Abstract
Purpose: :
The efficacy of "wet" AMD treatment may be limited by secondary and superimposed inflammatory reactions to the retina or retinal pigment epithelium (RPE). Therefore we hypothesize that exudative AMD patients that do not respond to anti-vascular endothelial growth factor (VEGF) therapy may have increase inflammatory reactions to the retina and RPE. We examined both dry (40) and wet (30) AMD patients and correlated serum anti-retinal and anti-RPE reactions to AMD disease and response to therapy.
Methods: :
Serum samples were collected from patients in 4 categories: normal (30 patients), non-exudative AMD (40 patients), and exudative AMD (30 patients) including poor-responder to anti-VEGF therapy. Patients with exudative AMD were enrolled for 6 months of anti-VEGF (randibizumab) therapy and serum was collected at on enrollment and at months 3 and 6. Poor-responders were defined as those patients with residual cystoid macular edema or subretinal fluid at month 4 and having less than 100 microns improvement of central retinal thickness by OCT. Western blot reactions on extracts of pig retina and in vitro cultivated human retinal pigment epithelium (ATCC ARPE-19) were used in the evaluations of patient’s antibody activity with the protein components of these tissues.
Results: :
We found a series of abnormal antibody reactions to both retinal and RPE protein antigens correlating with exudative AMD and poor-response to therapy. In addition, specific reactions were noted that were previously described by others as being associated with, or suspected of being associated with immune-mediated loss of vision.
Conclusions: :
Evidence of abnormal immunological activity within the eyes of treatment-refractive AMD patients may explain their failure to respond to conventional treatments is due to immunological complications suspected to be autoimmune in nature. Modifying treatments to accommodate these findings could prove beneficial in some cases of refractory AMD, especially with those involving abnormal antibody activity with recognized ocular autoantigens.
Keywords: age-related macular degeneration • immunomodulation/immunoregulation • vitreous