The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates

This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in
subjects with diabetic macular edema and lipid exudates in the central subfield.

Consented, enrolled subjects will receive multiple open-label intravitreal injections on
0.3mg ranibizumab administered every 30 days for 12 months per the treatment algorithm.

The patients will be randomized to 1 of 2 treatment groups. Group 1: Treatment algorithm
based on the Diabetic Retinopathy Clinical Research (DRCR) protocol I 4:2:7 strategy based on
the presence of macular edema.

Group 2: Continue treatment until not only the macular edema is resolved but also until the
lipid exudate is resolved.

Sample size: 30 eyes Follow-up Schedule: Every 4 weeks throughout the study.

Subjects will be eligible if the following criteria are met:

Inclusion Criteria

- Ability to provide written informed consent and comply with study assessments for the
full duration of the study

- Age ≥ 18 years

- Type 1 or Type 2 Diabetes mellitus

- Best corrected ETDRS visual acuity (20/32-20/320) or letter score 78 to 24

- Diabetic macular edema on clinical examination involving the center of the macula
assessed to be the main cause of visual loss

- Retinal thickness measured on spectral domain optical coherence tomography (OCT).
Zeiss Cirrus: ≥290μm in women and ≥305 μm in men in the central subfield. Heidelberg
Spectralis: ≥305μm in women and ≥320 μm in men in the central subfield

- Lipid exudates involving the central subfield on spectral domain OCT.

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from this study:

- Treatment for diabetic macular edema within the prior 4 months.

- Panretinal photocoagulation within the prior 4 months or anticipated need for
panretinal photocoagulation within the next 6 months

- major ocular surgery within the prior 4 months

- myocardial infarction, other cardiac event requiring hospitalization, cerebrovascular
accident, transient ischemic attack, or treatment for acute congestive heart failure
occurred within 4 months before randomization

- Pregnancy (positive pregnancy test) or lactation

- Premenopausal women not using adequate contraception. The following are considered
effective means of contraception: surgical sterilization or use of oral
contraceptives, barrier contraception with either a condom or diaphragm in conjunction
with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant
or patch.

- Any other condition that the investigator believes would pose a significant hazard to
the subject if the investigational therapy were initiated

- Participation in another simultaneous medical investigation or trial