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To evaluate pre-lens tear film volume, stability and lipid interferometry patterns with a silicone hydrogel water content contact lens, a novel, noninvasive, ocular-surface-analyzer technology was used. A prospective, longitudinal, single-center, self-control study was performed in daily or monthly replacement silicone hydrogel contact lens wearers. A tear film analysis was achieved with the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA) from SBM System. The subjects were reassessed, with the contact lens, after 30 min of wearing to quantify the volume, stability and lipid pattern of the short-term pre-lens tear film. Lipid layer thickness decreased from 2.05 ± 1.53 to 1.90 ± 1.73 Guillon patterns (p = 0.23). First pre-lens NIBUT decreased from 5.03 ± 1.04 to 4.63 ± 0.89 s (p = 0.01). Mean pre-lens NIBUT significantly increased from 15.19 ± 9.54 to 21.27 ± 11.97 s (p < 0.01). Lid opening time significantly increased from 26.36 ± 19.72 to 38.58 ± 21.78 s (p < 0.01). The silicone hydrogel contact lens with water gradient technology significantly increased the mean pre-lens NIBUT and lid opening time. Lehfilcon A suggested an improvement in contact lens wearers with tear film instability or decreased subjective symptoms of dry eye disease.

The goal of this study was to analyze the agreement between the Medmont E300 and the Visionix VX120+ systems in terms of non-invasive tear break-up time (NIBUT) and tear meniscus height (TMH) measurements. A total of 60 eyes (30 healthy subjects) were enrolled. NIBUT and TMH were evaluated with Medmont E300; first NIBUT, NIBUT50%, and TMH were evaluated with Visionix VX120+. Both evaluations were performed in a random order by the same clinician for right, left, and both eyes. The Medmont E300 provided significantly higher NIBUT than Visionix VX120+ for first NIBUT in right, left, and both eyes (p ≤ 0.003) and NIBUT50% in left and both eyes (p ≤ 0.042). The TMH measured with VX120+ was significantly higher than with Medmont E300 considering both eyes (p = 0.037). No significant correlations were found between both devices for either NIBUT (p ≥ 0.11) or TMH (p ≥ 0.09). Passing–Bablok regression analyses revealed poor agreement between devices for NIBUT and TMH outcomes. VX120+ is expected to provide substantial lower first NIBUT values than the NIBUT measured by Medmont E300. Clinicians should consider not using both instruments as interchangeable for dry eye diagnosis.

Purpose: To evaluate seasonal variation in intraocular pressure (IOP) with and without short tear break-up time (SBUT, BUT ≤5 s) since dry eye and IOP are known to have seasonal variation. Methods: This study enrolled 176 patients who visited one of six eye clinics, in Japan, four times for IOP measurement, in every season. The mean patient age was 67.9 years, including 79 males. Participants were divided into four groups based on the presence of glaucoma and/or SBUT and we compared the seasonal variation in IOP (winter and summer) among the four groups. Results: The IOP (mmHg) in winter and summer, respectively, was 12.8 ± 3.7 and 12.8 ± 3.1 for non-glaucoma patients without SBUT (n = 47, p = 0.964), 14.8 ± 3.4 and 13.3 ± 3.4 for non-glaucoma patients with SBUT (n = 57, p < 0.001), 14.3 ± 3.2 and 14.1 ± 3.4 for glaucoma patients without SBUT (n = 36, p = 0.489), and 13.3 ± 3.0 and 11.6 ± 2.9 for glaucoma with SBUT (n = 36, p < 0.001). Seasonal variation was largest across the seasons in the glaucoma with the SBUT group, and the magnitude of seasonal variation correlated with BUT (β = 0.228, p = 0.003). Conclusions: Seasonal variation tended to be larger in patients with SBUT than those without SBUT.

Dry eye disease may develop and persist after cataract surgery; however, unilateral cases have not been fully documented. This cross-sectional, observational study was conducted in five eye clinics in Japan. A total of 1023 outpatients were initially enrolled, and 89 unilateral pseudophakic subjects with 1+ year of follow-up after uncomplicated cataract surgery were included. The tear break-up times (TBUTs) and keratoconjunctival staining results were compared between phakic and pseudophakic eyes. The mean age of the patients was 69.3 ± 10.4 years (32 men, 36.0%), and the mean postoperative period was 4.6 ± 4.4 (1–20) years. For the ophthalmic parameters, the TBUTs were 4.4 ± 1.9 and 3.8 ± 1.9 s (p < 0.001), the keratoconjunctival staining scores were 0.11 ± 0.38 and 0.22 ± 0.56 (p = 0.02), the spherical equivalents were −1.27 ± 2.51 and −0.99 ± 1.45 D (p = 0.21), the astigmatic errors were 0.79 ± 0.66 and 0.78 ± 0.58 D (p = 0.80), and the intraocular pressures were 13.6 ± 2.9 and 13.5 ± 2.6 mmHg (p = 0.62) for the phakic and pseudophakic eyes, respectively. The corneal status was significantly worse in the pseudophakic eyes than in the contralateral phakic eyes, even after more than one year after implant surgery. The present results suggested that long-term ocular surface problems should be examined further since they may not originate only from surgery or postoperative ocular surface diseases.

Objective: To evaluate the accuracy of diagnosing dry eye disease (DED) by using the Visionix VX120+, to establish reference values for tear meniscus height (TMH) and non-invasive break-up time (NIBUT), and to compare the NIBUT measurements with the fluorescein tear break-up time (FBUT), Methods: fifty-eight subjects (34 dry eye and 24 control) were enrolled. The TMH, first NIBUT, and NIBUT50% were evaluated with the Visionix VX120+, and the FBUT was measured with a slit-lamp. The Receiver Operating Characteristic (ROC) curve was used to evaluate the diagnostic performance, and the Bland–Altman method was performed to analyze the agreement. Results: The areas under the curve were 0.62, 0.60, and 0.70 for the TMH, first NIBUT, and NIBUT50%, respectively. The optimal cut-off values (sensitivity, specificity) were 0.29 (0.62, 0.67), 5.05 (0.85, 0.46), and 7.35 (0.65, 0.79) for the TMH, first NIBUT, and NIBUT50%, respectively. The mean differences (lower, upper limits of agreement) were −1.10 (−8.78, 6.58) and 1.55 (−5.68, 8.78) for the first NIBUT vs. FBUT and the NIBUT50% vs. FBUT, respectively. Conclusions: In conclusion, the NIBUT50% can be a useful tool for dry eye screening, with acceptable values of sensitivity and specificity. First, the NIBUT and NIBUT50% should not be used interchangeably with the FBUT.

In this study, we aimed to investigate the effect of different hyaluronic acid (HA)-containing artificial tears on dry eye disease (DED) treatment in combination with intense pulsed light (IPL) therapy. A retrospective cohort study was conducted, and the participants received IPL therapy and HA-containing artificial tears. There were 42 and 40 eyes in the 0.10% and 0.15% HA groups after selection, respectively. The main outcomes were the postoperative non-invasive tear break-up time (NITBUT), Schirmer II test results, ocular surface stain, and numbers of DED-related symptoms. A generalized linear model was utilized to produce the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the main outcomes between groups. At the three-month follow-up, the NITBUT was significantly higher in the 0.15% HA group (p = 0.023), and the NITBUT recovery was also significantly better in the 0.15% HA group compared to the 0.10% HA group (p = 0.039). The multiple DED-related symptoms significantly correlated with no DED symptom improvement in both the 0.10% and 0.15% HA groups (both p < 0.05), while the low pre-treatment NITBUT was marginally related to no DED symptom improvement in the 0.10% HA group (p = 0.047). A low NITBUT and Schirmer II test result correlated with no DED symptom improvement in both the groups (all p < 0.05). In conclusion, the application of 0.10% and 0.15% HA-containing artificial tears revealed similar effects to IPL therapy for DED.

The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events.

Background: The prevalence of dry eye disease (DED) is increasing globally, resulting in a variety of eye symptoms characterized by discomfort and visual disturbances. The accurate diagnosis of the disease is often challenging and complex, requiring specialized diagnostic tools. This study aimed to investigate the impact of tear film instability on visual function and to evaluate the value of post-blink blur time (PBBT) as an alternative method for assessing tear film stability. Methods: The study included 62 subjects: 31 with subjective symptoms of DED (Group A) and a control group consisting of 31 healthy participants (Group B). Symptoms were assessed using the standard Schein questionnaire, supplemented with additional questions. PBBT was measured using standard Snellen charts to investigate a potential association between PBBT and tear film dysfunction. Additional clinical assessments included tear film break-up time (TBUT). Results: Statistically significant differences were observed in the average values of PBBT and TBUT between the examined groups. The average PBBT was 8.95 ± 5.38 s in the group with DED and 14.66 ± 10.50 s in the control group, p < 0.001. Group A exhibited an average TBUT of 4.77 ± 2.37 s, while Group B had a TBUT of 7.63 ± 3.25 s, p < 0.001. Additionally, a strong positive correlation was identified between PBBT and TBUT values (r = 0.455; p < 0.001). Conclusions: The research confirms that tear film stability has an important role in the refraction of light and the maintenance of optical quality of vision. PBBT could potentially function as an objective and clinically significant screening test for DED.

This study aimed to evaluate the non-invasive and subjective symptoms associated with Lehfilcon A water gradient silicone hydrogel contact lenses with bacterial and lipid resistance technology. A prospective, longitudinal, single-centre, self-controlled study was conducted among silicone hydrogel contact lens wearers. Non-invasive analysis of the pre-lens tear film was performed using the Integrated Clinical Platform (ICP) Ocular Surface Analyzer (OSA), and the meibomian glands were evaluated with the Cobra® HD infrared meibographer. After 30 days of contact lens wear, the subjects were re-evaluated to determine the changes in conjunctival redness, subjective dry eye disease, tear meniscus height, lipid pattern, and non-invasive break-up time. Results showed that the lipid layer thickness decreased significantly from 2.05 ± 1.53 to 0.92 ± 1.09 Guillon patterns, and the tear meniscus height decreased from 0.21 ± 0.04 to 0.14 ± 0.03. The mean pre-lens non-invasive break-up time (NIBUT) significantly increased from 15.19 ± 9.54 to 25.31 ± 15.81 s. The standard Patient Evaluation of Eye Disease (SPEED) score also decreased from 7.39 ± 4.39 to 5.53 ± 4.83. The results suggest that Lehfilcon A significantly reduced lipid and aqueous tear film volume but improved break-up time and subjective dry eye symptoms.

(1) Background: Changes in blink parameters have been found to influence ocular surface exposure, eliciting symptoms of dry eye and ocular signs. The aim of the study was to highlight the relevance of including blink regularity as a new parameter to fully characterize blinking; (2) Methods: A novel characterization of blink parameters is described, including spontaneous eyeblink rate (SEBR), percentage of incomplete blinks, and blink regularity. A pilot study was designed in which tear film break-up time (TFBUT), blink parameters, and the time percentage of ocular surface exposure were determined in eight subjects (52.0 ± 16.6 years, 4 females) in three experimental conditions (baseline, reading a hard-copy text, and reading from an electronic display). Blink parameters were monitored through asynchronous image analysis of one minute video segments; (3) Results: All blink parameters were influenced by experimental conditions. A trend was observed in which both reading tasks resulted in an increase in ocular surface exposure, mainly related to a combination of reduced SEBR, increased percentage of incomplete blinks, and loss of blink regularity; (4) Conclusions: A complete characterization of blink parameters is relevant to better understand ocular dryness related to surface exposure and to advice patients towards a reeducation of their blinking habits.

Purpose: This study aims to compare dry eye parameters before and after COVID-19 infection in dry eye patients. Methods: We included 44 dry eye patients (88 eyes) from our existing dry eye cohort, with 22 belonging to the post-COVID-19 group due to a prior COVID-19 infection and the other 22 forming the non-COVID-19 group as they had no history of COVID-19. We examined and compared the dry eye parameters of the post-COVID-19 group, including the ocular surface disease index (OSDI), Schirmer’s test results (ST), non-invasive Keratography tear break-up time (NIKBUT), lipid layer thickness (LLT), Meibomian gland dysfunction (MGD), and the grading of papillae and follicles, both before and after the COVID-19 infection. We also compared the dry eye parameters difference of the post-COVID-19 group with the non-COVID-19 group. Results: The post-COVID-19 group was comprised of individuals with an average age of 38.36 ± 14.99 years, of which 82% were female. The time interval between the two tests was 16.92 ± 5.40 months, which did not differ significantly from the non-COVID-19 group. Compared to the pre-COVID-19 eyes, the post-COVID-19 eyes showed a significant decrease in the average LLT (52.86 ± 18.00 nm vs. 63.00 ± 22.40 nm, p < 0.001), as well as the maximum LLT (67.89 ± 20.81 nm vs. 78.48 ± 20.55 nm, p < 0.001). The MGD in both the upper (1.75 ± 0.84) and lower eyelids (1.43 ± 0.73) worsened after a COVID-19 infection. Additionally, the grading of papillae was worse following a COVID-19 infection (0.61 ± 0.69 vs. 0.16 ± 0.37, p < 0.001). The multivariate linear regression model revealed a negative association between COVID-19 infection and NIKBUT-average (β = −2.98, 95%CI: (−5.82, −0.15), p = 0.039), LLT-average (β = −14.12, 95%CI: (−22.66, −5.59), p = 0.001), and LLT max (β = −15.65, 95%CI: (−23.09, −8.20), p < 0.001). Conclusion: From preliminary results, we concluded that dry eye patients who have been infected with COVID-19 appear to have a more severe dry eye condition, as evidenced by lower LLT, worse papillae and MGD, and shorter NIKBUT. It is important to raise awareness of this potential long-term symptom of COVID-19, especially among existing dry eye patients.

The purpose of this study is to evaluate the tear film dynamics between individuals with low and high Contact Lens Dry Eye Disease Questionnaire (CLDEQ-8) scores when wearing Lehfilcon A silicone hydrogel water gradient contact lenses. In this study, we implemented a longitudinal, single-location, self-comparison investigation. Variables measured included conjunctival redness, lipid layer thickness, tear meniscus height, first and mean non-invasive break-up time, CLDEQ-8, and standard patient evaluation of eye dryness (SPEED). In the second phase, participants were re-evaluated after 30 days of wearing the contact lenses to assess the tear film wearing the lenses. In a longitudinal comparison by group, we found that lipid layer thickness decreased 1.52 ± 1.38 (p < 0.01) and 0.70 ± 1.30 (p = 0.01) Guillon patterns degrees in the low and high CLDEQ-8 group, respectively. MNIBUT increased in 11.93 ± 17.93 (p < 0.01) and 7.06 ± 12.07 (p < 0.01) seconds. Finally, LOT increased in 22.19 ± 27.57 (p < 0.01) and 16.87 ± 25.09 (p < 0.01). In conclusion, this study demonstrates the effectiveness of Lehfilcon A silicone hydrogel water gradient contact lenses in improving tear film stability and reducing subjective dry eye symptoms in individuals with low and high CLDEQ-8 scores. However, it also led to an increase in conjunctival redness and a decrease in tear meniscus height.

The purpose of this study was to assess the effect of environmental working conditions on the symptoms and signs of dry eye disease and to examine whether and how those conditions impact the ocular surface. Methods: This single-center, prospective clinical study with a 1-year follow-up included 150 patients. The following parameters were evaluated: non-invasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and conjunctival and limbal hyperemia. We also performed staining of the surface of the eye for simulated fluorescein images, Schirmer’s test I, assessment of Meibomian gland dysfunction (MGD), and an Ocular Surface Disease Index (OSDI) questionnaire. Results: In the OW (office workers) group, in people working >4 h at the computer, the NIKBUT before work and the Schirmer test results were statistically significantly lower than in people working 4 h at a computer in both groups and after work in the MW (medical workers) group. Low relative air humidity in the building and air-conditioned rooms negatively affects the tear film, causing the symptoms of dry eye disease. At the 1-year follow-up, there was a statistically significant reduction in conjunctival and limbal hyperemia in the OW group as well as a statistically significant reduction in TMH at the first examination before and after work, and in the second examination after 1 year in both groups. Conclusions: Environmental factors such as reduced relative air humidity, increased air temperature, and decreased illumination have a negative impact on the ocular surface.

The purpose of the present study was to evaluate changes of signs and symptoms in patients with meibomian gland dysfunction (MGD) treated with intense regulated pulsed light (IRPL), and to further investigate which parameter could predict positive outcomes of the procedure. Twenty-eight patients who bilaterally received three IRPL sessions at day 1, 15, and 45 satisfied the criteria and were included in the study. Non-invasive break-up time (NIBUT), lipid layer thickness (LLT), meibography, tear osmolarity, and ocular discomfort symptoms were measured before and 30 days after the last IRPL session. Qualified or complete success was defined in the presence of an improvement of symptoms associated with an increase of NIBUT (< or ≥ 20%). After IRPL treatment, median NIBUT and LLT increased from 7.5 to 10.2 s and 2.0 to 3.0, respectively (p p = 0.002). Subjective symptoms improved after IRPL in 26 patients. Qualified success was reached in 34 eyes, while complete success in 16 eyes. Patients with lower baseline break-up time (BUT) values showed better response to treatment (p = 0.04). In conclusion, IRPL improved signs and symptoms in MGD patients, while lower baseline NIBUT values were predictive of better response to IRPL.

The goal of this study was to investigate the effects of two commonly used oral antihistamines—diphenhydramine and loratadine—on tear volume, tear breakup time, and intraocular pressure. Placebo, diphenhydramine, and loratadine were administered for one week to 33 subjects experimentally blind to the treatment given. All the subjects received all three treatments over a period of six weeks. The outcome measures were the change in phenol red thread test (PRT), the tear breakup time (TBUT), and the intraocular pressure (IOP) of both eyes evaluated by experimentally masked observers. Neither of the mean changes in TBUT or IOP depended on the treatment given, but there was a significant monocular decrease in tear volume from diphenhydramine use. While we used an adequate treatment washout period of seven days, our investigation was limited by the short treatment times and inclusion of only young healthy patients. Overall, however, these results suggest that systemic diphenhydramine use should be limited to increase the effectiveness of conventional therapies. Clinicians should have fewer reservations about recommending the use of loratadine concurrent with dry eye treatments.

Background and Objectives: Human umbilical cord blood serum (HUCBS) stands out as a potent adjunct to conventional therapies for ocular surface disorders (OSDs) caused by, among many, autoimmune systemic syndromes. By expediting ocular surface regeneration and fostering epithelial integrity, HUCBS not only enhances subjective patient experiences but also improves objective clinical indicators. This makes it particularly useful in patients with corneal ulcers through ocular surface regeneration and anti-inflammatory activity. This study aims to explore the efficacy of HUCBS in patients who had previously received other treatments unsuccessfully. Materials and Methods: This study was a prospective, non-comparative, interventional case series study involving 49 patients (30 females and 19 males) aged 15–82 years with severe OSDs who were unresponsive to standard treatments. The study was conducted at the San Marco Hospital, Catania, Italy. Patients were categorized into four groups based on the etiology of their severe OSDs: Group I consisted of twenty four patients with filamentary keratitis and corneal ulcers associated with rheumatologic diseases such as Sjogren’s syndrome and systemic sclerosis; Group II comprised thirteen patients with graft-versus-host disease; Group III consisted of nine patients with corneal neurotrophic ulcers; and Group IV included three patients with Steven–Johnson syndrome. The outcomes were evaluated before and after treatment using the following assessments: OSDI (Ocular Surface Disease Index) and SANDE (Symptom Assessment in Dry Eye) questionnaires, VAS (Visual Analog Scale), Slit Lamp Examination, Esthesiometry, Lissamine Green Staining, NIBUT (Non-Invasive Break-Up Time), BUT (Break-Up Time), Fluorescein Staining with Photography and Oxford Classification, The Schirmer Test, Best-Corrected Visual Acuity (BCVA), and Meibography. Results: We observed a significant improvement in the outcomes from the SANDE, VAS, and OSDI questionnaires, The Schirmer Test, BUT, BCVA, and Oxford Classification, after treatment with UCBS. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, and pain, were also considered individually. Nevertheless, pain and inflammation reduced markedly over time until complete healing was achieved in all cases. Conclusions: Our pilot study highlights the substantial efficacy of HUCBS in patients with systemic autoimmune diseases who have shown inadequate responses to prior treatments for dry eye. This underscores the need for further comprehensive investigations in this field.

Most persons with obesity who have undergone gastric bypass surgery present depressive symptoms. Depression and anxiety have been associated with tear film disorders. This study aimed to investigate whether there is a correlation between tear film conditions and depression symptoms in patients subjected to bariatric surgery. The participants completed a Patient Health Questionnaire to detect depression symptoms. The break-up time and Schirmer test were subsequently applied; the measurements were performed three times, and the average time was subsequently recorded. The results revealed that the Schirmer test score and PH-9 score were negatively correlated, but this was not the case for the break-up time test. Depression symptoms may correlate with lower tear production from the principal tear gland, but they may not have the same effect on meibomian gland production in adults undergoing bariatric surgery. In addition to routine control, bariatric surgery patients should be periodically evaluated by an ophthalmologist and/or psychologist who is aware of potential comorbidities. Furthermore, the observed association between depression symptoms and tear deficiencies highlights the importance of further investigations to gain a better understanding of these mechanisms.

Purpose: The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease. Methods: In this prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment. Results: During the treatment period, Group 1 showed statistically significant improvement in OSDI score (p = 0.002), SANDE score (p = 0.01), NIBUT (p < 0.0001), LLT (p < 0.0001), TBUT (p = 0.01), and CFS (p = 0.02). In Group 2, significant improvement was observed only in the TBUT score (p < 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment (p = 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period (p > 0.05). Conclusions: The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.

Accurate diagnosis of dry eye disease (DED) is challenging, and even today there is no gold standard biomarker of DED. Hypothesis-free global metabolomic studies of tears from DED patients have great potential to discover metabolites and pathways affected in the pathophysiology of DED, and to identify possible future biomarkers. These metabolites and biomarkers could be important for diagnosing and monitoring disease as well as for new therapeutic targets and strategies. As DED is associated with dry mouth, this study aimed to perform metabolomic analyses of tears and saliva from patients with decreased tear film break-up time but normal Schirmer test, and age-matched controls with both tear production and stability within physiological range. We applied strict inclusion criteria to reduce sampling bias in the metabolomic analyses and selected only age-matched females with Schirmer test values between 10–15 mm/5 min. The tear film analysis arm included 19 patients (with tear film break-up time 0–5 s) and 12 controls (with tear film break-up time 10–30 s), while the salivary analysis arm consisted of a subset which included 18 patients and six controls. Metabolomic analyses were performed using liquid chromatography and high-resolution mass spectrometry. Analyses using a global database search detected a total of 56 metabolites in tear samples that were significantly different between the groups. Of these, several have known associations with DED. These metabolites are present in meibum and have anti-oxidative characteristics or associations with the ocular microbiome, and altered concentrations suggest that they may play a significant role in DED associated with decreased tear film stability. In saliva, hypotaurine levels were lower among patients with tear film instability. In this pilot study, we found different levels of several metabolites in patients with decreased tear film break-up time that may have associations with DED. Future studies are required to replicate our findings and clarify the exact roles of these metabolites.

Purpose: To describe the clinical and morphologic changes in the ocular surface microstructure of patients affected with moderate-to-severe Atopic Dermatitis (AD) before and during Dupilumab treatment. Methods: This is a monocentric observational study on thirty-three patients affected with AD before and during Dupilumab treatment. All patients underwent a slit-lamp examination: complete clinical assessment, Break Up Time test (BUT), Schirmer test, and corneal staining grading (Oxford scale) were performed. Meibomian Glands Dysfunction (MGD) evaluation (Meibography), Non-invasive Keratograph Break Up Time test (NIKBUT), Tear Meniscus Height (TMH), and ocular Redness Score (RS) have been investigated using an OCULUS Keratograph. In vivo images of the conjunctiva, cornea, and meibomian glands have been acquired by confocal microscopy. Results: Sixty-six eyes were included in our study: twenty-two eyes of 11 naive patients with indication for treatment but not in therapy yet (Group 1) and forty-four eyes of 22 patients treated with Dupilumab for at least 4 months (subcutaneous administration of 300 mg every 2 weeks) (Group 2). Either patients treated with Dupilumab or naive patients with moderate-to-severe forms of AD had a tear film instability (TBUT and NIKBUT reduced), whereas the quantity of the tear film was overall normal (Schirmer test and TMH), without statistically significant differences between the two groups. When Meibography was performed with the Keratograph, the difference between Group 1 and Group 2 was statistically significant in terms of Meiboscore (p = 0.0043 and p = 0.0242, respectively), as well as the difference in terms of mean RS. These results paired well with the confocal microscopy results in which we found a decrease in the goblet cell population in the conjunctival epithelium in the treated group (5.2 cells/mm), along with inflammatory cells that were more concentrated around the adenoid lumina of the meibomian glands. Conclusions: In recent years, the use of Dupilumab has been increasing, but mild-to-severe conjunctivitis is a common side effect. Our major results demonstrate a loss of meibomian glands at the Keratograph examination: we can assume a reduced meibum secretion and an evaporative dry eye with MGD. We suggest that the inflammation of the ocular surface may involve not only the cornea and the conjunctiva, but also the meibomian glands, and Dupilumab may play a role. However, the frequency of clear conjunctivitis is not as common as reported in the literature.

Background/Objectives: This study aimed to evaluate the therapeutic effects of combined 5% lifitegrast (LF) and tocopherol (TCP) eye drops in a murine experimental dry eye (EDE) model. Methods: Female C57BL/6 were divided into seven groups: untreated controls, EDE control, EDE + 0.05% cyclosporin A (CsA), EDE + tocopherol (TCP), EDE + 5% LF, EDE + 5% LF + TCP (once daily), and EDE + 5% LF + TCP (twice daily). Clinical parameters (tear volume, tear break-up time (TBUT), corneal fluorescein staining score (CFSS), tear film lipid layer grade (TFLLG)) were assessed on days 7 and 14. Goblet cell density in the conjunctiva, CD4+ IFN-γ+ T cells, interleukin levels, reactive oxygen species (ROS) levels, and corneal apoptotic cells were analyzed on day 14. Results: Monotherapy with 0.05% CsA and LF showed improvements in all clinical parameters compared to the EDE control (p < 0.05). Combination therapy groups demonstrated superior improvements in clinical parameters compared to the EDE control, 0.05% CsA, and 5% LF groups. CD4+ IFN-γ+ T cell percentages and ROS levels in the cornea and conjunctiva were markedly reduced in the combination groups compared with the 0.05% CsA and 5% LF groups (p < 0.01). Furthermore, corneal apoptotic cells significantly decreased in the combination groups compared to the 0.05% CsA and TCP groups (p < 0.05). Conclusions: Combined 5% LF and TCP eye drops improved tear film parameters and reduced inflammatory and oxidative stress markers. The combination therapy can mitigate ocular surface damage by managing inflammation and oxidative stress in dry eye.

Background: This study aimed to evaluate the impact of image enhancement techniques on the interobserver reliability of tear break-up time (TBUT), tear meniscus height (TMH), corneal fluorescein staining (CFS) scoring, and conjunctivochalasis detection using the Smart Eye Camera (SEC), a portable device for anterior segment examination. Methods: A retrospective analysis was conducted on video recordings captured by the SEC from 46 patients with dry eye disease (DED). Separate sets of images were created for each level of enhancement: unenhanced (G0), mildly enhanced (G3), and strongly enhanced (G7). These sets were not intermixed, ensuring that each enhancement level was assessed independently. Three observers—two DED specialists and one general ophthalmologist—assessed TBUT, TMH, CFS scores, and conjunctivochalasis. Interobserver reliability was evaluated using intraclass correlation coefficients (ICCs) for each image set. Results: Interobserver reliability for CFS scores significantly improved with G3, yielding an ICC of 0.8413. In contrast, G7 improved reliability for TBUT measurements (ICC = 0.7381), but led to a notable decrease in reliability for both CFS scoring (ICC = 0.2259) and conjunctivochalasis detection (ICC = 0.0786). Furthermore, the assessment of TMH demonstrated a progressive decline in accuracy with increasing levels of image enhancement. Conclusions: Image enhancement using the SEC improved the diagnostic consistency of dry eye specialists and general ophthalmologists, especially for TBUT and CFS assessments. However, excessive enhancement may obscure key diagnostic features, indicating the need for careful optimization of image processing techniques depending on the diagnostic focus.

Purpose: To evaluate how Video Display Terminal (VDT) use, Contact Lens (CL) wear, and eyedrop use affect ocular surface parameters in participants with ocular discomfort and how these factors may vary across different age groups. Methods: The current cross-sectional study initially involved a total of 252 participants who completed a self-administered survey to collect information about ocular discomfort and lifestyle factors. This online survey was composed of an Ocular Surface Disease Index (OSDI) questionnaire and three extra questions regarding lifestyle factors (VDT use, CL wear, and eyedrop use). Only 185 symptomatic participants, those with OSDI values > 12, were scheduled to undergo a comprehensive ocular examination that included tear film osmolarity, Fluorescein Break-Up Time (FBUT), Maximum Blink Interval (MBI), and corneal staining. Results: Differences in ocular parameters and lifestyle factors across age groups (60 years) were analyzed, along with their correlations and regression. Significant age group differences were found in OSDI, osmolarity, FBUT, and MBI (One-way ANOVA, all p ≤ 0.029). Correlations were observed between CL wear and osmolarity and MBI (Pearson’s correlation, both p ≤ 0.049). Multiple regression confirmed age associations with OSDI, osmolarity, FBUT, and MBI (Multiple linear regression, all p ≤ 0.040) and found links between VDT use and osmolarity and MBI (Multiple linear regression, both p ≤ 0.038) and between eyedrop use and OSDI (Multiple linear regression, p = 0.040). Conclusion: Aging is a primary factor affecting ocular homeostasis, with older adults showing lower FBUT and MBI values and higher osmolarity. Prolonged use of VDTs exacerbates this effect, further contributing to ocular discomfort and destabilized tear film. No associations between CL wear and any of the ocular parameters were found. Eyedrop use shows varied effects on ocular comfort across age groups, emphasizing the need for age-specific ocular care. Overall, these findings confirm that aging and extended VDT use play a significant role in ocular surface discomfort.

We evaluated the efficacy and safety of eye drops with antiseptic and re-epithelizing properties (Keratosept®, Bruschettini, Genova, Italy) on 50 eyes affected by punctate keratitis of suspected microbial origin. A biomicroscopic examination, fluorescein dye staining test (Fluotest), tear break-up time test (TBUT), and the ocular surface disease Index (OSDI) questionnaire were used to assess treatment efficacy. Treatment success was defined as a negative Fluotest and an OSDI score ®, either alone or in combination with antibiotics, was effective in over 80% of microbial and nonmicrobial forms. Conjunctival swabs were taken from all patients for culture examination with an antibiogram and sensitivity test for Keratosept®; 32/43 (74.4%) forms with positive culture for the bacteria were sensitive to Keratosept®. A total of 35/38 (92%) eyes treated with this product alone achieved full treatment success without any apparent adverse effects. These results suggest the use of Keratosept® eye drops in punctate keratitis as an alternative or in combination with established antibiotic therapies. Further studies are needed to evaluate its efficacy in different infectious forms and identify other indications for using this product.

Background: Graft-versus-host disease (GvHD) is an overactive systemic inflammatory response that can arise following allogeneic hematopoietic stem cell transplantation (HSCT). This condition occurs when the transplanted donor immune cells recognize the recipient’s tissues as foreign and trigger an immune response against them. The ocular surface (eyelids, conjunctiva, meibomian glands, lacrimal glands, and cornea) is particularly involved in GvHD, and its response to existing treatments, including potent immunosuppressants and new targeted therapies, is undesirable, with such treatments often being ineffective. Human allogeneic umbilical cord blood platelet lysate stands out as a potent adjunct to conventional therapies for ocular surface disorders related to severe Dry Eye Disease. This study aimed to evaluate the safety and efficacy of umbilical cord blood platelet lysate eyedrops for the treatment of severe ocular surface disorders in graft-versus-host disease patients who have received previous unsuccessful treatments. Methods: This study was a prospective, non-comparative, interventional case series study involving 22 patients (10 females and 12 males) aged 25–46 years with severe ocular surface disorders that were unresponsive to standard treatments. The GvHD patients were categorized based on the severity of their ocular surface disorders into three groups: Group I: five patients with severe Dry Eye Disease and filamentary keratitis; Group II: eight patients suffering from severe blepharo-kerato-epitheliopathy; Group III: nine patients with corneal ulcers. Fresh umbilical cord blood (UCB) was obtained from healthy donors and subjected to centrifugation using a novel PRP preparation kit provided by Sciacca (AG) Cord blood bank, Italy in a one-step process. In all groups, the outcomes before and after treatment were evaluated by means of the OSDI (Ocular Surface Disease Index), SANDE (Symptom Assessment in Dry Eye) questionnaire, VAS (Visual Analogue Scale), slit lamp examination, Esthesiometry, Lissamine Green Staining, the NIBUT (Non-Invasive Break-Up Time) and BUT, fluorescein staining with digital photography and Oxford classification, the Schirmer Test, the Best Corrected Visual Acuity (BCVA), and Meibography. In Group III at each evaluation time, the size of the ulcer and its relative reduction compared to the baseline size were recorded. Clinical variables, such as corneal inflammation, conjunctivalization, corneal neovascularization, or pain, were also considered individually. Results: We observed a significant improvement in the SANDE, VAS, and OSDI scores; Schirmer Test; BUT; BCVA; and Oxford classification after treatment with allogeneic cord blood serum eyedrops. Nevertheless, pain and inflammation reduced markedly over time until complete healing in all cases. The mean reduction in the ulcer surface area (compared to baseline values) was significantly higher at all assessment points (p = 0.001 for day 7 and p < 0.001 for subsequent time points every 30 days for 90 days). At the last check-up (after 90 days of treatment), the number of ulcers (Group III, nine patients) with a reduction in size of greater than 50% was eight (88.8%), of which seven ulcers were completely healed. None of the patients experienced treatment-related local or systemic adverse events. In this study, using a relatively large number of cases, we demonstrated that the use of umbilical cord blood platelet lysate eyedrops is a safe, feasible, and effective curative approach for severe ocular surface disease in patients with GvHD. Conclusions: Our pilot study highlights the remarkable effectiveness of allogeneic cord blood serum eyedrops in patients with severe ocular surface disorders following GvHD who have shown an inadequate response to the usual treatments. It is mandatory to design future studies on the efficacy of this therapeutic approach for acute ocular, mucosal, and cutaneous GvHD.

We aim to evaluate the effectiveness of an acupuncture steam-warming eye mask (ASEM) on dry eye disease (DED) in visual display terminal (VDT) users. This prospective randomized clinical trial included VDT users with DED-related features who were randomly assigned to the ASEM group (ASEM for 2 weeks, 20 participants) or the steam-warming eye mask (SEM) group (SEM for 2 weeks, 20 participants). The tear film break-up time (TBUT), Schirmer test, tear meniscus height, ocular surface staining scores, eyelid and meibomian gland exam, subjective symptoms, and quality of life (QoL) scores before and after treatment were collected. A generalized linear mixed model was applied to compare the improvement of symptoms and signs between the two groups. After the 2-week treatment, all the subjective symptoms and questionnaire scores in the ASEM group improved significantly (all p < 0.05), whereas the feelings of relaxation, comfortable, and refreshment did not change in the SEM group (both p > 0.05). The TBUT, tear meniscus height, and meibum quality in the lower eyelid were significantly better in the ASEM group than the SEM group (all p < 0.05), whereas no significant changes were observed in the Schirmer test and ocular surface staining scores. Compared with the SEM group, the ASEM group experienced a stronger feeling of refreshment (p = 0.013), lower sensation of ocular discharge (p = 0.031), higher TBUT (p = 0.045), better meibomian gland expressibility of both eyelids (both p < 0.05), and better meibum quality of both eyelids (both p < 0.05), even after adjustments for age and sex. In conclusion, comparing with SEM, ASEM can improve some subjective DED symptoms, tear film stability, and meibum status in VDT users.

The authors performed an ex vivo and in vivo evaluation of the ultrastructural effects on the conjunctival epithelial cells of a new multiple-action tear substitute containing cross-linked hyaluronic acid, lipids and trehalose (Trimix®), using scanning electron microscopy (SEM) with conjunctival impression cytology. The ex vivo study highlights the persistence and distribution of the product at 5 and 60 min on a monolayer of conjunctival epithelial cells and an increase in microvilli density at the 60 min evaluation. In vivo examination was conducted on three subjects with different grades of ocular surface inflammation, treated with one drop of the product twice daily for thirty days. At the baseline (T0) and twelve hours after the last administration of the tear drop (T30), impression cytology of the upper bulbar conjunctiva for SEM evaluation of conjunctival epithelial cells was carried out. Slit lamp examination (SLE), corneal and conjunctival Fluotest, tear film break-up time (TBUT), and ocular surface disease index (OSDI) questionnaires were also performed to correlate the ultrastructural results with the clinical findings. After 30 days of treatment, a significant improvement in all clinical and symptomatic parameters and in the condition of the ocular surface was detected, with microvillar regeneration and strengthening in all the patients, and a complete restoration in 2/3 of them. The persistence and distribution of the product on the epithelial cells was also noted 12 h after the last administration. The results, therefore, suggest a marked epitheliotropic effect along with a high residence time of the tear substitute.

Cataracts are characterized by the crystalline lens of the eye becoming cloudy, and dry eye disease (DED) is a multifactorial disease in which the homeostasis of the tear film is lost. As the prevalence of both diseases increases with age, there is a high prevalence of DED among patients who are candidates for cataract surgery. In recent years, cataract surgery has evolved from vision restoration surgery to refractive surgery. To achieve good surgical outcomes, it is necessary to minimize postoperative refractive error in intraocular lens (IOL) power calculation, which requires accurate preoperative keratometry measurements. A stable tear film is important for the accuracy and reproducibility of keratometry measurements, and DED may have a deleterious effect. In this study, original articles that focused primarily on findings related to this topic were evaluated. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Although appropriate DED diagnoses were not presented in the articles evaluated in this review, it was confirmed that the clinical signs of DED, particularly the shortening of the tear film break-up time (TBUT), negatively impact IOL power calculations. Improvement in these clinical signs might mitigate the negative effects on these calculations.

This prospective case-control study investigated gender-related differences in dry eye symptoms following surgery for involutional ectropion and entropion. A total of 109 patients, aged between 65 and 89, were categorized by eyelid condition and gender. Postoperative assessments included the Tear Film Break-Up Time (TBUT) test, Schirmer I test results, corneal and conjunctival staining, eyelid margin characteristics, and scores from the Ocular Surface Disease Index (OSDI) questionnaire. The analysis revealed notable gender-related differences in dry eye manifestations. Initially, men exhibited lower TBUT scores but higher Schirmer test readings compared to women; however, these disparities diminished over time. No significant gender differences were detected in corneal and conjunctival staining, indicating similar levels of ocular surface damage across genders. Males showed significantly higher values in several eyelid margin characteristics (LMI, LMT) at various postoperative time points. According to the OSDI questionnaire, women experienced more severe symptoms of dry eye both pre- and post-operatively, suggesting a greater subjective symptom burden. When comparing surgical outcomes for ectropion and entropion, both conditions showed improvement in eyelid positioning and dry eye symptoms post-surgery. Despite these improvements, women with either condition reported more severe dry eye symptoms compared to men throughout the postoperative period. This study highlights the gender-specific variations in dry eye symptoms following eyelid malformation surgery and emphasizes the importance of adopting gender-sensitive approaches in postoperative care to improve outcomes and ocular health.

Background: To clinically evaluate how dry eye symptoms in preoperatively diagnosed dry eye patients change with the use of sodium hyaluronate- and dexpanthenol-containing eye drops (HYLO CARE (HC), URSAPHARM Arzneimittel GmbH, Saarbruecken, Germany) after cataract surgery. The aim of the study was not to compare different eye drops but to implement standard treatment in patients with dry eye undergoing cataract surgery. The impact of treatment was evaluated using Symptom Assessment Tools for Dry Eye. Methods: In this prospective, single-center, open-label clinical trial, 49 patients undergoing cataract surgery were included who showed signs and symptoms of dry eye disease assessed by the Symptom Assessment in Dry Eye (Visual Analogue Scale (VAS)) questionnaire, Ocular Surface Disease Index (OSDI), and fluorescein tear break-up Time (TBUT). Patients were instructed to apply HC three to four times a day for 5 weeks in the operated eye in addition to the standard postoperative topical anti-inflammatory regimen. The primary endpoint was the change in TBUT. Secondary endpoints were the assessment of the subjective symptoms (VAS), corrected distance visual acuity (CDVA), and slit-lamp examination including the corneal staining score, Schirmer test, and intraocular pressure. Results: At 5 weeks after operation, the mean TBUT increased from 6.42 ± 1.57 s (s) to 7.81 ± 1.83 s in the per-protocol (PP) population (p > 0.001) and from 6.33 ± 1.64 s to 7.71 ± 2.05 s in the intention-to-treat (ITT) population (p < 0.001). There was a statistically significant decrease in all scores (p < 0.05) from the VAS questionnaire except for the tearing score (p = 0.062) at 5 weeks after operation. The mean total corneal staining score also decreased statistically significantly from 8.85 ± 2.49 before operation to 5.61 ± 3.37 at 5 weeks after operation on a 15-point scale. Conclusions: Controlled standardized dry eye treatment (with HC) improved tear film stability, ocular surface defects, and subjective symptoms of dry eye disease in patients 5 weeks after undergoing cataract surgery. Both the patient and physician assessments indicated high efficacy, tolerability, and a reliable safety profile, as indicated by the low number of at least possibly related adverse events (AE), suggesting its beneficial role in the postoperative management of the ocular surface (OS) in patients with dry eye symptoms prior to and after cataract surgery.

Polyunsaturated fatty acids (PUFAs) generate pro- and anti-inflammatory eicosanoids via three different metabolic pathways. This study profiled tear PUFAs and their metabolites and examined the relationships with dry eye (DE) and meibomian gland dysfunction (MGD) symptoms and signs. A total of 40 individuals with normal eyelids and corneal anatomies were prospectively recruited. The symptoms and signs of DE and MGD were assessed, and tear samples (from the right eye) were analyzed by mass spectrometry. Mann–Whitney U tests assessed differences between medians; Spearman tests assessed correlations between continuous variables; and linear regression models assessed the impact of potential confounders. The median age was 63 years; 95% were male; 30% were White; and 85% were non-Hispanic. The symptoms of DE/MGD were not correlated with tear PUFAs and eicosanoids. DE signs (i.e., tear break-up time (TBUT) and Schirmer’s) negatively correlated with anti-inflammatory eicosanoids (11,12-dihydroxyeicosatrienoic acid (11,12 DHET) and 14,15-dihydroxyicosatrienoic acid (14,15, DHET)). Corneal staining positively correlated with the anti-inflammatory PUFA, docosahexaenoic acid (DHA). MGD signs significantly associated with the pro-inflammatory eicosanoid 15-hydroxyeicosatetranoic acid (15-HETE) and DHA. Several relationships remained significant when potential confounders were considered. DE/MGD signs relate more to tear PUFAs and eicosanoids than symptoms. Understanding the impact of PUFA-related metabolic pathways in DE/MGD may provide targets for new therapeutic interventions.

This study investigated the prevalence of pigmentary keratitis (PK) in Pug-breed dogs and described the ocular surface characteristics associated with this disease. A total of 219 eyes from 110 dogs were examined, with 94.5% of them affected by PK. Age, previous ocular diseases, corneal vascularization, and corneal sensitivity were significantly associated with the presence of PF and the severity of corneal pigmentation. The study also found that low tear production and blinks incomplete with tear signs, as well as reduced corneal sensitivity, were linked to more severe forms of corneal pigmentation. The Tear Ferning Test (TFT) was identified as a valuable tool for evaluating tear quality in dogs, with worse test results indicating a higher risk of severe PK. A lower mean Tear Break-Up Time (TBUT) test was observed in dogs with PK. Additionally, the study observed a statistically significant difference in corneal thickness between the nasal and temporal zones, with the nasal zone being thicker. It was also suggested that sex and fertility status may influence the incidence of PK and the severity of corneal pigmentation. Overall, these findings provide insight into the underlying causes of PK in Pugs and can inform future treatment strategies for this breed.

Background and Objectives: Dry eye disease (DED) affects 5–50% of the global population and deeply influences everyday life activities. This study compared the efficacy, tolerability, and safety of novel Respilac artificial tears containing lipidure and hypromellose (HPMC) with the widely used Nextal artificial tears, which are also HPMC-based, for the treatment of moderate DED in contact lenses (CL) wearers. Materials and Methods: In a prospective, single-center, randomized investigation, 30 patients aged ≥18 years, diagnosed with moderate DED, and wearing CL were randomly assigned to the Respilac (n = 15) or Nextal group (n = 15). Patients self-administrated one drop of Respilac or Nextal in both eyes three times daily for 21 days. Changes in the endpoint (visual analogue scale (VAS) score for ocular tolerability, symptom assessment in dry eye (SANDE) score, non-invasive first break-up time (NIF-BUT) results, tear analysis value, meibography results, and CL tolerability results were assessed, comparing treatment groups and time-point evaluations. Adverse events (AEs) were also recorded and evaluated. Results: VAS scores decreased with time (p < 0.001) in both groups, showing no statistically significant difference among them (p = 0.13). Improvements were also detected from screening to end-of-treatment, which were indicated by the SANDE scores for severity and frequency (p < 0.001) and by tear analysis results (p < 0.001) with no observed difference between the Nextal and Respilac arms. NIF-BUT, meibography, and CL tolerability values were shown to be non-significantly affected by treatment and time. There were no AEs detected in this study cohort. Conclusions: Respilac was confirmed to be effective, safe, and well-tolerated. Lipidure-based ophthalmic solution was shown not to be inferior to the currently used Nextal, however, showing improvements in DED symptoms. Within the existing literature, our study is one of the first to report that MPC plus HPMC-containing eye drops are an effective option for the treatment of moderate dry eye disease and desiccation damage prevention in contact lens wearers.

Punctal occlusion (PO) is considered to improve both tear-film instability and increased friction during blinking and may consequently affect blinks. The purpose of this study was to investigate the effect of PO on blinks. This study involved 16 eyes of 16 severe aqueous deficient dry eye (ADDE) patients (mean age: 65.7 years). In all eyes, tear meniscus radius (TMR), spread grade (SG) of the tear-film lipid layer (i.e., SG 1-5: 1 being the best), fluorescein break-up time (FBUT), corneal epithelial damage score (CED), conjunctival epithelial damage score, corneal filament (CF) grade, lid-wiper epitheliopathy (LWE) grade, and superior limbic keratoconjunctivitis (SLK) grade were evaluated at before and at more than 1-month after PO. Moreover, using a custom-made high-speed blink analyzer, palpebral aperture height, blink rate, upper-eyelid closing-phase amplitude/duration/maximum velocity, and upper-eyelid opening-phase amplitude/duration/maximum velocity were measured at the same time point. After PO, TMR, SG, FBUT, CED, and the CF, LWE, and SLK grades were significantly improved, and upper-eyelid opening/closing-phase amplitude and maximum velocity significantly increased (all p < 0.04). The findings of this study suggest that PO improves ocular surface lubrication and that blink-related parameters can reflect the friction that occurs during blinking in eyes with severe ADDE.

Background and Objectives: Tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA) have mucoadhesive properties that improve drug absorption and delay in drug elimination from the ocular surface. We aimed to evaluate TSP/HA-containing formulation for its efficiency in dry-eye symptoms induced by adverse environments and the interaction between mucomimic polymer and tear-film parameters. Materials and Methods: The participants were exposed to 5% relative humidity (RH) in a Controlled Environment Chamber (CEC) under constant room temperature (21 °C). Tear-film parameters were assessed at 40% RH and 5% RH. Rohto Dry Eye Relief drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment) and relief (drops instilled after exposure to the dry environment). The HIRCAL grid, Servomed EP3 Evaporimeter, and Keeler’s TearScope-Plus were used to screen for non-invasive tear break-up time (NITBUT), tear evaporation rate, and lipid-layer thickness (LLT) using protection and relief treatment methodology. Results: LLT was found to be significantly thinner at 5% RH compared with at 40% RH (p = 0.007). The median LLT dropped from 50–70 nm (grade 3) at 40% RH to 10–50 nm (grade 2) at 5% RH. TSP/HA eye drops significantly augment LLT in both treatment modalities, protection (p = 0.01) and relief (p = 0.004) at 5% RH. The mean evaporation rate doubled from 40.93 at 40% RH to 82.42 g/m2/h after exposure to 5% RH. In protection mode, the TSP/HA allowed the average evaporation rate to be much lower than when no TSP/HA was used at 5% RH (p < 0.008). No alteration in evaporation rate was recorded when the TSP/HA drop was used after exposure (relief). The mean NITBUT was reduced from 13 s in normal conditions to 6 s in the dry environment. Instillation of TSP/HA eye drops resulted in significant improvement (p = 0.006) in tear stability, where the NITBUT increased to 8 s in both protection (before exposure) and relief (after exposure) (p = 0.001). Although improved, these values were still significantly lower than NITBUT observed at 40% RH. Conclusions: Significant protection of tear-film parameters was recorded post instillation of TSP/HA eye drop under a desiccating environment. Both treatment methods (protection and relief) were shown to be effective. The presence of TSP/HA enhances the effectiveness of teardrops in protecting the tear-film parameters when exposed to adverse environments.

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.

Background and Objectives: Dry eye disease (DED) is a multifactorial ailment of the tears and ocular surface. The purpose of this study was to assess the tear film physiology under controlled dry environmental conditions and compare the efficacy of oil-in-water emulsion drops on tear film parameters in protection and relief treatment modalities under low-humidity conditions. Emustil eye drops were used after exposure to a low-humidity environment in the relief method, whereas, in the protection method, the drops were applied before exposure to low humidity. Materials and Methods: 12 normal male subjects (mean age 34.0 ± 7.0 years) were exposed to ultra-dry environmental conditions. A number of tear film measurements were carried out under desiccating environmental conditions in a controlled environment chamber (CEC), where the chamber temperature sat at 21 °C with a relative humidity (RH) of 5%. Keeler’s TearScope Plus and an HIRCAL grid were used to assess the tear break-up time and lipid layer thickness (LLT), and the evaporation rate was evaluated using a Servomed EP3 Evaporimeter. Results: LLT measurements showed that the dry environment affected LLT significantly (p = 0.031). The median grade of LLT dropped from grade 3 (50–70 nm) at 40% RH to grade 2 (13–50 nm) at 5% RH. A significant increase in LLT was seen after both modes of treatment, with a median LLT grade of 3 when the Emustil was used for both protection (p = 0.004) and relief (p = 0.016). The mean tear evaporation rate in normal environmental conditions (40%) was 40.46 ± 11.80 g/m2/h (0.11 µL/min) and increased sharply to 83.77 ± 20.37 g/m2/h (0.25 µL/min) after exposure to the dry environment. A minimal decrease in tear film evaporation rate was seen in relief; however, statistical tests showed that the decrease in tear film evaporation rate was not significant. Mean NITBUT dropped from 13.6 s at 40% RH to 6.6 s at 5% RH (p = 0.002). All NITBUT measurements at 5% RH (with or without the instillation of Emustil) were significantly lower than those at 40%. The instillation of Emustil at 5% RH resulted in a significant improvement in NITBUT for protection (p = 0.016) but this was not the case for relief (p = 0.0.56). Conclusions: A control environmental chamber (CEC) enables the analysis of tear film parameters comparable to those found in dry eye patients. This enables us to examine the capability of oil in emulsion drops to manage tear film disruption in healthy individuals. This study suggests that using Emustil oil-in-water emulsion before exposure to a dry environment should be advocated for people who work in dry environments.

Dry eye disease (DED) can be extremely distressing and is common in type 2 diabetes (T2D). To investigate potential biomarkers of DED in T2D, panels of proteins in tears, alongside clinical signs and symptoms of DED, were assessed. Patients were classified into four groups: T2D + DED (n = 47), T2D-only (n = 41), DED-only (n = 17) and healthy controls (n = 17). All patients underwent the Ocular Surface Disease Index (OSDI) and Dry Eye-Related Quality of Life (DEQS) questionnaires, tear evaporation rate (TER), fluorescein tear break-up time (fTBUT), corneal fluorescein staining (CFS) and Schirmer 1 test assessments. Six metabolic proteins and 14 inflammatory cytokines were analyzed with multiplex bead analysis. Interleukin (IL)-6 and IL-8 concentrations in tears were significantly higher in the T2D + DED group, and these biomarkers were positively correlated with CFS. In addition, tear IL-6 was negatively correlated with fTBUT in the T2D + DED group. Clinical signs of DED in the T2D + DED group were similar to the DED-only group. The T2D + DED group had more patients with moderate and severe DED (versus the DED-only group), suggesting a different pathogenesis for DED in T2D versus DED-only. Therefore, IL-6 and IL-8 could potentially be diagnostic biomarkers of DED in T2D.

Background and Objectives: Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). Materials and Methods: Patients were divided into two groups of treatment: standard treatment group (n = 43 eyes) and PRGF group (n = 59). Patients’ symptomatology (inferred from OSDI and SANDE questionnaires), ocular inflammation, tear stability, and ocular surface damage were analyzed at baseline and after 3 months of treatment. Results: OSDI test scores were significantly lower in both groups (p < 0.001). SANDE frequency test scores also improved statistically, with differences between groups (p = 0.0089 SANDE frequency and p < 0.0119 SANDE severity). There was a greater reduction in ocular redness (ocular inflammation) in the PRGF group (p < 0.0001) and fluorescein tear break-up time was significantly improved in the PRGF group (p = 0.0006). No significant changes were found in terms of ocular surface damage. No adverse events were obtained in either group. Conclusions: The addition of PRGF to the standard treatment of DED, according to the results obtained, proved to be safe and produced an improvement in ocular symptomatology and signs of inflammation, particularly in moderate and severe cases, when compared to standard treatment.

Introduction: Pro-inflammatory cytokines are important contributors to dry eye disease (DED). The cytokine interleukin (IL)-6 has become a therapeutic target in several DED drug studies. This randomized controlled trial aimed to determine the effectiveness of topical cyclosporin-A 0.1% compared to the combination of topical cyclosporin-A 0.1% and sodium hyaluronate in reducing tear IL-6 levels in DED patients. Methods: The participants were 20 patients, each with two eyes, who had moderate-to-severe DED. Before and after treatment, the clinical degree of DED was examined in each group, using ocular surface disease index (OSDI) scores, tear break-up time (TBUT), fluorescent tests, and Schirmer I tests. In addition, tear samples were taken to examine IL-6 levels through the ELISA method. The results were analyzed using the t-test, Wilcoxon test, and Mann–Whitney test. The correlation between tear IL-6 levels and the severity of DED was analyzed using the Spearman correlation test. Results: The study showed a significantly lower tear IL-6 level, OSDI score, and degree of ocular staining after either topical cyclosporin-A 0.1% or a combination of topical cyclosporin-A 0.1% and sodium hyaluronate (all values p < 0.05). Conclusions: The combination therapy was superior in reducing tear IL-6 levels. In addition, a correlation existed between tear IL-6 levels and the severity of DED based on the TBUT, although it was weak and not statistically significant.

(1) Background: Meibomian gland dysfunction (MGD) among patients with diabetes mellitus (DM) is a common manifestation of dry eye syndrome (DES). (2) Methods: The purpose of this study is to identify clinical parameters and biomarkers useful to improve the follow-up and the treatment of these patients. We have used an ocular surface disease index (OSDI) questionnaire, Schirmer test I/II, tear film break-up time (TF-BUT), fluorescein plus lissamine green staining, Marx’s line (ML), and meibomian gland (MGs) morphology using Sirius® Topographer (CSO, Costruzione Strumenti Oftalmici, Florence, Italy). Blood sample analysis included glucose, glycated hemoglobin, lipid profile, cortisol, dehydroepiandrosterone sulfate (DHEA-S), androstenedione (ASD) and testosterone. (3) Results: Cortisol and ASD were positively correlated with an increase of MG tortuosity, and an Increased level of triglycerides was associated with a reduction of MGs length. DHEAS levels lowered with age and were associated with ocular surface staining. (4) Conclusions: Future studies, perhaps including meibum lipid analysis and tear cytokine levels, may also further elucidate the connection between these parameters, MG architecture and function.

This cross-sectional study aimed to investigate the connection between meibomian gland (MG) excreta quantity and quality after MG expression (MGX), dry eye disease (DED) symptoms, and objective DED signs and to clarify the relationship between dry eye and MG function in DED pathophysiology. The study included 200 subjects, 100 with and 100 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms and self-reported skin type for facial skin dryness self-evaluation. Objective dry eye signs were assessed by monitoring conjunctival hyperemia, lid parallel conjunctival folds (LIPCOF), tear break-up time (TBUT), fluorescein surface staining and digital MGX. Subjects with DED symptoms had significantly lower MG quantity scores than healthy controls (p < 0.001). Meibum quality and quantity scores significantly correlated with female gender (p = 0.002), Schein questionnaire score (p < 0.001), fluorescein corneal staining score (p = 0.019), self-reported skin type (p < 0.001), TBUT (p < 0.001) and LIPCOF (p = 0.041). After adjustment for age and gender in a logistic regression analysis, dry eye was independently and significantly associated with self-reported skin type (OR 0.73, p < 0.001), LIPCOF (OR 1.04, p < 0.001), fluorescein corneal staining (OR 1.05, p = 0.019), TBUT (OR 0.77, p < 0.001) and meibum quantity score (OR 0.59, p < 0.001). Dry eye symptoms and objective signs correlated well in this study. MGX discriminated between the subjects with and without DED symptoms and was associated with other objective DED signs. Results showed a significant association between meibum quality and quantity, MG function, DED and facial skin dryness self-perception. This paper established a correlation between dry eye symptoms caused by MG dysfunction and dry skin, which can help general health practitioners consider dry eye as a cause of chronic eye complaints with patients who report dry skin.

The aim of this study was to investigate ocular surface changes associated with face mask (FMs) use of healthcare personnel during the COVID-19 pandemic. We prospectively evaluated 200 eyes of 100 individuals during working hours and 40 eyes of 20 individuals during their rest days as a control group. Dry eye symptoms were assessed with the Ocular Surface Disease Index (OSDI) and McMonnies questionnaire. The clinical investigation included the best corrected visual acuity (BCVA), corneal fluorescein staining (FS), break-up time (BUT), and Schirmer test I before and after a 7-h work shift with a continuative use of surgical or N95 masks. The control group was evaluated similarly twice a day, at 8:00 a.m. and at 3:00 p.m.. In the study group, BCVA, FS, BUT, and Schirmer test were investigated and there was a significant negative variation at the end of the shift. On the contrary, the control group did not show significant variations of any clinical feature. Furthermore, no significant changes in clinical parameters were observed during the use of surgical or N95 masks. In conclusion, FMs continuative use resulted in daily ocular surface modifications specifically in healthcare personnel.

As contact lens (CL) wear affects the ocular surface, this cross-sectional study aims to assess the effects of soft CL wear and its duration on the tear film and meibomian gland (MG) drop-out and visibility. Thirty non-CL wearers (22.5 ± 2.3 years) and twenty-four soft CL wearers (23.8 ± 2.2 years) participated in this study. The Keratograph 5M was used to assess the ocular surface. CL users were surveyed on years of CL wear and hours per week. MG visibility was assessed using a previously developed method based on analysing pixel intensity of meibographies. The CL group showed higher gland drop-out (p < 0.001) and lower gland visibility (p < 0.022). Gland drop-out was independently associated with CL wear (p = 0.006). When gland drop-out was excluded, the relative energy of pixel intensity values showed an independent association with CL wear (p = 0.005). Prolonged hours of CL wear were associated with higher dry eye symptoms and entropy of MGs (p < 0.029). A reduction in non-invasive keratograph break-up time was associated with using CLs for ≥8 years (p = 0.030). Overall, gland drop-out was higher and gland visibility lower in soft CL wearers. New gland visibility metrics might help to assess MGs in soft CL wearers quickly and objectively.

Background: To determine efficacy of two lacrimal substitutes on signs and symptoms of ocular surface disease after phacoemulsification; to determine impact of surgery on patients’ vision related quality of life. Monocentric, randomised, physician blinded, three parallel groups clinical trial. Design and Methods: Patients in the operative list for phacoemulsification have been screened for eligibility; they underwent (at time 0, 15, 45 and 90 days): slit lamp examination; tear film break-up time (BUT); corneal staining; tear volume; 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ); Ocular Surface Disease Index (OSDI). Treatments to be compared were: 1. standard of care-SOC (lomefloxacine and tobramicine/dexamethasone fixed combination 4 times a day for 2 weeks), 2. SOC + carboxymethylcellulose sodium 0.5% and glycerin 0.9%, 3. SOC + Sodium Hyaluronate 0.15%. Study treatment started at T15. Groups were compared with parametric or nonparametric tests, and with Pearson’s χ2 test. Correlation between continuous variables was assessed by means of Pearson’s or Spearman’s coefficient. Results: Fifty-three patients were enrolled. At 45 and at 90 days from surgery, the group receiving lacrimal substitutes presented better BUT and Schirmer I test (p = 0.009, p = 0.019). General vision, near activity and vision-specific dependency subscales improved after surgery (p = p < 0.001).Conclusions: Cataract surgery causes the onset or the worsening of dry eye. Use of artificial tears can significantly reduce symptoms and signs of dry eye in patients after phacoemulsification.

Dry eye disease (DED) is most commonly caused by evaporative subtypes and mainly induced by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) combined with meibomian gland expression (MGX) is a noninvasive treatment for improvement of ocular discomfort symptoms and MGD. In this prospective study between November 2020 and May 2022, the patients with MGD and abnormal meibomian expressibility that met the criteria of both ocular surface disease index (OSDI) ≥ 13 scores and standardized patient evaluation of eye dryness (SPEED) ≥ 8 scores were enrolled in Kaohsiung Veteran General Hospital. Three separate treatment sessions of IPL therapy combined with MGX were administered to the lower lids, with an interval of 28 days. Further tear film assessment included lipid layer thickness (LLT), tear meniscus height (TMH), noninvasive tear break-up time (NIBUT), and meibomian gland loss (MGL) either before or after first and third IPL therapy combined with MGX. In addition, lissamine green staining and pain scores were also recorded. We totally enrolled 37 patients of 74 eyes. Men accounted for 18.92% (7/37). The mean age was 54.51 ± 11.72 years. The mean OSDI scores were 58.12 ± 22, while the SPEED scores were 17.03 ± 5.98. The mean Schirmer’s test was 3.66 ± 2.43 mm. After three sessions of IPL treatment with MGX, the OSDI, SPEED, LLT, TMH, MGL, MGXS, and pain scores were significantly improved. For the MGX scores (MGXS) ≤ 20 group, lissamine green scores showed nearly significant improvements. For the MGXS > 20 group, TMH revealed statistical improvement. Noninvasive IPL therapy with MGX statistically improved not only dry eye symptoms, but also tear film assessments, including LLT, TMH, and MGL.

Dry eye disease (DED) is a multifactorial disease that represents one of the most common ophthalmologic conditions encountered in everyday clinical practice. Traditional diagnostic tests for DED, such as subjective questionnaires, tear film break-up time and the Schirmer test, are often associated with poor reproducibility and reliability, which make the diagnosis, follow-up, and management of the disease challenging. New advances in imaging technologies enable objective and reproducible measurements of DED parameters, thus making the diagnosis a multimodal imaging-based process. The aim of this review is to summarize all the current and emerging diagnostic tools available for the diagnosis and monitoring of DED, such as non-invasive tear breakup time, thermography, anterior segment optical coherence tomography, meibography, interferometry, in vivo confocal microscopy, and optical quality assessment. Although there is not a gold standard imaging technique, new multi-imaging-integrated devices are precious instruments to help clinicians to better cope with the diagnostic complexity of DED.

Purpose: To report the ocular surface pathology of patients suffering from acute/subacute mercury vapor intoxication. Design: Cross-sectional study. Participants: Male workers intoxicated with inorganic mercury referred for ophthalmic involvement and healthy control subjects. Methods: The following tests were performed: dry eye (DE)-related symptoms indicated by the ocular surface disease (OSDI) index questionnaire; tear osmolarity; analysis of 23 tear cytokine concentrations and principal component and hierarchical agglomerative cluster analyses; tear break-up time (T-BUT); corneal fluorescein and conjunctival lissamine green staining; tear production by Schirmer and tear lysozyme tests; mechanical and thermal corneal sensitivity (non-contact esthesiometry); and corneal nerve analysis and dendritic cell density by in vivo confocal microscopy (IVCM). Results: Twenty-two out of 29 evaluated patients entered the study. Most had DE-related symptoms (OSDI values > 12), that were severe in 63.6% of them. Tear osmolarity was elevated (>308 mOsms/L) in 83.4% of patients (mean 336.23 (28.71) mOsm/L). Corneal and conjunctival staining were unremarkable. T-BUT was low (2), nerve branching density (2 (2.50) n/mm2), and dendritic cell density (9.1 (8.84) n/mm2) in patients. Tear levels of IL-12p70, IL-6, RANTES, and VEGF were increased, whereas EGF and IP-10/CXCL10 were decreased compared to controls. Based on cytokine levels, two clusters of patients were identified. Compared to Cluster 1, Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels. Conclusions: Patients suffering from systemic mercury intoxication showed symptoms and signs of ocular surface pathology, mainly by targeting the trigeminal nerve, as shown by alterations in corneal sensitivity and sub-basal nerve morphology.

The concentrations of insulin, leptin, active ghrelin, C-peptide and gastric inhibitory polypeptide (GIP) and their inter-day variations were examined in normal human tears. In addition, correlations between the concentrations of these metabolic proteins and ocular surface parameters were determined. Subjects with healthy ocular surfaces attended three visits, with 7-day intervals. Tear evaporation rate (TER) and non-invasive tear break-up time (NITBUT) were assessed, and a total of 2 µL tears were collected from all subjects. Tear fluid concentrations of insulin, leptin, active ghrelin, C-peptide and GIP were measured by multiplex bead analysis. Insulin was the most highly expressed metabolic protein, followed by leptin, C-peptide, active ghrelin and GIP. Of these, only active ghrelin had a significant inter-day variation (p < 0.05). There was no inter-day variation in the mean concentrations of the other metabolic proteins. Leptin had a strong intra-class reproducibility. No correlation was detected between tear metabolic protein concentrations and ocular surface parameters. This pilot study shows, for the first time, that active ghrelin and GIP are detectable in healthy tears. The strong intra-class reproducibility for leptin shows that it could be used as a potential tear fluid biomarker and, possibly, in determining the effects of metabolic disorders on the ocular surface.

Background and Objectives: To evaluate the clinical efficacy of periocular botulinum toxin A (BTA) injection in patients with intractable dry eye disease (DED). Materials and Methods: Medical records of patients with intractable DED who underwent periocular BTA injection from December 2019 to March 2020 were reviewed retrospectively. Patients were injected with 2.5 units of BTA in the medial part of the lower eyelids. The clinical data collected included age, sex, ocular surface disease index (OSDI) score, tear film break up time (TBUT), Schirmer test results, tear osmolarity (I-PEN), and tear meniscus height (TMH) measured by anterior segment optical coherence tomography. All subjective and objective data were collected before treatment and at 1 month after treatment. Results: Twenty-eight consecutive patients were eligible for chart review and analysis. Significant improvements in OSDI, tear osmolarity, and TMH were observed at 1 month after periorbital BTA injection. At the baseline and 1-month follow-up examinations, OSDI scores were 62.22 ± 21.30 and 47.98 ± 17.23, respectively (p < 0.001). TMH increased significantly after treatment (82.25 ± 40.50 at baseline vs. 138.02 ± 66.62 1-month after treatment; p < 0.001). Tear osmolarity using I-PEN showed a significant decrease after treatment (320.82 ± 24.66 at baseline vs. 302.75 ± 22.33 at 1 month after treatment; p < 0.001). No significant differences were found in TBUT or Schirmer test results before and after BTA injection. Conclusions: BTA injection into the medial part of the eyelid improves dry eye symptoms, the amount of tear retention, and tear osmolarity. Based on the objective parameters of the tear condition, this study supports the idea of BTA use as a potential treatment option for patients with intractable DED.