OCULOPLASTICS AND ORBIT The levels of 12 cytokines and growth factors in tears: hyperthyreosis vs euthyreosis Jelena Juri Mandić 1 & Ana Kozmar 2 & Sanja Kusačić-Kuna 3 & Anamarija Jazbec 4 & Krešimir Mandić 1 & Danijela Mrazovac 1 & Nenad Vukojević 1 Received: 3 January 2017 /Revised: 22 December 2017 /Accepted: 28 December 2017 /Published online: 14 January 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Purpose Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves’ hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO). Methods Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1β) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer. Results We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL- 10, VEGF, IL-1α, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-γ levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group. Conclusion There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves’ hyperthyreosis patients. Keywords Hyperthyroidism . Ocular surface inflammation . Thyroid-associated orbitopathy . Tear cytokines . Dysfunctional tear syndrome Introduction The role and importance of healthy tear film production by the lacrimal glands for optimal ocular function is well known. Changes in tear content — tear osmolarity and osmolality regardless of its etiology — can affect numerous tear functions such as local anti-microbial defense, wound-healing and in- flammatory response, and lead to ocular surface discomfort, redness, and visual deterioration [1]. There have been many studies investigating changes on ocular surface in various ocular diseases as well as in systemic diseases, suggesting that ocular surface changes may originate from both local and systemic inflammatory response [2, 3]. Earlier studies investigated effects of Graves’ orbitopathy (GO), Graves’ disease, and Hashimoto thyroiditis on ocular surface condition and tear composition. * Jelena Juri Mandić jjuri@kbc-zagreb.hr 1 Department of Ophthalmology, Clinical Hospital Centre Zagreb, Medical School University of Zagreb, Kispaticeva 12, 10000 Zagreb, Croatia 2 Department of Laboratory Diagnostics, Clinical Hospital Centre Zagreb, Zagreb, Croatia 3 Department of Nuclear Medicine and Radiation Protection, Clinical Hospital Centre Zagreb, Zagreb, Croatia 4 Department for Mathematics and Statistical Analysis, Faculty of Forestry, University of Zagreb, Zagreb, Croatia Graefe's Archive for Clinical and Experimental Ophthalmology (2018) 256:845–852 https://doi.org/10.1007/s00417-017-3892-6