 This first-in-human study will be conducted in 2 parts. Part 1 is an ascending dose design to assess the safety, tolerability, pharmacodynamics and pharmacokinetics of various single IVT doses of LKA651 in up to 48 subjects with diabetic macular edema. Subjects will be randomized to receive active or sham injections in a 3:1 ratio. A total of 6 cohorts 8 subjects per cohort may be enrolled in Part 1. Each subject will participate in a screeningeligibility period up to 60 days, a treatment period single day, and an 84 day follow up period. A total of up to 11 visits will take place, all on an out-patient basis. An independent data monitoring committee DMC will be chartered to review cumulative safety data and approve each dose escalation and cohort progression in this first-in-human trial. 