Livestream: Beyond VEGF: Understanding Blood-Retinal Barrier Biology and Emerging Mechanisms in DME and Neovascular AM

Anti-vascular endothelial growth factor (anti-VEGF) therapy transformed the management of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD), but it has not solved either disease. Roughly 40% to 60% of patients with DME and 40% to 50% with nAMD never achieve or cannot sustain an optimal response, leaving them with persistent fluid, progressive vision loss, and an injection burden few can maintain. The explanation is coming into focus: breakdown of the blood-retinal barrier (BRB) drives the vascular leakage behind vision loss in both diseases, and VEGF-A suppression alone does not directly address it. The therapeutic response has been swift. Dual VEGF-A/angiopoietin-2 (Ang-2) inhibition has already validated multi-pathway targeting in the clinic, and agents aimed at Wingless integration site (Wnt)/β-catenin and Tunica internal endothelial cell kinase 2 (Tie2)/angiopoietin signaling are now in pivotal trials.

This CME Outfitters livestream symposium at American Academy of Ophthalmology (AAO) 2026 will ground learners in the biology of BRB breakdown, weigh the mechanistic rationale behind therapies designed to restore barrier stability, and share practical strategies for recognizing and managing the anti-VEGF incomplete responder, essential context for retina specialists, ophthalmologists, optometrists, and the teams who care for these patients.

At the conclusion of this activity, learners will be able to better:

• Evaluate the cellular and molecular mechanisms by which BRB breakdown drives vascular leakage and vision loss in DME and nAMD
• Assess the mechanistic rationale for emerging therapeutic approaches targeting BRB stability and vascular regulation in DME and nAMD
• Identify patients with DME or nAMD who demonstrate suboptimal anti-VEGF response to inform timely evidence-based management strategies

This activity is supported through an independent educational grant from Merck & Co., Inc., Rahway, NJ, USA.

Retina specialists and other ophthalmologists; optometrists and allied healthcare professionals (HCPs) w/medical retina interest

It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all of their CE activities. Faculty must disclose to the participants any relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CE activity. CME Outfitters, LLC, has evaluated, identified, and mitigated any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/research, and a multidisciplinary peer review process. The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

Dr. Avery reports the following financial relationships:

Consultant: 4D Molecular Therapeutics (4DMT); AbbVie Inc.; Adverum Biotechnologies, Inc.; Alcon Inc.; Allergan Aesthetics; Amgen Inc.; Apellis Pharmaceuticals; Asclepix Therapeutics; Astellas Pharma Inc.; Aviceda Therapeutics; Bausch + Lomb; Belite Bio Inc; Cardinal Health; Clearside Biomedical; Coherus BioSciences; EyeBio; EyePoint, Inc.; ForwardVue Pharma; Genentech, Inc,; Ikarovec; Imprimis; INGENIA Therapeutics; Kriya Therapeutics; KYS Vision, Inc.; Merck & Co., Inc.; Merit; Nanoscope Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Nvasc, Inc.; Ocular Therapeutix, Inc.; Ocugen, Inc.; Ocugenix; Opthea; Optigo Biotherapeutics Inc.; Outlook Therapeutics, Inc.; Pixium Vision; Pr3vent AI; PulseMedica; Regeneron Pharmaceuticals Inc.; Regenxbio Inc.; Replenish, Inc.; RetInSight; Re-Vana Therapeutics; Roche; Tenpoint Therapeutics; and Thea Pharma Inc.

Research Support: Adverum Biotechnologies, Inc.; Genentech, Inc.; Regeneron Pharmaceuticals Inc.; Rehenxbio, Inc.; and RetInSight

Speakers Bureau: Genentech, Inc.

Stock Shareholder (ownership interest): 4D Molecular Therapeutics (4DMT); AbbVie Inc.; Adverum Biotechnologies, Inc.; Alcon; Aviceda Therapeutics; EyePoint Inc.; ForwardVue Pharma; INGENIA Therapeutics; KYS Vision, Inc.; Nanoscope. Therapeutics, Inc.; Novartis Pharmaceuticals Corporation; Nvasc, Inc.; Ocular Therapeutix, Inc.; PulseMedica; Regeneron Pharmaceuticals Inc.; Replenish, Inc.; and ReVana Therapeutics

Other financial or material support: Patents, Royalties: Replenish, Inc.

Dr. Singh reports the following financial relationships:

Advisory Board: EyePoint Pharmaceuticals Inc. and Ollin Biosciences, Inc.

Consultant: AbbVie Inc.; Alcon Inc.; Apellis Pharmaceuticals; Astellas Pharma Inc./Iveric Bio, Inc.; Bausch + Lomb; Carl Zeiss Meditec AG; Genentech, Inc./Roche; Harrow; Ocular Therapeutix, Inc.; Regeneron Pharmaceuticals Inc.; and Topcon Healthcare, Inc.
Ended: EyePoint Pharmaceuticals Inc. and Boehringer Ingelheim

Grants: Janssen Pharmaceuticals, Inc. (ended in 2024)

Stock Shareholder (ownership interest): Ollin Biosciences, Inc. and Ocugen, Inc.

The following individuals have no financial relationships to disclose:

Rebecca Vargas-Jackson, MD (Peer Reviewer)
Mary Gleason, PhD, CHCP (Planning Committee)
Warren Beckman (Planning Committee)
Siddharth Mohan, MPH (Planning Committee)
Andrea Perseghin, EdD (Planning Committee)
Sandra Caballero, PharmD (Planning Committee)
Sharon Tordoff (Planning Committee)

*All identified conflicts of interest have been mitigated.

Unlabeled Use Disclosure
Faculty of this CME/CE activity may include discussions of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices. CME Outfitters, LLC, the faculty, planners, and reviewers do not endorse the use of any product outside of the FDA labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

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