Retina World Congress 2026: The case for earlier surgical intervention in diabetic macular edema

Anti-VEGF therapy has transformed the management of diabetic macular edema (DME), but treatment burden, adherence challenges, and incomplete responses remain persistent limitations in real-world practice. Internal limiting membrane (ILM) peeling via pars plana vitrectomy (PPV) has traditionally been reserved for cases with refractory disease or vitreoretinal interface abnormalities, but emerging evidence suggests it may have a role earlier in the treatment course.

In this Q&A conversation with the Eye Care Network, Matias Iglicki, MD, PhD, a certified teacher of ophthalmology at the University of Buenos Aires, Argentina, shares his perspective on ILM peeling as a primary treatment strategy in carefully selected patients with DME, drawing on findings from the VITAL Study (NCT01121965). Iglicki presented on this topic at Retina World Congress 2026, May 14 to 17, in Fort Lauderdale, Florida.

Note: Transcript edited for clarity and length.

Anti-VEGF therapy remains the standard first-line approach for DME. What clinical rationale led you to investigate ILM peeling as a potential primary treatment strategy in selected patients with DME?

Matias Iglicki, MD, PhD: Although anti-VEGF therapy has significantly improved outcomes in DME, real-world experience continues to demonstrate important limitations related to treatment burden, adherence, frequent visits, and incomplete functional response in a substantial proportion of patients. In daily practice, many patients struggle to maintain intensive injection regimens over long periods of time.

The rationale behind the VITAL Study [NCT01121965] was to explore whether early pars plana vitrectomy with ILM peeling could provide a durable anatomical and functional benefit in carefully selected treatment-naive patients with DME, potentially reducing long-term treatment burden while addressing important pathophysiologic mechanisms not directly targeted by pharmacologic therapy.

Vitrectomy may improve retinal oxygenation, increase cytokine and VEGF clearance, relieve subtle vitreoretinal interface abnormalities, and enhance retinal fluid dynamics. ILM peeling additionally helps eliminate residual tangential traction and may reduce future epiretinal membrane formation. Our study demonstrated that early surgical intervention achieved significant long-term anatomical and visual improvement over 24 months without requiring additional DME treatment in most patients.

From a pathophysiologic perspective, how does ILM peeling influence retinal architecture, tractional components, or fluid dynamics in DME?

Iglicki: DME is not exclusively a VEGF-mediated disease. The vitreoretinal interface also plays an important role in chronic edema persistence and retinal dysfunction.

ILM peeling may influence DME through several complementary mechanisms. First, it relieves microscopic tangential traction that may not always be clinically evident on OCT but still contributes to retinal thickening and cyst persistence. Second, removal of the posterior hyaloid and ILM may improve oxygen diffusion and retinal metabolic exchange while increasing clearance of VEGF and inflammatory cytokines from the vitreous cavity.

In diabetic eyes, chronic hyperglycemia also induces structural alterations of the posterior hyaloid and internal limiting membrane, strengthening vitreoretinal adhesion. By completely releasing these interfaces, surgery may interrupt chronic mechanical and inflammatory stimuli contributing to edema persistence.

Additionally, vitrectomy appears to improve intravitreal fluid currents and retinal oxygenation, which may contribute to long-term edema resolution. These mechanisms likely explain why many patients in the VITAL Study maintained stable anatomical outcomes without requiring additional intravitreal therapy during follow-up.

Which patient populations may benefit most from a surgical-first approach, and are there imaging or clinical biomarkers that help identify ideal candidates for ILM peeling?

Iglicki: One of the most important findings of the VITAL Study was the identification of biomarkers associated with better visual outcomes after early PPV with ILM peeling.

Patients presenting with subretinal fluid (SRF) and preserved outer retinal layers, particularly intact photoreceptor architecture, demonstrated better long-term functional outcomes. Conversely, delayed intervention and significant photoreceptor disruption were associated with worse visual prognosis.

Importantly, timing emerged as a major predictor of success. For every day surgery was delayed, the probability of gaining meaningful visual improvement progressively decreased. This suggests that earlier intervention before irreversible retinal damage develops may be critical in selected patients.

In clinical practice, I believe the best candidates may include patients with diffuse DME, evidence of vitreoretinal interface contribution, persistent SRF, high treatment burden concerns, or patients in whom long-term adherence to frequent injection regimens may be difficult. Multimodal OCT evaluation is essential when selecting these patients.

Do you envision ILM peeling becoming part of a broader shift toward earlier surgical intervention in DME management, particularly in patients with incomplete response or treatment burden concerns?

Iglicki: I believe we are moving toward a more individualized treatment paradigm in DME, where imaging biomarkers, disease phenotype, treatment burden, and patient-specific factors increasingly guide decision-making rather than relying on a single universal algorithm.

Anti-VEGF therapy will certainly remain a cornerstone of DME management. However, surgery may become increasingly relevant in selected patients, particularly those with incomplete response, chronic edema, high injection burden, or biomarkers suggesting vitreoretinal interface involvement.

The concept of earlier surgical intervention is especially interesting because many patients eventually develop irreversible photoreceptor damage after prolonged chronic edema. Our findings suggest that waiting too long may reduce the potential for visual recovery.

I do not believe vitrectomy with ILM peeling should replace pharmacologic therapy broadly, but I do believe it deserves greater consideration as an earlier therapeutic option in carefully selected cases. Future prospective randomized studies comparing modern surgical approaches with pharmacologic strategies will be essential to better define its role within the evolving DME treatment landscape.

Matias Iglicki, MD, PhD

E: matiasiglicki@gmail.com

Iglicki is certified teacher of ophthalmology with the University of Buenos Aires, in Argentina.