Noninfectious Intraocular Inflammation After Intravitreal Aflibercept

JAMA Ophthalmol. 2025 Jun 1;143(6):499-506. doi: 10.1001/jamaophthalmol.2025.0969.

Abstract

Importance: Aflibercept, 8 mg, is an anti-vascular endothelial growth factor (VEGF) formulation for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). While clinical trials report a comparable safety profile as aflibercept, 2 mg, clinical practice setting (so-called real-world) data on the incidence of intraocular inflammation (IOI) should be of value.

Objective: To determine the clinical practice setting incidence of IOI after intravitreal injection of aflibercept, 8 mg, for nAMD and DME.

Design, setting, and participants: This retrospective case series involved a review of medical records at a single tertiary care center. Participants were all patients who received an intravitreal injection of aflibercept, 8 mg, for nAMD or DME from March 2024 to October 2024. Patients had received injections with other VEGF inhibitors before. Standard care included slitlamp examination before each injection and follow-up examination within 4 days after every injection.

Exposure: IOI adverse events (AEs) after injections.

Main outcomes and measures: Incidence of IOI after intravitreal injection of aflibercept, 8 mg. Secondary outcomes included the time point of IOI and best-corrected visual acuity (BCVA) during and after recovery of IOI.

Results: Forty-one patients were treated with intravitreal aflibercept, 8 mg, injections: 23 with nAMD (56%) and 18 with DME (44%). Twenty-seven patients (66%) were male and 14 patients female (34%). A total of 136 intravitreal injections of aflibercept, 8 mg, were administered during the observation period. Five patients of 41 developed mild sterile IOI within 1 to 3 days after the intervention (incidence per injection, 3.7%; 95% CI, 1.6%-8.3%; incidence per patient, 12%; 95% CI, 5.3%-25.5%). Four patients had prior exposure to aflibercept, 8 mg, before the inflammation occurred; only 1 patient developed inflammation after the first dose. All patients were treated with local anti-inflammatory therapy (topical or subconjunctival corticosteroids), and 2 patients received additional systemic oral corticosteroids. No reduction of BCVA was observed after IOI-associated AEs receded.

Conclusions and relevance: This analysis in a clinical practice setting revealed a more frequent occurrence of IOI-associated AEs compared with previous clinical trials. All observed cases showed a mild IOI, which resolved under anti-inflammatory therapy without loss of BCVA.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / adverse effects
  • Diabetic Retinopathy / drug therapy
  • Endophthalmitis* / chemically induced
  • Endophthalmitis* / diagnosis
  • Endophthalmitis* / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Intravitreal Injections / adverse effects
  • Macular Edema / drug therapy
  • Male
  • Middle Aged
  • Receptors, Vascular Endothelial Growth Factor* / administration & dosage
  • Recombinant Fusion Proteins* / administration & dosage
  • Recombinant Fusion Proteins* / adverse effects
  • Retrospective Studies
  • Uveitis* / chemically induced
  • Uveitis* / diagnosis
  • Uveitis* / epidemiology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Visual Acuity
  • Wet Macular Degeneration* / drug therapy

Substances

  • aflibercept
  • Receptors, Vascular Endothelial Growth Factor
  • Recombinant Fusion Proteins
  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A