• Number of treatments [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
• 3-line change in VA (15 letters on ETDRS chart) [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
• Change in subretinal and intraretinal fluid on optical coherent tomography [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
• Change in lesion size on fluorescein angiography [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]
• Incidence of endophthalmitis, retinal detachment, cataract, uveitis [ Time Frame: 12 and 24 months ] [ Designated as safety issue: Yes ]
• Incidence of adverse events [ Time Frame: 12 and 24 months ] [ Designated as safety issue: Yes ]
• Cost [ Time Frame: 12 and 24 months ] [ Designated as safety issue: No ]

The purpose of the study is to evaluate the relative efficacy and safety of treatment of neovascular AMD with Lucentis on a fixed schedule, Avastin on a fixed schedule, Lucentis on a variable schedule, and Avastin on a variable schedule.

Age related macular degeneration (AMD) is the leading cause of severe vision loss in people over the age of 65 in the United States and other Western countries. More than 1.6 million people in the US currently have one or both eyes affected by the advanced stage of AMD.

Lucentis® is the most effective treatment for neovascular AMD studied to date. Bevacizumab (Avastin®) and Lucentis® are derived from the same monoclonal antibody. Following the encouraging clinical trial results with Lucentis®, several investigators began evaluating intravitreal Avastin® for the treatment of CNV. Given its molecular similarity to Lucentis, its low cost, and its availability, the interest in Avastin® has been considerable. Avastin® has not been evaluated relative to Lucentis®.

In addition, previous studies do not answer the question of whether a reduced dosing schedule is as effective as a fixed schedule of monthly injections. Treatment dependent on clinical response has the potential to reduce the treatment burden to patients as well as to reduce the overall cost of therapy.

• Drug: ranibizumab
• Drug: bevacizumab

• Active Comparator: Lucentis® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis® every 4 weeks or to variable dosing.
• Experimental: Avastin® on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin® every 4 weeks or to variable dosing.
• Experimental: Lucentis® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
• Experimental: Avastin® on a variable dosing schedule for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.

Inclusion Criteria:

• Active, subfoveal choroidal neovascularization (CNV)
• Fibrosis < 50% of total lesion area
• Visual acuity (VA) 20/25-20/320
• Age ≥ 50 yrs
• At least 1 drusen (>63μ) in either eye or late AMD in fellow eye

Exclusion Criteria:

• Previous treatment for CNV in study eye
• Other progressive retinal disease likely to compromise VA
• Contraindications to injections with Lucentis or Avastin