title: A randomized pilot study of systemic immunosuppression in the treatment of age-related macular degeneration with choroidal neovascularization.
abstract: BACKGROUND
  Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti–vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration.
  
  
  METHODS
  This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated.
  
  
  RESULTS
  The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups.
  
  
  CONCLUSIONS
  These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated.
authors.affiliation: Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. drbob@nei.nih.gov
authors.forename: Robert B
authors.initials: RB
authors.lastname: Nussenblatt
authors.forename: Gordon
authors.initials: G
authors.lastname: Byrnes
authors.forename: H Nida
authors.initials: HN
authors.lastname: Sen
authors.forename: Steven
authors.initials: S
authors.lastname: Yeh
authors.forename: Lisa
authors.initials: L
authors.lastname: Faia
authors.forename: Catherine
authors.initials: C
authors.lastname: Meyerle
authors.forename: Keith
authors.initials: K
authors.lastname: Wroblewski
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Li
authors.forename: Baoying
authors.initials: B
authors.lastname: Liu
authors.forename: Emily
authors.initials: E
authors.lastname: Chew
authors.forename: Patti R
authors.initials: PR
authors.lastname: Sherry
authors.forename: Penelope
authors.initials: P
authors.lastname: Friedman
authors.forename: Fred
authors.initials: F
authors.lastname: Gill
authors.forename: Frederick
authors.initials: F
authors.lastname: Ferris
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000503:physiopathology; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000069285:Infliximab; D007262:Infusions, Intravenous; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D020123:Sirolimus / Q000627:therapeutic use; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D014792:Visual Acuity / Q000502:physiology; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069285:Infliximab; D000077561:Daclizumab; D020123:Sirolimus