The present invention provides methods and devices for delivering an active agent into the eye of a subject. In one aspect, for example, the present invention provides an ocular drug delivery device including a housing configured to couple to the eye of the subject and a corneal seal coupled to the housing and positioned in the housing to encircle the cornea during use to form a corneal region, where the housing extends outward from the corneal seal to form a scleral region, and where the scleral region being positioned over the eye's sclera during use. The device further includes an active agent reservoir coupled to the housing and positioned to release active agent into the scleral region and a pressure regulator coupled to the housing that is operable to introduce negative pressure between the housing and the eye. Thus the corneal seal is operable to fluidically isolate the corneal region from the scleral region in response to the negative pressure.