Fluorescein Tear Breakup Time Research Articles

Influential Signs of Dry Eye-Related Ocular Symptoms in Participants With Unstable Tear Film.

The aim of this study was to investigate the factors influencing dry eye disease (DED)-related ocular symptoms in participants with short fluorescein tear break-up time (FTBUT). This cross-sectional study included 82 participants with short FTBUT (<10 seconds). Examinations included Ocular Surface Disease Index (OSDI), FTBUT, average noninvasive tear break-up time (NIBUTave), lid wiper epitheliopathy, lipid layer thickness, blink rate, partial blink, tear meniscus height, and meibomian gland (MG) evaluation which included ratio of residual MG area (RMGA) and MG grade in tarsal plates. One-way analysis of variance was used to detect differences between symptomatic tear film instability group (FTBUT <5 s, OSDI ≥13), asymptomatic tear film instability group (FTBUT <5 s, OSDI <13), and control group (FTBUT ≥5 s, OSDI <13). A bivariate correlation, partial correlation, and multiple linear regression analyses were used to identify major factors. Only the right eye was included. Among the participants with FTBUT <5 seconds, symptomatic group showed less upper RMGA ( P < 0.001) and NIBUTave ( P = 0.010). OSDI was negatively associated with upper RMGA ( r = -0.450, P < 0.001) and NIBUTave ( r = -0.414, P = 0.001), and positively associated with upper MG grade ( r = 0.277, P = 0.027). Linear regression analysis showed that the upper RMGA significantly affected OSDI (B = -41.895, P = 0.001), while not significantly correlated with age, upper MG grade, and NIBUTave. The upper RMGA might be the main factor affecting DED-related discomfort in participants with unstable tear film, indicating an early ocular change in DED.

The topical azithromycin meibomian gland dysfunction survey: The effect of topical azithromycin on signs and symptoms of meibomian gland dysfunction.

The aim of this study was to assess the long-term effects of topical azithromycin on signs, symptoms and self-management of meibomian gland dysfunction (MGD). Forty participants were assessed for MGD and its effect on the fluorescein tear break-up time (FTBUT). Participants were treated with topical azithromycin twice daily for 2 weeks and then once daily for a further 2 weeks. One year after treatment, 31 participants completed a survey assessing pre- and post-treatment effect on symptoms, lifestyle and self-treatment methods. Following treatment, there was a significant reduction in MGD grading from a median of grade 2 to grade 0 (z = 4.40, p < 0.0001) and an increase in FTBUT from a median of 3-8 s (z = 4.75, p < 0.0001). One year afterwards, the survey showed a significant improvement in symptoms (sensitivity to light, grittiness, burning, blurred vision, all p < 0.03) and reduction in required self-treatments (lid wipes, tear substitutes, both p < 0.03). There was also a reduced impact on lifestyle (reading, night driving, computer use and watching television, all p < 0.0001) and in all environmental conditions (all p < 0.0001). This study confirms the positive effect of topical azithromycin on MGD and shows it has a long-term impact on symptoms, self-treatment methods and lifestyle. This has implications for both chair time and healthcare costs when managing patients with MGD. Pending further clinical trials in a larger population with different demographics, topical azithromycin should be considered by all eyecare practitioners as a viable pharmacological treatment when managing MGD.

Efficacy of far infrared functional glasses in the treatment of meibomian gland dysfunction-related dry eye.

Meibomian gland dysfunction (MGD)-related dry eye disease (DED) is a significant subtype of DED. In this research, we investigate the effectiveness of far infrared (FIR) functional glasses in the treatment of MGD-related DED. According to the TFO DEWS II diagnostic criteria, 61 eyes with MGD-related DED were included. All participants wore functional FIR glasses throughout the day for a period of 4weeks and were followed up three times during the treatment. All subjects were followed up thoroughly in accordance with the DED clinical examination procedure. Ultimately, the treatment's impact was assessed. We found the Visual Analogue Scale and Ocular Surface Disease Index scores after FIR treatment were significantly lower than the baseline values (p<0.05). Compared with the baseline, fluorescein tear breakup time and corneal fluorescein staining score after FIR treatment were significantly improved (p<0.05). The eyelid margin signs, meibum quality, and meibomian gland expressibility after the 4-week treatment were significantly better than those at baseline (p<0.05). We can see that wearing the FIR functional glasses significantly relieves the symptoms and signs of patients. We believe FIR therapy could be considered as a new method of MGD-related DED.

Symptomatic dry eye disease among university students.

Dry eye disease (DED) is a multifactorial condition often characterized by a reduction in tear film quantity or quality. This study aimed to determine the frequency of DED and its associated subjective symptoms among students of Mu'tah University. In this cross-sectional study conducted at Mu'tah University, Mu'tah, Jordan, from January to April 2022, 489 students completed an online patient-reported DED symptom questionnaire and the ocular surface disease index (OSDI) questionnaire. Moreover, 106 participants underwent clinical examinations using the Schirmer test I and fluorescein tear breakup time (TBUT). Approximately 74.6% of the students self-reported experiencing DED symptoms, and 72.6% had an OSDI score > 12, which is considered the threshold for an abnormal ocular surface. Clinical examinations revealed low Schirmer test scores ( < 10 mm) in 26.4% (n = 28) and 25.5% (n = 27) of the right and left eyes, respectively. We observed low TBUT scores ( < 5 s) in 19.8% (n = 21) and 18.9% (n = 20) of the right and left eyes, respectively. We noted significant differences between the self-reported DED symptoms and the Schirmer test scores (P = 0.003 for both right and left eyes), TBUT (P < 0.001 for both right and left eyes), and OSDI score (P < 0.001 for each self-reported DED symptom). We observed a weak significant positive correlation between Schirmer test scores and TBUT in the right (r = + 0.30; P = 0.002) and left (r = + 0.34; P < 0.001) eyes; a negligible significant inverse correlation between OSDI scores and Schirmer test scores in the right (r = - 0.24; P = 0.013) and left (r = - 0.23; P = 0.019) eyes; and a negligible significant inverse correlation between the OSDI score and TBUT of the left eye (r = - 0.25; P = 0.011) but not of the right eye (r = - 0.17; P = 0.077). The frequency of DED symptoms in this study was higher than that previously reported based on foreign statistics. The presence of self-reported DED symptoms was significantly associated with higher OSDI scores. Self-reported DED symptoms were more frequent than the abnormalities detected using objective methods. Therefore, a combination of subjective and objective measures may provide higher diagnostic yield for DED. Further studies are required to confirm this hypothesis.

Validation of the phenol red thread test in a Chinese population

BackgroundTo investigate the validation of phenol red thread (PRT) test in a Chinese population by evaluating the intraobserver repeatability and interobserver reproducibility, determining correlations between the PRT test and other dry eye disease (DED) parameters including tear meniscus height (TMH) and Schirmer I test, and testing the accuracy of diagnosing DED when using the PRT test alone.MethodsA total of 108 eyes were involved in this prospective and diagnostic study, and were divided into two groups (with and without DED). Each subject underwent a series of ocular surface examinations, including Ocular Surface Disease Index (OSDI) questionnaire, non-invasive tear breakup time (NIBUT), tear meniscus height (TMH) assessment, PRT test, fluorescein tear breakup time (FBUT), corneal fluorescein staining and Schirmer I test.ResultsIn the experimental group and the control group, the intra-class correlation coefficients (ICCs) of the repeatability were 0.747 and 0.723, respectively (all P < 0.05). The ICCs of the reproducibility in both groups were 0.588 and 0.610, respectively (all P < 0.05). The PRT test correlated weakly with the Schirmer I test and the tear meniscus height, with Spearman coefficients of 0.385 and 0.306, respectively (all P < 0.05). The PRT test is available to diagnose DED, with an area under the curve of 0.806 and a Youden index of 0.556 at the cutoff point of 8.83 mm.ConclusionsThe PRT test can provide patients a comfortable, timesaving and less irritating approach to screening and diagnosing DED compared to Schirmer I test.

Safety and Efficacy of Human Amniotic Epithelial Stem Cells Eye Dropin Ocular Chronic Graft-Versus-Host Disease

Background Approximately 50% of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) suffer from ocular chronic GVHD (ocGVHD), which causes severe dryness and visual impairment. However, current clinical treatments for ocGVHD, such as artificial tears, immunosuppression therapy, and punctual occlusion, typically offer only limited benefits. Amniotic membrane transplantation (AMT) can significantly alleviate ocular symptoms in patients with ocGVHD, but it is an invasive procedure that is not appropriate for all patients with ocGVHD. Therefore, we designed a clinical trial to demonstrate the safety and efficacy of eye drops containing human amniotic epithelial stem cells (hAESC) in ocGVHD. M ethods Register Number: ChiCTR2200057857. The enrolled eyes received 1*10 6 cells/mL of hAESC eye drops four times daily for one to three treatment cycles (A cycle was defined as two weeks of continuous administration and two weeks without hAESC eye drops). The primary outcome measure is safety following treatment with hAESC eye drops. In addition, other clinical indices, such as the ocular surface disease index (OSDI), NIH score(eye), Schirmer's test, corneal fluorescein staining (CFS) score, fluorescein tear breakup time (FTBUT), and in vivo confocal microscopy (IVCM) were essential parameters. Results ： 19 of the 25 patients included in the study completed at least one round of treatment. The average length of follow-up was 9.4 months. There were no adverse events associated with hAESC. After one round of treatment(n=19), there was a significant decrease in OSDI score (P=0.0003) and eye NIH score (P0.0001), an increase in Schirmer basal secretion score (P=0.0237), and a significant improvement in CFS score (P0.0001), corneal subbasal nerve density(P=0.006), and corneal epithelial cell density(P=0.0349). It also produced statistically significant improvements in FTUBT after two rounds of treatment (n=14) (P= 0.024). After three rounds of treatment (n=11), we observed additional improvements in the OSDI (P=0.0001) and CFS (P0.001) scores. Conclusion ： The findings of this study indicated that hAESC eye drops are safe and effective at alleviating symptoms and signs in patients with ocGVHD, making them a promising therapeutic option for the treatment of ocGVHD.

Clinical Study on Cytokines Panel in the Diagnosis of Ocular Chronic Graft-Versus-Host Disease

Background Chronic graft-versus-host disease (cGVHD) is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), affecting 30-70% of patients after allo-HSCT. Sixty to ninety percent of cGVHD patients suffer from ocular chronic GVHD (ocGVHD), which is characterized by new-onset dry, “gritty”, or painful eyes, cicatricial conjunctivitis, keratoconjunctivitis sicca, and confluent areas of punctate keratopathy, significantly affecting patients' quality of life. Nevertheless, the clinical diagnosis of ocGVHD relies heavily on observing symptoms and clinical signs. Treatment is typically initiated during the symptomatic stage, by which time the damage to the ocular tissues may be irreversible. Consequently, it is crucial to investigate methods of early diagnosis for early intervention. Methods The cGVHD mouse model was established to explore the correlation between cGVHD and serum cytokines. Based on the findings from animal experiments and literature review, a panel of 16 cytokine combinations was identified. Enzyme-linked immunosorbent assay (ELISA) was employed to compare the levels of cytokines in serum and tear samples obtained from patients who underwent allogeneic hematopoietic stem cell transplantation. The inclusion criteria were set as post-allo-HSCT patients between the ages of 18 and 60 who were willing to participate in the study. The visual acuity, ocular pressure, Ocular Surface Disease Index (OSDI) score, Schirmer's test without anesthesia, corneal fluorescein staining (CFS), and fluorescein tear breakup time (FTBUT) were evaluated. The tear sample was collected via Schirmer's strips. Qualitative data were compared with the chi-square test. The Spearman test was used to analyze correlations (ChiCTR2200062516). Results In comparison to the control group, cGVHD mice exhibited elevated concentrations of serum IL-1β, IL-6, IL-8, IL-17, IFN-γ, CX3CL1, CXCL11, CXCL13, CCL11, and CCL19 (P&amp;lt;0.05). A total of 26 post-allo-HSCT ocGVHD patients (38±11y; range 19-57y) and 27 patients without ocGVHD (34±9y; range 20-52y) were recruited. Between patients with and without ocGVHD, there were significant differences in ocular surface parameters (p&amp;lt;0.0001). Analysis of serum and tear cytokine profiles in patients revealed that, when compared to patients without ocular cGVHD, those with ocular cGVHD exhibited increased serum IL-8 levels (P=0.0319, AUC value=0.678), decreased serum IL-10 levels (P=0.0305, AUC value=0.701), elevated tear fluid levels of IL-8, IFN-γ, CXCL9, and CCL17, and lower tear fluid levels of IL-10 and CCL19 (P&amp;lt;0.05, AUC values were &amp;gt;0.7). Moreover, the correlation analysis between tear cytokine levels and ophthalmic indices showed that 3 cytokines were correlated with ophthalmic indices: IL-10, IFN-γ and CXCL9, indicating the superior diagnostic capabilities and correlation with ocGVHD severity. (Figure 1) Conclusions Tear fluid demonstrates greater specificity and sensitivity as biomarkers for diagnosing ocular cGVHD compared to serum biomarkers. Among the identified tear cytokines, IL-8, IL-10, IFN-γ, CXCL9, CCL17, and CCL19 can serve as diagnostic biomarkers for ocular cGVHD post-transplantation offering practical reference value for diagnosis. IL-10, IFN-γ and CXCL9 levels could evaluate the severity of ocGVHD. In addition, large-scale prospective studies are warranted to confirm our findings.

Immediate effects of artificial tears with and without preservatives containing hyaluronic acid and carboxymethyl cellulose

Background: Currently, hyaluronic acid (HA) and carboxymethyl cellulose sodium (CMC) are common polymers incorporated in artificial tears (ATs). The aim of the present study was to evaluate the immediate effect of preservative- and preservative-free HA- and CMC-containing ATs on tear-film parameters and determine patient preference after AT instillation.&#x0D; Methods: In this prospective, double-blind, randomized, comparative study, we assessed fluorescein tear break-up time (TBUT), bulbar redness, and tear ferning pattern (TFP) up to 60 min after the instillation of ATs with and without preservatives containing HA and CMC in the recruited participants. To test patient preference, each patient was administered with the Ora Calibra™ Ocular Discomfort and 4-Symptom Questionnaire (OOD4SQ; scale of 0–5) before and 60 min after the instillation of ATs. The selection of 14 descriptive words based the 11-point Ora Calibra™ Drop Comfort Scale (ODCS; scale of 0–10) was administered immediately after instillation of each AT to test the drop comfort score.&#x0D; Results: We enrolled 200 eyes of 200 patients, including 163 (81.5%) women and 37 (18.5%) men, with a mean (standard deviation) age of 28.38 (5.42) years. Immediately or 5, 15, or 60 min after the instillation, the mean TBUT did not differ by presence of preservatives, HA, or CMC (all P &gt; 0.05). However, it was significantly higher 5-min post-instillation compared to baseline and significantly lower 15- and 60-min post-instillation (all P &lt; 0.05). The mean grade of bulbar redness immediately or 3, 5, 15, or 60 min after instillation did not differ by presence of preservatives for HA or CMC containing ATs (all P &lt; 0.05). It did not differ significantly 3-, 5-, 15-, or 60-min post-instillation compared to baseline (all P &gt; 0.05). The mean drop comfort scale after the instillation of ATs did not differ significantly by presence of preservatives, HA, or CMC (all P &lt; 0.05). Positive descriptive words were selected by a higher proportion of participants in both groups. According to OOD4SQ, the overall discomfort and mean dryness scores improved significantly after instillation of HA-containing ATs (both P &lt; 0.05), while the mean burning sensation, grittiness, and stinging scores remained unchanged (all P &gt; 0.05). The overall discomfort and mean scores for each ocular symptom (P &lt; 0.05), except for stinting (P &gt; 0.05), improved significantly after instillation of CMC-containing ATs. The TFP did not change significantly from baseline to 60 min after the instillation of any AT (P &gt; 0.05).&#x0D; Conclusions: Both ATs with and without preservatives containing HA and CMC produced positive short-term objective and subjective effects. However, TBUT, TFP, bulbar redness, and patient feedback were comparable for both HA- and CMC-containing ATs. Further trials with longer observation periods or the recruitment of patients with different severities of dry eye could provide more robust and clinically applicable conclusions.

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

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)). 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. 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. Our findings suggest that in patients with RA, tear meniscus osmolarity measured by the TearLab® showed low sensitivity, low specificity, and limited agreement with the TFOS DEWS II composite reference standard for DED diagnosis.

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

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

Dry eye clinical practice patterns of UK optometrists

PurposeIn light of the increased roles of optometrists working in primary care in the UK, this research study aimed to gain an insight into perceptions of dry eye disease (DED), knowledge and confidence in diagnosis and management, and satisfaction with currently available treatment options. MethodsLinks to an online survey were distributed to optometrists across the UK via optometry websites newsletters, conferences, and local optical committee data bases, between October 2021 and July 2022. The anonymous questionnaire contained a variety of question types including multiple choice, likert-type scale, and free text questions. ResultsThe survey was completed by 131 optometrists, with a broad range of experience, who reported examining 33.3 ± 31.0 dry eye patients per month. Forty-eight percent of respondents were involved in the provision of an extended service. Fluorescein tear breakup time, corneal fluorescein staining, and anterior lid assessment were the most used clinical procedures, both for diagnosis and monitoring purposes. Sixty percent of respondents reported that they believed their patients were satisfied/managed with artificial tear alone, with the availability of a preservative free option being the top consideration, particularly with increasing severity. Of the 18.7% of respondents who held Independent prescriber status, 68% felt this had widened their ability to diagnose and treat DED. This was evidenced by an increase in steroid recommendation for moderate and severe disease. ConclusionsAlthough dry eye disease was perceived to be an important condition, opinions varied widely regarding knowledge and confidence in diagnosis and management. Involvement in an extended service did not alter patient management. However, an increase in therapeutic management and the employment of a stepwise approach to management has been identified.

Lactobacillus fermentum HY7302 Improves Dry Eye Symptoms in a Mouse Model of Benzalkonium Chloride-Induced Eye Dysfunction and Human Conjunctiva Epithelial Cells.

(1) We investigated the effects of the Lactobacillus fermentum HY7302 (HY7302) in a mouse model of benzalkonium chloride (BAC)-induced dry eye, and the possibility of using HY7302 as a food supplement for preventing dry eye. (2) The ocular surface of Balb/c mice was exposed to 0.2% BAC for 14 days to induce dry eye (n = 8), and the control group was treated with the same amount of saline (n = 8). HY7302 (1 × 109 CFU/kg/day, 14 days, n = 8) was orally administered daily to the mice, and omega-3 (200 mg/kg/day) was used as a positive control. To understand the mechanisms by which HY7302 inhibits BAC-induced dry eye, we performed an in vitro study using a human conjunctival cell line (clone-1-5c-4). (3) The probiotic HY7302 improved the BAC-induced decreases in the corneal fluorescein score and tear break-up time. In addition, the lactic acid bacteria increased tear production and improved the detached epithelium. Moreover, HY7302 lowered the BAC-induced increases in reactive oxygen species production in a conjunctival cell line and regulated the expression of several apoptosis-related factors, including phosphorylated protein kinase B (AKT), B-cell lymphoma protein 2 (Bcl-2), and activated caspase 3. Also, HY7302 alleviated the expression of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, and IL-8, and also regulated the matrix metallopeptidase-9 production in the conjunctival cell line. (4) In this study, we showed that L. fermentum HY7302 helps prevent dry eye disease by regulating the expression of pro-inflammatory and apoptotic factors, and could be used as a new functional food composition to prevent dry eye disease.

Tear Fluid Biomarkers and Quality of Life in People with Type 2 Diabetes and Dry Eye Disease.

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.

Non-invasive and objective tear film breakup detection on interference color images using convolutional neural networks.

Dry eye disease affects hundreds of millions of people worldwide and is one of the most common causes for visits to eye care practitioners. The fluorescein tear breakup time test is currently widely used to diagnose dry eye disease, but it is an invasive and subjective method, thus resulting in variability in diagnostic results. This study aimed to develop an objective method to detect tear breakup using the convolutional neural networks on the tear film images taken by the non-invasive device KOWA DR-1α. The image classification models for detecting characteristics of tear film images were constructed using transfer learning of the pre-trained ResNet50 model. The models were trained using a total of 9,089 image patches extracted from video data of 350 eyes of 178 subjects taken by the KOWA DR-1α. The trained models were evaluated based on the classification results for each class and overall accuracy of the test data in the six-fold cross validation. The performance of the tear breakup detection method using the models was evaluated by calculating the area under curve (AUC) of receiver operating characteristic, sensitivity, and specificity using the detection results of 13,471 frame images with breakup presence/absence labels. The performance of the trained models was 92.3%, 83.4%, and 95.2% for accuracy, sensitivity, and specificity, respectively in classifying the test data into the tear breakup or non-breakup group. Our method using the trained models achieved an AUC of 0.898, a sensitivity of 84.3%, and a specificity of 83.3% in detecting tear breakup for a frame image. We were able to develop a method to detect tear breakup on images taken by the KOWA DR-1α. This method could be applied to the clinical use of non-invasive and objective tear breakup time test.

The effect of topical steroids and non-steroidal anti inflammatory drugs on epiphora of unknown cause: Optical coherence tomography study.

The aim of this study is to evaluate using topical non-steroidal antiinflammatory and low-potency steroid drugs for the treatment of epiphora without an underlying cause using anterior segment-optical coherence tomography (AS-OCT) and Munk epiphora grading system. Thirty patients with epiphora who had no underlying cause were evaluated prospectively.A detailed ophthalmological examination, tear meniscus height on slit-lamp, fluorescein tear break-up time, schirmer test, lisamin green conjonctival staining, lacrimal syringing of the upper and lower canaliculus were done in all patients. The patients with contact lens wear,punctal stenosis, lacrimal system disorders, dry eye disease, eyelid malpositions, pterygium, conjunctivochalasis, conjunctivitis, blepharitis, ocular infection, and corneal disease, used topical anti-glaucomatous drugs were excluded. All patients were treated with a combination of topical low-potency drug (loteprednol etabonate 0.5%) twice daily for ten days and topical non-steroidal anti-inflammatory drug (nepafenac 0.3%)once a day for 1 month. Before and after the medical treatment protocol, tear meniscus area (TMA) and tear meniscus height (TMH) were measured by AS-OCT and patients were asked to subjectively rate their epiphora according to the Munk epiphora grading system. The effectiveness of treatment were evaluated by AS-OCT measurements and the Munk epiphora grading system. Fourteen males and sixteen females were included. The mean age at presentation was 60.1±7.35 years and duration of symptoms was 10.03±5.08 months. The mean duration of follow-up was 8.7±3.2 months. Munk epiphora grading system was significantly decreased from 2.5 to 1.6 after treatment (p: 0.004). TMH and TMA were significantly decreased on AS-OCT (TMH:402vs 309µm, p:0.001, TMA:0.797vs 0.347 mm2, p=0.006).Six of thirty patients subjectively reported that their symptoms had not improved but TMH and TMA were significantly decreased on AS-OCT. The combined use of topical non-steroidal anti-inflammatory and low-potency steroid drops may be a good option in patients with epiphora who does not have an underlying cause.

Association between mask-associated dry eye (MADE) and corneal sensations

To determine the risk of mask-associated dry eye (MADE), we investigated the fluorescein tear break-up time (FBUT), ocular surface temperature and blood flow, along with corneal sensitivity, in mask wearers. We enrolled 60 mask wearers (mean age, 27.1 ± 5.2 years) and then measured FBUT, corneal temperature and conjunctival blood flow without wearing masks (no mask), with masks, and with taped masks. We defined MADE as the condition in which dry eye symptoms appeared and the FBUT with mask was less than 5 s. The FBUT with a mask was significantly shorter compared to the no mask and taped mask groups (P < 0.01 and P < 0.05). The corneal temperature difference and conjunctival blood flow difference were significantly higher after wearing a mask than after wearing a taped mask (P < 0.01). Of the 60 subjects, 13 were diagnosed with MADE. Pain sensitivity and the Ocular Surface Disease Index (P < 0.05 and P < 0.01) were significantly higher in the MADE group, with the FBUT without masks (P < 0.05) significantly shorter than in the non-MADE group. MADE may be associated with corneal hypersensitivity. Wearing masks decreased FBUT and increased ocular surface temperature and blood flow. Taping the top edge of masks prevented these changes. Fitting masks properly may reduce MADE risk.

Botulinum Neurotoxin Type a Injection Combined with Absorbable Punctal Plug Insertion: An Effective Therapy for Blepharospasm Patients with Dry Eye.

Blepharospasm patients often have dry eye manifestations. Botulinum neurotoxin type A (BoNT-A) injection has been the main management for blepharospasm and absorbable punctal plug (APP) insertion is shown to be effective in the treatment of dry eye. However, there have been no studies investigating the combined treatment of BoNT-A and APP in blepharospasm patients with dry eye. In this retrospective study, 17 blepharospasm patients with dry eye treated by BoNT-A injection and 12 receiving BoNT-A plus APP treatment were enrolled. The efficacy was evaluated according to the Jankovic rating scale, Ocular Surface Disease Index (OSDI), fluorescein staining (FL), fluorescein tear break-up time (FBUT) and Schirmer I test (SIT). Both BoNT-A and BoNT-A+APP treatment effectively reduced the functional impairment of blepharospasm. At baseline, all the patients had high OSDI scores (BoNT-A group: 82.48 ± 7.37, BoNT-A+APP group: 78.82 ± 4.60, p = 0.112), but relatively low degrees of FL (BoNT-A group: 3.18 ± 1.01, BoNT-A+APP group: 3.50 ± 1.24, p = 0.466), FBUT (BoNT-A group: 1.71 ± 0.77, BoNT-A+APP group: 2.17 ± 0.58, p = 0.077) and SIT (BoNT-A group: 2.53 ± 0.99, BoNT-A+APP group: 3.17 ± 1.23, p = 0.153). After treatment, OSDI, FL, FBUT and SIT were all obviously restored in the two groups. When comparing the changing rates, only OSDI (BoNT-A group: -52.23% ± 15.57%, BoNT-A+APP group: -61.84% ± 9.10%, p = 0.047) and FL (BoNT-A group: -22.55% ± 25.98%, BoNT-A+APP group: -41.94% ± 14.46%, p = 0.016) showed significant differences between the two groups. This study suggests that OSDI is not applicable in the diagnosis of dry eye among blepharospasm patients. For blepharospasm patients with severe dry eye symptoms, especially those with fluorescein staining in the cornea, the combined treatment of BoNT-A and APP is more effective than using BoNT-A alone.

Symptoms and signs of dry eye in children with Graves' ophthalmopathy.

The purpose of this study is to evaluate the tear secretion and ocular surface properties in children with Graves' ophthalmopathy (GO) and to compare the results with those of healthy children. This was a cross-sectional study. Forty-three patients with GO (Group 1) and 41 healthy children without any ocular and/or systemic disorder (Group 2) were examined clinically and underwent tests for dry eye. We performed analyses including the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer's test under topical anesthesia (<5 mm was abnormal), slit-lamp biomicroscopy (corneal fluorescein staining and tear breakup time (TBUT) under blue-light illumination), and fundoscopic evaluation. Dry eye symptoms and the mean OSDI score were significantly (P < 0.02) higher (15.6 ± 18.7) in patients with GO compared with controls (5.67 ± 3.6). The mean Schirmer's (basal tear secretion) tests value was significantly reduced in Group 1 (5.25 ± 3.1 mm) compared with Group 2 (17.1 ± 5.2), respectively. The difference was statistically significant (p < 0.005), suggesting inadequate tear production. The mean tear film breakup time in children was lower in patients with GO (8.3 ± 3.42 s,) compared with controls (13.2 ± 4.74 s), (P < 0.001) suggesting an unstable tear film. Decrease of corneal sensitivity (23.3%) was noted in patients with GO compared with controls. GO patients showed a significant increase of the frequency of corneal fluorescein staining (6.9%) in patients with GO compared with controls. Patients with GO had a statistically significant higher incidence of dry eye symptoms and the increase of OSDI score. Significantly lower Schirmer's and TBUT tests results were seen in the study group when compared with the controls. These findings may indicate a tendency for dry eye in pediatric GO patients.

Evaluating the Differences Between Fluorescein Tear Break-up Time and Noninvasive Measurement Techniques.

To compare fluorescein tear break-up time (BUT) and noninvasive BUT measured using interferometry and corneal topography. We investigated 34 eyes of 34 patients with dry eye (mean age 39.2±8.3 years) and 16 eyes of 16 non-dry eye subjects (33.5±6.5 years). Tear film stability was measured using fluorescein BUT, noninvasive BUT (NIBUT)-DR1 with an interferometer, and noninvasive keratographic BUT (NIKBUT)-first and average using corneal topography. Correlations between fluorescein BUT and noninvasive BUT parameters were determined statistically. The noninvasive BUTs were compared between the dry eye and non-dry eye groups. The agreement between fluorescein and noninvasive BUTs was described using Bland-Altman analysis. Fluorescein BUT was significantly correlated with NIBUT-DR1, NIKBUT-first, and NIKBUT-average. The Bland-Altman analysis revealed bias and 95% limits of agreement between fluorescein BUT and noninvasive BUTs as follows: NIBUT-DR1: 2.07 s, -5.33 to 9.46 s; NIKBUT-first: 3.39 s, -5.46 to 12.24 s; NIKBUT-average: 6.61 s, -1.58 to 14.79 s. The noninvasive BUTs were significantly different between the two groups. When NIBUT-DR1, NIKBUT-first, and NIKBUT-average with Bland-Altman correction were used as an index for dry eye, the cut-off values were 7.1, 8.4, and 11.6 s, respectively. The sensitivities were 0.735, 0.818, and 0.727 and specificities were 0.500, 0.437, and 0.562, respectively. Fluorescein BUT and noninvasive BUTs were significantly correlated, and noninvasive BUTs had higher values than fluorescein BUT. Considering the differences between fluorescein BUT and noninvasive BUTs, noninvasive methods can be used as effective tool for diagnosing dry eye.

Tear film layers and meibomian gland assessment in patients with type 1 diabetes mellitus using a noninvasive ocular surface analyzer: a cross-sectional case–control study

PurposeTo assess the tear film layers and Meibomian glands by a noninvasive ocular surface analyzer in patients with and without type 1 diabetes mellitus (T1DM).MethodsEighty-eight participants were enrolled in this study: 44 patients with T1DM without diabetic retinopathy, and 44 patients as a control group, between 18 and 49 years old. Limbal and bulbar redness classification, lipid layer thickness (LLT), tear meniscus height (TMH), first and mean noninvasive tear break-up time (FNIBUT and MNIBUT, respectively), and Meibomian glands loss (MGL) were assessment through the ICP Ocular Surface Analyzer (OSA). Schirmer’s I test (SIT), the fluorescein tear break-up time test (TFBUT), OSDI and SPEED questionnaires, and percentage of glycosylated hemoglobin (HbA1c) were also tested.ResultsThe T1DM group showed higher limbal and bulbar redness (p = 0.010) and lower LLT (p < 0.001), TMH (p < 0.001), FNIBUT (p < 0.001), MNIBUT (p < 0.001), SIT (p = 0.001), and TFBUT (p < 0.001) than the control group. A higher percentage of MGL was found in the T1DM group in the upper (p = 0.097) and lower (p < 0.001) eyelids. No significant differences were found in dry eye symptoms across the OSDI and SPEED questionnaires between the two groups.ConclusionPatients with T1DM without signs of retinopathy showed involvement of the mucoaqueous and lipid layers of the tear film, as well as a higher percentage of MGL, using a noninvasive analyzer. Dry eye disease in people with T1DM cannot be ruled out by anamnesis and subjective symptom questionnaires alone; therefore, these patients should undergo regular anterior pole examinations.