Dry Eye Disease Patients Research Articles

Matrix Metalloproteinase 9 Point-of-Care Immunoassay Result Predicts Response to Topical Cyclosporine Treatment in Dry Eye Disease.

PurposeWe evaluate a matrix metalloproteinase-9 (MMP-9) point-of-care immunoassay (InflammaDry) as a prognostic tool for topical cyclosporine treatment.MethodsA total of 20 healthy subjects and 40 patients meeting >3 dry eye disease (DED) criteria (ocular surface disease index [OSDI] score ≥ 12, tear film breakup time [TBUT] ≤10 seconds, Schirmer I test result ≤10 mm/5 minutes, corneal staining ≥1) were included. DED patients were treated with topical cyclosporine ophthalmic emulsion 0.05% twice daily for 1 month. The InflammaDry test was used to grade MMP-9 levels in the tear film. Treatment response was monitored using the OSDI score, TBUT, and Schirmer, corneal staining, and InflammaDry tests.ResultsOf the eyes, 18 (22.5%) were negative, 29 (36.3%) trace-positive, 16 (20.0%) weak-positive, 11 (13.8%) positive, and six (7.5%) strong-positive for MMP-9 at baseline. MMP-9 levels correlated with OSDI (P = 0.049), TBUT (P = 0.001), corneal staining (P = 0.002), and Schirmer test (P = 0.027) results. MMP-9–positive patients displayed decreased post-treatment MMP-9 levels (P = 0.001) and corneal staining score (P < 0.001), improved OSDI score (P < 0.001), and increased TBUT (P < 0.001) and Schirmer (P = 0.009) test values.ConclusionsSemiquantitative MMP-9 grading correlated well with DED symptoms and signs, and could be used to predict patient status and monitor treatment response. MMP-9–positive patients responded more favorably to topical cyclosporine than did MMP-9–negative patients. Thus, the InflammaDry test may inform decisions regarding initiating topical cyclosporine treatment.Translational RelevanceSemiquantitative MMP-9 could be used to predict patient status and monitor treatment response.

Spontaneous Eye Blink Patterns in Dry Eye: Clinical Correlations.

To evaluate spontaneous eye blink patterns and their correlations with clinical tests in dry eye disease (DED). Twenty-five DED patients and 25 healthy subjects were included in this prospective case-controlled study. Clinical evaluations included the Ocular Surface Disease Index (OSDI), lipid layer thickness (LLT), spontaneous eye blink pattern analysis, fluorescein tear film break-up time (FBUT), and so on. Eye blinks were recorded for 20 seconds with a high-speed camera. Eye blink patterns were divided into the following five phases: the eyelid closing phase (ECP), eyelid closed phase (CDP), early opening phase (EOP), late opening phase (LOP), and interblink intervals (IBI). The correlations between blink parameters and clinical tests were analyzed. Compared with the control group, mean ECP, CDP, and EOP were significantly longer in DED patients (P < 0.001, P = 0.029, and P < 0.001, respectively). DED patients also had significantly shorter LOP and blink intervals (both P < 0.001) and more partial blinks as compared with control subjects (P = 0.001). FBUT was negatively correlated with ECP (r = -0.618, P=0.001) and the number of partial blinks (r = -0.413, P = 0.040). There was a positive correlation between OSDI and the number of partial blinks (r = 0.446, P = 0.026). The LLT coefficient of variation (LLT-CV) also showed a positive correlation with ECP, CDP, and LOP (P = 0.001, P = 0.050, P = 0.049, respectively). Corneal and conjunctival staining was positively correlated with ECP, CDP, and the number of blinks (r = 0.449, P = 0.024; r = 0.526, P = 0.007; r = 0.456, P = 0.022, respectively) and negatively correlated with IBI (r = -0.420, P = 0.037). Partial blinks, prolonged eyelid closed time and short blink intervals were the three main characteristics of DED patients' spontaneous blink patterns.

Tear Luminex Analysis in Dry Eye Patients.

BackgroundThe purpose of this study was to analyze tear inflammatory cytokines of different subclasses of dry eye disease (DED) patients using Luminex technology.Material/MethodsForty-five DED patients including 20 Sjogren syndrome aqueous tear deficiency (SS-ATD) patients, 20 non-Sjogren syndrome aqueous tear deficiency (NSS-ATD) patients, 15 meibomian gland dysfunction (MGD) patients, and 15 normal participants were enrolled in this study. Concentrations of 11 inflammatory cytokines in tear samples of study participants were measured by Luminex assay; ELISA assay was further applied for validation.ResultsThe levels of cytokines were mostly increased (TNF-α, IL-1α, IL-1β, IL-6, IL-8, IL-12P70, IL-13, IFN-γ, and MIP-1α) in DED patients compared with normal participants. And the levels of TNF-α, IL-6, IL-8, and IL-12P70 were significantly elevated in tears of the patient groups compared to tears of participants in the normal group (P<0.05). Statistical differences were also observed among the patient groups (SS-ATD, NSS-ATD, and MGD) for the level of IL-8 and TNF-α. The results of ELISA assay demonstrated the consistence with Luminex assay, confirming the practicality of Luminex technology for the analysis of multiple cytokines in DED patient tears.ConclusionsThe levels of inflammatory cytokines were mostly elevated in DED patients, and statistical differences of some cytokines were also found between SS-ATD, NSS-ATD, and MGD groups, suggesting that inflammatory cytokines could be potential supplements for the diagnosis of DED subclasses and therapeutic targets for DED patients.

Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort

ABSTRACT Purpose To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p ≤ 0.05). Results The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.

Dry Eye and its Relationship with Status of Serum Calcium in the Body at a Tertiary Care Institute: A Case Control Study

Background: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of dryness, grittiness, redness, burning sensation or any discomfort, visual disturbance and tear film instability leading to potential damage to ocular surface. The tear film consists of three layers starting from within outwards mucus, the aqueous layer and the lipid layer. The tear film and ocular surface form a complex and stable system that can lose its equilibrium through numerous disturbing factors. Studies which also involve tests of tear functions including Schirmer's test, Tear break-up time, Fluorescein staining for determination of dry eye have found generally low prevalence rates.Hence the physiology of tear film and its binding with the eye shows that there is some involvement of serum calcium level with dry eye. The present study encourages us to assess the role of serum calcium level with patients of dry eye. Aims and Objective: To assess the role of calcium with dry eye. Material and Methods: Total 90 subjects (30 cases and 60 controls) who met the selection criteria were included in the study. Serum analysis has been done for calcium level in the body in the patients of dry eye.The study was conducted between August 2014 to November 2016. Results: The lower serum level of calcium was significantly associated with dry eyes in the study. Conclusion: Calcium plays an important role in the causative mechanism of dry eye in the patients of dry eye disease.

Assessment of meibomian glands using a custom\u2013made meibographer in dry eye patients in Ghana

BackgroundMeibomian Gland Dysfunction (MGD) is a leading cause of evaporative Dry Eye Disease (DED). This makes non-invasive meibography an important procedure in the clinical evaluation of DED patients. Our purpose was to conduct a lead-off investigation focused on the practicality of performing meibography in a developing country, with limited access to complex ophthalmic imaging systems, using a custom meibographer, as a step to future comparative studies on meibomian glands and DED in Africa.MethodsMeibomian glands(MG) in 76 upper eyelids (UL) and 49 lower eyelids (LL) in 1 eye each of 125 patients randomly selected from a patient population presenting with subjective DED symptoms at a clinic were photographed using a custom meibographer. Single frames were captured, and the MG area determined by intensity threshold segmentation and area calculation using Image J software. MG loss (MGL) was quantified by outlining its area and expressing it as a percentage of the total MG per Pult’s grading scheme. Dry eye measures included Tear Film Break Up - Time (TUBT), Schirmer’s test and Ocular Surface Staining (OSS). Symptoms were evaluated using the SPEED II questionnaire. Correlations between MGL and age, ocular signs and symptoms were analyzed by Pearson’s. Differences between comparable groups were analyzed by Mann - Whitney test; p < 0.05 was considered significant.ResultsOverall mean MGL was 32.10% ± 25.0% (26.25% ± 22.40% for UL and 40.33% ± 26.70% for LL). MGL correlated significantly with age [r = 0.91, p = 0.001], SPEED scores [r = 0.90, p = 0.001], OSS [r = 0.75, p = 0.001] and TBUT [r = − 0.81, p = 0.001]. MGL scores were significantly higher in the UL than LL [U = 1293.5 p = 0.004].ConclusionThis study for the first time presents data on the status of Meibomian glands in Africa. It furthermore suggests that it is feasible to examine Meibomian glands using a custom meibographer in developing countries with limited access to complex imaging systems. It also demonstrates the benefit and cost-effectiveness of a simple device by the observed significant relations between meibomian gland loss and DED in these patients.

Blue light phototoxicity toward human corneal and conjunctival epithelial cells in basal and hyperosmolar conditions

AimsThe ocular surface is the very first barrier between the visual system and external environment. It protects the eye from the exposure to various light sources that significantly emit in blue spectrum. However, the impact of blue light on the ocular surface has been poorly explored so far. In this study, we investigated in vitro the phototoxicity of blue light illumination in human epithelial cells of the ocular surface. We worked either in basal conditions or under hyperosmolar stress, in order to mimic dry eye disease (DED) that is the most common disease involving the ocular surface. ResultsCorneal and conjunctival epithelial cells suffered the most from violet-blue light but also from longer-wave blue light. Exposure to blue wavebands significantly decreased cellular viability, impacted on cellular morphology and provoked reactive oxygen species (ROS) over-production. Conjunctival epithelial cell line had a greater photosensitivity than the corneal epithelial one. Hyperosmolar stress potentiated the blue light phototoxicity, increasing inflammation, altering mitochondrial membrane potential, and triggering the glutathione-based antioxidant system. InnovationIn human epithelial corneal and conjunctival cells of the ocular surface, we demonstrated the harmful impact of blue light on viability, redox state and inflammation processes, which was modified by hyperosmolarity. ConclusionBlue light induced cell death and significant ROS production, and altered the expression of inflammatory genes and operation of the cellular defensive system. We established for the first time that hyperosmolar stress impacted phototoxicity, further suggesting that DED patients might be more sensitive to blue light ocular toxicity.

Subjective versus objective dry eye disease in patients with moderate-severe thyroid eye disease

PurposeTo compare the subjective versus Objective dry eye disease (DED) in patients with moderate-severe thyroid eye disease (TED). MethodIncluded were the patients with moderate-severe TED and ≥18 years old. They completed the ocular surface disease index (OSDI) questionnaire and had Schirmer, Tear breakup time (TBUT), fluorescein staining, osmolarity, corneal aesthesiometry, and meibomian gland dysfunction (MGD) tests. Excluded were patients with history of any disease, surgery and or medications which might be affecting the ocular surface and incomplete tests results. Subjective DED was defined as OSDI score of ≥13 and objective as one abnormal sign (TBUT, Schirmer, Osmolarity, and Staining). Presence of both was defined as definite DED. ResultsIncluded were 38 patients (74 eyes) with mean age of 40 years. Subjective DED was detected in 77%, objective in 89.2%, and definite in 67.7% of the eyes. Severe subjective and objective DED were found in 36.5% and 24.3% of the eyes, respectively. TBUT was the most frequent positive test (63.5%). MGD was observed in 56.8% of the eyes. Mean clinical activity score, palpebral fissure, rundle grading, proptosis, corneal aesthesiometry, and presence of MGD were not significantly different between the eyes with and without subjective, objective, or definite DED. ConclusionDefinite DED was found in more than 2/3 of the eyes with moderate-severe TED. While frequency of objective DED was higher, severe form of subjective DED was more frequent. No variable was significantly different between the eyes with and without subjective, objective and definite DED.

Efficacy of polyethylene glycol-propylene glycol-based lubricant eye drops in reducing squamous metaplasia in patients with dry eye disease.

PurposeSquamous metaplasia in dry eye disease (DED) manifesting as the loss of conjunctival goblet cells results in reduced mucin secretion and tear film instability. The objective of this study was to evaluate the efficacy of a polyethylene glycol–propylene glycol/hydroxypropyl-guar (PEG-PG/HP-guar) artificial tear formulation in reducing the squamous metaplasia in patients with DED using conjunctival impression cytology (CIC).MethodsIn this Phase IV, single-arm, open-label study, DED patients (aged ≥18 years) with a corneal staining sum score ≥3 and tear film break-up time (TFBUT) <7 s self-administered the PEG-PG/HP-guar artificial tears, 3 times a day for a period of 90 days. The primary end point was the change from baseline in goblet cell density (Nelson’s CIC grading score) over the treatment period. Other end points were change in the corneal and conjunctival staining scores, and TFBUT. Statistical evaluation was performed using a paired t-test.ResultsIn total, 49 patients (n=98 eyes) completed the study. Compared with baseline, there was a significant reduction in the mean CIC scores (ie, improvement in goblet cell density) at Days 30, 60, and 90 (1.6±0.5 vs 1.2±0.5, 0.9±0.5, and 0.8±0.5; P<0.0001). At Day 90, 22% of eyes demonstrated squamous metaplasia Grade 0 (ie, normal epithelium). Similar improvements were observed in the corneal staining scores (5.7 vs 3.1, 1.1, and 0.5; P<0.0001), conjunctival staining scores (5.5 vs 3.6, 1.6, and 0.9; P<0.0001), and TFBUT (4.8 vs 5.8, 6.3, and 6.8 s; P<0.0001) at Days 30, 60, and 90, respectively.ConclusionIn this study, treatment with PEG-PG/HP-guar artificial tears for 90 days decreased CIC score, reduced corneal and conjunctival staining, and increased TFBUT in patients with DED. These results suggest that PEG-PG/HP-guar artificial tears can improve the ocular surface health and reverse the changes induced by squamous metaplasia in DED.

Dry Eye and its Relationship with Status of Serum Calcium in the Body at a Tertiary Care Institute: A Case Control Study

Background: Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of dryness, grittiness, redness, burning sensation or any discomfort, visual disturbance and tear film instability leading to potential damage to ocular surface. The tear film consists of three layers starting from within outwards mucus, the aqueous layer and the lipid layer. The tear film and ocular surface form a complex and stable system that can lose its equilibrium through numerous disturbing factors. Studies which also involve tests of tear functions including Schirmer’s test, Tear break-up time, Fluorescein staining for determination of dry eye have found generally low prevalence rates.Hence the physiology of tear film and its binding with the eye shows that there is some involvement of serum calcium level with dry eye. The present study encourages us to assess the role of serum calcium level with patients of dry eye. Aims and Objective: To assess the role of calcium with dry eye. Material and Methods: Total 90 subjects (30 cases and 60 controls) who met the selection criteria were included in the study. Serum analysis has been done for calcium level in the body in the patients of dry eye.The study was conducted between August 2014 to November 2016. Results: The lower serum level of calcium was significantly associated with dry eyes in the study. Conclusion: Calcium plays an important role in the causative mechanism of dry eye in the patients of dry eye disease.

Sleep outcomes associated with dry eye disease: a systematic review and meta-analysis

ObjectiveTo summarize and quantitatively evaluate sleep outcomes of dry eye disease (DED) patients. DesignA systematic review and meta-analysis. ParticipantsDED patients were individuals with dry eye symptoms or primary Sjogren’s syndrome (pSS). Controls were healthy, non-pSS, or non-DED patients. MethodsA systematic search of MEDLINE, EMBASE, PsycINFO, and grey literature was conducted. Studies were screened using Covidence software. Outcomes included sleep quality, duration, daytime sleepiness, prevalence/incidence/severity of sleep disorders, and sleep disturbances. Meta-analysis was conducted using STATA 13.0. The weighted mean difference (WMD) was calculated as the effect size for continuous scale outcomes. Random-effects models were developed based on the presence of heterogeneity. ResultsSeventeen full-text articles (16 370 subjects) and 2 conference abstracts (571 763 subjects) were included. Compared to controls, DED patients score higher on the Pittsburgh Sleep Quality Index (WMD = 1.69, 95% CI: 0.82, 2.56; I2 = 88.8%, p < 0.001) and Epworth Sleepiness Scale (WMD = 2.26, 95% CI: 0.96, 3.56; I2 = 82.4%, p < 0.001). Additionally, DED patients spend less time asleep (WMD = −0.59 hours, 95% CI: −0.94, −0.24; I2 = 85.1%, p < 0.001), experience more sleep disturbances, and may have increased prevalence, incidence, severity of sleep disorders. ConclusionDED patients may have poorer sleep quality, greater daytime sleepiness, less sleep, more sleep disturbances, increased prevalence, incidence, and severity of sleep disorders compared to non-DED patients. Further research is needed to identify potential causes of these outcomes given the paucity and heterogeneity of included studies. It may be worthwhile to consider sleep in the clinical management of DED.

Severity, therapeutic, and activity tear biomarkers in dry eye disease: An analysis from a phase III clinical trial

PurposeTo evaluate the effect of 0.1%-fluorometholone (FML) on tear inflammatory molecule levels after 22-days treatment in dry eye disease (DED) patients exposed to an adverse controlled environment (ACE), identifying different biomarkers. MethodsAnalysis of a double-masked randomized clinical trial. Forty-one DED patients received 4-drops daily of topical FML (FML-group) or polyvinyl-alcohol (PA-group) for 22 days. At day 21, patients were exposed to an ACE. Tear samples were collected at V1 (baseline), V2 (pre-ACE), V3 (post-2-h-ACE) and V4 (24-h post-ACE). Concentrations of 18 molecules (EGF, IFN-γ, TNF-α, IL-1β, IL-1RA, IL-2, IL-4, IL-6, IL-8/CXCL8, IL-10, IL-12, IL-13, IL-17A, IP-10/CXCL10, MCP-1/CCL2, MIP-1α/CCL3, RANTES/CCL5 and MMP-9) were analyzed. Similarities among patients in molecule concentrations at V1 were evaluated. A linear-mixed effect model analyzed the influence of different variables on concentrations changes. ResultsMultidimensional scaling (MDS) divided patients into two groups based on differences in EGF, IFN-γ, IL-8/CXCL8, RANTES/CCL5, and MMP-9 levels at V1. Groups had different clinical severities based on Schirmer test and conjunctival and corneal staining. IL-1RA, IL-2, and TNF-α were differentially affected by time, depending on treatment. Between V2-V3, there were significant changes in EGF, IL-1RA, IL-2, IL-8/CXCL8, IL-13, IP-10/CXCL10, TNF-α, and MMP-9. The strongest biomarker candidates were IFN-γ, RANTES/CCL5, and MMP-9 as DED severity biomarkers; IL-2 as DED therapeutic biomarker; and EGF as DED activity biomarker. ConclusionsThis clinical trial design using a controlled environment and the identified tear biomarkers could be useful to objectively select target patients, to define stress response, and to evaluate therapeutic endpoints in clinical trials.

Outcomes of Thermal Pulsation Treatment for Dry Eye Syndrome in Patients With Sjogren Disease.

To evaluate the clinical outcomes of thermal pulsation treatment in patients with meibomian gland dysfunction (MGD) and dry eye secondary to Sjogren disease. Twenty-four eyes from 13 patients with previously diagnosed Sjogren disease who presented to our institution with dry eye symptoms and had thermal pulsation treatment were prospectively followed up. Patients underwent comprehensive slit-lamp examination, including MGD grading, gland oil flow, corneal and conjunctival staining scores, and tear break-up time (TBUT). Tear osmolarity was tested before and after treatment. The average patient age was 62.4 years (range, 31-78 yrs); 12 were women and 1 a man. The average meibomian gland oil flow score showed an increase from pretreatment 0.71 to 1.75 at 1 year posttreatment (range 9-15 months) (P = 0.001). The average corneal staining score decreased from a pretreatment grade of 1.04 to a posttreatment grade of 0.36 (P < 0.001). The average conjunctival staining score decreased from a pretreatment grade of 1.5 to a posttreatment grade of 0.48 (P < 0.001). The average tear break-up time improved from 3.8 seconds before treatment to 7.5 seconds after thermal pulsation treatment (P < 0.001). There was no statistically significant change in the tear osmolarity or Ocular Surface Disease Index score. Our findings suggest that MGD is an important contributor to dry eye disease in patients with Sjogren disease and should not be overlooked when considering treatment options. Thermal pulsation is a therapeutic option for patients with Sjogren disease who have MGD and dry eye symptoms. After a single treatment, patients exhibited increased oil flow and tear break-up time with an associated decrease in corneal and conjunctival staining.

Proinflammatory Markers, Chemokines, and Enkephalin in Patients Suffering from Dry Eye Disease.

Dry eye symptoms are among the leading complaints in ophthalmology. Dry eye disease (DED) is associated with significant pain affecting quality of life. Cellular and molecular mechanisms underlying ocular pain associated with DED are not fully understood. In this study, we investigated the ocular surface of patients with DED using in vivo confocal microscopy (IVCM) to quantify corneal nerve density and its relation with corneal inflammation. Gene expression of the proinflammatory markers HLA-DR, IL-6, CXCL12, and CCL2 and the receptors CXCR4 and CCR2, as well as PENK (enkephalin precursor), was therefore quantified in conjunctival impression cytology specimens. Thirty-two patients with DED and 15 age-matched controls were included. Subbasal nerve density was significantly lower in DED patients compared to controls. IVCM analysis revealed that DED patients had a significantly higher corneal dendritic cell density compared to controls. Conjunctival impression cytology analysis revealed that HLA-DR, IL-6, CXCR4, and CCL2/CCR2 mRNA levels were significantly increased in DED patients compared to controls, whereas PENK mRNA levels were significantly decreased. Similar results were obtained in vitro on immortalized human conjunctiva-derived epithelial cells challenged with osmotic stress that mimics the DED condition. These results demonstrate that proinflammatory molecules and endogenous enkephalin have opposite gene regulation during DED.

The Effect of Topical Ocular Anesthetic Proparacaine on Conjunctival and Nasal Mucosal Flora in Dry Eye Disease Patients.

The aim of this study was to investigate the effect of topically applied ocular anesthetic proparacaine on conjunctival and nasal bacterial mucosal flora in patients with dry eye disease. A Schirmer test was done with (group 1) and without (group 2) topical anesthetic proparacaine to 40 patients in each group. Conjunctival and nasal cultures were obtained before and 10 min after performing the Schirmer test. The bacterial culture results and the isolated bacteria were recorded in two groups. Patients’ mean age was 62 years (70 female, 10 male). Before the application of topical anesthetic, 50 (62.5%) and 62 (77.5%) had positive conjunctival and nasal culture, respectively, with the most commonly isolated organism being coagulase-negative Staphylococcus in each group. In group 1 the conjunctival bacterial culture positivity rate decreased from 26 (65%) to six (15%) eyes (p < 0.001); however, this rate decreased slightly from 24 (60%) to 20 (50%) eyes in group 2 (p > 0.05). For the nasal cultures, the bacterial culture positivity rate decreased from 80% to 20% and from 75% to 65% in groups 1 (p < 0.001) and 2 (p > 0.05), respectively. Topical ocular anesthetic proparacaine has antibacterial activity in both conjunctival and nasal flora in patients with dry eye disease.

Microvascular abnormalities in dry eye patients

This study was conducted to evaluate conjunctival blood flow velocities and microvascular network density in patients with dry eye disease (DED). Twenty-five patients with DED and 25 healthy controls were recruited. The microvasculature and microcirculation of the temporal bulbar conjunctiva of the right eyes were assessed using a functional slit-lamp biomicroscope. Vascular variables included blood flow velocity (BFV), blood flow rate (BFR), microvascular network density and vessel diameter. A fractal analysis was performed using the box counting method to measure the fractal dimension (Dbox) representing the vessel density. The bulbar BFV was 0.59 ± 0.09 mm/s in the DED group and 0.47 ± 0.12 in the control group (P < 0.001). BFR was 169.5 ± 1.8 in the DED group compared to the control group (107.2 ± 49.6) (P < 0.001). Dbox was higher in DED patients (1.65 ± 0.04) than controls (1.60 ± 0.07, P < 0.05). Moreover, the vessel diameter was larger in the DED group (21.8 ± 1.8 μm) compared with controls (17.9 ± 2.2 μm, P < 0.001). Dbox was positively related with ocular surface disease index (OSDI) in patients with DED (r = 0.54, P = 0.008). Microvascular alterations were found in the bulbar conjunctiva of DED patients, including increased blood flow velocity, higher vessel density and larger vessel diameter.

Reduced Efficacy of Low-dose Topical Steroids in Dry Eye Disease Associated With Graft-versus-Host Disease

To compare the response of dry eye disease (DED) to treatment with topical steroid in patients with and without graft-vs-host disease (GVHD). Post hoc analysis of a double-masked, randomized clinical trial. This single-center study included 42 patients with moderate-to-severe DED associated with (n= 21) or without (n= 21) chronic GVHD. In each group, patients received either loteprednol etabonate 0.5% ophthalmic suspension or artificial tears twice daily for 4weeks. Clinical data, including Ocular Surface Disease Index (OSDI) questionnaire, corneal fluorescein staining (CFS), conjunctival lissamine green staining, tear break-up time (TBUT), and Schirmer test, were evaluated before and after treatment. There were no significant differences in signs and symptoms of DED between the groups at baseline. In non-GVHD patients receiving loteprednol treatment, the average OSDI score decreased by 34% from 49.5 ± 5.9 to 32.6 ± 4.8 (mean ± standard error of the mean, P= .001) and the average CFS score decreased by 41% from 5.6 ± 0.6 to 3.3 ± 0.9 (P= .02). On the other hand, loteprednol treatment in GVHD patients resulted in minimal change in OSDI (59.2 ± 6.7 to 61.1 ± 7.1, 3% increase, P= .66) and CFS (5.5 ± 0.5 to 5.3 ± 1.1, 4% decrease, P= .85) scores. Treatment with artificial tears resulted in 22% decrease of OSDI (P= .10) and 32% decrease of CFS (P= .02) scores in non-GVHD patients, and had minimal effect in patients with GVHD. DED patients with ocular GVHD have a less favorable response to a low-dose topical steroid regimen compared with those without ocular GVHD even with similar baseline disease severity.

Narrow Spectrum Kinase Inhibitors Demonstrate Promise for the Treatment of Dry Eye Disease and Other Ocular Inflammatory Disorders.

The purpose of this study is to determine the potential of narrow spectrum kinase inhibitors (NSKIs) to treat inflammatory eye disorders. Human conjunctival epithelial (HCE) cells were retrieved from subjects via impression cytology. Real-time quantitative PCR (qPCR) was performed on HCE cells to determine gene expression of NSKI kinase targets and proinflammatory cytokines in dry eye disease (DED) patients versus healthy controls. qPCR also assessed p38α expression in hyperosmolar-treated Chang conjunctival epithelial cells. Interaction of NSKI TOP1362 with the kinases was evaluated in ATP-dependent Z-LYTE and competition binding assays. Anti-inflammatory activity was assessed in human peripheral blood mononuclear cells and primary macrophages. In an endotoxin-induced uveitis (EIU) study, lipopolysaccharide (LPS) was administered intravitreally to Lewis rats. TOP1362, dexamethasone, or vehicle was administered topically, and inflammatory cytokine levels were measured 6 hours after LPS injection. HCE cells from DED patients showed significantly increased expression of p38α, spleen tyrosine kinase (Syk), Src, lymphocyte-specific protein tyrosine kinase (Lck), interleukin one beta (IL-1β), interleukin eight (IL-8), monocyte chemotactic protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9). TOP1362 strongly inhibited the kinase targets p38α, Syk, Src, and Lck, blocked the rise in p38α expression in hyperosmolar Chang cells, and potently reduced inflammatory cytokine release in cellular models of innate and adaptive immunities. In the EIU model, TOP1362 dose-dependently attenuated the LPS-induced rise in inflammatory cell infiltration and ocular cytokine levels with efficacy comparable to that of dexamethasone. TOP1362 is a potent inhibitor of kinases upregulated in DED and markedly attenuates proinflammatory cytokine release in vitro and in vivo, highlighting the therapeutic potential of NSKIs for treating ocular inflammation, such as that observed in DED.

Gender differences in adolescent dry eye disease: a health problem in girls.

To evaluate the signs and symptoms of dry eye disease (DED) in adolescents. This was a cross-sectional, case-control study and outpatients aged 10 to 19y were recruited from six eye clinics of various practices and locations in Japan, and 253 non-DED subjects and 70 DED patients were enrolled. Participants were examined for DED-related signs. Patients were also interviewed to ascertain the presence or absence of six common DED-related symptoms: dryness, irritation, pain, eye fatigue, blurring, and photophobia. Main outcome measures were differences in signs and symptoms of dry eye disease between boys and girls. Of the 323 adolescents recruited, 70 (21.7%) were diagnosed with DED. Significant differences between the non-DED and DED groups were found for short tear break-up time (BUT; ≤5s; P=0.000) and superficial punctate keratopathy (SPK; staining score ≥3; P=0.000). Late adolescent girls reported fewer symptoms than late adolescent boys, although their DED-related signs were worse compared to other groups. The prevalence and severity of DED were similar in the Tokyo area compared with suburban and local areas but myopic errors were worse. We find that adolescents reported symptoms of DED similar to those found in adults, and the majority have short BUT-type DED. The prevalence and severity of DED in late adolescent girls is comparable with adults. Adolescents with DED are underserved and we believe that DED is a hidden but potentially serious health problem for this age group.

Topical ocular 0.1% cyclosporine A cationic emulsion in dry eye disease patients with severe keratitis: experience through the French early-access program.

PurposeThe objective of this study was to report the evaluation of efficacy and safety of cyclosporine A cationic emulsion (CsA CE) 0.1% for the treatment of severe keratitis in adults with dry eye disease (DED) in a French early-access program.MethodsPatients with DED and severe keratitis (corneal fluorescein staining [CFS] score of 3–5 on the Oxford scale and/or the presence of corneal lesions [filaments or ulcers]) were enrolled in a compassionate use program (Authorization for Temporary Use [ATU]) for once-daily CsA CE, which was approved by French health authorities prior to its registration. Efficacy and safety at 1, 3, 6, and 12-month follow-up visits were evaluated.ResultsThe ATU cohort (n=1,212; mean age =60.5 years; 79.5% female; 98.1% with severe keratitis; 74.5% with corneal lesions) consisted of 601 CsA-naïve patients and 611 patients treated previously with other CsA formulations. The primary DED etiology was Sjögren’s syndrome (48.7%). Clinical benefit could be discerned among 548 evaluable patients from months 1 to 12: keratitis improvement, 44.8% at month 1 and 42.1% at month 12; keratitis stabilization, 47.2% and 45.7%, respectively; symptom improvement, 47.2% and 48.6%; and symptom stabilization, 44.8% and 45.0%. Corneal clearing (CFS score =0) increased from 4.8% (month 1) to 11.4% (month 12). No unexpected safety concerns were identified; instillation site pain (10.2%) and eye irritation (7.8%) were the most common adverse events.ConclusionThe French ATU cohort provides supportive data on the clinical benefit of CsA CE in improving/stabilizing symptoms and corneal damage in DED patients with severe keratitis in real-world clinical practice.