Anti-VEGF therapy is the established first-line treatment for diabetic macular edema (DME), yet response to the therapy still remains frustratingly variable. A retrospective Frontiers in Endocrinology study of 691 patients and 1,039 eyes suggests that part of that variability may lie beyond the retina itself, with systemic metabolic health playing an important role in short-term anatomical outcomes.
Researchers based at the First Affiliated Hospital of Ningbo University in China evaluated patients with type 2 diabetes and DME who received three consecutive monthly intravitreal injections of Conbercept. Anatomical response was assessed using central macular thickness (CMT), measured one month after the third injection. Eyes achieving a reduction in CMT of more than 10 percent from baseline were classified as responders.
Overall, treatment produced significant anatomical and functional improvement. Median CMT fell from 325 µm at baseline to 291 µm after the loading phase, while median best-corrected visual acuity also improved. However, only 431 eyes (41.5 percent) met the study’s definition of response; the remaining 608 eyes were classified as non-responders.
The metabolic differences between the groups were notable. Responders had a lower median fasting glucose than non-responders and lower mean HbA1c. After multivariable adjustment, elevated fasting glucose and HbA1c remained independently associated with poor anatomical response; baseline CMT and visual acuity were also independent predictors.
LDL cholesterol added another layer. In the linear model, higher LDL-C was independently associated with a smaller degree of CMT reduction, although it did not independently predict whether an eye crossed the 10-percent responder threshold.
That threshold itself deserves caution. Eyes with lower baseline CMT had less room for measurable improvement, creating what the authors describe as an anatomical “floor effect.” As a result, some eyes classified as non-responders may simply have been structurally unable to achieve a 10%reduction rather than genuinely refractory to treatment.
The study is retrospective, single-center, limited to Conbercept, and only captures the three-month loading phase. It also lacked data on diabetes duration and several ocular biomarkers.
Even so, the findings do point towards the fact that DME treatment may need to be considered as both ocular and systemic. For retina specialists, HbA1c and fasting glucose may offer some useful context when discussing prognosis, as well as strengthening the rationale for coordinated metabolic optimization alongside anti-VEGF therapy.
