Efficacy of hypertonic saline in treatment of corneal edema: A randomized crossover trial.

Background: To determine the efficacy of sodium chloride (NaCl) 5% drops in comparison to 6% ointment and study tear Osmolarity as an objective measure correlating with clinical findings in the treatment of corneal edema. Methods: This is a prospective, randomized, interventional, open-label, crossover study of 40 eyes of 40 patients with corneal edema due to Bullous keratopathy and Fuchs endothelial dystrophy. Subjects were divided into 2 groups by simple randomization: group A received NaCl 5% drops and group B received NaCl 6% ointment. Both treatments were administered four times daily for seven days. Subsequently, after a 1-week wash-out period, switch over of treatment was done. Central corneal thickness (CCT) and tear osmolarity were primarily efficacy variables. Results: Baseline parameters were comparable. The median reduction in CCT from baseline (706.7 ± 58.41 µm), at 6 hours with NaCl 5% drops was 23 µm (-27, 74) and that with NaCl6% ointment was 37.5 µm (-7, 85). The reduction in CCT was more with 6% ointment (p = 0.013). The difference in reduction in CCT between two treatments at one week was not statistically significant, although there was a substantial reduction in thickness with each treatment individually. The change in tear osmolarity from the baseline at 2 Hours with both NaCl5% drops and 6% ointment was significant, and it remained so till 6 h. Side-effects such as stickiness, stinginess, blurring, and foreign body sensation were more with 6% eye ointment. Conclusion: Topical NaCl 6% eye ointment in QID dosage is more effective than NaCl 5% drops in the medical management of corneal edema. In patients symptomatically intolerant to ointment, NaCl 5% eye drops may be prescribed as an effective option.

Elevated osmol gaps in patients with alcoholic ketoacidosis.

INTRODUCTION: The use of the osmol gap as a surrogate marker of toxic alcohol poisoning is common. Unfortunately, many patients with alcoholic ketoacidosis have elevated osmol gaps and are misdiagnosed with toxic alcohol poisoning. We aimed to characterize the range of osmol gaps in patients with alcoholic ketoacidosis. METHODS: This was a retrospective poison center study. Data from 24 years were reviewed using the following case definition of alcoholic ketoacidosis: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or an elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential cases of alcoholic ketoacidosis that failed to fulfill all three criteria were adjudicated by three toxicologists. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other diagnoses that lead to a metabolic acidosis. Demographics, pH, anion gap, lactate concentration, and osmol gap were extracted. RESULTS: Of 1,493 patients screened, 55 met criteria for alcoholic ketoacidosis. Sixty-four percent were male, and their median age was 52 years. The median osmol gap was 27 [IQR 18-36]. The largest anion gap was 57 mmol/L, and the lowest pH was 6.8. Forty-five (82%) of the patients with alcoholic ketoacidosis had osmol gaps >10; 38 (69%) had osmol gaps >20; 24 (44%) had osmol gaps >30; 11 (20%) had osmol gaps > 40. DISCUSSION: The large range of osmol gaps in patients with alcoholic ketoacidosis often reaches values associated with toxic alcohol poisoning. The study is limited by the potential for transcribing errors and the inability to identify the cause of the osmol gap. CONCLUSIONS: In this retrospective study, patients with alcoholic ketoacidosis had a median osmol gap of 26. Given that alcoholic ketoacidosis is easily and inexpensively treated, proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

Management of Pediatric Parenteral Fluids.

Parenteral fluid therapy in children requires careful consideration of patient-specific factors such as weight, hydration status, and concomitant disease states. Recent literature has changed the standard of care for maintenance fluids for children in the past decade and brought to light more questions. Concentrations of electrolytes in fluids and the use of balanced fluids are still controversial. This article will review the use of parenteral fluids in children, including fluid content, maintenance fluid rate, treatment of dehydration, and the basics of parenteral fluid ingredients. All pediatric patients should have a plan for fluid therapy that includes careful consideration of hydration status and individual response to therapy.

Association between hydration status and the risk and all-cause mortality of diabetic kidney disease.

BACKGROUND: This cohort study aimed to explore the relationship between hydration status and the risk of diabetic kidney disease (DKD) as well as all-cause death in DKD patients. METHODS: Weighted univariable and multivariable logistic regression models were used to explore the association between hydration status and DKD risk in diabetic population while weighted univariable and multivariable Cox regression models were used to identify the association between hydration status and all-cause mortality in DKD patients. Kaplan-Meier curve was plotted to present the survival probability of patients with different hydration status. Estimates were presented as odds ratio (OR), and hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The mean follow-up time was 79.74 (±1.89) months. There were 2041 participants with DKD, and 2889 participants without. At the end of the follow-up, 965 participants were alive. The risk of DKD was increased as the increase of osmolarity level (OR = 1.07, 95%CI: 1.05-1.08). The elevated risk of DKD was observed in patients with impending dehydration (OR = 1.49, 95%CI: 1.19-1.85) or current dehydration (OR = 2.69, 95%CI: 2.09-3.46). The association between increased osmolarty level and elevated risk of all-cause mortality in DKD patients was statistically different (HR = 1.02, 95%CI: 1.01-1.03). Current dehydration was correlated with increased all-cause mortality risk in DKD patients (HR = 1.27, 95%CI: 1.01-1.61). Compared to DKD patients with normal hydration, the survival probability of DKD patients with current dehydration was significant lower (p < 0.001). CONCLUSION: Increased osmolarity level was associated with increased risk of DKD and elevated risk of all-cause mortality in DKD patients.

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.

Chondroprotection of articular cartilage integrity: Utilizing ultrasonic scalpel and hyperosmolar irrigation solution during cutting.

Objectives: Ultrasonic (US) cutting of cartilage in orthopaedic surgery has received little attention despite its potential to reduce chondrocyte death which could enhance cartilage repair. We aimed to investigate whether an ultrasonically-vibrating scalpel to cut human articular cartilage could reduce chondrocyte death, and to determine if hyper-osmolarity could provide chondroprotection during the procedure. Methods: A scalpel (no. 15) was mounted on an ultrasonic transducer to resonate at 35 â€‹kHz with 30 â€‹µm vibrational displacement. Thirty-six fresh human femoral cartilage samples were divided into four groups based on ultrasonic activation (US or non-US) and saline osmolarity (300 or 600 mOsm/L). Cell viability was assessed using a live/dead cell assay and analysed quantitatively by confocal microscopy. Histology illustrated tissue surface changes at the cut site. Results: The overall chondrocyte death percentage at both the US and non-US cut sites showed comparable results (p â€‹> â€‹0.05) in both osmolarities. However, the zone of chondrocyte death was reduced by 31 â€‹± â€‹5% and 36 â€‹± â€‹6%, respectively, when comparing US cutting at 300 mOsm/L and 600 mOsm/L to the control group (non-US cutting; 300 mOsm/L) (p â€‹< â€‹0.05). The width of the cut was consistent at both sites, regardless of the method of cutting. Conclusion: Cutting human cartilage with US in the presence of 300 or 600 mOsm/L media was chondroprotective compared to normal (non-US) scalpel cutting in 300 mOsm/L medium. These results suggest chondroprotection can be achieved while cutting using a US scalpel and raised osmolarity, potentially improving cartilage regeneration and repair following injury.

Effect of Artificial Tears on Preoperative Keratometry and Refractive Precision in Cataract Surgery.

Purpose: The primary objective was to investigate if treatment with artificial tears affected the variability of keratometry measurements for subjects with dry eyes prior to cataract surgery. The secondary objectives were to investigate whether treatment with artificial tears improved refractive precision and whether subjects with non-dry eyes had better refractive precision than subjects with dry eyes. Design: Prospective randomized controlled trial with three arms. Patients and methods: Dry eye diagnostics according to DEWS II were performed, and subjects with dry eyes were randomized to no treatment (group A1) or treatment with artificial tears two weeks prior to cataract surgery (group A2), with the third group (Group B, non-dry eyes) as a control. Keratometry was performed twice at baseline and twice after two weeks at the time of cataract surgery with three different optical biometers. The change in mean variability of keratometry (average K and magnitude of vector differences) and percentages of outliers after two weeks versus baseline were compared for group A2. The refractive and astigmatism prediction errors were calculated eight weeks after cataract surgery and compared for all three groups. Results: One hundred thirty-one subjects were available for analysis. There was no statistically significant difference in the mean variability of keratometry or percentages of outliers for group A2 from baseline to the time of cataract surgery. There was no statistically significant difference in refractive precision (absolute error and astigmatism prediction error) between any groups. Conclusion: Subjects with dry eyes (treated and non-treated) achieved the same refractive precision and percentages of outliers as subjects with non-dry eyes. Treatment with artificial tears for two weeks appeared inadequate to significantly affect variability in biometric measurements for patients with dry eyes prior to cataract surgery. DEWS II criteria for DED may not be optimal in a cataract setting.

Microtubule-associated protein MAP7 promotes tubulin posttranslational modifications and cargo transport to enable osmotic adaptation.

Cells remodel their cytoskeletal networks to adapt to their environment. Here, we analyze the mechanisms utilized by the cell to tailor its microtubule landscape in response to changes in osmolarity that alter macromolecular crowding. By integrating live-cell imaging, ex vivo enzymatic assays, and in vitro reconstitution, we probe the impact of cytoplasmic density on microtubule-associated proteins (MAPs) and tubulin posttranslational modifications (PTMs). We find that human epithelial cells respond to fluctuations in cytoplasmic density by modulating microtubule acetylation, detyrosination, or MAP7 association without differentially affecting polyglutamylation, tyrosination, or MAP4 association. These MAP-PTM combinations alter intracellular cargo transport, enabling the cell to respond to osmotic challenges. We further dissect the molecular mechanisms governing tubulin PTM specification and find that MAP7 promotes acetylation and inhibits detyrosination. Our data identify MAP7 in modulating the tubulin code, resulting in microtubule cytoskeleton remodeling and alteration of intracellular transport as an integrated mechanism of cellular adaptation.

ARV1 deficiency induces lipid bilayer stress and enhances rDNA stability by activating the unfolded protein response in Saccharomyces cerevisiae.

The stability of ribosomal DNA (rDNA) is maintained through transcriptional silencing by the NAD+-dependent histone deacetylase Sir2 in Saccharomyces cerevisiae. Alongside proteostasis, rDNA stability is a crucial factor regulating the replicative lifespan of S. cerevisiae. The unfolded protein response (UPR) is induced by misfolding of proteins or an imbalance of membrane lipid composition and is responsible for degrading misfolded proteins and restoring endoplasmic reticulum (ER) membrane homeostasis. Recent investigations have suggested that the UPR can extend the replicative lifespan of yeast by enhancing protein quality control mechanisms, but the relationship between the UPR and rDNA stability remains unknown. In this study, we found that the deletion of ARV1, which encodes an ER protein of unknown molecular function, activates the UPR by inducing lipid bilayer stress. In arv1Δ cells, the UPR and the cell wall integrity pathway are activated independently of each other, and the high osmolarity glycerol (HOG) pathway is activated in a manner dependent on Ire1, which mediates the UPR. Activated Hog1 translocates the stress response transcription factor Msn2 to the nucleus, where it promotes the expression of nicotinamidase Pnc1, a well-known Sir2 activator. Following Sir2 activation, rDNA silencing and rDNA stability are promoted. Furthermore, the loss of other ER proteins, such as Pmt1 or Bst1, and ER stress induced by tunicamycin or inositol depletion also enhance rDNA stability in a Hog1-dependent manner. Collectively, these findings suggest that the induction of the UPR enhances rDNA stability in S. cerevisiae by promoting the Msn2-Pnc1-Sir2 pathway in a Hog1-dependent manner.

Maltose accumulation-induced cell death in Saccharomyces cerevisiae.

Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here, we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.

Response of Articular Cartilage to Hyperosmolar Stress: Report of an Ex Vivo Injury Model.

BACKGROUND: Physiological 0.9% saline is commonly used as an irrigation fluid in modern arthroscopy. There is a growing body of evidence that a hyperosmolar saline solution has chondroprotective effects, especially if iatrogenic injury occurs. PURPOSE: To (1) corroborate the superiority of a hyperosmolar saline solution regarding chondrocyte survival after mechanical injury and (2) observe the modulatory response of articular cartilage to osmotic stress and injury. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral explants were isolated from bovine stifle joints and exposed to either 0.9% saline (308 mOsm) or hyperosmolar saline (600 mOsm) and then damaged with a sharp dermatome blade to attain a confined full-thickness cartilage injury site, incubated in the same fluids for another 3 hours, and transferred to chondropermissive medium for further culture for 1 week. Chondrocyte survival was assessed by confocal imaging, while the cellular response was evaluated over 1 week by relative gene expression for apoptotic and inflammatory markers and mediator release into the medium. RESULTS: The full-thickness cartilage cut resulted in a confined zone of cell death that mainly affected superficial zone chondrocytes. Injured samples that were exposed to hyperosmolar saline showed less expansion of cell death in both the axial (P < .007) and the coronal (P < .004) plane. There was no progression of cell death during the following week of culture. Histological assessment revealed an intact cartilage matrix and normal chondrocyte morphology. Inflammatory and proapoptotic genes were upregulated on the first days postexposure with a notable downregulation toward day 7. Mediator release into the medium was concentrated on day 3. CONCLUSION: This in vitro cartilage injury model provides further evidence for the chondroprotective effect of a hyperosmolar saline irrigation fluid, as well as novel data on the capability of articular cartilage to quickly regain joint homeostasis after osmotic stress and injury. CLINICAL RELEVANCE: Raising the osmolarity of an irrigating solution may be a simple and safe strategy to protect articular cartilage during arthroscopic surgery.

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.

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.

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.

A Preservative-Free Approach - Effects on Dry Eye Signs and Symptoms After Cataract Surgery.

Purpose: To compare the effect of treatment with preservative-free dexamethasone, NSAIDs and trehalose/hyaluronic acid eye drops with the preservative benzalkonium chloride containing dexamethasone and NSAIDs after cataract surgery in dry versus non-dry eyes. Patients and Methods: In this prospective randomized intervention study, dry eye tests were performed before and 6 weeks after cataract surgery. Patients were considered as having dry eye, SDE (sign of dry eye), if at least one of the following dry eye tests were abnormal; corneal fluorescein staining (CFS), non-invasive keratograph breakup time (NIKBUT) or tear osmolarity. Patients with SDE were randomly assigned to one of two groups. Group 1 patients were treated with dexamethasone and bromfenac eye drops with the preservative benzalkonium chloride (BAC). Group 2 patients were treated with preservative-free dexamethasone and preservative-free diclofenac, as well as a preservative-free lubricant with trehalose and hyaluronic acid both before and after surgery. Patients with normal tear film status acted as the control group (group 3) and received same treatment as group 1. Results: A total of 215 patients were enrolled six weeks after surgery, the number of patients with SDE decreased significantly in groups 1 and 2 (p <0.001). Subjective symptoms and objective measures including osmolarity, NIKBUT, CFS, and tear film thickness (TFT) improved after surgery, tear production remained unchanged, while corneal sensitivity and meibomian gland dysfunction (MGD) parameters worsened. In the control group with normal tear-film status, SDE increased significantly after the surgery (p <0.001). There were no statistically significant differences in tear film parameters between the three groups after surgery. Conclusion: After cataract surgery, patients with mild to moderate dry eyes may experience improved tear film status and reduced symptoms. However, we found no additional beneficial effect on dry eye parameters with treatment with preservative-free dexamethasone, NSAIDs, and lubricants compared to preservative-containing eye drops.

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.

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.

Influence of serial intravitreal injections on measures of dry eye: A systemic review and meta-analysis.

PURPOSE: The aim of this study was to evaluate the long-term effects of serial intravitreal injections (IVI) on measures of dry eye. METHODS: The PubMed, EMBASE, and Cochrane databases were searched according to the PROSPERO protocol (CRD42023455727). Studies evaluating the influence of serial IVI on the ocular surface compared with untreated fellow eyes were included. The measures of dry eye after IVI were used as outcome variables. The results are presented as mean difference (MD) with a corresponding 95% confidence interval (CI). RESULTS: A total of 4 studies with 259 participants were included in this meta-analysis. Significant increases in ocular surface disease index (OSDI) scores (MD 10.26, 95 % CI 5.05 to 15.46, p ＜ 0.01) and tear film osmolarity (TOsm; MD 4.40, 95 % CI 0.87 to 7.92, p = 0.01) were observed in the IVI treated eyes compared to the untreated fellow eyes. There was no significant difference between the groups with respect to fluorescein tear film break-up time (TBUT; p = 0.05), average non-invasive tear film break-up time (NITBUT; p = 0.94), first NITBUT (p = 0.78) and Schirmer test (p = 0.94). CONCLUSION: Repeated IVI of anti-VEGF agents with preoperative povidone-iodine application was associated with increased OSDI scores and TOsm, while no significant difference was found in fluorescein TBUT, average NITBUT, first NITBUT and Schirmer test. The ocular surface may partially recover after the procedures, but IVI still has deleterious effects on the ocular surface.