Although infectious endophthalmitis after intravitreal antivascular endothelial growth factor injections is rare, it is the most feared and potentially devastating complication of this procedure. There is no high-level evidence to provide definitive guidance on the management of endophthalmitis occurring after intravitreal injection (IVI). This clinical practice update reviews the published literature regarding post-IVI endophthalmitis and highlights areas in which further research is needed to better guide its management.
McLaughlinMDHwangJC.Trends in vitreoretinal procedures for Medicare beneficiaries, 2000 to 2014. Ophthalmology. 2017;124(5):667-673. doi:10.1016/j.ophtha.2017.01.001
2.
McCannelCA.Meta-analysis of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents: causative organisms and possible prevention strategies. Retina. 2011;31(4):654-661. doi:10.1097/IAE.0b013e31820a67e4
3.
FiletaJBScottIUFlynnHWJr.Meta-analysis of infectious endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents. Ophthalmic Surg Lasers Imaging Retina. 2014;45(2):143-149. doi:10.3928/23258160-20140306-08
4.
MeraniRHunyorAP.Endophthalmitis following intravitreal anti-vascular endothelial growth factor (VEGF) injection: a comprehensive review. Int J Retina Vitreous. 2015;1:9. doi:10.1186/s40942-015-0010-y
5.
Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group. Arch Ophthalmol. 1995;113(12):1479-1496.
6.
SchwartzSGFlynnHWEmersonGG, et al. Distinguishing between infectious endophthalmitis and noninfectious inflammation following intravitreal anti-VEGF injection. J Vitreoretin Dis. 2018;3(1):42-44. doi:10.1177/2474126418806832
7.
PieramiciDJAveryRLCastellarinAANasirMARabenaM.Case of anterior uveitis after intravitreal injection of bevacizumab. Retina. 2006;26(7):841-842. doi:10.1097/01.iae.0000234629.22614.cd
8.
GeorgopoulosMPolakKPragerFPrunteCSchmidt-ErfurthU.Characteristics of severe intraocular inflammation following intravitreal injection of bevacizumab (Avastin). Br J Ophthalmol. 2009;93(4):457-62. doi:10.1136/bjo.2008.138479
9.
BakriSJLarsonTAEdwardsAO.Intraocular inflammation following intravitreal injection of bevacizumab. Graefes Arch Clin Exp Ophthalmol. 2008;246(5):779-781. doi:10.1007/s00417-007-0754-7
10.
KayCNTarantolaRMGehrsKM, et al. Uveitis following intravitreal bevacizumab: a non-infectious cluster. Ophthalmic Surg Lasers Imaging. 2011;42(4):292-296. doi:10.3928/15428877-20110603-04
11.
HahnPKimJEStinnettS, et al. Aflibercept-related sterile inflammation. Ophthalmology. 2013;120(5):1100-101 e1-5. doi:10.1016/j.ophtha.2012.11.018
SouiedEHDugelPUFerreiraAHashmonayRLuJKellySP.Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration: a retrospective claims database analysis. Ophthalmic Epidemiol. 2016;23(2):71-79. doi:10.3109/09286586.2015.1090004
14.
DaienVNguyenVEssexRW, et al. Incidence and outcomes of infectious and noninfectious endophthalmitis after intravitreal injections for age-related macular degeneration. Ophthalmology. 2018;125(1):66-74. doi:10.1016/j.ophtha.2017.07.005
15.
YannuzziNAGregoriNZRosenfeldPJ, et al. Endophthalmitis associated with intravitreal injections of anti-VEGF agents at a tertiary referral center: in-house and referred cases. Ophthalmic Surg Lasers Imaging Retina. 2018;49(5):313-319. doi:10.3928/23258160-20180501-04
16.
BaumalCRSpaideRFVajzovicL, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology. 2020;127(10):1345-1359. doi:10.1016/j.ophtha.2020.04.017
17.
WitkinAJHahnPMurrayTG, et al. Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis. 2020;4(4):269-279. doi:10.1177/2474126420930863
18.
SharmaAKumarNKuppermannBDFrancescoBLowensteinA.Ophthalmic biosimilars: lessons from India. Indian J Ophthalmol. 2019;67(8):1384-1385. doi:10.4103/ijo.IJO_430_19
19.
HoevenaarsNEGansDMissottenTvan RooijJLesaffreEvan MeursJC.Suspected bacterial endophthalmitis following intravitreal anti-VEGF injection: case series and literature review. Ophthalmologica. 2012;228(3):143-147. doi:10.1159/000339584
20.
ChenYShahGKShahV, et al. Outcomes and practice preferences after endophthalmitis following anti-VEGF intravitreal injection. J Vitreoretin Dis. 2019;3(6):411-419. doi:10.1177/2474126419858492
21.
RayessNRahimyEStoreyP, et al. Postinjection endophthalmitis rates and characteristics following intravitreal bevacizumab, ranibizumab, and aflibercept. Am J Ophthalmol. 2016;165:88-93. doi:10.1016/j.ajo.2016.02.028
22.
PatelSNStoreyPPPancholyM, et al. Changes in management based on vitreous culture in endophthalmitis after intravitreal anti-vascular endothelial growth factor injection. Am J Ophthalmol. 2019;207:224-231. doi:10.1016/j.ajo.2019.06.008
23.
XuKChinEKBennettSR, et al. Endophthalmitis after intravitreal injection of vascular endothelial growth factor inhibitors: management and visual outcomes. Ophthalmology. 2018;125(8):1279-1286. doi:10.1016/j.ophtha.2018.01.022
24.
LeeAYAkileswaranLTibbettsMDGargSJVan GelderRN.Identification of torque teno virus in culture-negative endophthalmitis by representational deep DNA sequencing. Ophthalmology. 2015;122(3):524-530. doi:10.1016/j.ophtha.2014.09.001
25.
FlineyGDPecenPECathcartJNPalestineAG.Trends in treatment strategies for suspected bacterial endophthalmitis. Graefes Arch Clin Exp Ophthalmol. 2018;256(4):833-838. doi:10.1007/s00417-018-3910-3
26.
XuDNagielARahimyEMcCannelCA.Practice patterns of endophthalmitis treatment: an international survey of retina specialists. Ophthalmol Retina. 2018;2(9):979-980. doi:10.1016/j.oret.2018.04.008
27.
SolimanMKGiniGKuhnF, et al. International practice patterns for the management of acute postsurgical and postintravitreal injection endophthalmitis: European Vitreo-Retinal Society Endophthalmitis Study report 1. Ophthalmol Retina. 2019;3(6):461-467. doi:10.1016/j.oret.2019.03.009
28.
BarzaMPavanPRDoftBH, et al. Evaluation of microbiological diagnostic techniques in postoperative endophthalmitis in the endophthalmitis vitrectomy study. Arch Ophthalmol. 1997;115(9):1142-1150. doi:10.1001/archopht.1997.01100160312008
29.
BhikooRWangNWelchSPolkinghornePNiedererR.Factors associated with positive microbial culture in patients with endophthalmitis based on clinical presentation and multimodal intraocular sampling. Asia Pac J Ophthalmol (Phila). 2020;9(1):4-8. doi:10.1097/APO.0000000000000263
30.
HanDPWisniewskiSRKelseySFDoftBHBarzaMPavanPR.Microbiologic yields and complication rates of vitreous needle aspiration versus mechanized vitreous biopsy in the endophthalmitis vitrectomy study. Retina. 1999;19(2):98-102. doi:10.1097/00006982-199902000-00002
31.
AlBloushiAFAjamil-RodanesSTestiIWaglandCGrant-McKenzieNPavesioC.Diagnostic value of culture results from aqueous tap versus vitreous tap in cases of bacterial endophthalmitis. Br J Ophthalmol. 2022;106:815-819. doi:10.1136/bjophthalmol-2021-318916
32.
JoondephBCFlynnHWJr.MillerDJoondephHC.A new culture method for infectious endophthalmitis. Arch Ophthalmol. 1989;107(9):1334-1337. doi:10.1001/archopht.1989.01070020404044
33.
TanHSGhyczy-CarlborgEASpanjaardLde SmetMD.The additional value of blood culture bottles in the diagnosis of endophthalmitis. Eye (Lond). 2011;25(8):1069-1073. doi:10.1038/eye.2011.142
34.
PongsachareonnontPHonglertnapakulWChatsuwanT.Comparison of methods for identifying causative bacterial microorganisms in presumed acute endophthalmitis: conventional culture, blood culture, and PCR. BMC Infect Dis. 2017;17(1):165. doi:10.1186/s12879-017-2264-5
35.
ChunLYDolle MolleLSchneewindOMissiakasDBeavisKGSkondraD.Rapid pathogen identification with direct application of MALDI-TOF mass spectrometry on an endophthalmitis vitreous sample without prior Culture. J Vitreoretin Dis. 2019;3(4):255-259. doi:10.1177/2474126419847635
36.
PatelSNCaiLZMahmoudzadehR, et al. Endophthalmitis after intravitreal anti-vascular endothelial factor injections: outcomes of eyes managed without microbiologic cultures. Am J Ophthalmol. 2022;235:1-6. doi:10.1016/j.ajo.2021.08.012
37.
SimonettJMIgelmanATaylorSC, et al. Culture-proven endophthalmitis after intravitreal injection: a 10-year analysis. Ophthalmic Surg Lasers Imaging Retina. 2019;50(1):33-38. doi:10.3928/23258160-20181212-05
38.
ChenELinMYCoxJBrownDM.Endophthalmitis after intravitreal injection: the importance of viridans streptococci. Retina. 2011;31(8):1525-1533. doi:10.1097/IAE.0b013e318221594a
39.
KurniawanEDRockeJRSandhuSSAllenPJ.Predictors of visual outcome and the role of early vitrectomy in streptococcal endophthalmitis. Clin Exp Ophthalmol. 2018;46(4):424-431. doi:10.1111/ceo.13077
40.
Reyes-CapoDPYannuzziNASmiddyWEFlynnHWJr., Endophthalmitis/Anti VSG. Trends in endophthalmitis associated with intravitreal injection of anti-VEGF agentsat a tertiary referral center. Ophthalmic Surg Lasers Imaging Retina. 2021;52(6):319-326. doi:10.3928/23258160-20210528-04
41.
SimunovicMPRushRBHunyorAPChangAA.Endophthalmitis following intravitreal injection versus endophthalmitis following cataract surgery: clinical features, causative organisms and post-treatment outcomes. Br J Ophthalmol. 2012;96(6):862-866. doi:10.1136/bjophthalmol-2011-301439
OngAPAngbue TeNZagoraSL, et al. Post-surgical versus post-intravitreal injection endophthalmitis: changing patterns in causative flora. Clin Exp Ophthalmol. 2019;47(1):57-62. doi:10.1111/ceo.13345
44.
PatelSNHsuJSivalingamMD, et al. The impact of physician face mask use on endophthalmitis after intravitreal anti-vascular endothelial growth factor injections. Am J Ophthalmol. 2021;222:194-201. doi:10.1016/j.ajo.2020.08.013
45.
HebertMYouEHammamjiK, et al. Impact of patient face mask use on endophthalmitis after intravitreal anti-VEGF injections. Can J Ophthalmol. Published online August 20, 2021. doi:10.1016/j.jcjo.2021.06.015
46.
Writing committee for the Post-Injection Endophthalmitis Study Group, PatelSNTangPH, et al. The influence of universal face mask use on endophthalmitis risk after intravitreal anti-vascular endothelial growth factor injections. Ophthalmology. 2021;128(11):1620-1626. doi:10.1016/j.ophtha.2021.05.010
47.
KodatiSEllerAWKowalskiRP.The susceptibility of bacterial endophthalmitis isolates to vancomycin, ceftazidime, and amikacin: a 23 year-review. Ophthalmol Retina. 2017;1(3):206-209. doi:10.1016/j.oret.2016.11.010
48.
WitkinAJChangDFJumperJM, et al. Vancomycin-associated hemorrhagic occlusive retinal vasculitis: clinical characteristics of 36 eyes. Ophthalmology. 2017;124(5):583-595. doi:10.1016/j.ophtha.2016.11.042
49.
MuidJAwanMA.Haemorrhagic occlusive retinal vasculitis caused by intravitreal vancomycin. J Pak Med Assoc. 2020;70(9):1648-1650. doi:10.5455/JPMA.46528
50.
CampochiaroPALimJI.Aminoglycoside toxicity in the treatment of endophthalmitis. The aminoglycoside toxicity study group. Arch Ophthalmol. 1994;112(1):48-53. doi:10.1001/archopht.1994.01090130058017
51.
MeyerBIBerryDECribbsBE, et al. Outcomes of infectious endophthalmitis in patients with systemic antibiotic allergies to penicillins, cephalosporins, or vancomycin. Ophthalmol Retina. 2021;5(9):901-909. doi:10.1016/j.oret.2020.11.015
52.
HariprasadSMShahGKMielerWF, et al. Vitreous and aqueous penetration of orally administered moxifloxacin in humans. Arch Ophthalmol. 2006;124(2):178-182. doi:10.1001/archopht.124.2.178
53.
SchimelAMMillerDFlynnHWJr.Endophthalmitis isolates and antibiotic susceptibilities: a 10-year review of culture-proven cases. Am J Ophthalmol. 2013;156(1):50-52 e1. doi:10.1016/j.ajo.2013.01.027
54.
GrzybowskiATurczynowskaMSchwartzSGRelhanNFlynnHWJr.The role of systemic antimicrobials in the treatment of endophthalmitis: a review and an international perspective. Ophthalmol Ther. 2020;9(3):485-498. doi:10.1007/s40123-020-00270-w
55.
BrockhausLGoldblumDEggenschwilerLZimmerliSMarzoliniC.Revisiting systemic treatment of bacterial endophthalmitis: a review of intravitreal penetration of systemic antibiotics. Clin Microbiol Infect. 2019;25(11):1364-1369. doi:10.1016/j.cmi.2019.01.017
56.
DaveVPPathengayANishantKReddyVSPappuruRRDasT.Management of endophthalmitis with and without topical antibiotics: a case-control study. Ophthalmologica. 2021;244(3):208-212. doi:10.1159/000508133
57.
SolimanMKGiniGKuhnF, et al. Visual outcome of early vitrectomy and intravitreal antibiotics in acute postsurgical and postintravitreal injection endophthalmitis: European vitreo-retinal society endophthalmitis study report two. Retina. 2021;41(2):423-430. doi:10.1097/IAE.0000000000002856
58.
ChaudharyKMRomeroJMEzonIFastenbergDMDeramoVA.Pars plana vitrectomy in the management of patients diagnosed with endophthalmitis following intravitreal anti-vascular endothelial growth factor injection. Retina. 2013;33(7):1407-1416. doi:10.1097/IAE.0b013e3182807659
59.
SiddiquiFCrippenCHutnikCM.Do we heed the endophthalmitis vitrectomy study in Canada?Can J Ophthalmol. 2002;37(7):395-398. doi:10.1016/s0008-4182(02)80041-2
60.
GowerEWKeayLJStareDE, et al. Characteristics of endophthalmitis after cataract surgery in the United States medicare population. Ophthalmology. 2015;122(8):1625-1632. doi:10.1016/j.ophtha.2015.04.036
61.
NgJQMorletNPearmanJW, et al. Management and outcomes of postoperative endophthalmitis since the endophthalmitis vitrectomy study: the endophthalmitis population study of Western Australia (EPSWA)’s fifth report. Ophthalmology. 2005;112(7):1199-1206. doi:10.1016/j.ophtha.2005.01.050
KuhnFGiniG.Ten years after. . . are findings of the endophthalmitis vitrectomy study still relevant today?Graefes Arch Clin Exp Ophthalmol. 2005;243(12):1197-1199. doi:10.1007/s00417-005-0082-8
64.
DibBMorrisREOltmannsMHSappMRGloverJPKuhnF.Complete and early vitrectomy for endophthalmitis after cataract surgery: an alternative treatment paradigm. Clin Ophthalmol. 2020;14:1945-1954. doi:10.2147/OPTH.S253228
65.
ChoiEYHanJYLeeH, et al. Impact of antibiotic resistance of pathogens and early vitrectomy on the prognosis of infectious endophthalmitis: a 10-year retrospective study. Graefes Arch Clin Exp Ophthalmol. 2019;257(4):805-813. doi:10.1007/s00417-019-04261-x
66.
HoIVFernandez-SanzGLevasseurS, et al. Early pars plana vitrectomy for treatment of acute infective endophthalmitis. Asia Pac J Ophthalmol (Phila). 2019;8(1):3-7. doi:10.22608/APO.2018414
67.
KimCHChenMFColemanAL.Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure. Cochrane Database Syst Rev. 2017;2:CD012131. doi:10.1002/14651858.CD012131.pub2
68.
BuiDKCarvounisPE.Evidence for and against intravitreous corticosteroids in addition to intravitreous antibiotics for acute endophthalmitis. Int Ophthalmol Clin. 2014;54(2):215-224. doi:10.1097/IIO.0000000000000020
69.
ShahGKSteinJDSharmaS, et al. Visual outcomes following the use of intravitreal steroids in the treatment of postoperative endophthalmitis. Ophthalmology. 2000;107(3):486-489. doi:10.1016/s0161-6420(99)00139-6
70.
HallEFScottGRMuschDCZacksDN.Adjunctive intravitreal dexamethasone in the treatment of acute endophthalmitis following cataract surgery. Clin Ophthalmol. 2008;2(1):139-145. doi:10.2147/opth.s2128
71.
PijlBJTheelenTTilanusMARentenaarRCramaN.Acute endophthalmitis after cataract surgery: 250 consecutive cases treated at a tertiary referral center in the Netherlands. Am J Ophthalmol. 2010;149(3):482-487 e1-2. doi:10.1016/j.ajo.2009.09.021
72.
DevSHanDPMielerWF, et al. The role of intravitreal dexamethasone as an adjunct in the management of postoperative bacterial endophthalmitis. EVRS Educational Electronic Journal. 2005;1(5):10-17.
73.
EifrigCWScottIUFlynnHWJr.MillerD.Endophthalmitis caused by pseudomonas aeruginosa. Ophthalmology. 2003;110(9):1714-1717. doi:10.1016/S0161-6420(03)00572-4
74.
MillerJJScottIUFlynnHWJr.SmiddyWECoreyRPMillerD.Endophthalmitis caused by Streptococcus pneumoniae. Am J Ophthalmol. 2004;138(2):231-236. doi:10.1016/j.ajo.2004.03.008
75.
DasTJalaliSGothwalVKSharmaSNaduvilathTJ.Intravitreal dexamethasone in exogenous bacterial endophthalmitis: results of a prospective randomised study. Br J Ophthalmol. 1999;83(9):1050-1055. doi:10.1136/bjo.83.9.1050
76.
AlbrechtERichardsJCPollockTCookCMyersL.Adjunctive use of intravitreal dexamethasone in presumed bacterial endophthalmitis: a randomised trial. Br J Ophthalmol. 2011;95(10):1385-1388. doi:10.1136/bjo.2010.187963
77.
KoehrerPBronAMChiquetC, et al. Early versus delayed intravitreal betamethasone as an adjuvant in the treatment of presumed postoperative endophthalmitis: a randomised trial. Br J Ophthalmol. 2016;100(8):1076-1080. doi:10.1136/bjophthalmol-2015-307063
78.
GanIMUgaharyLCvan DisselJT, et al. Intravitreal dexamethasone as adjuvant in the treatment of postoperative endophthalmitis: a prospective randomized trial. Graefes Arch Clin Exp Ophthalmol. 2005;243(12):1200-1205. doi:10.1007/s00417-005-0133-1
79.
ManningSUgaharyLCLindstedtEW, et al. A prospective multicentre randomized placebo-controlled superiority trial in patients with suspected bacterial endophthalmitis after cataract surgery on the adjuvant use of intravitreal dexamethasone to intravitreal antibiotics. Acta Ophthalmol. 2018;96(4):348-355. doi:10.1111/aos.13610
80.
RobbinsCBMaJFengHLFekratS.Clinical decision making and visual outcomes in endophthalmitis treated with systemic corticosteroids. Ophthalmol Retina. 2020;4(11):1103-1108. doi:10.1016/j.oret.2020.04.026
81.
Ching Wen HoDAgarwalALeeCS, et al. A review of the role of intravitreal corticosteroids as an adjuvant to antibiotics in infectious endophthalmitis. Ocul Immunol Inflamm. 2018;26(3):461-468. doi:10.1080/09273948.2016.1245758
82.
ClarkeBWilliamsonTHGiniGGuptaB.Management of bacterial postoperative endophthalmitis and the role of vitrectomy. Surv Ophthalmol. 2018;63(5):677-693. doi:10.1016/j.survophthal.2018.02.003
EmotoHEmotoYLimJISadunAASebagJ.Regression of choroidal neovascularization after vitrectomy for postinjection endophthalmitis. Retin Cases Brief Rep. 2010;4(4):312-316. doi:10.1097/ICB.0b013e3181d426e8
85.
KallyPMSidikaroYMcCannelCA.Resolution of treatment-resistant subretinal fluid in a patient with exudative age-related macular degeneration following endophthalmitis. Retin Cases Brief Rep. 2017;11(4):316-318. doi:10.1097/ICB.0000000000000352
86.
KokameGTYannuzziNAShanthaJG, et al. Involution of neovascular age-related macular degeneration after endophthalmitis. Retin Cases Brief Rep. 2021;15(5):495-499. doi:10.1097/ICB.0000000000000866
87.
ArnettJJBrodowskaKGallagherDS, et al. Relative quiescence of exudative age-related macular degeneration after resolution of postinjection endophthalmitis. Retina. 2020;40(9):1719-1723. doi:10.1097/IAE.0000000000002666
MichalewskaZNawrockiJ.Antivascular endothelial growth factor treatment might be continued even after vitrectomy for endophthalmitis in neovascular age-related macular degeneration. J Vitreoretin Dis. 2019;4(1):6-12. doi:10.1177/2474126419883561
