Syfovre, Izervay Side Effects May Thicken Retinal Nerves, Research Warns

Study comes amid continuing concerns about the risk of eye inflammation and other side effects of Syfovre and Izervay, which are used for treatment of AMD.

Two eye drugs were linked to increased retinal nerve thickness in a new study, although researchers said it remains unclear whether the changes are beneficial or harmful.

The research was presented last month by Dr. David Brown of Retina Consultants of Texas at the American Society of Retina Specialists (ASRS) annual meeting, examining side effects of a class of drugs known as complement inhibitors, including Syfovre (pegcetacoplan) and Izervay (avacincaptad pegol). Brown reported that patients treated with the medications experienced an annual increase of more than four micrometers in retinal nerve fiber layer (RNFL) thickness.

Syfovre and Izervay were both approved by the U.S. Food and Drug Administration in 2023 for the treatment of geographic atrophy (GA), a side effect of age-related macular degeneration (AMD). Both were released by Appellis Pharmaceuticals, with Syfovre introduced in February 2023, and Izervay released that August.

Syfovre Eye Inflammation Reports

Just months after Syfovre hit the market, the ASRS sent a letter to healthcare providers warning that the organization was receiving reports of eye inflammation linked to Syfovre injections.

At that time, ASRS indicated Syfovre was linked to at least six cases of occlusive retinal vasculitis, which blocks blood flow to the retina and can cause inflammation or total vision loss. The group warned doctors to closely follow up with patients who received the injections to detect potential adverse events as soon as possible.

Syfovre, Izervay Side Effects Study

In the new study, which has not yet been published for peer review, Brown and his team looked at 331 eyes that suffered from AMD, along with 4,870 optical coherence tomography measurements, which measure RNFL thickness. They looked at both compliment inhibitors, and anti-vascular endothelial growth factor (VEGF) treatments.

According to the findings, anti-VEGF drugs like Eylea slightly reduced retinal nerve thickness. However, patients taking Syfovre saw a 4.37 µm annual increase in RNFL thickness, and Izervay side effects resulted in a 5.72 µm annual increase.

The researchers found that the highest rate of thickening occurred in the first year of treatment. After the first year, the rate of increase leveled off. However, they concluded the nerves continued to thicken over time.

At issue is whether that nerve thickening is good or bad. The researchers note that the retinal nerve thickening could be neuroprotective, providing extra defense from nerve injuries, or detrimental, putting increasing pressure on the nerve itself.

Originally, the team believed the thickening would be a benefit, but upon realizing that the thickening never actually stopped, they raised concerns about nerve damage, telling attendees at the conference they did not have enough data to determine one way or the other.

In the meantime Dr. Brown advised doctors to closely monitor patients who are on drugs like Syfovre and Izervay for signs of RNFL thickening.

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