Inflammatory mediators in the vitreal reflux of patients with diabetic macular edema

  • Andrea Cacciamani
  • Graziana Esposito
  • Fabio Scarinci
  • Mariacristina Parravano
  • Lucia Dinice
  • Marta Di Nicola
  • Alessandra MiceraEmail author
Medical Ophthalmology



To quantify inflammatory, growth/angiogenic, and tissue remodeling mediators in vitreal reflux (VR) in patients with diabetic macular edema (DME), as collected at first and third intravitreal anti-vascular endothelial growth factor (anti-VEGF, ranibizumab) injection.


Thirty (30) consecutive patients (type-2 diabetes mellitus) with visual impairments due to DME and undergoing the first (untreated DME) or the third (treated DME) intravitreal injection of anti-VEGF were included in the study. At the time of surgery, patients were subjected to clinical assessment and spectral domain-optical coherence tomography (SD-OCT), including central retinal thickness (CRT), macular volume, and outer nuclear layer/retinal pigment epithelial (ONL/RPE) measurements. VR sampling was performed at the time of needle removal and subjected to customized protein-array, Western blotting (WB), Ella™ microfluidic, and/or enzyme-linked immunosorbent assay (ELISA) analysis. Biostrumental and biochemical data were collected just prior to the surgery and are representative of disease state. Clinical, biostrumental, and numerous biomarkers and cytokines were statistically compared.


Decreased CRT values were detected in treated DME retinas, as compared to untreated ones (p ≤ 0.05). Differences in VEGF and other mediator expressions between treated and untreated DME were detected in VR samples. Particularly, osteopontin (p ≤ 0.05), interleukin 6 (IL6) (p ≤ 0.05), and VEGF (p ≤ 0.1) values were decreased after treatment. Significant changes were validated by WB, ELISA, and Ella™ analysis.


Overall, the biostrumental and biochemical data suggest the presence of a specific pattern of inflammation in VR after treatment. The data would suggest the presence of other mechanisms and mediators, in addition to VEGF, accountable for DME progression.


Anti-VEGF DME Inflammation Vitreal reflux Osteopontin 



The study was partially supported by the Italian Ministry of Health (RC2016), Fondazione Roma (Italy), and MaBIOS-kit Grant (AC, GE, AM; Regione Lazio; LR13/2015; FILAS-RU-2014-112).


Italian Ministry of Health and Fondazione Roma (Italy).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the intramural IFO/Bietti Ethics committee and conducted in accordance with the ethical standards stated in the Declaration of Helsinki. Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.IRCCS – Fondazione BiettiRomeItaly
  2. 2.Department of Medical, Oral and Biotechnological Sciences, Laboratory of BiostatisticsUniversity G. d’Annunzio Chieti-PescaraChietiItaly

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