Effect of Periodontitis on Dry Eye Disease Signs and Symptoms: A Cross-sectional Study.

PURPOSE: Gingivitis and periodontitis are oral disorders characterised by chronic inflammation, impacting the supportive structures around teeth due to bacterial accumulation. While the role of inflammation in both periodontitis and dry eye disease (DED) has been established individually, their potential association remains unclear. This study aimed to investigate the association between periodontitis and the manifestation of signs and symptoms related to DED in patients aged 18-40. MATERIALS AND METHODS: A cross-sectional study was conducted involving healthy controls, DED patients with or without periodontitis, and patients with periodontitis without DED. Ophthalmic and oral examinations were performed, and demographic, ocular, and systemic disease data were collected. Statistical analysis was conducted using ANOVA and chi-squared tests. RESULTS: A total of 684 participants were included in the study. Significant elevations in tear osmolarity levels, increased Ocular Surface Disease Index scores (OSDI), and decreased tear break-up time (TBUT) and Schirmer (ST-I) values were observed in DED patients with periodontitis compared to individuals with DED but without periodontitis, as well as control and periodontitis groups. Furthermore, higher neutrophil-to-lymphocyte ratios (NLR) were found in DED patients with periodontitis. CONCLUSION: The findings suggest an association between periodontitis and the severity of signs and symptoms related to DED. The study highlights the importance of interdisciplinary approaches in understanding the systemic implications of periodontal disease and its potential impact on ocular health.

Efficacy of hydroxypropyl-guar drops in improving tear film index and ocular surface dynamics using two treatment methods under a controlled desiccating environment.

AIM: This study aimed to assess the efficacy of hp-guar eye drops on tear film index and ocular surface dynamics under desiccating conditions using protection and relief treatment modalities. METHODOLOGY: The 12 normal, non-dry eye participants were subjected to adverse environmental conditions using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the ambient temperature was 21 °C. The participants were screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST), tear production using the Ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and Schirmer strips. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296 mOsm/L at 40% RH to 285 mOsm/L at 5% RH (p = 0.01). Conflicting responses were seen for osmolarity in protection and relief. Mean tear osmolarity was significantly higher in the protection method in comparison to the relief method (p = 0.005). The mean TFI increased from 557 at 40% to 854 at 5% (p = 0.02). A significant increase in TFI was observed in the relief method in comparison with both 40% (p = 0.001) and 5% (p = 0.04). In the relief method, the mean TFI score went up to 1139 when hp-guar was installed. A significant improvement in ocular comfort was experienced in both the protection (p = 0.041) and relief (p = 0.010) methods at 5% RH. The instillation of hp-guar drops in the relief method resulted in a significant reduction in OST. The mean OST dropped to 33.01 ºC, significantly lower than the recorded OST for both normal (p = 0.040) and dry (p = 0.014) environmental conditions. CONCLUSION: Hp-guar drops significantly improve tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, an improvement in tear production and a decrease in ocular surface temperature were seen. Hp-guar performance could be maximized for the management of exposure to adverse environments by using a treatment protocol that targets the most affected parameters in each group of patients. Using CEC has the potential to provide researchers with a readily available method to evaluate the efficiency of tear supplementation.

Machine learning-based prediction of tear osmolarity for contact lens practice.

PURPOSE: This study addressed the utilisation of machine learning techniques to estimate tear osmolarity, a clinically significant yet challenging parameter to measure accurately. Elevated tear osmolarity has been observed in contact lens wearers and is associated with contact lens-induced dry eye, a common cause of discomfort leading to discontinuation of lens wear. METHODS: The study explored machine learning, regression and classification techniques to predict tear osmolarity using routine clinical parameters. The data set consisted of 175 participants, primarily healthy subjects eligible for soft contact lens wear. Various clinical assessments were performed, including symptom assessment with the Ocular Surface Disease Index and 5-Item Dry Eye Questionnaire (DEQ-5), tear meniscus height (TMH), tear osmolarity, non-invasive keratometric tear film break-up time (NIKBUT), ocular redness, corneal and conjunctival fluorescein staining and Meibomian glands loss. RESULTS: The results revealed that simple linear regression was insufficient for accurate osmolarity prediction. Instead, more advanced regression models achieved a moderate level of predictive power, explaining approximately 32% of the osmolarity variability. Notably, key predictors for osmolarity included NIKBUT, TMH, ocular redness, Meibomian gland coverage and the DEQ-5 questionnaire. In classification tasks, distinguishing between low (<299 mOsmol/L), medium (300-307 mOsmol/L) and high osmolarity (>308 mOsmol/L) levels yielded an accuracy of approximately 80%. Key parameters for classification were similar to those in regression models, emphasising the importance of NIKBUT, TMH, ocular redness, Meibomian glands coverage and the DEQ-5 questionnaire. CONCLUSIONS: This study highlights the potential benefits of integrating machine learning into contact lens research and practice. It suggests the clinical utility of assessing Meibomian glands and NIKBUT in contact lens fitting and follow-up visits. Machine learning models can optimise contact lens prescriptions and aid in early detection of conditions like dry eye, ultimately enhancing ocular health and the contact lens wearing experience.

Evaluation of therapeutic efficacy of Emustil drops for ocular discomfort and tear film osmolarity using different treatment management modes under dry environmental conditions.

BACKGROUND: We aimed to check the efficacy of Emustil (oil in water emulsion) drops on tear film index and ocular surface dynamics in dry environments through protection and relief treatment modalities. METHODS: The subjects were exposed to a dry environment using a Controlled Environment Chamber (CEC) where the relative humidity (RH) was 5% and the temperature was 21 °C and screened for ocular symptoms, tear osmolarity, ocular surface temperature (OST) and tear production using ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620 and Schirmer strips/phenol red test respectively. Tear production was calculated by the Tear Function Index test (TFI). RESULTS: The mean tear film osmolarity decreased significantly from 296.8 mOsm/l at 40% RH to 291 mOsm/l at 5%. (p = 0.01). Instillation of Emustil resulted in a significant increase in tear osmolarity in the relief method compared with osmolarity seen at 5% RH when no drop was used. The mean PRT value decreased from 26 ± 9 in normal conditions (40% RH) to 22 ± 4 mm in dry conditions (5% RH). Emustil drops did not induce any significant change in tear production in the PRT test. No significant change was found in OST following exposure to 5% RH. OST did not show a statistically significant change with the emulsion when used for relief (p > 0.05). The mean score of ocular discomfort observed was 70 at 5% RH. Still, the instillation of the oil-in-water emulsion (Emustil) resulted in a noticeable decrease in visual discomfort to 37 (p = 0.00) in protection and 59 in relief (p = 0.05). Emustil drops substantially improved tear film parameters under a desiccating environment, however, tear film parameters respond differently to the management modalities. In the protection method, tear film osmolarity was protected against a dry environment, while in the relief mode, tear production was improved. CONCLUSION: CEC allows for a thorough evaluation of tear film parameters and dry eye treatment protocols in labs, providing greater confidence when applying them to patients. In addition, our study showed that Emustil not only provides protection and relief for dry eyes but also helps to maintain ocular homeostasis in desiccating environments. This indicates a promising potential for improving dry eye treatment protocols.

Impact of Clinician Subjectivity on the Assessment of Dry Eye Disease Prevalence in a UK Public Health Care Patient Population.

Purpose: To understand the impact of subjectivity on diagnosis rates of dry eye disease (DED) in an unbiased population. Patients and Methods: A multicenter study enrolled 818 subjects with complete report forms (465 females, 67.1 ± 16.7 years, 353 males, 65.0 ± 15.9 years). Subjects were evaluated for staining, TBUT, tear osmolarity, meibomian gland disease, and OSDI. Results: Physicians diagnosed 48.7% of subjects as having DED, ranging from 42.9% to 62.3% between sites. Positivity rates for staining (≥ grade 1) ranged from 41.3% to 84.1% (mean = 0.8 ± 0.9 grade), TBUT (<10s) ranged from 39.1% to 61.6% (mean = 10.4 ± 6.6 seconds), osmolarity (>308 mOsm/L) ranged from 63.7% to 72.4% (mean = 319.7 ± 20.8), MGD grading ranged from 28.9% to 51.3% (mean = 0.5 ± 0.7), and symptoms measured by OSDI ranged from 57.6% to 71.0% (mean = 23.5 ± 20.5) between sites. Tear osmolarity was the most consistent between sites (max/min positivity = 114%), followed by OSDI (123%), TBUT (158%), MGD (178%), and staining (204%). DED markers were uncorrelated (average r2 = 0.05 ± 0.07). A substantial number of subjects (N = 110) exhibited positive symptoms (OSDI = 32.4 ± 15.7) and hyperosmolarity (338.1 ± 20.1 mOsm/L) but no other obvious signs of DED (MGD grade = 0.2 ± 0.4, TBUT = 13.5 ± 7.0 seconds, staining grade = 0.4 ± 0.5). Conclusion: Subjective signs of DED varied considerably, whereas objective measurements of OSDI and osmolarity were the most consistent between sites. A large proportion of subjects exhibited high symptoms and hyperosmolarity but no other obvious signs of dry eye disease, most of whom were undiagnosed by clinical assessment without access to the osmolarity measurement.

Characterizing the Robustness of Distinct Clinical Assessments in Identifying Dry Eye Condition of Animal Models.

PURPOSE: The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells. METHODS: Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination. RESULTS: Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED. CONCLUSION: The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.

Evaluation of ocular surface following PreserFlo Microshunt implantation: Functional outcomes and quality of life.

BACKGROUND: This study aimed to evaluate the impact of PreserFlo Microshunt on the ocular surface, focusing on both objective and subjective parameters. METHODS: Prospective-observational study on 48 eyes undergoing PreserFlo Microshunt implantation, standalone or combined with phacoemulsification. At baseline, 1-month, 6-months and 12-months post-operative follow-ups, we performed Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test (ST), Tear-film break-up time (TBUT), fluoresceine staining (FS), tear osmolarity and minimum corneal epithelial thickness (Epi-ThkMIN. ) measurements. RESULTS: OSDI score improved from 37.43 ± 17.49 at baseline, to 24.13 ± 12.55 at 1-month (p = 0.003) and to 12.89 ± 8.54 and 13.09 ± 10.22 at 6-months and 12-months (p < 0.0001). TBUT and ST, in a similar way, non-significantly increased at 1-month, but then improved at 6-months and 12-months (p < 0.05 for both). Tear osmolarity significantly decreased from 308.2 ± 7.3 mOsm/L at baseline, to 303.3 ± 8.2 mOsm/L, 295.6.2 ± 7.0 mOsm/L and 297.6 ± 6.8 mOsm/L at 1-month, 6-months and 12-months (p < 0.05 for all). Epi-ThkMIN was stable when comparing baseline (44.9 ± 5.7 µm) and 1-month (p = 0.28), and successively increased in 6-months (47.8 ± 5.5 µm, p = 0.02) and 12-months (48.0 ± 3.6 µm, p = 0.01). In subgroup analysis, OSDI score and tear osmolarity were significantly higher at 1-month in combined group compared to standalone group (p = 0.03 and p = 0.02, respectively), but reaching comparable values in successive follow-ups. Further, Oxford scale grades for FS were significantly improved when comparing baseline-6-months and baseline-12-months. CONCLUSION: PreserFlo implantation improved ocular surface subjective symptoms, increased TBUT and ST, and reduced FS, highlighting the potential benefits of this surgical intervention. Moreover, we reported significant improvements of tear osmolarity and corneal epithelium.

A Comprehensive Analysis of the Influence of Temperature and Humidity on Dry Eye Disease.

PURPOSE: To investigate the effects of humidity and temperature on dry eye disease (DED). METHODS: A retrospective, clinic-based study was conducted on DED patients undergoing dry eye treatment. Patients were followed up at least twice, and symptoms and signs were evaluated using the Symptoms Assessment Questionnaire in Dry Eye (SANDE) score, tear secretion, tear film breakup time (TBUT), ocular staining score, and tear osmolarity. Mean humidity and temperature values for 1 week before ocular examinations were used as the environmental exposure level. The relationship between humidity and temperature, with DED clinical parameters was analyzed in single- and multi-environmental factor models. RESULTS: The study included 33 patients with a mean age of 53.9 ± 12.2 years. The low humidity group showed significantly higher SANDE scores (p = 0.023) and tear osmolarity (p = 0.008), and the low temperature group had higher SANDE scores (p = 0.004), ocular staining scores (p = 0.036), and tear osmolarity (p < 0.001). In the linear mixed model, single factor analysis showed that an increase in humidity resulted in decreased SANDE scores (p = 0.043), and an increase in temperature led to a decrease in SANDE score (p = 0.007), ocular staining score (p = 0.007), and tear osmolarity (p = 0.012). In the multifactor analysis, changes in humidity had no significant effect on dry eye parameters, but an increase in temperature was significantly correlated with decreased SANDE score (p = 0.026), ocular staining score (p = 0.024), and tear osmolarity (p = 0.002). CONCLUSIONS: Lower temperature led to aggravated symptoms and signs of DED and the effect of temperature on DED was more pronounced than humidity. Tear osmolarity was the most sensitive clinical parameter to be affected by climate factors in DED patients.

Diagnostic Performance of the Tear Meniscus Osmolarity Measurement for Dry Eye Disease in Rheumatoid Arthritis Patients.

BACKGROUND: The aim of our study was to evaluate the diagnostic capacity of the tear meniscus osmolarity measurement for dry eye disease (DED) in patients with rheumatoid arthritis (RA), using a portable osmometer based on electrical impedance and an integrated circuit technology (TearLab® (Escondido, CA, USA)). METHODS: We included 101 RA patients, 81 patients with DED and 20 without DED (controls). We measured tear osmolarity and assessed other clinical diagnostic tests as suggested by the TFOS DEWS II composite reference standard diagnostic criteria for DED using Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), fluorescein tear break-up time (F-TUBT), ocular surface staining (SICCA score), and other clinical parameters to classify DED subtypes. We analyzed the agreement between osmolarity and the TFOS DEWS II composite reference standard for DED diagnosis. We conducted receiver operating characteristic (ROC) curve analyses using the DED variable and its subtypes as dependent variables and the continuous variable for osmolarity or the inter-eye difference in osmolarity as independent variable. Sensitivity, specificity, and area under the curve for all potential cut-off points were obtained and reported from ROC curves. RESULTS: We found that tear meniscus osmolarity had a low diagnostic capacity for DED (AUC = 0.57). Tear meniscus osmolarity measurement had a sensitivity of 35% and a specificity of 80% with a kappa level of agreement of 0.08 compared to the TFOS DEWS II composite reference standard. The low diagnostic capacity of the tear meniscus osmolarity was similar for aqueous-deficient DED and for evaporative DED, being only fair for severe DED with a 57% sensitivity and 80% specificity and a kappa level of agreement of 0.36. CONCLUSIONS: Our findings suggest that in patients with RA, tear meniscus osmolarity measured by the TearLab® showed low sensitivity, low specificity, and limited agreement with the TFOS DEWS II composite reference standard for DED diagnosis.

Comparative Evaluation of Matrix Metalloproteinase-9 Immunoassay and Tear Osmolarity Measurement for Diagnosing Severity of Dry Eye Disease.

PURPOSE: To evaluate and compare the clinical efficacy of matrix metalloproteinase-9 (MMP-9) immunoassay and tear osmolarity measurement in diagnosing dry eye severity. METHODS: Dry eye disease (DED) patients underwent diagnostic tests including MMP-9 assay, tear osmolarity measurement, fluorescein tear breakup time, ocular surface staining, anesthetized Schirmer test, Ocular Surface Disease Index questionnaire, and slit-lamp examination. The dry eye parameters were compared according to positive MMP-9 status and increased tear osmolarity. The correlation between dry eye profiles and MMP-9 positivity and high tear osmolarity was also analyzed. RESULTS: Those who tested positive in MMP-9 immunoassay had significantly higher corneal fluorescein staining score and worse DED severity than those who tested negative. The intensity of MMP-9 positivity showed positive correlation with the corneal staining score and DED severity. However, DED patients with high tear osmolarity above 308 mOsm/L did not show significantly different dry eye signs and symptoms compared to those with lower tear osmolarity values. Tear osmolarity was associated with ocular surface staining score in severe DED patients. CONCLUSIONS: MMP-9 positivity was associated with ocular surface staining and worse dry eye severity. Therefore, it may be used as a useful indicator of disease severity in conjunction to other diagnostic tests.

The effect of non-ablative thermomechanical skin treatment (Tixel®) on dry eye disease: A prospective two centre open-label trial.

PURPOSE: To determine the effects of a thermo-mechanical action-based peri-orbital fractional skin treatment (Tixel®) on dry eye disease. METHODS: This prospective, controlled, open labelled study was conducted at two study centres: Midland Eye, Solihull, UK, and Vallmedic Vision, Andorra. Participants were screened at the baseline visit (visit-1), received three Tixel® treatments at 2-weeks intervals including further assessment (visits 2, 3 and 4). Participants were followed up for three months post-treatment (visit 5). Vision, intraocular pressure (IOP), dry eye symptomatology were assessed, including the Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear break-up time (NIBUT) and tear osmolarity as well as detailed ophthalmic assessments. RESULTS: Seventy-four participants (41 in Birmingham and 33 in Andorra) with periorbital wrinkles and moderate to severe dry eye disease (DED) were enrolled. The mean age was 59.3 ± 13.3 years and 57 were females. No adverse events, no change in vision (p = 0.310) or IOP (p = 0.419) were observed. Tixel treatment was associated with clinically and statistically significant improvement in the DED symptoms, which was supported by a reduction of 21.40 ± 15.08 (P < 0.001) of the OSDI index. Non-invasive tear break-up time improved by 2.10 ± 0.91 s (p < 0.001) in the Birmingham cohort and 6.60 ± 2.13 s (p < 0.001) in the Andorra cohort. Tear osmolarity reduced from 299.8 ± 13.3 mOsm/L to 298.8 ± 15.6 mOsm/L following the Tixel treatment (p = 0.271). CONCLUSIONS: Thermo-mechanical action-based peri-orbital fractional skin treatment Tixel® could be an attractive, safe and effective treatment for DED. This treatment is associated with high clinical and statistically significant improvement in DED signs and symptoms with no adverse events.

Reduced tear break-up time in the fellow eye of patients with unilateral primary acquired nasolacrimal duct obstruction.

PURPOSE: To measure tear osmolarity, Schirmer I test and tear break-up time (TBUT) values in the obstructed and non-obstructed fellow eye of unilateral primary acquired nasolacrimal duct obstruction (PANDO) patients and compare them with healthy controls. METHODS: In this prospective noninterventional study, the tear osmolarity, Schirmer I test, and TBUT values from unilateral PANDO eyes, fellow eyes, and control eyes of all subjects were measured. RESULTS: The study included 114 eyes of 30 PANDO patients as well as 27 healthy controls. There was a significant difference between TBUT and Schirmer values of fellow eyes and PANDO eyes (p = 0,035; p = 0,001). There was no significant difference in any of the ocular surface parameters between PANDO eyes and control eyes (p > 0.05). When fellow eyes were compared to control eyes, there was a significant difference in TBUT (p = 0.046). CONCLUSIONS: Decreased TBUT was exhibited by the fellow eye of unilateral PANDO patients, compared to the PANDO side and controls. Compensatory changes in PANDO eyes due to a decrease in the tear secretion reflex may lead to tear dysfunction of the fellow eye. Clinicians should assess tear stability in the fellow eye of PANDO patients as this could be leading to added symptomatic complaints.

The Effect of Prolactinoma on Tear Film Function.

Objectives: To compare dry eye parameters in prolactinoma patients and healthy controls and evaluate their correlation with prolactin (PRL) levels and the duration of hyperprolactinemia. Materials and Methods: Consecutive patients with prolactinoma and healthy controls were included in the study. Schirmer, tear break-up time (TBUT), tear osmolarity values, and ocular surface disease index (OSDI) scores were evaluated for each patient. Follow-up time and total duration of hyperprolactinemia were recorded for prolactinoma patients. Results: The study included 39 eyes of 39 patients with prolactinoma and 39 eyes of 39 age- and gender-matched healthy controls. Prolactinoma patients showed lower Schirmer (14.1±8.4 vs. 24.8±8.9 mm; p<0.001) and TBUT values (7.0±3.2 vs. 11.6±2.6 s; p<0.001) and higher OSDI scores (20.6±16.6 vs. 5.8±2.4; p<0.001) compared to the healthy controls. While the mean osmolarity of the prolactinoma patients was 301.6±8.3 mOsm/L, it was 297.7±12.5 mOsm/L for the healthy controls (p=0.07). The duration of hyperprolactinemia in prolactinoma patients showed a negative correlation with Schirmer (r=-0.395; p=0.013) and TBUT values (r=-0.377; p=0.018) and a positive correlation with OSDI scores (r=0.337; p=0.036). Conclusion: Prolactinoma patients had significantly lower Schirmer and TBUT levels and higher OSDI scores compared to the healthy controls, but no significant difference in tear osmolarity. The effect of high PRL levels on tear film function was duration-dependent.

Correlation between osmolarity measurements using the TearLab™ and I-Pen® systems in subjects with a high body mass index.

BACKGROUND: Osmolarity is used to detect symptoms of dry eye disease (DED) and can be measured using TearLab™ and I-Pen® systems. OBJECTIVES: To investigate the correlation between osmolarity measurements using the TearLab™ and I-Pen® systems in subjects with a high body mass index (BMI). MATERIAL AND METHODS: Thirty male subjects with a high BMI (27-48 kg/m2; 23.3 ±2.1 years old) participated in this study. The control group consisting of 30 healthy males (24.9 kg/m2; 22.9 ±2.1 years old) was also enrolled. Osmolarity measurements were recorded from the right eye using the TearLab™ and I-Pen® systems, and interviews were conducted to determine ocular surface disease index (OSDI) scores. RESULTS: The OSDI (p = 0.042), TearLab™ (p < 0.001) and I-Pen® (p < 0.001) scores were significantly higher in the study group than in the control group. In the study group, OSDI scores ranged from 2 to 16 (median 8.0, interquartile range (IQR) 6.8), while it was from 0 to 10 (median 6.3, IQR 4.1) in the control group. The TearLab™ osmolarity scores were in the range of 278-309 mOsm/L in the study group, whereas the I-Pen® osmolarity measurements were in the range of 294-336 mOsm/L in the study group, compared with 263-304 mOsm/L and 278-317 mOsm/L in the control group, respectively. In the study group, there was a strong correlation between the TearLab™ and I-Pen® osmolarity scores (r = 0.934; p = 0.001). In addition, strong correlations were found between the BMI and both TearLab™ (r = 0.736; p = 0.001) and I-Pen® (r = 0.707; p = 0.001) scores, as well as between the OSDI scores and both TearLab™ (r = 0.731; p = 0.001) and I-Pen® measurements (r = 0.666; p = 0.001). CONCLUSION: Osmolarity measurements using the I-Pen® system were significantly higher than those recorded using the TearLab™ system in subjects with a high BMI. The I-Pen® measurements showed large variations in osmolarity scores and were highly unreliable in correctly identifying normal eyes compared to the TearLab™ system. Also, a strong correlation was found between the osmolarity scores obtained from the TearLab™ and I-Pen® systems.

Prevention of localized corneal hyperosmolarity spikes by soft-contact-lens wear.

PURPOSE: To determine whether localized hyperosmotic spikes on the pre-lens tear film (PrLTF) due to tear break up results in hyperosmotic spikes on the ocular surface during soft-contact-lens (SCL) wear and whether wear of SCLs can protect the cornea against PrLTF osmotic spikes. METHODS: Two-dimensional transient diffusion of salt was incorporated into a computationally designed SCL, post-lens tear film (PoLTF), and ocular surface and solved numerically. Time-dependent localized hyperosmolarity spikes were introduced at the anterior surface of the SCL corresponding to those generated in the PrLTF. Salt spikes were followed in time until spikes penetrate through the lens into the PoLTF. Lens-salt diffusivities (Ds) were varied to assess their importance on salt migration from the PrLTF to the ocular surface. SCL and PoLTF initial conditions and the lens anterior-surface boundary condition were varied depending on the value of Ds and on dry-eye symptomatology. Determined corneal surface osmolarities were translated into clinical pain scores. RESULTS: For Ds above about 10-7cm2/s, it takes around 5-10 s for the PrLTF hyperosmotic break-up spikes to diffuse across the SCL and reach the corneal surface. Even if localized hyperosmotic spikes penetrate to the ocular surface, salt concentrations there are much lower than those in the progenitor PrLTF spikes. For Ds less than 10-7cm2/s, the SCL protects the cornea from hyperosmotic spikes for both normal and dry eyes. When localized corneal hyperosmolarity is converted into transient pain scores, pain thresholds are significantly lower than those for no-lens wear. CONCLUSIONS: A cornea can be protected from localized PrLTF hyperosmolarity spikes with SCL wear. With regular blinking (e.g., less than 10 s), SCL wear shields the cornea from significant hyperosmotic pain. Decreasing Ds increases that protection. Low-Ds soft contact lenses can protect against hyperosmotic spikes and discomfort even during infrequent blinking (e.g., > 10 s).

Non-invasive Tear Film Assessment in Normal Population: Effect of Age, Sex, and Interparametric Relationship.

Purpose: To investigate age- and sex-related differences in tear film parameters of normal Indian population and study interparametric relationships. Methods: Healthy subjects with no ocular disease (median ocular surface disease index = 0) were subjected to an automated evaluation of tear meniscus height (TMH), non-invasive tear breakup time (NIBUT) using Keratograph 5M (OCULUS GmbH, Wetzlar, Germany), and tear osmolarity using the TearLab Osmolarity System (TearLab Corporation, California, USA). A mixed-effects model with random intercepts at the patient level was used to evaluate the relationships between explanatory (age, gender, and tear osmolarity) and outcome variables (TMH and NIBUT). Results: A total of 237 subjects (474 eyes; 150 males) were enrolled with a mean age of 40 ± 17 years (range, 10-78 years). The mean values (± standard deviation) of TMH, NIBUT, and tear osmolarity were 0.34 ± 0.07 mm, 10.95 ± 2.02 s and 289.0 ± 5.8 mOsm/L, respectively. Age had a significant positive relationship with TMH (p < 0.0001; 0.002 mm/year; r = 0.12), but there was no effect on NIBUT (p = 0.26) and tear osmolarity (p = 0.27). There were no sex-based differences in tear film parameters. Interparametric relationship revealed no significant association between TMH and NIBUT (p = 0.12) or tear osmolarity and TMH (p = 0.83) or tear osmolarity and NIBUT values (p = 0.48). Conclusions: In a normal Indian population, TMH is weakly affected by age and is independent of sex, NIBUT, and tear osmolarity. Tear breakup time and osmolarity show no significant age- and sex-related variation.

A Practical Approach to Severity Classification and Treatment of Dry Eye Disease: A Proposal from the Mexican Dry Eye Disease Expert Panel.

Dry eye disease (DED) has a higher prevalence than many important systemic disorders like cardiovascular disease and diabetes mellitus, representing a significant quality of life burden for the affected patients. It is a common reason for consultation in general eye clinics worldwide. Nowadays, the diagnostic and therapeutic approach at the high corneal and ocular surface specialty level should be reserved for cases of severe and chronic dry eye disease associated with systemic autoimmune diseases or complicated corneal and ocular surface pathologies. In such cases, the diagnostic and therapeutic approach is often complex, elaborate, time-consuming, and costly due to the use of extensive dry eye questionnaires, noninvasive electronic diagnostic equipment, and clinical laboratory and ancillary tests. However, other eye care specialists attend a fair amount of DED cases; therefore, its diagnosis, classification, and management should be simple, practical, achievable, and effective. Considering that many patients attending non-specialized dry eye clinics would benefit from better ophthalmological attention, we decided to elaborate a practical DED classification system based on disease severity to help clinicians discriminate cases needing referral to subspecialty clinics from those they could attend. Additionally, we propose a systematic management approach and general management considerations to improve patients' therapeutic outcomes according to disease severity.

Analysis of tear film in cystinosis patients treated with topical viscous cysteamine hydrochloride (Cystadrops®).

PURPOSE: The aim of this study was to evaluate in vivo the tear film in infantile nephropathic cystinosis patients with corneal crystals treated with topical viscous cysteamine hydrochloride (Cystadrops®). METHODS: Ten eyes of five patients with nephropathic cystinosis aged from 10 to 35 years were included in this study. The patients were under treatment with viscous cysteamine hydrochloride formulation containing 3.8 mg/mL cysteamine (vCH 0.55%, equivalent to 0.55% CH; Cystadrops®; Recordati rare Diseases, Puteaux, France) to reduce corneal crystal density. Five age and sex matched individuals were randomly selected as control group. Tear osmolarity testing (TearLabTM) was performed to assess the in vivo osmolarity of patients under treatment and compared to control group values. Tear film break-up time (TBUT) and basic tear secretion (Schirmer test) were also assessed. RESULTS: Mean tear osmolarity was 294.8 mOsms/L (±10.4), with a mean absolute difference of 1.85 mOsms/L (±2.13) between the eyes. There was no statistically significant difference between the osmolarity readings of cystinosis and the control group (294.8 ± 10.4 vs 299.4 ± 6.2mOsm/L, respectively; p = 0.39). The mean TBUT was 10.2 ± 0.83 s in the study group versus 10 ± 0.7 s in controls (p = 0.62). The mean Schirmer test score was 9.2 ± 0.83 mm in the patients versus 10.2 ± 0.83 mm in the controls (p = 0.14). CONCLUSIONS: The TearLabTM osmolarity system test showed good reliability and precision in repeated measurements. This is the first report using the TearLab osmolarity system to assess tear film in patients with cystinosis treated with vCH 0.55%. TearLabTM examination showed that the use of vCH 0.55% drops does not determine alterations of the tear film quality.

The relationship of tear osmolarity with tear meniscus curvature and contact angles in healthy subjects: anterior segment optical coherence tomography study.

PURPOSE: To evaluate the relationship of tear osmolarity (TO) with tear meniscus curvature and contact angles by anterior segment optical coherence tomography (AS-OCT) in healthy subjects. METHODS: The right eyes of 64 consecutive healthy subjects were included in the study. The eyes were scanned by AS-OCT for the measurements of upper and lower tear menisci. The geometrical components of the upper and lower menisci, including height, depth, area, and radius of the menisci, cornea-meniscus angle (α-angle), meniscus-eyelid angle (ß-angle), and curvature angle (θ-angle) were measured. TO was obtained by TearLab. All participants were administered Ocular Surface Disease Index questionnaires (OSDI), and tear film break-up time (TBUT), Schirmer I and II test measurements were also performed. RESULTS: There was no association of TO with height, depth, and area of both menisci while TO was negatively correlated to θ-angle and radius of the lower eyelid meniscus (r = - 0.41, P < 0.001 and r = - 0.40, P < 0.01, respectively). The θ-angle and the radius of the lower meniscus were also significantly associated with OSDI score, TBUT, Schirmer I and II (P < 0.01 for all). There was a statistically strong correlation between the θ-angle and the radius of the lower meniscus (r = 0.91, P < 0.001). CONCLUSION: The curvature angle and radius of the lower meniscus are significantly associated with TO. The curvature angle of the lower meniscus is a useful non-contact measure that may provide information indirectly about the osmolarity and the quality of the tear.

The validity of point of care tear film osmometers in the diagnosis of dry eye.

PURPOSE: To determine the repeatability of TearLab and I-PEN osmometers in vivo and their accuracy in vitro. DESIGN: Prospective, single-visit study. METHODS: The tear osmolarity of 28 participants was evaluated with TearLab and I-PEN on two occasions in random order, over a 2-h period. Both eyes were measured in a randomised order. Coefficients of repeatability (CoR) were determined for each device, together with the bias and limits of agreement between them. For the in vitro experiment, the osmolarity was measured by both osmometers in five solutions (290, 297, 342, 338 and 383 mOsm/L) at two different temperatures (22 and 37°C) with a total of four consecutive measures. RESULTS: The CoRs for the TearLab and I-PEN in the right and left eyes were 26.2, 21.3, 33.6 and 28.3 mOsm/L, respectively. Across the first and second repeats, TearLab showed consistency of diagnosis for 50% of participants with 29% as dry eye positive, while I-PEN indicated 68% consistency of diagnosis with 57% dry eye positive. The instruments agreed on the diagnosis in 46.5% of cases. In vitro comparison showed that the average measurement errors for TearLab and I-PEN were -10 ± 13 and 31 ± 39 mOsm/L at 22°C, and 4 ± 13 and 20 ± 51 mOsm/L at 37°C. CONCLUSIONS: In vitro, both instruments showed reasonable accuracy and repeatability at mid-range osmolarities, but repeatability generally declined at higher and lower levels. While TearLab accuracy remained consistent across the osmolarity range, measurement errors for I-PEN noticeably increased outside the mid-range. In vivo, both instruments displayed poor repeatability. This casts doubt on the value of utilising either instrument to establish osmolarity as a factor in the diagnosis of dry-eye, according to currently recommended diagnostic guidelines (TFOS DEWS II), if only a single measurement is taken from each eye.