Purchase this article with an account.
Yasir Sepah, Mohamed Ibrahim, Alyssa Morimoto, Abeer Akhtar, Mauricio Maia, Kyu Hong, Montserrat Carrasco-Triguero, Diana Do, Menno van Lookeren Campagne, Quan Dong Nguyen; To determine changes in levels of cytokines in the anterior chamber (AC) fluid of eyes in patients with diabetic macular edema (DME)whom have been treated with repeated injections of ranibizumab (RBZ). Invest. Ophthalmol. Vis. Sci. 2013;54(15):1149.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To determine changes in levels of cytokines in aqueous fluid of eyes of patients with diabetic macular edema (DME) treated with serial injections of ranibizumab (RBZ).
Aqueous levels of the pro-inflammatory cytokine IL6 and the angiogenic chemokine IL8 were measured in serial samples from 131 patients, collected at baseline (BL), months (M) 3, 6, 9 and 12 from eyes with DME receiving treatment in the READ-3 Study. Patients received 6 monthly mandatory injections starting at BL. Thereafter, starting at M6, patients were retreated with RBZ if: 1) central foveal thickness reached 250 µm on Stratus TD-OCT; and/or 2) intraretinal fluid was detected on Spectralis SD-OCT. The aqueous samples were tested undiluted in an antibody-based multiplex immunoassay. Levels of IL6 and IL8 in the samples were quantitated from seven-point standard curves using recombinant IL6 and IL8. Minimum quantifiable concentration for both analytes was 0.61 pg/mL.
A decreasing trend was noted in the level of IL-8, a pro-angiogenic chemokine, from BL to M12 upon RBZ treatment. The mean changes (decrease from BL) at Ms 3, 6, 9 and 12 were 2.4 pg/mL (p< 0.19), 3.4 pg/mL (p< 0.07), 4.7 pg/mL (p< 0.02) and 5.0 pg/mL (p<0.01), respectively, when compared to BL (Mean=17.5,σ=27.1). An increasing trend was noted in the level of IL-6, a pro-inflammatory cytokine, from BL to M12. The mean changes (increase from BL) at Ms 3, 6, 9 and 12 were 21.4 pg/mL (p< 0.23), 35.0 pg/mL (p< 0.11), 5.8 pg/mL (p< 0.51) and 42.7 pg/mL (p< 0.05), respectively when compared to BL (Mean= 49.4,σ=90.5). The ratio of IL8 to IL6 primarily decreased throughout the course of treatment. Changes in IL8 and IL6 levels were not correlated to the changes in either retinal thickness or visual acuity obtained at the corresponding visits.
Therapy with RBZ for DME results in alterations in aqueous levels of IL6 and IL8. Repeated administrations of a VEGF antagonist (RBZ) suppressed IL8, implying that IL8 may act downstream of VEGF and play a role in VEGF-dependent development of DME, while increased IL-6 levels suggests that aqueous levels of this cytokine are regulated independently of VEGF. Further analyses using larger patient numbers are needed to determine whether IL6 plays a VEGF-independent role in the pathogenesis of DME.
This PDF is available to Subscribers Only