This study objectives is to evaluate the efficacy of YD312 to improve visual acuity in patients with diabetic macular edema (DME) compared to placebo and determine optimal dose of phase 2b study.

These study results present the possibility that imatinib can be used as a new DME inhibiting agent by involving VEGF-independent ocular angiogenesis, not action points of existing agents, in effectively inhibiting excessive vascular angiogenesis observed in oxygen-induced retinopathy.

Inclusion Criteria:

1. Screening Inclusion Criteria

   Study subjects must be eligible for the following criteria at screening:

   1. Subject who is male or female ≥ 19 years of age
   2. Subject who has a diagnosis of Type 1 or 2 diabetes
   3. Subject who has study eye with definite retinal thickening due to diabetic macular edema involving the center of the macula
   4. Subject who has voluntarily signed an informed consent form

2. Randomization Inclusion Criteria

Study eye must be eligible for the following criteria at randomization:

1. Subject who has study eye with central subfield thickness (CST) of ≥ 300 μm on optical coherence tomography (OCT)
2. Subject who has study eye with an early treatment diabetic retinopathy study (ETDRS) best-corrected visual acuity (BCVA) letter score ranging from 39 to 78, inclusive (approximate Snellen equivalent of 20/32 - 20/160)

Exclusion Criteria:

1. Subject who has study eye with any of the following criteria:

   1. Subject whose primary cause of macular edema is non-diabetic disease/condition (e.g., cataract extraction, vitreomacular interface abnormalities)

   2. Subject who is expected to have no improvement of decreased visual acuity in the opinion of investigator, even if macular edema is resolved (e.g., foveal atrophy, abnormal pigmentation, dense subfoveal hard exudate)

   3. Subject who has proliferative diabetic retinopathy.

   4. Subject who took the following within 3 months before randomization

      ① Focal/grid laser photocoagulation

      ② Intravitreal/circumbulbar corticosteroid, anti-VEGF and pro-VEGF (but, no wash-out period is required for the corticosteroid eyedrops)

   5. Subject who took panretinal photocoagulation (PRP) or intravitreal dexamethasone implant within 6 months before randomization

   6. Subject who has a history of vitrectomy

   7. Subject who took major ophthalmic surgeries (all intraocular surgeries including cataract extraction and scleral buckle) within 6 months before randomization

2. Subject who had systemic treatment of corticosteroid or anti-VEGF within 3 months before randomization.

3. Subject who administered vaccinium myrtillus extract or dobesilate calcium within 2 weeks before randomization

4. Subject who is suspected to require administration/treatment of drug/procedure that may affect the efficacy evaluation before the participation of clinical trial or during clinical trial (refer to '10.4 Combination Therapy and Contraindication').

5. Subject who has the following illness or abnormal laboratory test values:

   1. Subject who has a hypersensitivity to any excipients of the investigational product or similar class of drug and ingredient

   2. Subject who has uncontrolled hypertension (SBP > 160 mmHg or DBP >100 mmHg)

   3. Subject who has uncontrolled diabetes (HbA1c > 10.0%)

   4. Subject who has uncontrolled glaucoma in either eye (intraocular pressure (IOP) > 24 mmHg on medication or according to the investigator's judgment)

   5. ANC < 1.5 × 109/L

   6. Platelet < 125 × 109/L

   7. Total bilirubin > 1.5 × ULN

   8. AST or ALT > 2 × ULN

   9. Clcr* < 40 mL/min

      * Clcr (Cockcroft-Gault formula)

      = [(140 - age) x weight(kg) (x 0.85 for females)] / [72 x serum creatinine (Scr) (mg/dL)]

   10. Severe heart failure (NYHA class III/IV)

   11. Malignant tumor within 5 years before randomization

   12. Subject who is known to be HIV positive, is active hepatitis B patient or carrier, or is hepatitis C patient

   13. Ocular inflammatory diseases such as uveitis, conjunctivitis, and blepharitis in either eye. However, the participation of subject in this study is considered at the discretion of investigator.

   14. Unstable angina, myocardial infarction, transient ischemic attack, cerebral infarction, coronary artery bypass surgery, or transluminal coronary angioplasty within 6 months before screening

6. Pregnant woman, lactating woman, or female or male subject of childbearing potential

   *hormonal contraceptives, intrauterne contraceptive device, sterilization of spouse (e.g., vasectomy, tubal ligation), double-barrier method (e.g., combinational use of spermicides and condoms, diaphragm, contraceptive sponge, of FemCap)

7. Subject who took administraion/procedure of other investigational products or medical devices within longer period between 30 days before screening or over 5time half-life.

8. Subject, at the discretion of the investigator, who is unsuitable to participate in the study.