Treatment of choroidal subretinal neovascularization with immune agents

National Eye Institute

Investigators

Linked publications & trials

Abstract

As our population gets older, age related macular degeneration [unreadable] (AMD) will reach epidemic proportions in the United States. Therapies to [unreadable] date have focused on the anti-angiogenic therapy with mixed results. [unreadable] Recent studies would suggest that the immune system plays a significant [unreadable] role in the pathogenesis of AMD. The composition of drusen, one of the [unreadable] earliest clinical findings in AMD, have been extensively investigated. [unreadable] Complement, lipids, and lipoproteins B and E are commonly found in ocular [unreadable] drusen as they are in atherosclerotic plaques. Hageman et al have proposed [unreadable] that drusen are the product of a localized inflammatory response which [unreadable] would occur after retinal pigment epithelium injury. Recent reports have [unreadable] supported further the notion of the immune system playing a role (but yet [unreadable] to be fully defined) in AMD. The age related eye disease study (AREDS) [unreadable] evaluated the risk factors for the incidence of advanced age related [unreadable] macular degeneration and found that using anti-inflammatory medication [unreadable] significantly reduced (Odds Ratio 0.22, C.I. 0.08-0.59) the risk of [unreadable] developing the geographic atrophy form of AMD. Experimental models and [unreadable] patient material have, to date, suggested a role for macrophages and [unreadable] complement. We hypothesize that the underlying mechanism that leads to [unreadable] choroidal neovascularization (CNV) is similar to those at play in [unreadable] atherosclerosis. If this is the case, then CNV treatment should be [unreadable] amenable to new immunomodulatory agents directed against specific parts of [unreadable] the immune system.[unreadable] After therapy with anti-angiogenic agents not leading to a persistent [unreadable] remission of choroidal neovascularization due to age related macular [unreadable] degeneration, participants will be treated with one of three [unreadable] immunomodulatory agents or will be observed in conjunction with their [unreadable] continued anti-angiogenic therapy. Thus the participant will continue with [unreadable] the anti-angiogenic therapy they are receiving after randomization. We [unreadable] hypothesize that this combination therapy will inhibit progression of [unreadable] choroidal neovascularization (CNV) associated with age related macular [unreadable] degeneration (AMD).This is an open-label, phase II, randomized, single [unreadable] center clinical trial of 20 study participants randomized to receive one [unreadable] of three immunomodulatory agents or will be observed in conjunction with [unreadable] their anti-angiogenic therapy. Patients will be randomized to receive other [unreadable] rapamycin, daclizumab, remicade, or observation in conjunction with any [unreadable] anti-angiogenic therapy the treating physician deems necessary. Patients [unreadable] will be evaluated after 6 months of therapy. While recruitment has not yet been completed and numbers are small, trends may become evident in the near future.