Abstract
The objective was to investigate the usefulness of the “liquid biopsy” of aqueous humor (AH) to predict the clinical response after intravitreal injections (IVT) of anti-VEGF agents for treating diabetic macular edema (DME). For this purpose, AH samples obtained during the first anti-VEGF IVT from 31 type two diabetic patients were analyzed. Patients were classified into three groups according to their anti-VEGF response: rapid responders (n = 11), slow responders (n = 11), and non-responders (n = 9). In addition, patients (n = 7) who showed good response to corticosteroids but a delayed or no response to anti-VEGF therapy were analyzed. Levels of 17 different cytokines, chemokines, and growth factors in AH were measured using a multiplex immunoassay. We found higher concentrations of VEGF in rapid responders to anti-VEGF therapy compared to non-responders. In addition, slow responders to anti-VEGF treatment showed higher levels of inflammatory markers than rapid responders, but did not reach statistical significance. Finally, those patients who responded to corticosteroids but not to anti-VEGF therapy showed significantly lower levels of VEGF than patients with rapid response (p = 0.01). In conclusion, “liquid biopsy” of AH could be useful to determine whether the predominant pathogenic event is primarily angiogenic or inflammatory in nature. This approach would allow physicians to select a more rational and cost-effective treatment. Further studies to validate these preliminary results are warranted.
Highlights
Diabetic retinopathy (DR) prevalence in the diabetic population is around one-third, and one-tenth has vision-threatening states such as diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR) [1]
It is worth mentioning that we found a strong correlation between the concentration of vascular endothelial growth factor (VEGF) in vitreous and aqueous samples obtained simultaneously, demonstrating that our samples of aqueous humor (AH) reflected the events that occurred at retinal level
We have found that levels of VEGF were significantly higher in vitreous fluid than in serum of patients with PDR but not in non-diabetic subjects [29]
Summary
Diabetic retinopathy (DR) prevalence in the diabetic population is around one-third, and one-tenth has vision-threatening states such as diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR) [1]. The results of major randomized controlled clinical trials investigating the use of anti-VEGF therapy for DME have been reported. These trials provide robust evidence that intraocular administration of anti-VEGF agents is better than laser therapy both in preserving and in improving vision for patients with DME. It is not surprising that approximately half of patients with DME do not show adequate response to anti-VEGF treatment. In this subgroup of non-responders other growth factors and/or proinflammatory cytokines unrelated to VEGF probably play a more relevant pathogenic role
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