disorders are prevalent in women of child-bearing age thus it is commonly present in pregnancy and the puerperium.[35] Hyperthyroidism occurs in 2/1000 pregnancies, the most common cause (85%) being Graves’ disease.[35]

Recognition of hyperthyroidism during pregnancy can be elusive because signs overlap with pregnancy symptoms such as nausea and vomiting, increased appetite, heat intolerance, fatigue, and irritable or anxious mood. Symptoms uncommon in normal pregnancy, but found in hyperthyroidism, are weight loss or failed weight gain despite increased dietary intake, resting tachycardia, hypertension, tremor, thyroid enlargement or nodule, and ocular manifestations.[35,36] Abnormal eye findings in Grave's diseases are common. These include, eye stare, eyelid lag, proptosis, and extraocular muscle palsy.[35]

Graves's disease is known to exacerbate in the first trimester and to improve in the second and third trimesters of pregnancy. Close monitoring in the postpartum period is important, as disease flares have been reported. Care of women with Graves's disease in pregnancy should be multidisciplinary and involve an obstetrician familiar with the management of maternal medical conditions, an endocrinologist, and an ophthalmologist. Women with proptosis or other eye findings should be referred to an ophthalmologist for evaluation and management of ophthalmopathy, which may be present in as many as half the cases of Graves's disease. Management with anti-thyroid medications is standard during pregnancy, reserving surgery for complicated cases.[35,36]

IIH

IIH is a disease of unknown etiology associated with increased intracranial pressure. The disease predominantly affects obese females of child-bearing age, thus occurring frequently in pregnancy.[37] The annual incidence of IIH is 1-2 per 100,000 populations, with at least a three-fold higher incidence in obese females between the ages of 15 and 44.[37] Headache is the most common symptom, presenting in 92% of patients and is frequently associated with nausea and vomiting.[37,38]

Ocular manifestations of IIH include, obscuration of vision, blurring, scotomata, photopsias, diplopia, and retrobulbar pain.[37,38] On physical examination, most patients exhibit papilledema as the only objective finding. Papilledema is typically bilateral, but may be markedly asymmetric, unilateral, or even absent in some cases. The degree of optic nerve head swelling does not always correlate well with intracranial pressure, but may correlate with higher risk of permanent visual loss.[37,38] Up to 20% of IIH patients may also exhibit abducens nerve palsy, a false localizing sign secondary to elevated intracranial pressure. Patients may less commonly exhibit other signs that can affect visual function such as coulometer and trochlear cranial nerve deficits.[37,38]

Major goals of IIH treatment include alleviation of symptoms and preservation of visual function. Once diagnosed, the decision to treat depends on VA and VF loss. Medical treatment and observation are usually effective.[37,38]

The APS

Is an autoimmune disorder characterized by either a history of vascular thrombosis (one or more clinical episodes of arterial, venous, or small vessel thrombosis in any tissue or organ) or pregnancy morbidity in association with the presence of antiphospholipid antibodies.[39]

Ocular complications of APS involve both the anterior and posterior segment of the eye. Anteriorly there are conjunctival telangiectasia or conjunctival microaneurysms, episcleritis, limbal or filamentary keratitis, and iritis. Posteriorly, there are vitritis, retinal detachment, posterior scleritis, branch or central retinal vein occlusion, bilateral choroidal infarction, cilioretinal artery occlusion, venous tortuosity, retinal hemorrhages, cotton-wool spots, and central serous type chorioretinopathy.[39]

Other manifestations include monocular or bilateral transient visual loss, transient VF loss, ischemic optic neuropathy and progressive optic nerve atrophy.[39]

DIC

Is an acquired syndrome characterized by the systemic intravascular activation of coagulation There are several obstetric causes of DIC during pregnancy and postpartum.[40] The common obstetric causes of DIC are: Amniotic fluid embolism; intrauterine fetal demise; pre-eclampsia/eclampsia; placental abruption and placenta praevia; septic abortion, intrauterine infection; and acute fatty liver of pregnancy.[40,41]

The choroid is the most common intraocular structure involved. Occlusion of the choriocapillaris by a thrombus lead to disruption of the overlying retinal pigment epithelium causing serous retinal detachment (SRD).[42]

Conclusion

Visual disturbances are very common during pregnancy. Physicians should have a firm understanding of the various ocular conditions that might appear pregnancy or get modified by pregnancy. In addition, it is very important to be vigilant about the rare and serious conditions that may occur in pregnant women with visual complaints. Prompt evaluation may be required and the immediate transfer of care of the patient may help saving the lives of both the mother and the baby.