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Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramCitationExclude ReasonFeijo ED. Intracameral moxifloxacin after cataract surgery: a prospective study.Response: Intracameral moxifloxacin after cataract surgery: a prospective study.Long-term safety of intracameral moxifloxacin after cataract surgery Intracameralantibiotics during cataract surgery: evidence and barriers. Arquivos Brasileiros deOftalmologia. 2018;81(5):455-456.E7Ferreira BG, Cardoso da Silva I, Melega MV, et al. Macular and choroidalthickness after intracameral moxifloxacin for prevention of postcataractendophthalmitis. Journal of Cataract & Refractive Surgery. 2021;47(1):40-45.E4Group EES. Prophylaxis of postoperative endophthalmitis following cataractsurgery: Results of the ESCRS multicenter study and identification of risk factors.Journal of Cataract & Refractive Surgery. 2007;33(6):978-988.E2Grzybowski A, Koerner JC, George MJ. Postoperative endophthalmitis aftercataract surgery: a worldwide review of etiology, incidence and the most studiedprophylaxis measures. Expert Review of Ophthalmology. 2019;14(4/5):247-257.E7Guttman Krader C. Clinical trial suggests safety of unpreserved levofloxacin:Intracameral injection of cefuroxime, moxil oxacin decrease risk ofendophthalmitis. Ophthalmology Times. 2019;44(11):14-14.E10Halachmi-Eyal O, Lang Y, Keness Y, Miron D. Preoperative topical moxifloxacin0.5% and povidone-iodine 5.0% versus povidone-iodine 5.0% alone to reducebacterial colonization in the conjunctival sac. J Cataract Refract Surg.2009;35(12):2109-2114.E2He L, Ta CN, Hu N, Sinnar S, Miño de Kaspar H. Prospective randomizedcomparison of 1-day and 3-day application of topical 0.5% moxifloxacin ineliminating preoperative conjunctival bacteria. J Ocul Pharmacol Ther.2009;25(4):373-378.E2Inoue Y, Usui M, Ohashi Y, Shiota H, Yamazaki T. Preoperative disinfection of theconjunctival sac with antibiotics and iodine compounds: a prospective randomizedmulticenter study. Jpn J Ophthalmol. 2008;52(3):151-161.E2Jabbarvand M, Hashemian H, Khodaparast M, Jouhari M, Tabatabaei A, RezaeiS. Endophthalmitis Occurring after Cataract Surgery: Outcomes of More Than 480000 Cataract Surgeries, Epidemiologic Features, and Risk Factors.Ophthalmology. 2016;123(2):295-301.E7Li A, Shao J, Gans R, Bena J, Goshe J. Postoperative Endophthalmitis Before andAf ter Preferred Utilization of Prophylactic Intracameral Antibiotics forPhacoemulsification Cataract Surgeries at Cole Eye Institute. Eye & Contact Lens:Science & Clinical Practice. 2019;45(5):306-309.E2Li B, Miño de Kaspar H, Haritoglou C, et al. Comparison of 1-day versus 1-hourapplication of topical neomycin/polymyxin-B before cataract surgery. J CataractRefract Surg. 2015;41(4):724-731.E2Linnehan R. Triamcinolone-moxifloxacin stabilizes macular thickness after cataractsurgery in DR. Ocular Surgery News. 2020;38(19):18-18.E2Linnehan R. Optimal dose, concentration of moxifloxacin needed to preventendophthalmitis. Ocular Surgery News. 2021;39(8):15-15.E7Lucena NP, Pereira IMS, Gaete MIL, Ferreira KSA, Melega MV, Lira RPC.Intracameral moxifloxacin after cataract surgery: a prospective study. ArquivosBrasileiros de Oftalmologia. 2018;81(2):92-94.E35

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramCitationExclude ReasonMamalis N. Reducing the risk of endophthalmitis. Journal of Cataract & RefractiveSurgery. 2019;45(9):1217-1218.E7Miño de Kaspar H, Kreutzer TC, Aguirre-Romo I, et al. A prospective randomizedstudy to determine the efficacy of preoperative topical levofloxacin in reducingconjunctival bacterial flora. Am J Ophthalmol. 2008;145(1):136-142.E2Mitchell W, Tom L, Durai I, et al. The Effectiveness of Intracameral MoxifloxacinEndophthalmitis Prophylaxis for Trabeculectomy. Ophthalmology Glaucoma.2021;4(1):11-19.E1Moss JM, Nguyen D, Liu YI, et al. Comparison of one-day versus one-hourapplication of topical gatifloxacin in eliminating conjunctival bacterial flora.Ophthalmology. 2008;115(11):2013-2016.E2Myneni J, Desai SP, Jayamanne DG. Reduction in postoperative endophthalmitiswith intracameral cefuroxime. J Hosp Infect. 2013;84(4):326-328.E2Patel SB, Reddy NK, He YG. Toxic Posterior Segment Syndrome after DroplessCataract Surgery with Compounded Triamcinolone-Moxifloxacin. Retina.2020;40(3):446-455.E3Rahman N, Murphy CC. Impact of intracameral cefuroxime on the incidence ofpostoperative endophthalmitis following cataract surgery in Ireland. Ir J Med Sci.2015;184(2):395-398.E2Rathi V, Sharma S, Das T, Khanna R, Rathi VM, Khanna RC. EndophthalmitisProphylaxis Study, Report 2: Intracameral antibiotic prophylaxis with or withoutpostoperative topical antibiotic in cataract surgery. Indian Journal ofOphthalmology. 2020;68(11):2451-2455.E2Röck T, Bramkamp M, Bartz-Schmidt K, et al. Using intracameral cefuroximereduces postoperative endophthalmitis rate: 5 years experience at the UniversityEye Hospital Tübingen. Klinische Monatsblatter fur Augenheilkunde.2014;231(10):1023-1028.E9Rudnisky CJ, Wan D, Weis E. Antibiotic choice for the prophylaxis of post-cataractextraction endophthalmitis. Ophthalmology. 2014;121(4):835-841.E2Rush SW, Vu D, Rush RB. The Safety and Efficacy of Routine Administration ofIntracameral Vancomycin during Cataract Surgery. J Ophthalmol.2015;2015:813697.E2Sharma S, Sahu SK, Dhillon V, Das S, Rath S. Reevaluating intracameralcef uroxime as a prophylaxis against endophthalmitis after cataract surgery inIndia. J Cataract Refract Surg. 2015;41(2):393-399.E2Shorstein NH, Winthrop KL, Herrinton LJ. Decreased postoperativeendophthalmitis rate after institution of intracameral antibiotics in a NorthernCalif ornia eye department. J Cataract Refract Surg. 2013;39(1):8-14.E2Ta CN, Chan I, Dhatt HS, et al. Prospective comparison of topical moxifloxacin ineliminating conjunctival bacterial flora following a one-day or one-hour application.J Ocul Pharmacol Ther. 2008;24(4):427-431.E2Ta CN, Egbert PR, Singh K, Shriver EM, Blumenkranz MS, Miño De Kaspar H.Prospective randomized comparison of 3-day versus 1-hour preoperative ofloxacinprophylaxis for cataract surgery. Ophthalmology. 2002;109(11):2036-2040;discussion 2040-2031.E26

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramCitationExclude ReasonTa CN, Sinnar S, He L, Myung D, Miño De Kaspar H. Prospective randomizedcomparison of 1-day versus 3-day application of topical levofloxacin in eliminatingconjunctival flora. Eur J Ophthalmol. 2007;17(5):689-695.E2Tan CS, Wong HK, Yang FP. Epidemiology of postoperative endophthalmitis in anAsian population: 11-year incidence and effect of intracameral antibiotic agents. JCataract Refract Surg. 2012;38(3):425-430.E2Vidyadevi M, Anuradha A, Rashmi G, Shilpa R, Nishath S. Safety of Fixed drugCombination in Post -Operative Cataract Patients, at Tertiary Care Centre - InSouth India. Nepalese Journal of Ophthalmology : A Biannual Peer-reviewedAcademic Journal of the Nepal Ophthalmic Society : NEPJOPH. 2017;9(18):24-29.E2Yu-Wai-Man P, Morgan SJ, Hildreth AJ, Steel DH, Allen D. Efficacy of intracameraland subconjunctival cefuroxime in preventing endophthalmitis after cataractsurgery. Journal of Cataract & Refractive Surgery. 2008;34(3):447-451.E27

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramAPPENDIX C: EVIDENCE TABLESCHARACTERISTICS OF INCLUDED PRIMARY STUDIESAuthorYearNArshinoff,20111N 104,914Bhatta,20212N 11,983Cetinkaya,20153N 65Study DesignSurgery TypeCountryOutcome TimingRetrospective cohortPEGlobalNRRetrospective cohortPE or MSICSNepal6 weeksRetrospective cohortPETurkey52.1 weeksDave, 20224 Retrospective cohortIndiaEkinci,20125Retrospective cohortPETurkey0.43 weeks8Pre- and PostoperativeInterventionsVariable acrossVariablesurgical centers (0.1 to0.5 mg/01. to 0.2 mL)ComparatorNo IC antibiotic orIC cef uroxime0.5 mg in 0.1 mL direct Preoperative: 5% PINo IC antibioticf rom vialPostoperative: gentamycin anddexamethasone injection, topicalof loxacin (1 month), topicalsteroid (prednisone ordexamethasone) (1–2 weeks)0.1 mL of undiluted0.5% MOXPreoperative: 0.5% topical MOX, No IC antibiotic10% PIPostoperative: topical MOX0.5% (1 week) and topicalsteroid (1 month)PE, MSICS, or ECCE 0.5 mg MOX in 0.1 mL Preoperative: 5% PIPostoperative: Topicalcorticosteroid (1 month) and6 weekstopical antibiotic (1 week)N 66,967N 60MoxifloxacinConcentration andPreparation0.1 mL of undiluted0.5% MOXNo IC antibioticPreoperative: 5–10% PINo IC antibioticPostoperative: 5% PI, topicalMOX (5 days until bottle empty),topical prednisolone (3 weeks)

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisAuthorYearNFrilling,20136N 464,755Galvis,20147N 2,674Haripriya,20168N 75,937Haripriya,20179N 617,453Haripriya,201910N 2,062,643Herrinton,201611N 294,6499Study DesignSurgery TypeCountryOutcome TimingRetrospective cohortPE or "other"Sweden4 weeksRetrospective cohortPEColumbia2 weeksRetrospective cohortEvidence Synthesis ProgramMoxifloxacinConcentration andPreparationPre- and PostoperativeInterventionsComparatorVariable acrosssurgical centersVariableNo IC antibiotic orIC cef uroxime0.05 mL of undilutedMOX 0.5%Preoperative: fluoroquinolone,5–10% PIPostoperative: fluoroquinolone(8–10 days)No IC antibioticPE, MSICS, or ECCE 0.5 mg in 0.1 mL or0.5% MOX6 weeksPreoperative: topical ofloxacin,PIPostoperative: topical ofloxacin(15 days), topical gatifloxacinand dexamethasone (42 days)No IC antibioticPE, MSICS, or ECCE 0.5 mg in 0.1 mL or0.5% MOX6 weeksPreoperative: topical ofloxacin,PIPostoperative: topical ofloxacin(15 days), topical gatifloxacinand dexamethasone (4–6weeks)No IC antibioticPreoperative: topical ofloxacin,PIPostoperative: topical ofloxacin(15 days), topical gatifloxacinand dexamethasone (4–6weeks)No IC antibioticIndiaPE, MSICS, or ECCE 0.5 mg in 0.1 mL or0.5% MOX6 weeksRetrospective cohortPENRTopical antibiotics orIC Cef uroximeUSA12.9 weeksIndiaRetrospective cohortIndiaRetrospective cohortNR

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisAuthorYearNLane,200812N 57Matsuura,201313N 34,755Matsuura,201414N 138Melega,201915N 3,640Porwal,202116N 40392Rathi,202117N 42,46610Study DesignSurgery TypeCountryOutcome TimingRCTPEUSA12.9 weeksRetrospective cohortPEJapan4.3 weeksRetrospective cohortPEJapan12.9 weeksRCTPEBrazil6 weeksRetrospective cohortMSICSIndiaNRProspective cohortPE or MSICSIndia11 weeksEvidence Synthesis ProgramMoxifloxacinConcentration andPreparationPre- and PostoperativeInterventions0.25 mg in 0.05 mL ofundiluted 0.5% MOXPreoperative: Topical MOXSalt solution0.5%, PIinjectionPostoperative: Topical MOX0.5% (1 week), topicalprednisolone acetate (1 month),topical nepafenac (1 month)Varied amonginstitutions: 0.05mg/mL to 0.5 mg/mLMOXNR0.15 mg/mL to 0.5mg/mL of 0.5% MOXPreoperative: topicalSalt solutionlevofloxacin, 10% PI plus iodine irrigationirrigationPostoperative: topical MOX,topical betamethasone sodiumphosphate, and topicalbromfenac (1 month)0.15 mg in 0.03 mL ofundiluted 0.5% MOXPreoperative: 10% PINo IC antibioticPostoperative: 0.5% MOX and0.1% dexamethasone eyedrops(1 week)NRNR0.1 mL of MOX at 0.5% Preoperative: 5% PIweight/volume directPostoperative: Topicalf rom vialcorticosteroids (4-6 weeks).Topical antibiotic prescribed atdiscretion of surgeon.ComparatorNo IC antibioticNo IC antibioticIC Cef uroxime

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisAuthorYearNShenoy,202118N 214,782Shorstein,202119N 204,655Vieira,201720N 7,195Zhou,201621N 222Study DesignSurgery TypeCountryOutcome TimingRetrospective cohortPE or MSICSIndia25.7 weeksRetrospective cohortIC Cef uroximeUSA12.9 weeksRetrospective cohortPEBrazil6 weeksRetrospective cohortPEUSA4.3 weeksEvidence Synthesis ProgramMoxifloxacinConcentration andPreparationPre- and PostoperativeInterventionsComparator0.1 mL of 0.5%weight/volume MOXPreoperative: 5% and 10% PIPostoperative: topical steroidantibiotic (Ofloxacin andPrednisolone) (2 weeks) andoral Ciprofloxacin wasprescribed (3 days)No IC antibiotic0.1 mL – 1 mL of 0.1% VariableMOXIC Cef uroxime0.05 mL of MOXhydrochloride at 5.45mg/mLPreoperative: 5% PINo IC antibioticPostoperative: topical antibiotics(10 days)0.5 mg in 0.1 mL of0.5% MOXPreoperative: 5% PI,proparacaine, phenylephrine,cyclopentolate, ketorolac, andlidocaineIntraoperative: 5% PI,prednisolone acetatePostoperative: nepafenac,prednisolone acetate drops (2weeks), 0.5% MOX drops (1week - no IC group only)Topical MOXAbbreviations. ECCE Extracapsular cataract extraction; IC Intracameral; MOX Moxifloxacin; MSICS Manual small incision cataract surgery; NR Not reported;PE Phacoemulsification; PI Povidone-iodine.Notes. N number of eyes.11

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramOUTCOME DATA OF INCLUDED PRIMARY torArshinoff,20111PEBhatta,20212PE orMSICSDave,20224N MOXN Comp.# w/ Endop.MOX# w/oEndop.MOX# w/ EndopComp.#w/o Endop.Comp.No IC antibiotic 59,041(no antibiotic ortopicalantibiotic)35,19423,847135,1931223835No IC antibiotic 111,98331,34080,643831,33211680527PE,No IC antibiotic 66,967MSICS, orECCE34,31832,6491534,3032132,628Frilling,20136PE or"other"No IC antibiotic 9,701(no antibiotic 147PENo IC antibiotic 2,6741,6181,05601,61811055Haripriya,20168PE,No IC antibiotic 75,937MSICS, ,No IC antibiotic 617,453MSICS, 01910PE,No IC antibiotic 2,062,643MSICS, orECCE10696349930091851,069,449 37,54212TopicalantibioticN Overall258,859167

Evidence Brief: Moxifloxacin for Preventing uura,201313PEMelega,201915N OverallEvidence Synthesis ProgramN MOXN Comp.# w/ Endop.MOX# w/oEndop.MOX# w/ EndopComp.#w/o Endop.Comp.No IC antibiotic 34,75518,79715,958318,794815,950PENo IC antibiotic 3,6401,8181,82211,81771815Porwal,202116MSICSNo IC antibiotic 4039219,85920,533319,8561020523Shenoy,202118PE orMSICSNo IC antibiotic 0PE withNo IC antibiotic iations. Comp comparator; ECCE extracapsular cataract extraction; Endop endophthalmitis; IC intracameral; MSICS manual small incision cataractsurgery; MOX moxifloxacin; PE phacoemulsification; w with event; w/o without event.Notes. N number of eyes.Other Adverse EventsAuthorYearNSurgeryTypeTASSCorneal or Macular EdemaOther Adverse EventsArshinoff,20111N 104,914PENRCorneal: NRMacular: NRNRBhatta, 20212 PE orMSICSN 11,983No cases of TASSCorneal: NRMacular: NRNo adverse reactions to MOXCetinkaya,20153N 65No cases of TASSCorneal: Corneal edema: 6% MOX vs 9%control (p 0.623).Macular: NRAnterior chamber reaction (cells 1 ):12% MOX vs 9% control (p 0.726)13PE

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisAuthorYearNSurgeryTypeDave, 20154N 66,967PE, MSICS, NRor ECCEEckinci, 20125 PEN 60TASSOther Adverse EventsCorneal: Among eyes with endophthalmitis: Lid edema among eyes with33.3% MOX vs 71.4% no MOX (p 0.03)endophthalmitis: 40% MOX vs 76.2%no MOX (p 0.03)Macular: NRCorneal: There were no corneal edemaevents in either study groupMacular: NRNo study-related adverse eventsCorneal: NRMacular: NRNRNRCorneal: NRMacular: NRNRHaripriya,20168N 75,937PE, MSICS, No cases of TASSor ECCECorneal: NRMacular: NRNo adverse reactions to MOX, includingcorneal decompensationHaripriya,20179N 617,453PE, MSICS, No cases of TASSor ECCECorneal: NRMacular: NRNo adverse reactions to MOX, includingcorneal decompensationHaripriya,201910N 2,062,643PE, MSICS, No cases of TASSor ECCECorneal: Rate of persistent postoperativeNo adverse reactions to MOX, includingcorneal edema not different between groups corneal decompensation(data NR)Macular: NRHerrinton,201611N 294,649PENRCorneal: NRMacular: Only reported for any IC, notspecific to MOXLane, 200812N 57PE2 patients in MOX group Corneal: Trace (1-5 cells): 1 MOX vs 0 saltexcluded from analysissolution (p 0.2706)due to TASSMacular: NRNo study-related adverse eventsMatsuura,201313N 34,755PENo cases of TASSNo adverse reactions to MOX, includingsevere corneal damageFriling, 20136N 464,755PE or "other" NRGalvis, 20147 PEN 2,67414NRCorneal or Macular EdemaEvidence Synthesis ProgramCorneal: NRMacular: NROnly reported for any IC, not specific toMOX

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramAuthorYearNSurgeryTypeTASSCorneal or Macular EdemaOther Adverse EventsMatsuura,201414N 138PENo cases of TASSCorneal: NRMacular: NRNo adverse reactions to MOX, includingcorneal damageMelega,201915N 3,640PENRCorneal: NRMacular: NRNo ocular or systemic study-relatedadverse eventsPorwal,202116N 40,392MSICSNRCorneal: NRMacular: NRNRRathi, 202117N 42,466PE orMSICSNo cases of TASSCorneal: 2 cef uroxime vs 0 MOXMacular: NRAny complications (MOX vscef uroxime): aOR 1.90, 95% CI [0.248–14.583], p 0.536Shenoy,202118N 214,782PE orMSICSNRCorneal: NRMacular: NRNRShorstein,202119N 204,655NRNRCorneal: NRMacular: NRNRVieira, 201720 PEN 7,195NRCorneal: NRMacular: NRNRZhou, 201621N 222NRCorneal: 1 day postoperative: 0.188 IC MOXvs 0.083 topical (p 0.069)1 month postoperative: 0.011 IC MOX vs0.023 topical (p 0.512)Macular: 0 eyes in MOX vs 2 eyes (1patient) in the topical groupAnterior chamber reaction (cells 1 ):1 day postoperative: 0.06 IC MOX vs0.033 topical (p 0.370)1 month postoperative: 0.011 IC MOXvs 0.023 topical (p 0.512)2 eyes (1 patient) in MOX vs 1 eye inthe topical group developed iritisPEAbbreviations. ECCE extracapsular cataract extraction; IC Intracameral; MOX Moxifloxacin; MSICS Manual small incision cataract; NR Not reported;OR Odds ratio; PE Phacoemulsification, TASS Toxic anterior segment syndrome.Notes. N number of eyes.15

Evidence Brief: Moxifloxacin for Preventing EndophthalmitisEvidence Synthesis ProgramQUALITY ASSESSMENT OF INCLUDED PRIMARY STUDIESRandomized Controlled TrialsAuthorYearRisk of BiasfromRandomizationProcessRisk of Bias fromDeviation fromIntendedInterventions(Assignment)Risk of Bias from Risk of BiasDeviation fromfrom MissingIntendedOutcome DataInterventions(Adherence)Risk of Bias inMeasurement ofOutcomeLane200812Some concernsUnclear how therandomizationwas done and ifallocation wasconcealed.Some concernsNo blinding ofsurgeons and noapparent blindingof patients.Unclear if allpatients receivedintervention asassigned.Some concernsNo blinding ofsurgeons and noapparent blindingof patients.Unclear if therewas deviation fromintervention in anycases. All patientsappear to havereceived the sameco-interventions.Some concerns 17% excludedf rom analysisdue to lost tof ollow-up orunrelatedadverse events.Some concernsSome concerns Some concernsUnclear ifNo

Cavalcanti Lira RP, Lucena NP, Ferreira KS, Santos BM. Long -term safety of intracameral moxifloxacin after cataract surgery. Journal of Cataract & Refractive Surgery. 2017;43(1):139-140. E4 Colleaux KM, Hamilton WK. Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol.