Prospective, Randomized, Multicenter, Open Label, Phase II Study to Access Efficacy and Safety of Lucentis® Monotherapy Compared With Lucentis® Plus Panretinal Photocoagulation (PRP) and PRP in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy

• Regression of neovascularization [ Time Frame: 12-month treatment ] [ Designated as safety issue: No ]
  To demonstrate superiority of one of the treatment arms: ranibizumab 0.5 mg monotherapy, panretinal photocoagulation monotherapy or combination therapy (ranibizumab 0.5 mg plus panretinal photocoagulation) over a 12-month treatment period in the regression of neovascularization.
  
  

• Changes from baseline in Best-Corrected Visual Acuity [ Time Frame: 12-month treatment ] [ Designated as safety issue: Yes ]
  Best-Corrected Visual Acuity will be assessed during the trial (Baseline, Month 3, Month 6 and Month 12).
  
  
• Changes from baseline in macular retinal thickness by Optical Coherent Tomography [ Time Frame: 12-month treatment ] [ Designated as safety issue: Yes ]
  Optical Coherent Tomography will be assessed during the trial (Baseline, Month 3, Month 6 and Month 12).
  
  
• Recurrence of neovascularization [ Time Frame: 12-month treatment ] [ Designated as safety issue: Yes ]
  To assess if there is recurrence of neovascularization.
  
  
• Number of treatments needed [ Time Frame: 12-month treatment ] [ Designated as safety issue: No ]
  To analyse the number treatments given to each subject during the the 12-month treatment.
  
  
• Additional focal or grid laser for Diabetic Macular Edema [ Time Frame: 12 month treatment ] [ Designated as safety issue: Yes ]
  To assess the number of patients that received additional focal or grid laser for Diabetic Macular Edema.
  
  
• Adverse events [ Time Frame: 12-month treatment ] [ Designated as safety issue: Yes ]
  Drug safety profile.
  
  
• Need for vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment relative to the three treatment arms. [ Time Frame: 12-month treatment ] [ Designated as safety issue: Yes ]
  To assess the number of subjects who needed vitrectomy due to occurrence of vitreous hemorrhage or retinal detachment relative to the three treatment arms.
  
  

Panretinal photocoagulation can cause regression of retinal neovascularization and reduce the risk of severe vision loss in people with proliferative diabetic retinopathy. However, this destructive treatment may be associated with side effects (such as: pain, transient blurring, loss of peripheral and/or night vision, increased risk of macular edema and central vision loss) and it is not always efficient in the regression of the neovascularization.

Vascular endothelial growth factor (VEGF) has been shown to play a role in retinal neovascularization and retinal vascular leakage related with proliferative diabetic retinopathy and diabetic macular edema. Anti-vascular endothelial growth factor treatments have been hypothesized as an alternative adjunctive treatment for the management of retinal neovascularization and macular edema related with diabetic retinopathy.

There are a few reports of retinal traction detachment in patients with proliferative diabetic retinopathy and fibrovascular proliferation (although it is not frequent). However, from our clinical experience, we think that the risk of detachment only exists when there is in place a fibrovascular proliferation with retinal traction previous to the injection.

We injected ranibizumab prior to surgery in patients with severe proliferative diabetic retinopathy, that were submitted later to a posterior vitrectomy, to reduce neovascularization and minimize the risk of an intraoperatory hemorrhage caused by the manipulation of the fibrovascular membranes. In total, we already injected and submitted to surgery 15 eyes with the above mentioned condition, with excellent results. The results of the first 10 eyes were presented in the congress of the Portuguese Society of Ophthalmology (2008).