Anti-VEGF (bevacizumab/ranibizumab) versus RPE-choroid graft in the treatment of 1) non-responders to 3 intravitreal anti-VEGF injections, or 2) patients with AMD and pigment epithelium rip, or 3) patients with AMD and massive haemorrhage. A randomized trial.

Rationale:
Standard treatment for patients with exudative age-related macular degeneration (AMD) is intravitreal injection of anti-VEGF. Because alternatives are not available, at present, also those patients for whom this therapy probably does not help to improve prospects are initially treated with anti-VEGF. Recently, however, it has been shown that a retinal pigment epithelium (RPE)-choroid graft translocation in the treatment of patients with choroidal neovascular lesions of AMD can stabilize or even improve visual acuity. In this study, it will be investigated whether RPE-choroid graft translocation provides a better alternative to anti-VEGF medication for AMD patients for whom prospects are rather poor otherwise.
Objective:
To compare visual outcome and foveal function after (initiation of) treatment between patients receiving an RPE-choroid graft and patients with anti-VEGF medication.
Study design: 
Prospective, international multicenter, randomized intervention study.
Study population: 
Patients with exudative AMD, aged 65 years or older, in combination with either of the following conditions: 1) visual loss of > 15 letters on the ETDRS chart after 3 anti-VEGF injections, 2) subfoveal RPE-tear, 3) massive submacular haemorrhage.
Intervention:
Arm 1: RPE-choroid graft translocation. 
Arm 2: intravitreal anti-VEGF (Avastin or Lucentis) injections (PrONTO protocol). 
Irrespective of study arm, blood will always be surgically removed in patients with massive haemorrhage.
Main study parameters:
Visual acuity, reading vision and foveal fixation at 1 and 2 years.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: 
Prognosis for exudative AMD complicated by RPE-rip or massive haemorrhage, and for non-responders to anti-VEGF therapy, is very poor. At this moment the only available alternative option for treatment may be an RPE-choroid graft translocation. It has been shown that with this technique vision loss can be limited. The RPE-choroid graft arm requires two surgical procedures (local or general anaesthesia), i.e. one for the translocation procedure and a second to remove silicone oil. Complications consist of retinal detachment (8%), recurrence of CNV (13%) and haemorrhage (10%). Massive haemorrhage will always be surgically removed (arm 1: in combination with the first surgical procedure, i.e. the RPE-choroid graft; in arm 2: as single surgical procedure). The risk of complications of haemorrhage removal alone (arm 2) will be less than in combination with the transplantation part.The anti-VEGF arm receives intravitreal injections (topical anaesthesia) in accordance with the PrONTO protocol24. Most patients will receive an injection once every two or three months. Repeated intravitreal anti-VEGF injections pose a (cumulative) risk for endophthalmitis. Each injection is associated with a risk of 0.1% to develop endophthalmitis. Number of visits during year 1 will be 11 (arm 1) and 8 (arm 2) respectively.

Visual outcome in patients receiving RPE-choroid graft will be better than in patients receiving anti-VEGF medication.

Baseline, 12 months, 24 months.

RPE-choroid graft, intravitreal anti-VEGF injection.