Treat & Extend Versus Fixed Dosing with Faricimab for Management of Diabetic Macular Edema: a Pragmatic, Multi-center, Open-label, Randomized, Controlled Trial

Inclusion Criteria:

1. Age ≥ 18 years

2. Diagnosis of diabetes mellitus (type 1 or type 2).

3. Macular thickening secondary to DME (CI-DME) involving the center of the fovea onOptical Coherence Tomography - Central subfield thickness (CST) ≥ 325 μm onSpectralis at screening.***

4. Visual impairment due to DME, with best corrected visual acuity of 80 to 20 letters (Snellen VA 20/25 - 20/400).

5. Media clarity, pupillary dilation, and individual cooperation sufficient foradequate OCT and fundus photographs.

6. Hemoglobin A1c must be <10% within 2 months prior to 1st study treatment.

7. Provide signed informed consent.

Exclusion Criteria:

1. Active or history of ocular inflammation or suspected/active ocular infection ineither eye.

2. High-risk proliferative diabetic retinopathy in the study eye.**

3. Tractional retinal detachment, preretinal fibrosis or visually significantepiretinal membrane involving the macula.

4. Uncontrolled glaucoma (intraocular pressure >30 with or without medications).

5. Any intravitreal, periocular or implant corticosteroids within 26 weeks (6 months)before day 1 or any use of Iluvien implants.

6. Treatment with Panretinal photocoagulation (PRP) within 12 weeks before day 1.

7. Treatment with macular laser.

8. Any cataract surgery or any other intraocular surgery within 12 weeks before day 1.

9. Macular edema in study eye due to a cause other than DME.

10. If clinical exam and/or OCT and/or wide-field fluorescein angiography (WF-FA)suggest that (a) macular edema is considered to be related to ocular surgery such ascataract extraction or (b) if primary cause for macular edema is vitreoretinalinterface abnormalities (e.g. a taut posterior hyaloid or epiretinal membrane).

11. Any ocular condition is present such that visual acuity loss would not improve fromresolution of macular edema in opinion of the investigator (e.g. foveal atrophy,pigment abnormalities, dense subfoveal hard exudates, nonretinal condition)

12. Any history of ocular conditions that might affect macular edema (e.g. veinocclusion, idiopathic or infectious or non-infectious uveitis, ocular inflammatorydisease, neovascular glaucoma etc.)

13. Women of child-bearing potential who are lactating, pregnant, or intending to becomepregnant within the next 100 weeks.

14. Current or anticipated incarceration.

15. Terminal illness with expected survival less than 100 weeks.

16. Known hypersensitivity to faricimab or any of the excipients in the faricimabinjection.

17. Currently enrolled in a study that does not permit co-enrollment.

18. Unable to obtain informed consent due to language or other operational barriers.

19. Anticipated problems, in the judgment of the site investigator, maintainingcompliance with the protocol, including attending study visits, completingassessments or procedures.

20. Prior enrollment in this trial.

21. Other reason to exclude the patient, as approved by the sponsor and siteinvestigator.

22. Previous treatment with anti-VEGF and:

• <12 weeks prior to day 1 (washout period).*or,

• Diagnosis of DME is > 2 years of enrollment or,

• Do not have a demonstrated response to anti-VEGF treatment based on clinicaldiscretion.