SUMMARY AND CONCLUSIONS

Pre- or postoperative levels of the tear fluid cytokines TGF- 1, TNF- and PDGF-BB did not correlate with the development of corneal haze, as estimated by IVCM at 3 months after PRK.

However, it is noteworthy that none of our patients showed severe grade 3 or 4 haze. Subbasal nerve fibers were observed in the central cornea in 18/20 eyes. A positive correlation was observed between the regeneration of subbasal innervation (based on the IVCM nerve count at 3 months after PRK) and the thickness of regenerated epithelium, possibly reflecting the trophic effect of corneal nerves on epithelium. However, the CMTF haze estimate did not correlate with regeneration of the subbasal nerve plexus.

The majority of patients reported ongoing dry eye symptoms long after high myopic LASIK, although objective clinical signs were not demonstrable. No difference in corneal sensitivity was observed between patients and controls. I assume that at least some of the symptoms may be derived from aberrantly regenerated corneal nerves after LASIK surgery, thus representing a form of corneal neuropathy rather than conventional dry eye.

Primary Sjögren’s syndrome patients presented with corneal mechanical hypersensitivity, although their corneal subbasal nerve density did not differ from that of controls. Corneal mechanical sensitivity appeared to correlate with subjective symptoms and objective ocular signs, but not with corneal nerve density. However, alterations in corneal nerve morphology (nerve sprouting and thickened stromal nerves) and an increased number of APCs among subbasal nerves, implicating the role of inflammation, were observed. We suggest that these findings offer an explanation for the corneal hypersensitivity or even ocular hyperalgesia often observed in these patients.

ACKNOWLEDGMENTS

This study was carried at the Department of Ophthalmology, Helsinki University Central Hospital, from 2000 to 2007. I am sincerely grateful to Professor Leila Laatikainen and her successor, Professor Tero Kivelä, the current head of the Department of Ophthalmology, for providing excellent working facilities.

My deepest gratitude goes to my supervisor, Professor Timo Tervo, with whom I have had numerous inspiring conversations on scientific issues as well as on other common subjects of interest. Without his innovative ideas, my thesis would not be the same.

I am sincerely grateful to Professor Yrjö T. Konttinen. I have been privileged to be able to collaborate with him and to share thoughts and ideas 24 hours a day, 365 days a year, literally.

His consistent enthusiasm and positive thinking were instrumental to the completion of this thesis.

I am deeply grateful to Docent Minna Vesaluoma. Without her, I would not have been able to start my scientific career in 1998.

My thanks also belong to my collaborators and colleagues Carola Grönhagen-Riska, Maaret Helintö, Juha Holopainen, Eija Kaila, Sissi Katz, Liisa Konttinen, Maria Lamberg, Nina Lindbohm, Jukka Moilanen, Waldir Neira, Anna-Maija Teppo, Tuuli Valle, and Steven Wilson.

Professors Hannu Uusitalo and Marja-Liisa Vuori, the official reviewers of the thesis, are thanked for constructive criticism that vastly improved the manuscript.

I am deeply grateful to my author-editor Carol Ann Pelli for editing the language of this manuscript, and also to architect Anna Pakkala for drawing the pictures of my thesis.

Special thanks go to my teacher of ophthalmology in medical school in 1997, Docent Paula Summanen. She inspired my interest in ophthalmology at the beginning of my career. I also owe special thanks to Jouko Larinkari, MD and Tapio Stenborg, MD, for their encouragement and for teaching me the basics of ocular surgery and ophthalmology.

I am very grateful to Richard C. Troutman, MD, and the International Society of Refractive Surgery of the American Academy of Ophthalmology for the prestigious Troutman Award in 2007. I was privileged to meet Dr. Troutman, a pioneer in microsurgery of the eye, and really appreciate his encouragement.

Scientific work has brought an enormous amount of joy and contentment into my life. I cannot imagine my years as an ophthalmic resident without being involved in academic research.

Several interesting congresses around the world and many new friends are but a few examples.

Research has opened my eyes in so many ways and given me courage to make my own decisions, not always blindly accepting information written by others.

I am deeply grateful to have wonderful parents-in-law, Arja and Tapani Tuisku, who have always been there for me and lent a helping hand.

I have been blessed with loving parents, my mother Marja-Leena and my late father Seppo Tuominen. They have always been supportive and understanding and have encouraged me to follow in their footsteps as an MD. I remember discussions between my father and myself as a little boy about the definition of an academic dissertation. It was not easy to understand why people have to argue about things – why can’t they just agree? It took some thirty years for me to discover the answer. I also wish to thank my sister Anna and my brothers Jouni and Joonas for their interest in my project.

This work is dedicated to my family, to whom I owe my warmest thanks, especially to my wonderful wife Johanna, who has encouraged and sometimes even pressured me to finish this thesis. She has always taken such good care of us boys (see below), although it has sometimes required exceptionally long nerve fibers. My two lively sons, Tom (4 years) and Matias (3 years), have brought an enormous amount of energy and joy into my life. Unfortunately, I have not been able to do things with them as much as I would have liked. Thankfully, though, they understand that we are not always able to do our men’s jobs, such as fixing things with our different tools, because daddy must sometimes leave to fix eyes...

This work was supported by the Mary and Georg C. Ehrnrooths Foundation, the Finnish Eye Foundation, the Finnish Medical Society Duodecim, the Finnish Eye and Tissue Bank Foundation, the Friends of the Blind Foundation, the Paulo Foundation, and State EVO grants.

Helsinki, January 2008

Ilpo S. Tuisku

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In document Corneal nerves in refractive surgery and dry eye (sivua 57-73)