Complement Inhibitors for Advanced Dry Age-Related Macular Degeneration (Geographic Atrophy): Some Light at the End of the Tunnel?

Geographic atrophy (GA) affects around 5 million individuals worldwide. Genome-wide, histopathologic, in vitro and animal studies have implicated the activation of the complement system and chronic local inflammation in the pathogenesis of GA. Recently, clinical trials have demonstrated that an intr...

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Published inJournal of clinical medicine Vol. 12; no. 15; p. 5131
Main Authors Cruz-Pimentel, Miguel, Wu, Lihteh
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 04.08.2023
MDPI
Subjects
Atrophy
Clinical medicine
Clinical trials
Complement system
Drug therapy
Health aspects
Immune system
Immunosuppressive agents
Inflammation
Lectins
Macular degeneration
Photoreceptors
Proteins
Review
Canada
United States > US
C3
C5
geographic atrophy
cRORA
avacincaptad
iRORA
complement inhibitors
age-related macular degeneration
pegcetacoplan
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Summary:Geographic atrophy (GA) affects around 5 million individuals worldwide. Genome-wide, histopathologic, in vitro and animal studies have implicated the activation of the complement system and chronic local inflammation in the pathogenesis of GA. Recently, clinical trials have demonstrated that an intravitreal injection of pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, both statistically significantly reduce the growth of GA up to 20% in a dose-dependent fashion. Furthermore, the protective effect of both pegcetacoplan and avacincaptad appear to increase with time. However, despite these anatomic outcomes, visual function has not improved as these drugs appear to only slow down the degenerative process. Unexpected adverse events included conversion to exudative NV-AMD with both drugs. Occlusive retinal vasculitis and anterior ischemic optic neuropathy have been reported in pegcetacoplan-treated eyes.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
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ObjectType-Review-1
ISSN:2077-0383
2077-0383
DOI:10.3390/jcm12155131