As retinal care continues to advance, ophthalmologists are navigating a rapidly evolving landscape of therapies, imaging tools, and patient management strategies. The Eye Care Network caught up with leaders in the retina community for an overview of timely topics in retinal disease management. They share their insights on how anti-VEGF therapy has evolved in clinical practice, the most promising pipeline treatments for geographic atrophy (GA) and diabetic macular edema (DME), strategies for balancing efficacy, injection frequency, and patient quality of life, and the role of adjunctive imaging modalities in guiding therapeutic decisions.

Participating in this Q&A discussion were the following:

• David R.P. Almeida, MD, MBA, PhD, vitreoretinal surgeon and clinician scientist with Erie Retina Research in Erie, PA, and The Centers for Advanced Surgical Exploration (CASEX).
• David S. Boyer, MD, senior partner, Retina-Vitreous Associates Medical Group, and adjunct clinical professor of ophthalmology, University of Southern California/Keck School of Medicine, Los Angeles, CA

The focus begins with a look at the evolution of anti-VEGF therapy in clinical practice—a cornerstone of modern retinal care and a topic that continues to generate interest among retina specialists.

How has anti-VEGF therapy evolved in your practice?

Almeida: In my practice, anti-VEGF therapy has evolved from a paradigm of frequent, fixed-interval injections to a more personalized and sustainable approach focused on reducing treatment burden without compromising efficacy. Initially, the goal was simply to control exudation. Now, with the advent of more durable molecules and novel delivery systems, the focus has shifted to extending the time between treatments. My active involvement as a principal investigator in numerous clinical trials for neovascular AMD and DME with numerous sponsors reflects a commitment to advancing this evolution.

Boyer: A “wow” effect of a treatment for neovascular AMD and then diabetes. Since that time, it has become the mainstay of treatment for all retinal vascular diseases, neovascular AMD, and on rare occasions inflammatory macular leak in a steroid responder or even a rare patient with central serous. Though I tend to use aflibercept or a biosimilar, I do use second-generation drugs in difficult to treat patients or patients I am trying to extend treatment intervals in.

Which pipeline therapies for GA or DME are most promising?

Almeida: For GA, the most promising frontier is gene therapy. I am currently an investigator for multiple gene therapy platforms, including viral vector approaches. This modality has the potential to offer a one-time treatment that could slow or halt the progression of GA by providing sustained expression of a therapeutic protein, a significant leap beyond current treatment options. For DME, therapies focusing on extended delivery are particularly promising.

Boyer: For GA, I believe companies looking at long-chain polyunsaturated lipids, macrophages, and mitochondria enhancers may play a role in improving intermediate AMD and potentially decreasing GA formation. The problem basically is you need either an easy way of administering (pill or drops) or a long interval between injections if they are the route of administration. For DME, I believe that gene therapy or a multivalent injection with an anti-VEGF and interleukin 6 (IL-6) and tyrosine kinase inhibitors (TKIs) will decrease the vision loss associated with this multifactorial disease and make treatment intervals longer.

How do you balance efficacy, injection frequency, and patient quality of life?

Almeida: Balancing these 3 critical factors is the cornerstone of modern retinal care, achieved through a patient-centered, data-driven approach. Efficacy, meaning the best possible visual outcome, is always the primary goal. However, achieving this at the cost of an unsustainable injection frequency can negatively impact a patient's quality of life, leading to treatment fatigue and non-adherence. My clinical philosophy, underscored by receiving multiple patient experience awards, is to engage in shared decision-making. We use advanced imaging to monitor disease activity and personalize treatment intervals with treat-and-extend regimens. Furthermore, my extensive research into next-generation, longer-acting therapeutics is driven by the goal of finding a better equilibrium where we can maximize efficacy and quality of life by minimizing treatment frequency.

Boyer: The balance is related to the age of the patient, the visual acuity, and the disease you are treating. Obviously, less-invasive treatment has to be weighed against reduced efficacy. The balance will differ from person to person.

What role do adjunctive imaging modalities play in guiding retinal therapies?

Almeida: Adjunctive imaging modalities are indispensable tools that have moved beyond simple diagnosis to become critical guides for therapeutic management. In my practice, optical coherence tomography (OCT) is fundamental not only for quantifying macular thickness but also for identifying subtle biomarkers of disease activity, such as outer retinal tubulations or subclinical fluid, which may not be apparent on clinical examination. This allows for more precise and proactive treatment decisions. My research has explored the application of advanced imaging techniques, such as positional OCT, to understand retinal pathology better. Moreover, the use of intraoperative OCT, as shown in my surgical work, provides real-time anatomical feedback that directly influences surgical maneuvers and improves outcomes in complex cases.

Boyer: The use of optical coherence tomography angiography (OCTA) has reduced my need for fluorescein angiography. OCT has allowed more accurate determination of early areas of incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA.) Autofluorescence allows me to see the growth of GA lesions very easily. Hopefully, AI will be able to predict who would benefit from certain treatments “personalized medicine.”

David R.P. Almeida, MD, MBA, PhD
E: drpa@pm.me
Almeida is a vitreoretinal surgeon and clinician scientist with Erie Retina Research in Erie, PA, and The Centers for Advanced Surgical Exploration (CASEX).

David S. Boyer, MD
E: vitdoc@laretina.com
Boyer is senior partner, Retina-Vitreous Associates Medical Group, and adjunct clinical professor of ophthalmology, University of Southern California/Keck School of Medicine, Los Angeles, CA

Both authors report multiple financial relationships with commercial entities, including consulting, advisory roles, research funding, and speaking engagements. A comprehensive list of their affiliations and financial disclosures is available upon request.