Hypoglossal-Facial Nerve Reconstruction Using a Y-Tube-Conduit Reduces Aberrant Synkinetic Movements of the Orbicularis Oculi and Vibrissal Muscles in Rats

The facial nerve is the most frequently damaged nerve in head and neck trauma. Patients undergoing facial nerve reconstruction often complain about disturbing abnormal synkinetic movements of the facial muscles (mass movements, synkinesis) which are thought to result from misguided collateral branching of regenerating motor axons and reinnervation of inappropriate muscles. Here, we examined whether use of an aorta Y-tube conduit during reconstructive surgery after facial nerve injury reduces synkinesis of orbicularis oris (blink reflex) and vibrissal (whisking) musculature. The abdominal aorta plus its bifurcation was harvested (N = 12) for Y-tube conduits. Animal groups comprised intact animals (Group 1), those receiving hypoglossal-facial nerve end-to-end coaptation alone (HFA; Group 2), and those receiving hypoglossal-facial nerve reconstruction using a Y-tube (HFA-Y-tube, Group 3). Videotape motion analysis at 4 months showed that HFA-Y-tube group showed a reduced synkinesis of eyelid and whisker movements compared to HFA alone

Bionic Lid Implant for Natural Closure (BLINC)

Facial nerve palsy (FNP) leads to an inability to blink. The exposed eye is at risk of developing corneal keratopathy and currently there is a lack of solution to active eye closure that is immediate and reliable. Bionic Lid Implant for Natural Closure (BLINC) proposes the use of an implantable actuator combined with the effects of an eyelid sling for dynamic eye closure. The aims of this thesis are to 1) explore the clinical need for BLINC, 2) describe the BLINC technology, and 3) present the results of its application in cadaveric and live models. Methods The aims of this project are addressed in three parts. In part one, the current therapies addressing key clinical end points in FNP from an ocular perspective and the setting where BLINC may first be used are explored. In part two the science behind BLINC is outlined. Finally in part three application of BLINC in cadaveric and live models are studied followed by a discussion on future steps preceding a pilot study in humans. Results Patients with FNP consistently identify issues related to the eye a primary concern. Current reanimation strategies offer the possibility of dynamic eye closure but the results are delayed and often unpredictable. BLINC reliably achieves active eye closure in cadaveric models by means of a wireless-powered, implantable electromagnetic actuator in conjunction with an eyelid sling. BLINC closes the eye in a similar fashion to natural closure for a symmetrical blink in FNP. Successful application of an inactive device in its complete form is achieved in a live animal without significant morbidity. Conclusion BLINC offers the possibility of restoring active eye closure with use of an implantable actuator. The concept has been successfully demonstrated in cadaveric models with successful device implantation in a live model. Future live trials are needed to address the remaining biocompatibility issues in preparation for human application

A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY

This thesis highlights the current gold-standard surgical procedures for the rehabilitation of mimicry in individuals with facial paralysis and explores the potential application of functional electrical stimulation (FES) as a novel treatment restoring the face mimicry. Closed-loop facial pacing represents an innovative solution for prosthetically assisted movements. In particular, blinking is typically symmetrical, enabling healthy eye blink on one side of the face to serve as a trigger to pace assisted blinks on the contralateral side, in case of unilateral peripheral facial palsy. The goals of this research are developing an eyeblink detection system and advancing the understanding of performing surface FES of the facial nerve in order to elicit artificial eyeblinks. The application of a biomimetic device to individuals with acute reversible facial palsy would provide immediate restoration of the periocular function and could be used until either the patient recovers sufficient function to no longer require assistance for eye closure, or the decision is made to proceed with further surgery

Engineering Solutions To The Characterisation Of Clinical Disorders Of Upper Eyelid Movement

This project is about improving functioning in patients with ptosis associated with poor levator palpebrae superioris (LPS) function. LPS is a highly specialised muscle responsible for raising the eyelid. Defective LPS may cause the eyelid to droop uncontrollably, thereby covering the visual axis and affecting vision. The current method of correction relies heavily on the experience of the surgeon. Rarely, the implanted materials are at risk of exposure, infection, rejection. More commonly, the ability to completely shut the eyelids is impaired, leading to the danger of corneal exposure that can lead to severe pain and sight-threatening complications. Many patients will require repeat surgeries for correction in the future. One reason for such mechanical failure includes the lack of understanding of the mechanical characteristics of the muscle involved in blinking, and the current surgical suspension material used in replacing it. This lack of a scientific basis means that ptosis is a major challenge in ophthalmic surgery. The aim of this work will include analysing and characterising LPS and blinking dynamics, in the hope of improving future clinical procedures and perhaps provide insights on surgical materials. Two separate approaches are running in parallel to investigate blinking dynamics: to define the mechanical characteristics and properties of the muscles involved in blinking, a new apparatus was designed and constructed to measure the force in eyelid closure, particularly the maximum force of contraction and natural force of closure. On another aspect, a high-speed camera was used at Moorfields Eye Hospital to record and analyse blinking in 32 patients with ptosis, thyroid eye disease and Blepharospasm. The collected and analysed data are used to investigate how eye blinking dynamics in diseased patients are different from healthy individuals and to attempt to separate them from controls using a modelling system. In addition, the blinking dynamics of dermatochalasis patients before and after blepharoplasty surgery were also compared with healthy individuals using high-speed camera and later advanced statistical analysis

The Ocular Surface Control of Blinking, Tearing and Sensation

Thesis (Ph.D.) - Indiana University, Optometry, 2014Dry eye is a common condition that affects millions in the US and worldwide. It is considered to be a multifactorial disease of the tear film and ocular surface and is associated with symptoms of ocular discomfort and visual disturbance. Low blink rate has been identified as a potential risk factor for the development of dry eye because it can result in increased evaporative loss from the tear film. Failure of tear secretion has also been recognized as one of the main factors for dry eye development, characterized as low tear volume and slow tear turnover rate. Both factors in turn may lead to increased tear film hyperosmolarity and instability, which are considered core mechanisms of dry eye. In the natural condition, the ocular surface is mainly protected by blinking and tear secretion in that the newly secreted tears flow into the upper and lower meniscus and the blink spreads the new tear film from the meniscus to the ocular surface. Therefore, the ocular surface control over blinking and tear secretion is important in the etiology of the dry eye condition. In this proposal, we develop a laboratory model using human subjects to test how input from the ocular surface affects both blinking and tear secretion. We hypothesize that ocular surface stimuli will activate corneal receptors to signal a high blink rate, reflex tear secretion and ocular sensations of discomfort. These probably act together for the purpose of preventing ocular damage. These results will help us to understand the manner in which the ocular surface responds to adverse stimuli, which may ultimately lead toward further development of treatments or methods in dry eye patients

Dopaminergisten geenien variaatioiden yhteys keskushermoston dopamiinitoiminnan mahdolliseen mittariin: silmien räpytystiheyteen

Tavoitteet. Silmien räpytystiheys (sEBR) on behavioraalinen mittari, joka on yhdistetty dopamiinitoimintaan otsalohkon ja aivojuovion alueilla. Lukuisissa tutkimuksissa dopamiinitoimintaan kiihdyttävästi tai heikentävästi vaikuttavien neurologisten häiriöiden ja farmakologisten agenttien on todettu vastaavasti lisäävän tai vähentävän sEBR:ää. Näin ollen sEBR voisi toimia ihmisaivojen dopamiinitoiminnan epäsuorana mittarina, joka olisi edullisempi ja vähemmän invasiivinen kuin esimerkiksi positroniemissiotomografia. Ei kuitenkaan tiedetä, ovatko dopaminergisten geenien variaatiot yhteydessä sEBR:ään. Tässä poikittaistutkimuksessa sEBR:n ja dopaminergisen genotyypin yhteyttä tarkasteltiin kahdessa otoksessa. Tutkimuksessa keskityttiin kahteen variaatioon dopaminergisissa geeneissä: COMT Val158Met polymorfismiin ja Taq1A polymorfismin A1 alleeliin. Hypoteeseina oli, että COMT Val158Met polymorfismi olisi yhteydessä korkeampaan ja Taq1A polymorfismin A1 alleeli matalampaan sEBR:ään. Koska BMI ja ruokavalio on myös yhdistetty poikkeavuuksiin aivojuovion dopamiinitoiminnassa, tutkimuksessa tarkasteltiin BMI:n, ruokavalion ja sEBR:n yhteyttä eksploratiivisesti. Menetelmät. Tutkimuksessa käytettiin otoksia kolmesta poikittaistutkimuksesta: Interventiotutkimus (n = 31) on kokeellinen tutkimus, joka tarkastelee akuutin fenyylialaniinin/tyrosiinin puutoksen vaikutuksia kognitiivisiin mittareihin. GREADT- tutkimus (n = 86) selvittää genotyypin ja ruokavalion vaikutuksia dopamiinitoimintaan, ja BEDOB-tutkimus (n=69) tarkastelee liikalihavuuden ja ahmimishäiriön neurokognitiivisia mekanismeja. GREADT- ja BEDOB-tutkimuksissa hyödynnettiin samanlaisia menetelmiä, minkä vuoksi tutkimusotokset yhdistettiin analyyseja varten. Räpytystiheyttä mitattiin infrapuna-silmänliikemittausjärjestelmällä. Osallistujat täyttivät itsearviointikyselyn (the Dietary Fat and free Sugar Questionnaire, DFS), jonka avulla arvioitiin, kuinka paljon he kuluttivat tyydyttyneitä rasvoja ja prosessoitua sokeria. GREADT/BEDOB-otoksessa yhteyksiä polymorfismien, BMI:n, DFS-pistemäärän ja sEBR:n välillä tarkasteltiin varianssianalyyseilla. Interventiotutkimuksessa tutkittiin yleistetyn lineaarisen sekamallin avulla, muuttuiko sEBR intervention seurauksena ja vaikuttivatko genotyypit, BMI tai DFS-pistemäärä sEBR:ään. Tulokset. Genotyypillä ei ollut vaikutusta sEBR:ään kummassakaan otoksessa. BMI:llä oli merkitsevä päävaikutus sEBR:ään GREADT/BEDOB-otoksessa. Yhteys oli merkitsevä ylipainoisten ja liikalihavien ryhmässä muttei normaalipainoisten ryhmässä. DFS-pistemäärällä ei ollut vaikutusta sEBR:ään kummassakaan otoksessa. Johtopäätökset. Tulokset tukevat näkemystä, jonka mukaan sEBR:n käyttöön terveen ihmisen dopamiinitoiminnan mittarina tulisi suhtautua varauksella. Tulevissa tutkimuksissa metodologiaan tulisi kiinnittää erityistä huomiota.The aim of the study. Spontaneous eye blink rate (sEBR) is a behavioral index that has been linked to frontostriatal dopaminergic activity. Reduced or increased dopaminergic activity due to clinical conditions tends to be associated with lower or higher sEBR, respectively, and sEBR can be modulated by pharmacological agents that affect dopamine signaling. Consequently, sEBR could serve as an easily accessible method of assessing brain dopaminergic tone indirectly in humans. It might be preferable to more expensive and invasive techniques such as positron emission tomography. However, it remains unclear whether variations in dopaminergic genes predict sEBR. In this cross-sectional study, the relationship between sEBR and dopaminergic genotype was examined in two samples. Two genetic polymorphisms were focused on: the COMT Val158Met polymorphism and the A1 allele of the Taq1A polymorphism. It was hypothesized that the COMT Val158Met polymorphism is associated with higher sEBR, and that the A1 allele of the Taq1A polymorphism is associated with lower sEBR. As BMI and diet have been linked with altered striatal dopamine function, the possible association between BMI, diet, and sEBR was studied exploratively. Methods. Data from three cross-sectional studies was used in this study: The intervention study (n = 31) is an experimental study that examines the effect of acute phenylalanine/tyrosine depletion on cognitive measures. The GREADT study (n = 86) focuses on the effects of genotype and diet on dopamine tone. The BEDOB study (n = 69) investigates neurocognitive mechanisms in obesity and binge eating disorder. Similar methodologies were used in the GREADT and the BEDOB studies, which is why these datasets were combined for the analyses. Blink rates were measured using an infrared eye tracking system. The participants completed the Dietary Fat and free Sugar Questionnaire (DFS) to assess how much they consumed saturated fat and refined sugar. In the GREADT/BEDOB sample, the associations between the polymorphisms, BMI, DFS-score, and sEBR were examined with univariate analyses of variance. In the intervention study sample, a generalized linear mixed model was run to check whether sEBR changed in the intervention and whether the genotypes, BMI, or DFS-score affected sEBR. Results. No influence of the genotypes was found on sEBR in either of the samples. BMI had a significant effect on sEBR in the GREADT/BEDOB sample. The association was significant in the overweight/obese group but not in the normal weight group. DFS-score did not influence sEBR in either of the samples. Conclusions. The results of this study converge with those of authors suggesting caution in using sEBR as a proxy for central dopamine functioning of healthy humans. In future studies, particular attention should be paid to methodological considerations when studying sEBR

Epiphora : impact on vision, outcome of lacrimal surgery and investigations with ultra-high-frequency ultrasound

Epiphora is a common condition that often receives little attention. Excessive tear production creates an irregular and ever-changing ocular surface, affecting refraction and reducing vision. However, in a standard test situation the visual acuity is seldom affected, leading to the misinterpretation that epiphora is a minor problem. Patients report social discomfort as a result of red eyes and constant eye wiping, and the misperception that they are sad or crying. The aims of the present studies were to quantify the functional visual disability experienced by patients with epiphora, to survey current management practices, and to present the long-term outcome of two lacrimal drainage procedures. In addition, a novel imaging technique, ultra-high-frequency (UHF) ultrasound, was used to visualize the upper lacrimal drainage anatomy and the lacrimal pump. Limitations on activities in daily life due to visual disability have long been recorded in the Swedish National Cataract Register and used as an outcome measure. The tool used, a questionnaire named Catquest-9SF, was validated in this study for epiphora patients, and their visual disability was found to be in parity with those of patients awaiting cataract surgery in their second eye (Paper I). A survey of current management practices in the Nordic countries regarding acquired lacrimal drainage obstruction (ALDO) indicated that canaliculodacryocystoplasty (CDCP) is used when treating obstructions below the lacrimal sac (Paper II), a practice less common elsewhere. However, approximately half of patients with multiple obstructions or nasolacrimal duct obstructions (NLDO) treated with CDCP require additional surgery due to the recurrence of obstruction (Paper III). This proportion is significantly higher than when stenosis is confined to the canaliculi. There is no consensus regarding the use of silicone stent intubation in conjunction with dacryocystorhinostomy (DCR). The duration of intubation has received little attention as a factor contributing to outcome. A 97% long-term success rate was found with a comparatively short intubation duration of one week (Paper IV). This shows that a high success rate is possible with a one-week intubation period. I suggest that there may be an optimal duration of intubation, with which the possible positive effects are achieved while the negative effects minimized. Using UHF ultrasound and motion tracking, it was demonstrated that the motion of the lateral lacrimal sac wall is greatest in the anterior-posterior direction during blinking (Paper V). This is in contrast to an existing theory regarding the mechanics of the lacrimal pump. In conclusion, the findings presented in this thesis suggest that epiphora should be recognized as a debilitating condition affecting everyday life, and that the use of CDCP to treat NLDO should be reconsidered in the Nordic countries, as it may be an inadequate form of treatment. Furthermore, a very high success rate is possible with a short duration of intubation in DCR. Finally, the current theory regarding the lacrimal pump should be re-evaluated

Central nervous system physiology

This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology

Compensatory strategies in humans performing active and passive gaze fixation and re-fixation tasks after unilateral vestibular deafferentation

The human vestibulo-ocular reflex (VOR) stabilizes gaze during head movement. The reflex is typically tested in a clinic or laboratory using passive rotations or artificial stimuli which measure the amount of damage the vestibular apparatus has suffered. However, during everyday activities the vestibular system is stimulated by active, self generated head movements. Head movements are often rapid and associated with the goal of achieving either gaze-fixation or re-fixation. Patients who complain of on-going symptoms will typically identify a particular position or movement that aggravates their symptoms in their everyday life. There is a need to identify objective parameters which correlate with the subjective complaints of patients whose symptoms persist after vestibular damage. In the first study, a gaze-refixation task, patients who complain of ongoing symptoms (poorly-compensated), during rapid head turns, after unilateral vestibular de-afferentation (uVD) were compared with those who did not have the same complaints (well-compensated) and normal subjects. Well- and poorly-compensated groups were sorted according to responses on a standardized questionnaire. All subjects were then located in a real-world, non-laboratory environment in which poorly-compensated subjects reported experiencing symptoms. Each subject’s head, eye and gaze displacement and velocity, head rotation frequency and blink or eye-lid closure were measured and analysed and compared between ipsi- and contra-lesional head rotations within and between subject groups. When subjects are able to generate their own active head rotations it has been suggested that a number of vestibular and extra-vestibular strategies might be employed to compensate for an impaired VOR. In subsequent studies, high resolution scleral search coils were used to identify the compensatory mechanisms used during active head rotations during a gaze-fixation task. A corrective saccade is typically observed during passive ipsilesional head rotations or “impulses” and might be potentiated during rapid, active or self-generated head rotations. The conditions which predict or contribute to the generation of the rapid, corrective eye movement were investigated. The results were compared with responses to passive head impulses of matched velocity and acceleration to determine if active head impulses could be used to identify a lesioned vestibular apparatus as is routinely clinically achieved with passive head impulses

Contemporary Diagnosis and Management of Dry Eye

Introduction Dry eye (DE) disease is characterized by symptoms including, but not limited to, ocular stinging, burning, and tearing. The symptoms can range from being mildly irritating, to severely debilitating and negatively impacting quality of life. The impairment of the tear film, lacrimal functional unit, and meibomian glands (MGs) causes desiccation of the ocular surface, which in turn promotes and exacerbates inflammation. Dry eye is a multifactorial disease and the many causative factors can be completely exclusive from each other. This necessitates that the management of DE be multi-faceted. Dry eye disease affects millions of people around the world and this number will increase as the elderly population rise over the next few decades. However, emerging technologies are allowing clinicians and scientists to constantly discover new ways to diagnose and manage various aspects of DE. The global aim of this thesis was to evaluate some of the contemporary methods used in the diagnosis and management of DE disease. The specific aims of each chapter were as follows: • Chapter 3: To determine whether an experimental spectral domain ultra-long optical coherence tomographer (UL-OCT) can image MGs, and to compare its performance to the Heidelberg Retina Tomograph 3 (HRT3) with Rostock Cornea Module (RCM) in vivo laser scanning confocal microscope (Heidelberg Engineering GmbH, Heidelberg, Germany) and the Keratograph 5M (K5M) (OCULUS, Wetzlar, Germany). • Chapter 4: To determine the inter- and intra-observer repeatability in using the Keratograph 4 (K4) and K5M to grade MG dropout using meibography grading scales. • Chapter 5: To quantify the association of DE diagnostic tests to DE symptoms in an age-matched female cohort. • Chapter 6: To determine the effectiveness of an eyelid warming device in the management of MG dysfunction (MGD). • Chapter 7: To evaluate the effect of lid debridement-scaling (LDS) on DE signs and symptoms in individuals with Sjӧgren’s syndrome (SS). • Chapter 8: To determine the combined effect of a lubricant eye drop, lid hygiene, and omega 3 fatty acids on DE signs and symptoms. Methods • Chapter 3: The superior eyelids of 12 participants were everted and imaged using the UL-OCT. The inferior and superior eyelids were then everted and imaged using the K5M. Finally, the inferior eyelids were everted and imaged with the HRT3/RCM. • Chapter 4: The inferior and superior eyelids of 40 participants were imaged 3 times each on both the K4 and K5M. The images were split into one training and two study sets; the latter were graded (4-point meibography scale) by two observers on two separate occasions (24hrs apart) to examine repeatability. Semi-objective grading of MG dropout was conducted using ImageJ on K4 and K5M images. A 7-point meibography scale was used to grade a separate set of K5M images. • Chapter 5: Twenty females symptomatic of DE (Ocular Surface Disease Index, OSDI, ≥ 13) were age-matched to 20 asymptomatic females (OSDI < 13). Non-invasive tear breakup time (NIBUT), ocular staining, meibum quality, number of obstructed glands, lid wiper epitheliopathy (LWE), Line of Marx (LOM) placement, eyelid margin score, Schirmer’s test, meibography, and visual acuity were compared between the two groups. • Chapter 6: This was a prospective, randomized, controlled, single-masked, bilateral eye study that enrolled 29 participants. Participants were randomized into either the EyeBag group or the control group. Participants in the EyeBag group were instructed to use the EyeBag 10 minutes 2x/day, and the control group remained on their own DE treatment regimen (if applicable). All participants were seen at baseline, 2 weeks and 4 weeks. At 4 weeks, participants in the EyeBag group were asked to stop using the EyeBag. All participants were seen again at the 8 week mark. Primary outcomes were the OSDI, Current Symptoms Questionnaire (CSQ), MG score (MGS), and non-invasive tear break-up time (NIBUT). • Chapter 7: This prospective randomized controlled study enrolled 14 female participants with SS. Seven participants were randomized into the treatment group, where they were selected to receive LDS, the remainder did not receive LDS and served as controls. Lid debridement-scaling was conducted using a stainless steel golf club spud (Hilco Wilson Ophthalmics, Plainville, MA) on both the upper and lower eyelids of both eyes. Outcome variables were assessed prior to LDS and again 1 month later. The outcome variables were the OSDI, Symptoms iN Assessment of Dry Eye (SANDE) visual analogue scores, Sjӧgren’s International Collaborative Clinical Alliance Ocular Staining Score (SICCA OSS), fluorescein tear breakup time (FLBUT), MGS, MG yielding liquid secretions score (MGYLS), and LOM position. • Chapter 8: This prospective study enrolled 28 DE participants. Participants were instructed to use the TheraTears® Lubricant Eye Drops at least 2-4x a day, TheraTears® SteriLid 1-2x a day, and TheraTears® Nutrition 3 gel caps once a day. Participants were followed up at baseline, 1 month and 3 months. Outcome variables were the OSDI, SANDE, NIBUT, osmolarity, number of MGs blocked (#MG blocked), meibum quality, eyelid margin features, Schirmer’s test, tear film lipid layer thickness (LLT), meniscus height, corneal and conjunctival staining. Results • Chapter 3: All twelve participants (7 female, 5 male) completed the study. The only instrument that was able to successfully image MGs was the K5M. • Chapter 4: When using the 4-point scale, inter-observer mean difference (MD) was 0.08±0.55 on day 1 and 0.13±0.50 on day 2, and the concordance correlation coefficient (CCC) was 0.79 and 0.81 on days 1 and 2 respectively. Intra-observer MD was 0.04±0.54, CCC=0.79 for observer 1, and -0.09±0.60, CCC=0.74 for observer 2. For the 7-point scale, inter-observer MD was 0.05±0.45, CCC=0.89 on day 1 and 0.01±0.41, CCC=0.91 on day 2. Intra-observer MD was -0.10±0.35, CCC=0.93 for observer 1 and -0.06±0.30, CCC=0.95 for observer 2. Percentage dropout measured between the K4 and K5M images showed lack of agreement, with only a 21.8% coefficient of repeatability. • Chapter 5: Twenty participant-pairs completed the study. The age (median/interquartile range(IQR)) of the symptomatic group was (60/15) and the asymptomatic group was (62/15). The diagnostic tests (median/IQR, p-value) that were significantly different between the symptomatic group vs. the asymptomatic group were OSDI (35.4/35.4 vs. 3.1/6.7, p 0.05), and similarly, no significant association to DE symptoms (all p > 0.05). • Chapter 6: Twenty five participants completed the study (mean age 38±15 years, 7 male). There was a significant change in OSDI over time for the EyeBag group (mean values±SD, baseline: 39.1±12.5, week 2: 26.8±11.2, week 4: 26.6±26.6, week 8: 27.7±14.6; p<0.05), but no significant change in the control group. There was a significant improvement in symptoms immediately after conducting the EyeBag based on at-home CSQ scores (Δ=-5.0 points, p<0.05), but no significant change in the control group. There was no significant change in MGS and NIBUT over time for either group. • Chapter 7: There were 13 participants that completed the study. Data from the right eye only were analyzed. For the control group (n=6, mean age=62±12), the pre LDS, post LDS, and significance level (pre-mean±SD, post-mean±SD; p-value) were: OSDI (58.3±22.1, 48.3±29.0; p=0.051), SANDE (77.4±22.1, 89.6±32.6; p=0.20), SICCA OSS (7.0±4.5, 8.2±3.5; p=0.25), MGS (1.3±1.5, 1.0±0.9; p=0.75), MGYLS (0.3±0.5, 0.0±0.0; p=0.50), FLBUT (2.99 ±1.54, 2.85±1.79; p=0.63), LOM (2.0±0.0, 2.0±0.0, p=n/a). For the treatment group (n=7, mean age=58±8), the pre LDS, post LDS, and significance level were: OSDI (63.2±13.3, 46.9±19.4; p=0.04), SANDE (72.6±17.1, 77.0±28.0; p=0.54), SICCA OSS (6.6±2.9, 5.0±3.9; p=0.02), MGS (1.0±1.2, 3.1±1.7; p=0.01), MGYLS (0.0±0.0, 0.6±1.0; p=0.50), FLBUT (3.13±0.81, 3.45±1.03; p=0.53), LOM (0.9±0.9, 1.0±1.0, p=1.00). • Chapter 8: There were 20 participants (mean age = 43, from 23 to 66, 17F, 3M) that completed the study. On average, participants used the Lubricant Eye Drop 2.4x/day, the SteriLid 1.1x/day, and the Nutrition 3 gel caps 1x/day. There was a significant change over time (p<0.05) for OSDI (-21.2 points), SANDE (-32.4 points), NIBUT (+0.43s), eyelid margin features (-1.1 grade), meibum quality (-1.0 grade), and #MG blocked (-4.0 glands). Conclusions • Chapter 3: The UL-OCT was unable to image MGs. The HRT3/RCM imaged structures that resembled dermal rete pegs and papillae. Of the three methods used in this study, the only device that was able to successfully image MGs was the K5M. • Chapter 4: Observers graded from -1 to +1 grade units between and within themselves for a 4-point scale, 95% of the time. Although the inter- and intra-observer repeatability of the K4 and K5M were very similar, a low level of agreement in percentage dropout between K4 and K5M images suggests that the two instruments cannot be interchanged. Using a finer scale may be beneficial for detecting change over time. • Chapter 5: The diagnostic tests that were most strongly associated with DE symptoms in older women were ocular staining, meibum quality, number of glands obstructed, and tear film stability. • Chapter 6: The MGDRx® EyeBag was effective at relieving symptoms in participants with DE, but the effect on MG function and tear stability when used for only 4 weeks was modest. • Chapter 7: This pilot study showed that LDS improved symptoms, ocular staining and MG function for the group that received LDS. This indicates that LDS can aid in the management of SS DE. • Chapter 8: After using a combination of TheraTears® Lubricant Eye Drop, SteriLid, and Nutrition, participants experience significant relief in both DE symptoms and signs. This thesis was able to evaluate and suggest improvements to meibography techniques and grading. In addition, this thesis was also able to evaluate the effectiveness of various contemporary methods for DE treatment. The methods used in this study are clinically accessible and clinicians are free to use these findings and apply them directly to their clinical practice