Safety and Efficacy of Ranibizumab for Diabetic Macular Edema

This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab
(Lucentis) in subjects with DME (diabetic macular edema) previously treated with intravitreal
bevacizumab (Avastin) with a randomized comparative dosing strategy, monthly vs
"treat-and-extend." Thirty patients total will be enrolled in the study, 15 in each group.
This study will have a 1-year treatment period. The recruitment period will occur over 1 year
with total potential study duration of 2 years.

Inclusion Criteria:

- Subjects will be eligible if the following criteria are met:

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

- Age > 18 years

- ETDRS best-corrected visual acuity of 20/25 to 20/320 in the study eye

- Willing, committed, and able to return for ALL clinic visits and complete all
study related procedures

- At least 6 previous bevacizumab injections for diabetic macular edema in the last
12 months in the study eye.

- At least 2 bevacizumab injections within 10 weeks and the most recent bevacizumab
injection within 6 weeks of baseline study visits in the study eye.

- Persistent foveal-involving diabetic macular edema based on presence of
intraretinal and/or subretinal fluid by SDOCT in the foveal center at study entry
in the study eye.

Exclusion Criteria:

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

- 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 IUD (intrauterine device), or contraceptive hormone implant
or patch.

- Intravitreal steroid or periocular steroid treatment within 3 months of study entry in
the study eye.

- Focal/grid laser photocoagulation treatment within 3 months of study entry in the
study eye.

- Panretinal photocoagulation treatment within 3 months of study entry in the study eye.

- Prior vitrectomy in the study eye

- History of retinal detachment in the study eye

- Prior trabeculectomy or other filtration surgery in the study eye

- Active intraocular inflammation in either eye

- Active ocular or periocular infection in either eye

- Active scleritis or episcleritis in either eye

- History of any other retinal vascular disease (e.g., retinal vein occlusion, retinal
artery occlusion) in the study eye.

- Coexistent retinal disease other than diabetic retinopathy (e.g., AMD (age related
macular degeneration), inherited retinal disease) in the study eye.

- Intraocular surgery within 3 months of study entry in the study eye.

- History of corneal transplant or corneal dystrophy in the study eye.

- Significant media opacities in study eye which may interfere with visual acuity in the
study eye.

- Participation as a subject in any clinical study within 3 months of study entry.

- History of allergy to topical iodine

- 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