Dr Arunima Jain*1,2, Dr Emma Hartley*1, Dr Michael Chilov3, Dr Sarah Lyons4, Dr Natalie Cromer5,6,7, Justine Darling1,8, Dr Amanda Beech1,8, A/Prof Helen Barrett1,2,8
1Department of Obstetric Medicine, Royal Hospital for Women, Sydney, Australia, 2School of Clinical Medicine, Faculty of Medicine & Health, University of New South Wales, Sydney, Australia, 3Department of Opthalmology, Sydney Eye Hospital, Sydney, Australia, 4Department of Obstetrics & Gynaecology, Royal Hospital for Women, Sydney, Australia, 5MotherSafe, Royal Hospital for Women, Sydney, Australia, 6Department of Haematology and Transfusion Medicine, Royal North Shore Hospital, Sydney, Australia, 7Department of Obstetrics, Royal North Shore Hospital, Sydney, Australia, 8Department of Endocrinology, Prince of Wales Hospital, Sydney, Australia
Biography:
Dr Arunima Jain is an early career Nephrologist, currently dual training in Obstetric Medicine at the Royal Hospital for Women in Sydney. She has been awarded a NHMRC Postgraduate Scholarship to pursue her PhD next year, which focuses on improving diagnosis and management of kidney disease in and beyond pregnancy.
Abstract:
Background: Diabetic retinopathy frequently progresses in pregnancy.[1] Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections play a crucial therapeutic role, with limited pregnancy data.[2,3]
Inhibition of circulating VEGF is a key aspect of preeclampsia pathophysiology. Iatrogenic VEGF reduction with anti-VEGF therapy may be theoretically detrimental in pregnancy – with case reports of miscarriage and preeclampsia.[2,3] Ranibizumab is an option with relatively short-lived VEGF suppression and rapid clearance.
Case report: A 36-year-old woman, G5P2 with poorly-controlled Type-1 diabetes and proliferative diabetic retinopathy, presented with worsening vision at 16 weeks in an unplanned pregnancy. Co-morbidities included bipolar disorder and anxiety, treated with prazosin and clonidine during pregnancy.
Pre-pregnancy ophthalmologic treatment included intravitreal aflibercept (anti-VEGF), with one dose (2mg/0.05mL) administered approximately four weeks after estimated date of conception and ceased after pregnancy confirmation. Laser therapy was considered but not administered given patient preference. Worsening vision was attributed to macular oedema with Ophthalmology recommendation for intravitreal anti-VEGF.
Following multidisciplinary discussion between Opthalmology, MotherSafe NSW, Maternal-Fetal Medicine, Obstetric Medicine teams and the patient – consensus to proceed with ranibizumab (0.5mg/0.05ml). Intravitreal injections were administered every 8-12 weeks thereafter with improvement of visual symptoms, control of proliferative retinopathy and macular oedema. Serum VEGF levels assessed on Days -1, +1, +3, and +7 after initial injection were unchanged at <31 ng/L (range 62-707; Quantikine ELISA Human VEGF immunoassay, R&D Systems).
The patient birthed a 3375 gram (95-97th centile) baby at 36+1 weeks gestation via caesarean section (CS), due to preterm labour and prior CS. She did not develop gestational hypertension or preeclampsia.
Conclusion: We report a case of single-dose aflibercept and regular intravitreal ranibizumab administered during pregnancy with clinical improvement. Birth was preterm, with no evidence of preeclampsia or significant complication. Serum VEGF levels are difficult to interpret. Further collaborative research will help determine maternal and fetal safety.
Keywords
VEGF, ranibizumab, pregnancy
References
1) Ong AY, Kiire CA, Frise C, Bakr Y, de Silva SR. Intravitreal anti-vascular endothelial growth factor injections in pregnancy and breastfeeding: a case series and systematic review of the literature. Eye (Lond). 2024;38(5):951-963. doi: 10.1038/s41433-023-02811-6.
2) Ben Ghezala I, Mariet AS, Benzenine E, Bardou M, Bron AM, Gabrielle PH, et al. Association between Obstetric Complications and Intravitreal Anti-Vascular Endothelial Growth Factor Agents or Intravitreal Corticosteroids. J Pers Med. 2022;12(9):1374. doi: 10.3390/jpm12091374.
3) Polizzi S, Mahajan VB. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature. J Ocul Pharmacol Ther. 2015;31(10):605-10. doi: 10.1089/jop.2015.0056.