Objective:

To summarize the current data and future directions for investigational tyrosine kinase inhibitors (TKIs) in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), highlighting their potential to address unmet needs.

Key Findings:

• Vorolanib, axitinib, and migaldendranib show potential for sustained therapy in nAMD and DME, with implications for long-term patient outcomes.
• Duravyu, a sustained-release intravitreal insert combining vorolanib, demonstrated noninferior vision outcomes compared to aflibercept, indicating its potential as a viable alternative.
• Significant reductions in treatment burden were observed with Duravyu, with many patients remaining injection-free for up to 6 months, enhancing patient quality of life.

Interpretation:

Investigational TKIs may provide a new therapeutic approach for retinal diseases, addressing limitations of current anti-VEGF therapies by offering sustained treatment options that could improve patient quality of life.

Limitations:

• Oral administration of TKIs was poorly tolerated in trials, leading to discontinuation, which raises concerns about patient adherence.
• Long-term safety and efficacy of TKIs in ophthalmology remain to be fully established, necessitating further research.

Conclusion:

The development of TKIs with novel mechanisms of action and sustained-release delivery systems could significantly improve treatment outcomes and patient adherence in retinal exudative diseases, addressing the critical issue of treatment burden.