Intraocular Inflammation Following Intravitreal Injection
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Post-intravitreal injection IOI is an inflammatory complication following intravitreal drug administration, including anti-VEGF agents and complement inhibitors. It ranges from mild sterile inflammation (anterior chamber cells, vitritis, sterile endophthalmitis) to severe retinal vasculitis, occlusive retinal vasculitis, and infectious endophthalmitis. Noninfectious IOI results from immune-mediated reactions related to drug immunogenicity, patient susceptibility, and delivery factors such as silicone oil contamination, whereas infectious endophthalmitis results from microbial contamination during injection. High-risk agents include brolucizumab which may cause delayed immune-mediated retinal vasculitis and vascular occlusion. Diagnosis relies on timing of onset, clinical examination, OCT, fluorescein angiography, and intraocular sampling when infection cannot be excluded. Management includes urgent antibiotics for suspected infection and corticosteroid-based therapy for sterile inflammation, with escalation to intravitreal steroids, systemic therapy, or vitrectomy in severe cases. Prevention includes strict aseptic technique, optimized syringe systems, careful drug handling, and avoidance of rechallenge after significant inflammatory events. Prognosis is generally favorable for mild sterile IOI but guarded for occlusive retinal vasculitis, which may result in permanent vision loss.
Disease Entity
Post-intravitreal injection IOI is an inflammatory complication that occurs after intravitreal administration of therapeutic agents, most commonly anti-vascular endothelial growth factor (anti-VEGF) drugs, but also complement inhibitors and other intravitreal medications. It encompasses a spectrum ranging from mild sterile anterior or vitreous inflammation to severe retinal vasculitis, occlusive retinal vasculitis, and infectious endophthalmitis. Early recognition and accurate classification are essential because management and visual prognosis differ substantially.[1][2][3] There is no specific ICD-10-CM code for post-intravitreal injection IOI; coding depends on the clinical manifestation, including:
- H44.131–H44.139 – Endophthalmitis (eye-specific)
- H20.9 – Unspecified iridocyclitis (anterior uveitis)
- H30.90 – Unspecified chorioretinal inflammation
- H35.06 – Retinal vasculitis
- T50.905A – Adverse effect of unspecified drug or medicament, initial encounter (or the appropriate adverse-effect code for the specific drug)
Disease
Intraocular inflammation after intravitreal injection denotes any inflammatory response within the eye following intravitreal drug administration. Implicated agents include anti-VEGF drugs (bevacizumab, ranibizumab, aflibercept, brolucizumab, faricimab), complement inhibitors (pegcetacoplan, avacincaptad pegol), and their biosimilars. The clinical spectrum includes:
- Anterior chamber inflammation (cells and flare)
- Vitritis
- Sterile endophthalmitis (pseudoendophthalmitis)
- Retinal vasculitis (arteritis and/or phlebitis)
- Occlusive retinal vasculitis with vascular occlusion
The term "noninfectious IOI" or "sterile endophthalmitis" distinguishes these drug-related reactions from infectious endophthalmitis.[2][3]
Etiology
Intraocular inflammation is classified as infectious or noninfectious.
Infectious endophthalmitis results from microbial contamination during injection. Gram-positive cocci — primarily coagulase-negative staphylococci (~70%), Staphylococcus aureus, and streptococci — account for more than 90% of cases in the United States. Streptococcal endophthalmitis is disproportionately common after intravitreal injection compared with cataract surgery and carries a poor prognosis. Gram-negative bacilli and fungi cause 10–20% of cases in tropical regions.[4] Outbreaks linked to glucose non-fermenters (Pseudomonas aeruginosa, Enterobacterales) and molds have been reported with intravitreal drug injections.[5]
The overall rate of endophthalmitis after anti-VEGF injection is approximately 0.02–0.035% per injection (1 in 2,857 to 1 in 4,897 injections).[6][7] The cumulative risk per eye increases with the number of injections but at a decelerating rate: from 0.028% after 1 injection to 0.50% after 126 injections.[7] Prefilled syringes are associated with lower endophthalmitis risk than non-prefilled syringes (incidence rate ratio [IRR] 1.63–1.82 for non-prefilled).[8]
Noninfectious IOI is a sterile, drug-related inflammatory reaction. Three categories are recognized[9][10][11][12][13]:
1. Patient-specific factors — Individual immune susceptibility, including autoimmune predisposition and preexisting or treatment-emergent antidrug antibodies (ADAs). The prevalence of ADAs is approximately 44% for brolucizumab and 3% for aflibercept. Cross-reactive ADAs unrelated to anti-VEGF exposure may also yield positive assays. For ranibizumab, ADAs were present in approximately 1–9% of participants after 6–24 months of treatment, and some participants with the highest ADA levels developed vitritis or iritis.[9][10][14]
2. Medication-specific factors — Immunogenic properties of the biologic itself. The fragment crystallizable (Fc) portion present in aflibercept and bevacizumab (absent in ranibizumab) may engage intraretinal Fc receptors, promoting immune complex formation — a mechanism that would account for the higher rate of sterile IOI after aflibercept compared with ranibizumab. Protein aggregates within drug formulations can also trigger inflammation. Brolucizumab carries additional immunogenic risk due to a bacterial-shared linear epitope, non-natural surfaces inherent to its single-chain variable fragment (scFv) format, and non-native drug species that accumulate during prolonged intraocular residence. Complement inhibitors (pegcetacoplan, avacincaptad pegol) have distinct molecular structures — pegcetacoplan is a PEGylated cyclic peptide targeting complement component 3 (C3), while avacincaptad pegol is a PEGylated ribonucleic acid (RNA) aptamer targeting complement component 5 (C5) — and their IOI profiles differ from those of anti-VEGF agents.[10][15][16][17]
3. Delivery-specific factors — Silicone oil (SiO) droplets shed from syringe lubricant coatings incite a foreign body reaction. A meta-analysis of 1,583 eyes found intravitreal SiO prevalence of 57.6% after injection, with floaters in 27.9% of eyes. Staked-in needles produced significantly higher SiO contamination than attachable needles (72.3% vs. 17.1%; p 0.01), and SiO-free syringes markedly reduced contamination (odds ratio [OR] 0.05; 95% confidence interval [CI] 0.02–0.12). Freeze-thaw cycles, mechanical agitation, and improper plunger handling are additional contributors.[18][19]
A five-pillar susceptibility model integrates these categories — drug properties, delivery factors, disease substrate, patient susceptibility, and immunogenicity — and distinguishes acute innate-driven inflammation from delayed adaptive-immune vasculitic phenotypes.[1]
Risk Factors
Drug-related:
- Brolucizumab: highest IOI risk among anti-VEGF agents. Incidence of IOI was 4.6% in HAWK/HARRIER (IOI + vasculitis 3.3%; IOI + vasculitis + occlusion 2.1%); up to 10.5% in OCTOPUS/SWIFT (7.1% IOI only, 3.4% with retinal involvement); 11.5% with every-4-week dosing in MERLIN (vs. 6.1% for aflibercept); real-world cohorts report 4–10% of treated eyes.[20][21][22][23]
- Faricimab: IOI incidence of 2.0% in TENAYA/LUCERNE (neovascular age-related macular degeneration [nAMD]) and 0.6–2.2% in YOSEMITE/RHINE (diabetic macular edema [DME]); up to 1.6% in real-world data. Retinal vasculitis with or without occlusion was reported at 0.17 per 10,000 injections (occlusive vasculitis 0.06 per 10,000) based on postmarketing data through August 2023. As of mid-2026, at least 13 cases of faricimab-associated occlusive retinal vasculitis (ORV) have been published — 5 rechallenge-associated and 8 initial-exposure — with 84.6% of cases never regaining baseline visual acuity. Bilateral hemorrhagic ORV with panuveitis has been documented, including a case with markedly elevated intraocular pressure (IOP) of 48–49 mmHg bilaterally and diffuse mutton-fat keratic precipitates.[9][24][25][26]
- Aflibercept 8 mg: real-world IOI incidence of 3.7% per injection (12% per patient) in one German series of 136 injections, exceeding clinical trial data (PULSAR: low IOI, no endophthalmitis or vasculitis at 48 weeks; CANDELA: 1 case of mild iritis in 53 patients).[10][27][28]
- Aflibercept 2 mg: IOI incidence of 0.004–0.37% per injection in registry data.[6][10]
- Bevacizumab: higher noninfectious endophthalmitis rate than ranibizumab or aflibercept (0.081% vs. 0.005% and 0%).[6]
- Ranibizumab: IOI incidence of 0.02–0.16% per injection.[2]
- Pegcetacoplan (Syfovre): 0.24% per injection at 24 months in OAKS/DERBY (25 patients, 28 events); 1.9% IOI in the GALE extension at 36 months (all mild or moderate); no vasculitis in trials. Hemorrhagic ORV and iris neovascularization were reported in postmarketing pharmacovigilance (reporting odds ratio [ROR] 4606 and 1248, respectively).[29][30][31]
- Avacincaptad pegol (Izervay): No events of IOI, endophthalmitis, ischemic optic neuropathy, or occlusive vasculitis were reported in the study eye at 12 months in GATHER2. Over 24 months across GATHER1 and GATHER2, vitritis, and endophthalmitis were each reported in 1% or fewer of treated patients. No events of retinal vasculitis, ischemic optic neuropathy, or serious IOI occurred over 2 years. In GATHER1, one patient had mild, transient IOI at 12 months that was not related to the injection procedure or study drug. In postmarketing pharmacovigilance, vitritis (ROR 782) and cystoid macular edema (ROR 445) were disproportionately reported for avacincaptad pegol, though the overall spectrum of reported adverse events was narrower than for pegcetacoplan. [16][31][32][33]
- Compounded bevacizumab preparations.[2]
Patient-related:
- Prior retinal vascular occlusion (hazard ratio [HR] 1.56 for brolucizumab-associated IOI).[34]
- Prior IOI with any anti-VEGF agent.[10]
- Autoimmune disease or uveitis history.[10]
- Small cup-to-disc ratio ("disc at risk") — risk factor for nonarteritic anterior ischemic optic neuropathy (NAION) precipitated by injection-related IOP spikes.[35]
Delivery-related:
- Siliconized syringes and staked-in needles.[18][19]
- Excessive mechanical agitation of viscous drugs.[19]
- Non-prefilled syringes (higher endophthalmitis risk).[8]
Female sex and diabetes are associated with decreased risk of clinically significant IOI after brolucizumab.[34]
General Pathology
Noninfectious IOI shows sterile inflammatory infiltrates — predominantly lymphocytes and macrophages — in the anterior chamber and vitreous, without culturable organisms.[36]
Retinal vasculitis demonstrates perivascular inflammation with endothelial damage and thrombotic occlusion of arterioles and venules. Histopathologic findings include segmental arterial sheathing and discontinuity, sclerotic arteries, vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber, perivenular hemorrhages, and phlebitis.[37]
Faricimab-associated ORV has been characterized at the tissue level. Yavari et al. (2026) reported the first clinicopathologic study of bilateral hemorrhagic ORV following faricimab, in which cytopathology of vitreous samples obtained during pars plana vitrectomy (PPV) demonstrated chronic inflammatory cells — providing direct histopathologic evidence of a sustained inflammatory infiltrate in the vitreous.[24] At the molecular level, Hung et al. (2026) performed proteomic profiling of aqueous humor in faricimab-associated ORV, offering novel insight into the specific inflammatory mediators and pathways activated during this complication.[38]
Silicone oil-related inflammation produces a foreign body reaction with macrophage chemotaxis and phagocytosis. Macrophage counts are significantly elevated in membranes exposed to SiO (p 0.001), and this response persists even after SiO removal.[36]
Particle-induced sterile endophthalmitis (studied with triamcinolone) is characterized by immediate granulocytic infiltration with elevated interleukin-6 (IL-6) and interleukin-8 (IL-8) in the aqueous humor. Direct contact of drug particles with lens epithelial cells and retinal pigment epithelial cells increases IL-8 production, suggesting a mechanical/rheologic stress mechanism.[39]
Pathophysiology
Two distinct phenotypes of sterile IOI are recognized[1][9]:
Phenotype 1 — Acute-onset (1–5 days post-injection): Decreased vision, anterior chamber cells and flare, variable pain, vitreous cells. This phenotype is driven by innate immune activation. It is clinically difficult to distinguish from infectious endophthalmitis. Most patients recover baseline acuity.
Phenotype 2 — Delayed-onset (14 days or more post-injection): Floaters predominate (52.8% in OCTOPUS/SWIFT).[21] Findings include keratic precipitates, mild anterior chamber cells, and — in severe cases — retinal vasculitis with arteriolar occlusion characteristically not at branch points.[9] This phenotype is driven by adaptive immune responses and ADAs.
Brolucizumab immunopathology has been the most extensively characterized. Anti-brolucizumab ADAs are detectable even in treatment-naïve individuals, indicating prior immune exposure to structurally similar proteins. Patients who are ADA-positive develop class-switched, high-affinity responses with recognition of multiple linear epitopes. Critically, only patients who develop retinal vasculitis/vascular occlusion (RV/RO) demonstrate a meaningful T cell recall response to brolucizumab — yet only 2.1% of ADA-positive patients develop RV/RO, indicating that immunogenicity is necessary but not sufficient.[15] Root cause analysis identified additional drivers: a bacterial-shared epitope, non-natural scFv surfaces, and non-native drug species forming during prolonged intraocular residence. Quantitative modeling suggests immune complexes reach immunologically relevant concentrations modulated by dose intensity, triggering antigen presentation, platelet aggregation, endothelial activation, and cytokine release.[40][41]
Faricimab, a bispecific anti-VEGF-A/anti-angiopoietin-2 antibody, produces a distinctive vitritis pattern with dense, grayish vitreous bands predominantly in the peripheral fundus.[42] Occlusive retinal vasculitis has occurred upon rechallenge in patients with initially mild IOI — 3 of 4 eyes in the Bruening et al. series developed ORV during subsequent rechallenge, resulting in profound, irreversible vision loss — underscoring the danger of re-exposure after even mild inflammation.[43] The delayed onset and accentuated inflammatory response after rechallenge support a drug-sensitization or ADA mechanism, consistent with immunological memory.[25] Toolan et al. (2026) reported the most severe faricimab-associated ORV case to date, with bilateral vascular nonperfusion and vision deteriorating to counting fingers and hand motions following rechallenge.[25] Yavari et al. (2026) documented bilateral hemorrhagic ORV with panuveitis after bilateral faricimab injections from different lots, with vitreous cytopathology confirming chronic inflammatory cells — the first clinicopathologic characterization of this entity.[24] Hung et al. (2026) provided the first proteomic profile of faricimab-associated ORV, characterizing the molecular inflammatory signature in aqueous humor and advancing understanding of the specific pathways involved.[38]
Aflibercept 8 mg may trigger a type III hypersensitivity reaction in which the Fc region activates complement, depositing antigen-antibody complexes on vascular endothelium and causing occlusive vasculopathy.[44] Cross-reactivity between agents is suggested by a reported case of RV/RO after aflibercept 8 mg in a patient with prior brolucizumab-associated IOI.[10]
Complement inhibitors: Pegcetacoplan inhibits C3, blocking the entire downstream complement cascade including C3a, C5a, and the membrane attack complex (MAC). Avacincaptad pegol inhibits C5, preserving upstream complement activity including the neuroprotective and anti-inflammatory effects of C3 and C3a.[17] This mechanism of action difference may partly explain the differing safety profiles: pegcetacoplan has a broader spectrum of reported inflammatory adverse events in pharmacovigilance data (including hemorrhagic ORV, iris neovascularization, and iris hemorrhage), whereas avacincaptad pegol has a narrower adverse event profile with no vasculitis or serious IOI reported in clinical trials through 2 years.[30][32]
Biosimilar immunogenicity: For ranibizumab biosimilar SB11 (Byooviz), a post hoc analysis of a phase 3 trial found that some participants with the highest ADA levels developed vitritis or iritis, raising concerns about a potential association between immunogenicity and IOI propensity. However, it remains unclear whether ADAs are the consequence or cause of inflammatory changes.[14]
Primary Prevention
Procedural:
- Povidone-iodine antisepsis with aseptic injection technique.[4]
- Face masks for patient and physician (does not increase and may decrease endophthalmitis risk).[45]
- Prefilled syringes when available (lower endophthalmitis risk than non-prefilled).[8]
- Topical antibiotic prophylaxis does not reduce endophthalmitis rates after intravitreal injection based on a large Japanese multicenter study of 147,440 eyes.[46]
- Active IOI is a contraindication to injection of both pegcetacoplan and avacincaptad pegol per their United States Food and Drug Administration (FDA) labels.[33][47]
Delivery optimization:
- Silicone oil-free or low-SiO syringe systems (OR 0.05 vs. siliconized syringes).[18]
- Attachable rather than staked-in needles (SiO prevalence 17.1% vs. 72.3%).[18]
- Gentle handling; avoid agitation of viscous drugs, freeze-thaw cycles, and forceful plunger depression.[19]
Patient selection and education:
- Instruct patients to report decreased vision, floaters, pain, redness, or photophobia promptly.[21][33][48]
- Avoid brolucizumab in patients with prior IOI or retinal vascular occlusion.[34][48]
- Do not rechallenge with the same agent after even mild IOI — ORV may develop upon rechallenge, as demonstrated with both faricimab and brolucizumab.[24][25][43]
- Avoid every-4-week brolucizumab dosing; brolucizumab should not be used more frequently than every 8 weeks after the loading regimen (IOI incidence 11.5% vs. 6.1% for aflibercept at every-4-week frequency).[22][49]
- Consider prophylactic IOP-lowering measures or anterior chamber paracentesis in eyes with a small cup-to-disc ratio and other risk factors for NAION.[35][50]
Diagnosis
A thorough history and comprehensive ocular examination are essential for evaluating suspected post–anti-VEGF IOI. Particular attention should be given to the timing of symptom onset, clinical features, and retinal findings, as these help differentiate noninfectious IOI from infectious endophthalmitis and guide timely management.
History
- Timing of onset relative to injection (acute, 5 days or fewer, vs. delayed, 14 days or more)
- Agent administered, lot number, syringe type (prefilled vs. non-prefilled, siliconized vs. SiO-free)
- Cumulative injection count with current and prior agents
- Prior IOI episodes (including mild)
- Symptoms: vision loss, floaters, pain, redness, photophobia
- Autoimmune, uveitis, or retinal vascular occlusion history
- Compounded vs. commercially prepared drug
- Unilateral vs. bilateral injection (bilateral involvement has been reported with faricimab even when injections were from different lots)[24]
- Cup-to-disc ratio and glaucoma history (relevant to NAION risk from IOP spikes)[35]
Physical Examination
- Best-corrected visual acuity (BCVA)
- Slit-lamp biomicroscopy: anterior chamber cells/flare (Standardization of Uveitis Nomenclature [SUN] grading), keratic precipitates, fibrin, hypopyon, posterior synechiae
- Intraocular pressure (IOP) — markedly elevated IOP (48–49 mmHg) has been reported in severe faricimab-associated panuveitis[24]
- Cup-to-disc ratio assessment — a small cup ("disc at risk") increases susceptibility to NAION from injection-related IOP spikes[35]
- Dilated fundus examination: vitreous cells/haze (National Eye Institute [NEI]/SUN grading), vascular sheathing, cotton-wool spots, hemorrhages, vascular occlusion, Kyrieleis plaques, disc edema
- Widefield fundus imaging, with attention to the periphery where early vasculitis may first appear[48]
Signs
Acute-onset noninfectious IOI:
- Mild-to-moderate anterior chamber cells
- Vitreous cells and haze
- Minimal or absent hypopyon, fibrin, conjunctival injection, or lid edema
Delayed-onset noninfectious IOI:
- Keratic precipitates (may be granulomatous; diffuse mutton-fat keratic precipitates have been reported bilaterally in faricimab-associated panuveitis)[24]
- Few anterior chamber cells
- Vitreous cells and haze
- Retinal vascular sheathing
- Segmental arteriolar or venular occlusion not at branch points (relatively specific for drug-related vasculitis)[9][44]
- Cotton-wool spots, Kyrieleis plaques, perivenular hemorrhages, phlebitis
- Vascular nonperfusion, sclerotic arteries[37]
- Hemorrhagic occlusive vasculitis with diffuse retinal hemorrhages, optic disc leakage, and bilateral involvement[24]
Faricimab-specific: dense, grayish peripheral vitreous bands; painless anterior uveitis with retrocorneal precipitates.[42] Severe cases may present as panuveitis with markedly elevated IOP.[25]
Infectious endophthalmitis: severe anterior chamber reaction with fibrin and hypopyon, dense vitritis, lid edema, conjunctival injection, corneal edema, moderate-to-severe pain. Eye pain, sudden onset, hypopyon, and diffuse (rather than clumped) inflammation favor bacterial over fungal etiology.[4]
Symptoms
Noninfectious IOI presents with painless decreased vision at a mean of 8 days (range 1–20) post-injection. In delayed-onset cases, floaters are the leading symptom (52.8%), followed by blurred vision (37.8%). Mild ocular pain may be present.[3][10][21] In the Yavari et al. case, the patient presented with blurry vision and ocular pain after bilateral faricimab injections.[24]
Infectious endophthalmitis presents with pain, red eye, and vision loss at a mean of 3 days (range 1–9) post-injection.[3]
Clinical Diagnosis
The distinction is primarily clinical. No single feature is diagnostic. When infection cannot be excluded, vitreous tap and intravitreal antibiotics should proceed without delay. Culture-negative results do not exclude endophthalmitis (30% of postoperative cases are culture-negative).[4]
Key distinguishing clues:
- Keratic precipitates with delayed onset (14 days or more) and floaters as the dominant symptom favor noninfectious IOI.[9][21]
- Vascular occlusion not at branch points is relatively specific for drug-related vasculitis.[9][44]
Diagnostic Procedures
Fluorescein angiography (FA) is essential when retinal vasculitis is suspected. Widefield FA with peripheral sweeps is recommended.[48] Findings include delayed arterial filling, vascular nonperfusion, dye leakage from affected vessels and the optic nerve, arteriolar occlusion not at branch points with distal vessel staining, and retinal telangiectasis near occluded arterioles.[37][44] In the Yavari et al. case, FA demonstrated optic disc leakage and bilateral hemorrhagic occlusive vasculitis.[24]
Optical coherence tomography (OCT): macular edema, subretinal fluid, vitreous hyperreflective dots, epiretinal membrane, retinal layer integrity.
B-scan ultrasonography: indicated when media opacity precludes fundoscopy; evaluates vitreous opacities, retinal detachment, choroidal thickening.
Anterior chamber/vitreous tap: indicated when infection cannot be excluded. Vitrectomy samples yield the highest culture positivity, followed by vitreous aspirate, then aqueous aspirate.[4] Cytopathology of vitreous samples may reveal chronic inflammatory cells, as demonstrated in faricimab-associated ORV.[24]
Proteomic analysis of aqueous humor: Hung et al. (2026) performed the first proteomic profiling of aqueous humor in faricimab-associated ORV, identifying the molecular inflammatory signature of this complication. While not yet a routine clinical tool, proteomic analysis may advance understanding of the pathways driving drug-associated vasculitis and inform future biomarker development.[38]
Optical coherence tomography angiography (OCTA): may detect capillary nonperfusion and monitor vascular recovery; its role in acute IOI remains under investigation.
Laboratory Test
Intraocular fluid:
- Gram stain, aerobic/anaerobic/fungal cultures
- Polymerase chain reaction (PCR) (increasingly used for culture-negative cases)[4][5]
- Cytopathology of vitreous samples (chronic inflammatory cells identified in faricimab-associated ORV)[24]
Systemic workup (when atypical features warrant exclusion of other etiologies):
- Complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)
- Angiotensin-converting enzyme (ACE), lysozyme ([sarcoidosis](/rare-disease/sarcoidosis))
- Rapid plasma reagin (RPR)/Venereal Disease Research Laboratory (VDRL), fluorescent treponemal antibody absorption (FTA-ABS) (syphilis)
- QuantiFERON-TB Gold
- Antineutrophil cytoplasmic antibodies (ANCA) ([granulomatosis with polyangiitis](/rare-disease/granulomatosis-with-polyangiitis))
- Human leukocyte antigen B27 (HLA-B27)
- Chest radiograph
- Embolic workup if vascular occlusion is present[37][44]
Antidrug antibody testing is not clinically available but has been used in research.[9][15]
Differential Diagnosis
- Infectious endophthalmitis (bacterial, fungal)
- Toxic anterior segment syndrome (TASS)
- Exacerbation of underlying uveitis
- Sympathetic ophthalmia
- Masquerade syndromes (intraocular lymphoma, retinoblastoma)
- Rhegmatogenous retinal detachment
- Vitreous hemorrhage
- Retinal artery or vein occlusion (embolic, thrombotic, vasospastic)
- Systemic vasculitis (granulomatosis with polyangiitis, Behçet disease, sarcoidosis)
- Herpetic uveitis
- Nonarteritic anterior ischemic optic neuropathy precipitated by injection-related IOP spike[35]
Management
Management of post-intravitreal injection IOI depends on excluding infection. Suspected endophthalmitis requires urgent vitreous sampling and intravitreal antibiotics, with vitrectomy for severe cases. Noninfectious IOI is treated primarily with corticosteroids, ranging from topical therapy for mild cases to periocular, intravitreal, or systemic steroids for retinal vasculitis or occlusive disease. The causative drug should be discontinued. Close follow-up with visual acuity, OCT, and widefield angiography is essential. Pars plana vitrectomy (PPV) is reserved for severe, refractory inflammation, diagnostic uncertainty, or complications such as retinal detachment.
General Treatment
Management hinges on the infectious vs. noninfectious distinction. When infection is suspected or cannot be excluded, vitreous tap and intravitreal antibiotics (vancomycin 1 mg/0.1 mL + ceftazidime 2.25 mg/0.1 mL) should proceed without delay. Intravitreal antibiotics alone fail to sterilize some eyes; vitrectomy can improve outcomes in severe cases.[4] When noninfectious IOI is the leading diagnosis, intensive topical corticosteroids with close observation constitute first-line therapy. In all cases, the offending agent should be permanently discontinued and an alternative agent selected for ongoing retinal disease.[48][43][25][21]
Medical Therapy
Noninfectious IOI without retinal involvement:
- Prednisolone acetate 1% every 1–2 hours initially, tapered on clinical response (used in 75.5% of treated cases in OCTOPUS/SWIFT).[48][51]
- Empiric topical antibiotics may be added while awaiting cultures if infection is not fully excluded.[51]
- Subconjunctival corticosteroids as adjunctive therapy.[51]
Intraocular inflammation with retinal vasculitis or vascular occlusion requires escalated therapy[48]:
- Sub-Tenon triamcinolone
- Intravitreal dexamethasone implant or triamcinolone acetonide
- Systemic corticosteroids (oral prednisone; used in 28.3% of treated IOI events in OCTOPUS/SWIFT)[21]
- Intraocular corticosteroids (used in 26.8% of treated events)[21]
- Systemic immunosuppression in refractory cases[48]
In the Yavari et al. case of bilateral hemorrhagic ORV with panuveitis following faricimab, a multimodal escalation strategy was employed: systemic corticosteroids, followed by unilateral intravitreal dexamethasone implant, and PPV. This approach achieved significant resolution of inflammation and normalization of IOP.[24]
Infectious endophthalmitis:
- Intravitreal vancomycin 1 mg/0.1 mL + ceftazidime 2.25 mg/0.1 mL (cornerstone of treatment)[4]
- Intravitreal antifungals (amphotericin B or voriconazole) if fungal infection is suspected
- Systemic antibiotics as adjunctive therapy
Medical Follow-up
Close monitoring (every 1–3 days initially) should include serial BCVA, anterior chamber cell grading (SUN), vitreous haze grading (NEI), and dilated fundoscopy. Repeat widefield FA is recommended to track vasculitis resolution and detect new nonperfusion.[48] Serial OCT should be performed for macular edema and structural changes.
Most noninfectious IOI resolves within 2–12 weeks; faricimab-associated vitritis persists 2–10 weeks.[42] Visual acuity improvement in noninfectious IOI occurs over approximately 2 months (mean BCVA from 35 ± 25 to 49 ± 24 Early Treatment Diabetic Retinopathy Study [ETDRS] letters, p = 0.022).[3] In OCTOPUS/SWIFT, 81.1% of IOI events occurred during the loading phase; median BCVA change at resolution was 1 letter (range -74 to +32).[21] Long-term follow-up is warranted: scleritis has been reported up to 158 days after brolucizumab injection.
Surgery
Pars plana vitrectomy indications:
- Infectious endophthalmitis[4]
- Diagnostic vitrectomy when etiology remains uncertain despite anterior chamber/vitreous tap[4]
- Severe noninfectious IOI refractory to medical therapy[24][48]
- Dense vitreous opacification precluding fundus visualization[48]
- Retinal detachment complicating endophthalmitis or vasculitis
In the Yavari et al. case of bilateral hemorrhagic ORV with panuveitis following faricimab, PPV was performed after systemic corticosteroids and intravitreal dexamethasone implant failed to achieve adequate control. Vitreous cytopathology confirmed chronic inflammatory cells, and the procedure contributed to significant resolution of inflammation and normalization of IOP.[24]
Panretinal photocoagulation or targeted laser may be required for ischemic retina with neovascularization secondary to occlusive vasculitis.[48]
Anti-vascular endothelial growth factor (anti-VEGF) injection for neovascular complications of ischemic vasculitis requires careful agent selection — the offending agent must be permanently avoided, and an alternative anti-VEGF agent from a different molecular class should be used.[25][48][51]
Surgical Follow-up
- Serial widefield FA to monitor reperfusion, persistent nonperfusion, and neovascularization.[48]
- Serial OCT and OCTA to assess macular structure and capillary recovery.
- Monitor for neovascular complications (neovascularization of the disc, neovascularization elsewhere, neovascular glaucoma) in eyes with extensive nonperfusion.[48]
- Long-term IOP monitoring, particularly in eyes that required PPV or had sustained IOP elevation.[52]
Complications
Complications of IOI itself:
- Permanent vision loss (84.6% of faricimab-associated ORV cases never regained baseline BCVA)[26]
- Retinal ischemia and neovascularization
- Neovascular glaucoma
- Macular edema (persistent or recurrent)
- Epiretinal membrane formation
- Optic atrophy
- Phthisis bulbi (end-stage)
- Scleritis (reported up to 158 days after brolucizumab injection)[53]
Complications of treatment:
- Corticosteroid-induced IOP elevation and cataract
- Vitrectomy-related complications (retinal detachment, cataract progression, endophthalmitis)
- Systemic corticosteroid side effects (hyperglycemia, immunosuppression)
While not a direct manifestation of IOI, optic nerve complications represent an important consideration in the safety profile of intravitreal injections.
Nonarteritic anterior ischemic optic neuropathy (NAION): Acute elevation of IOP may precipitate NAION, particularly in eyes with a small cup-to-disc ratio — the so-called "disc at risk." Intravitreal injection routinely raises IOP to a mean of approximately 40 mmHg immediately post-injection, with a corresponding mild but significant decrease in optic nerve head perfusion on OCTA (p = 0.03 for flux, p = 0.02 for vessel area density).[35][54] In eyes with a physiologically small cup (cup-to-disc ratio 0.2), this transient IOP spike may compromise perfusion of the already structurally crowded optic nerve head, triggering ischemic optic neuropathy.[35]
Chronic optic nerve head structural changes: Repeated intravitreal injections cause acute Bruch's membrane opening (BMO) enlargement, cup widening and deepening, and prelaminar tissue thinning — changes that may become irreversible with cumulative injections. Gómez-Mariscal et al. demonstrated significant BMO expansion (p = 0.003), prelaminar tissue thinning (p = 0.011), and cup deepening (p = 0.006) in the inferior optic nerve head region after more than 6 injections compared with baseline.[55]
IOP-related considerations: Acute IOP spikes occur in nearly all eyes following intravitreal injection, typically resolving within an hour, but recovery is delayed in eyes with glaucoma and ocular hypertension, increasing optic nerve risk. Sustained IOP elevation is less predictable, with higher rates for bevacizumab and ranibizumab than aflibercept. Cumulative injection burden correlates with reduced outflow facility, retinal nerve fiber layer thinning, and greater need for glaucoma surgery.[52]
Prophylactic measures in high-risk eyes:
- Document cup-to-disc ratio before initiating intravitreal injection therapy
- Consider prophylactic IOP-lowering drops (e.g., brimonidine, timolol) or anterior chamber paracentesis in eyes with a small cup-to-disc ratio, glaucoma, or ocular hypertension[52]
- Monitor IOP recovery time post-injection in susceptible patients
- Individualize agent selection and delivery parameters based on patient-specific risk factors[52]
Prognosis
Noninfectious IOI without retinal involvement generally carries a favorable prognosis. Visual acuity improves over approximately 2 months (mean BCVA from 35 ± 25 to 49 ± 24 Early Treatment Diabetic Retinopathy Study [ETDRS] letters, p = 0.022).[3] In OCTOPUS/SWIFT, median BCVA change at IOI resolution was 1 letter (range -74 to +32).[21]
Occlusive retinal vasculitis carries a guarded-to-poor prognosis. Among faricimab-associated ORV cases, 84.6% never regained baseline BCVA.[26] In the Toolan et al. case, bilateral vision deteriorated to counting fingers and hand motions despite aggressive treatment.[25] In the Yavari et al. case, significant inflammation resolution was achieved with multimodal therapy including PPV, though long-term visual outcomes remain to be determined.[24]
Brolucizumab-associated retinal vasculitis/vascular occlusion resulted in vision loss of 15 or more ETDRS letters in 50% of affected eyes in HAWK/HARRIER.[20]
Infectious endophthalmitis prognosis depends on the causative organism, presenting acuity, and time to treatment. Streptococcal endophthalmitis after intravitreal injection carries a particularly poor prognosis.[4]
Global Variants
Geographic variation in IOI epidemiology reflects differences in drug availability, compounding practices, syringe types, and microbial flora:
- Gram-negative and fungal endophthalmitis is more prevalent in tropical regions (10–20% of cases) compared with temperate climates.[4]
- Compounded bevacizumab — widely used in low- and middle-income countries — carries higher noninfectious endophthalmitis risk than commercially prepared agents.[2][6]
- Syringe types and needle configurations vary by market, influencing silicone oil contamination rates.[18][19]
- Brolucizumab has been withdrawn or restricted in several markets following IOI safety signals; availability varies globally.[56]
- Regulatory approval timelines for newer agents (faricimab, aflibercept 8 mg, pegcetacoplan, avacincaptad pegol) differ across regions, affecting the local IOI risk landscape.
- Antibiotic prophylaxis practices vary: topical antibiotics are routinely used in Japan but not recommended in the United States or Europe based on available evidence.[46][49]
Additional Resources
- American Academy of Ophthalmology Age-Related Macular Degeneration Preferred Practice Pattern[49]
- Baumal et al. Expert Opinion on Management of IOI, Retinal Vasculitis, and Vascular Occlusion After Brolucizumab Treatment[48]
- Ferro Desideri et al. Ocular Inflammation After Intraocular Drug Delivery: Mechanisms, Risk Factors, and Implications for Clinical Practice[1]
- United States Food and Drug Administration drug labels: Syfovre (pegcetacoplan), Izervay (avacincaptad pegol)[47][33]
- Kailani et al. Ocular Adverse Events Associated With Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: A Population-Based Pharmacovigilance Study[30]
- Khanani et al. Avacincaptad Pegol for Geographic Atrophy: Two-Year Efficacy and Safety Results From the GATHER2 Phase 3 Trial[32]
- Yavari et al. Bilateral Hemorrhagic Occlusive Retinal Vasculitis and Panuveitis Following Intravitreal Faricimab Injection: A Clinicopathologic Case Study[24]
- Hung et al. Proteomic Profile of Faricimab-Associated Occlusive Retinal Vasculitis[38]
References
Add text here
- ↑ 1.0 1.1 1.2 1.3 Ocular Inflammation After Intraocular Drug Delivery: Mechanisms, Risk Factors, and Implications for Clinical Practice. Ferro Desideri L, Fukuhara PS, Wintergerst MWM, et al. Survey of Ophthalmology. 2026 Jul-Aug;71(4):1170-1187. doi:10.1016/j.survophthal.2026.02.005.
- ↑ 2.0 2.1 2.2 2.3 2.4 Inflammatory Complications of Intravitreal Anti-Vegf Injections. Cox JT, Eliott D, Sobrin L. Journal of Clinical Medicine. 2021;10(5):981. doi:10.3390/jcm10050981.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Intraocular Inflammation Following Intravitreal Injections of Anti-Vascular Endothelial Growth Factor Drugs. Ferreira AM, Mendes AF, Beato JN, et al. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2025;:10.1007/s00417-025-06875-w. doi:10.1007/s00417-025-06875-w.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Eye Infections. Durand ML, Barshak MB, Sobrin L. The New England Journal of Medicine. 2023;389(25):2363-2375. doi:10.1056/NEJMra2216081.
- ↑ 5.0 5.1 Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM). Miller JM, Binnicker MJ, Campbell S, et al. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America. 2024;:ciae104. doi:10.1093/cid/ciae104.
- ↑ 6.0 6.1 6.2 6.3 Incidence and Outcomes of Infectious and Noninfectious Endophthalmitis After Intravitreal Injections for Age-Related Macular Degeneration. Daien V, Nguyen V, Essex RW, et al. Ophthalmology. 2018;125(1):66-74. doi:10.1016/j.ophtha.2017.07.005.
- ↑ 7.0 7.1 Risk of Endophthalmitis Based on Cumulative Number of Anti-Vegf Intravitreal Injections. Israilevich RN, Mansour H, Patel SN, et al. Ophthalmology. 2024;131(6):667-673. doi:10.1016/j.ophtha.2023.12.033.
- ↑ 8.0 8.1 8.2 Association of Acute Endophthalmitis With Intravitreal Injections of Corticosteroids or Anti-Vascular Growth Factor Agents in a Nationwide Study in France. Baudin F, Benzenine E, Mariet AS, et al. JAMA Ophthalmology. 2018;136(12):1352-1358. doi:10.1001/jamaophthalmol.2018.3939.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 9.7 9.8 Severe Intraocular Inflammation Following Intravitreal Faricimab. Thangamathesvaran L, Kong J, Bressler SB, et al. JAMA Ophthalmology. 2024;142(4):365-370. doi:10.1001/jamaophthalmol.2024.0530.
- ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 10.7 10.8 10.9 Noninfectious Intraocular Inflammation After Intravitreal Aflibercept. Binder KE, Bleidißel N, Charbel Issa P, Maier M, Coulibaly LM. JAMA Ophthalmology. 2025;143(6):499-506. doi:10.1001/jamaophthalmol.2025.0969.
- ↑ Qedair J, Youssif AA, Shehada R, Abu Serhan H. Intraocular Inflammation Following Intravitreal Faricimab: A Systematic Review and Meta-Analysis. Pharmacoepidemiology. 2026; 5(1):5. https://doi.org/10.3390/pharma5010005
- ↑ Alkhawaldeh, I. M., & Abu Serhan, H. (2024). Intraocular Inflammation with faricimab: insights from Manufacturer and User Facility Device Experience (MAUDE) database. Eye (London, England), 38(13), 2494–2496. https://doi.org/10.1038/s41433-024-03079-0
- ↑ Abu Serhan, H., Hassan, A. K., Rifai, M., Elsayed, R. A., Djeffal, C., Cherif, Y., … Elnahry, A. G. (2025). Effect Modifiers and Risk Factors of Intraocular Inflammation Following Brolucizumab: A Systematic Review and Meta-analysis. Current Eye Research, 50(3), 241–251. https://doi.org/10.1080/02713683.2024.2402319
- ↑ 14.0 14.1 14.2 Immunogenicity With Ranibizumab Biosimilar SB11 (Byooviz) and Reference Product Lucentis and Association With Efficacy, Safety, and Pharmacokinetics: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial. Bressler NM, Kim T, Oh I, et al. JAMA Ophthalmology. 2023;141(2):117-127. doi:10.1001/jamaophthalmol.2022.5403.
- ↑ 15.0 15.1 15.2 Anti-Brolucizumab Immune Response as One Prerequisite for Rare Retinal Vasculitis/Retinal Vascular Occlusion Adverse Events. Karle AC, Wrobel MB, Koepke S, et al. Science Translational Medicine. 2023;15(681):eabq5241. doi:10.1126/scitranslmed.abq5241.
- ↑ 16.0 16.1 Efficacy and Safety of Avacincaptad Pegol in Patients With Geographic Atrophy (GATHER2): 12-Month Results From a Randomised, Double-Masked, Phase 3 Trial. Khanani AM, Patel SS, Staurenghi G, et al. Lancet (London, England). 2023;402(10411):1449-1458. doi:10.1016/S0140-6736(23)01583-0.
- ↑ 17.0 17.1 C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Jaffe GJ, Westby K, Csaky KG, et al. Ophthalmology. 2021;128(4):576-586. doi:10.1016/j.ophtha.2020.08.027.
- ↑ 18.0 18.1 18.2 18.3 18.4 Prevalence of Intravitreal Silicone Oil Following Intravitreal Injections: A Meta-Analysis: Silicone Oil Droplets After Intravitreal Injections. Chavez MP, Rassi TNO, Yate CM, et al. American Journal of Ophthalmology. 2025;:S0002-9394(25)00521-5. doi:10.1016/j.ajo.2025.09.043.
- ↑ 19.0 19.1 19.2 19.3 19.4 Silicone Oil Migration During Intravitreal Anti-Vegf Injections: A Review of Clinical Evidence and Factors Related to Transmission. Rahmani K, Rajeswaren V, Im JJ, Hodges B, Yoganathan P. Retina (Philadelphia, Pa.). 2026;:00006982-990000000-01354. doi:10.1097/IAE.0000000000004829.
- ↑ 20.0 20.1 Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events With Brolucizumab: Post Hoc Review of HAWK and HARRIER. Monés J, Srivastava SK, Jaffe GJ, et al. Ophthalmology. 2021;128(7):1050-1059. doi:10.1016/j.ophtha.2020.11.011.
- ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 21.7 21.8 21.9 Detection and Management of Intraocular Inflammation After Brolucizumab Treatment for Neovascular Age-Related Macular Degeneration. Bodaghi B, Souied EH, Tadayoni R, et al. Ophthalmology. Retina. 2023;7(10):879-891. doi:10.1016/j.oret.2023.06.009.
- ↑ 22.0 22.1 MERLIN: Two-Year Results of Brolucizumab in Participants With Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid. Brown DM, Jaffe GJ, Wykoff CC, et al. Ophthalmology. 2025;132(2):131-140. doi:10.1016/j.ophtha.2024.08.022.
- ↑ Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review. Alali NM, Aljahdali A, AlBalawi HB, et al. Pharmaceuticals (Basel, Switzerland). 2025;18(11):1620. doi:10.3390/ph18111620.
- ↑ 24.00 24.01 24.02 24.03 24.04 24.05 24.06 24.07 24.08 24.09 24.10 24.11 24.12 24.13 24.14 24.15 24.16 Bilateral Hemorrhagic Occlusive Retinal Vasculitis and Panuveitis Following Intravitreal Faricimab Injection: A Clinicopathologic Case Study. Yavari N, Gupta AS, Mitsios A, et al. American Journal of Ophthalmology Case Reports. 2026;41:102532. doi:10.1016/j.ajoc.2026.102532.
- ↑ 25.0 25.1 25.2 25.3 25.4 25.5 25.6 25.7 Bilateral Occlusive Retinal Vasculitis After Faricimab Rechallenge. Toolan KJ, Dihowm F, Leveque TK, et al. JAMA Ophthalmology. 2026;:2849775. doi:10.1001/jamaophthalmol.2026.1610.
- ↑ 26.0 26.1 26.2 Sterile Intraocular Inflammation Associated With Faricimab. Cozzi M, Ziegler A, Fasler K, et al. JAMA Ophthalmology. 2024;:2824219. doi:10.1001/jamaophthalmol.2024.3828.
- ↑ Intravitreal Aflibercept 8 Mg in Neovascular Age-Related Macular Degeneration (PULSAR): 48-Week Results From a Randomised, Double-Masked, Non-Inferiority, Phase 3 Trial. Lanzetta P, Korobelnik JF, Heier JS, et al. Lancet (London, England). 2024;403(10432):1141-1152. doi:10.1016/S0140-6736(24)00063-1.
- ↑ Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial. Wykoff CC, Brown DM, Reed K, et al. JAMA Ophthalmology. 2023;141(9):834-842. doi:10.1001/jamaophthalmol.2023.2421.
- ↑ Pegcetacoplan for the Treatment of Geographic Atrophy Secondary to Age-Related Macular Degeneration (OAKS and DERBY): Two Multicentre, Randomised, Double-Masked, Sham-Controlled, Phase 3 Trials. Heier JS, Lad EM, Holz FG, et al. Lancet (London, England). 2023;402(10411):1434-1448. doi:10.1016/S0140-6736(23)01520-9.
- ↑ 30.0 30.1 30.2 Ocular Adverse Events Associated With Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: A Population-Based Pharmacovigilance Study. Kailani Z, Mihalache A, Popovic MM, Kertes PJ, Muni RH. American Journal of Ophthalmology. 2025;276:252-260. doi:10.1016/j.ajo.2025.04.022.
- ↑ 31.0 31.1 Pegcetacoplan Treatment for Geographic Atrophy in Age-Related Macular Degeneration Over 36 Months: Data From OAKS, DERBY, and GALE. Wykoff CC, Holz FG, Chiang A, et al. American Journal of Ophthalmology. 2025;276:350-364. doi:10.1016/j.ajo.2025.04.016.
- ↑ 32.0 32.1 32.2 Avacincaptad Pegol for Geographic Atrophy Secondary to Age-Related Macular Degeneration: Two-Year Efficacy and Safety Results From the GATHER2 Phase 3 Trial. Khanani AM, Danzig CJ, Heier JS, et al. Ophthalmology. 2026;133(4):451-465. doi:10.1016/j.ophtha.2025.12.011.
- ↑ 33.0 33.1 33.2 33.3 IZERVAY. Food and Drug Administration. Updated date: 2026-02-27.
- ↑ 34.0 34.1 34.2 Incidence of Intraocular Inflammation and Its Risk Factors in Patients Treated With Brolucizumab: A Nationwide Cohort Study. Park HS, Lee SW, Park H, et al. Scientific Reports. 2024;14(1):22913. doi:10.1038/s41598-024-73782-1.
- ↑ 35.0 35.1 35.2 35.3 35.4 35.5 35.6 Ischemic Optic Neuropathies. Biousse V, Newman NJ. The New England Journal of Medicine. 2015;372(25):2428-36. doi:10.1056/NEJMra1413352.
- ↑ 36.0 36.1 Immunopathology of Intraocular Silicone Oil: Retina and Epiretinal Membranes. Wickham LJ, Asaria RH, Alexander R, Luthert P, Charteris DG. The British Journal of Ophthalmology. 2007;91(2):258-62. doi:10.1136/bjo.2006.103549.
- ↑ 37.0 37.1 37.2 37.3 Retinal Vasculitis and Intraocular Inflammation After Intravitreal Injection of Brolucizumab. Baumal CR, Spaide RF, Vajzovic L, et al. Ophthalmology. 2020;127(10):1345-1359. doi:10.1016/j.ophtha.2020.04.017.
- ↑ 38.0 38.1 38.2 38.3 Proteomic Profile of Faricimab-Associated Occlusive Retinal Vasculitis. Hung JH, Iyer I, Thng ZX, et al. Eye (London, England). 2026;40(3):293-296. doi:10.1038/s41433-025-04175-5.
- ↑ Particle-Induced Endophthalmitis: Possible Mechanisms of Sterile Endophthalmitis After Intravitreal Triamcinolone. Otsuka H, Kawano H, Sonoda S, Nakamura M, Sakamoto T. Investigative Ophthalmology & Visual Science. 2013;54(3):1758-66. doi:10.1167/iovs.12-11247.
- ↑ A Root Cause Analysis to Identify the Mechanistic Drivers of Immunogenicity Against the Anti-Vegf Biotherapeutic Brolucizumab. Kearns JD, Wassmann P, Olgac U, et al. Science Translational Medicine. 2023;15(681):eabq5068. doi:10.1126/scitranslmed.abq5068.
- ↑ Abu Serhan, H., Taha, M. J. J., Abuawwad, M. T., Abdelaal, A., Irshaidat, S., Abu Serhan, L., … Elnahry, A. G. (2024). Safety and Efficacy of Brolucizumab in the Treatment of Diabetic Macular Edema and Diabetic Retinopathy: A Systematic Review and Meta-Analysis. Seminars in Ophthalmology, 39(4), 251–260. https://doi.org/10.1080/08820538.2023.2271095
- ↑ 42.0 42.1 42.2 Vitritis Following Intravitreal Faricimab: A Retrospective Monocentric Analysis. Bourdin A, Cohen SY, Nghiem-Buffet S, et al. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2025;263(4):965-972. doi:10.1007/s00417-025-06736-6.
- ↑ 43.0 43.1 43.2 Inflammation and Occlusive Retinal Vasculitis Post Faricimab. Bruening W, Kim S, Yeh S, Rishi P, Conrady CD. JAMA Ophthalmology. 2025;143(3):232-235. doi:10.1001/jamaophthalmol.2024.5889.
- ↑ 44.0 44.1 44.2 44.3 44.4 Occlusive Retinal Vessels Associated With Intravitreal Aflibercept, 8.0 mg. Dail R, Bertolucci G, Thinda S. JAMA Ophthalmology. 2025;143(11):978-980. doi:10.1001/jamaophthalmol.2025.3027.
- ↑ Complications of Intravitreal Injections: 2022. Patel D, Patel SN, Chaudhary V, Garg SJ. Current Opinion in Ophthalmology. 2022;33(3):137-146. doi:10.1097/ICU.0000000000000850.
- ↑ 46.0 46.1 Incidence of Endophthalmitis After Intravitreal Injection of an Anti-Vegf Agent With or Without Topical Antibiotics. Morioka M, Takamura Y, Nagai K, et al. Scientific Reports. 2020;10(1):22122. doi:10.1038/s41598-020-79377-w.
- ↑ 47.0 47.1 Syfovre. Food and Drug Administration. Updated date: 2025-09-16.
- ↑ 48.00 48.01 48.02 48.03 48.04 48.05 48.06 48.07 48.08 48.09 48.10 48.11 48.12 48.13 48.14 48.15 Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion After Brolucizumab Treatment. Baumal CR, Bodaghi B, Singer M, et al. Ophthalmology. Retina. 2021;5(6):519-527. doi:10.1016/j.oret.2020.09.020.
- ↑ 49.0 49.1 49.2 Age-Related Macular Degeneration Preferred Practice Pattern®. Vemulakonda GA, Bailey ST, Kim SJ, et al. Ophthalmology. 2025;132(4):P1-P74. doi:10.1016/j.ophtha.2024.12.018.
- ↑ The Association Between Intravitreal Injections and Glaucoma: An Update. Phan C, Qiu M, Zhang AY. Current Opinion in Ophthalmology. 2025;:00055735-990000000-00277. doi:10.1097/ICU.0000000000001191.
- ↑ 51.0 51.1 51.2 51.3 Noninfectious Intraocular Inflammation After Intravitreal Aflibercept. Binder KE, Bleidißel N, Charbel Issa P, Maier M, Coulibaly LM. JAMA Ophthalmology. 2025;143(6):499-506. doi:10.1001/jamaophthalmol.2025.0969.
- ↑ 52.0 52.1 52.2 52.3 The Association Between Intravitreal Injections and Glaucoma: An Update. Phan C, Qiu M, Zhang AY. Current Opinion in Ophthalmology. 2025;:00055735-990000000-00277. doi:10.1097/ICU.0000000000001191.
- ↑ Occlusive Retinal Vasculitis and Scleritis Following Brolucizumab Treatment: A Case Report. Onagawa S, Miura M. Medicine. 2024;103(42):e40154. doi:10.1097/MD.0000000000040154.
- ↑ Optic Nerve Head Perfusion Before and After Intravitreal Antivascular Growth Factor Injections Using Optical Coherence Tomography-Based Microangiography. Wen JC, Chen CL, Rezaei KA, et al. Journal of Glaucoma. 2019;28(3):188-193. doi:10.1097/IJG.0000000000001142.
- ↑ Acute and Chronic Optic Nerve Head Biomechanics and Intraocular Pressure Changes in Patients Receiving Multiple Intravitreal Injections of Anti-Vegf. Gómez-Mariscal M, Puerto B, Muñoz-Negrete FJ, de Juan V, Rebolleda G. Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Fur Klinische Und Experimentelle Ophthalmologie. 2019;257(10):2221-2231. doi:10.1007/s00417-019-04354-7.
- ↑ Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review. Alali NM, Aljahdali A, AlBalawi HB, et al. Pharmaceuticals (Basel, Switzerland). 2025;18(11):1620. doi:10.3390/ph18111620.
