A recent case series highlighted the potential risk of occlusive retinal vasculitis following rechallenge with faricimab, a vascular endothelial growth factor and angiopoietin-2 inhibitor used to treat neovascular age-related macular degeneration and diabetic macular edema. The study, conducted at the University of Nebraska Medical Center, described 3 patients who developed irreversible vision loss after receiving additional doses of intravitreal faricimab following an initial episode of mild intraocular inflammation.

The retrospective case series examined 3 patients (4 eyes) treated with faricimab between October 2023 and August 2024. The study aimed to assess the clinical course of patients who developed occlusive retinal vasculitis (ORV) after an initial episode of mild intraocular inflammation (IOI), as well as any potential immunologic mechanisms contributing to ORV development upon retreatment, and safety considerations regarding rechallenging patients who had prior IOI from antivascular endothelial growth factor (VEGF) agents.

Mild IOI was observed in all 4 eyes following initial faricimab treatment, and 3 eyes developed ORV after retreatment, resulting in profound, irreversible vision loss. Despite treatment with topical and systemic steroids, vision loss persisted. The 1 eye that did not develop ORV upon rechallenge was able to continue faricimab injections without recurrence of inflammation.

Will Bruening, BS, of Truhlsen Eye Center, Department of Ophthalmology and Visual Sciences at the University of Nebraska Medical Center, and researchers detailed each case in their recent JAMA Ophthalmology review:

• Case 1 was an 89-year-old female with neovascular age-related macular degeneration (nAMD) in both eyes, who received faricimab following inadequate response to bevacizumab. She developed anterior chamber inflammation 4 weeks after her second injection, which resolved with topical steroids. Despite initial inflammation, her provider restarted faricimab, and after 4 additional injections, her visual acuity (VA) deteriorated to 20/200 OS, though no further inflammation occurred.
  
  
• Case 2 was an 86-year-old female with nAMD in her right eye who received 3 injections of faricimab before developing anterior chamber inflammation with keratic precipitates. After inflammation resolved with topical steroids, she received a fourth injection. She developed ORV 1 week later and her VA declined from 20/70 to light perception (LP). Fluorescein angiography revealed extensive retinal nonperfusion, and despite aggressive steroid therapy and antiviral treatment, her vision loss was irreversible.
  
  
• Case 3 was a 63-year-old male with diabetic macular edema (DME) and proliferative diabetic retinopathy who received faricimab after prior aflibercept treatment. Following mild bilateral IOI, inflammation resolved with steroid therapy. However, after a subsequent injection, vision in both eyes deteriorated to LP OD and 20/400 OS, with retinal hemorrhages, arterial occlusions, and elevated intraocular pressure (IOP > 30 mm Hg). Despite aggressive management, the patient required tube shunt placement for IOP control. His VA showed only partial recovery to 20/200 OS.

Similar cases of ORV have been observed with other anti-VEGF agents, including brolucizumab and pegcetacoplan. The researchers noted that “endophthalmitis-like presentations and vasculitis with or without occlusions,” have been reported with faricimab: "reported [ORV] rates [were] 0.06 case per 10, 000 injections.”

While faricimab was well tolerated in clinical trials with low rates of severe IOI (0.2%–0.6%), these real-world cases show a potential “immunological memory response [that] is elicited with these repeated exposures, resulting in the development of ORV,” the researchers wrote.

Proposed mechanisms of ORV include “the presence of antidrug antibodies, protein aggregates, or a delayed hypersensitivity reaction,” they continued. While the etiology of ORV remains up for debate, the researchers advised caution when rechallenging with the same biologic in cases of IOI.

A full list of author disclosures can be found in the published study.