Dry Eye Disease Subjects Research Articles

Detection of Subclinical Neurotrophic Keratopathy by Noncontact Esthesiometry.

This study aimed to analyze corneal sensitivity with a new noncontact and handheld esthesiometer (Brill Engines, Spain) in patients with dry eye disease (DED) and patients on hypotensive drops, and to compare it with healthy subjects. A total of 31 patients (57 eyes) with DED, 23 patients (46 eyes) with glaucoma, and 21healthy patients (33 eyes) were recruited. In all patients, corneal sensitivity was measured. Subsequently, a keratography test (Keratograph 5M, Oculus) was carried out to measure tear meniscus height (TMH), non-invasive breakup time (NIBUT), bulbar redness (Jenvis scale), and corneal staining (CS, Oxford scale). Both corneal sensitivity and ocular surface parameters were compared between DED, glaucoma, and healthy subjects. Linear mixed models were constructed to utilize data from both eyes of patients. An alpha level of 0.05 was considered statistically significant. The mean age was 56.1 ± 16.1years in the DED group, 69.5 ± 11.7years in the glaucoma group, and 37.190 ± 11.677years in the control group. After adjustment for age and sex, corneal sensitivity was significantly reduced in DED and glaucoma vs control group (P = 0.02 and P = 0.009, respectively). NIBUT was lower in DED and glaucoma groups (P < 0.001 and P = 0.001, respectively). Redness and CS values were higher in the DED group (P = 0.04 and P = 0.001, respectively). TMH was lower in the glaucoma group (P = 0.03). Corneal sensitivity measured with a novel noncontact esthesiometer was reduced in DED and glaucoma groups compared to controls. In clinical practice, this esthesiometer could be an easy-to-use device to screen for patients with subclinical neurotrophic keratopathy.

Development of a dry eye index as a new biomarker of dry eye disease.

To evaluate signs and symptoms in patients diagnosed with dry eye disease (DED), divided into dry eye (DE) groups, in order to find a new biomarker that allows an accurate diagnosis, management and classification of DED. This cross-sectional, observational study included 71 DED subjects. Subjective symptoms, visual quality and DE signs were assessed using the Ocular Surface Disease Index (OSDI), the Quality of Vision (QoV) questionnaire, best corrected distance visual acuity (VA), functional visual acuity (FVA), contrast sensitivity (CS), high- and low-order corneal aberrations (HOA and LOA, respectively), tear break-up time (TBUT), Meibomian Gland Dysfunction (MGD), Schirmer test, corneal staining, lid wiper epitheliopathy (LWE) and meibography. Participants were classified into three groups based on dryness severity using a cluster analysis, i.e., mild (N = 17, 55.8 ± 15.4 years), moderate (N = 41, 63.5 ± 10.6 years) and severe (N = 13, 65.0 ± 12.0). A new Dry Eye Severity Index (DESI) based on ocular surface signs has been developed and its association with symptoms, visual quality and signs was assessed. Comparisons between groups were made using Kruskal-Wallis and Chi-squared tests. Spearman correlation analysis was also performed. The DESI was based on three tests for DE signs: TBUT, Schirmer test and MGD. The DESI showed significant differences between different pairs of groups: Mild Dryness versus Moderate Dryness (p < 0.001), Mild Dryness versus Severe Dryness (p < 0.001) and Moderate Dryness versus Severe Dryness (p < 0.001). The DESI was significantly correlated with age (rho = -0.30; p = 0.01), OSDI score (rho = -0.32; p = 0.007), QoV score (rho = -0.35; p = 0.003), VA (rho = -0.34; p = 0.003), FVA (rho = -0.38; p = 0.001) and CS (rho = 0.42; p < 0.001) Also, significant differences between the severity groups were found for OSDI and QoV scores, VA, FVA, CS and MGD (p < 0.05). The DESI has good performance as a biomarker for the diagnosis, classification and management of DED.

Assessment of the systemic immune-inflammation index in type 2 diabetic patients with and without dry eye disease: A case-control study.

The inflammation plays a role in the pathophysiology of type-2 diabetes progression, and the mechanism remains unclear. The systemic immune-inflammation index (SII) is a novel inflammatory marker for type 2 diabetes patients and integrates multiple indicators in complete blood counts and routine blood tests. Since there is no international diagnostic standard for dry eye disease(DED), this study uses low-cost inflammatory blood biomarkers to investigate the correlation between SII and DM2-DED and determine the diagnosis indices of other biomarkers in DM2-DED. A case-control retrospective analysis of totel patients n = 293 randomly selected and categorized into four groups: DED, DM2, DM2-DED, and healthy subjects. Demographic and blood biomarker variables were classified as categorical and continuous variables. The platelet-to-lymphocyte ratio(PLR), lymphocytes-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio (NLR), and SII were calculated platelet count multiply by NLR and analyzed for their correlation for all groups. Focusing on DM2-DED patients was more common in females, 59.6%, than in males, 40.2%. The mean ages were 60.7 ± 11.85 years, a statistically significant difference with all groups. In the study group DM2-DED, there was an increase in all blood markers compared to all remaining groups except PLR. Only neutrophil, hemoglobin A1c (HbA1c), and fasting blood sugarlevels were statistically significant differences in DM2-DED patients (p > 0.001, p < 0.001, and p < 0.001, respectively) compared to all groups. There was a positive correlation between HbA1c and PLR, HbA1c and NLR, and HbA1c and SII (r = 0.037, p = 0.705; r = 0.031, p = 0.754; and r = 0.066, p < 0.501, respectively) in the DM2-DED group. This study demonstrated that elevated SII values were linked to elevated HbA1c in DM2-DED patients. The potential of SII and HbA1c as early diagnostic indicators for ocular problems associated with diabetes mellitus is highlighted by their favorable connection in diagnosing DM2-DED.

Post-Blink Blur Time-A Simple Test to Detect Dry Eye-Related Visual Disturbances.

Background: Dry eye disease (DED) stands out as one of the most common eye conditions encountered in clinical settings. This study aimed to determine the diagnostic ability and feasibility of post-blink blur time (PBBT) in detecting patients with DED symptoms. Methods: The study included 200 subjects, 100 with and 100 without DED symptoms defined by the Schein questionnaire, who underwent assessment of DED signs [visual acuity, PBBT, conjunctival hyperemia, lid-parallel conjunctival folds-LIPCOF, tear film break-up time-TBUT, fluorescein corneal staining, and meibum score]. Results: DED subjects had a lower PBBT than controls (p < 0.001), with subjective (6 (1-45) s vs. 8 (1-70) s) and objective (6 (2-33) s vs. 8 (2-50) s) PBBT measurements being similar between repeats. The correlations between subjective and objective PBBT measurements were significantly positive (R = 0.873, p < 0.001). Subjective PBBT was negatively related to the Schein questionnaire (R = -0.217, p = 0.002), conjunctival hyperemia (R = -0.105, p = 0.035), and corneal staining (R = -0.153, p = 0.031), while positively related to the TBUT (R = 0.382, p < 0.001) and meibum score (R = 0.106, p = 0.033). Logistic regression analysis showed DED symptoms were significantly associated with subjective PBBT (AOR 0.91, p = 0.001), TBUT (AOR 0.79, p < 0.001), meibum score (AOR 0.65, p = 0.008), LIPCOF (AOR 1.18, p = 0.002) and corneal staining (AOR 1.14, p = 0.028). Conclusions: Subjective self-reported PBBT is a reliable and non-invasive screening test for evaluating time-wise changes in visual acuity and detecting a tear film dysfunction.

Comparison of deep learning-assisted blinking analysis system and Lipiview interferometer in dry eye patients: a cross-sectional study

BackgroundAbnormal blinking pattern is associated with ocular surface diseases. However, blink is difficult to analyze due to the rapid movement of eyelids. Deep learning machine (DLM) has been proposed as an optional tool for blinking analysis, but its clinical practicability still needs to be proven. Therefore, the study aims to compare the DLM-assisted Keratograph 5M (K5M) as a novel method with the currently available Lipiview in the clinic and assess whether blinking parameters can be applied in the diagnosis of dry eye disease (DED).MethodsThirty-five DED participants and 35 normal subjects were recruited in this cross-sectional study. DED questionnaire and ocular surface signs were evaluated. Blinking parameters including number of blinks, number of incomplete blinking (IB), and IB rate were collected from the blinking videos recorded by the K5M and Lipiview. Blinking parameters were individually collected from the DLM analyzed K5M videos and Lipiview generated results. The agreement and consistency of blinking parameters were compared between the two devices. The association of blinking parameters to DED symptoms and signs were evaluated via heatmap.ResultsIn total, 140 eyes of 70 participants were included in this study. Lipiview presented a higher number of IB and IB rate than those from DLM-assisted K5M (P ≤ 0.006). DLM-assisted K5M captured significant differences in number of blinks, number of IB and IB rate between DED and normal subjects (P ≤ 0.035). In all three parameters, DLM-assisted K5M also showed a better consistency in repeated measurements than Lipiview with higher intraclass correlation coefficients (number of blinks: 0.841 versus 0.665; number of IB: 0.750 versus 0.564; IB rate: 0.633 versus 0.589). More correlations between blinking parameters and DED symptoms and signs were found by DLM-assisted K5M. Moreover, the receiver operating characteristic analysis showed the number of IB from K5M exhibiting the highest area under curve of 0.773.ConclusionsDLM-assisted K5M is a useful tool to analyze blinking videos and detect abnormal blinking patterns, especially in distinguishing DED patients from normal subjects. Large sample investigations are therefore warranted to assess its clinical utility before implementation.

Maximal tear secretion evoked by controlled stimulation of corneal sensory nerves in healthy individuals and dry eye subjects.

To measure, the tear flow changes evoked in healthy subjects and dry eye disease (DED) patients by controlled sensory stimulation of the eye surface with i-Onion™, a new stimulation device. Sensory corneal nerves were stimulated with an instrument (i-Onion™) that ejects puffs of CO2 gas (99.9%) at 200 ml.min-1 for 3s, delivered 5 mm from the cornea. Using Schirmer test strips, tear volumes were measured over 3 min in the cornea of one eye before (basal tear volume -BTV) and in the other eye after stimulation of the sensory nerves with CO2 (stimulated tear volume -STV). These measurements were obtained from a control group of adults of either sex (17 students aged 20-30 and 29 subjects without signs of dry eye aged 25-61), a cohort of DED patients (aged 34-75) that included 12 asymptomatic, suspected DED subjects (Schirmer <7 mm and/or TBUT <10s), and 30 Sjögren's syndrome (SS) patients. CO2 stimulation significantly increased the tear volume (BTV = 14.6 ± 1.0 mm, STV = 19.0 ± 1.1 mm: n = 46) in 78% of control subjects, reflecting a mean tear reserve volume (TRV = STV-BTV) of 4.4 ± 0.8 mm. Individual differences were wide, and while no increase in reflex tearing was evoked in 30% of subjects with a BTV >10 mm, the remaining 70% responded vigorously to stimulation, even those with a BTV >18 mm. Asymptomatic DED subjects displayed weaker responses to CO2 stimulation, with lower STVs. Both the BTV and STV of SS patients were low, significantly below those of the healthy controls. Measuring the rise in reflex tearing volume evoked by controlled corneal stimulation provides objective information about the tear glands' secretory capacity in health and disease.

The repeatability of corneal topography measurements in severe Dry Eye disease

BackgroundTo determine the repeatability of corneal topography measurements in severe dry eye disease (DED). A comparison of corneal topography parameters between severe DED and healthy subjects was a secondary goal of this study.MethodsSixty-nine patients with severe DED and 46 healthy subjects were enrolled in the study. All participants underwent repeated corneal topography measurements with Pentacam (Oculus, Germany) within a half hour time. Both eyes of the participants were used in statistical analysis. A further subcategorization of severe DED patients was performed according to Ocular Surface Disease Index (OSDI) scores: 32–50, 51–70 and 71–100. The repeatability of corneal parameters was assessed with correlation coefficients (CC).ResultsThe mean age of dry eye patients and healthy subjects were 40.8 ± 13.2 (17–66) and 39.8 ± 8.2 (18–61) years (p:0.604) respectively. No significant differences were found between severe DED and control groups according to analysed corneal parameters in both eyes (p:>0.05). All CCs were greater than 0.9 in severe DED group (p:<0.001). All CCs were also greater than 0.9 in severe DED patients among different OSDI groups (p:<0.001).ConclusionsCorneal topography measurements are highly repeatable in severe DED with Pentacam. This is the first report about this topic. Nonetheless, further studies are needed with different topography devices for validation.

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

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

Comparative of meibomian gland morphology in patients with evaporative dry eye disease versus non-dry eye disease

Many recent studies have showed that morphological changes are one of the key signs of meibomian gland disease (MGD). These changes can be seen even before symptom onset, potentially underestimating the prevalence of MGD; however, until now, there is no conclusive information about the impact of meibomian gland (MG) morphology in tear film physiology and disease. This study aimed to investigate the prevalence of anatomical and morphological MG alterations between patients with evaporative dry eye disease (DED) and healthy controls. Retrospective chart review of seventy-five patients with evaporative DED and healthy individuals who had dry eye assessments included Ocular Surface Disease Index questionnaire, meibum quality, meibum expressibility, lid margin abnormality, ocular staining, non-invasive tear film break-up time, and meibography. We did not find significant differences in MG alterations in the upper lid between healthy and DED subjects. Patients with evaporative DED presented MG alterations in the lower lid more frequently than healthy subjects (54.8 vs. 30.3%; p = 0.03). The presence of shortened glands was the only MG alteration that was more prevalent in the lower lid in dry-eye patients than in healthy subjects (p < 0.05). Subjects with evaporative DED presented more alterations in the lower lid than healthy subjects.

Association of Dry Eye with Laryngopharyngeal Reflux in Clinical Practice

ABSTRACT Background Dry eye disease (DED) is a common disorder, accounting for up to 35% of the general population. Therefore, we hypothesized that laryngopharyngeal reflux (LPR), inducing refluxate rising into airways, may involve the ocular surface and may either induce or worsen DED. Aim To investigate the prevalence and relevance of suspected LPR in DED patients and subjects with refractive problems (RP) without DED, they were defined as non-dry eye group (NEG) in clinical practice. Methods This retrospective study included consecutive patients evaluated because of dry eye-like symptoms at eight tertiary ophthalmological clinics. Parameters included reflux symptom index (RSI), ocular surface disease index (OSDI), symptom assessment in dry eye (SANDE) for frequency and severity, Schirmer test, tear break-up time (BUT), and Oxford grading. Results The study included 245 subjects (72.5% females; mean age 56.3 years), 152 DED patients, and 93 sex- and age-matched NEG subjects. Pathological RSI (score>13) was detected in 80 subjects (32.6%); 68 (85%) with DED and 12 (15%) CG (OR = 8; p < .0001). In NEG, pathological RSI was associated with higher SANDE (Frequency and Severity), OSDI, and Schirmer scores (OR = 16.36; 14.51; 12.54; and 7.22, respectively. In DED patients, pathological RSI was associated with higher OSDI values (OR = 8.75). Conclusion Patients with DED are at eight times higher risk for having pathological RSI than NEG patients. Moreover, pathological RSI was associated with more severe ocular symptoms both in DED and non-DED patients. The role of LPR in definite DED patients remains to be clarified, but this condition deserves to be investigated in managing patients with DED symptoms.

The physical and mental burden of dry eye disease: A large population-based study investigating the relationship with health-related quality of life and its determinants

PurposeThis large cross-sectional population-based study investigated the relationship between dry eye disease (DED) and health-related quality of life (HR-QoL). MethodsDry eye and HR-QoL were assessed in 78,165 participants (19–94 yrs, 59.2% female) from the Dutch population-based Lifelines cohort, using the WHS and the SF36 questionnaire, respectively. Logistic regression was used to assess the relationship between DED and below median Physical Component Summary (PCS) and Mental Component Summary (MCS) score, corrected for age, sex, education, BMI, and 52 comorbidities. ResultsOverall, 8.9% of participants had DED. Participants with DED had an increased risk of low PCS (OR 1.54 (95% CI 1.46–1.62)) and MCS scores (OR 1.39 (95% CI 1.32–1.46)), corrected for age and sex. This risk remained significant after correction for comorbidities (P < 0.0005). Increasing DED symptom frequency was associated with decreasing HR-QoL (P < 0.0005). Undiagnosed DED subjects had a significantly increased risk of low mental HR-QoL with increasing dry eye symptoms compared to diagnosed subjects (P < 0.0005). Compared to allergic conjunctivitis, glaucoma, macular degeneration and retinal detachment, DED showed the highest risk of low HR-QoL. Compared to other common systemic and chronic disorders, such as depression, rheumatoid arthritis, and COPD, DED was distinctive by having a substantial reduction in both PCS and MCS. ConclusionDED is associated with substantial reductions in both physical and mental HR-QoL, also after correction for associated comorbidities. Not having a diagnosis is associated with worse mental HR-QoL in subjects with severe DED. Our results underline the importance of recognizing dry eye as a serious disorder.

Altered ocular surface immune cell profile in patients with dry eye disease

PurposeAberrant inflammation and immune dysregulation are known pathogenic contributors in dry eye disease (DED). Aim of the study was to determine the proportions of immune cell subsets on the ocular surface (OS) of DED patients. Methods15 healthy controls (22 eyes) and 48 DED subjects (36 eyes with evaporative DED – EDED; 60 eyes with aqueous deficient DED – ADED) were included in the study. Tear break up time (TBUT), Schirmer's test 1 (ST1), corneal staining (CS) and ocular surface disease index (OSDI) scoring were recorded. OS wash was used to collect immune cells on the OS of study subjects. The cells immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer–NK cells and T cell subsets (CD4; CD8; double positive–DP; gamma delta–γδ and NK T cells). ResultsSignificantly higher proportions of leukocytes, neutrophils, CD4 T cells, CD8 T cells, DP T cells and CD4/CD8 T cells ratio were observed in EDED and/or ADED patients. Significantly higher proportions of neutrophils and lower proportions of NK cells were observed in ADED subjects with corneal staining compared to those without and controls. Neutrophils/NK cells ratio was significantly higher in EDED and ADED subjects compared to controls. Correlation analysis revealed pathological relationships between proportions of leukocytes, neutrophils, CD4 T cells and Neutrophil/NK cells ratio with DED clinical parameters. ConclusionOS immune cell subset proportion changes in DED patients were associated with DED types and severity. The data suggests the potential for a new generation of therapies targeting immune cells on the ocular surface.

Tear Proteomics Study of Dry Eye Disease: Which Eye Do You Adopt as the Representative Eye for the Study?

Most studies about dry eye disease (DED) chose unilateral eye for investigation and drew conclusions based on monocular results, whereas most studies involving tear proteomics were based on the results of pooling tears from a group of DED patients. Patients with DED were consecutively enrolled for binocular clinical tests, tear biochemical markers of DED, and tear proteome. We found that bilateral eyes of DED patients may have similar but different ocular surface performance and tear proteome. Most ocular surface homeostatic markers and tear biomarkers were not significantly different in the bilateral eyes of DED subjects, and most clinical parameters and tear biomarkers were correlated significantly between bilateral eyes. However, discrepant binocular presentation in the markers of ocular surface homeostasis and the associations with tear proteins suggested that one eye’s performance cannot represent that of the other eye or both eyes. Therefore, in studies for elucidating tear film homeostasis of DED, we may lose some important messages hidden in the fellow eye if we collected clinical and proteomic data only from a unilateral eye. For mechanistic studies, it is recommended that researchers collect tear samples from the eye with more severe DED under sensitive criteria for identifying the more severe eye and evaluating the tear biochemical and proteomic markers with binocular concordance drawn in prior binocular studies.

Dry Eye Disease and Depression-Anxiety-Stress: A Hospital-based Case Control Study in UAE

Objective: The aim of the present study was to investigate the association between dry eye disease (DED) and psychosomatic conditions, such as depression, stress, and anxiety, and the distribution of associated risk factors. Methods: In this case control study, the sample consisted of 121 DED subjects and 242 control subjects. Each subjects was diagnosed as having DED or not by an ophthalmologist. Ocular Surface Disease Index and Depression Anxiety Stress Scales were administered to all subjects. Data were analysed using chi-square and Mann Whitney U tests as a univariate analysis and multiple logistic regression as a multivariate analysis. Results: Of 1,458 consecutive outpatients, clinically diagnosed DED was present in 121 individuals (8.3%). There was a significant relationship of family history of DED (OR, 1.43; 95% CI, 0.84-2.41), chronic disease history (OR, 2.84; 95% CI, 1.66-4.87), OSDI score (OR, 1.07; 95% CI, 1.97–4.06), depression (OR, 2.06; 95% CI, 1.30-3.27), anxiety (OR, 2.66; 95% CI, 1.67- 4.23), and stress (OR, 2.33; 95% CI, 1.48-3.67) with DED. Conclusion: Individuals with depression, anxiety and stress are more likely to experience DED. In addition to confirming some well-known risk factors, this study has found new associations between DED and a family history of DED and the presence of stress.

Infrared meibography allows detection of dimensional changes in meibomian glands following intranasal neurostimulation

PurposePatients with dry eye disease (DED) may suffer from decreased tear break-up time due to meibomian gland (MG) dysfunction. Infrared meibography (IR Meibography) uses infrared wavelength light to visualize meibomian glands in vivo. We aimed to explore the feasibility of using serial IR Meibography imaging to assess morphological changes in MGs as an indirect measure of functionality, following intranasal neurostimulation (ITN). MethodsFifteen DED subjects were prospectively enrolled in a single-center, single-arm study. Changes in MGs were captured using IR meibography (RTVUE-XR, Optovue, Inc. Fremont, CA, USA) on the lower eyelids before and after 3 min of ITN (TrueTear®, Allergan, Dublin, Ireland) use that delivers a microcurrent to sensory neurons of the nasal cavity. The same MGs were selected pre- and post-stimulation, and MG area and perimeter were analyzed by two masked observers. ResultsMean (±SD) pre- and post-stimulation MG areas were 2,187.60 ± 635.88 μm2 and 1,933.20 ± 538.55 μm2, respectively. The mean change in area, 254.49 μm2, representing an 11.6% reduction following ITN use, was statistically significant (p = 0.001). Mean (±SD) pre- and post-stimulation MG perimeters were 235.9 ± 51.38 μm and 222.2 ± 47.72 μm, respectively. The mean change in perimeter, 13.7 μm, representing a 5.81% reduction following ITN use, was statistically significant (p = 0.012). ConclusionsOur study shows that IR meibography can be used to detect immediate changes in gland area and perimeter, an indirect measure of MG activity following intervention by ITN.

Evaluation of the Safety and Efficacy of Intense Pulsed Light Treatment with Meibomian Gland Expression of the Upper Eyelids for Dry Eye Disease.

Objective: To investigate the safety of and change from baseline of tear breakup time and visual analog pain scales in dry eye disease subjects with upper lid Meibomian gland dysfunction after intense pulsed light (IPL) treatment assessing global ocular pain severity, ocular pain frequency, and ocular pain in the previous 24 h. This is a prospective single-site study. Methods: All patients received active treatment consisting of four treatments spaced no fewer than 2 weeks apart and no longer than 4 weeks apart. The IPL therapy was performed with a Lumenis M22 (Lumenis Ltd., Yokneam, Israel) xenon-based micropulsed IPL utilizing a 590 nm filter with a 6 mm clear SapphireCool cylindrical lightguide for the upper lids with a fluence of 10 J/cm2 across the upper eyelids, including the tragus for two passes. Patients then received expression of their meibomian glands using two cotton-tipped applicators. Tear breakup data were collected as well as global ocular pain, ocular pain episodes in the past 24 h and frequency of ocular pain episodes. Results: All of the assessments for the treated eyes improved over the course of treatment. Statistically significant physician increases in measured tear breakup times were measured for each eye independently. Statistically significant decreases in global eye dryness scale, eye dryness in the preceding 24 h, and frequency of ocular pain episodes between treatments were observed. There were no serious or nonserious adverse events in the trial. Conclusions: This pilot study suggests that a new specialized 6 mm cylindrical handpiece for the M22 Lumenis IPL machine is safe and effective in increasing physician-measured tear breakup time as well as several scales of the symptoms of ocular dryness, including global symptoms, frequency of symptoms, and ocular dryness occurring within the previous 24 h before the study visit.

Grading and baseline characteristics of meibomian glands in meibography images and their clinical associations in the Dry Eye Assessment and Management (DREAM) study

PurposeTo describe and evaluate a comprehensive grading system for meibomian gland (MG) digital infrared images developed for the Dry Eye Assessment and Management (DREAM) Study. MethodsCross-sectional study. Reading Center (RC) certified readers independently evaluated MG features of both lids from meibography images of dry eye disease subjects. Dropout areas were measured using planimetry software. Inter-reader and grade-regrade agreement and comparison of meiboscale scores (Meiboscale©; Pult) from clinical centers to RC percent dropout and of MG features with clinical parameters were evaluated. ResultsAmong 551 eyes of 277 patients at baseline, 62 (11%) upper lid and 5 (1%) lower lid images were missing. Lid eversion was poor in 63 (13%) of upper lids compared to 15 (3%) of lower lids. Intraclass correlation for inter-reader and grade-regrade agreement was moderate to substantial for most MG features. MG features were more frequent in the upper lid (p < 0.001), except for dropout glands, gaps, fluffy gland areas and dropout areas. Clinic meiboscale score was associated with RC percent dropout (p < 0.001), a clinic score of 0% having a mean RC score of 19%, and a clinic score of >75% having a mean RC score of 66%. MG plugging was associated with ghost glands (p = 0.009), dropout glands (p < 0.001) and a composite severity score (p = 0.02); turbid and absent secretions were associated with ghost glands (p = 0.046). ConclusionRC readers identified MG features with good reproducibility. Upper lids had more MG features. RC dropout areas correlated well with clinic meiboscale scores. Ghost glands were associated with paste like and absent meibomian secretions.

Incidence, demographics, types and risk factors of dry eye disease in India: Electronic medical records driven big data analytics report I

PurposeTo describe the incidence, demographics, types and risk-factors of dry eye disease (DED) in patients presenting to a multi-tier ophthalmology hospital network in India. MethodsThis was an observational hospital-based study of 1,458,830 new patients presenting between 2010 and 2018. Patients with recent onset of both symptoms and signs, as defined by the tear film and ocular surface society dry eye work shop (TFOS DEWS) II guidelines, were considered as DED subjects. The data was prospectively collected using an electronic medical record system. Multiple logistic regression with odds ratio (OR) estimation was performed to identify the high risk-factors of DED. ResultsOverall, 21,290 (1.46%) patients were diagnosed with recent-onset DED. The incidence of DED was 2688 and 16,482 per million population in children and adults, respectively (p < 0.0001). While incidence was significantly greater in males in 3rd, 4th, 9th and 10th decade (p < 0.03), it was greater in females in 5th and 6th decade (p < 0.0001) of life. Classified etiologically 35.5%, 20.6% and 39.9% of patients had evaporative, aqueous deficient and mixed type of DED, respectively. Age (OR 3.7–13.5), urban residence (OR 1.6), professional work (OR 1.5); homemaking (OR 1.42), retirement/unemployment (OR 1.24) and socio-economic affluence (OR 1.6–3.2) were identified as high risk-factors for developing DED. ConclusionThe study results indicate that age, sex, residence, occupation, and socio-economic status have significant impact on development of DED. Since India is an emerging economy with a growing middle-class, increasing urban-migration and large aging population, the country is on the brink of a DED epidemic.

A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease.

PurposeTo evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED).Patients and methodsA randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI© score ≥18; Schirmer’s test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and <7 seconds; and dry eye exacerbation in corneal staining and ocular discomfort in a Controlled Adverse Environment (CAE®). After a 7-day run-in period with placebo TID, eligible subjects were randomized to TOP1630 or placebo for 28 days. No supplemental artificial tears or rescue medication were allowed.ResultsTOP1630 was safe, well-tolerated, and efficacious in treating DED symptoms and signs. No serious adverse events (AEs) or withdrawals due to treatment emergent AEs occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable with placebo. Significant symptom improvements were seen for TOP1630 vs placebo for ocular discomfort (P=0.02 post-CAE), grittiness/foreign body sensation (on four independent assessment scales, each P<0.05), worst DED symptom (diary, P=0.06), and ocular pain (VAS, P=0.03). Sign improvements were seen for total ocular surface (all regions), corneal sum, and conjunctival sum staining with TOP1630 compared with placebo (each P<0.05).ConclusionTOP1630 had placebo-like tolerability and produced improvements in multiple symptom and sign endpoints in both environmental and challenge settings. The emergent TOP1630 benefit–risk profile for DED treatment is highly favorable and supports further development.

Inferior Quadrant of Tear Film Is More Likely to Break and Breaks Early in Patients With Dry Eyes.

To investigate the temporal and spatial distribution of tear film breakup time via a noninvasive topographer in normal subjects and patients with dry eye disease (DED). A total of 77 subjects were separated into normal and DED groups based on their symptoms and tear film instabilities. In noninvasive evaluation with Oculus Keratograph, the precorneal tear film was recorded and reconstructed into a two-dimensional map that evolved with time. Whether or not each sector broke and the breakup time if it did were recorded. The map was further grouped into 4 quadrants to reveal the spatial variation. By the end of recording, the inferior quadrant in DED subjects had a higher number of broken sectors than other quadrants (P < 0.01). Over the recording period, the cumulative percentage of sectors that were broken rose much quicker in the inferior quadrants, and the inferior quadrant is the only quadrant that showed a significant difference between the normal and DED groups (P < 0.01). This difference peaked at 12 seconds and declined after 15 seconds. Receiver operating characteristic curve for each index always showed the largest differential value in the inferior quadrant. Tear film breakup is not homogenously distributed, with sectors in the inferior quadrant being more likely to break and to break earlier. Between normal and DED subjects, a significant difference of tear film instability is more likely to be found in the inferior quadrant.