Pilot Study of Ranibizumab (Lucentis) for Uveitic Cystoid Macular Edema
Condition: Uveitic Cystoid Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: ranibizumab
Intervention description: This is an open-label, Phase I study of intravitreally administered 0.5mg ranibizumab in subjects with uveitic CME.
Intervention MeSH terms: Ranibizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Uveitis; Cystoid Macular Edema

Summary:

      Uveitic Cystoid Macular Edema (CME) is a major cause of visual loss associated with uveitis.
      Systemic and/or local corticosteroid therapy and systemic immunosuppression with
      steroid-sparing agents such as cyclosporine, methotrexate, azathioprine, or others,
      effectively treats uveitis and associated CME in many patients. However, in many cases, CME
      persists in spite of adequate suppression of uveitis. No consensus exists on how best to
      treat such cases. The further addition of immunosuppressive agents appears to have little
      effect on this form of CME. Oral corticosteroids are useful, but high dosage and prolonged
      use can be associated with serious side-effects. Periocular and intravitreal corticosteroid
      injections are associated with well-known, significant side effects such as glaucoma and
      cataract formation.

      Vascular endothelial growth factor (VEGF) is suspected to play a role in the loss of vascular
      integrity in the eye and known to be induced by inflammatory cytokines, such as interleukin
      interleukin (IL)-1β and IL-6, which are elevated intraocularly in uveitis. In addition, it
      has been demonstrated that aqueous VEGF concentrations are statistically significantly higher
      in those uveitis patients with CME than those without CME. Inhibition of inappropriate VEGF
      activity is a potential approach to treatment of CME in uveitis given our current knowledge
      of the pathophysiology of this condition and also because of the clinical need for additional
      treatment options for these patients. Ranibizumab, a recombinant, humanized monoclonal
      antibody antigen-binding fragment (Fab) that neutralizes all active forms of VEGF-A, would
      target this pathway and may be useful in cases of persistent CME in uveitis patients.

      The objective of this study is to determine if an anti-VEGF agent, Lucentis, is safe and
      effective in leading to regression of macular edema due to chronic non-infectious uveitis in
      patients with well-controlled uveitis.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects will be eligible if the following criteria are met:

          1. Ability to provide written informed consent and comply with study assessments for the
             full duration of the study.

          2. Age > 18 years

          3. Non-infectious uveitis in study eye.

          4. Stable anti-uveitis medical regimen for at least one month prior to injection and
             controlled uveitis in the judgment of the investigator.

          5. Vision 20/40 or worse in study eye.

          6. Cystoid Macular Edema (CME) on fluorescein angiography (FA)

          7. Optical Coherence Tomography (OCT) demonstrating thickness greater than 300 microns in
             the central subfield.

          8. Media clarity, pupillary dilation and patient cooperation sufficient to allow OCT
             testing and retinal photography.

        Only one eye will be assessed in the study. If both eyes are eligible, the investigator
        will determine which eye will be entered into the study.

        Exclusion Criteria:

          1. Previous intravitreal triamcinolone injection in study eye within 3 months of study
             injection.

          2. Use of more than two glaucoma medicines for study eye.

          3. Significant epiretinal membrane as judged by treating physician.

          4. Evidence of vitreomacular traction on OCT.

          5. Previous vitrectomy in study eye.

          6. Pregnancy (positive pregnancy test) or lactation.

          7. 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 intrauterine device (IUD), or contraceptive hormone implant
             or patch.

          8. Any other condition that the investigator believes would pose a significant hazard to
             the subject if the investigational therapy were initiated.

          9. Participation in another simultaneous IND trial.

         10. Treatment for CME with intravitreal Lucentis, Macugen, or Avastin within 6 weeks prior
             to enrollment in this study.

         11. Uncontrolled inflammation in the study eye.

         12. Current vitreous hemorrhage.

         13. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either
             eye.

         14. Known allergy to any component of the study drug.

         15. Intraocular pressure > 25 mm Hg despite treatment with glaucoma medications.

         16. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood
             pressure is brought below 180/110 by anti-hypertensive treatment, the subject can
             become eligible.

         17. Major non-ocular surgery planned during the next 6 months.

         18. Any other condition that the investigator believes would pose a significant hazard to
             the subject if the investigational therapy were initiated.

         19. No Avastin use permitted in fellow eye during study.

         20. Unwilling or unable to follow or comply with all study related procedures