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Advancing pregnancy induces obvious physical changes for women over time. However, numerous not-so-obvious physiologic, hormonal, and metabolic changes also occur during pregnancy of which ophthalmologists should make themselves aware. Some of these changes include: increased serum cortisol, increases in blood pressure during the third trimester, increased blood volume, insulin resistance with worsening glycemic control, and hypercoagulability.
Considering these complications, pregnancy might induce certain retinal and choroidal diseases, such as hypertensive retinopathy and choroidopathy, exudative retinal detachment, and retinal vascular occlusive diseases, as well as exacerbate other diseases, according to Mark Johnson, MD, and Julie M. Rosenthal, MD.
Hypertensive retinopathies and choroidopathies that might develop are the pregnancy-induced hypertension (PIH) syndromes of preeclampsia and eclampsia. The former includes hypertension, peripheral edema, and proteinuria, and the latter is defined as pre-eclampsia plus seizures.
The fundus findings associated with the PIH syndromes that ophthalmologists should be alerted are arteriolar constriction, retinal hemorrhages, cotton-wool spots, retinal edema, and lipid exudates; the presence of subretinal fluid (choriocapillaris infarction); and optic disc edema and/or ischemia.
Dr. Johnson, professor of ophthalmology and visual science, University of Michigan Kellogg Eye Center, Ann Arbor, recounted the case of a 41-year-old woman who presented with a three-day history of blurred vision, back pain, and hypertension late in the third trimester.
Her visual acuity levels were 20/100 and 20/400 in the right and left eyes, respectively. After the patient underwent a C-section, the visual acuity levels and the fundus findings returned to normal. In pregnant patients who develop an exudative retinal detachment, physicians should consider the presence of the HELLP syndrome [Hemolysis, Elevated Liver enzymes, Low Platelets], which is a life-threatening liver disorder.
“The HELLP syndrome occurs in up to 15% of women with pre-eclampsia and is associated with infant mortality in as high as 25% of cases,” noted Dr. Rosenthal, clinical instructor, ophthalmology and visual Sciences, University of Michigan Kellogg Eye Center.
In patients with HELLP syndrome, exudative retinal detachments can develop bilaterally along with yellow-white subretinal deposits, and vitreous hemorrhages. The only treatment is immediate delivery of the infant after the pregnant woman is stabilized.
Other disorders in pregnancy with which exudative retinal detachments can be associated are disseminated intravascular coagulation and thrombotic thrombocytopenic purpura.
Postpartum Purtcher-like retinopathy, an arterial occlusive disorder that can occur within 24 hours after infants are delivered, is associated with a complicated pregnancy. The patients often experience severe bilateral visual loss. Amniotic fluid embolism also can cause retinal arterial occlusions, but, while rare, is usually fatal, Dr. Rosenthal said. Retinal venous occlusions associated with pregnancy usually occur in the third trimester or during the postpartum period.
Pregnancy might exacerbate retinal/choroidal diseases, such as idiopathic central serous chorioretinopathy (ICSC) and diabetic retinopathy. Dr. Johnson explained that pregnancy is a known trigger of active episodes of ICSC, which are related to elevated serum cortisol levels. In this setting, there is up to a 90% incidence of subretinal fibrin deposition. He advised that patients with ICSC be managed with observation alone if they are close to delivery and no fibrin is present close to the fovea, since ICSC is expected to resolve after delivery.
However, in cases in which fibrin is present near the fovea, optical coherence tomography (OCT)-guided laser photocoagulation can be applied. Fluorescein angiography and photodynamic therapy (PDT) should be avoided if possible.
Dr. Johnson described the case of a physician, an obstetrician/gynecologist, who had progressive fibrin deposits late in the second trimester with a visual acuity of 20/60. By five months after treatment with OCT-guided thermal laser photocoagulation, her vision had recovered to 20/20.
In patients with diabetic retinopathy, the rate at which retinopathy progresses doubles in pregnant patients compared with those who are not pregnant. Dr. Johnson explained that after adjusting for hemoglobin A1C values, pregnancy itself is associated with retinopathy progression.
In the Diabetes in Early Pregnancy Study, the investigators found that in 55% of patients with moderate, non-proliferative diabetic retinopathy (NPDR) at baseline, there was two-step Early Treatment Diabetic Retinopathy progression and 29% progressed to PDR.
The Diabetes Control and Complications Trial also reported that retinopathy in type 1 diabetes progresses faster during pregnancy and further found that the long-term risk of progression of early retinopathy was not increased by pregnancy.
When managing patients with diabetes, Dr. Johnson suggested following the American Academy of Ophthalmology Preferred Practice Patterns. They involve maximization of glycemic control before conception and examination during the first trimester with follow-up determined based on the severity of the retinopathy.
Patients with no retinopathy or with mild-to-moderate NPDR should be examined every three to six months, and those with severe NPDR or worse every one to three months. Surveillance should continue during the first year postpartum.
Patients who develop gestational diabetes do not require an eye examination during pregnancy. Drs. Johnson and Rosenthal recommended that for patients with PDR, panretinal photocoagulation should be performed at diagnosis and anti-vascular endothelial growth factor (VEGF) therapy should be avoided.
Patients with mild diabetic macular edema can be observed as the disease might resolve after delivery. If treatment is needed, focal laser or intravitreal triamcinolone can be considered, but anti-VEGF treatments should be avoided.
Drs. Johnson and Rosenthal offered several pearls for treating pregnant patients with retinal diseases. For intravitreal injection, triamcinolone is safe in this patient population. Although small case series have reported that anti-VEGF agents had no harmful effects on the fetus, no large studies have addressed this issue and there is no available fetal safety data that compared anti-VEGF agents.
Anti-VEGF agents should be administered to pregnant women only if absolutely necessary, and pregnancy testing should be performed in women of child-bearing age, the doctors recommended.
When considering angiography, they pointed out that fluorescein dye crosses the placenta and is present in breast milk for 72 hours. No reports have documented any adverse effects on the fetus. Indocyanine green dye, however, does not cross the placenta and is used in pregnant women for non-ophthalmic indications. It is advisable that OCT or OCT-angiography be used instead of invasive angiography wherever possible.
Regarding surgery, such as vitreoretinal procedures, elective surgeries should be avoided during pregnancy. In cases in which surgery is necessary, the obstetrical team should be involved, and local rather than general anesthesia is preferred. Lidocaine is considered safe for use during pregnancy, whereas bupivacaine and mepivacaine should be avoided.
No data are available regarding gestational exposure to PDT with verteporfin. Whenever possible, thermal laser should be used instead of PDT. Drs. Johnson and Rosenthal emphasized that retinal specialists must be armed with knowledge about the changes in pregnancy and the manner in which retinal diseases affect these patients in order to effectively treat this population.