Triangular relationships might make life interesting, but they can be hard to untangle. In this issue of JAMA Ophthalmology, Cipriani et al1 have conducted an elegant study examining the triangular association between circulating concentrations of C-reactive protein (CRP), CRP (OMIM 123260) genetic variants, and risk of late age-related macular degeneration (AMD) (choroidal neovascularization or central geographic atrophy). Their findings have important implications for our understanding of the pathophysiology of AMD, particularly the distinction between systemic and local inflammation.