This randomized trial will compare treatment strategies for proliferative diabetic retinopathy (PDR). Participants will receive either combination a of faricimab + PRP or vitrectomy + endolaser. The participants will be followed for 3 years. The study will evaluate long-term visual acuity as well as differences in number of injections, procedures, and complications during follow-up (after completion of randomization treatment), and cost.

Although some combination of anti-VEGF plus PRP is the most common treatment approach for PDR with and without DME, there are currently no long-term data on a standardized approach. Vitrectomy is not currently used as first-line treatment for early PDR but advances in surgical technique have reduced associated complications and the ability to remove the posterior hyaloid during surgery may have advantages over nonsurgical approaches, especially in the reduction of vitreous hemorrhage and/or traction retinal detachment that may occur later when the hyaloid separates naturally. Protocol S demonstrated both PRP and anti-VEGF alone result in good visual acuity results long-term so it is expected that a combination treatment would also result in good visual acuity results.

This study will evaluate the safety and efficacy of two treatment strategies for PDR: faricimab plus PRP and Vitrectomy with endolaser with the goal to determine whether either approach decreases visit and treatment burden along with decreasing complications compared with the other treatment method while maintaining good visual acuity. The primary objectives of this study are to compare visual acuity at 3 years following vitrectomy with endolaser or faricimab+PRP and to compare number of treatments for PDR (i.e., injections, PRP, vitrectomy) following the end of randomized treatment over 3 years.

Inclusion Criteria:

Individual:

• ≥ 18 years old
• Diagnosis of diabetes mellitus (type 1 or type 2)

Study Eye:(A participant can have one or two study eyes if both eyes are eligible at screening.)

• Presence of PDR requiring treatment, defined as moderate PDR or worse on global grading of ultrawide field fundus photos or NV meeting criteria for moderate PDR or worse on global grading of ultrawide field FA, confirmed by a central reading center
• Best corrected visual acuity ≥49 letters (20/100 Snellen equivalent or better)

Exclusion Criteria:

• Individual:

  • Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.

  • Blood pressure > 160/100 (systolic above 160 or diastolic above 100).

    o If blood pressure is brought below 160/100 by anti-hypertensive treatment, individual can become eligible.

  • For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 3 years.

    • Women of childbearing potential will be required to have pregnancy testing or use an acceptable method of pregnancy prevention. Women who are potential study participants should be questioned about the potential for pregnancy at baseline and prior to each injection. Pregnancy test is required for all women of childbearing potential at baseline. Investigator judgment is used to determine when a pregnancy test is needed during follow up.

Study Eye: (A participant can have two study eyes.)

• Traction retinal detachment involving the macula
• Significant vitreous hemorrhage that would preclude completion of a full PRP
• Significant vitreomacular traction
• Any prior vitrectomy
• Any prior PRP (defined as ≥100 burns outside of the posterior pole)
• Treatment for DME within the prior 6 months
• Intravitreal anti-VEGF for any indication, other than DME, within the prior year