Optimizing nAMD and DME Treatment: Real-World Durability, and Fluid Outcomes with Second Generation Anti-VEGF Agents - Episode 4
Drying, Durability, and Disease Control: Evolving Metrics of Anti-VEGF Success in Retinal Diseases
Ehsan Rahimy, MD; David G. Miller, MD; and Esther Kim, MD, discuss how achieving retinal drying through anti-VEGF therapies remains a critical marker of treatment success in retinal diseases such as AMD and DME, while highlighting the benefits of newer agents such as aflibercept 8 mg and faricimab for providing better durability and sustained disease control with reduced treatment burden.
Summary: Retinal Drying and Disease Control in Anti-VEGF Therapy
This summary covers key points from a discussion between retina specialists Ehsan Rahimy, MD; Esther Kim, MD; and David G. Miller, MD, on anti-VEGF therapy for retinal diseases.
Importance of Retinal Drying in Treatment
- Retinal drying is a critical marker of treatment effectiveness as it correlates with better vision outcomes.
- Anatomy and drying effect serve as surrogate markers for vision due to challenges with reproducibility of visual acuity (VA) testing.
- Tolerance for residual fluid varies based on:
- Type of fluid (intraretinal vs subretinal)
- Disease state (age-related macular degeneration [AMD] vs diabetic macular edema [DME])
- Location of fluid (foveal vs extrafoveal)
Fluid Management Considerations
- Intraretinal fluid is generally considered worse for visual prognosis than subretinal fluid.
- Some subretinal fluid may be protective as “the retina’s attempt to heal itself.”
- For new patients, specialists typically aim for complete drying initially to establish baseline best potential vision.
- In DME, specialists may tolerate some intraretinal fluid outside the fovea with VA of 20/25 or better
Sustained Disease Control
Encompasses 4 key components:
- Retinal drying/fluid eradication
- Vision stabilization or improvement
- Treatment durability (extended intervals between injections)
- Patient subjective experience and satisfaction
Next-Generation Anti-VEGF Agents
Aflibercept 8 mg
Demonstrated improved durability compared with 2-mg formulation
- Quartile analysis from PHOTON trial showed less CST rebound despite fewer loading doses
- May provide “security blanket” for patients who miss appointments
- Label restricts minimum dosing interval to 7-8 weeks
Faricimab
- Offers dual mechanism targeting both VEGF and Ang-2 pathways
- Post hoc analyses suggest potential antifibrotic effects and reduced vascular leakage
- Allows more flexible dosing including q4 week intervals for recalcitrant cases
- May be particularly beneficial for patients with diffuse, spongy DME or cases with subretinal fibrosis
Treatment Approach Evolution
- Specialists increasingly favor using the most potent agents first line rather than starting with less expensive options
- “Why bench LeBron?” analogy: Using your best player from the beginning rather than saving them
- A trial showed high percentage of bevacizumab patients eventually needed to switch to more effective agents
- Starting with newer agents may reduce overall treatment burden and number of injections over time
Patient Variability and Setting Expectations
- Clinical trials show many patients can extend to 12- to 16-week intervals, but real-world experience shows significant variability.
- Biomarkers for predicting durability response remain elusive.
- When introducing therapy, specialists recommend:
- Focusing on loading doses before discussing long-term plans
- Maintaining hope about extending intervals where possible
- Mentioning ongoing research in gene therapy and implants
- Avoiding overwhelming patients with “forever” treatment projections
This discussion highlights the evolution toward treating with the most effective and durable agents available early in the disease course while individualizing fluid tolerance based on disease state and location.
