Efficacy and Safety of Phospholipid Nanoemulsion-Based Ocular Lubricant for the Management of Various Subtypes of Dry Eye Disease: A Phase IV, Multicenter Trial.
ABSTRACT: Purpose:To evaluate the clinical efficacy and safety of propylene glycol/hydroxypropyl-guar (PG-HPG)-based nanoemulsion (Systane® Complete) lubricant eye drops in participants with dry eye disease (DED). Participants and Methods:In this phase IV, open-label, single-arm, interventional, multicenter study, adult participants with DED - subtyped into aqueous deficient, evaporative, and mixed dry eye - were instructed to instill one drop of PG-HPG in each eye twice a day for 28 days. Endpoints included change from baseline in tear film break-up time (TFBUT) (primary) and ocular discomfort visual analog scale (VAS) score at Day 14 and TFBUT at Day 28 (secondary). Safety was assessed throughout the study. Data were analyzed for overall patient cohort and by DED subtypes. Results:A total of 134 participants received treatment (mean age: 56.6 years; female: 75.4%). At Day 14, the mean (standard deviation [SD]) TFBUT increased from 2.6 (1.00) seconds at baseline to 4.2 (2.92) seconds (mean change: 1.5 [2.80] seconds); median change was 0.8 seconds (95% CI: 0.52, 1.19) for the overall cohort; the change was maintained at Day 28 (mean change: 1.4 (2.80) seconds, median change: 0.8 seconds (95% CI: 0.49, 1.17). Subgroup analysis showed a mean change (SD) from baseline in TFBUT of 1.1 (2.41) seconds for aqueous deficient, 2.4 (3.17) seconds for evaporative, and 1.2 (2.63) seconds for mixed dry eye at Day 14, respectively. The ocular discomfort VAS score improved (decreased) from baseline at Day 14 (mean [SD] change: -17.3 [24.80]) for the overall cohort, -22.0 [21.73] for aqueous deficient, -17.6 [24.17] for evaporative and -13.1 [27.49] for mixed dry eye subgroups). Adverse events (AEs) were reported in 9 (6.7%) participants. No serious AEs were reported during the study. Conclusion:Our study findings demonstrated that PG-HPG-based nanoemulsion lubricant eye drops were effective and well tolerated in participants with DED and all of its subtypes.
Project description:Background:An artificial-tear formulation containing the dual polymers hydroxypropyl guar (HPG) and hyaluronic acid (HA) is approved for the treatment of dry-eye disease (DED). The present study compared the efficacy and safety of the HPG-HA dual-polymer formulation vs a sodium hyaluronate (SH)-containing artificial-tear formulation in patients with DED. Methods:In a prospective, 6-week, multicenter, double-masked, parallel-group study, patients with DED aged ?18 years and total ocular surface staining (TOSS) score ?4 and ?9 were randomized (1:1) to receive either HPG-HA or SH four times a day for 42 days. Changes from baseline in TOSS (primary end point), impact of dry eye on everyday life (IDEEL) treatment-satisfaction scores (effectiveness and inconvenience), and tear-film breakup time (TFBUT) at day 42 were assessed using a fixed-sequence testing strategy. Noninferiority was assessed on the primary end point based on the upper limit of two-sided 95% CIs for mean treatment difference (HPG-HA or SH) <2 units. Results:In total, 99 patients were randomized (HPG-HA, n= 50; SH, n= 49). At day 42, the least square (LS) mean ± SE change from baseline in TOSS was -1.16±0.24 and -0.92±0.23 in the HPG-HA and SH groups, respectively, and the treatment difference was -0.24±0.33 (95% CI -0.90 to 0.42). Noninfe-riority was demonstrated as the upper limit of the 95% CI was <2 units. LS mean change from baseline at day 42 for HPG-HA vs SH was -3.18 (P=0.4817) in IDEEL treatment-effectiveness scores, -12.56 (P=0.0001) in treatment-inconvenience scores, and 0.30 seconds (P=0.5789) in TFBUT. Conclusion:The HPG-HA dual-polymer formulation was noninferior to the SH lubricant eye-drops for improvement in ocular surface staining in DED. HPG-HA did not show improvement over SH in IDEEL treatment-satisfaction scores. No new safety findings were reported.
Project description:Purpose:To evaluate symptom relief in patients with dry eye disease (DED) following a single drop of propylene glycol-hydroxypropyl guar (PG-HPG) nanoemulsion (Systane® Complete) lubricant eye drops. Methods:This was a Phase IV, multicenter, open-label, interventional study in adult patients with DED of aqueous-deficient, evaporative, and mixed subtypes. Patients instilled one drop of PG-HPG in each eye at Day 1. Endpoints included change from baseline in dry eye symptom and soothing sensation scores on Day 1 at 0, 4, and 8 hours post-dose. Symptom scores were assessed on a 0-10 scale (0=no symptoms; 10=worst imaginable symptom). Tolerability of the drop was assessed based on assessment score on Day 1 following instillation for overall cohort and by DED subtype. Results:A total of 134 patients received treatment (mean age: 56.6 years; female: 75.4%). Median changes from baseline at Day 1 in dry eye symptom scores were -1.0 (95% confidence interval [CI]:-3.0,-1.0), -2.0 (95% CI:-3.0,-2.0), and -2.0 (95% CI:-2.0,-1.0) at 0, 4, and 8 hours respectively. Subgroup analysis showed a median change from baseline in dry eye symptom score of -2 (95% CI:-3.0,-1.0) for aqueous-deficient and evaporative subtypes and -1 (95% CI:-3.0,-1.0) for mixed subtype at 8 hours. Median soothing sensation scores were 3 at 0 and 4 hours and 3.5 at 8 hours, with a range of 0-10. Median (range) tolerability assessment scores were 0 (0-8) for burning sensation, stinging sensation, blurring, and 0 (0-10) for foreign body sensation. Tolerability assessment scores by DED subtype confirmed that the majority of patients reported scores in the range of 0-5 for all components and in all subgroups analyzed. Conclusion:Our study demonstrated that PG-HPG nanoemulsion provided instant/immediate and sustained symptom relief for 8 hours post-single application and was well tolerated in patients with DED, demonstrated by their responses on each of the assessment scales.
Project description:Tear film breakup time (TFBUT) is an essential parameter used to diagnose dry eye disease (DED). However, a robust method for examining TFBUT in murine models has yet to be established. We invented an innovative device, namely, the "Smart Eye Camera", which addresses several problems associated with existing methods and is capable of evaluating TFBUT in a murine DED model. We compared images taken by existing devices and the Smart Eye Camera in a graft-versus-host disease-related DED murine model. We observed that the quality of the images obtained by the Smart Eye Camera were sufficient for practical use. Moreover, this new technique could be used to obtain measurements for several consecutive ocular phenotypes in a variety of environments. Here, we demonstrate the effectiveness of our new invention in the examination of ocular phenotypes, including TFBUT in a murine model. We highlight the potential for future translational studies adopting the Smart Eye Camera in clinical settings.
Project description:PURPOSE:To determine the changes in dry eye disease (DED) severity and the percentage of cells expressing HLA-DR on the ocular surface following treatment with lubricant eyedrops containing polyethylene glycol and propylene glycol (PEG/PG) and the gelling agent hydroxypropyl guar (HP-Guar). PATIENTS AND METHODS:Nineteen patients with DED used PEG/PG + HP-Guar eyedrops four times per day for 30 days. Assessments included DED severity (Ocular Surface Disease Index [OSDI], corneal staining, conjunctival staining, tear film break-up time [TFBUT], and Schirmer testing) and impression cytology of the conjunctiva with masked flow cytometry at baseline and at 30 days. RESULTS:There was a significant decrease in corneal staining (P<0.01), OSDI (P=0.02), and TFBUT (P<0.01) following treatment with PEG/PG + HP-Guar. Results from flow cytometry revealed a significant decrease in cells expressing HLA-DR (P=0.02). CONCLUSION:Treatment with PEG/PG + HP-Guar eyedrops showed improvement in dry eye severity and reduction in surface inflammation as indicated by a reduction in HLA-DR expression.
Project description:<h4>Purpose</h4>The aim of this study was to analyze dry eye disease (DED) in patients with functioning filtering blebs and to explore the relationship between the morphology of filtering blebs and ocular surface instability.<h4>Methods</h4>This was a cross-sectional, case-comparison study. Seventy glaucomatous patients (70 eyes) with functioning blebs who had undergone trabeculectomy more than 6 months prior (study group) and 35 control subjects (35 eyes) (control group) were included. All subjects completed an ocular symptom questionnaire that referred to the Shihpai Eye Study. Evaluation of meibomian gland obstruction, a tear film break-up time test (TFBUT), fluorescein corneal staining and a Schirmer's tear test were then performed. Filtering bleb morphology was analyzed using Wuerzburg bleb classification scoring criteria in the study group. The presence of DED was defined as the concomitant presence of TFBUT <10 seconds and the presence of superficial punctate keratitis.<h4>Results</h4>The patients with functioning blebs presented higher corneal staining scores (P = 0.012) and lower TFBUT values (P = 0.043) than the control group. DED was present in 28/70 patients in the study group and 6/35 patients in the control group (P = 0.018). More patients in the study group complained of dryness (P = 0.001), a gritty or sandy sensation (P < 0.001) and redness (P = 0.048). In the study group, the patients with DED were significantly different from the patients without DED in both TFBUT (P < 0.001) and corneal staining (P < 0.001). More patients in the DED group were likely to report dryness (P = 0.013) and watery or teary eyes (P = 0.012). The differences in meibomian gland obstruction scores between the study and the control group, the DED and the non-DED group were not significant (P = 0.105 and P = 0.077, respectively). The values for microcysts and bleb heights were significantly higher in the DED group (P = 0.040 and P = 0.011, respectively). A Spearman's rank correlation showed that microcysts were positively correlated with corneal staining (r = 0.270, P = 0.024). Bleb height was negatively correlated with TFBUT (r = -0.299, P = 0.012) and positively correlated with corneal staining (r = 0.275, P = 0.021). The relationships between DED and microcysts and between DED and bleb height were significant (r = 0.247, P = 0.039 and r = 0.307, P = 0.010, respectively).<h4>Conclusion</h4>DED is relatively common in patients with functioning filtering blebs following trabeculectomy. In DED patients, dryness and watery are common symptoms. Microcysts and bleb height are related to ocular surface instability and DED.
Project description:Purpose:The objective of this study was to evaluate the safety and effectiveness of the TearCare® System in adult patients with clinically significant dry eye disease (DED). Patients and methods:This was a prospective, single-center, randomized, parallel-group, clinical trial. Subjects with DED were randomized to either a single TearCare treatment conducted at the clinic or 4 weeks of daily warm compress (WC) therapy. The TearCare procedure consisted of 12 minutes of thermal eyelid treatment immediately followed by manual expression of the meibomian glands. WC therapy consisted of once daily application of the compresses to the eyelids for 5 minutes. Subjects were followed until 6 months post-treatment. The primary effectiveness end point was defined as change from baseline to 4 weeks for tear breakup time (TBUT). Secondary effectiveness end points included meibomian gland assessment, corneal and conjunctival staining scores, and assessment of dry eye symptoms using validated questionnaires. Safety was evaluated by collecting device-related adverse events, intraocular pressure, and best spectacle-corrected Snellen Visual acuity. Results:Twenty-four subjects were enrolled and all subjects completed 6 months follow-up. At the 1-month follow-up, TearCare subjects demonstrated an improvement from baseline in mean (±SD) TBUT of 11.7±2.6 seconds compared with an average worsening of -0.3±1.1 seconds for subjects in the WC group (p<0.0001). Significantly greater improvements in the change from baseline in meibomian gland scores, as well as corneal and conjunctival staining scores, were observed in the TearCare group. Subjects in the TearCare group also showed significantly greater improvement in dry eye symptoms as measured by the 3 questionnaires. Both treatments were well-tolerated. Conclusion:The findings of this pilot study suggest that the TearCare System is an effective treatment option for patients with DED, with the effects on the signs and symptoms of DED persisting for at least 6 months.
Project description:Purpose:To compare the efficacy of the new lubricating product VisuEvo® (VSE) vs Cationorm® (CTN) in patients with dry eye disease (DED). Methods:Seventy-two patients with evaporative (n=54) and non-evaporative DED (n=18) were included in a multicenter, double-blind, 12-week cross-over study to receive VSE (6 weeks) and CTN (6 weeks) in randomized sequence. After baseline, two visits were performed during each period (intermediate and final visit, respectively at 2 and 6 weeks from the beginning of each period). Primary (tear break-up time, TBUT) and secondary endpoints (Schirmer I, Ferning, blink rate, osmometry, cytokine and lipid expression, ocular surface staining, patient satisfaction, and OSDI score) were compared. Results:Sixty-three patients were evaluated for efficacy and 68 patients for safety. The intergroup differences for mean TBUT values were not significant at any study visit (baseline 3.2 ±1.5 sec; intermediate visits 4.5 ± 1.9 and 4.5 ± 1.8 sec in VSE and CTN groups, respectively, p = 0.10; final visits 5.4 ± 2.4 and 6.0 ± 3.1, respectively, p=0.63). Also, the assessment of secondary endpoints showed no significant difference between the two groups. The two study treatments were equally effective in evaporative and non-evaporative DED. The safety profile was excellent for both ocular treatments; transient blurred vision was observed in 11 patients only during CTN, 10 patients only during VSE, and 16 during both treatments. Conclusion:VSE was non-inferior to CTN in restoring tear film composition, increasing its stability and reducing ocular surface damage in evaporative and non-evaporative DED patients. Study Identifier:NCT03833882.
Project description:Ocular dryness is a characteristic feature of primary Sjögren's syndrome (pSS). This may result in dry eye disease (DED), leading to damage of the ocular surface. Additional, non-invasive diagnostic techniques are needed when evaluating pSS patients. Hence, screening for disease-specific biomarkers in biological fluid could be promising. We have previously examined the proteome of tear fluid from pSS patients through Liquid chromatography-mass spectrometry (LC-MS), and conducted a thorough ocular evaluation of patients with pSS. In this study we further explored the association between dry eye manifestations and protein expression in tear fluid of pSS patients. Medical history of 27 patients and 32 healthy controls was gathered. Subjective complaints were registered through questionnaires. Objective findings including tear osmolarity, tear film break up time (TFBUT), Schirmer's test, and ocular and corneal surface staining were also recorded. LC-MS was conducted formerly on tear fluid from all subjects in order to generate proteomic biomarker profiles. Scaffold was employed to analyse the LC-MS data for quantitative differences between patient and control groups, and the mean spectral counts were calculated for the five most upregulated proteins in relation to DED manifestations. Dysregulated cellular processes were identified in pSS patients using FunRichv3 enrichment analysis. The five most upregulated proteins previously identified in pSS patients were DNA (apurinic or apyrimidinic site) lyase (APEX1), thioredoxin-dependent peroxidase reductase (PRDX3), copine (CPNE1), aconitate hydratase (ACO2), and LIM domain only protein 7 (LMO7), in descending order. A significant increase in mean spectral counts for these proteins were observed in pSS patients with pathological DED manifestations compared to healthy controls (p<0.0001). Consequently, dysregulated cellular pathways involving innate and adaptive immunity were also detected. In conclusion, our observations suggest a relationship between presence of dry eye signs and upregulated proteins in tear fluid from patients with pSS. Further studies are needed in order to replicate the concepts explored and analyses performed in a greater cohort of pSS patients, where sensitivity and specificity of the methods conducted can also be verified further.
Project description:Dry Eye Disease (DED) is part of several conditions, including Sjögren's syndrome (SS) and no single test to diagnosis DED. The present study intends to evaluate whether a set of signs and symptoms of DED can distinguish: a) SS from other non-overlapping systemic diseases related to DED; b) primary and secondary SS. 182 consecutive patients with DED were evaluated under five groups: SS, graft-versus-host disease (GVHD), Graves' orbitopathy (GO), diabetes mellitus (DM), glaucoma under treatment with benzalkonium chloride medications (BAK). Twenty-four healthy subjects were included as control group (CG). The evaluation consisted of Ocular Surface Disease Index (OSDI), Schirmer test (ST), corneal fluorescein staining (CFS) and tear film break up time (TFBUT). Indeed, a subset of DED patients (n = 130), classified as SS1, SS2 and nonSS (NSS) by the American-European Criteria were compared. Quadratic discriminant analysis (QDA) classified the individuals based on variables collected. The area under Receiver Operating Characteristics (ROC) curve evaluated the classification performance in both comparisons. Comparing SS with other diseases, QDA showed that the most important variable for classification was OSDI, followed by TFBUT and CFS. Combined, these variables were able to correctly classify 62.6% of subjects in their actual group. At the discretion of the area under the ROC curve, the group with better classification was the control (97.2%), followed by DM (95.5%) and SS (92.5%). DED tests were different among the NSS, SS1 and SS2 groups. The analysis revealed that the combined tests correctly classified 54.6% of the patients in their groups. The area under the ROC curve better classified NSS (79.5%), followed by SS2 (74.4%) and SS1 (69.4%). Diseases that causes DED, and also SS1, SS2 and NSS are distinguishable conditions, however a single ocular tools was not able to detect the differences among the respective groups.