Sukhuma WarrasakAtaya EuswasMark M. FukudaMali IttiverakulR. Scott MillerSrivicha KrudsoodColin OhrtBangkok Hospital Medical CenterBill and Melinda Gates FoundationArmed Forces Research Institute of Medical Sciences, ThailandFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityWalter Reed Army Institute of ResearchMahidol UniversityConsortium for Health Action2020-01-272020-01-272019-08-15International Ophthalmology. Vol.39, No.8 (2019), 1767-178215732630016557012-s2.0-85054319013https://repository.li.mahidol.ac.th/handle/20.500.14594/51468© 2018, The Author(s). Purpose: Ophthalmic safety observations are reported from a clinical trial comparing tafenoquine (TQ) efficacy and safety versus sequential chloroquine (CQ)/primaquine (PQ) for acute Plasmodium vivax malaria. Methods: In an active-control, double-blind study, 70 adult subjects with microscopically confirmed P. vivax malaria were randomized (2:1) to receive 400 mg TQ × 3 days or 1500 mg CQ × 3 days then 15 mg PQ × 14 days. Main outcome measures: clinically relevant changes at Day 28 and Day 90 versus baseline in the ocular examination, color vision evaluation, and corneal and retinal digital photography. Results: Post-baseline keratopathy occurred in 14/44 (31.8%) patients with TQ and 0/24 with CQ/PQ (P = 0.002). Mild post-baseline retinal findings were reported in 10/44 (22.7%) patients receiving TQ and 2/24 (8.3%) receiving CQ/PQ (P = 0.15; treatment difference 14.4%, 95% CI − 5.7, 30.8). Masked evaluation of retinal photographs identified a retinal hemorrhage in one TQ patient (Day 90) and a slight increase in atrophy from baseline in one TQ and one CQ/PQ patient. Visual field sensitivity (Humphrey™ 10-2 test) was decreased in 7/44 (15.9%) patients receiving TQ and 3/24 (12.5%) receiving CQ/PQ; all cases were < 5 dB. There were no clinically relevant changes in visual acuity or macular function tests. Conclusions: There was no evidence of clinically relevant ocular toxicity with either treatment. Mild keratopathy was observed with TQ, without conclusive evidence of early retinal changes. Eye safety monitoring continues in therapeutic studies of low-dose tafenoquine (300 mg single dose). Clinical trial registration: Clinicaltrials.gov identifier: NCT01290601.Mahidol UniversityMedicineArticleSCOPUS10.1007/s10792-018-1003-2