Objective:

To explore the potential of complement inhibition as a therapeutic strategy for slowing the progression of geographic atrophy (GA) associated with age-related macular degeneration (AMD), which significantly impacts patient vision and quality of life.

Key Findings:

• Complement dysregulation is implicated in GA and AMD progression, highlighting the need for targeted therapies.
• Pegcetacoplan slows GA growth but does not significantly improve secondary visual function endpoints, indicating a need for further research on functional outcomes.
• There is a dose-dependent risk of developing neovascular AMD with pegcetacoplan treatment, necessitating careful patient selection and monitoring.

Interpretation:

Complement inhibition represents a novel approach to managing GA, with the potential to improve patient outcomes despite some associated risks, emphasizing the importance of weighing benefits against potential adverse effects.

Limitations:

• OAKS and DERBY trials did not show significant visual function improvements, raising questions about the overall impact on patient quality of life.
• Risk of neovascular AMD and retinal vasculitis associated with pegcetacoplan treatment underscores the need for vigilant monitoring and patient education.

Conclusion:

Complement inhibitors may offer a new therapeutic avenue for GA, but careful monitoring for adverse effects is necessary, and ongoing research is essential to fully understand their long-term impact.