Collin Richards, MD
Wills Eye Hospital, Philadelphia, PA
Neil M. Bressler, MD
Anti-VEGF monotherapy for diabetic retinopathy and diabetic macular edema is an underappreciated but highly effective approach, particularly in patients with vision loss and central macular thickening. Data from ASRS surveys and DRCR Retina Network trials, including Protocol S, show that patients treated with anti-VEGF alone for proliferative diabetic retinopathy with DME achieved better visual acuity and experienced less peripheral visual field loss compared with combination therapy, though they required more injections early in their treatment course. These studies also demonstrate meaningful durability, with many patients needing few or no injections in later years without compromising vision. While newer agents may produce greater anatomic improvements on OCT, these changes may not translate into functional outcomes, like visual acuity, a result that was observed in Protocol T. Dr. Bressler reiterated that functional outcomes, not anatomic metrics alone, should remain the primary focus in managing diabetic retinal disease. In addition, when treatment for DME is deferred due to good visual acuity, a question posed by Protocol V, it is critical to monitor patients closely, up to every one to two months, and have systems in place to ensure patients are not lost to follow-up for long periods of time. Finally, it is important to note that the benefits of anti-VEGF monotherapy are wholly reliant on strict follow-up adherence.
Adrienne Scott, MD
Proliferative diabetic retinopathy can worsen rapidly, and although DRCR trials demonstrated that anti-VEGF monotherapy is non-inferior to panretinal photocoagulation for visual outcomes, real-world adherence significantly limits its effectiveness. In a large retrospective community-practice analysis of over 26,000 eyes from the Vestrum database, fewer than 12% of patients received care consistent with Protocol S, and more than 40% were lost to follow-up within one year. Nonadherence was more common among older patients, smokers, males, and those with government-sponsored insurance, and was associated with higher rates of severe complications such as vitreous hemorrhage, tractional retinal detachment, and need for vitrectomy. These findings emphasize that while anti-VEGF monotherapy can be highly effective, treatment selection for PDR must account for a patient’s likelihood of adherence and follow-up to achieve optimal real-world outcomes. Further discussion emphasized the importance of combination therapy with PRP and anti-VEGF and a call for future prospective trials to study the efficacy of combination therapy, as this is a commonly employed treatment algorithm.
Katherine Talcott, MD
Although current anti-VEGF therapies have significantly improved outcomes in proliferative diabetic retinopathy and diabetic macular edema, there remains a need for more durable treatments, and tyrosine kinase inhibitors (TKIs) represent a promising future direction. Unlike antibody-based anti-VEGF agents, TKIs are small molecules that inhibit multiple VEGF receptors and related inflammatory pathways, like IL-6, enabling sustained intracellular blockade of angiogenesis and vascular leakage. Advanced candidates such as OTX-TKI and EYP-1901 have shown encouraging early clinical results, including durable reductions in retinal vascular leakage, sustained anatomic and visual improvements, and fewer retreatments through extended-release delivery platforms. Ongoing and upcoming phase 3 trials will further define their role, but these agents have the potential to meaningfully reduce treatment burden and address persistent disease in diabetic retinal conditions. Further discussion centered on the potential role for TKIs in AMD and the hope that biomarkers in the phase 3 clinical trials may help identify patients that will benefit most from therapy.
Richard Rosen, MD
Central retinal artery occlusion causes sudden, severe vision loss with poor prognosis, largely due to delays in diagnosis and limited effectiveness of traditional treatments, but intraarterial thrombolysis may improve outcomes if administered early after vascular occlusion. The Rapid OCT-Confirmed eyestroKE Treatment (ROCKET) protocol streamlines care by using emergency department-based automated OCT, teleconsultation, and immediate stroke-team activation without requiring formal ophthalmology consultation, enabling faster identification of retinal ischemia and treatment initiation. This protocol is for patients with suspected embolic CRAO with vision loss within the past 12 hours, vision worse than 20/200, no suspicion of GCA, no pain, flashes, or floaters, and OCT confirmation of ischemia by a retina specialist. Coordinated care pathways such as this have the potential to improve outcomes in a subset of patients and enable more efficient care compared with prior workflows, highlighting that speed, system coordination, and increased awareness are critical factors in improving visual outcomes for CRAO. Important discussion points highlighted the importance of intraaterial thrombolysis, as intravenous is likely ineffective and concern that overlap in OCT features may lead to overtreatment.
Rishi Singh, MD
GLP-1 receptor agonists have been used for diabetes for decades, but their recent widespread use for obesity has revealed complex, multi-organ effects, including emerging ocular signals. Early concerns about worsening diabetic retinopathy from SUSTAIN-6 appear largely related to rapid glycemic improvement, as longer-term and real-world studies have not consistently confirmed increased risk and in some cases suggest reduced diabetic eye complications. Evidence strongly points to a protective association with glaucoma and possible protective association with AMD, though reports have linked GLP-1s to non-arteritic anterior ischemic optic neuropathy. Overall, most data are retrospective and observational, but current evidence suggests GLP-1 therapies are generally ocularly safe and potentially protective, with ongoing prospective trials such as the FOCUS trial expected to clarify long-term ophthalmic outcomes.
