Skip to main content

Advertisement

SpringerLink
Log in

Systemic and Ocular Adverse Events with Intravitreal Anti-VEGF Therapy Used in the Treatment of Diabetic Retinopathy: a Review

  • Microvascular Complications: Retinopathy (R Channa, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Intravitreal anti-vascular endothelial growth factor (VEGF) agents are used routinely in the management of neovascular conditions including proliferative diabetic retinopathy and diabetic macular edema. While the efficacy of anti-VEGF agents has been well-validated, their ocular and systemic adverse events should always be considered and discussed with patients. The aim of this review is to discuss the most recent literature reports regarding the various ocular and systemic adverse events associated with intravitreal anti-VEGF treatment in diabetic retinopathy.

Recent Findings

The most frequently reported adverse ocular events include subconjunctival hemorrhage, vitreous hemorrhage, increased intraocular pressure, uveitis, endophthalmitis, ocular surface disease, and traumatic cataract. Subconjunctival hemorrhage and vitreous hemorrhage are the most common ocular adverse events reported with intravitreal anti-VEGF treatment. The most serious (though rare) ocular adverse events include endophthalmitis and rhegmatogenous retinal detachment. A consensus regarding the association of systemic adverse events (such as myocardial infarction, stroke, and death) with intravitreal anti-VEGF treatments has not been established.

Summary

Intravitreal anti-VEGF therapy is used in the treatment of diabetic retinopathy, macular degeneration, and other diseases. These agents are associated with a variety of ocular and systemic adverse events that ophthalmologists should always consider.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843.

    Article  PubMed  Google Scholar 

  2. Cheloni R, Gandolfi SA, Signorelli C, Odone A. Global prevalence of diabetic retinopathy: protocol for a systematic review and meta-analysis. BMJ Open. 2019;9(3):e022188.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556–64.

    PubMed  PubMed Central  Google Scholar 

  4. Fogli S, Del Re M, Rofi E, Posarelli C, Figus M, Danesi R. Clinical pharmacology of intravitreal anti-VEGF drugs. Eye. 2018;32(6):1010–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Park SJ, Oh J, Kim Y-K, Park JH, Park JY, Hong HK, et al. Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model. Eye. 2015;29(4):561–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ahn J, Kim H, Woo SJ, Park JH, Park S, Hwang DJ, et al. Pharmacokinetics of intravitreally injected bevacizumab in vitrectomized eyes. J Ocul Pharmacol Ther. 2013;29(7):612–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ahn SJ, Ahn J, Park S, Kim H, Hwang DJ, Park JH, et al. Intraocular pharmacokinetics of ranibizumab in vitrectomized versus nonvitrectomized eyes. Invest Ophthalmol Vis Sci. 2014;55(1):567–73.

    Article  CAS  PubMed  Google Scholar 

  8. • Avery RL, Castellarin AA, Steinle NC, Dhoot DS, Pieramici DJ, See R, et al. Systemic pharmacokinetics and pharmacodynamics of intravitreal aflibercept, bevacizumab, and ranibizumab. Retina Phila Pa. 2017;37(10):1847. (This article discusses the pharmacokinetics of anti-VEGF agents.)

    Article  CAS  Google Scholar 

  9. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981;88(7):583–600.

  10. Photocoagulation for Diabetic Macular Edema. Early Treatment Diabetic Retinopathy Study Report Number 1 Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1985;103(12):1796–806.

    Article  Google Scholar 

  11. Writing Committee for the Diabetic Retinopathy Clinical Research Network, Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA. 2015;314(20):2137–46.

    Article  CAS  Google Scholar 

  12. Maturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, et al. Effect of intravitreous anti–vascular endothelial growth factor vs sham treatment for prevention of vision-threatening complications of diabetic retinopathy: the protocol w randomized clinical trial. JAMA Ophthalmol. 2021;139(7):701–12.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Brown DM, Wykoff CC, Boyer D, Heier JS, Clark WL, Emanuelli A, et al. Evaluation of intravitreal aflibercept for the treatment of severe nonproliferative diabetic retinopathy. JAMA Ophthalmol. 2021;139(9):1–10.

    Article  PubMed Central  Google Scholar 

  14. Heier JS, Korobelnik J-F, Brown DM, Schmidt-Erfurth U, Do DV, Midena E, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2016;123(11):2376–85.

    Article  PubMed  Google Scholar 

  15. Daien V, Nguyen V, Essex RW, Morlet N, Barthelmes D, Gillies MC, et al. Incidence and outcomes of infectious and noninfectious endophthalmitis after intravitreal injections for age-related macular degeneration. Ophthalmology. 2018;125(1):66–74.

    Article  PubMed  Google Scholar 

  16. Brown DM, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology. 2013;120(10):2013–22.

    Article  PubMed  Google Scholar 

  17. Shima C, Sakaguchi H, Gomi F, Kamei M, Ikuno Y, Oshima Y, et al. Complications in patients after intravitreal injection of bevacizumab. Acta Ophthalmol (Copenh). 2008;86(4):372–6.

    Article  Google Scholar 

  18. Haruta M, Ishibashi K, Ishibashi Y, Dake S, Sasaki K, Noda R, et al. Multiple retinal vein thromboses after intravitreal aflibercept injections for age-related macular degeneration. Acta Ophthalmol (Copenh). 2020;98(4):e527–8.

    Article  Google Scholar 

  19. Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ, Culliford LA, et al. Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial. The Lancet. 2013;382(9900):1258–67.

    Article  CAS  Google Scholar 

  20. Faruque LI, Lin M, Battistella M, Wiebe N, Reiman T, Hemmelgarn B, et al. Systematic review of the risk of adverse outcomes associated with vascular endothelial growth factor inhibitors for the treatment of cancer. PLoS ONE. 2014;9(7):e101145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Ladas ID, Karagiannis DA, Rouvas AA, Kotsolis AI, Liotsou A, Vergados I. Safety of repeat intravitreal injections of bevacizumab versus ranibizumab: our experience after 2,000 injections. Retina. 2009;29(3):313–8.

    Article  PubMed  Google Scholar 

  22. Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah ME, et al. Twelve-month safety of intravitreal injections of bevacizumab (Avastin®): results of the Pan-American Collaborative Retina Study Group (PACORES). Graefes Arch Clin Exp Ophthalmol. 2008;246(1):81–7.

    Article  CAS  PubMed  Google Scholar 

  23. Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789–801.

    Article  PubMed  Google Scholar 

  24. The Diabetic Retinopathy Clinical Research Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med. 2015;372(13):1193–203.

    Article  PubMed Central  CAS  Google Scholar 

  25. Rayess N, Rahimy E, Shah CP, Wolfe JD, Chen E, DeCroos FC, et al. Incidence and clinical features of post-injection endophthalmitis according to diagnosis. Br J Ophthalmol. 2016;100(8):1058–61.

    Article  PubMed  Google Scholar 

  26. Mccannel CA. Meta-analysis of endophthalmitis after intravitreal injection of anti–vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011;31(4):654–61.

    Article  CAS  PubMed  Google Scholar 

  27. Zafar S, Hamid A, Bin Mahmood SU, Burq MA, Maqsood N. Incidence of endophthalmitis after intravitreal injections at a tertiary care hospital. Can J Ophthalmol. 2018;53(2):94–7.

    Article  PubMed  Google Scholar 

  28. Xu Y, Tan CS. Safety and complications of intravitreal injections performed in an Asian population in Singapore. Int Ophthalmol. 2017;37(2):325–32.

    Article  PubMed  Google Scholar 

  29. Fintak DR, Shah GK, Blinder KJ, Regillo CD, Pollack J, Heier JS, et al. Incidence of endophthalmitis related to intravitreal injection of bevacizumab and ranibizumab. Retina Phila Pa. 2008;28(10):1395–9.

    Article  Google Scholar 

  30. •• Xu K, Chin EK, Bennett SR, Williams DF, Ryan EH, Dev S, et al. Endophthalmitis after intravitreal injection of vascular endothelial growth factor inhibitors. Ophthalmology. 2018;125(8):1279–86. (This study is a recent retrospective chart review of patients that received intravitreal anti-VEGF injections and the incidence of endophthalmitis.)

    Article  PubMed  Google Scholar 

  31. Torres-Costa S, Ramos D, Brandão E, Carneiro Â, Rosas V, Rocha-Sousa A, et al. Incidence of endophthalmitis after intravitreal injection with and without topical antibiotic prophylaxis. Eur J Ophthalmol. 2021;31(2):600–6.

    Article  PubMed  Google Scholar 

  32. Milder E, Vander J, Shah C, Garg S. Changes in antibiotic resistance patterns of conjunctival flora due to repeated use of topical antibiotics after intravitreal injection. Ophthalmology. 2012;119(7):1420–4.

    Article  PubMed  Google Scholar 

  33. VanderBeek BL, Bonaffini SG, Ma L. The association between intravitreal steroids and post-injection endophthalmitis rates. Ophthalmology. 2015;122(11):2311-2315.e1.

    Article  PubMed  Google Scholar 

  34. Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. Ophthalmology. 2016;123(6):1351–9.

    Article  PubMed  Google Scholar 

  35. Writing committee for the Post-Injection Endophthalmitis Study Group, Patel SN, Tang PH, Storey PP, Wolfe JD, Fein J, et al. The influence of universal face mask use on endophthalmitis risk after intravitreal anti-vascular endothelial growth factor injections. Ophthalmology. 2021;S0161–6420(21):00368–7.

    Google Scholar 

  36. Doshi RR, Leng T, Fung AE. Reducing oral flora contamination of intravitreal injections with face mask or silence. Retina Phila Pa. 2012;32(3):473–6.

    Google Scholar 

  37. Wen JC, McCannel CA, Mochon AB, Garner OB. Bacterial dispersal associated with speech in the setting of intravitreous injections. Arch Ophthalmol. 2011;129(12):1551–4.

    Article  PubMed  Google Scholar 

  38. Lau PET, Jenkins KS, Layton CJ. Current evidence for the prevention of endophthalmitis in anti-VEGF intravitreal injections. J Ophthalmol. 2018;24(2018):8567912.

    Google Scholar 

  39. Bhavsar AR, Glassman AR, Stockdale CR, Jampol LM. Diabetic retinopathy clinical research network. elimination of topical antibiotics for intravitreous injections and the importance of using povidone-iodine: update from the diabetic retinopathy clinical research network. JAMA Ophthalmol. 2016;134(10):1181–3.

    Article  PubMed  Google Scholar 

  40. Cheung CSY, Wong AWT, Lui A, Kertes PJ, Devenyi RG, Lam W-C. Incidence of endophthalmitis and use of antibiotic prophylaxis after intravitreal injections. Ophthalmology. 2012;119(8):1609–14.

    Article  PubMed  Google Scholar 

  41. Lyall DAM, Tey A, Foot B, Roxburgh STD, Virdi M, Robertson C, et al. Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom: incidence, features, risk factors, and outcomes. Eye. 2012;26(12):1517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Grzybowski A, Told R, Sacu S, Bandello F, Moisseiev E, Loewenstein A, et al. 2018 Update on intravitreal injections: euretina expert consensus recommendations. Ophthalmologica. 2018;239(4):181–93.

    Article  PubMed  Google Scholar 

  43. Jiang J, Wu M, Shen T. The toxic effect of different concentrations of povidone iodine on the rabbit’s cornea. Cutan Ocul Toxicol. 2009;28(3):119–24.

    Article  CAS  PubMed  Google Scholar 

  44. Ridder WH, Oquindo C, Dhamdhere K, Burke J. Effect of povidone iodine 5% on the cornea, vision, and subjective comfort. Optom Vis Sci. 2017;94(7):732–41.

    Article  PubMed  Google Scholar 

  45. Dohlman TH, Lertsuwanroj B, D’Amico DJ, Ciralsky JB, Kiss S. Evaluation of signs and symptoms of ocular surface disease after intravitreal injection. Acta Ophthalmol 1755375X. 2019;97(8):e1154-6.

    Google Scholar 

  46. Saedon H, Nosek J, Phillips J, Narendran N, Yang YC. Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections. Cutan Ocul Toxicol. 2017;36(4):343–6.

    Article  CAS  PubMed  Google Scholar 

  47. Srinagesh V, Ellenberg D, Scharper PH, Etter J. Intravitreal dry eye study. Invest Ophthalmol Vis Sci. 2014;55(13):3696.

    Google Scholar 

  48. Polat OA, Şener H, Erkiliç K. Corneal nerve fiber and sensitivity loss after repeated intravitreal Anti-VEGF Injections: an in vivo confocal microscopy study. Cornea. 2022;41(3):317–21.

    Article  PubMed  Google Scholar 

  49. ulutaş hafize gökben. Effects of intravitreal injection on ocular surface and anterior segment parameters. Beyoglu Eye J [Internet]. 2021 [cited 2021 Sep 29]; Available from: https://beyoglueye.com/jvi.aspx?un=BEJ-65487&volume=

  50. Jandorf S, Krogh Nielsen M, Sørensen TL. Irrigating the eye after intravitreal injection reduces epithelial damage but not patient discomfort. Acta Ophthalmol 1755375X. 2019;97(4):e670-1.

    Article  Google Scholar 

  51. Chong DY, Anand R, Williams PD, Qureshi JA, Callanan DG. Characterization of sterile intraocular inflammatory responses after intravitreal bevacizumab injection. Retina. 2010;30(9):1432–40.

    Article  PubMed  Google Scholar 

  52. Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY, MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419–31.

  53. Khanani AM, Cohen GL, Zawadzki R. A prospective masked clinical assessment of inflammation after intravitreal injection of ranibizumab or aflibercept. J Ocul Pharmacol Ther Off J Assoc Ocul Pharmacol Ther. 2016;32(4):216–8.

    Article  CAS  Google Scholar 

  54. Souied EH, Dugel PU, Ferreira A, Hashmonay R, Lu J, Kelly SP. Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration: a retrospective claims database analysis. Ophthalmic Epidemiol. 2016;23(2):71–9.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Baumal CR, Spaide RF, Vajzovic L, Freund KB, Walter SD, John V, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology. 2020;127(10):1345–59.

    Article  PubMed  Google Scholar 

  56. Agrawal S, Joshi M, Christoforidis JB. Vitreous inflammation associated with intravitreal anti-VEGF pharmacotherapy. Mediators Inflamm. 2013;2013:943409.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Bakri SJ, Pulido JS, McCannel CA, Hodge DO, Diehl N, Hillemeier J. Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab. Eye. 2009;23(1):181–5.

    Article  CAS  PubMed  Google Scholar 

  58. Swaminathan SS, Kunkler AL, Quan AV, Medert CM, Vanner EA, Feuer W, et al. Rates of RNFL thinning in patients with suspected or confirmed glaucoma receiving unilateral intravitreal injections for exudative AMD. Am J Ophthalmol. 2021;1(226):206–16.

    Article  Google Scholar 

  59. Du J, Patrie JT, Prum BE, Netland PA, Shildkrot Y (Eugene). Effects of intravitreal anti-VEGF therapy on glaucoma-like progression in susceptible eyes. J Glaucoma. 2019;28(12):1035–40.

  60. Mammo DA, Ringeisen AL, Parke DW. Frequency of rhegmatogenous retinal detachment after intravitreal therapy in neovascular age-related macular degeneration. Ophthalmol Retina. 2020;4(10):973–8.

    Article  PubMed  Google Scholar 

  61. Storey PP, Pancholy M, Wibbelsman TD, Obeid A, Su D, Borkar D, et al. Rhegmatogenous retinal detachment after intravitreal injection of anti–vascular endothelial growth factor. Ophthalmology. 2019;126(10):1424–31.

    Article  PubMed  Google Scholar 

  62. Arevalo JF, Maia M, Flynn HW, Saravia M, Avery RL, Wu L, et al. Tractional retinal detachment following intravitreal bevacizumab (Avastin) in patients with severe proliferative diabetic retinopathy. Br J Ophthalmol. 2008;92(2):213–6.

    Article  CAS  PubMed  Google Scholar 

  63. Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, Jhaveri CD, Punjabi OS, et al. Effect of intravitreous aflibercept vs vitrectomy with panretinal photocoagulation on visual acuity in patients with vitreous hemorrhage from proliferative diabetic retinopathy. JAMA. 2020;324(23):2383–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Scappaticci FA, Skillings JR, Holden SN, Gerber H-P, Miller K, Kabbinavar F, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. JNCI J Natl Cancer Inst. 2007;99(16):1232–9.

    Article  PubMed  Google Scholar 

  65. •• Avery RL, Gordon GM. Systemic safety of prolonged monthly anti–vascular endothelial growth factor therapy for diabetic macular edema: a systematic review and meta-analysis. JAMA Ophthalmol. 2016;134(1):21–9. (This meta-analysis found an increased risk of death in patients that received monthly anti-VEGF injections over 2 years.)

    Article  PubMed  Google Scholar 

  66. Maloney MH, Schilz SR, Herrin J, Sangaralingham LR, Shah ND, Barkmeier AJ. Risk of systemic adverse events associated with intravitreal anti–VEGF therapy for diabetic macular edema in routine clinical practice. Ophthalmology. 2019;126(7):1007–15.

    Article  PubMed  Google Scholar 

  67. Starr MR, Dalvin LA, AbouChehade JE, Damento GM, Garcia MD, Shah SM, et al. Classification of strokes in patients receiving intravitreal anti-vascular endothelial growth factor. Ophthalmic Surg Lasers Imaging Retina. 2019;50(5):e140–57.

    Article  PubMed  Google Scholar 

  68. Maloney MH, Payne SR, Herrin J, Sangaralingham LR, Shah ND, Barkmeier AJ. Risk of systemic adverse events after intravitreal bevacizumab, ranibizumab, and aflibercept in routine clinical practice. Ophthalmology. 2021;128(3):417–24.

    Article  PubMed  Google Scholar 

  69. Curtis LH, Hammill BG, Schulman KA, Cousins SW. Risks of mortality, myocardial infarction, bleeding, and stroke associated with therapies for age-related macular degeneration. Arch Ophthalmol. 2010;128(10):1273–9.

    Article  PubMed  Google Scholar 

  70. Virgili G, Parravano M, Evans JR, Gordon I, Lucenteforte E. Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis. Cochrane Eyes and Vision Group, editor. Cochrane Database Syst Rev [Internet]. 2018 Oct 16 [cited 2021 Aug 5]; Available from: https://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007419.pub6

  71. Hanna RM, Lopez EA, Hasnain H, Selamet U, Wilson J, Youssef PN, et al. Three patients with injection of intravitreal vascular endothelial growth factor inhibitors and subsequent exacerbation of chronic proteinuria and hypertension. Clin Kidney J. 2018;12(1):92–100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Touzani F, Geers C, Pozdzik A. Intravitreal injection of anti-VEGF antibody induces glomerular endothelial cells injury. Case Rep Nephrol. 2019;22(2019):e2919080.

    Google Scholar 

  73. Hanna RM, Barsoum M, Arman F, Selamet U, Hasnain H, Kurtz I. Nephrotoxicity induced by intravitreal vascular endothelial growth factor inhibitors: emerging evidence. Kidney Int. 2019;96(3):572–80.

    Article  CAS  PubMed  Google Scholar 

  74. Meredith GGB, Schkade PA, Joondeph BCM. Allergic reaction upon intravitreal administration of anti-vascular endothelial growth factor agents. Retin Cases Brief Rep Summer 2019. 2019;13(3):287–9.

    Google Scholar 

  75. Nagai N, Ibuki M, Shinoda H, Kameyama K, Tsubota K, Ozawa Y. Maculopapular rash after intravitreal injection of an antivascular endothelial growth factor, aflibercept, for treating age-related macular degeneration: a case report. Medicine (Baltimore). 2017;96(21):e6965.

    Article  CAS  Google Scholar 

  76. Kleris RS, Keswani A, Lugar P. The eyes have it: eyelid swelling and rash in a 79-year-old woman with macular degeneration. Allergy Rhinol. 2018;1(9):2152656718763385.

    Google Scholar 

  77. Galazios G, Papazoglou D, Tsikouras P, Kolios G. Vascular endothelial growth factor gene polymorphisms and pregnancy. J Matern Fetal Neonatal Med. 2009;22(5):371–8.

    Article  CAS  PubMed  Google Scholar 

  78. Choo PP, Md Din N, Azmi N, Bastion M-LC. Review of the management of sight-threatening diabetic retinopathy during pregnancy. World J Diabetes. 2021;12(9):1386–400.

    Article  PubMed  PubMed Central  Google Scholar 

  79. Almawi WY, Saldanha FL, Mahmood NA, Al-Zaman I, Sater MS, Mustafa FE. Relationship between VEGFA polymorphisms and serum VEGF protein levels and recurrent spontaneous miscarriage. Hum Reprod. 2013;28(10):2628–35.

    Article  CAS  PubMed  Google Scholar 

  80. Dalal PJ, Patel AL, Carle M, Rajanala A, Gill MK. Review of ophthalmic and breastfeeding medicine evidence: real and theoretical risks of intravitreal anti-vascular endothelial growth factor administration in lactating women. Retina. 2020;40(11):2065–9.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, University of North Carolina at Chapel Hill, 2226 Nelson Hwy Suite 200, Chapel Hill, NC, 27517, USA

    Jason A. Zehden, Xavier M. Mortensen & Alice Yang Zhang

  2. Athena Eye Institute, San Antonio, TX, USA

    Ashvini Reddy

  3. University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Ashvini Reddy

Authors
  1. Jason A. Zehden
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier M. Mortensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashvini Reddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alice Yang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alice Yang Zhang.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Microvascular Complications—Retinopathy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zehden, J.A., Mortensen, X.M., Reddy, A. et al. Systemic and Ocular Adverse Events with Intravitreal Anti-VEGF Therapy Used in the Treatment of Diabetic Retinopathy: a Review. Curr Diab Rep 22, 525–536 (2022). https://doi.org/10.1007/s11892-022-01491-y

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-022-01491-y

Keywords

Search

Navigation