Intravitreal pegfilgrastim for indirect traumatic optic neuropathy: a first-in-human phase 1/2a study

Abstract Background Indirect traumatic optic neuropathy (TON) is associated with severe vision loss and no proven treatment. Aim To evaluate the safety and exploratory functional outcomes of intravitreal pegfilgrastim in patients with indirect TON. Design Single-center, open-label, single-arm phase 1/2a proof-of-concept study. Methods Twelve adults with acute unilateral indirect TON received a single intravitreal injection of 0.15 mL pegfilgrastim and were followed for 3 months. Outcomes included adverse events, best-corrected visual acuity (BCVA), visual field mean deviation, retinal nerve fiber layer thickness, and flash visual evoked potentials (VEP). Results No serious ocular or systemic treatment-related adverse events were observed. Transient leukocytosis occurred after treatment and resolved spontaneously. Within-subject improvements in BCVA were observed at 1 week, 1 month, and 3 months (p < 0.05), and visual field mean deviation improved at 3 months (p < 0.05). Retinal nerve fiber layer thickness declined progressively during follow-up. No significant change was detected in VEP latency or amplitude. Conclusions Intravitreal pegfilgrastim was feasible and well tolerated in this first-in-human study of indirect TON. Exploratory functional improvements were observed in a subset of participants, but controlled studies are required to determine whether these changes exceed the natural history of the disease.