Changes in aqueous cytokine levels following treatment with aflibercept in treatment naïve patients with diabetic macular edema
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Paper Presentation | Présentation d'article
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11:40, niedziela 3 cze 2018
(10 min.)
Gdzie:
Author Block: Michael Y. Mak, Verena Juncal, Rajeev Muni
Author Disclosure Block: M.Y. Mak: None. V. Juncal: None. R. Muni: Grant/research support; Research funding support, Bayer Inc., Research funding support, Novartis. Employment/honoraria/consulting fees; Speaking Honorarium, Bayer Inc., Speaking Honorarium, Novartis.
Abstract Body:
Purpose: To determine changes in aqueous cytokine levels in treatment- naive DME patients during intravitreal aflibercept treatment. Study Design: Interventional, prospective clinical study.
Methods: Study approval was provided by St. Michael’s Hospital Research Ethics Board. Patients with treatment-naive DME, age greater than 18 years, with non-proliferative diabetic retinopathy (NPDR), and with central macular thickness of 310 μm or more on SD-Optical Coherence Tomography (SD-OCT) were included. Patients received aflibercept injections at baseline, and monthly injections for three months after baseline. On each visit Snellen BCVA, SD-OCT, and an anterior chamber (AC) tap was performed to collect aqueous fluid before each aflibercept injection. Multiplex immunoassay of aqueous samples were carried out for FGF-2, IL-6, IL-8, IL-10, IP-10, MCP-1, VEGF, PDGF-AA, HGF, PLGF, sICAM-1, sVCAM-1, TGF-β1, TGF-β2, and TGF-β3. Median Percent change in cytokines were determined by the formula (median month 2 cytokine levels - median baseline cytokine levels)/baseline cytokine levels. Percent change in CST and Macular Volume were determined by the formula (month 2 OCT measurement baseline OCT measurement)/baseline OCT measurement. A Wilcoxon analysis was used to compare change in cytokine levels at baseline and month 2.
Results: A total of 11 patients were included of which 6 were male and 5 females, 9 right eyes, median age 59±9.6 years. Mean LogMAR at baseline and month 3 were 0.34±0.18 and 0.31±0.17 respectively. Median baseline CST and macular volume were 451.0±92.0μm and 12.1±1.3mm3 respectively, and median month 3 CST and macular volume were 345.5±89.8μm and 11.2±1.0mm3 respectively. CST and macular volume percent change between month 3 and baseline was -19.7±15.3% and -9.6±4.6% respectively. There was no significant change in FGF-2, IL-10, IL-8, MCP-1, sICAM-1, sVCAM-1 and TGF-β3 levels. There were significant increases in TGF-β1 (baseline median=87.44ρg/mL, month 2 median=205.9ρg/mL, median %change=135.5%, p=0.007), IP-10 (baseline median=119.9ρg/mL, month 2 median=217.8ρg/mL, median %change =81.7%, p=0.007), and HGF (baseline median=854.4ρg/mL, month 2 median=1269.7ρg/mL, median %change=48.6%, p=0.047). There were significant decreases in VEGF (baseline median=97.1ρg/mL, month 2 median=0ρg/mL, median %change=-100%, p=0.005), PLGF (baseline median=4.4ρg/mL, month 2 median=0ρg/mL, median %change=-100%, p=0.028), IL-6 (baseline median=13.6ρg/mL, month 2 median=6.8ρg/mL, median %change =-49.9%, p=0.011) and PDGF-AA (baseline median=68.7ρg/mL, month 2=36.5ρg/mL, median %change=-5.6%, p=0.032).
Conclusions: In treatment naïve patients with DME, aflibercept resulted in reduced OCT CST and macular volume. VEGF, PLGF, IL-6 and PDGF-AA were reduced. However, there were increases in IP-10 and pro-inflammatory cytokines including TGF-β1 and HGF. Larger, longer-term studies should examine if cytokine changes correlate with anatomic findings with aflibercept treatment.
Author Disclosure Block: M.Y. Mak: None. V. Juncal: None. R. Muni: Grant/research support; Research funding support, Bayer Inc., Research funding support, Novartis. Employment/honoraria/consulting fees; Speaking Honorarium, Bayer Inc., Speaking Honorarium, Novartis.
Abstract Body:
Purpose: To determine changes in aqueous cytokine levels in treatment- naive DME patients during intravitreal aflibercept treatment. Study Design: Interventional, prospective clinical study.
Methods: Study approval was provided by St. Michael’s Hospital Research Ethics Board. Patients with treatment-naive DME, age greater than 18 years, with non-proliferative diabetic retinopathy (NPDR), and with central macular thickness of 310 μm or more on SD-Optical Coherence Tomography (SD-OCT) were included. Patients received aflibercept injections at baseline, and monthly injections for three months after baseline. On each visit Snellen BCVA, SD-OCT, and an anterior chamber (AC) tap was performed to collect aqueous fluid before each aflibercept injection. Multiplex immunoassay of aqueous samples were carried out for FGF-2, IL-6, IL-8, IL-10, IP-10, MCP-1, VEGF, PDGF-AA, HGF, PLGF, sICAM-1, sVCAM-1, TGF-β1, TGF-β2, and TGF-β3. Median Percent change in cytokines were determined by the formula (median month 2 cytokine levels - median baseline cytokine levels)/baseline cytokine levels. Percent change in CST and Macular Volume were determined by the formula (month 2 OCT measurement baseline OCT measurement)/baseline OCT measurement. A Wilcoxon analysis was used to compare change in cytokine levels at baseline and month 2.
Results: A total of 11 patients were included of which 6 were male and 5 females, 9 right eyes, median age 59±9.6 years. Mean LogMAR at baseline and month 3 were 0.34±0.18 and 0.31±0.17 respectively. Median baseline CST and macular volume were 451.0±92.0μm and 12.1±1.3mm3 respectively, and median month 3 CST and macular volume were 345.5±89.8μm and 11.2±1.0mm3 respectively. CST and macular volume percent change between month 3 and baseline was -19.7±15.3% and -9.6±4.6% respectively. There was no significant change in FGF-2, IL-10, IL-8, MCP-1, sICAM-1, sVCAM-1 and TGF-β3 levels. There were significant increases in TGF-β1 (baseline median=87.44ρg/mL, month 2 median=205.9ρg/mL, median %change=135.5%, p=0.007), IP-10 (baseline median=119.9ρg/mL, month 2 median=217.8ρg/mL, median %change =81.7%, p=0.007), and HGF (baseline median=854.4ρg/mL, month 2 median=1269.7ρg/mL, median %change=48.6%, p=0.047). There were significant decreases in VEGF (baseline median=97.1ρg/mL, month 2 median=0ρg/mL, median %change=-100%, p=0.005), PLGF (baseline median=4.4ρg/mL, month 2 median=0ρg/mL, median %change=-100%, p=0.028), IL-6 (baseline median=13.6ρg/mL, month 2 median=6.8ρg/mL, median %change =-49.9%, p=0.011) and PDGF-AA (baseline median=68.7ρg/mL, month 2=36.5ρg/mL, median %change=-5.6%, p=0.032).
Conclusions: In treatment naïve patients with DME, aflibercept resulted in reduced OCT CST and macular volume. VEGF, PLGF, IL-6 and PDGF-AA were reduced. However, there were increases in IP-10 and pro-inflammatory cytokines including TGF-β1 and HGF. Larger, longer-term studies should examine if cytokine changes correlate with anatomic findings with aflibercept treatment.
