Management of fibrosis in neovascular age-related macular degeneration

TL;DR

This paper reviews how fibrosis develops in a type of eye disease called neovascular age-related macular degeneration and how current treatments may not fully prevent it.

Contribution

The paper provides a comprehensive review of fibrosis mechanisms, risk factors, and treatment limitations in neovascular age-related macular degeneration.

Findings

Subretinal fibrosis is a late-stage complication of neovascular age-related macular degeneration linked to poor vision outcomes.

Current anti-VEGF therapies may reduce fibrosis severity but cannot prevent it entirely.

Optimizing anti-VEGF treatment and early detection can help minimize fibrosis risk.

Abstract

Subretinal fibrosis is a common end-stage sequela of neovascular age-related macular degeneration (nAMD), and it is associated with poor long-term visual outcomes. The pathogenesis of subretinal fibrosis in nAMD is largely driven by epithelial–mesenchymal and endothelial–mesenchymal transition within the retinal pigment epithelium and endothelium of the choroidal circulation. Upregulation of vascular endothelial growth factor (VEGF) expression further contributes to the observed fibrovascular content and increased vascular permeability. There is a substantial need for direct therapeutic strategies for fibrosis in nAMD, including anti-fibrotic agents. Until direct treatment strategies are developed, the management of nAMD using anti-VEGF agents must be optimized. However, fibrosis can occur in some patients otherwise successfully treated with anti-VEGF therapy, resulting in the loss of previous visual acuity (VA) gains experienced after treatment initiation. This review summarizes the current understanding of the mechanisms driving fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods. Available evidence on how different factors relating to anti-VEGF therapy (e.g., specific agent, delays in administration, extended administration intervals, dosing or treatment regimen) and the early detection of nAMD impact the risk of fibrosis is also discussed. Lastly, insights into potential future directions for the management of fibrosis in nAMD, particularly the development of anti-fibrotic agents, are deliberated.

Subretinal fibrosis is a common feature of late-stage neovascular age-related macular degeneration (nAMD) associated with poor long-term visual outcomes; current therapies may limit the severity of fibrosis but do not prevent its development

Subretinal fibrosis is a common feature of late-stage neovascular age-related macular degeneration (nAMD) associated with poor long-term visual outcomes; current therapies may limit the severity of fibrosis but do not prevent its development

This review summarizes the current understanding of the mechanisms of fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methodsThere are several risk factors associated with fibrosis development and anti-vascular endothelial growth factor therapies are the only treatment option for nAMD, and optimized use of such therapies can reduce the likelihood of fibrosis development in nAMDReducing incident fibrosis can help preserve visual acuity (VA) gains, through minimizing treatment delays and instituting appropriate monitoring strategies to ensure timely re-treatment in the event of reactivation of the nAMD lesion

This review summarizes the current understanding of the mechanisms of fibrosis in nAMD, risk factors for fibrosis development, and limitations of current detection methods

There are several risk factors associated with fibrosis development and anti-vascular endothelial growth factor therapies are the only treatment option for nAMD, and optimized use of such therapies can reduce the likelihood of fibrosis development in nAMD

Reducing incident fibrosis can help preserve visual acuity (VA) gains, through minimizing treatment delays and instituting appropriate monitoring strategies to ensure timely re-treatment in the event of reactivation of the nAMD lesion

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