Esther Kim, MD 

Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME

Summary of "Real World Treatment Strategies Using Next Generation Therapies for Neovascular AMD and DME"

This discussion among Dr Ehsan Rahimy, Dr David Miller, and Dr Michael Klufas covers practical strategies for managing neovascular AMD and DME with newer, more durable anti-VEGF therapies.

Real-world data supplements clinical trials by providing safety insights from larger patient populations

Clinical trials typically involve treatment-naive patients while physicians often use new agents in previously treated patients

Real-world practice often differs from trial protocols, especially regarding loading doses and switching therapies

For treatment-naive patients, physicians generally follow recommended loading doses to maximize vision gains

For previously treated patients switching to newer agents (faricimab, aflibercept 8 mg), complete reloading may not be necessary

Disease-specific considerations: AMD typically requires more strict adherence to loading protocols than DME

Both physicians have become more comfortable with 4-week extensions for DME patients

For neovascular AMD, especially in monocular patients, 1- to 2-week extensions remain standard practice due to risk of hemorrhage

Physicians note a sweet spot of 3- to 4-month intervals for most patients, as compliance drops significantly beyond this timeframe

Traditional 12-week caps are being reconsidered with newer agents

Some physicians now feel comfortable extending to 16 weeks in appropriate patients

For DME, extensions to 20 weeks may be appropriate, particularly when hemoglobin A

For neovascular AMD, most remain cautious about extending beyond 16 weeks due to monitoring concerns

Some patients prefer more frequent visits as a “security blanket” despite drug durability

Patient preferences and vision dependence should factor into treatment decisions

Physicians should balance optimal disease control with patient convenience

Extended intervals create challenges in monitoring fellow eyes for conversion

Home monitoring technologies (OCT) show promise but reimbursement and workflow concerns exist

Patient compliance decreases significantly with intervals beyond 4 months

When switching from aflibercept 2 mg to 8 mg, physicians typically see a 2- to 4-week extension in treatment intervals

Benefits of extension often improve over time rather than immediately after switching

Gene therapy shows promise, particularly subretinal injection approaches

Better geographic atrophy treatments remain an unmet need

Tyrosine kinase inhibitors may offer a balance between efficacy and delivery convenience

Suprachoroidal delivery for DME shows potential

This summary provides key clinical insights on treatment strategies using newer anti-VEGF agents, balancing protocol adherence with real-world considerations to optimize patient outcomes.

Videos

Ehsan Rahimy, MD; David G. Miller, MD; and Michael Klufas, MD, discuss how real-world treatment strategies for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) with next-generation anti-VEGF therapies differ from clinical trials, including individualized loading dose approaches, extension interval considerations, and the challenges of balancing durability with appropriate monitoring.

Real-World Treatment Strategies Using Next-Generation Therapies for Neovascular AMD and DME 

Podcasts

Drying, Durability, and Disease Control: Evolving Metrics of Anti-VEGF Success in Retinal Diseases 

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)

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

Treatment durability (extended intervals between injections)

Patient subjective experience and satisfaction

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

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

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.

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.

Esther Kim, MD

Articles