Inclusion Criteria: * ≥18 years of age * Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening * CST ≥ 350 μm (Spectralis SD-OCT) in the study eye at Screening, confirmed by the independent reading center * Demonstrate clinical response to on-study aflibercept injection in the study eye. * Decreased visual acuity attributable primarily to DME * BCVA in the study eye between 25 and 83 ETDRS letters, inclusive (\~20/320 and 20/25, respectively) at Screening * Study eye amenable to IVT injection * Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures * Provide written informed consent Exclusion Criteria: * Macular edema in the study eye considered to be secondary to a cause other than DME * Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation * Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months * Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1) * Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye * Any concurrent ocular condition in the study eye that is likely to require surgical intervention (e.g. cataract surgery) during the 2 year (104 week) study duration Note: Other inclusion/exclusion criteria apply.