A drug delivery device (100, 200) configured to be at least partially implanted in an eye through the sclera, the device comprising: a retention structure positioned near a proximal end region of the device comprising: a proximal flange element (110, 210, 2710) defining an access port (111, 2811, 3711, 3911) into the device; and a neck having a proximal region and a distal extension wherein the proximal region of the neck has a major axis dimension and a minor axis dimension; wherein, upon the at least partial implantation of the device in the eye through a penetration site in the sclera of the eye, the proximal flange element (110, 210, 2710) is configured to remain outside the sclera, the proximal region of the neck is configured to span the penetration site in the sclera and the distal extension is configured to be positioned inside the sclera; wherein the access port (111, 2811, 3711, 3911) extends through the proximal region of the neck defining a trans-scleral access port region of the access port (111, 2811, 3711, 3911) and extends through the distal extension of the neck defining a sub-scleral access port region of the access port (111, 2811, 3711, 3911); a penetrable element coupled to and extending within at least a portion of the access port (111, 2811, 3711, 3911), wherein the penetrable element has a first portion positioned within the trans-scleral access port region and a second portion positioned within the sub-scleral access port region, a maximum distance across the first portion being less than a maximum distance across the second portion; a porous drug release element positioned in fluid communication with an outlet of the device; and a reservoir (130, 230) having a volume configured to contain one or more therapeutic agents and to be in fluid communication with the outlet through the porous drug release element, wherein the device is configured to be at least partially inserted into the eye along an axis of insertion. a retention structure positioned near a proximal end region of the device comprising: a proximal flange element (110, 210, 2710) defining an access port (111, 2811, 3711, 3911) into the device; and a neck having a proximal region and a distal extension wherein the proximal region of the neck has a major axis dimension and a minor axis dimension; wherein, upon the at least partial implantation of the device in the eye through a penetration site in the sclera of the eye, the proximal flange element (110, 210, 2710) is configured to remain outside the sclera, the proximal region of the neck is configured to span the penetration site in the sclera and the distal extension is configured to be positioned inside the sclera; wherein the access port (111, 2811, 3711, 3911) extends through the proximal region of the neck defining a trans-scleral access port region of the access port (111, 2811, 3711, 3911) and extends through the distal extension of the neck defining a sub-scleral access port region of the access port (111, 2811, 3711, 3911); a proximal flange element (110, 210, 2710) defining an access port (111, 2811, 3711, 3911) into the device; and a neck having a proximal region and a distal extension wherein the proximal region of the neck has a major axis dimension and a minor axis dimension; wherein, upon the at least partial implantation of the device in the eye through a penetration site in the sclera of the eye, the proximal flange element (110, 210, 2710) is configured to remain outside the sclera, the proximal region of the neck is configured to span the penetration site in the sclera and the distal extension is configured to be positioned inside the sclera; wherein the access port (111, 2811, 3711, 3911) extends through the proximal region of the neck defining a trans-scleral access port region of the access port (111, 2811, 3711, 3911) and extends through the distal extension of the neck defining a sub-scleral access port region of the access port (111, 2811, 3711, 3911); a penetrable element coupled to and extending within at least a portion of the access port (111, 2811, 3711, 3911), wherein the penetrable element has a first portion positioned within the trans-scleral access port region and a second portion positioned within the sub-scleral access port region, a maximum distance across the first portion being less than a maximum distance across the second portion; a porous drug release element positioned in fluid communication with an outlet of the device; and a reservoir (130, 230) having a volume configured to contain one or more therapeutic agents and to be in fluid communication with the outlet through the porous drug release element, wherein the device is configured to be at least partially inserted into the eye along an axis of insertion.