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

November 30 2020

Makoto Yawata (IRCMS Visiting Associate Professor)

Paper information

Nobuyo Yawata, Sunita Awate, Yu-Chi Liu, Shi Yuan, Kaing Woon, Jay Siak, Yoh-Ichi Kawano, Koh-Hei Sonoda, Jodhbir S. Mehta, Makoto Yawata

Kinetics of Tear Fluid Proteins after Endothelial Keratoplasty and Predictive Factors for Recovery from Corneal Haze. J. Clin. Med. 2020, 9, 63.




  • Successful corneal transplantation entails an orderly progression of proper wound healing processes including support from the corneal stroma.

  • We characterized multi-parameter kinetic changes in immunological biomarkers indicative of a proper reconstructive process as reflected in the time-profiles of cytokine, chemokines and growth factors in the tear fluid.

  • Notably, the events occurring in the sugerical eye have clear effects on the anatomically-isolated contralateral eye.

  • A biomarker profile predictive of delayed clearance of corneal haze is proposed.


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.