Goblet Cells Contribute to Ocular Surface Immune Tolerance—Implications for Dry Eye Disease

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.

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

Pharmaceutics ◽

10.3390/pharmaceutics13060905 ◽

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22010422 ◽

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.

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

Acta Parasitologica ◽

10.1007/s11686-021-00382-8 ◽

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.

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

BMC Ophthalmology ◽

10.1186/s12886-021-01917-3 ◽

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.

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Comparison of treatment efficacy between 100% platelet-rich plasma and 100% serum eye drops in moderate-to-severe dry eye disease: a randomised controlled trial protocol

BMJ Open ◽

10.1136/bmjopen-2020-048479 ◽

2021 ◽

Vol 11 (6) ◽

pp. e048479

Author(s):

Passara Jongkhajornpong ◽

Pawin Numthavaj ◽

Thunyarat Anothaisintawee ◽

Kaevalin Lekhanont ◽

Gareth McKay ◽

...

Keyword(s):

Dry Eye ◽

Ocular Surface ◽

Platelet Rich Plasma ◽

Controlled Trial ◽

Dry Eye Disease ◽

Autologous Serum ◽

Eye Disease ◽

Eye Drops ◽

Department Of Ophthalmology ◽

Autologous Platelet

IntroductionDry eye disease (DED) is a common eye problem. Although the disease is not fatal, it substantially reduces quality of life and creates a high economic burden, especially in patients with moderate-to-severe DED. Several biological tear substitutes (eg, autologous serum (AS), autologous platelet-rich plasma (APRP) and autologous platelet lysate) could effectively improve dry eyes. However, evidence on their comparative efficacy is controversial. This study aims to compare the efficacy of 100% APRP with 100% AS eye drops in patients with moderate-to-severe DED.Methods and analysisThe study is a single-centre, double-blinded randomised, parallel, non-inferiority trial. One hundred and thirty patients with moderate-to-severe DED, aged 18–70 years will be recruited from outpatient clinic, Department of Ophthalmology, Ramathibodi Hospital, Bangkok from February 2021 to January 2023. Patients will be randomised to receive either 100% APRP or 100% AS eye drops (1:1 ratio) for 4 weeks. The primary outcomes are ocular surface disease index (OSDI) and ocular surface staining (OSS) evaluated using the Oxford scale. Secondary outcomes are fluorescein break-up time, Schirmer’s I test, meibomian gland parameters and adverse events. Other measured outcomes include best-corrected visual acuity, intraocular pressure and compliance.Ethics and disseminationThe study protocol and any supplements used in conducting this trial have been approved by the Ethics Committee of Faculty of Medicine, Ramathibodi Hospital, Mahidol University (MURA2020/1930). Informed consent will be obtained from all patients before study entry. Results will be presented in peer-reviewed journals and international conferences.Trial registration numberNCT04683796.

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