Lubricating drops for contact lens discomfort in adults.

BACKGROUND: Contact lens discomfort is a symptom-based clinical diagnosis that affects 13% to 75% of contact lens wearers. The Tear Film and Ocular Surface Society defines contact lens discomfort as "a condition characterized by episodic or persistent adverse ocular sensations related to lens wear either with or without visual disturbance, resulting from reduced compatibility between the lens and ocular environment, which can lead to decreased wearing time and discontinuation from lens wear." Signs of the condition include conjunctival hyperemia, corneal and conjunctival staining, altered blinking patterns, lid wiper epitheliopathy, and meibomian gland dysfunction. Eye care specialists often treat contact lens discomfort with lubricating drops, including saline, although there is no clear evidence showing this treatment is effective and safe. OBJECTIVES: To evaluate the efficacy and safety of lubricating drops for ocular discomfort associated with contact lens wear in adults. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase.com, two other databases, and two trials registries to May 2024, without date or language restrictions. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs) that evaluated lubricating drops, including saline, versus no treatment, or that evaluated lubricating drops versus saline, in adult contact lens wearers. We included studies regardless of publication status, language, or year of publication. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodology. The critical outcome was contact lens discomfort. Important outcomes were corneal fluorescein staining and conjunctival redness. Adverse outcomes were incident microbial keratitis, inflammatory corneal infiltrates, and participant discontinuation. We assessed risk of bias for outcomes reported in the summary of findings table using the Cochrane risk of bias tool RoB 2, and we rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven RCTs conducted in the USA, Canada, Italy, and France. They randomized a total of 463 participants to lubricating drops, saline, or no treatment. Four trials evaluated lubricating drops and saline versus no treatment, but one of them provided no usable outcome data. Three trials evaluated lubricating drops versus saline. Study characteristics All trial participants were adults, and the mean age ranged from 25.7 years to 36.7 years. The proportion of women varied from 15% to 82%. The trials lasted between one and four weeks. Of the five trials that reported contact lens discomfort, we judged three at high risk of bias, and considered the other two had some risk of bias concerns. Lubricating drops (including saline) versus no treatment Lubricating drops compared with no treatment may reduce contact lens discomfort, measured on a 37-point scale (lower is better), but the evidence is very uncertain (mean difference [MD] -5.9 points, 95% confidence interval [CI] -3.74 to -8.05; 2 RCTs; 119 participants). One trial found no difference between lubricating drops and no treatment in "end-of-day" comfort. The trial that compared saline with no treatment provided no results for the control group. Two studies measured corneal fluorescein staining on a scale of 0 to 20 (lower is better). We found low-certainty evidence of little to no difference between lubricating drops and no treatment in changes in the extent (MD -0.15 points, 95% CI -0.86 to 0.56; 2 RCTs; 119 participants), depth (MD -0.01 points, 95% CI -0.44 to 0.42; 2 RCTs; 119 participants), or type (MD 0.04 points, 95% CI -0.38 to 0.46; 2 RCTs; 119 participants) of corneal fluorescein staining scores. Regarding conjunctival redness, measured on a scale of 0 to 4 (lower is better), there was low-certainty evidence of little to no difference between lubricating drops and no treatment in nasal region scores (MD 0.10, 95% CI -0.29 to 0.49; 1 RCT; 73 participants) and temporal region scores (MD 0.00, 95% CI -0.39 to 0.39; 1 RCT; 73 participants). No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. All trials reported the proportion of participants who discontinued participation. In two trials, no participants left any treatment group. Our meta-analysis of another two studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the no treatment group (risk ratio [RR] 1.42, 95% CI 0.19 to 10.94; 138 participants; low-certainty evidence). Lubricating drops versus saline Lubricating drops may have little to no effect compared with saline on contact lens discomfort measured on a visual analog scale of 0 to 100 (lower is better), but the evidence is very uncertain (MD 9.5 points, 95% CI -4.65 to 23.65; 1 RCT; 39 participants). No studies reported corneal fluorescein staining or conjunctival redness. No studies reported microbial keratitis or inflammatory corneal infiltrates, and no trials reported vision-threatening adverse events up to four weeks of treatment. Our meta-analysis of three studies suggests little difference in the number of people who dropped out of the lubricating treatment group versus the saline group (RR 1.56, 95% CI 0.47 to 5.12; 269 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Very low-certainty evidence suggests that lubricating drops may improve contact lens discomfort compared with no treatment, but may have little or no effect on contact lens discomfort compared with saline. Low-certainty evidence also suggests that lubricating drops may have no unwanted effects that would lead to discontinuation over one to four weeks. Current evidence suggests that prescribing lubricating drops (including saline) to people with contact lens discomfort is a viable option. However, most studies did not assess patient-reported contact lens (dis)comfort using a validated instrument. Therefore, further well-designed trials are needed to generate high-certainty evidence on patient-reported outcomes as well as on longer-term safety outcomes.

TFOS Lifestyle: Impact of nutrition on the ocular surface.

Nutrients, required by human bodies to perform life-sustaining functions, are obtained from the diet. They are broadly classified into macronutrients (carbohydrates, lipids, and proteins), micronutrients (vitamins and minerals) and water. All nutrients serve as a source of energy, provide structural support to the body and/or regulate the chemical processes of the body. Food and drinks also consist of non-nutrients that may be beneficial (e.g., antioxidants) or harmful (e.g., dyes or preservatives added to processed foods) to the body and the ocular surface. There is also a complex interplay between systemic disorders and an individual's nutritional status. Changes in the gut microbiome may lead to alterations at the ocular surface. Poor nutrition may exacerbate select systemic conditions. Similarly, certain systemic conditions may affect the uptake, processing and distribution of nutrients by the body. These disorders may lead to deficiencies in micro- and macro-nutrients that are important in maintaining ocular surface health. Medications used to treat these conditions may also cause ocular surface changes. The prevalence of nutrition-related chronic diseases is climbing worldwide. This report sought to review the evidence supporting the impact of nutrition on the ocular surface, either directly or as a consequence of the chronic diseases that result. To address a key question, a systematic review investigated the effects of intentional food restriction on ocular surface health; of the 25 included studies, most investigated Ramadan fasting (56%), followed by bariatric surgery (16%), anorexia nervosa (16%), but none were judged to be of high quality, with no randomized-controlled trials.

Patient perspectives on dry eye disease and chronic ocular surface pain: Insights from a virtual community-moderated dialogue.

PURPOSE: To understand patients' perspectives on living with dry eye disease (DED), and on the unmet needs in DED and chronic ocular surface pain (COSP) management. METHODS: A moderated, structured discussion with patients with ocular surface diseases and healthcare professionals (HCPs) was conducted using a virtual platform to capture patients' journey with DED, their opinion on unmet needs, and design and conduct of clinical trials in DED and COSP. RESULTS: Nine participants, including four patient representatives from patient organisations, one ophthalmologist and one optometrist participated in the discussion. Patients had DED of varying severity and aetiology; three patients had Sjögren's. Over 4 weeks, 785 posts were entered on the platform. Prior to diagnosis, patients rarely associated their symptoms with DED. Convenience and symptomatic relief scored higher than treating the disease. Patients expressed the need for plain language information and dialogue with knowledgeable and sensitive HCPs. Online forums and social media were suggested as key recruitment resources, whereas convenience and safety concerns were highlighted as main barriers to enrolment. The need for the inclusion of outcome measures that have a real impact on patients' experience of their condition was highlighted. Both target product profiles were received positively by participants, highlighting the twice-daily dosing regimen and convenience of the products. Participants acknowledged the value of digital tools and suggested the need to feel valued post-trial. CONCLUSIONS: This moderated dialogue provided actionable insights on the unmet needs in DED and useful inputs for consideration when designing future clinical trials for DED and COSP.

The effect of time on grading corneal fluorescein and conjunctival lissamine green staining.

PURPOSE: To explore the effect of time on grading corneal fluorescein and conjunctival lissamine green staining in dry eye disease (DED). METHODS: Photographs of 68 subjects with non-Sjogren's DED (nSS DED) and 32 with Sjogren's DED (SS DED) were taken of corneal fluorescein staining, then conjunctival lissamine green staining every 30 s for at least 5 min. Photographs of one randomly selected eye were then randomly ordered and graded on a scale from 0 to 5 (severe staining) by two clinicians, masked to both site and subject. The average time required to reach the maximum grade of staining (Gmax) was calculated. RESULTS: The median time (upper and lower quartiles) to corneal fluorescein Gmax was 2.6 (1.3-5.3) minutes for nSS DED and 3.8 (2.6-5.4) minutes for SS DED, a statistically significant difference (Mann Whitney U test, p = 0.018). In contrast, the median time to the Gmax for lissamine green staining of the nasal and temporal conjunctiva was 0.5 (0.5-1.1 nasal, 0.5-0.8 temporal) minutes for nSS DED and 0.5 (0.5-0.8 nasal, 0.5-0.5 temporal) minutes for SS DED subjects, which was not statistically significant (p ≥ 0.383). CONCLUSIONS: The time required to reach the maximum grade of corneal fluorescein staining, but not conjunctival lissamine green staining, varied widely and was significantly longer in subjects with Sjögren's Syndrome. Early observation of corneal fluorescein staining can lead to under-grading, which may impact the diagnosis and assessment of treatment in DED. Further study of the best time to assess corneal fluorescein staining in various DED populations is warranted.

Proteomics Analysis of Tears and Saliva From Sjogren's Syndrome Patients.

Sjogren's syndrome (SS) is characterized by dysfunctional mucous membranes and dysregulated moisture-secreting glands resulting in various symptoms, including dry mouth and dry eyes. Here, we wanted to profile and compare the tear and saliva proteomes of SS patients to healthy controls. Tear and saliva samples were collected and subjected to an isotopic dimethylation labeling shotgun proteomics workflow to identify alterations in protein levels. In tear samples, we identified 83 upregulated and 112 downregulated proteins. Pathway enrichment analysis of the changing proteins by Metascape identified leukocyte transendothelial migration, neutrophil degranulation, and post-translation protein phosphorylation in tears of SS patients. In healthy controls' tears, an enrichment for proteins related to glycolysis, amino acid metabolism and apoptotic signaling pathway were identified. In saliva, we identified 108 upregulated and 45 downregulated proteins. Altered pathways in SS patients' saliva included cornification, sensory perception to taste and neutrophil degranulation. In healthy controls' saliva, an enrichment for proteins related to JAK-STAT signaling after interleukin-12 stimulation, phagocytosis and glycolysis in senescence were identified. Dysregulated protease activity is implicated in the initiation of inflammation and immune cell recruitment in SS. We identified 20 proteases and protease inhibitors in tears and 18 in saliva which are differentially expressed between SS patients and healthy controls. Next, we quantified endogenous proteoglycan 4 (PRG4), a mucin-like glycoprotein, in tear wash and saliva samples via a bead-based immune assay. We identified decreased levels of PRG4 in SS patients' tear wash compared to normal samples. Conversely, in saliva, we found elevated levels of PRG4 concentration and visualized PRG4 expression in human parotid gland via immunohistological staining. These findings will improve our mechanistic understanding of the disease and changes in SS patients' protein expression will help identify new potential drug targets. PRG4 is among the promising targets, which we identified here, in saliva, for the first time.

Canonical Grading Scales of Corneal and Conjunctival Staining Based on Psychophysical and Physical Attributes.

Purpose: In this study, we apply psychophysical scaling principles based on physical (photometric) attributes of images to better understand the factors involved in clinician judgement of ocular surface staining and, using that knowledge, to develop photographic scales for the assessment of staining for dry eye (DE) and related conditions. Methods: Subjects with noninfectious ocular surface staining were enrolled at five clinical sites. Following instillation of fluorescein, photographs of corneal staining were taken every 30 seconds for at least 5 minutes. The same procedure was followed for conjunctival staining after instillation of 2 µl of 1% lissamine green. A subset of the best corneal and bulbar conjunctival staining images were anonymized and a spectroradiometer measured photometric attributes (luminance and chromaticity). The images were scaled psychophysically by study investigators, who participated in constructing grading scales based on physical and psychophysical analyses. The final grading scales were refined following consultation with outside DE experts. Results: Photographs were collected from 142 subjects (81% women), with an average age of 58 ± 17 years; 89% were diagnosed with DE. There was a monotonic relationship between between physical measurements and psychophysically scaled staining of both corneal (fluorescein) and bulbar (lissamine green) staining. Michelson contrast and u' (chromaticity) accounted for 66% and 64% of the variability in the psychophysically scaled images of fluorescein corneal and lissamine green conjunctival staining, respectively. Translational Relevance: This paper provides examples of the first ever clinically usable ocular surface staining scales validated using psychophysical scaling and the physical attributes (luminance and chromaticity) of the staining itself. In addition, it provides a generalizable method for the development of other clinical scales of ocular appearance.

American Academy of Optometry Microbial Keratitis Think Tank.

SIGNIFICANCE: Think Tank 2019 affirmed that the rate of infection associated with contact lenses has not changed in several decades. Also, there is a trend toward more serious infections associated with Acanthamoeba and fungi. The growing use of contact lenses in children demands our attention with surveillance and case-control studies. PURPOSE: The American Academy of Optometry (AAO) gathered researchers and key opinion leaders from around the world to discuss contact lens-associated microbial keratitis at the 2019 AAO Annual Meeting. METHODS: Experts presented within four sessions. Session 1 covered the epidemiology of microbial keratitis, pathogenesis of Pseudomonas aeruginosa, and the role of lens care systems and storage cases in corneal disease. Session 2 covered nonbacterial forms of keratitis in contact lens wearers. Session 3 covered future needs, challenges, and research questions in relation to microbial keratitis in youth and myopia control, microbiome, antimicrobial surfaces, and genetic susceptibility. Session 4 covered compliance and communication imperatives. RESULTS: The absolute rate of microbial keratitis has remained very consistent for three decades despite new technologies, and extended wear significantly increases the risk. Improved oxygen delivery afforded by silicone hydrogel lenses has not impacted the rates, and although the introduction of daily disposable lenses has minimized the risk of severe disease, there is no consistent evidence that they have altered the overall rate of microbial keratitis. Overnight orthokeratology lenses may increase the risk of microbial keratitis, especially secondary to Acanthamoeba, in children. Compliance remains a concern and a significant risk factor for disease. New insights into host microbiome and genetic susceptibility may uncover new theories. More studies such as case-control designs suited for rare diseases and registries are needed. CONCLUSIONS: The first annual AAO Think Tank acknowledged that the risk of microbial keratitis has not decreased over decades, despite innovation. Important questions and research directions remain.

Prevalence of dry eye disease in Ontario, Canada: A population-based survey.

PURPOSE: Population-based cross-sectional survey in Ontario to estimate the 2016 prevalence of dry eye disease (DED) and associated risk factors among adults in Canada. METHODS: We emailed the 5-Item Dry Eye Questionnaire (DEQ-5) to 124,469 Ontario adults (age ≥18 years) in the IQVIA E360 database, March-April 2017. Inclusion criteria were: ≥2 visits to an Ontario based clinic, ≥1 visits in the 1 year before the study; database record with email. DED was defined as a DEQ-5 score of >6/22. The crude prevalence by age/sex of the Ontario sample was adjusted to the 2016 Canadian population (mean age 41.0 years, 51% female). Significance of DED risk factors (age, sex, selected diseases/medical conditions and medications) was evaluated by logistic regression analysis. RESULTS: Of the 5163 (4.1%) patients who completed the survey (59.5% female, median age, 46 years; 40.4% male, 56 years), 1135 respondents reported DED. Prevalence increased with age (p < 0.05) and was highest among those aged 55-64 years (24.7%; 95% CI, 22.1-27.3%) and lowest among those aged 25-34 years (18.4%; 95% CI, 15.9-21.0%). Prevalence was significantly higher (p < 0.001) among women (24.7%; 95% CI, 23.2-26.2%) than men (18.0%; 95% CI, 16.4-19.7%). Other risk factors were not significant. The age-/sex-adjusted Canadian DED prevalence estimate from this sample was 21.3% (95% CI, 19.8-23.2%), corresponding to ∼6.3 million people. CONCLUSIONS: Based on the Ontario sample, we estimate that >6 million Canadian adults may have DED, and that older people and females are more likely to be affected.

Review and analysis of grading scales for ocular surface staining.

Vital dye staining has been used for over a century to assess the severity of ocular surface disease. However, despite common usage, a universally accepted "gold standard" grading scale does not exist for corneal and conjunctival staining, which can impact the ability to diagnose and monitor ocular surface conditions such as dry eye. The Food and Drug Administration (FDA) and other international regulatory agencies rely on ocular surface staining as a primary endpoint for new drug approvals, so that absence of a "gold standard" scale may affect approval of new drug treatments. To begin to address this problem, we review existing, published grading scales in an integrated fashion, highlighting their differences and similarities to emphasize common themes and the methods and elements that are important in creating a standardized scale. Our goal is to aid the field in moving towards an accepted standardized grading scale for ocular surface staining that can be applied in clinic and research settings for a variety of ocular conditions.

Customary practices in the monitoring of dry eye disease in Sjogren's syndrome / Prácticas habituales en la supervisión de la enfermedad del ojo seco en el Síndrome de Sjogren

Purpose: Diagnostic testing for dry eye disease (DED) in Sjogren's syndrome (SS) is well described. Little is published about monitoring this systemic autoimmune DED. We analyzed the SS related DED tests used in North American optometric practices and compared academic settings to private practice settings. Methods: A retrospective chart review of 123 SS charts from 6 optometric practices in North America was conducted. Testing done during the first examination following a SS diagnosis was recorded on Research Electronic Data Capture (REDCap) database. The complete data file was reviewed and testing type and methodology were compared. Results: Symptoms of DED (98.4% of charts),meibomian gland dysfunction (76.4% of charts), corneal staining with fluorescein (75.6% of charts) and anterior blepharitis (73.2% of charts) were the most frequently recorded variables. Clinicians used different methodologies to measure and grade these variables. Private practitioners were more likely to use symptom questionnaires and grading scales and to describe anterior blepharitis. Academic settings were more likely to record TBUT and tear meniscus height. Conclusions: The monitoring of DED in SS is not uniform in optometric offices across North America. Creating accepted standards of testing will improve the ability of clinicians and researchers to communicate and understand the course of DED in SS

Objetivo: Las pruebas diagnósticas para la enfermedad del ojo seco en el síndrome de Sjogren (SS) están bien descritas. Se ha publicado poco acerca de la supervisión de este síndrome del ojo seco autoinmune sistémico. Analizamos el SS relacionado con las pruebas de ojo seco en las prácticas optométricas de Norte América, y comparamos los centros académicos con los centros de práctica privada. Métodos: Se realizó una revisión retrospectiva de 123 historias clínicas de SS procedentes de 6 centros optométricos de Norte América. Las pruebas realizadas durante el primer examen, tras el diagnóstico de SS, se registraron en la base de datos Research Electronic Data Capture (REDCap). Se revisó el archivo de datos completo y se compararon el tipo de prueba y la metodología. Resultados: Las variables más frecuentemente registradas fueron los síntomas de ojo seco (98,4% de las historias), disfunción de la glándula de Meibomio (76,4%), tinción corneal con fluoresceína (75,6%), y blefaritis anterior (73,2%). Los clínicos utilizaron diferentes metodologías para medir y clasificar dichas variables. Los facultativos privados tendieron a utilizar con mayor frecuencia los cuestionarios de síntomas y las escalas de clasificación, y a describir la blefaritis anterior. Los centros académicos tendieron a registrar con mayor frecuencia TBUT y la altura del menisco lagrimal. Conclusiones: La supervisión del ojo seco en el SS no es uniforme en los centros optométricos de Norte América. La creación de estándares de pruebas aceptados mejoraría la capacidad de comunicar y comprender el curso del ojo seco en el SS por parte de clínicos e investigadores

Sjogren's syndrome in optometric practices in North America.

PURPOSE: To describe the presentation of dry eye in Sjogren's syndrome (SS) in optometric practices, to report on the methodology used in dry eye monitoring and to explore the level of corneal staining versus age and time of disease. METHODS: Records of SS patients were reviewed in 6 optometric sites. A standardized abstraction tool was developed to collect data from the records including: health history, medications and symptoms and signs of dry eye. The methods of testing symptoms and signs of dry eye were recorded. Variables were recorded at each site and collated at the University of Waterloo. The first visit after January 1, 2000 was selected for description in this paper. RESULTS: 123 charts were included. The average time since diagnosis was 7.2 years ±5.1 years. Symptoms of dryness were present in 110/123 = 89.4% of charts. Corneal fluorescein staining was present in 96/123 = 78% of charts. MGD was present in 52% of charts. There were significant differences in the protocols and grading systems used in these 6 sites. Corneal staining levels did not change with greater age or length of disease. CONCLUSION: These 123 SS patients presented with a large variation in their symptoms and signs. Symptoms of dryness and corneal fluorescein staining were the most commonly recorded presentations. There was a great deal of inconsistency in dry eye protocols among offices. Future prospective research with standardized testing will contribute to our understanding of the best dry eye protocols for SS patients.

Customary practices in the monitoring of dry eye disease in Sjogren's syndrome.

PURPOSE: Diagnostic testing for dry eye disease (DED) in Sjogren's syndrome (SS) is well described. Little is published about monitoring this systemic autoimmune DED. We analyzed the SS related DED tests used in North American optometric practices and compared academic settings to private practice settings. METHODS: A retrospective chart review of 123 SS charts from 6 optometric practices in North America was conducted. Testing done during the first examination following a SS diagnosis was recorded on Research Electronic Data Capture (REDCap) database. The complete data file was reviewed and testing type and methodology were compared. RESULTS: Symptoms of DED (98.4% of charts),meibomian gland dysfunction (76.4% of charts), corneal staining with fluorescein (75.6% of charts) and anterior blepharitis (73.2% of charts) were the most frequently recorded variables. Clinicians used different methodologies to measure and grade these variables. Private practitioners were more likely to use symptom questionnaires and grading scales and to describe anterior blepharitis. Academic settings were more likely to record TBUT and tear meniscus height. CONCLUSIONS: The monitoring of DED in SS is not uniform in optometric offices across North America. Creating accepted standards of testing will improve the ability of clinicians and researchers to communicate and understand the course of DED in SS.

TFOS DEWS II Definition and Classification Report.

The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research.

Randomized comparison of in vivo performance of two point-of-care tear film osmometers.

PURPOSE: To compare the in vivo precision of two commercially available point-of-care osmometers among normal subjects with no dry eye disease. METHODS: Twenty healthy adults with healthy ocular surfaces were evaluated by licensed eye care practitioners. All subjects had low Ocular Surface Disease Index score (<5), normal tear breakup time (>10 seconds), and no evidence of corneal fluorescein staining. Five consecutive measurements of tear osmolarity were measured on each eye using each of the two osmometers: the TearLab Osmolarity System (TearLab) and the I-Med i-Pen (i-Pen), for a total of 200 measurements per device. Performance of the osmometers was determined by specificity, estimated by the percentage of osmolarity data at or below the clinical cutoff (308 mOsm/L) and precision, and represented by the standard deviation per subject. In addition, to assess analytical performance, on each day of patient testing, standardized osmolarity quality control solutions (338 mOsm/L) were tested on the TearLab per manufacturer instructions. i-Pen manufacturer instructions do not neither provide for, nor recommend quality control procedures. RESULTS: The mean age of the 20 subjects was 27±8 years (range: 19-48 years, 16 females, four males). Over 2 months of testing, the TearLab reported analytical performance on quality control solutions of 335.8±4.2 mOsm/L with a coefficient of variation of 1.3%. In the subject cohort, 90.9% of TearLab measurements were in the normal range ≤308 mOsm/L. The i-Pen reported 37.5% of all measurements in the normal range. The average intra-subject osmolarity of the TearLab was 295.4±8.6 mOsm/L, which was significantly lower and less variable than the i-Pen, which reported an average of 319.4±20.3 mOsm/L (P<0.001). When the measurements were grouped by subject, the TearLab accurately identified 100% of subjects as normal while the i-Pen accurately identified only 15% of subjects as normal. CONCLUSION: In this randomized comparative study of two point-of-care osmometers among normal, healthy non-dry eye subjects, the TearLab Osmolarity System demonstrated accuracy, precision, and agreement with clinical interpretation in line with the manufacturer claims. The i-Pen lacked sufficient performance to delineate subjects with and without dry eye disease.

Degradation of proteoglycan 4/lubricin by cathepsin S: Potential mechanism for diminished ocular surface lubrication in Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune disease affecting the lacrimal and salivary glands with hallmark clinical symptoms of dry eye and dry mouth. Recently, markedly increased cathepsin S (CTSS) activity has been observed in the tears of SS patients. Proteoglycan 4 (PRG4), also known as lubricin, is an effective boundary lubricant that is naturally present on the ocular surface. While PRG4 is susceptible to proteolytic digestion, the potential effect of CTSS on PRG4 remains unknown. The objective of this study was to assess the ability of CTSS to enzymatically degrade purified PRG4, and PRG4 naturally present in human tears, and alter ocular surface boundary lubricating properties. To assess the potential time course and dose-dependency of PRG4 digestion by CTSS, full-length recombinant human PRG4 (rhPRG4) was incubated at 37 °C with or without CTSS in an enzymatic digestion buffer. Digestion of PRG4 by CTSS was also examined within normal human tear samples, both with and without supplementation by rhPRG4. Finally, digestion of endogenous PRG4 by CTSS, and the effect of a CTSS inhibitor, was examined in SS tears on Schirmer strips. Digestion products were separated on 3-8% SDS-PAGE and visualized by protein staining and western blotting. The boundary lubricating ability of rhPRG4 samples was assessed using an in vitro human eyelid-cornea friction test. Finally, SDS-PAGE protein stain bands resulting from rhPRG4 digestion were submitted for tandem mass spectrometry analysis to confirm their identity as PRG4 and identify non-tryptic cleavage sites. CTSS digested rhPRG4 in a time and dose dependent manner. CTSS digestion of rhPRG4 at 1% (where % is the mass ratio of CTSS to rhPRG4) resulted in a time dependent decrease in the full-length, ∼460 kDa, monomeric rhPRG4 band, and an appearance of lower MW fragments. After 20 h, no full-length rhPRG4 was observed. Furthermore, with an increased relative enzyme concentration of 3%, no protein bands were observed after 2 h, indicating complete digestion of rhPRG4. Western blotting demonstrated PRG4 is present in normal human tears, and that rhPRG4, tears, and tears supplemented with rhPRG4 incubated with 3-9% CTSS demonstrated decreased intensity of high MW PRG4 bands, indicative of partial degradation by CTSS. Similarly, western blotting of PRG4 in SS tears incubated with CTSS demonstrated decreased intensity of high MW PRG4 bands, which was reversed in the presence of the CTSS inhibitor. CTSS treatment of rhPRG4 resulted in an increased friction coefficient, compared to untreated controls. Lastly, the lower MW bands were confirmed to be PRG4 fragments by tandem mass spectrometry, and 6 non-tryptic cleavage sites were identified. rhPRG4 is susceptible to proteolytic digestion by CTSS, both alone and in human tears, which results in diminished ocular surface boundary lubricating ability. Moreover, endogenous PRG4 is susceptible to proteolytic digestion by CTSS, both in normal and SS tears. Given the elevated activity of CTSS in SS tears, and the role intact PRG4 plays in ocular surface health and lubrication, degradation of PRG4 by CTSS is a potential mechanism for diminished ocular surface lubrication in SS. Collectively these results suggest that tear supplementation of PRG4 may be beneficial for SS patients.

Effect of Lid Debridement-Scaling in Sjögren Syndrome Dry Eye.

PURPOSE: To evaluate the effect of lid debridement-scaling (LDS) on dry eye signs and symptoms in subjects with Sjögren syndrome (SS). METHODS: This prospective randomized controlled study enrolled 14 female subjects with SS. Seven subjects were randomized into the treatment group where they were selected to receive LDS; the remainder did not receive LDS and served as control subjects. 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 before LDS and again 1 month later. The outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) visual analog scores, ocular staining (SICCA OSS [Sjögren's International Collaborative Clinical Alliance Ocular Staining Score]), fluorescein tear breakup time (FLBUT), meibomian gland score (MGS), meibomian gland yielding liquid secretions (MGYLS) score, and line of Marx's (LOM) position. RESULTS: Thirteen subjects completed the study. Data from only the right eye were analyzed. For the control group (n = 6; mean [± SD] age, 62.3 [± 11.6] years), the pre-LDS, post-LDS, and significance level (pre-LDS mean [± SD] vs. post-LDS mean [± SD]; p value) were as follows: OSDI (58.3 [± 22.1] vs. 48.3 [± 29.0]; p = 0.051), SANDE (77.4 [± 22.1] vs. 89.6 [± 32.6]; p = 0.20), SICCA OSS (7.0 [± 4.5] vs. 8.2 [± 3.5]; p = 0.25), MGS (1.3 [± 1.5] vs. 1.0 [± 0.9]; p = 0.75), MGYLS (0.3 [± 0.5] vs. 0.0 [± 0.0]; p = 0.50), FLBUT (2.99 [± 1.54] vs. 2.85 [± 1.79]; p = 0.63), and LOM (2.0 [± 0.0] vs. 2.0 [± 0.0]; p = n/a). For the treatment group (n = 7; mean [± SD] age, 58.0 [± 8.1] years), the pre-LDS, post-LDS, and significance level were as follows: OSDI (63.2 [± 13.3] vs. 46.9 [± 19.4]; p = 0.04), SANDE (72.6 [± 17.1] vs. 77.0 [± 28.0]; p = 0.54), SICCA OSS (6.6 [± 2.9] vs. 5.0 [± 3.9]; p = 0.02), MGS (1.0 [± 1.2] vs. 3.1 [± 1.7]; p = 0.01), MGYLS (0.0 [± 0.0] vs. 0.6 [± 1.0]; p = 0.50), FLBUT (3.13 [± 0.81] vs. 3.45 [± 1.03]; p = 0.53), and LOM (0.9 [± 0.9] vs. 1.0 [± 1.0]; p = 1.00). CONCLUSIONS: This pilot study showed that LDS improved symptoms, ocular staining, and meibomian gland function for the group that received LDS. This indicates that LDS can aid in the management of SS dry eye.

Quantification of conjunctival TNF-α in aqueous-deficient dry eye.

PURPOSE: This study aimed to quantify and compare conjunctival epithelial tumor necrosis factor (NF) α mRNA expression in Sjögren syndrome (SS), non-Sjögren syndrome aqueous-deficient dry eye (non-SS DE), and non-dry eye (NDE) control subjects. METHODS: A total of 76 subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 non-SS DE (confirmed by symptoms and Schirmer scores ≤ 10 mm), and 26 NDE. Superior and temporal bulbar conjunctival epithelial cells were collected via impression cytology. Epithelial RNA was extracted, and TNF-α mRNA expression was quantified by real-time quantitative polymerase chain reaction. RESULTS: The expression of TNF-α mRNA was found to be significantly higher in the SS group (2.48 ± 1.79) compared to both non-SS DE (0.95 ± 1.18; p < 0.05) and NDE (0.84 ± 0.51; p < 0.05) groups. No difference in TNF-α mRNA expression was found between the non-SS DE and NDE groups (p = 0.67). CONCLUSIONS: These results demonstrate that SS-associated aqueous-deficient dry eye is associated with a significant upregulation of conjunctival epithelial TNF-α mRNA relative to both non-SS DE and control groups. The degree to which TNF-α mRNA is upregulated in SS may contribute to the severe ocular surface damage observed in these patients.