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Aqueous cytokine levels as indicators of disease severity and predictors of treatment response to ranibizumab in diabetic macular edema

Session Details

Session Title: Quick Fire Free Paper 1

Session Date/Time: Thursday 11/09/2014 | 08:00-10:00

Paper Time: 08:30

Venue: Boulevard D

First Author: : R.Hillier UK

Co Author(s): :    E. Ojaimi   D. Wong   A. Berger   S. Boyd   R. Kohly   R. Muni

Abstract Details


(i) To determine aqueous cytokine levels and their association with indicators of disease severity at baseline, and (ii) To prospectively investigate aqueous cytokine level changes in response to intravitreal ranibizumab therapy in patients with diabetic macular oedema (DMO).


Ophthalmology Department, St. Michael's Hospital and Sunnybrook Health Sciences Centre, Toronto, Canada


A prospective, non-randomised observational study with 3 months follow-up. Participants: adults with type I or II diabetes mellitus and centre involving DMO (central macular thickness ≥310µ on Cirrus OCT). Exclusions: proliferative retinopathy, vitreomacular traction or epiretinal membrane, previous intravitreal injection, and intraocular surgery or laser ≤3 months of baseline visit. Patients received monthly intravitreal ranibizumab 0.5mg for 3 months, followed by deferred laser before 6 months. Anterior chamber paracentesis was performed at baseline and month 2. Multiplex immunoassay (Ciraplex™) of aqueous samples was carried out in duplicate for candidate cytokines that could play a potential role in the pathogenesis of diabetic maculopathy (including VEGF, PLGF, TGF-B, ICAM-1, IL-6, IL-8, IL-10, VCAM and MCP-1).


n = 49. In a multivariate model controlling for patient age, lens status, baseline severity of retinopathy and size of foveal avascular zone, elevated aqueous ICAM-1 was the sole cytokine correlate of baseline disease severity as assessed by OCT macular volume. There was no association between any aqueous cytokine and OCT central macular thickness. Aqueous levels of the following cytokines were significantly reduced (month 2 versus baseline) in response to ranibizumab therapy: VEGF; p<0.0001, ICAM-1; p<0.0001, PLGF; p<0.0001, IL-6; p=0.0005 and MCP-1; p=0.01. High baseline ICAM-1 levels were predictive of a favourable response to ranibizumab therapy in terms of reduction in OCT macular volume.


Current management of centre-involving DMO focuses on modulation of vascular endothelial growth factor (VEGF). We found baseline aqueous VEGF levels to have no predictive value in terms of disease severity or response to intravitreal ranibizumab therapy. Conversely, baseline aqueous ICAM-1 served as a biomarker for disease severity and predicted treatment response. Identification of an aqueous cytokine that predicts favourable treatment response offers the future possibility of cytokine guided treatment algorithms. Additionally, modulation of ICAM-1 may offer a novel potential therapeutic target for patients with centre involving DMO.

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