A Study to Evaluate Efficacy, Safety & Pharmacokinetics of the Port Delivery System (PDS) With Ranibizumab in Participants With Diabetic Macular Edema (DME) Compared With Intravitreal Ranibizumab; A Subtudy to Evaluate the Safety of Re-Implanting the PDS With Ranibizumab in Participants With DME

Inclusion Criteria:

• Age ≥18 years at time of signing Informed Consent Form

• Documented diagnosis of diabetes mellitus (Type 1 or Type 2)

• HbA1c level of ≤10% within 2 months prior to screening or at screening

Study eye

• Macular thickening secondary to DME involving the center of the fovea with CST ≥325um on SD-OCT at screening

• BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)

Exclusion Criteria:

• High-risk proliferative diabetic retinopathy

• Active intraocular inflammation (grade trace or above)

• Suspected or active ocular or periocular infection of either eye

• Uncontrolled ocular hypertension or glaucoma and any such condition the investigatordetermines may require a glaucoma-filtering surgery during a patient's participationin the study

• Cerebrovascular accident or myocardial infarction within 6 months prior torandomization

• Atrial fibrillation diagnosis or worsening within 6 months prior to randomization

• Uncontrolled blood pressure

Substudy:

Inclusion Criteria:

• Having experienced a septum dislodgement in the original implant while in the mainstudy or after exiting the main study

• Sufficiently clear ocular media and adequate pupillary dilation to allow foranalysis and grading by central reading center

Exclusion Criteria (Cohort 1 Only):

• Recent history (in the last 3 months prior to enrollment) of other disease, othernon-diabetic metabolic dysfunction, physical examination finding, or clinicallaboratory finding giving reasonable suspicion of a condition that contraindicatesthe use of ranibizumab or surgical placement of the PDS implant; that might affectinterpretation of the results of the study; or that renders the participant at highrisk for treatment complications

• Active cancer within the last 12 months, except for appropriately treated carcinomain situ of the cervix, non-melanoma skin carcinoma, or prostate cancer

• Current systemic treatment for a confirmed active systemic infection

• Participation in an investigational trial that involves treatment with any drug ordevice (with the exception of vitamins and minerals or enrollment in Study GR40550)within 6 months prior to enrollment

• Use of antimitotic or antimetabolite therapy within 30 days

Ocular Exclusion Criteria for Study Eye:

• Any ocular condition that may render the participant at high risk for surgical ortreatment complications

• Intraocular surgery (including cataract surgery) within 1 month preceding theenrollment visit

• Any use of medicated intraocular implants (other than the PDS implant), at any timeprior to enrollment

• History of rhegmatogenous retinal tears or peripheral retinal breaks within 3 monthsprior to the enrollment visit

• Any concurrent ocular condition that would require surgical intervention during thestudy to prevent or treat visual loss

• Concurrent conjunctival, Tenon's capsule, and/or scleral condition in thesupero-temporal quadrant of the eye (e.g., scarring, thinning, mass) that may affectthe refill-exchange procedure of the PDS implant

• Ongoing ocular complications that might affect participant safety Ocular ExclusionCriteria for Either Eye

• Suspected or active ocular or periocular infection (e.g., infectious conjunctivitisor endophthalmitis)

• Any history of uveitis

• Active blepharitis