Specific optical coherence tomography (OCT) biomarkers can significantly predict the likelihood of treatment failure with anti-VEGF agents in patients with diabetic macular edema (DME), according to a recent study in the British Journal of Ophthalmology.

The study authors noted that the findings support earlier use of dexamethasone implants (DEX-i) in select patients to improve outcomes and avoid delays in vision-saving therapy.

The study included 275 eyes from patients who were diagnosed with DME. Of these, 209 eyes (76%) required a switch from anti-VEGF therapy to DEX-i due to suboptimal response, while 66 eyes (24%) experienced a good clinical response and continued anti-VEGF treatment.

The objective of the study was to determine the predictive value of optical coherence tomography (OCT)-detected retinal biomarkers at baseline for switching therapies. These biomarkers included:

• Subretinal fluid (SRF)
• Hyperreflective cystoid walls (HCW)
• Dense intraretinal cysts (DIR)
• Vitreomacular interface (VMI) abnormalities
• Disorganization of retinal inner (DRIL) and outer layers (DROL)
• Hyperreflective foci (HRF)
• Intraretinal fluid (IRF)

Patients were classified as nonresponders based on failure to reduce central retinal thickness (CRT) by at least 20%, lack of BCVA improvement, or recurrence of DME despite monthly injections.

Patients who required a treatment switch had worse baseline parameters compared with those who did not require a switch in treatment. They were a mean age of 69 years (vs 64.2 years), showed worse initial BCVA of 0.3 (vs 0.5), and had higher CRT of 492.3 µm (vs 351.4 µm). More patients who need a switch were also women (43.5% vs 18.2%).

OCT biomarkers significantly associated with switching included:

• SRF: Present in 34.9% of switched cases vs 3% of controls
• HCW: 33% vs 1%
• DIR: 39.7% vs 19.7%
• VMI abnormalities: 30.1% vs 3%

Conversely, HRF and DROL were more prevalent in the control group and correlated with reduced likelihood of switching:

• HRF: 80.4% (study group) vs 98.5% (controls)
• DROL: 38.8% (study group) vs 59.1% (controls)

Multivariate logistic regression identified the following as significant predictors of switching from anti-VEGF to DEX-i:

• SRF: Odds ratio (OR) = 20.81
• HCW: OR = 40.78
• DIR: OR = 5.07
• VMI abnormalities: OR = 16.91

Protective factors for reducing the risk of switching included:

• Male gender: OR = 0.27
• DROL presence: OR = 0.21
• HRF presence: OR = 0.06

The presence of any two markers among SRF, HCW, and VMI abnormalities at baseline raised the odds of treatment failure by a factor of 49. The presence of all three of these markers correlated with a near-certain failure of anti-VEGF therapy (OR ≈ 4.56×10¹⁶).

While anti-VEGF remains the first-line therapy for DME, early identification of poor responders could justify an earlier switch to steroids, particularly in patients with high CRT; those who present with SRF, HCW, or VMI alterations on OCT; or those who are pseudophakic or have compliance challenges. “Multiple studies have shown that in some patients with DME, VEGF levels may be normal, with elevated levels of inflammatory markers such as interleukin (IL)-8, IL-6, IL-1b and intercellular adhesion molecule 1 (ICAM-1) in serum or aqueous humor. It is these patients who do not respond adequately to standard anti-VEGF treatment,” the authors noted.

Although the study was retrospective and involved variability in switch criteria among centers, it reflects real-world clinical practice across several international institutions.

“It would be desirable to be able to repeat this multicentric study with a larger number of cases that would allow us to reach a higher degree of certainty in our conclusions and avoid the waste of time and money involved in making three to six intravitreal injections to confirm the patient as an insufficient responder and make the switch to steroids,” the authors concluded. RP