Clinical Study to Evaluate PRO-169 for Diabetic Macular Edema

Inclusion Criteria:

• Age ≥ 18 years

• Diagnosis of Diabetes Mellitus (type 1 or 2) evidenced by: use of insulin or use oforal hypoglycemic medications or diagnosis for DM according to OMS or ADA criteria.

• Is capable of rendering informed consent.

• HbA1c <8.5% in selection visit.

• All men and women capable of reproduction may agree to use a barrier birth controlmethod during the study and 3 months after the last intravitreal injection applied.

• Only one eye may be randomized per participating individual, in case both areeligible, the investigator may choose either eye according his/her criteria.

• BVCA according to ETDRS between <78 (20/32 or worse) and >24 (20/320 or better)within 8 days prior to the randomization.

• Clinically evident diabetic macular edema, with central macular thickening.

• Diabetic macular edema demonstrated in OCT scan (macular central thickness > 300 μmfor men and > 290 μm for women) within 8 days prior to the randomization.

• Presenting characteristics that allow an adequate fundus examination (transparentmeans, adequate pupil dilation, etc).

Exclusion Criteria:

• Chronic renal disease with renal insufficiency that requires dialysis or transplant.

• Individuals with conditions that may compromise their participation during the spanof the study (unstable concomitant diseases, possible change of residence, etc)

• Individuals with a poor glycemic control who have started insulin treatment within 4months previous to the study.

• Participation in another clinical study (at least 90 days must have elapsed betweenthe finalization of his/her participation in a previous essay and randomization inthe present study).

• Known allergies to the treatment.

• Poorly controlled blood pressure (average of 3 readings while sitting with ≥160 mmHgsystolic or ≥100 mmHg diastolic in the selection visit.

• Heart attack or other cardiovascular event (cerebral vascular disease, transitoryischemia, hospitalization for cardiac insufficiency) during the 4 months prior tothe start of the study, or patients with active myocardial insufficiency.

• Previous systemic treatment with VEGF-related medications within 4 months prior tothe start of the study.

• Women of child-bearing age who are pregnant, lactating of planning to get pregnantwithin the time span of the study.

• Known allergy to anesthetic medications used during the procedures, intravitrealinjection and photocoagulation.

• Diagnosis of non-diabetic macular edema.

• Ophthalmic conditions that interfere with the evaluation of BCVA (for example:foveal atrophy, pigmentary abnormalities, dense foveal exudates, etc)

• Additional conditions to DM that may compromise the evaluation of the edema (forexample: venous occlusions, uveitis or other inflammatory diseases, neovascularglaucoma, etc)

• Lens opacities that according to the LOCS III classification system exceed one ormore of the following: > NO3C3, > C2, > P1.

• Previous history of anti-VEGF treatment for diabetic macular edema or any treatmentfor diabetic macular edema within 4 months prior to the start of the study (corticosteroids, photocoagulation, etc)

• Anticipation of the need of panphotocoagulation (for example: proliferative diabeticretinopathy or any other indication) during the period of the study or history ofpanphotocoagulation within the 4 months prior to the start of the study.

• History of ocular surgery (cataract extraction, any intraocular surgery, aphakia,etc) within 4 months prior to the start of the study, or planned to occur within thetime span of the study.

• Intraocular pressure > 21 mmHg, measured through Goldmann tonometry during theselection visit.

• Presence of macular ischemia or important loss of perifoveal capilaries (avascularfoveal zone greater than 350 μm) demonstrated through fluorescein angiography duringthe selection visit.

• Evidence of macular traction and hyaloid thickening in OCT scan.

• History of YAG capsulotomy within 2 months prior to the randomization.

• Evidence of external ocular infections or any important disease of the ocularsurface.

• History of vitrectomy.