Eye Drug for Macular Degeneration Linked to Rare Optic Nerve Stroke — Early Warning Detected

Pegcetacoplan (brand name Syfovre) is a complement C3 inhibitor approved for geographic atrophy (GA), the advanced dry form of age-related macular degeneration — a leading cause of vision loss in older adults. While effective at slowing GA progression, emerging post-approval safety signals have raised concern about optic nerve complications, specifically nonarteritic anterior ischemic optic neuropathy (NAION), a condition caused by ischemia to the optic nerve head that can cause sudden, often permanent visual field loss.

This retrospective case series documents three patients who developed NAION during pegcetacoplan treatment at a single retina practice in Houston, Texas. All three received between 6 and 11 intravitreal injections administered every 6 to 8 weeks before NAION was identified. The cases span a range of clinical presentations: two patients likely noticed visual symptoms, while one was completely asymptomatic — the diagnosis discovered only because of systematic optic nerve monitoring during routine follow-up visits.

The key finding is that peripapillary RNFL thickness, measured serially by spectral-domain OCT, increased gradually in the affected eye of each patient before the clinical diagnosis of NAION was established. Importantly, this increase was greater in the eventually affected eye compared with the fellow (untreated or unaffected) eye. In some cases, automated OCT segmentation required manual correction to ensure accurate RNFL measurements, underscoring the importance of image quality verification in clinical monitoring. This progressive RNFL thickening may reflect early axonal swelling or edema associated with subclinical optic nerve ischemia — analogous to the disc edema seen in established NAION — and could represent a detectable preclinical phase.

The authors propose that serial peripapillary RNFL monitoring via OCT could serve as a practical, noninvasive surveillance tool for patients receiving pegcetacoplan. Because one patient was asymptomatic, purely symptom-based monitoring would have missed this case entirely. Earlier structural detection could allow clinicians to intervene — whether by suspending injections, adjusting treatment intervals, or initiating closer follow-up — potentially before irreversible visual field loss occurs.

Caveats are important to acknowledge. This is a small case series of only three patients from a single center, which limits generalizability and precludes causal inference. It is unclear whether NAION in these patients is directly caused by pegcetacoplan or represents an incidental finding in an older, cardiovascular risk-laden population already predisposed to ischemic optic neuropathy. Larger pharmacovigilance datasets and controlled studies will be essential to establish incidence rates and determine whether the association is drug-specific.