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Open AccessArticle

Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze

by Nobuyo Yawata 1,2,3,4,*, Sunita Awate 4,†, Yu-Chi Liu 2,3,5,†, Shi Yuan 2,†, Kaing Woon 2,†, Jay Siak 2,3,5,6, Yoh-Ichi Kawano 7, Koh-Hei Sonoda 1, Jodhbir S. Mehta 2,3,5,6,† and Makoto Yawata 4,8,9,10,11,†
Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan
Singapore Eye Research Institute, Singapore 168751, Singapore
Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research, A*STAR, Singapore 117609, Singapore
Singapore National Eye Centre, Singapore 168751, Singapore
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
Department of Ophthalmology, Fukuoka Dental College, Fukuoka 814-0193, Japan
Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
National University Health System, Singapore 119228, Singapore
Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore
International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-8555, Japan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Clin. Med. 2020, 9(1), 63;
Received: 4 November 2019 / Revised: 10 December 2019 / Accepted: 21 December 2019 / Published: 26 December 2019
(This article belongs to the Special Issue Corneal Transplant Immunology)
Endothelial keratoplasty (EK) is less invasive with faster recovery as compared to conventional penetrating keratoplasty, however, it relies on the clarity of the host corneal stroma. Corneal transplantation involves the induction of immune tolerance for allogeneic tissues as well as the corneal wound healing process, in which coordinated interactions between cytokines and growth factors are critical. In this study, we profiled the expression of 51 soluble factors in the tear fluid over the course of EK and have provided evidence of dynamic changes in cytokine expression in the ipsilateral and contralateral eyes. Cluster analyses classified the cytokine expression kinetics into five groups. Group 1 proteins included TGF-b1, IL-1b, and innate proinflammatory cytokines, which bilaterally increased after surgery, despite the use of topical corticosteroid in the transplanted eyes. Local corticosteroids suppressed cytokines involved in adaptive immunity in the transplanted eyes but not in the contralateral eyes. We found tear protein expression at baseline and one week post-surgery to be a potential predictive biomarker of delayed recovery after EK in terms of the corneal haze and visual acuity. Furthermore, Group 1 tear proteins were most associated with persistent corneal haze pre-surgery as well as visual acuity at one month-post transplant. View Full-Text
Keywords: endothelial keratoplasty; tear fluid cytokines; corneal haze endothelial keratoplasty; tear fluid cytokines; corneal haze
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MDPI and ACS Style

Yawata, N.; Awate, S.; Liu, Y.-C.; Yuan, S.; Woon, K.; Siak, J.; Kawano, Y.-I.; Sonoda, K.-H.; Mehta, J.S.; Yawata, M. Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze. J. Clin. Med. 2020, 9, 63.

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