The role of anti-inflammatory agents in age-related macular degeneration (AMD) treatment

Abstract

Although age-related macular degeneration (AMD) is not a classic inflammatory disease like uveitis, inflammation has been found to have an important role in disease pathogenesis and progression. Innate immunity and autoimmune components, such as complement factors, chemokines, cytokines, macrophages, and ocular microglia, are believed to be heavily involved in AMD development. Targeting these specific inflammatory molecules has recently been explored in an attempt to better understand and treat AMD. Although antivascular endothelial growth factor therapy is the first line of defence against neovascular AMD, anti-inflammatory agents such as corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents (eg, methotrexate and rapamycin), and biologics (eg, infliximab, daclizumab, and complement inhibitors) may provide an adjunct or alternative mechanism to suppress the inflammatory processes driving AMD progression. Further investigation is required to evaluate the long-term safety and efficacy of these drugs for both neovascular and non-neovascular AMD. Two clinically recognized subtypes of AMD are non-neovascular geographic atrophic ('dry') AMD and neovascular exudative ('wet') AMD. Non-neovascular AMD is characterized by the accumulation of lipo-glyco-proteinaceous deposits (drusen) as well as the degeneration of the retinal pigment epithelium (RPE) and photoreceptors. Geographic atrophy (GA) accompanies the advanced form of non-neovascular AMD and results in RPE atrophy, degeneration of the outer retinal layer, and sclerosis of choriocapillaris. Choroidal neovascularization (CNV) is the hallmark of neovascular AMD, which affects the choroid/ Bruch's membrane/RPE complex and leads to exudation and bleeding within the macula. Disciform scarring, characterized by predominantly fibrotic tissue, few remaining neovascular lumens, and neural tissue loss, is often present during the late stages of neovascular AMD. Although neovascular AMD accounts for only 10-20% of total AMD cases, it is responsible for the sudden and severe vision loss in the majority of AMD patients. 4 In contrast, GA, the end-stage of non-neovascular AMD, usually results in gradual and less severe loss of vision.

Common coding variants in the HLA-DQB1 region confer susceptibility to age-related macular degeneration

“…[1][2][3][4] Immune response and inflammation play a causal role in the pathogenesis and progression of AMD. [5][6][7][8][9][10][11] The human leukocyte antigen (HLA) region on chromosome 6p21.31 encodes gene products that regulate immune response. Drusen, a pathologic hallmark of AMD, contain HLA class II antigens, 12 and increased HLA class II immunoreactivity has been associated with drusen formation, 13 suggesting that HLA may influence the development of AMD.…”

Efficacy and Safety of Combined Intravitreal Bevacizumab and Retrobulbar Corticosteroids for Neovascular Age-Related Macular Degeneration

“…The rationale for the use of corticosteroids in CNV therapy lies in the well-proven role of inflammation in the pathogenesis and progression of AMD [6,22].…”

“…Inflammatory cells and cytokines play an important role in AMD pathogenesis and progression [6]. In addition to the anti-inflammatory effects, corticosteroids reduce the permeability of choroidal endothelial cells and suppress VEGF expression [7].…”

Amžinės geltonosios dėmės degeneracijos gydymas: dabartinis požiūris (literatūros apžvalga)

“…Atliekama daug klinikinių studijų, kurios padėtų išsiaiškinti šiuos aspektus [69]. Taip pat kuriami nauji farmakologiniai preparatai, kurių veikimo mechanizmas būtų panašus į KEAF preparatą ranibizumabą.…”