Usefulness of Liquid Biopsy Biomarkers from Aqueous Humor in Predicting Anti-VEGF Response in Diabetic Macular Edema: Results of a Pilot Study

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.

Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients

“…This analysis is not without limitations. Although the Protocol T study was carried out with patients from the United States, the patient characteristics of anti-VEGF treated patients are very similar between Western countries, as shown in several published case series studies carried out in Europe and US [20][21][22][23][24][25][26]. A multicenter US study included patients treated with the 3 available anti-VEGF therapies with a mean age of 63.4 years and 80.8% with type 2 diabetes.…”

“…In another Spanish observational study that included patients treated with ranibizumab and aflibercept, the patients had a mean age of 69 years, 90% had type 2 diabetes, and they had a baseline visual acuity of 0.52 logMAR and a CST of 456 μm [ 25 ]. Additionally, a more recent study with anti-VEGF-treated type 2 diabetes patients showed similar baseline characteristics regardless of anti-VEGF responses with a mean age between 67.5 and 71 years, a mean BVCA of 62.5–67.2 letters and a mean CST from 443 to 542 μm [ 26 ]. All these patient characteristics could be considered similar.…”

Intraocular fluid biomarkers (liquid biopsy) in human diabetic retinopathy

“…Prognosis and response to treatment are two of the main points potentially addressed by the liquid biopsy approach. Recently, different studies have reported the response to DME treatment, by means of aqueous and vitreous samples [32,104,105,[111][112][113][114][115][116]. Sohn et al compared the AH concentration of VEGF and inflammatory molecules after the administration of triamcinolone and bevacizumab, showing that the first one was able to reduce several inflammatory molecules (IL-6, IP-10, MCP-1, PDGF-AA) and VEGF concentration, while bevacizumab just reduced VEGF concentration [32].…”

Intraocular biopsy in uveitis

“…Combining PCR, GWC and Western blot technique increased the sensitivity by up to 97%[ 11 ] Increased levels of TGF beta- 2 in the AH could indicate an increased risk of secondary glaucoma in uveitis associated with juvenile idiopathic arthritis Levels of IL-10 (interleukin - 10) alone from an AH sample when more than 50 pg/ml can be can be a marker of intraocular lymphoma. [ 12 13 ] Cytokines, metalloproteinases and chemokines detected by ELISA in the AH are being studied for their diagnostic and prognostic significance as pro- or anti- inflammatory mediators in uveitis. [ 14 ] …”

“…Levels of IL-10 (interleukin - 10) alone from an AH sample when more than 50 pg/ml can be can be a marker of intraocular lymphoma. [ 12 13 ] Cytokines, metalloproteinases and chemokines detected by ELISA in the AH are being studied for their diagnostic and prognostic significance as pro- or anti- inflammatory mediators in uveitis. [ 14 ]…”