Evaluation of Ranibizumab in Proliferative Diabetic Retinopathy (PDR) Requiring Vitrectomy

This is an open-label, Phase I/II study of multiple doses of intravitreally administered
ranibizumab in patients with severe NPDR and PDR prior to, during, and after vitrectomy
therapy.

40 subjects will be enrolled and randomized 3:1 to ranibizumab or vitrectomy alone. 30
consented, enrolled subjects will receive 3 intravitreal injections of 0.5 mg ranibizumab
administered 1-3 weeks pre-procedure, intraoperatively, and 1 month post-vitrectomy.

Inclusion Criteria:

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

- Age > 20 years

- Best corrected visual acuity of 20/40 to 20/800 in the study eye

- Very servere nonproliferative diabetic retinopathy (ETDRS level 53E) OR moderate
proliferative diabetic retinopathy (ETDRS level 65)

- Visual reduction attributable to diabetic vitreous hemorrhage or diabetic macular
edema

- Candidate for vitrectomy procedure

Exclusion Criteria:

- 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, 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.

- Visual impairment attributable to causes other than diabetic macular edema or
diabetic vitreous hemorrhage.

- Use of intraocular or periocular corticosteroids within 6 months.

- History of panretinal photocoagulation

- History of macular laser photocoagulation

- History of pars plana vitrectomy

- Prior or concomitant treatment with ranibizumab, bevacizumab, or pegaptanib sodium,
either as part of an investigational study or as an off-label medication.

- Current treatment of a systemic infection