scholarly journals Two Patients with Dry Eye Disease Followed Up Using an Expression Assay of Ocular Surface Mucin

2016 ◽  
Vol 7 (1) ◽  
pp. 208-215 ◽  
Author(s):  
Yumiko Machida ◽  
Jun Shoji ◽  
Natsuko Harada ◽  
Noriko Inada
Keyword(s):  
Foreign Body ◽  
Dry Eye ◽  
Ocular Surface ◽  
Combined Treatment ◽  
Eye Disease ◽  
Subjective Symptoms ◽  
Once Daily ◽  
Expression Levels ◽  
Body Sensation ◽  
Ophthalmic Suspension

Purpose: We report 2 patients with dry eye disease followed up using the expression levels of ocular surface mucin. Case Reports: Patient 1: a 57-year-old woman with Sjögren's syndrome-associated dry eyes experienced severe dryness and foreign body sensation in both her eyes, and instilled sodium hyaluronate ophthalmic solution 0.3% about 10-15 times daily. We measured the expression levels of MUC5AC mRNA (MUC5AC) and MUC16 mRNA (MUC16) by using real-time reversed transcription polymerase chain reaction for the specimens of modified impression cytology. Expression levels of MUC5AC and MUC16 on her ocular surface were very low. Subjective symptoms and expression levels of ocular surface mucin improved after combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Patient 2: a 62-year-old man with chronic graft-versus-host disease-associated dry eye experienced severe foreign body sensation and developed superficial punctate keratopathy with mucous thread and filamentary keratitis. Expression level of MUC5AC was very high at baseline. Subjective symptoms and expression levels of ocular surface mucin improved by combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Conclusion: Clinical test for MUC gene expression on the ocular surface was found to be useful in the follow-up of dry eye treatment.

scholarly journals One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease

2017 ◽  
Vol 27 (6) ◽  
pp. 678-685 ◽  
Author(s):  
Christophe Baudouin ◽  
Maite Sainz de la Maza ◽  
Mourad Amrane ◽  
Jean-Sébastien Garrigue ◽  
Dahlia Ismail ◽  
...  
Keyword(s):  
Dry Eye ◽  
Cyclosporine A ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Efficacy And Safety ◽  
Open Label ◽  
Once Daily ◽  
Surface Inflammation ◽  
Ocular Surface Inflammation

Purpose The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE). Methods In this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups). Results A total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (≥2 CFS points, ≥30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA. Conclusions In this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.

scholarly journals The role of KPI-121 0.25% in the treatment of dry eye disease: penetrating the mucus barrier to treat periodic flares

2021 ◽  
Vol 13 ◽  
pp. 251584142110127
Author(s):  
Preeya K. Gupta ◽  
Nandini Venkateswaran
Keyword(s):  
Drug Delivery ◽  
Dry Eye ◽  
Ocular Surface ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Short Term ◽  
Short Term Treatment ◽  
Loteprednol Etabonate ◽  
Mucus Barrier

The tear film, which includes mucins that adhere to foreign particles, rapidly clears allergens and pathogens from the ocular surface, protecting the underlying tissues. However, the tear film’s ability to efficiently remove foreign particles during blinking can also pose challenges for topical drug delivery, as traditional eye drops (solutions and suspensions) are cleared from the ocular surface before the drug can penetrate into the conjunctival and corneal epithelium. In the past 15 years, there has been an increase in the development of nanoparticles with specialized coatings that have reduced affinity to mucins and are small enough in size to pass through the mucus barrier. These mucus-penetrating particles (MPPs) have been shown to efficiently penetrate the mucus barrier and reach the ocular surface tissues. Dry eye disease (DED) is a common inflammatory ocular surface disorder that often presents with periodic flares (exacerbations). However, currently approved immunomodulatory treatments for DED are intended for long-term use. Thus, there is a need for effective short-term treatments that can address intermittent flares of DED. Loteprednol etabonate, an ocular corticosteroid, was engineered to break down rapidly after administration to the ocular surface tissues and thereby reduce risks associated with other topical steroids. KPI-121 is an ophthalmic suspension that uses the MPP technology to deliver loteprednol etabonate more efficiently to the ocular tissues, achieving in animal models a 3.6-fold greater penetration of loteprednol etabonate to the cornea than traditional loteprednol etabonate ophthalmic suspensions. In clinical trials, short-term treatment with KPI-121 0.25% significantly reduced signs and symptoms of DED compared with its vehicle (placebo). Recently approved KPI-121 0.25%, with its novel drug delivery design and ease of use, has the potential to effectively treat periodic flares of DED experienced by many patients.

scholarly journals Dexamethasone-Loaded Nanostructured Lipid Carriers for the Treatment of Dry Eye Disease

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 905
Author(s):  
Sangeeta Kumari ◽  
Madhuri Dandamudi ◽  
Sweta Rani ◽  
Elke Behaeghel ◽  
Gautam Behl ◽  
...  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Pilot Scale ◽  
Dry Eye Disease ◽  
Rapid Screening ◽  
Eye Disease ◽  
Topical Steroids ◽  
Nanostructured Lipid Carrier ◽  
The Impact ◽  
Ophthalmic Formulation

Dry eye disease (DED) or keratoconjunctivitis sicca is a chronic multifactorial disorder of the ocular surface caused by tear film dysfunction. Symptoms include dryness, irritation, discomfort and visual disturbance, and standard treatment includes the use of lubricants and topical steroids. Secondary inflammation plays a prominent role in the development and propagation of this debilitating condition. To address this we have investigated the pilot scale development of an innovative drug delivery system using a dexamethasone-encapsulated cholesterol-Labrafac™ lipophile nanostructured lipid carrier (NLC)-based ophthalmic formulation, which could be developed as an eye drop to treat DED and any associated acute exacerbations. After rapid screening of a range of laboratory scale pre-formulations, the chosen formulation was prepared at pilot scale with a particle size of 19.51 ± 0.5 nm, an encapsulation efficiency of 99.6 ± 0.5%, a PDI of 0.08, and an extended stability of 6 months at 4 °C. This potential ophthalmic formulation was observed to have high tolerability and internalization capacity for human corneal epithelial cells, with similar behavior demonstrated on ex vivo porcine cornea studies, suggesting suitable distribution on the ocular surface. Further, ELISA was used to study the impact of the pilot scale formulation on a range of inflammatory biomarkers. The most successful dexamethasone-loaded NLC showed a 5-fold reduction of TNF-α production over dexamethasone solution alone, with comparable results for MMP-9 and IL-6. The ease of formulation, scalability, performance and biomarker assays suggest that this NLC formulation could be a viable option for the topical treatment of DED.

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

2021 ◽  
Vol 22 (1) ◽  
pp. 422
Author(s):  
Ming-Tse Kuo ◽  
Po-Chiung Fang ◽  
Shu-Fang Kuo ◽  
Alexander Chen ◽  
Yu-Ting Huang
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Mechanistic Studies ◽  
Clinical Tests ◽  
Tear Proteins ◽  
Proteomic Data ◽  
Surface Performance

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.

scholarly journals A combination of CMC and α-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ying Lv ◽  
Chenchen Chu ◽  
Ke Liu ◽  
Yusha Ru ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Dry Eye ◽  
Nlrp3 Inflammasome ◽  
Ocular Surface ◽  
Combined Treatment ◽  
Underlying Mechanism ◽  
Oxygen Species ◽  
Corneal Epithelial ◽  
Melanocyte Stimulating Hormone ◽  
Human Corneal Epithelial Cells ◽  
Conjunctival Goblet Cells

AbstractAn important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and α-melanocyte stimulating hormone (α-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with α-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC + α-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.

scholarly journals A Survey on How Ocular Surface Demodex Infestation Interactively Associates with Diabetes Mellitus and Dry Eye Disease

2021 ◽  
Author(s):  
Chang Huang ◽  
Shuze Chen ◽  
Sheng Fu ◽  
Yingli Li ◽  
Zhenhao Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dry Eye ◽  
Ocular Surface ◽  
Cross Sectional Study ◽  
General Information ◽  
Potential Interaction ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Cross Sectional ◽  
Demodex Infestation

Abstract Purpose Prevention of ocular surface (OS) Demodex infestation plays an important role in OS hygiene and variety of factors may be associated with it, in which diabetes mellitus (DM) or dry eye disease (DED) has caught the attention of most scholars. However, there has been no research on whether there was a potential interaction between DM and DED in the process of OS Demodex infestation. This cross-sectional study was implemented in Zhujiang Hospital of Southern Medical University. Methods Ophthalmologic interviews, questionnaires, and examinations were conducted. Factors including general information, DM status, dry eye condition, etc. were collected to study the correlation of DM and DED on OS Demodex infestation. Results After statistical analysis, we found that both DM (P < 0.001) and DED (P = 0.013 < 0.05) are closely associated with OS Demodex infestation. Compared with DED, DM has higher priority association with OS Demodex infestation, and patients with both diseases have a significant higher risk of OS Demodex infestation (R = 0.197, P < 0.001). Meanwhile, age (R = 0.299, P < 0.001) and hypertension (P < 0.05) were also correlated with OS Demodex infestation. Conclusion This study provides a new evidence-based basis for clinical prevention and management of OS Demodex infestation.

scholarly journals Dry eye disease among Glaucoma patients on topical hypotensive medications, in a tertiary hospital, Ethiopia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Miraf Sahlu ◽  
Abeba T. Giorgis
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Signs And Symptoms ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Schirmer Test ◽  
Ocular Surface Disease Index ◽  
Cross Sectional ◽  
Corneal Staining

Abstract Background Dry eye disease is a multifactorial disease; causing various ocular symptoms with potential damage to the ocular surface. Applying hypotensive eye drops are presumed to initiate or exacerbate existing dry eye disease. The purpose of this study was to determine the frequency of signs and symptoms and severity of dry eye disease among glaucoma patients on topical hypotensive medications and controls. Methods A cross-sectional comparative study, involving 320 glaucoma patients and controls. Ocular Surface Disease Index (OSDI) symptoms score and Schirmer, tear breakup time and corneal staining tests were used to assess dry eye disease. Data was analyzed using SPSS version 24 software; p-value less than 0.05 was considered as statistically significant. Results Among the 160 study glaucoma patients, the mean duration of topical hypotensive medication use was 5.2 ± 5.21 years (range, 4 months - 32 years). Mild to severe level of OSDI score was found in 122 (76%) glaucoma patients and in 137 (86%) controls (p = 0.033). Mild to sever abnormal clinical tests in the glaucoma patients and control, respectively, were 106 (66%) vs 80 (50%) corneal staining (p = 0.045), 79 (49%) vs 72 (45%) TBUT (p = 0.021), and 91 (57%) vs 83 (52%) Schirmer test (p = 0.242). Test results at the level of sever: 2 (1%) vs 0 (0%) corneal staining, 50 (31%) vs 39 (24%) TBUT and 65 (41%) vs 60 (38%) Schirmer test in the glaucoma patents and controls, respectively. Corneal staining and TBUT had correlation with the number of drugs (p = 0.004 and 0.031, respectively), and more relationship of the two tests with total number of drops applied per day (p = 0.01 and p <  0.001, respectively). Patients on pilocarpine and timolol had more corneal staining and lower TBUT [(p = 0.011 and p <  0.001) and (p = 0.04 and 0.012), respectively]. Conclusions The study has identified glaucoma patients to be more affected by dry eye disease than non-glaucoma patients, and presence of significantly lower TBUT and higher corneal staining in the glaucoma patients on multidrops and multidose per day. We recommend consideration of evaluation and management of DED for glaucoma patients on multidrops and multidose hypotensive medications.

scholarly journals Reliability and validity of the Japanese version of the Ocular Surface Disease Index for dry eye disease

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e033940 ◽  
Author(s):  
Akie Midorikawa-Inomata ◽  
Takenori Inomata ◽  
Shuko Nojiri ◽  
Masahiro Nakamura ◽  
Masao Iwagami ◽  
...  
Keyword(s):  
Internal Consistency ◽  
Dry Eye ◽  
Ocular Surface ◽  
Discriminant Validity ◽  
Reliability And Validity ◽  
Japanese Version ◽  
Disease Index ◽  
Eye Disease ◽  
Ocular Surface Disease Index ◽  
Test Retest Reliability

ObjectivesThe Ocular Surface Disease Index (OSDI) questionnaire is widely used to evaluate subjective symptoms of dry eye disease (DED) as a primary diagnostic criterion. This study aimed to develop a Japanese version of the OSDI (J-OSDI) and assess its reliability and validity.Design and settingHospital-based cross-sectional observational study.ParticipantsA total of 209 patients recruited from the Department of Ophthalmology at Juntendo University Hospital.MethodsWe translated and culturally adapted the OSDI into Japanese. The J-OSDI was then assessed for internal consistency, reliability and validity. We also evaluated the optimal cut-off value to suspect DED using an area under the receiver operating characteristic curve (AUC) analysis.Primary outcome measuresInternal consistency, test–retest reliability and discriminant validity of the J-OSDI as well as the optimal cut-off value to suspect DED.ResultsOf the participants, 152 had DED and 57 did not. The J-OSDI total score showed good internal consistency (Cronbach's alpha=0.884), test–retest reliability (interclass correlation coefficient=0.910) and discriminant validity by known-group comparisons (non-DED, 19.4±16.0; DED, 37.7±22.2; p<0.001). Factor validity was used to confirm three subscales within the J-OSDI according to the original version of the questionnaire. Concurrent validity was assessed by Pearson correlation analysis, and the J-OSDI total score showed a strong positive correlation with the Dry Eye-Related Quality-of-Life Score (γ=0.829). The optimal cut-off value of the J-OSDI total score was 36.3 (AUC=0.744).ConclusionsThe J-OSDI was developed and validated in terms of reliability and validity as an effective tool for DED assessment and monitoring in the Japanese population.

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