Traumatic Optic Neuropathy Treatment Trial 2 (TONTT-2): evaluating the efficacy of different doses of erythropoietin - a multicentre, randomised, double-blind clinical trial

Aim The aim is to compare the efficacy and safety of three different weight-adjusted intravenous erythropoietin (EPO) doses in patients with indirect traumatic optic neuropathy (TON). Methods This study is a multicentre, randomised, parallel-group, double-blind, dose-finding trial on patients aged >= 7 years with a confirmed diagnosis of indirect TON in <= 3 weeks. The trial had a 3-day treatment period and a 3-month follow-up period. Patients were randomly allocated (1:1:1) to receive EPO at doses of 900 IU/kg (300 IU/kg/day), 1800 IU/kg (600 IU/kg/day) or 3600 IU/kg (600 IU/kg/day on presentation and then 1 month later) EPO. The changes in the best-corrected visual acuity (BCVA), colour vision and relative afferent pupillary defect (RAPD) were assessed. Results Out of 118 eligible patients, 95 were randomised and 93 (31 in each group) completed the follow-ups. Three groups were not different regarding baseline BCVA (p=0.66), colour vision (p=0.25) and RAPD (p=0.79). All three groups showed a significant improvement of BCVA and RAPD with no significant differences among the groups. Colour vision showed a significant improvement only in the group with 3600 IU/kg EPO (p=0.005), even though final colour vision was not significantly different between the groups (p=0.49). Initial vision of no light perception (OR=7.79 (95% CI: 2.98 to 20.36), p<0.001), older age (OR=4.76 (95% CI: 1.92 to 11.76), p<0.001), longer trauma-treatment interval (OR=2.72, 95% CI: 1.16 to 6.33, p=0.02) and posterior orbital fractures (OR=2.63 (95% CI: 1.13 to 6.13), p=0.02) led to a significantly worse visual recovery. Conclusion Increasing dose of EPO in patients with TON did not result in a better BCVA, colour vision and RAPD improvement. Trial registration number NCT03308448.