Treating uveitis requires a balancing act between therapeutic choices, control of the disease, and side effects of therapy. During pregnancy, multiple hormonal and immunologic changes can impact the severity of uveitis and considerations for therapy.¹ The impact of pregnancy on uveitis has not been extensively studied, and there are no randomized, prospective studies, but general trends exist within reports of singular cases, case series, and retrospective reviews. Additionally, multiple therapeutic options available that are safe for the mother, fetus, and the newborn if breastfeeding. The consensus in the literature is that although uveitis flares may worsen or increase in frequency during the first trimester, uveitis tends to be less active in the second and third trimester, although a few reports have shown the opposite to be true. In general, reports have shown that uveitis flares tend to increase in the postpartum period.²

Course During Pregnancy

Overall, the literature has shown that uveitis flares tend to decrease during the later parts of pregnancy and increase in the postpartum period. A retrospective review from 2003 analyzed 76 pregnancies in 50 women; 33 (43%) of the pregnancies were in women with Vogt-Koyanagi-Harada disease, 19 (25%) were in women with Bechet disease, and 24 (32%) were in women with idiopathic disease. Interestingly, the authors found that the uveitis tended to flare more within the first 4 months of pregnancy (64%). The authors also concluded that uveitis flares tend to decrease during the later parts of pregnancy, with rebound flare rates noted within the first 6 months of pregnancy.³

Similarly, a review from 2013, with a more heterogenous group of uveitis conditions, showed that the flare rate per person per year during pregnancy was 1.188, which decreased to 0.540 per person during pregnancy, and increased to 0.972 postpartum with a significant difference found between prepregnancy and during pregnancy, and again a significant difference between pregnancy and postpartum rates. The authors also found that rates began to increase during the second trimester.⁴ 

Contrastingly, a review of 16 patients with multifocal chorioretinitis and punctate inner choroidopathy showed a relapse rate of 44% during pregnancy, and in contrast to the above studies, the relapse rate occurred more in the third trimester. The authors did state that due to the small size of the study, no definitive conclusions could be drawn. Regardless, most of the literature shows a decrease in uveitis flares during pregnancy, with the most noticeable decline within the later stages of pregnancy. 

Therapeutic Options

If a patient’s uveitis does flare during pregnancy, there are a few therapeutic options that are considered safe, although there are limited data regarding their use. On the other hand, there are certain medications that should be avoided as they are known teratogens. The Food and Drug Administration uses 5 categories to classify the risk of medications during pregnancy (categories A, B, C, D, X). Category A is comprised of drugs that have good evidence to show that no harm to the fetus occurs with their administration. Category B includes medications that have animal studies that show no harm to the fetus, but the drug has not been well studied in humans. Category C is comprised of those drugs that may have adverse effects in human studies, but the drug has not been well studied in humans; despite this, the drug may have potential benefits for the mother. Category D includes medications with evidence of fetal risk with investigations in humans, but these may provide benefit to pregnant women despite these. Category X includes drugs that are proven to result in fetal abnormalities in both human and animal studies, and their risks outweigh the benefit of their use.²

Typically, in cases of uveitis that require short-term control, local steroids are ideal. These can include topical drops (with punctal occlusion), posterior sub-Tenon injection of steroid, intravitreal triamcinolone, dexamethasone implants, fluocinolone acetonide, suprachoroidal triamcinolone, a surgical implant of fluocinolone, or intravenous methylprednisolone. In the case that local steroids is not enough, systemic steroids can be considered. Generally, oral steroids are classified as category C, except for prednisone, which is category B. Steroids have been linked to an increased risk of cleft palate formation, especially in the first trimester, as well as an increased risk of premature rupture of membranes and intrauterine infection rates.^5,6 The American College of Obstetrics and Gynecology has deemed these medications low risk.⁷

If a patient requires immunosuppression during the family planning period of their life, there are a few options that are considered safe (Table 1). Azothiaprine and TNF inhibitors are thought to be safe, with other options that may be started under the guidance of a rheumatologist. In general, steroids are considered safe during the lactation period, but there are other options for immunosuppression that may also be used. All therapeutic options should be investigated thoroughly with a rheumatologist, obstetrician, and pediatrician. RP

Sruthi Arepalli, MD, is an assistant professor of vitreoretinal surgery and uveitis at Emory Eye Center in Atlanta, Georgia. She reports no relevant disclosures. Reach her at sruthiarepalli@gmail.com.

References

1. Chiam NP, Lim LL. Uveitis and gender: the course of uveitis in pregnancy. J Ophthalmol. 2014;2014:401915. doi:10.1155/2014/401915
2. Grotting LA, Papaliodis GN. A review of the course and treatment of non-infectious uveitis during pregnancy. Semin Ophthalmol. 2017;32(1):75-81. doi:10.1080/08820538.2016.1228402
3. Rabiah PK, Vitale AT. Noninfectious uveitis and pregnancy. Am J Ophthalmol. 2003;136(1):91-98. doi:10.1016/s0002-9394(03)00110-7
4. Chiam NP, Hall AJ, Stawell RJ, Busija L, Lim LL. The course of uveitis in pregnancy and postpartum. Br J Ophthalmol. 2013;97(10):1284-1288. doi:10.1136/bjophthalmol-2013-303358
5. Carmichael SL, Shaw GM. Maternal corticosteroid use and risk of selected congenital anomalies. Am J Med Genet. 1999;86(3):242-244. doi:10.1002/(sici)1096-8628(19990917)86:3<242::aid-ajmg9>3.0.co;2-u
6. Park-Wyllie L, Mazzotta P, Pastuszak A, et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology. 2000;62(6):385-392. doi:10.1002/1096-9926(200012)62:6<385::Aid-tera5>3.0.Co;2-z
7. ACOG Committee Opinion No. 776: Immune modulating therapies in pregnancy and lactation. Obstet Gynecol. 2019;133(4):e287-e295. doi:10.1097/aog.0000000000003176
8. Singh M, Qualie J, Currie A, Howarth ES, Khare MM. Is breastfeeding safe with azathioprine? Obstet Med. 2011;4(3):104-107. doi:10.1258/om.2011.110013
9. Angelberger S, Reinisch W, Messerschmidt A, et al. Long-term follow-up of babies exposed to azathioprine in utero and via breastfeeding. J Crohn's Colitis. 2011;5(2):95-100. doi:10.1016/j.crohns.2010.10.005
10. ACOG Committee opinion no. 776: immune modulating therapies in pregnancy and lactation. Obstet Gynecol. 2019;133(4):e287-e295. doi:10.1097/aog.0000000000003176
11. Krause ML, Amin S, Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014;6(5):169-184. doi:10.1177/1759720X14551568
12. Nevers W, Pupco A, Koren G, Bozzo P. Safety of tacrolimus in pregnancy. Can Fam Physician. 2014;60(10):905-906.