Department of Ophthalmology, Regional Institute of Ophthalmology, Bhimrao Ambedkar Memorial Hospital, Pt.JNM, Raipur,Chhattisgarh, IndiaIndia
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Objective: To evaluate the clinical efficacy, safety, novelty and patient-reported outcomes of intravitreal faricimab in Indian patients presenting with diabetic macular edema (DME) and refractory cystoid macular edema (CME) secondary to branch retinal vein occlusion (BRVO). Methods: This descriptive case series documents two distinct adult patients with macular edema who received intravitreal faricimab injections.Key outcome measures evaluated over a 3-month follow-up period included best-corrected visual acuity (BCVA), central macular thickness, ocular and systemic adverse events, and subjective patient satisfaction measured on a standardized scale (ranging from "not satisfied" to "very satisfied"). Results: Both eyes demonstrated substantial anatomical resolution and functional visual improvement.Better visual recovery correlated with shorter diabetes duration and better baseline BCVA. No intraocular inflammation, intraocular pressure spikes, or other ocular complications were reported. Subjective patient satisfaction shifted from "moderate" at baseline to "very satisfied" post-treatment. Conclusion: Intravitreal faricimab demonstrates promising therapeutic potential for managing DME and treatment-resistant CME secondary to BRVO in an Indian demographic. Dual-pathway targeting offers strong anatomical stabilization and visual gains, warranting broader clinical evaluation.
Keywords: Angiopoietin-2 (Ang-2); CrossMAb (Cross Over Monoclonal Antibody); DME-Diabetic Macular Edema; Macular BRVO (Macular Branch Retinal Vein Occlusion); Angiopoietin-2(Ang-2); CrossMAb(CrossOverMonoclonalAntibody); DME-DiabeticMacular Edema; MacularBRVO(MacularBranchRetinalVeinOcclusion)
Retinalvasculardisorders—specificallydiabeticmacularedema(DME)andneovascularage-relatedmacular degeneration(nAMD)—remainmajorcausesofvision lossamongworking-agepopulationsandolderadults worldwide. Asharedpathologicalhallmarkofthese conditionsistheupregulationofvascularendothelial growthfactor-A(VEGF-A),apowerfulpro-angiogeniccytokinethattriggersmicrovascularhyperpermeability, breakdownoftheblood-retinalbarrier,andabnormal angiogenesis. Thisresultsinpathologicalneovascularization,fluidaccumulation,andprogressivevisual decline[1].Anti-VEGFtherapyhastraditionallyserved asthemainstayoftreatment,aimingtomitigatevesselleakageandsuppressneovascularproliferationto stabilizevisualfunction.
Despitethewidespreadadoptionofanti-VEGFagents, theglobalhumanandeconomicburdenofretinaldiseases continues to surge. Diabetic retinopathy (DR) currently affects roughly 30% to 40% of individuals diagnosedwithdiabetesmellitusandisaleadingcontributortopreventableblindness[3].Epidemiological projectionsestimatethattheglobalprevalenceofDR will escalate from 103 million individuals in 2020 to morethan161millionby2045[4].
Becausemanypatientsdisplaysub-optimalresponses or treatment fatigue under conventional anti-VEGF regimens, addressing complementary biological pathways—suchasAngiopoietin-2(Ang-2)inhibition toenhancevascularstability—hasemergedasapriority. Faricimab, anovelbispecificantibodytargeting both VEGF-A and Ang-2, represents an innovative approachtomanagingresistantmacularedemaand optimizedlong-termdiseasecontrol.
Purpose: Toreportcaseseriesof2patientstreated withINTRAVITREALFARICIMAB.
A64-year-oldmalepresentedintheoutpatientdepartmentwithahistoryofgradualpainlessdiminutionof vision in both eye for 2 years, which was gradual in onset,progressiveinnatureandnotassociatedwith pain.Heisknowncaseofhypertensionsince6months andknowncaseofdiabetesmellitussince1.5years. Hehadhistoryoflaser(panretinalphotocoagulation) doneelsewhere6monthsback.
avisionofcountingfinger1metrenotimprovingwith pinholeand6/36visioninlefteye.Bestcorrectedvisual acuitywasnotimprovinginbotheyesandonanterior segmentevaluationrevealednuclearsclerosisgrade3 withposteriorsubcapsularcataractgradeIIintheright eyeandnuclearsclerosisgrade1inlefteye.
Onfundusexaminationofrighteyerevealedcupdisc ratioof0.3,multiplehardexudateincircinatepattern inmacularareawithfewdotblothaemorrhagesinall quadrantwithlasermarks.
retinopathyS/Ppanretinalphotocoagulationwithdiabeticmacularedema.
Onocularexamination,thepatienthad6/36visionin lefteye.Bestcorrectedvisualacuitywasnotimprovinginbotheyes.OPTICALCOHERENCETOMOGRAPHY (OCT). OCT of left eye also showed cystoid macular edemawithhardexudatesinouterplexformlayer;CMT (centralmacularthickness)inthelefteyewas572 µm.
Informedconsentwasobtainedfromthepatientafter discussingriskbenefits. Patientwasadvisedlefteye intravitrealfaricimabindoseof6mgin0.05mL,8days afterintravitrealinjectioninrighteyeandwastreated withthesame.After1month14daysoffollowup,patienthad6/18aidedvisioninlefteye.OnOCTexaminationlefteyeagainrevealedcystoidandserousmacular edema.Patientwasadvised2nddoseoflefteyeintravitrealfaricimabindoseof6mgin0.05mL,theinterval ofseconddosewas1month14days.Onfollow-upafter1monthpatienthad6/18aidedvisioninthelefteye, OCTexaminationrevealedresolvingmacularedema inlefteye.Patientwasmonitoredforadverseeventin everyfollowupandnoadverseeventswereobserved. Patientsatisfactionimprovedfrommoderateatearly follow-upstoverysatisfiedby3months.
avisionofcountingfingersat1metrenotimproving withpinhole.Bestcorrectedvisualacuitywasnotimprovinginbotheyes. OPTICALCOHERENCETOMOG- RAPHY(OCT)oftherighteyeshowedcystoidmacular edemawithhardexudatesinouterplexformlayer,I was599 µm.
Thisispreoppicture PatientwasadvisedRighteyeintravitrealranibizumab andwastreatedwiththesame.Visioninrighteyeimproved to counting finger 2 meter on day 1 post intravitreal injection. After 1 month 14 days of follow up,patienthad6/36aidedvisioninrighteye.OnOCT examinationrighteyeagainrevealedcystoidmacular edema.
Patientwasplannedforrighteyecataractsurgerywith IOLwithintravitrealtriamcinoloneacetonideandwas treatedwithsame.Visioninrighteyewas6/36on1st postoperativeday. Onfollowupafter1month,OCT examinationinrighteyeagainrevealedresolvingdiabeticmacularedema,CMTwas245 µm.
Thisispostoppicture
A55-year-oldfemalepresentedintheoutpatientdepartmentwithahistoryofgradualpainlessdiminution ofvisioninlefteyesince4months.Sheisknowncase ofhypertensionsince3yearsonregulartreatmentand recentlydiagnosedcaseofdiabetesmellitussince2 months.
avisionbestcorrectedvisualacuityof6/18and6/36 visioninlefteyeandonanteriorsegmentevaluation revealedpseudophakiainbotheyes.
Onfundusexaminationofrighteyerevealedcupdisc ratioof0.3,multiplehypopigmentedlesionininferior quadrant.Onfundusexaminationoflefteyerevealed, cupdiscratioof0.3,multipledotblotandflameshaped haemorrhagesandhardexudateinmaculararea,FR (Fovealreflex)-wasdull,cystoidmacularedemawas present,multiplehypopigmentedlesionwaspresent ininferiorquadrant.
OPTICALCOHERENCETOMOGRAPHY(OCT)oftheleft eyeshowedcystoidmacularedemawithhardexudates inouterplexformlayer.
Patientwasadvisedlefteyeintravitrealranibizumab andwastreatedwiththesame. Inthenextfollowup after2monthsvisioninrighteyewas6/18and6/24 visioninlefteye. OnOCTexaminationlefteyeagain revealedcystoidmacularedema,CMTwas564 µm.
Patient was switched to faricimab after inadequate ranibizumab response. Informed consent was obtained from patient after discussing risk benefits. Patient was advised left eye intravitreal faricimab in dose of 6 mg in 0.05 mL, the interval between seconddosewas2months.Afteronemonthfollowup visionimprovedto6/18inlefteye.OnOCTtherewas resolutionofcystoidmacularedemaandCMTwas180 µm.
Patientwasmonitoredforadverseeventineveryfollow upandnoadverseeventswereobserved.Patientsatisfactionimprovedfrommoderateatearlyfollow-ups toverysatisfiedby3months.
Faricimabisanovelbispecificmonoclonalantibody composedoftwoheavychainsandtwolightchains. Itisdesignedtotargettwopathwayssimultaneously: oneligand-bindingarmneutralizesVEGF-A,whilethe otherbindsangiopoietin-2(Ang-2).Faricimabtargets twokeypathwaysinvolvedinDMEpathogenesis[5]. Faricimabisafullyhuman150-kDamonoclonalantibody of bispecific design. Its unique architecture is bornfromtheCROSSMAB(CROSSOVERMONOCLONAL ANTIBODY)technology,whichallowsforthedevelopment of bispecific antibodies that closely resemble thenaturalimmunoglobulin,featuringtwoseparate antigen-bindingdomains[6,7].
Recentstudieshavedemonstratedthatthetyrosinekinasewithimmunoglobulin-likeandepidermalgrowth factor-likedomains2(Tie2)playsacriticalroleinangiogenesisaswellasvascularstability,andinhibiting Ang2leadstoTie2activation.Tie2isatransmembrane receptorexpressedonendothelialcellsanditserves asabindingsitefortheangiopoietinfamilyofligands, whichincludesangiopoietin-1(Ang1)andAng2[8,9]. OnceboundtoTie2,Ang1functionstophosphorylate thereceptorandthenactivatesthedownstreampathwaysthatultimatelysuppressvascularpermeability andmaintainvascularstability[10,11].Ang2isanendogenous,partialagonistofTie2thatcompeteswith Ang1todownregulatethephosphorylationandactivationofTie2.
Ang2levelsareelevatedinretinalvasculardiseases, includingnAMD,DR,proliferativeDR,andRVO.Ang-1 ensuresvascularstabilityinhealthytissues,Ang-1activatestheTie2receptor.Ang-2isupregulatedinretinal diseases.Ang-2andVEGF-AareupregulatedinthevitreousofpeoplewithnAMD,DR,andRVO,supportinga rolefortheAng-2/Tie2pathwayinthesepathologies. Ang-2andVEGF-Abothactsynergistically. Ang-2inhibitstheTie2receptor,promotesinflammation,and sensitisesbloodvesselstotheactivityofVEGF-A,leadingtoleakageandneovascularization.
1891patients(YOSEMITEn=940,RHINEn=951)were randomized to intravitreal faricimab 6.0 mg every 8 weeks,faricimab6.0mgperpersonalizedtreatment interval(PTI),oraflibercept2.0mgevery8weeksup toweek100.
PTI is based on a protocol-driven dosing regimen, similarly to the so-called treat-and-extend regimen, wherein patients receive faricimab 6.0 mg every 4 weeks until CENTRAL SUBFIELD THICKNESS (CST) islessthan325 µmat/orafterweek12, afterwhich treatment intervals could be increased by 4 weeks (up to 16 weeks) or reduced by 4 or 8 weeks (down to 4weeks)based onCSTandbestcorrectedvisual acuity (BVCA). Across both trials, Faricimab showed non-inferior vision gains and improved anatomical outcomeswhencomparedtoAflibercept[15].
TheTAHOEtrialnotedimprovementsinvisualacuity (as measured in ETDRS letters) and central subfield thicknessparametersforbothtreatment-naïveandpreviouslytreatedpatientswithDMEwhoreceivedatleast oneintravitrealinjectioninareal-worldsetting[19]. Long-termhyperglycemiacontributestobreakdown of the blood–retina barrier with an increase in vascular permeability and a macular exudative fluid accumulation—hallmarks of DIABETIC MACU- LAR EDEMA (DME). Since the advent of intravitreal ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR (ANTI-VEGF) therapies in 2010, visual outcomes in patients with DME have significantly improved, establishing these agents as the standard first-line treatmentforcenter-involvedDME[16,17].However, a substantial proportion of patients—over 30%— continuetoexhibitpersistentedemadespiteoneyear ofappropriatetherapy[18].
Repeatedintravitrealinjectionsareoftenrequiredfor management,whichcanprolongthetreatmentcourse andcreatesignificantfinancialandemotionalstressfor patients.Inaddition,repeatedinjectionsmayincrease theriskofocularcomplications,includingpersistent elevationofintraocularpressure,retinalpigmentepitheliumtears,andgeographicatrophy[20].
HYPERREFLECTIVEFOCI(HRF)areidentifiedonOCT asdiscrete,well-circumscribed,dot-shapedlesionsup to50 µmindiametershowingreflectivityequaltoor greater than that of the retinal pigment epithelium band[21].HRFarebelievedtoberepresentativeofactivatedmicrogliaandmaybeabiomarkerofaninflammatorymicroenvironmentinretinaldiseases[21,22].
OCTservestoassessCRT(µm)inthecentral1mmcircleoftheETDRSgrid.SUPERFICIALCAPILLARYPLEXUS (SCP) AND DEEP CAPILLARY PLEXUS (DCP), FOVEAL
AVASCULARZONE(FAZ),OUTERRETINALFLOWAREA (ORFA)ANDCHORIOCAPILLARISFLOWAREA(CCFA)are measuredautomaticallyusingOCTAsoftware.
InstudybyDorotaetalandSpiewakOCTandOCTA were performed before the first injection and one month after each subsequent administration of 6 mg faricimab. NON-PERFUSION AREAS (NPA) were measured manually but by examining ophthalmologist. Automatic measurements of ORFA and CCFA demonstratesthegenerationofvesseldensitymaps coveringa6.4 × 6.4mmarea.
SCP and DCP vessel density is measured across the ETDRSgridwithconcentriccirclesat1,3,and6mm centredatthefovea. Pre-treatmentscansrevealnumerousNPAfocimeasuredinthesuperficiallayersof theretina;thesoftwaresumstheirareaanddisplays the result in mm2. In Optovue Solix, NPA areas are markedinyellow.
Followingtreatment,theseareasshowednoticeable improvementincapillaryperfusionisseenasareduction in the area of NPA zones marked in yellow. Improvedretinalvascularizationprotectsagainstthedevelopmentofpathologicalretinalneovascularization withitsnumerousconsequences,includingblindness. However,theSCPshowedsignificantincreasebythe fourmonth,indicatingadelayedbutnotabletherapeuticeffectonperfusionstatus.Thelinearmixed-effects modelfortheDCPdemonstratedaclearandstatisticallyrobustincreaseinDCPdensityfrombaselineover thefour-monththerapyperiod.
InmostpatientswithDME,anti-VEGFtherapyimproves vascularperfusion.Additionallyintravitrealfaricimab ledtoameaningfulreductioninFAZ,whichwasmore pronounced at two, three and four months. An improvementintheFAZcircularitywasalsoobserved, whichmayindicatetherestorationofparafovealperfusion.LiteraturereportsalsoindicateanincreaseinFAZ circularitywithinthesuperficialretinalvasculatureafteranti-VEGFtherapy.Thus,thelossofFAZcircularity mightbeconsistentwithcapillaryatrophyattheFAZ border[23].
Traditionalfirst-lineanti-VEGFmonotherapies(such as ranibizumab or bevacizumab) exclusively target VASCULARENDOTHELIALGROWTHFACTORA(VEGF-A). However,asdemonstratedinCase2,asignificantsubsetofpatientsexhibitanatomicalnon-responsiveness orearlyrecalcitrancetoselectiveVEGF-Ablockade. ThecasereportisuseaboutintravitrealFaricimab,in secondcaseofrefractoryBRVOwithcystoidmacular edemaasitwasinadequateresponsetoranbizumab, sothePatientwasswitchedtofaricimab.Therehave beenveryfewercasereportsonintravitrealfaricimab, sothiscasereporthighlightstheimportanceofnovel drugintravitrealfaricimabinDMEandrefractoryBRVO withcystoidmacularedema.
FaricimabrepresentsastructuralshiftintreatingrefractoryDMEthroughitsdesignasabispecificantibody.It simultaneouslytargetstwodistinctdiseasepathways.
WhileVEGF-Adrivesendothelialcellproliferationand initialleakage,ANGIOPOIETIN-2(Ang-2)actssynergisticallytodestabilizethevascularendothelium,increase sensitivitytoVEGF,andpromotestructuralinflammation.
Case1 64M,HTN(6mon),DM RE: Vision - CF 1m; NS3 + PSC2 RE:IVRanibizumabrighteye; Pha- RE:Visionimprovedto6/36;CMTre- (1.5yr),S/PPRP(6mon) Cataract;CMT599 µm(DMEpresent). coemulsification+IOL+IVTriamci- solvedto245 µm. LE:Vision6/36;NS1Cataract;CMT noloneAcetonide(IVTA). LE:Visionimprovedto6/18;resolv- 572 µm(DMEpresent). LE:2dosesofIVFaricimab6mgin ingmacularedema;veryhighpatient Case2 55F,HTN(3yr),recently RE:Vision6/18;Pseudophakic. LE:InitialIVRanibizumab. LE: Vision improved to 6/18; resodiagnosedDM(2mon) LE:Vision6/36;Pseudophakic;CMT SwitchedtoIVFaricimab6mgin0.05 lutionofresistantcystoidmacular 564 µm (CME present with haem- mLduetoinadequateresponseto edema;highpatientsatisfactionby orrhages,hardexudatesinmacular ranbizumab. 3months. area).
Byinhibitingbothligands,Faricimab: • Restoresendothelialjunctionstability(viathe Tie-2receptorpathway).
• Decreasesvascularpermeabilitymoreeffectively thanVEGF-Ainhibitionalone.
• Suppressesunderlyinginflammatorycascades thatcontributetochroniccystoidspaces.
AsseeninthepseudophakiceyeofCase2,structural fluidpersistence(CMT564 µm)despiteranibizumab therapyhighlightsthelimitationsofsoloVEGFinhibition.Switchingtofaricimabyieldssecondaryvisualimprovementsto6/18withinasinglemonth.Thisunderscoresitsroleforeyesshowingsuboptimalresponse totraditionalmolecules.
Faricimab’sstabilizingeffectonthecapillarybedsresultsinextendedfluidcontrol.Inbothclinicalscenarios,stabilizingthemaculaledtoamarkedpivotinpatientexperience.
Wereportcaseseriesof2patientstreatedwithIntravitrealFARICIMAB.FARICIMABisthefirstintraocularbispecificantibodyuniquelydesignedtosimultaneously inhibitbothAng-2andVEGF-A.Anti-VEGF-Areduceneovascularisationandvascularleakage. Anti-Ang-2Reduceinflammationandvascularleakageandstabilise vessels.Additionally,themodifiedFcregionminimizes 0.05mL. satisfactionby3months.
systemicexposureandlowersinflammatorypotential. The visual and anatomical improvements observed withfaricimabhighlightitskeyimportantroleinDME andrefractorymacularBRVOwithCME.Thelimitation wereverysmallsamplesize,shortfollow-up,heterogeneousdiagnoses,andconfoundingbyotherocular treatmentsinthefelloweye.
Sangeeta Thakur, Nidhi Pandey, Swati Kujur and JayshreeSalam(2026).OptimizingOutcomewithIntravitrealFaricimabinCaseofDiabeticMacularOdema andRefractoryMacularBrvowithCME. PublicHealth OpenJournal.11(1):802–8xx.10.17140/PHOJ-11-802