Targeted Fluorescence Imaging in AMD (LEAF)

Targeted Fluorescence Imaging Using Bevacizumab-800CW Within Age-related Macular Degeneration (AMD) Patients to Evaluate the Upregulation of VEGF

Rationale: To track performance of intravitreal distribution of anti-VEGF-A (Bevazicumab-800CW) and provide information about neovascularization and inflammation in Age-Related Macular Degeneration (AMD), thereby predicting progression and optimizing treatment Objective: To determine the safety and feasibility of fluorescence imaging of the eye with the fluorescent tracer bevacizumab-800CW for identification AMD with scanning laser angiography Study design: A non-randomized, non-blinded, prospective, single-center feasibility study. Study population: Patients group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal. Control group: patients with naïve wet AMD and wet AMD aged >60 years old with current treatment of anti-VEGF intravitreal Intervention (if applicable): Intravenous injection of bevacizumab-800CW in the patient group and vedolizumab-800CW in the control group. Main study parameters/endpoints: Safety and feasibility of the intravenous tracer bevacizumab-800CW in patients with naïve wet AMD and wet AMD by observing the uptake in retinal, choroid and neovascular tissue. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: No risk described in other (running) studies on intravenous injection with bevacizumab-800 CW. Patients need to come back 48-96 hours after injection and the eye measurements take about half an hour longer. There is no benefit with participation.

First a dose finding study is performed using bevacizumab-800CW within the AMD patient group. Using the optimal dose and if fluorescence is visible, the vedolizumab group is added.

Bevacizumab-800CW is administered to the patient and angiography is performed before and directly after tracer administration and after 48-96 hours.

Vedolizumab-800CW is administered to the patient and angiography is performed before and directly after tracer administration and after 48-96 hours.

Safety: number of participants with symptoms or changes in vital signs (blood pressure, heart rate and temperature) that are related to administration of bevacizumab-800CW

To determine the safety of bevacizumab-800CW in patients with AMD by monitoring of vital signs (blood pressure, heart rate and temperature), before and until one hour after administration.

Feasibility: the possibility of measuring the specific uptake of fluorescence within the eye using both scanning laser angiography and optical coherence tomography.

The target-to-background radio will be measured during fluorescence imaging and compared with imaging before tracer administration.

Determination of the most optimal dose of bevacizumab-800CW for fluorescence imaging of the eye vascularization.

The target-to-background radio will be calculated and the dose with the highest ratio will be used as most optimal dose.

Correlation of the fluorescence intensity, target-to-background ratio (TBR), with disease identification

Verification the specific uptake of bevazicumab-800CW by comparing the target-to-background ratio to the control antibody vedolizumab-800CW

Gather tear fluid with Schirmer strips and using ELISA to extract the VEGF concentration and correlate this with the fluorescence signal

Inclusion Criteria: Patients with either naïve wet AMD or wet AMD receiving standard care of anti-VEGF therapy Aged >60 years old Optional: Patients already included in fluorescence study which involves Bevacizumab-800CW Exclusion Criteria: Eye pathology interfering with retinal imaging; Patients with psychological diseases or medical issues who are not able to sign informed consent form; Concurrent uncontrolled medical conditions; Received a different investigational drug within 30 days prior to the dose of bevacizumab-800CW; History of infusion reactions to bevacizumab or other monoclonal antibody.