Various factors influence the progression of diabetic retinopathy in pregnancy. They include the pregnant state itself, duration of diabetes, degree of retinopathy at conception, metabolic control before and during pregnancy, and the presence of coexisting hypertension.

Pregnancy
Klein et al. [12] reported that the pregnant state itself is considered a major risk factor for the progression of diabetic retinopathy.  Likewise,  DCCT’s findings supported this observation;  the pregnant state and the rapid institution of intensive diabetic therapy were related to the changes in retinopathy noted during pregnancy [9].

Duration of diabetes
The duration of diabetes is another risk factor for the progression of diabetic retinopathy during pregnancy.

Diabetic retinopathy progression is more likely to occur in pregnant women who have had diabetes for a longer time.

Several investigators found an association between earlier diabetes onset and retinopathy progression during pregnancy [5,13–15]. In Axer-Siegel et al.‘s study [5], patients whose disease progressed had diabetes for an average of 15.4 years (±  5.3 years),  compared with patients whose retinopathy did not progress, whose disease duration was an average of 10.86 years (± 6.7 years).

Degree of retinopathy at conception
The degree of retinopathy at conception is also an important risk factor in retinopathy progression during pregnancy [4–6,16].  The Diabetes in Early Pregnancy Study found that the risk of retinopathy progression increased with increasing severity of retinopathy at baseline [16].  Women with moderate to severe retinopathy at conception had a higher risk of retinopathy progression than patients with no to minimal retinopathy. Of the 140 patients in this study who did not have proliferative retinopathy at baseline,  retinopathy progression was seen in 10.3%, 21.1%, 18.8%, and 54.8% of   patients   with   no   retinopathy,  microaneurysms only,  mild nonproliferative retinopathy,  and moderate-to-severe nonproliferative retinopathy at baseline, respectively.  Progression to proliferative retinopathy without the initial presence of nonproliferative retinopathy in early pregnancy is rare, but has been reported in three pregnant diabetic patients who were treated with an insulin analogue, insulin lispro [17]. Of note, other studies comparing insulin lispro with regular insulin use during pregnancy found no progression of retinopathy in the insulin lispro group [18,19].

Metabolic control
Several studies have shown that higher glycosylated hemoglobin levels at conception and the rapid tightening of glycemic control during pregnancy have been associated with a higher risk of retinopathy progression [6,16].  The Diabetes in Early Pregnancy Study examined the role of metabolic control in diabetic retinopathy progression [16].  In this study,  elevated glycosylated hemoglobin at baseline was associated with a higher risk of retinopathy progression. Progression rates almost doubled in women with glycosylated hemoglobin levels greater than 6 SD above the control mean. In Axer-Siegel et al.‘s study [5], patients who had progression of their retinopathy during the pregnancy’s course had higher glycohemoglobin levels compared with those patients who did not progress, although this difference reached statistical significance only in the last trimester of pregnancy. Phelps et al. [6] concluded that the rapid tightening of glycemic control during pregnancy was associated with a higher risk of retinopathy progression. Similarly, Chew et al. [16] noted that patients in whom retinopathy was most likely to progress had the poorest control at baseline and the largest improvement during early pregnancy.

Coexisting hypertension
Coexistent hypertensive disorders in pregnancy are also considered important risk factors for the progression of diabetic retinopathy [2,5,20]. Retinopathy progression is more likely to occur in patients with chronic hypertension or pregnancy-induced hypertension [20].  High diastolic blood pressure and high systolic blood pressure have been reported in some studies to be associated independently with diabetic retinopathy progression [5,12].

Disclosure
This work is supported in part by an unrestricted grant from the Research to Prevent Blindness, New York, NY.

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Provides American Academy of Opthalmology guidelines for monitoring acute changes in pregnant diabetic patients.

Corresponding author
Bhavna P. Sheth, MD
Eye Institute, Medical College of Wisconsin, 8701 Watertown Plank
Road, Milwaukee, WI 53226, USA.
E-mail: .(JavaScript must be enabled to view this email address)
Current Diabetes Reports 2008, 8:270–273
Current Medicine Group LLC ISSN 1534-4827

Bhavna P. Sheth, MD