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Invest Ophthalmol Vis Sci. 2019 Mar 1;60(4):868-876. doi: 10.1167/iovs.18-25761.

Mediators of Corneal Haze Following Implantation of Presbyopic Corneal Inlays.

Fenner BJ1,2, Liu YC1,2,3, Koh SK2, Gao Y2, Deng L4, Beuerman RW2,3,5, Zhou L2,3,6, Theng JTS7, Mehta JS1,2,3.

Author information

Singapore National Eye Centre, Singapore.
Singapore Eye Research Institute, Singapore.
Eye Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore.
Department of Statistics and Applied Probability, National University of Singapore.
Neuroscience Signature Research Program, Duke-NUS Graduate Medical School, Singapore.
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Eagle Eye Centre, Singapore.



To identify protein mediators of corneal haze following presbyopic corneal inlay surgery.


Tears were collected from eyes with corneal haze following surgery with a shape-changing corneal inlay. Samples were subjected to quantitative proteomic analysis using iTRAQ and proteins significantly increased or decreased (1.3-fold or more) in haze eyes relative to fellow eyes were identified. Expression ratios were compared to postoperative eyes without corneal haze to identify proteins selectively increased or decreased in corneal haze eyes.


Inlay-associated haze occurred in 35% of eyes (6 of 17). Of 1443 unique tear proteins identified, eight proteins were selectively reduced in tears from postoperative haze eyes and one protein selectively increased. Proteins reduced in haze eyes included complement 4a (level relative to nonhaze eyes 0.464, P = 0.037), complement factor H (0.589, P = 0.048), immunoglobulin kappa variable 2-29 (0.128, P = 0.006), immunoglobulin kappa variable 2D-28 (0.612, P = 0.025), immunoglobulin lambda variable 7-46 (0.482, P = 0.007), S100 calcium binding protein A4 (0.614, P = 0.048), Shootin-1 (0.614, P = 0.048), and tissue inhibitor of metalloproteinase-1 (0.736, P = 0.023). The Xaa-Pro aminopeptidase 1 was increased in haze eyes relative to nonhaze eyes (1.517, P = 0.023).


Corneal haze following corneal inlay surgery is associated with reduction in levels of known inflammatory and immune mediators. These findings represent a starting point for elucidation of pathways involved in corneal haze following synthetic inlay implantation and may enable development of targeted therapies that modulate the haze response.


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