Faricimab Again Linked to Rare but Severe Eye Adverse Effects

Three patients developed occlusive retinal vasculitis following rechallenge with faricimab (Vabysmo) after initially developing mild intraocular inflammation for the treatment of neovascular age-related macular degeneration (nAMD) or diabetic macular edema, according to a retrospective case series.

At a single academic tertiary referral center, mild intraocular inflammation developed in four eyes following intravitreal faricimab injections, and occlusive retinal vasculitis developed in three eyes with repeated challenge, which led to irreversible vision loss, despite treatment with topical and systemic steroids, reported Christopher D. Conrady, MD, PhD, of Truhlsen Eye Center at the University of Nebraska Medical Center in Omaha, and colleagues.

In the eye that did not develop occlusive retinal vasculitis following rechallenge, there have been no other adverse events despite restarting the vascular endothelial growth factor (VEGF) and angiopoietin-2 inhibitor, they noted in JAMA Ophthalmology.

“In cases where inflammation develops from any anti-VEGF medication, we would recommend not rechallenging the patient with the same drug,” Conrady told MedPage Today. “While it may be okay in some patients, the risk of really bad complications — blindness — is real.”

Faricimab, a humanized, bispecific, immunoglobulin G monoclonal antibody, received FDA approval as an intravitreal injection for the treatment of nAMD and diabetic macular edema in 2022, and macular edema secondary to retinal vein occlusion in 2023.

“We know that faricimab works well in nAMD and macular edema, and that it is safe according to large real-world studies,” Conrady said. “The question that was still relatively unclear was whether patients that had a prior minor inflammatory reaction to the drug should be re-treated with the drug.”

The new report is the latest in a series that have reported rare but serious adverse events in patients taking faricimab. In October 2024, a Swiss team reported on two eyes that developed retinal vasculitis following noninfectious intraocular inflammation that developed after faricimab treatment. One eye had irreversible vision damage. This year, a French team reported on six eyes with nAMD that were switched to faricimab and developed severe intraocular inflammation.

Ghazala O’Keefe, MD, of the Emory University School of Medicine in Atlanta, told MedPage Today that “the [new] report is intriguing because it focuses on patients who had an initial mild level of inflammation after an injection and then developed worsening inflammation and vision loss. It gives us some insight into a process we have seen with the newer anti-VEGF injections that can have severe visual consequences.”

It’s not known why some patients are having this reaction, she said. “We have seen it with other medications like brolucizumab [Beovu], but I wouldn’t say we have a clear picture yet.”

For now, she added, clinicians can use the report to guide their discussions with patients about worst-case scenarios. “The reports about adverse effects from faricimab are few and far between, but they emphasize the need to have that conversation with the patient.”

In this case series, Conrady and colleagues reported on three patients treated at the University of Nebraska Medical Center from October 2023 to August 2024: an 89-year-old woman who was switched to faricimab in both eyes after unsuccessful treatment with bevacizumab (Avastin) for nAMD; an 86-year-old woman who was treated with faricimab for nAMD in her right eye; and a 63-year-old man who was being treated with aflibercept (Eylea) for diabetic macular edema but developed presumed herpes simplex virus keratitis in his right eye.

After the second treatment with faricimab for the 89-year-old woman, her left eye developed intraocular inflammation, which has been reported to occur in 0.2% to 0.6% of patients treated with faricimab. She was treated with steroids and stopped faricimab. Upon restarting the therapy, she received four injections. While inflammation resolved, her vision in her left eye declined.

The 86-year-old woman developed inflammation with keratic precipitates 4 weeks after her third treatment with faricimab. Inflammation resolved after steroid treatment, and she received a fourth treatment. She then developed eye pain and her visual acuity declined. Four months after her last faricimab treatment, she noted a subjective improvement in pain and vision.

The 63-year-old man was treated with valacyclovir (Valtrex) and topical steroids for his presumed herpes simplex virus keratitis. A month later, he began faricimab therapy in both eyes. Steroids resolved redness and a mild anterior chamber reaction. He later noted worsening vision and pain in both eyes. He was prescribed maximum medical therapy for ocular hypertension, a topical and oral steroid taper, and continued valacyclovir. At 1 month, visual acuity was unchanged in the right eye and mildly improved in the left eye with normal intraocular pressure.

“We were surprised that the patients did so poorly with rechallenge of the drug after documented prior inflammatory response to it,” Conrady said. “We think that this is likely an inflammatory reaction similar to that seen with a vaccine. You induce immunity to whatever it is with the vaccine, and then with subsequent challenge, the immune system recognizes the pathogen and responds more vigorously.”

“This is likely not faricimab-specific but should be considered with all intravitreal injections that are antibodies currently in use within the ophthalmic community,” he added. Still, “it is safe to say that the drug is as safe as many other drugs on the market that we use for nAMD. Mild or even severe ocular complications can occur with any of them.”