INCLUSION CRITERIA:
-Subjects will include adults being treated for exudative AMD, or macular edema secondary to DR or venous occlusion. The 3 clinical categories, which will each be composed of 10 subjects, are:
a) Category 1: Patients treated with long term (greater than 1 year) with bevacizumab or ranibizumab in which decreased drug efficacy has been documented. They must have received at least one treatment in the prior 3 months.
Decreased drug efficacy will be defined as follows: Presence of a therapeutic response (reduction in macula fluid as determined by optical coherence tomography (OCT) or reduction in extent of leakage on fluorescein angiography (FA)) in the first 3 injections, followed by a subsequent decrease in response as evidenced by persistence of intraretinal cysts and/or subretinal fluid on OCT and/or leakage on fluorescein angiography (FA).
b) Category 2: Patients treated with long term (greater than 1 year) bevacizumab or ranibizumab in which decreased drug efficacy has not been documented. They must have received at least one treatment in the prior 3 months.
The presence of continued drug efficacy will be defined as follows: Patients who are being treated with bevacizumab or ranibizumab and are demonstrating a good clinical response as demonstrated by the presence of a fluid-free macula on OCT and/or the absence of leakage on FA after treatment.
c) Category 3: Patients who are na ve to treatment with bevacizumab and ranibizumab
When possible, patients in the 3 categories will be matched by underlying retinal disease type, race, gender, and age.
EXCLUSION CRITERIA:
Patients in the following categories will be excluded from participating in this study:
a) Patients who are currently receiving any form of systemic immunosuppressive or immunomodulatory therapy, including corticosteroids. Immunosuppressive medication could lower the titers of neutralizing that are present in a given patient, and this could give the false impression that such a patient has little to no immune response against bevacizumab or ranibizumab.
b) Patients who have autoimmune or rheumatologic disease. Patients with autoimmune diseases tend to have various autoantibodies in their serum. These naturally present autoantibodies in this patient group could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these naturally occurring cross-reactive autoantibodies were present in the patient all along and are not related to bevacizumab or ranibizumab exposure.
c) Patients with evidence of active systemic infection. Patients with active systemic infection could have various antibodies in the serum, and some of these could cross-react with bevacizumab or ranibizumab. This would give the false impression that these patients have developed neutralizing antibodies against bevacizumab or ranibizumab, when in fact these cross-reactive antibodies were present in the patient secondary to the presence of active systemic infection and are not related to bevacizumab or ranibizumab.
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/30/2009