Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY (2014) Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2:e106–e116. https://doi.org/10.1016/S2214-109X(13)70145-1

Article  PubMed  Google Scholar 

Deng Y, Qiao L, Du M, Qu C, Wan L, Li J, Huang L (2022) Age-related macular degeneration: epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy. Genes Dis 9:62–79. https://doi.org/10.1016/j.gendis.2021.02.009

Article  CAS  PubMed  Google Scholar 

Kwak N, Okamoto N, Wood JM, Campochiaro PA (2000) VEGF Is Major Stimulator in Model of Choroidal Neovascularization. Invest Ophthalmol Vis Sci 41:3158–3164

CAS  PubMed  Google Scholar 

Hood JD, Meininger CJ, Ziche M, Granger HJ (1998) VEGF upregulates ecNOS message, protein, and NO production in human endothelial cells. Am J Physiol Heart Circ Physiol 274:H1054–H1058. https://doi.org/10.1152/ajpheart.1998.274.3.H1054

Article  CAS  Google Scholar 

Maguire MG, Martin DF, Ying GS, Jaffe GJ, Daniel E, Grunwald JE, Toth CA, Ferris FL 3rd, Fine SL (2016) 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. Ophthalmology 123:1751–1761. https://doi.org/10.1016/j.ophtha.2016.03.045

Article  PubMed  Google Scholar 

Hosseini H, Rabina G, Pettenkofer M, Au A, Chehaibou I, Heilweil G, Weiner AJ, Ip M, Loewenstein A, Schwartz SD (2021) Clinical characteristics and visual outcomes of non-resolving subretinal fluid in neovascular AMD despite continuous monthly anti-VEGF injections: a long-term follow-up. Graefes Arch Clin Exp Ophthalmol 259:1153–1160. https://doi.org/10.1007/s00417-020-05024-9/Published

Article  CAS  PubMed  Google Scholar 

Lee A, Garg PG, Lyon AT, Mirza R, Gill MK (2020) Long-term outcomes of treat and extend regimen of anti-vascular endothelial growth factor in neovascular age-related macular degeneration. J Ophthalmic Vis Res 15:331–340. https://doi.org/10.18502/jovr.v15i3.7452

Article  PubMed  PubMed Central  Google Scholar 

Papapetropoulos A, García-Cardeña G, Madri JA, Sessa WC (1997) Nitric oxide mediates the actions of VEGF nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100:3131–3139. https://doi.org/10.1172/JCI119868

Article  CAS  PubMed  PubMed Central  Google Scholar 

Resch MD, Balogh A, Kurth T, Nagy ZZ, DeBuc DC, Papp A (2022) Atrophy of retinal vessels in neovascular age-related macular degeneration following long-term treatment with 20 intravitreal anti-VEGF injections. BMC Ophthalmol 22:469. https://doi.org/10.1186/s12886-022-02700-8

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mursch-Edlmayr AS, Luft N, Podkowinski D, Ring M, Schmetterer L, Bolz M (2020) Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy. Br J Ophthalmol 104:53–57. https://doi.org/10.1136/bjophthalmol-2019-313919

Article  PubMed  Google Scholar 

Hatamnejad A, Dadak R, Orr S, Wykoff C, Choudhry N (2023) Systematic review of efficacy and meta-analysis of safety of ranibizumab biosimilars relative to reference ranibizumab anti-VEGF therapy for nAMD treatment. BMJ Open Ophthalmol 8:e001205. https://doi.org/10.1136/bmjophth-2022-001205

Article  PubMed  PubMed Central  Google Scholar 

Mottet B, Aptel F, Geiser MH, Hera R, Zhou T, Almanjoumi A, Vinh V, Chiquet C (2018) Choroidal blood flow after the first intravitreal ranibizumab injection in neovascular age-related macular degeneration patients. Acta Ophthalmol 96:e783–e788. https://doi.org/10.1111/aos.13763

Article  CAS  PubMed  Google Scholar 

Nguyen QD, Das A, Do DV, Dugel PU, Gomes A, Holz FG, Koh A, Pan CK, Sepah YJ, Patel N, MacLeod H, Maurer P (2020) Brolucizumab: Evolution through preclinical and clinical studies and the implications for the management of neovascular age-related macular degeneration. Ophthalmology 127:963–976. https://doi.org/10.1016/j.ophtha.2019.12.031

Article  PubMed  Google Scholar 

Dugel PU, Singh RP, Koh A, Ogura Y, Weissgerber G, Gedif K, Jaffe GJ, Tadayoni R, Schmidt-Erfurth U, Holz FG (2021) HAWK and HARRIER: 96 week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 129:593–596

Google Scholar 

Holz FG, Dugel PU, Weissgerber G, Hamilton R, Silva R, Bandello F, Larsen M, Weichselberger A, Wenzel A, Schmidt A, Escher D, Sararols L, Souied E (2016) Single-Chain antibody fragment VEGF Inhibitor RTH258 for neovascular age-related macular degeneration: a randomized controlled study. Ophthalmology 123:1080–1089

Article  PubMed  Google Scholar 

Pignatelli F, Niro A, Passidomo F, Addabbo G (2021) Molecular structure, pharmacokinetics and clinical evidence of brolucizumab: a narrative review. Ann Eye Sci 6:37. https://doi.org/10.21037/aes-21-41

Article  Google Scholar 

Bird A, Bressler N, Bressler S, Chisholm IH, Coscas G, Davis MD, de Jong PT, Klaver CC, Klein BE, Klein R et al (1995) An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM epidemiological study group. Surv Ophthalmol 39:367–374. https://doi.org/10.1016/s0039-6257(05)80092-x

Article  CAS  PubMed  Google Scholar 

Guymer R, Wu Z (2020) Age-related macular degeneration (AMD): more than meets the eye. The role of multimodal imaging in today’s management of AMD-A review. Clin Exp Ophthalmol 48:983–995. https://doi.org/10.1111/ceo.13837

Article  PubMed  Google Scholar 

Kiyota N, Shiga Y, Ichinohasama K, Yasuda M, Aizawa N, Omodaka K, Honda N, Kunikata H, Nakazawa T (2018) The impact of intraocular pressure elevation on optic nerve head and choroidal blood flow. Invest Ophthalmol Vis Sci 59:3488–3496. https://doi.org/10.1167/iovs.18-23872

Article  CAS  PubMed  Google Scholar 

Sugiyama T, Araie M, Riva CE, Schmetterer L, Orgul S (2010) Use of laser speckle flowgraphy in ocular blood flow research. Acta Ophthalmol 88:723–729. https://doi.org/10.1111/j.1755-3768.2009.01586.x

Article  PubMed  Google Scholar 

Mallinckrodt CH, Clark WS, David SR (2001) Accounting for dropout bias using mixed-effects models. J Biopharm Stat 11:9–21. https://doi.org/10.1081/BIP-100104194

Article  CAS  PubMed  Google Scholar 

Lenth RV (2023) emmeans: estimated marginal means, aka least-squares means. The comprehensive R archive network. https://CRAN.R-project.org/package=emmeans. Accessed 11 January 2024

Posit team (2023) RStudio: integrated development environment for R. Posit. https://posit.co/downloads/. Accessed 11 January 2024

Asano T, Kunikata H, Yasuda M, Nishiguchi KM, Abe T, Nakazawa T (2021) Ocular microcirculation changes, measured with laser speckle flowgraphy and optical coherence tomography angiography, in branch retinal vein occlusion with macular edema treated by ranibizumab. Int Ophthalmol 41:151–162. https://doi.org/10.1007/s10792-020-01562-7

Article  PubMed  Google Scholar 

Shiga Y, Asano T, Kunikata H, Nitta F, Sato H, Nakazawa T, Shimura M (2014) Relative flow volume, a novel blood flow index in the human retina derived from laser speckle flowgraphy. Invest Ophthalmol Vis Sci 55:3899–3904. https://doi.org/10.1167/iovs.14-14116

Article  PubMed  Google Scholar 

Calzetti G, Mora P, Borrelli E, Sacconi R, Ricciotti G, Carta A, Gandolfi S, Querques G (2021) Short-term changes in retinal and choroidal relative flow volume after anti-VEGF treatment for neovascular age-related macular degeneration. Sci Rep 11:23723. https://doi.org/10.1038/s41598-021-03179-x

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hoshi K, Kunikata H, Aizawa N, Yasuda M, Okabe T, Takizawa H, Abe T, Nakazawa T (2023) Baseline characteristics associated with the incidence of intraocular inflammation after the intravitreous injection of brolucizumab. Int Ophthalmol 43:4701–4709. https://doi.org/10.1007/s10792-023-02870-4

Article  PubMed  Google Scholar 

Kato N, Haruta M, Furushima K, Arai R, Matsuo Y, Yoshida S (2023) Decrease in ocular blood flow 30 minutes after intravitreal injections of brolucizumab and aflibercept for neovascular age-related macular degeneration. Clin Ophthalmol 17:1187–1192. https://doi.org/10.2147/OPTH.S407249

Article  CAS  PubMed  PubMed Central  Google Scholar