ABSTRACT.Purpose: The purpose of this study was to evaluate the ICare tonometers precision and accuracy and the extent to which intraocular pressure (IOP) measurements are influenced by measuring position. Methods: This was carried out by comparing the central and peripheral ICare-IOP readings and comparing ICare-with the Goldmann applanation tonometer (GAT)-IOP readings. IOP was measured using the ICare rebound tonometer on the right eye of 40 subjects, straight at the centre of the cornea (CS), straight 2 mm from the nasal and temporal limbus (NS and TS), and in 10 degrees nasally and temporally angled positions measured from the same location as CS (NA and TA). The IOP was also assessed with the GAT. Results: Central IOP (CS) was significantly (p < 0.001) greater than peripheral measurements (NS, TS, NA and TA) by approximately 3-4 mmHg. Centre IOP (CS) significantly overestimated by mean 2 mmHg and the peripheral measurements significantly underestimates approximately 1.4-2 mmHg compared with GAT readings. Conclusion: The ICare tonometer may be useful in a routine clinical setting for IOP screening, but the ICare measurement is not a substitute for the GAT measurement, when a precise and accurate IOP is desired.

Corneal epithelium is maintained throughout life by well-orchestrated proliferation of limbal epithelial stem cells (LESCs), followed by migration and maturation centripetally towards the ocular surface. Disturbance of LESCs can potentially lead to a blinding condition, which can be reversed by reconstitution of a functional LESC pool. The current clinical procedures are effective to some degree, however, deeper knowledge of the molecular interplay within the limbal niche is necessary to achieve a fully satisfactory patient outcome. The present study was thus undertaken to carry out a comprehensive transcriptome analysis of four distinct human limbal compartments, including basal limbal crypts (BLCs), superficial limbal crypts (SLCs), cornea, and the supporting stroma, with the aid of laser capture microdissection and deep RNA sequencing. The tissue harvest pipeline was rigorously optimized so that the exposure to cold ischemia would be less than five minutes. The global gene ontology analysis confirmed existence of primitive cells in BLCs, migratory and activated cells in SLCs, and differentiated cells in cornea. Interestingly, many significantly upregulated genes in SLCs mapped to processes involved in regulation of vasculature, such as sFLT1. In contrast, BLCs exhibited many genes mapping to neurogenic processes and processes related to cell development. The primitive nature of BLCs was, furthermore, confirmed by the KEGG pathway analysis, and some potential regulators of LESCs were revealed, such as Lrig1 and SOX9. The analysis also yielded comprehensive lists of uniquely expressed genes in both BLCs and cornea, which may be useful to identify possible biomarkers. In conclusion, the current investigation provides new insight into the relationship between distinct cell populations within the limbal niche, identifies candidates to be verified for novel biological functions, and yields a wealth of information for prospective data mining.

List of Papers This PhD dissertation is based on a review and the following three original manuscripts. The manuscripts are referred to in text by their corresponding Roman numerals: I. Bath C, Yang S, Muttuvelu D, Fink T, Emmersen J, Vorum H, Hjortdal J, Zachar V (2013): Hypoxia is a key regulator of limbal epithelial stem cell growth and differentiation. Stem Hospital during a period from 2009 to 2013. The initial main goals of this dissertation were twofold. Firstly, we wanted to establish the necessary skills and laboratory techniques for the successful culturing of human limbal epithelial stem cells, but also to optimize these cultures to a defined and serum-free environment to facilitate later clinical translation. Secondly, we wanted to use highly advanced laboratory techniques for the precise characterization of different cellular compartments within the corneal epithelium. This should in theory provide us with an important knowledge of both possible biomarkers and the molecular genetics of corneal epithelial cells. As a medical doctor with very limited laboratory experience, the process of reaching these goals proved very demanding and labour-intensive. With the help of many people mentioned in acknowledgements, but especially my supervisors, I am very happy that the hard work has proven fruitful in not only reaching our goals, but also taking our work further than initially outlined. I am confident, that the struggle of exploring the previously unknown territory of laboratory work will prove helpful during my clinical career, as molecular medicine is rapidly evolving with the surfacing of new exciting possibilities within the field of regenerative medicine. The journey has been long and challenging, but also exciting, and it is my hope, that this work will supply a piece of the greater puzzle needed to be solved before Danish patients can benefit from the new fascinating prospects of corneal bioengineering. Acknowledgements This section acknowledges friends, family, colleagues, and funding sources that has been indispensable in the completion of my dissertation. Being blessed with the opportunity to work within the most exciting specialty in medicine, Ophthalmol-ogy, I am grateful to all my colleagues at the Departments of Ophthalmology in Aalborg and Aarhus, who have provided me with this chance. I would like to express my gratefulness to my main supervisor and Professor at the Department of Ophthalmology, Aarhus University Hospital, Jesper Hjortdal, for willingly accepting the role as my main supervisor. Throughout the PhD study, he has been indispensable for the completion of this dissertation by his excellent insight and advice at all hours, his efforts in supplying tissues for research, and finally, but not least, for help with all sorts of problems along the way. Another person, whom I cannot thank enough, is my supervisor and head of the Laboratory for Stem Cell Research, Aalborg University, Professor Vladimir Zachar. I am grateful to him for letting me use his lab and for tirelessly teaching me...

The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light is reduced in depressed patients. These results further emphasize the interaction of light exposure with depression.

ObjectiveThe purpose of this study was to evaluate the stratification of follow-up and referral pathways after implementation of a systematic cloud-based electronic-referral teleophthalmological service for optometry-initiated ocular posterior segment disease referrals to the Danish national eye care system.Methods and AnalysisA retrospective cohort study was conducted in the period from 1 August 2018 to 31 July 2019. Patients with suspected ocular posterior segment disease reviewed by the telemedical ophthalmology service were included. The service stratified patients into the categories: no need for follow-up, follow-up by optometrist, follow-up by the telemedical service and referral to the national Danish eye care service.ResultsFrom a pool of 386 361 customers, 9938 patients were enrolled into this study. 19.5% of all patients were referred to the Danish national eye care system, while 80.5% of the patients in the telemedical service were not, in the period from 1 August 2018 to 31 July 2019. 14.4% of the optometrist referrals did not need any follow-up, while a majority of 66.1% needed some follow-up either by the optometrist themselves or within the telemedical service.ConclusionOptometrist posterior segment disease referrals can be considerably reduced with a risk stratified approach and optimal use of technology. New models can improve and streamline the healthcare system.