Many patients with diabetic macular edema (DME) remain untreated well after diagnosis. Findings from a global Delphi panel suggest this gap reflects not only access barriers but also limitations in therapeutic fit—particularly in earlier-stage disease, when clinicians may hesitate to initiate invasive treatment.

Presenting results from the DME AWARE Delphi Study at the Association for Research in Vision and Ophthalmology (ARVO) meeting in Denver, Baruch D. Kuppermann, MD, PhD, director of the Gavin Herbert Eye Institute at the University of California, Irvine, described a set of consensus findings that point to unmet needs across the continuum of DME management, with particular emphasis on early intervention and noninvasive treatment options (Figure 1).

“This work was based on the notion that we know DME is a leading cause of vision loss in working-age adults,” Dr. Kuppermann explained. “But I’m not sure we fully appreciate how many patients are left untreated.” He noted that “fully a year after diagnosis of DME, about 60% of patients remain untreated.”^1-5

The study brought together 25 global experts, including a 5-member steering committee and a 20-member panel, to evaluate 284 statements across 3 survey rounds using a modified Delphi methodology. Consensus was achieved on approximately two-thirds of statements, including several that define current gaps in care. In his presentation, Dr. Kuppermann focused on the results of Survey 3.

Among the most consistent findings was the lack of early treatment options that align with clinical decision-making in patients with mild or early-stage disease. “Patients with less severe or early-stage DME are typically observed because of the risk-benefit ratio of invasive therapies,” Dr. Kuppermann said. “What we primarily have in hand is anti-VEGF injections as first-line therapy for most of us.”

That reliance on intravitreal therapy appears to contribute to a treatment gap, particularly when visual acuity remains relatively preserved. Panelists identified a lack of noninvasive treatment options as a central unmet need, along with improved adherence, therapies for concomitant use with standard of care, and better safety and tolerability profiles.

The preference for less-invasive approaches was reflected in responses tied to visual acuity thresholds. When presented with a one-line loss from 20/20 vision, 70% of panelists supported early intervention with a noninvasive treatment, while only 5% favored initiating intravitreal therapy. With a two-line loss, 85% supported noninvasive intervention, compared with 40% for intravitreal treatment (Figure 2). These findings suggest a mismatch between available therapies and clinician thresholds for beginning treatment.

The panel also reached consensus on key definitions for evaluating the response to treatment. Poor response to treatment was defined as “less than a 10% reduction in central subfield thickness (CST) when baseline CST is at least 350 µm,” said Dr. Kuppermann. There also was agreement that visual function should be used to help define non-response to DME treatment.

In evaluating retinal biomarkers, most panelists placed greater emphasis on intraretinal fluid than subretinal fluid. Seventy-five percent indicated that intraretinal fluid is more important when assessing retinal thickening in DME, reinforcing its role in both monitoring and treatment decisions.

The study further addressed how clinicians define early detection and intervention. Consensus was reached that detection can occur before the presence of fluid and that intervention should ideally take place before functional decline.

The panel also acknowledged limitations of existing therapies in later stages. Even with anti-VEGF agents, a substantial proportion of patients do not achieve optimal outcomes. “Up to 40%, and certainly at least 25%, of patients have an inadequate response,” Dr. Kuppermann said, citing data derived from studies conducted by the Diabetic Retinopathy Clinical Research Network and others.

Taken together, the findings highlight a continuum of unmet need, from early-stage disease—where treatment may be deferred due to invasiveness—to later stages, where response to therapy may be incomplete. Dr. Kuppermann noted that a manuscript detailing the full results of the DME AWARE Delphi Study is being prepared for publication. RP

References

1. Real-world data from the American Academy of Ophthalmology IRIS Registry.

2. Ciulla TA, Amador AG, Zinman B. Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care. 2003;26(9):2653-2664. doi:10.2337/diacare.26.9.2653

3. Petrella RJ, Blouin J, Davies B, Barbeau M. Prevalence, demographics, and treatment characteristics of visual impairment due to diabetic macular edema in a representative Canadian cohort. J Ophthalmol. 2012;2012:159167. doi:10.1155/2012/159167

4. Baker CW, Glassman AR, Beaulieu WT, et al. Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular edema involving the center of the macula and good visual acuity: a randomized clinical trial. JAMA. 2019;321(19):1880-1894. doi:10.1001/jama.2019.5790

5. Gonzalez VH, Campbell J, Holekamp NM, et al. Early and long-term responses to anti-vascular endothelial growth factor therapy in diabetic macular edema: analysis of Protocol I data. Am J Ophthalmol. 2016;172:72-79. doi:10.1016/j.ajo.2016.09.012