Most normal pregnancies are blessedly free of any significant retinal changes. But an important subset of patients—those with preexisting diabetes—is at risk of experiencing progression of diabetic retinopathy. “Any patient who is diabetic and who has visible retinopathy is at substantial risk of having it progress [during pregnancy], whether or not she has type 1 or type 2 diabetes,” said William F. Mieler, MD, chairman of ophthalmology at the University of Chicago.
Why is pregnancy a risk factor for the progression of diabetic retinopathy? “No one really knows,” said Janet S. Sunness, MD, a retina specialist at the Greater Baltimore Medical Center and an expert on maternal ocular changes that may occur in association with pregnancy. “There are a lot of things going on during pregnancy—hormonal, metabolic, cardiovascular—so it’s hard to separate them.” Presumed mechanisms include changes in retinal hemodynamics and increased levels of various growth factors and hormones.
Assessing the risk. Overall, an individual woman’s risk profile is affected by the length of time she’s been diabetic and the severity of her retinopathy before conception. Other factors that increase the risk of progression are nephropathy and hypertension.
In one prospective study of 139 pregnant women with type 1 diabetes, the progression rates were 10 percent for those who had diabetes for 10 to 19 years vs. 0 percent for those who had the disease for less than 10 years. In addition, progression was noted in 30 percent of cases of moderate to severe retinopathy and in only 3.7 percent of cases of less severe retinopathy.1
“In the past, a woman with significant retinopathy was putting her vision at significant risk by becoming pregnant, and the risk of congenital defects and perinatal problems with the baby was significant. At that time, the prepregnancy level of retinopathy was considered a better indicator of outcome than it is now,” Dr. Sunness pointed out. “That’s probably because of better management during pregnancy” seen today.
Glycemic control. There’s no question that glycemic control is essential during pregnancy. “If you have a diabetic woman of childbearing age who is contemplating getting pregnant, get her into optimal control before pregnancy,” said Dr. Sunness. “The goal is to get her stabilized, on many different levels. There is evidence that good glycemic control leads to lesser levels of retinopathy. It also determines what will happen afterward—that is, good control reduces risk of adverse outcomes with the fetus or infant. The main thing is to stabilize the person beforehand.” This is because the major periods of organogenesis occur before the woman may even realize that she is pregnant, she noted.
But Dr. Mieler cautioned that while glycemic control “is a commonsense approach and is strongly encouraged, it’s not an absolute guarantee of preventing progression.” In fact, in some studies, the imposition of tight glycemic control during pregnancy has led to transient worsening of retinopathy.
However, Dr. Sunness said, “I do think that some of the problems seen in previous years will shift somewhat, given that more people are under better control, [with] some using the insulin pump” and thus are better managed before they even become pregnant.
Chance of Regression
In many instances, the retinopathy regresses after delivery. Only a few long-term studies of the impact of pregnancy on retinopathy level have been conducted, Dr. Sunness said. “Several studies report that there is regression of retinopathy postpartum, but not all the way back to prepregnancy levels. On the other hand, a few studies have looked at retinopathy level as a function of a history of prior pregnancies and have found that when the duration of diabetes is taken into account, the number of pregnancies did not have an impact on retinopathy level. One possible confounding factor, though, is that healthier diabetic women are more likely to experience several pregnancies.”
She added, “Overall, and this is true also for most other retinal conditions noted during pregnancy, it makes sense to think of pregnancy as a temporary condition. If you can make it through, a lot of these conditions will clear up.”
When to treat. For women who have nonproliferative disease, the primary concern is macular edema, Dr. Sunness noted. “In nonpregnant populations of people who have macular edema, the goal is to stabilize them. You don’t necessarily get improvement, even with focal laser treatment. But those who get macular edema during pregnancy are in a different setting. They do tend to recover vision postpartum. Thus, it makes a lot of sense to hold back and temporize to see whether things clear up.”
With these patients, the challenge comes in assessing the likelihood of progression to proliferative disease, she said. “Are they going to get something so damaging—retinal detachment, for instance—that it’s irreversible? If they fall into the group characterized as high-risk, then it makes sense to go ahead and treat.”
But even proliferative retinopathy may regress near the end of pregnancy or in the postpartum period. Thus, deciding whether or not to treat proliferative retinopathy usually is made on a case-by-case basis, depending on not only the extent of high-risk disease but also on other factors such as an elevated glycosylated hemoglobin level.
If laser treatment is deemed medically necessary, “overall, we use the same criteria as for nonpregnant patients,” said Dr. Mieler. “However, we generally recommend putting treatment off until the third trimester if possible, when the patient is generally more stable and there is probably less risk to the developing fetus. And there will be some differences in choice of anesthesia—topical drops vs. retrobulbar injection, for instance.”
Ideally, every diabetic woman would be evaluated by an ophthalmologist before she even becomes pregnant. Once she is pregnant, she should be evaluated during the first trimester, and regularly throughout the course of her pregnancy.
The precise monitoring schedule after the first trimester depends upon her baseline retinal status. If she has no retinopathy or mild to moderate nonproliferative disease, she may be reevaluated once or twice more during the pregnancy. If she has proliferative retinopathy, she may be reevaluated every four to six weeks.
Women who develop gestational diabetes do not need additional follow-up; a retrospective review of 100 women with gestational diabetes concluded that routine eye examinations had little value.2
1 Temple, R. C. Diabet Med 2001;18(7): 573–577.
2 Puza, S. W. and Malee, M. P. J Matern Fetal Med 1996;5:7–10.
|Other Problems to Watch For|
Overall, the majority of patients will not experience any ocular difficulties during the course of a routine pregnancy. But “any patient who notes new ocular symptoms during the course of pregnancy warrants an ocular examination,” Dr. Mieler said. Other retinal and choroidal changes that may occur during pregnancy include the following:
Changes associated with preeclampsia. Preeclampsia (proteinuria, edema and hypertension) typically develops in the second half of pregnancy. Diabetes is itself a risk factor for preeclampsia, as are hypertension and older maternal age. Preeclampsia (and eclampsia) have been associated with a retinopathy similar to hypertensive retinopathy, bullous retinal detachments, retinal pigment epithelium lesions and cortical blindness. Arterial and venous occlusive disease also may occur.
Central serous chorioretinopathy (CSCR). This condition has a 10:1 male predominance outside the context of pregnancy. A number of cases of CSCR have been reported in the literature, but it is not clear whether it is truly more common in pregnancy.1 Most cases occurred during the third trimester and spontaneously resolved during the early postpartum timeframe. There are reports of CSCR recurring in subsequent pregnancies; other reports document a lack of recurrence. Unlike the bilateral serous retinal detachments that occur in association with preeclampsia, CSCR generally is unilateral and occurs in healthy women. Fibrin formation may be seen in this setting as well, although it likewise spontaneously clears.
Retinal artery occlusion. A handful of cases of branch and central retinal artery occlusion, both of which can lead to permanent loss of vision, have been reported. Some of the cases occurred within 24 hours of delivery, suggesting that this is a susceptible period. In some reports, patients lost central vision on a permanent basis.
1 Sheth, B. P. and W. F. Mieler. Curr Opin Ophthalmol 2001;12(6):455–463.