MONTREAL -- Complement inhibitors to treat geographic atrophy (GA) were associated with thickening of the retinal nerve fiber layer (RNFL), which could be helpful or pathologic, according to a study reported here.
Both FDA-approved complement inhibitors were linked to an increase in the RNFL, whereas untreated GA, or dry age-related macular degeneration (AMD), and anti-VEGF injections were associated with a reduction in RNFL thickness. RNFL thickness increased by 4.37 µm annually in patients on pegcetacoplan (Syfovre) and by 5.72 µm in those on avacincaptad pegol (Izervay). The highest rate of RNFL thickening occurred during the first year of anti-complement treatment, then leveled off after that but continued to increase.
RNFL thickening appears to be a class effect of complement inhibitors, and the difference between pegcetacoplan and avacincaptad pegol did not differ significantly, said David Brown, MD, of Retina Consultants of Texas in Houston, at the American Society of Retina Specialists meeting. Whether the thickening represents pathologic swelling or infiltrate or a neuroprotective response remains unclear.
"The scary part is that it never plateaus," said Brown. "What you're doing is thickening the nerve. You're increasing ischemic optic neuropathy. Is this neuroprotection, edema, or infiltration? If it was neuroprotection it would go from [nerve fiber loss] to zero."
