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The anterior refracting surface of the eye is the thin tear film that forms on the surface of the cornea. When a contact lens is on worn, the tear film covers the contact lens as it would a bare cornea, and is affected by the contact lens material properties. Tear film irregularity can cause both discomfort and vision quality degradation. Under normal conditions, the tear film is less than 10 microns thick and the thickness and topography change in the time between blinks. In order to both better understand the tear film, and to characterize how contact lenses affect tear film behavior, two interferometers were designed and built to separately measure tear film behavior in vitro and in vivo. An in vitro method of characterizing dynamic fluid layers applied to contact lenses mounted on mechanical substrates has been developed using a phase-shifting Twyman- Green interferometer. This interferometer continuously measures light reflected from the surface of the fluid layer, allowing precision analysis of the dynamic fluid layer. Movies showing this fluid layer behavior can be generated. The fluid behavior on the contact lens surface is measured, allowing quantitative analysis beyond what typical contact angle or visual inspection methods provide. The in vivo interferometer is a similar system, with additional modules included to provide capability for human testing. This tear film measurement allows analysis beyond capabilities of typical fluorescein visual inspection or videokeratometry and provides better sensitivity and resolution than shearing interferometry methods. The in vitro interferometer system has measured the formation and break up of fluid layers. Different fluid and contact lens material combinations have been used, and significant fluid layer properties have been observed in some cases. This dissertation discusses the design of this interferometer along with analysis methods used. Example measurement results of different contact lens are presented highlighting the capabilities of the instrument. This dissertation also provides the in vivo interferometer design, along with the considerations that must be taken when designing an interferometer for on-eye diagnostics. Discussions include accommodating eye movement, design of null optics for a range of ocular geometries, and laser emission limits for on-eye interferometry in general.

<b>Purpose:</b> Assess the relationship between tear film drying and sensation between blinks. <b>Methods:</b> MATLAB sampled a slitlamp video camera, a potentiometer and a microphone while subjects kept one eye open for as long as possible. 23 subjects rated the intensity of the ocular sensation while video and voice data were collected simultaneously. The tear drying on the cornea was measured. <b>Results:</b> The sensation was triphasic. Two linear functions described the latter 2 parts of the data (r &#8805; 0. 95). The correlation between TBUT and the elbow in the time-discomfort function was 0. 72. Extent of tear film drying was linearly correlated to time (median correlation = 0. 88). The correlation between the discomfort elbow and image elbow was 0. 93 with single data pair for each subject. Analysis of sensation characteristics showed significant differences between itching and burning for both intensity and time (p = 0. 03 and p = 0. 02 respectively). <b>Conclusions:</b> Simultaneous recording of ocular surface appearance, discomfort intensity and attributes of sensation provide novel information about the development of discomfort during ocular surface drying. The rapid increase in discomfort proceeding blinking has been quantified and the relationship between the time course of drying and discomfort is elucidated.

The visual quality effects from the dynamic behavior of the tear film have been determined through measurements acquired with a high resolution Twyman-Green interferometer. The base shape of the eye has been removed to isolate the aberrations induced by the tear film. The measured tear film was then combined with a typical human eye model to simulate visual performance. Fourier theory has been implemented to calculate the incoherent point spread function, the modulation transfer function, and the subjective quality factor for this system. Analysis software has been developed for ease of automation for large data sets, and outputs movies have been made that display these visual quality metrics alongside the tear film. Post processing software was written to identify and eliminate bad frames. As a whole, this software creates the potential for increased intuition about the connection between blinks, tear film dynamics and visual quality.

Syfte: Syftet med studien var att utvärdera om det fanns någon variation av tårfilmens osmolariet, morgon och kväll hos personer utan symptom av torra ögon. Metod: Tårfilmens osmolaritet mättes på totalt 30 patienter, två gånger på en dag; morgon och kväll. Mätningarna utfördes med TearLabTM osmolarity system. Både höger och vänster öga mättes på varje patient. Samtliga deltagande ombads fylla i en symptomenkät vid namn TERTC-DEQ. Endast personer utan symptom på torra ögon tilläts delta i studien. Alltså personer med totalt  17 poäng på TERTC-DEQ. Resultat: Ingen statistisk signifikant skillnad kunde iakttas hos personernas osmolaritet mellan morgon och kväll (P &gt; 0.05). Slutsats: I studien kunde ingen skillnad på osmolaritet i tårfilmen iakttas mellan morgon och kväll hos personer utan symptom på torra ögon. Därmed tros tårfunktionen hos dessa personer fungera korrekt. Tårfilmens osmolaritet upprätthåller rätt balans och förändras därför inte från morgon till kväll. / Aim: The aim of this study was to determine if there is an diurnal variation in tear osmolarity among healty non dry-eye subjects. Method: The osmolarity of the tearfilm was measured in a total of 30 subjects twice a day; morning and evening, using the TearLabTM osmolarity system. Measurements were performed on both right and left eye in all the subjects. All subjects were asked to fill in a symptom questionnaire named TERTC-DEQ and only those with a total score of  17 points were allowed to participate in the study. Subjects below this score had therefore no symptoms of dry eye. Results: There was no statistical significant difference between the subjects tear osmolarity comparing the morning and evening values (P&gt;0,05). Conclusion: This study did not show any difference in the subjects tear osmolarity, comparing morning and evening measurements. None of the individuals had any symptoms of dry eye. Therefore it is believed that in subjects with no symptoms of dry eye, the tear osmolarity remains stable between morning and evening.

<b>Purpose:</b> Assess the relationship between tear film drying and sensation between blinks. <b>Methods:</b> MATLAB sampled a slitlamp video camera, a potentiometer and a microphone while subjects kept one eye open for as long as possible. 23 subjects rated the intensity of the ocular sensation while video and voice data were collected simultaneously. The tear drying on the cornea was measured. <b>Results:</b> The sensation was triphasic. Two linear functions described the latter 2 parts of the data (r &#8805; 0. 95). The correlation between TBUT and the elbow in the time-discomfort function was 0. 72. Extent of tear film drying was linearly correlated to time (median correlation = 0. 88). The correlation between the discomfort elbow and image elbow was 0. 93 with single data pair for each subject. Analysis of sensation characteristics showed significant differences between itching and burning for both intensity and time (p = 0. 03 and p = 0. 02 respectively). <b>Conclusions:</b> Simultaneous recording of ocular surface appearance, discomfort intensity and attributes of sensation provide novel information about the development of discomfort during ocular surface drying. The rapid increase in discomfort proceeding blinking has been quantified and the relationship between the time course of drying and discomfort is elucidated.

The cornea is the anterior most surface of the eye and plays a critical role in vision. A thin fluid layer, the tear film, coats the outer surface of the cornea and serves to protect, nourish, and lubricate the cornea. At the same time, the tear film is responsible for creating a smooth continuous surface where the majority of refraction takes place in the eye. A significant component of vision quality is determined by the shape of the cornea and stability of the tear film. It is desirable to possess an instrument that can measure the corneal shape and tear film surface with the same accuracy and resolution that is currently performed on common optical elements. A dual interferometer system for measuring the dynamic corneal topography is designed, built, and verified. The completed system is validated by testing on human subjects. The system consists of two co-aligned polarization splitting Twyman-Green interferometers designed to measure phase instantaneously. The primary interferometer measures the surface of the tear film while the secondary interferometer simultaneously tracks the absolute position of the cornea. Eye motion, ocular variation, and a dynamic tear film surface will result in a non-null configuration of the surface with respect to the interferometer system. A non-null test results in significant interferometer induced errors that add to the measured phase. New algorithms are developed to recover the absolute surface topography of the tear film and corneal surface from the simultaneous interferometer measurements. The results are high-resolution and high-accuracy surface topography measurements of the in vivo cornea that are captured at standard camera frame rates. This dissertation will cover the development and construction of an interferometer system for measuring the dynamic corneal topography of the human eye. The discussion starts with the completion of an interferometer for measuring the tear film. The tear film interferometer is part of an ongoing research project that has spanned multiple dissertations. For this research, the instrument was tested on human subjects and resulted in refinements to the interferometer design. The final configuration of the tear film interferometer and results from human subjects testing are presented. Feedback from this instrument was used to support the development and construction of the interferometric corneal topographer system. A calibration is performed on the instrument, and then verified against simulated eye surfaces. Finally, the instrument is validated by testing on human subjects. The result is an interferometer system that can non-invasively measure the dynamic corneal topography with greater accuracy and resolution than existing technologies.

Purpose: Lectins play an important role in many biological processes. The aim of this work was to analyse mainly the expression of endogenic lectins, such as galectins and plant lectin, e.g. Dolichos biflorus agglutinin (DBA), and their glycoligands in the tear fluid, human corneal and conjunctival epithelium in physiological and disease conditions. Further, we studied the human natural antibody against Galα1,3Gal-R, which is mainly responsible for hyperacute rejection of xenografts transplants. We tried to investigate its localization in human corneal epithelium, lacrimal gland and tears. Material and Methods: Human tissue (lacrimal gland, tear fluid, conjunctiva, cornea, epidermis, keratinocyte and cultured corneal epithelium), as well as porcine tissue (cornea, liver and epidermis) were examined. Endogenous galectins (galectins-1, -3 and -7) were detected using immunohistochemistry methods. Binding sites for galectins, as well as binding sites for plant lectin Dolichos biflorus agglutinin, were localized by lectin histochemistry. Reverse lectin histochemistry was used for the study of binding reactivity of endogenous lectins using labelled (neo)glycoligands. Employing biotinylated natural human IgG anti -galactosides, as well as anti -galactosides, we detected reactive epitopes in human...

abstract: This dissertation presents methods for the evaluation of ocular surface protection during natural blink function. The evaluation of ocular surface protection is especially important in the diagnosis of dry eye and the evaluation of dry eye severity in clinical trials. Dry eye is a highly prevalent disease affecting vast numbers (between 11% and 22%) of an aging population. There is only one approved therapy with limited efficacy, which results in a huge unmet need. The reason so few drugs have reached approval is a lack of a recognized therapeutic pathway with reproducible endpoints. While the interplay between blink function and ocular surface protection has long been recognized, all currently used evaluation techniques have addressed blink function in isolation from tear film stability, the gold standard of which is Tear Film Break-Up Time (TFBUT). In the first part of this research a manual technique of calculating ocular surface protection during natural blink function through the use of video analysis is developed and evaluated for it's ability to differentiate between dry eye and normal subjects, the results are compared with that of TFBUT. In the second part of this research the technique is improved in precision and automated through the use of video analysis algorithms. This software, called the OPI 2.0 System, is evaluated for accuracy and precision, and comparisons are made between the OPI 2.0 System and other currently recognized dry eye diagnostic techniques (e.g. TFBUT). In the third part of this research the OPI 2.0 System is deployed for use in the evaluation of subjects before, immediately after and 30 minutes after exposure to a controlled adverse environment (CAE), once again the results are compared and contrasted against commonly used dry eye endpoints. The results demonstrate that the evaluation of ocular surface protection using the OPI 2.0 System offers superior accuracy to the current standard, TFBUT. / Dissertation/Thesis / Ph.D. Industrial Engineering 2012

Purpose: The aim of the study was to quantify the isolated tear film adhesion error in a Goldmann applanation tonometer (GAT) prism and in a correcting applanation tonometry surface (CATS) prism. Methods: The separation force of a tonometer prism adhered by a tear film to a simulated cornea was measured to quantify an isolated tear film adhesion force. Acrylic hemispheres (7.8 mm radius) used as corneas were lathed over the apical 3.06 mm diameter to simulate full applanation contact with the prism surface for both GAT and CATS prisms. Tear film separation measurements were completed with both an artificial tear and fluorescein solutions as a fluid bridge. The applanation mire thicknesses were measured and correlated with the tear film separation measurements. Human cadaver eyes were used to validate simulated cornea tear film separation measurement differences between the GAT and CATS prisms. Results: The CATS prism tear film adhesion error (2.74 +/- 0.21 mmHg) was significantly less than the GAT prism (4.57 +/- 0.18 mmHg, p<0.001). Tear film adhesion error was independent of applanation mire thickness (R-2=0.09, p=0.04). Fluorescein produces more tear film error than artificial tears (+0.51 +/- 0.04 mmHg; p<0.001). Cadaver eye validation indicated the CATS prism's tear film adhesion error (1.40 +/- 0.51 mmHg) was significantly less than that of the GAT prism (3.30 +/- 0.38 mmHg; p=0.002). Conclusion: Measured GAT tear film adhesion error is more than previously predicted. A CATS prism significantly reduced tear film adhesion error by similar to 41%. Fluorescein solution increases the tear film adhesion compared to artificial tears, while mire thickness has a negligible effect.