Retinal and Retinal Pigment Epithelium (RPE) Autoimmunity in Age-related Macular Degeneration (AMD)
Condition: Age Related Macular Degeneration
MeSH terms: Macular Degeneration; Autoimmune Diseases
Intervention: ranibizumab (Lucentis(R))
Intervention description: 0.5 mg intravitreal injection once a month for 4 months, then as needed for 2 months
Intervention MeSH terms: Ranibizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Age Related Macular Degeneration; Lucentis; Ranibizumab; Antibodies; Retinal and RPE Autoimmunity

Summary:

      The investigators hope to determine if "wet" AMD patients differ from patients with "dry" AMD
      or normal eyes in the production of anti-retinal pigment epithelium (anti-RPE) or
      anti-retinal antibody formation. To explain: the immune system can make antibodies that
      attack our own cells, specifically the RPE and the retina. Normally the RPE and retinal cells
      are ignored by the immune system, but when disease occurs, immune reactions can occur, making
      an autoantibody that can attack the patient's own cells and make things worse. This
      production of autoantibodies that react with our own RPE and retinal cells is what the
      investigators want to test in this proposal to see if they may contribute to, or are
      responsible for, a poor response to treatment.

      The investigators also want to know how those patients who initially respond to the
      standard-of-care treatment, ranibizumab injections, differ in the production of anti-RPE or
      anti-retinal antibody formation, from those patients who do not respond initially after 4
      consecutive injections.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Group 1 (Ranibizumab Responders):

               -  Ability to provide written informed consent and comply with study assessments for
                  the full duration of the study

               -  Age > 50 years

               -  Patients with active neovascular "wet" AMD naïve to treatment

          -  Group 2 (Normal Controls):

               -  Age-sex-race matched to Group 1 patients

               -  Non-AMD

               -  Ability to provide written informed consent

          -  Group 3 (Anti-VEGF Initial Non-responders):

               -  "Wet" AMD patient treated with 4 or more monthly injections of anti-VEGF
                  treatment without an adequate response (persistent fluid on OCT)

               -  Ability to provide written informed consent and comply with study assessments for
                  the full duration of the study

               -  Age > 50 years

          -  Group 4 ("Dry" AMD):

               -  Age-sex-race matched to Group 1 patients

               -  "Dry" AMD, category 2 or 3 by AREDS (Age-Related Eye Disease Study) criteria

               -  Ability to provide written informed consent

        Exclusion Criteria:

          -  Pregnancy (positive pregnancy test) or lactation

          -  Premenopausal women not using adequate contraception. The following are considered
             effective means of contraception: surgical sterilization or use of oral
             contraceptives, barrier contraception with either a condom or diaphragm in conjunction
             with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

          -  Any other condition that the investigator believes would pose a significant hazard to
             the subject if the investigational therapy were initiated

          -  Participation in another simultaneous medical investigation or trial

          -  Concurrent eye disease in the study eye that could compromise visual acuity (e.g.,
             diabetic retinopathy, advanced glaucoma)

          -  Previous AMD therapy

          -  Patients being treated for autoimmune or other disease with immunomodulatory drugs
             (i.e., prednisone, infliximab, methotrexate)

          -  Patients with recent (less than 6 months) ocular or systemic surgery