Beyond VEGF
DME and nAMD are multifactorial diseases driven by various signalling pathways, with factors other than VEGF involved in pathogenesis.

Opportunities to optimise outcomes in the real world
Real-world analyses of >78,000 patient eyes have shown that patients with DME or nAMD tend to receive fewer anti-VEGF injections in clinical practice compared with clinical trials, and may fall short of efficacy expectations, potentially leading to suboptimal vision.1,2
Real-world injection frequency correlates with vision improvement
nAMD
Reprinted from Ophthalmology Retina, 4(1), Ciulla TA, et al., Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis of 49485 eyes, 19–30, Copyright (2020), with permission from Elsevier.
DME
Reproduced from Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28658 eyes, Ciulla TA, et al. 0:1–6, Copyright (2020), with permission from BMJ Publishing Group Ltd
Beyond VEGF: Signalling pathways in vascular instability
DME and nAMD are multifactorial diseases3,4 driven by vascular instability, characterised by vascular leakage, inflammation, and neovascularisation.5
Multiple signalling pathways, including the Ang–Tie pathway, work together to contribute to this vascular instability, and are stimulated by conditions of cellular stress.5,6
Clinical relevance of angiopoietins
What happens to Ang-1 and Ang-2 levels in retinal diseases?

AMD, age-related macular degeneration; Ang, angiopoietin; DME, diabetic macular edema; DR, diabetic retinopathy; IVT, intravitreal; nAMD, neovascular age-related macular degeneration; PDR, proliferative diabetic retinopathy; RVO, retinal vein occlusion; Tie, tyrosine kinase with immunoglobulin-like domains; VEGF, vascular endothelial growth factor.
References
- Ciulla TA, et al. Ophthalmol Retina. 2020;4:19–30
- Ciulla TA, et al. Br J Ophthalmol. 2021;105:216–21
- Chakravarthy U, et al. Retina. 2018;38:343–51
- Swaroop A, et al. Annu Rev Genomics Hum Genet. 2009;10:19–43
- Joussen AM, et al. Eye. 2021;35:1305–16
- Saharinen P, et al. Nat Rev Drug Discov. 2017;16:635–61
- Regula JT, et al. EMBO Mol Med. 2016;8:1265–88
- Regula JT, et al. EMBO Mol Med. 2019;11:e10666