1 Congdon, N. et al. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol122, 477-485, doi:10.1001/archopht.122.4.477 (2004).
2 Wong, W. L. et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health2, e106-e116, doi:https://doi.org/10.1016/S2214-109X(13)70145-1 (2014).
3 Cheung, C. M. G. et al. Pachychoroid disease. Eye (Lond)33, 14-33, doi:10.1038/s41433-018-0158-4 (2019).
4 Klein, R. J. et al. Complement factor H polymorphism in age-related macular degeneration. Science308, 385-389, doi:10.1126/science.1109557 (2005).
5 Zhou, J., Jang, Y. P., Kim, S. R. & Sparrow, J. R. Complement activation by photooxidation products of A2E, a lipofuscin constituent of the retinal pigment epithelium. Proc Natl Acad Sci U S A103, 16182-16187, doi:0604255103 [pii]10.1073/pnas.0604255103 (2006).
6 Nozaki, M. et al. Drusen complement components C3a and C5a promote choroidal neovascularization. Proc Natl Acad Sci U S A103, 2328-2333, doi:10.1073/pnas.0408835103 (2006).
7 Hugli, T. Biochemistry and Biology of Anaphylatoxins. Complement3, 111-127, doi:10.1159/000467889 (1986).
8 Schick, T. et al. Local complement activation in aqueous humor in patients with age-related macular degeneration. Eye (Lond)31, 810-813, doi:10.1038/eye.2016.328 (2017).
9 Maguire, M. G. et al. Five-Year Outcomes with Anti-Vascular Endothelial Growth Factor Treatment of Neovascular Age-Related Macular Degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology123, 1751-1761, doi:10.1016/j.ophtha.2016.03.045 (2016).
10 Datta, S., Cano, M., Ebrahimi, K., Wang, L. & Handa, J. T. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res60, 201-218, doi:10.1016/j.preteyeres.2017.03.002 (2017).
11 Starita, C., Hussain, A. A., Pagliarini, S. & Marshall, J. Hydrodynamics of ageing Bruch's membrane: implications for macular disease. Exp Eye Res62, 565-572, doi:10.1006/exer.1996.0066 (1996).
12 Sohn, E. H. et al. Choriocapillaris Degeneration in Geographic Atrophy. Am J Pathol189, 1473-1480, doi:10.1016/j.ajpath.2019.04.005 (2019).
13 Paraoan, L. et al. Secretory proteostasis of the retinal pigmented epithelium: Impairment links to age-related macular degeneration. Prog Retin Eye Res, 100859, doi:10.1016/j.preteyeres.2020.100859 (2020).
14 Kurihara, T., Westenskow, P. D., Bravo, S., Aguilar, E. & Friedlander, M. Targeted deletion of Vegfa in adult mice induces vision loss. J Clin Invest122, 4213-4217, doi:10.1172/JCI65157 (2012).
15 Xu, L. et al. Geographic atrophy in patients receiving anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Retina35, 176-186, doi:10.1097/iae.0000000000000374 (2015).
16 Young, M. et al. Exacerbation of choroidal and retinal pigment epithelial atrophy after anti-vascular endothelial growth factor treatment in neovascular age-related macular degeneration. Retina34, 1308-1315, doi:10.1097/iae.0000000000000081 (2014).
17 Chen, G. et al. Pharmacogenetics of Complement Factor H Y402H Polymorphism and Treatment of Neovascular AMD with Anti-VEGF Agents: A Meta-Analysis. Scientific reports5, 14517, doi:10.1038/srep14517 (2015).
18 Sato, T., Takeuchi, M., Karasawa, Y., Takayama, K. & Enoki, T. Comprehensive expression patterns of inflammatory cytokines in aqueous humor of patients with neovascular age-related macular degeneration. Scientific reports9, 19447, doi:10.1038/s41598-019-55191-x (2019).
19 Keir, L. S. et al. VEGF regulates local inhibitory complement proteins in the eye and kidney. J Clin Invest127, 199-214, doi:10.1172/jci86418 (2017).
20 Ferris, F. L. et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Archives of ophthalmology123, 1570-1574, doi:10.1001/archopht.123.11.1570 (2005).
21 Pang, C. E. & Freund, K. B. Pachychoroid neovasculopathy. Retina35, 1-9, doi:10.1097/iae.0000000000000331 (2015).
22 Terao, N. et al. Distinct Aqueous Humour Cytokine Profiles of Patients with Pachychoroid Neovasculopathy and Neovascular Age-related Macular Degeneration. Scientific reports8, 10520, doi:10.1038/s41598-018-28484-w (2018).
23 Hara, C. et al. Tachyphylaxis during treatment of exudative age-related macular degeneration with aflibercept. Graefes Arch Clin Exp Ophthalmol257, 2559-2569, doi:10.1007/s00417-019-04456-2 (2019).
24 Koike, N. et al. Results of switchback from ranibizumab to aflibercept in patients with exudative age-related macular degeneration. Clin Ophthalmol13, 1247-1251, doi:10.2147/opth.S206910 (2019).
25 Luo, C., Chen, M. & Xu, H. Complement gene expression and regulation in mouse retina and retinal pigment epithelium/choroid. Mol Vis17, 1588-1597 (2011).
26 Sakamoto, S. et al. Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy. Br J Ophthalmol102, 448-454, doi:10.1136/bjophthalmol-2017-310284 (2018).
27 Dansingani, K. K., Balaratnasingam, C., Klufas, M. A., Sarraf, D. & Freund, K. B. Optical Coherence Tomography Angiography of Shallow Irregular Pigment Epithelial Detachments In Pachychoroid Spectrum Disease. Am J Ophthalmol160, 1243-1254.e1242, doi:10.1016/j.ajo.2015.08.028 (2015).
28 Voigt, A. P. et al. Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration. Proc Natl Acad Sci U S A116, 24100-24107, doi:10.1073/pnas.1914143116 (2019).
29 Zeng, S. et al. Molecular response of chorioretinal endothelial cells to complement injury: implications for macular degeneration. J Pathol238, 446-456, doi:10.1002/path.4669 (2016).
30 Maruko, I. et al. Two-Year Outcomes of Treat-and-Extend Intravitreal Aflibercept for Exudative Age-Related Macular Degeneration: A Prospective Study. Ophthalmology retina4, 767-776, doi:10.1016/j.oret.2020.03.010 (2020).
31 Itagaki, K. et al. Three-year outcome of aflibercept treatment for Japanese patients with neovascular age-related macular degeneration. BMC ophthalmology20, 276, doi:10.1186/s12886-020-01542-6 (2020).
32 Fauser, S., Schwabecker, V. & Muether, P. S. Suppression of intraocular vascular endothelial growth factor during aflibercept treatment of age-related macular degeneration. Am J Ophthalmol158, 532-536, doi:10.1016/j.ajo.2014.05.025 (2014).
33 Omori, T. et al. Evidence for Activation of Lectin and Classical Pathway Complement Components in Aqueous Humor of Neovascular Age-Related Macular Degeneration. Ophthalmic Res, 1-7, doi:10.1159/000503258 (2019).
34 Pober, J. S. Activation and injury of endothelial cells by cytokines. Pathol Biol (Paris)46, 159-163 (1998).
35 Carneiro, A., Falcão, M., Azevedo, I., Falcão Reis, F. & Soares, R. Multiple effects of bevacizumab in angiogenesis: implications for its use in age-related macular degeneration. Acta Ophthalmol87, 517-523, doi:10.1111/j.1755-3768.2008.01257.x (2009).
36 Basiglio, C. L. et al. Complement activation and disease: protective effects of hyperbilirubinaemia. Clin Sci (Lond)118, 99-113, doi:10.1042/cs20080540 (2009).
37 Williams, P. D., Chong, D., Fuller, T. & Callanan, D. Noninfectious vitritis after intravitreal injection of anti-vegf agents: variations in rates and presentation by medication. Retina36, 909-913, doi:10.1097/iae.0000000000000801 (2016).
38 Baumal, C. R. et al. Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab. Ophthalmology, doi:10.1016/j.ophtha.2020.04.017 (2020).
39 Greenberg, J. P. et al. Aflibercept-Related Sterile Intraocular Inflammation Outcomes. Ophthalmology retina3, 753-759, doi:10.1016/j.oret.2019.04.006 (2019).
40 Kunimoto, D. et al. Evaluation of Abicipar Pegol (an Anti-VEGF DARPin Therapeutic) in Patients With Neovascular Age-Related Macular Degeneration: Studies in Japan and the United States. Ophthalmic surgery, lasers & imaging retina50, e10-e22, doi:10.3928/23258160-20190129-13 (2019).
41 Yanagi, Y. Pachychoroid disease: a new perspective on exudative maculopathy. Jpn J Ophthalmol64, 323-337, doi:10.1007/s10384-020-00740-5 (2020).
42 Takahashi, H. et al. Vascular Endothelial Growth Factor (VEGF) Concentration Is Underestimated by Enzyme-Linked Immunosorbent Assay in the Presence of Anti-VEGF Drugs. Invest Ophthalmol Vis Sci57, 462-466, doi:10.1167/iovs.15-18245 (2016).