Elham Sadeghi, University of Pittsburgh
Sameen Meshkin, Mass Eye & Ear
Macula 2025 started with a fantastic keynote lecture by Dr. Daniel Martin to explore the global influence of NIH funded retina networks.
Dr. Martin talked about the history of the DRCR Retina Network, which was funded in 2002 initially as the Diabetic Retinopathy Clinical Research (DRCR) Network, and then expansion of NIH support in 2017 to allowed expansion to study retinal diseases beyond diabetic retinopathy. Over the last 21 years, the Network has performed 38 multicenter clinical trials at 160 clinical studies and has produced more than 120 publications. They currently have more ongoing clinical trials than they ever have, including 10 AI projects.
The first successful NIH sponsored clinical trial was the Diabetic Retinopathy Study in the early 1970s. The traditional approach to clinical trials often centered around a single study question with a cohort of patients supported by a single grant. This method, while focused, had drawbacks, including lengthy protocol development and the dissolution of infrastructure post-study. Notable examples of this approach include the Diabetes Control and Complications Trial (DCCT), Early Treatment Diabetic Retinopathy Study (ETDRS), Retinal Vein Occlusion studies, Age-Related Eye Disease Study (AREDS), and Collaborative Ocular Melanoma Study (COMS). The macular photocoagulation study (MPS) in the 1980s operated similarly to a network through consecutive grants, establishing key treatments for neovascular age-related macular degeneration (AMD) and influencing future research.
The development of standing clinical trial groups, like the DRCR Network, has allowed for more efficient and cost-effective research in other retinal diseases. Foscarnet-Ganciclovir Cytomegalovirus Retinitis Trial (FGCRT) and the Monoclonal Antibody CMV Retinitis Trial (MACRT) are two examples. These efforts not only established global standards of care but also set infrastructure models replicated by subsequent networks, highlighting the importance of sustained, collaborative research initiatives.
The Comparison of Age-related Macular Degeneration Treatments Trials (CATT) was pivotal in the more extensive AMD network, leading to 67 published papers and influencing both Medicare and NIH policies. The trial’s results necessitated a congressional amendment to allow public funding for drug costs in NIH clinical trials, a mechanism now widely used by other specialties and countries. This work significantly reduced the total cost of AMD care in the US by over $50 billion and fostered international collaboration. The CATT trial, along with related studies like the Prospective OCT Imaging of Patients with Neovascular AMD Treated with Intraocular Ranibizumab (PrONTO) study, established OCT as a key tool for treating neovascular AMD, setting a paradigm for patient management that continues to guide treatment principles today.
The DRCR network has conducted numerous landmark trials, including Protocol I, which established anti-VEGF treatment as a standard of care for diabetic macular edema (DME) and showed that the need for injections decreases over time. Protocol T highlighted the effectiveness of anti-VEGF therapy based on visual acuity, while Protocol V demonstrated that patients with good vision do not necessarily require immediate treatment. These protocols have provided critical insights and shaped treatment guidelines worldwide. The Network’s work has had a profound global impact, establishing anti-VEGF therapy as a standard of care and influencing national guidelines in various countries.
Dr. Martin’s talk followed by a Q&A session. Dr. Neil Bressler asked: “If a patient had stable vision and OCT readings after three injections, even with some remaining abnormalities, monthly monitoring was acceptable without necessarily achieving complete dryness?” Dr Martin answered: “Throughout the CATT study, we maintained a treat-to-dry policy because setting up a protocol with quantifiable fluid allowances for hundreds of ophthalmologists would have been too complex. So, we kept it simple: patients with fluid at 14 months still received an injection despite recognizing potential futility in some cases.”
Dr Fernando Arevalo asked: “I wonder how the results of the upcoming Protocol AP, comparing Faricimab plus PRP to vitrectomy and endolaser or PRP, could supersede or influence the current understanding from Protocol S in managing PDR.” Dr Martin answered: “Many of us started using anti-VEGF therapy as a primary treatment after it was published, but due to missed appointments leading to severe consequences like neovascular glaucoma, the network has focused on studying combination therapy to determine if a single combined treatment with a laser could be sufficient.”
Dr Yoshihiro Yonekawa asked: “Since other countries are interested in establishing their own networks, I was wondering if you could teach us what are the most important elements to have in place.” Dr Martin answered: “The most critical element for successful clinical trials is having a strong leadership team, including experts like biostatisticians, a dedicated coordinating center, and consistent funding to support and maintain this infrastructure.”
International Keynote Speaker
The afternoon sessions of Macula 2025 kicked off with the International Keynote Talk in honor of the 100th Anniversary Celebration of Wilmer Eye Institute introduced by Drs. Neil Bressler and Fernando Arevalo. Haotian Lin, MD, PhD was the invited International Keynote speaker. His talk, AI Revolution in Retina, served to highlight the contributions his research team has made to the AI revolution in retina at the Zhongshan Ophthalmic Center (ZOC) in Guangzhou, China. He began his talk by acknowledging Professor Eugene Chan – the 1st Chinese fellow at Wilmer (in 1929) who went on to become the founding director of ZOC. He similarly expressed heartfelt gratitude to the Wilmer Eye Institute for its valuable collaboration on its 100th anniversary.
Given the widening gap between growing demand for eyecare and limited medical resources, AI poses a unique solution. Dr. Lin described several challenges to the application of AI to real-world clinical practice including 1) poor quality images in the real world and 2) lack of effective application patterns. He described several solutions his team has devised including an image quality assistant (Deep Quality) to help optimize image quality by signaling the need for re- imaging at the time of image acquisition if certain image quality parameters are not met.
His group trained a deep-learning system, the Comprehensive AI Retinal Expert (CARE) system, to identify the 14 most common retinal abnormalities using over 200,000 color fundus photographs from 16 clinical settings. CARE was internally validated and externally tested using over 18,000 photographs prospectively collected from 35 real-world settings across China where CARE could be adopted. CARE became the first class III medical device in ophthalmic AI in China.
Dr. Lin also described the application of AI to rural areas where screening needs are high. His team combined an AI model with cloud-based AI screening to extend screening capabilities through China. Additionally, an innovative ophthalmic mobile vehicle screening program has enabled screening of 150,000 patients across 108 cities around China.
He concluded his keynote talk by sharing briefly about the Zhongshan Ophthalmic Center, which he reported is a leading eye hospital in China, performed over 110,000 surgeries last year, and serves as a leader in pioneering research and education.
Read All Atlantic Coast Retina Club / Macula 2025 Articles:
Mystery Cases 1 & 2
Mystery Cases 3 & 4
Mystery Cases 5 & 6
Mystery Cases 7, 8, 9
Imaging, GA, and IRDs
Keynote Lectures
DR and DME
Choroidal Neovascularization
Retinal Vascular Diseases
Ocular Oncology
Special Topics & Women in Retina