Impact of the COVID-19 pandemic on patients receiving intravitreal injections


  • Ningzhi Zhang Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
  • Xuejun He Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
  • Yiqiao Xing Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China
  • Ning Yang Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, China



anti-vascular endothelial growth factor (VEGF), COVID-19, intravitreal injection, post-injection endophthalmitis, vial splitting


Paper description:

  • Splitting one vial of anti-vascular endothelial growth factor (VEGF) is no longer carried out after COVID-19, exerting increased financial pressure on patients receiving anti-VEGF intravitreal injections (IVIs).
  • The cost and incidence of post-injection endophthalmitis (PIE) before and after the pandemic were analyzed in a retrospective study.
  • A single vial used for only one patient dramatically increased the financial burden on IVI patients but did not reduce PIE incidence.
  • After the COVID-19 pandemic has been contained, splitting vials into syringes for IVI patients could resume.

Abstract: We analyzed the economic benefits versus safety risks of sharing anti-vascular endothelial growth factor (VEGF) vials during the coronavirus disease (COVID-19) pandemic. This single-center retrospective study analyzed the data of patients with neovascular age-related macular degeneration (nAMD), proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO) who received anti-VEGF between January 2016 and July 2021 at Renmin Hospital, Wuhan University, China. Costs were compared of the two protocols of intravitreal injections (IVIs) of ranibizumab, aflibercept and conbercept after (i) splitting the vial content for use in two patients and after (ii) disposal of the remaining vial content after use in a single patient, with the COVID-19 outbreak considered as the demarcation point. The incidence rates of post-injection endophthalmitis (PIE) pre- and post-outbreak were analyzed. The mean cost of a single IVI increased by 33.3%, from 3917.67±71.69 to 5222.67±84.98 Chinese Yuan during the pandemic. The incidences of IVI-related culture-positive PIE were 0.0134% (3 in 22448) and 0.0223% (1 in 4479), respectively, before and after the pandemic (P=0.6532). We conclude that vial sharing of IVIs in a large clinical institution is not associated with increased PIE risk and can significantly reduce the cost of therapy.


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Ferrara N, Adamis AP. Ten years of anti-vascular endothelial growth factor therapy. Nat Rev Drug Discov. 2016;15(6):385-403.

Chen L, Lin G, Chen K, Liang R, Wan F, Zhang C, Tian G, Zhu X. VEGF promotes migration and invasion by regulating EMT and MMPs in nasopharyngeal carcinoma. J Cancer. 2020;11(24):7291-301.

Lavoz C, Alique M, Rodrigues-Diez R, Pato J, Keri G, Mezzano S, Egido J, Ruiz-Ortega M. Gremlin regulates renal inflammation via the vascular endothelial growth factor receptor 2 pathway. J Pathol. 2015;236(4):407-20.

Li W, Hsiao K, Wang C, Chang N, Hsu P, Sun C, Wu S, Wu M, Tsai S. Extracellular vesicle-associated VEGF-C promotes lymphangiogenesis and immune cells infiltration in endometriosis. Proc Natl Acad Sci U S A. 2020;117(41):25859-68.

Chen Y, Zhao B, Zhu Y, Zhao H, Ma C. HIF-1-VEGF-Notch mediates angiogenesis in temporomandibular joint osteoarthritis. Am J Transl Res. 2019;11(5):2969-82.

Wang H, Ramshekar A, Kunz E, Sacks DB, Hartnett ME. IQGAP1 causes choroidal neovascularization by sustaining VEGFR2-mediated Rac1 activation. Angiogenesis. 2020;23(4):685-98.

Ling S, Yang S, Hu X, Yin D, Dai Y, Qian X, Wang D, Pan X, Hong J, Sun X, Yang H, Paludan S, Cai Y. Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice. Nat Biomed Eng. 2021;5(2):144-56.

Ng D, Fung N, Yip F, Lai T. Ranibizumab for myopic choroidal neovascularization. Expert Opin Biol Ther. 2020;20(12):1385-93.

Lim L, Mitchell P, Seddon J, Holz F, Wong T. Age-related macular degeneration. Lancet. 2012;379(9827):1728-38.

Wells J, Glassman A, Ayala A, Jampol L, Bressler N, Bressler S, Brucker A, Ferris F, Hampton G, Jhaveri C, Melia M, Beck R. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016;123(6):1351-9.

Wong T, Cheung C, Larsen M, Sharma S, Simó R. Diabetic retinopathy. Nat Rev Dis Primers. 2016;2:16012.

Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, Gandorfer A, Ulbig M, Kampik A. Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina. 2006 Nov;26(9):999-1005.

Mitry D, Bunce C, Charteris D. Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev. 2013;(1):Cd009510.

Li Y, Teng D, Shi X, Qin G, Qin Y, Quan H, Shi B, Sun H, Ba J, Chen B, Du J, He L, Lai X, Li Y, Chi H, Liao E, Liu C, Liu L, Tang X, Tong N, Wang G, Zhang J, Wang Y, Xue Y, Yan L, Yang J, Yang L, Yao Y, Ye Z, Zhang Q, Zhang L, Zhu J, Zhu M, Ning G, Mu Y, Zhao J, Teng W, Shan Z. Prevalence of diabetes recorded in mainland China using 2018 diagnostic criteria from the American Diabetes Association: national cross sectional study. BMJ. 2020;369:m997.

Song P, Du Y, Chan KY, Theodoratou E, Rudan I. The national and subnational prevalence and burden of age-related macular degeneration in China. J Glob Health. 2017;7(2):020703.

Feng J, Qian J, Jiang Y, Zhao M, Liang J, Yin H, Chen Y, Yu W, Li X. Efficacy of Primary Intravitreal Ranibizumab for Retinopathy of Prematurity in China. Ophthalmology. 2017;124(3):408-9.

Cai S, Yang Q, Li X, Zhang Y. The efficacy and safety of aflibercept and conbercept in diabetic macular edema. Drug Des Devel Ther. 2018;12:3471-83.

Liu K, Song Y, Xu G, Ye J, Wu Z, Liu X, Dong X, Zhang M, Xing Y, Zhu S, Chen X, Shen Y, Huang H, Yu L, Ke Z, Rosenfeld P, Kaiser P, Ying G, Sun X, Xu X. Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study. Am J Ophthalmol. 2019;197:156-67.

Xu T, Wang B, Liu H, Wang H, Yin P, Dong W, Li J, Wang Y, Yusufu M, Briant P, Reinig N, Ashbaugh C, Adelson J, Vos T, Bourne R, Wang N, Zhou M. Prevalence and causes of vision loss in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019. Lancet Public Health. 2020;5(12):e682-e91.

Sodré S, Barbosa I, Pacheco I, Ferreira F, David M, Nascimento M, Arieta C, Vasconcellos J. Costs and benefits of bevacizumab vial sharing for the treatment of retinal diseases. BMC Public Health. 2019;19(1):1252.

Blom K, Bragadóttir R, Sivertsen M, Moe M, Jørstad Ø. Does Pharmaceutical Compounding of Vascular Endothelial Growth Factor Inhibitors for Intravitreal Use Alter the Risk of Post-injection Endophthalmitis? Ocul Immunol Inflamm. 2020;1-4.

Storey P, Tauqeer Z, Yonekawa Y, Todorich B, Wolfe J, Shah S, Shah A, Koto T, Abbey A, Morizane Y, Sharma P, Wood E, Morizane-Hosokawa M, Pendri P, Pancholy M, Harkey S, Jeng-Miller K, Obeid A, Borkar D, Chen E, Williams P, Okada A, Inoue M, Shiraga F, Hirakata A, Shah C, Prenner J, Garg S. The Impact of Prefilled Syringes on Endophthalmitis Following Intravitreal Injection of Ranibizumab. Am J Ophthalmol. 2019;199:200-8.

Du Q, Zhang D, Hu W, Li X, Xia Q, Wen T, Jia H. Nosocomial infection of COVID‑19: A new challenge for healthcare professionals (Review). Int J Mol Med. 2021;47(4):31.

Jayaweera M, Perera H, Gunawardana B, Manatunge J. Transmission of COVID-19 virus by droplets and aerosols: A critical review on the unresolved dichotomy. Environ Res. 2020;188:109819.

Sodré S, Barbosa I, Pacheco I, Ferreira F, David M, Nascimento M, Arieta C, Vasconcellos J. Costs and benefits of bevacizumab vial sharing for the treatment of retinal diseases. BMC Public Health. 2019;19(1):1252.

Sivertsen M, Jørstad Ø, Grevys A, Foss S, Moe M, Andersen J. Pharmaceutical compounding of aflibercept in prefilled syringes does not affect structural integrity, stability or VEGF and Fc binding properties. Sci Rep. 2018;8(1):2101.

Gomi F, Toyoda R, Yoon A, Imai K. Factors of Anti-Vascular Endothelial Growth Factor Therapy Withdrawal in Patients with Neovascular Age-Related Macular Degeneration: Implications for Improving Patient Adherence. J Clin Med. 2021;10(14):3106.

Lode H, Gjølberg T, Foss S, Sivertsen M, Brustugun J, Andersson Y, Jørstad Ø, Moe M, Andersen J. A new method for pharmaceutical compounding and storage of anti-VEGF biologics for intravitreal use in silicone oil-free prefilled plastic syringes. Sci Rep. 2019;9(1):18021.

Sassalos T, Paulus Y. Prefilled syringes for intravitreal drug delivery. Clin Ophthalmol. 2019; 13: 701-6.

Durand M. Bacterial and Fungal Endophthalmitis. Clin Microbiol Rev. 2017;30(3):597-613.

Durand M. Endophthalmitis. Clin Microbiol Infect. 2013;19(3):227-34.

Borkar D, Obeid A, Su D, Storey P, Gao X, Regillo C, Kaiser R, Garg S, Hsu J. Endophthalmitis Rates after Bilateral Same-Day Intravitreal Anti-Vascular Endothelial Growth Factor Injections. Am J Ophthalmol. 2018;194:1-6.

VanderBeek B, Bonaffini S, Ma L. Association of compounded bevacizumab with postinjection endophthalmitis. JAMA Ophthalmol. 2015;133(10):1159-64.

Stem M, Rao P, Lee I, Woodward M, Faia L, Wolfe J, Capone A, Covert D, Dass A, Drenser K, Garretson B, Hassan T, Margherio A, Oh K, Raephaelian P, Randhawa S, Sneed S, Trese M, Yedavally S, William G, Ruby A. Predictors of Endophthalmitis after Intravitreal Injection: A Multivariable Analysis Based on Injection Protocol and Povidone Iodine Strength. Ophthalmol Retina. 2019;3(1):3-7.

Bavinger J, Yu Y, VanderBeek B. Comparative risk of endophthalmitis after intravitreal injection with bevacizumab, aflibercept, and ranibizumab. Retina. 2019;39(10):2004-11.

Rayess N, Rahimy E, Shah C, Wolfe J, Chen E, DeCroos F, Storey P, Garg S, Hsu J. Incidence and clinical features of post-injection endophthalmitis according to diagnosis. Br J Ophthalmol. 2016;100(8):1058-61.




How to Cite

Zhang N, He X, Xing Y, Yang N. Impact of the COVID-19 pandemic on patients receiving intravitreal injections. Arch Biol Sci [Internet]. 2022Apr.1 [cited 2024Feb.26];74(1):49-55. Available from: