Intravitreal Ranibizumab to Treat Macular Edema After Panretinal Photocoagulation (Phase II)

• Mean change from pre-PRP Optical Coherence Tomography (OCT) in central foveal thickness and macular volume as assessed by OCT at 1, 2 and 3 months. [ Time Frame: March 2010 ] [ Designated as safety issue: No ]
• Percentage of patients that maintain pre-PRP visual acuity at the 3 month time point [ Time Frame: March 2010 ] [ Designated as safety issue: No ]
• Change between baseline and each efficacy outcome assessment in best-corrected ETDRS visual acuity score (e.g. mean visual acuity score) [ Time Frame: March 2010 ] [ Designated as safety issue: No ]
• Change in the hyperfluorescence of the macula as assessed by 2 readers blinded to the 2 arms of the study. [ Time Frame: March 2010 ] [ Designated as safety issue: No ]
• Injection-related events including severe uveitis, infectious endophthalmitis, non-infectious endophthalmitis, retinal detachment, and vitreous hemorrhage. [ Time Frame: Ongoing ] [ Designated as safety issue: Yes ]

• Mean change from pre-PRP Optical Coherence Tomography (OCT) in central foveal thickness and macular volume as assessed by OCT at 1, 2 and 3 months.
• Percentage of patients that maintain pre-PRP visual acuity at the 3 month time point
• Change between baseline and each efficacy outcome assessment in best-corrected ETDRS visual acuity score (e.g. mean visual acuity score)
• Change in the hyperfluorescence of the macula as assessed by 2 readers blinded to the 2 arms of the study.
• Injection-related events including severe uveitis, infectious endophthalmitis, non-infectious endophthalmitis, retinal detachment, and vitreous hemorrhage.

This is a randomized, open-label Phase II study evaluating the safety and efficacy of intravitreally administered ranibizumab 0.5mg in subjects with Proliferative Diabetic Retinopathy experiencing post- Panretinal Photocoagulation (PRP) macular edema.

Levels of VEGF are elevated in eyes wth Diabetic Macular Edema and the expression of VEGF was found to be elevated temporarily following the photocoagulation of human Retinal Pigment Epithelial (RPE) cells. Ranibizumab (Lucentis TM, Genentech) is an anti-VEGF antibody shown to have properties to prevent macular edema. We hypothesize that VEGF inhibition can effectively treat PRP-induced macular edema, thereby minimizing post-PRP vision loss.

Subjects who meet eligibility criteria will receive 0.5mg ranibizumab administered 7-14 days post-PRP. Additional intravitreal injections of 0.5 mg of ranibizumab at Day 30 and/or Day 60 may be also be administered. All subjects will be followed for 90 days for safety and efficacy assessments. There is no placebo or sham arm of this trial.

• Proliferative Diabetic Retinopathy
• Macular Edema

• Drug: ranibizumab
  Ranibizumab 0.5mg at baseline and then again at 30 days and/or 60 days after PRP as deemed appropriate by the Investigator.
  Other Name: Lucentis
• Drug: Ranibizumab
  Ranibizumab 0.5mg at baseline, then again at 30 days and/or 60 days post PRP per Investigator discretion.
  Other Name: Lucentis

Inclusion Criteria:

• Pre-PRP protocol refraction, fluorescein angiography, and optical coherence tomography AND 7-14 day post-PRP OCT
• Ability to provide written informed consent and comply with study assessments for the full duration of the study
• Age 21 years or older
• Previously untreated PDR patients with high risk characteristics who develop edema within 7-14 days post PRP therapy. This edema, determined by a masked investigator, will be characterized as either increased foveal thickness (>10% increase from pre-PRP foveal thickness), and/or increased macular volume on OCT (>10% increase from pre-PRP macular volume).

Exclusion Criteria:

• Pregnancy (positive pregnancy test) prior to enrollment in the study
• 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
• Pre-PRP clinically significant diabetic macular edema (CSME) that would make the patient eligible for macular laser prior to PRP
• Neovascularization of the iris or neovascular glaucoma
• Increased central foveal thickness for any other reason
• Concurrent macular diseases that could confound the results of this study
• Prior vitrectomy in the study eye
• Prior treatment with intravitreal injection including pegaptanib sodium, ranibizumab, bevacizumab or triamcinolone acetonide