Dataset Information

The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

ABSTRACT: Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet-Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from in vivo confocal microscopy images before and 3 months after treatment were performed. Results: The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (P?

SUBMITTER: Simsek C

PROVIDER: S-EPMC6659741 | biostudies-literature | 2019 Jul/Aug

REPOSITORIES: biostudies-literature

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The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

Simsek Cem C Dogru Murat M Shinzawa Megumi M Den Seika S Kojima Takashi T Iseda Hiroyuki H Suzuki Mai M Shibasaki Yoshiyuki Y Yoshida Naoshi N Shimazaki Jun J

Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics 20190628 6

Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom sc ...[more]

PMID: 31259647

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Project description:Squamous metaplasia of the ocular surface epithelium in severe Sjögren syndrome (SS) dry eye has been implicated to be associated with chronic engagement of immune-mediated inflammation. While the detailed immunopathological mechanism underlying keratinization of the ocular muco-epithelium in this setting remains unclear, mice deficient in the autoimmune regulator gene (Aire) demonstrate SS-like pathological changes in the exocrine organs and ocular surface including squamous metaplasia. Using this murine model, we sought to determine the specific immune events that predict squamous metaplasia of the cornea in Aire deficiency.Lissamine green staining, goblet cell density, and corneal small proline-rich protein 1B (SPRR1B) were compared in Aire-sufficient and -deficient mice at 4, 8, and 16 weeks of age. Corneal, limbal and conjunctival infiltration of CD4(+) and CD8(+) T cells as well as CD11c(+) and MHC class II (I-A(d+)) dendritic cells (DCs) were examined at the same time points. Ordinary least squares regression was used to model SPRR1B's relationship with lissamine green staining, goblet cell density, and immune cell infiltration.Lissamine green staining was present in Aire-deficient mice by four weeks of age and increased over time. Compared to Aire-sufficient controls, conjunctival goblet cell density (GCD) decreased and corneal SPRR1B increased in Aire-deficient mice with significant differences noted at both 8 and 16 weeks. Immune-mediated CD4(+) T cell infiltration of the conjunctiva and limbus peaked at eight weeks and then decreased. In contrast, corneal T cell infiltration continued to increase over time, reaching a maximum cell number at 16 weeks. CD11c(+) myeloid-derived DCs were found in the conjunctiva and limbus at all time points. As the mice aged, there was a notable increase in corneal CD11c(+) cell counts. Interestingly, the dynamic of activated MHC class II(+) DCs was nearly identical to that of CD4(+) T cells, peaking first in the limbus at eight weeks with maximum infiltration of the cornea by 16 weeks. Regression analysis showed that squamous metaplasia biomarker, SPRR1B, is strongly related to the lissamine green staining of the ocular surface. Corneal infiltration of activated DCs was most prognostic of corneal SPRR1B expression while the presence of precursor DCs, activated DCs, and CD4(+) T cells in the limbus were also significant predictors of SPRR1B.Aire-deficient mice represent a useful model to study Sjögren-like autoimmune-mediated ocular surface disease. Results of the current study suggest that squamous cell precursor protein, SPRR1B, provides an important readout to evaluate ocular surface damage and specific events related to immune-mediated inflammation. Results also define an appropriate time frame for interventional studies to develop more effective therapies for keratinizing ocular surface disease.

Project description:IntroductionDry eye disease is characterized by a persistently unstable or deficient tear film causing discomfort or visual impairment. Varenicline is a small-molecule nicotinic acetylcholine receptor agonist recently approved for use as a preservative-free nasal spray (OC-01 [varenicline solution] nasal spray [OC-01 VNS]) to treat signs and symptoms of dry eye disease, but its effect on conjunctival goblet cells has not been studied.MethodsIn this phase 2, single-center, vehicle-controlled study, patients aged 18 years or more with a diagnosis of dry eye disease and Ocular Surface Disease Index© score of at least 23 were randomized 2:1 to receive a 50-µL single dose of OC-01 0.06 mg VNS or vehicle nasal spray in each nostril. Image assessments for area and perimeter were performed pre and 10 min post treatment for goblet cells by in vivo confocal microscopy and for meibomian glands by infrared meibography. Non-parametric Wilcoxon signed-rank test compared pre- and post-treatment measurements for each treatment group. Treatment-emergent adverse events (TEAEs) were assessed.ResultsThe study randomized 18 patients (mean age 61 years); 6 received vehicle (3/6 [50%] female) and 12 patients received OC-01 VNS (11/12 [92%] female). OC-01 VNS treatment decreased mean goblet cell area (pre-treatment, 106.4 µm2; post-treatment, 67.6 µm2; p = 0.02) and perimeter (pre-treatment, 38.9 µm; post-treatment, 31.2 µm; p = 0.03) but not vehicle did not (p = 0.25). There were no significant changes in mean meibomian gland area with either treatment (p ≥ 0.05). All TEAEs were non-ocular, non-serious, and mild.ConclusionsThis study demonstrated that a single administration of OC-01 0.06 mg VNS in patients with dry eye disease reduced conjunctival goblet cell area and perimeter, suggesting goblet cell degranulation and associated release of lubricating mucin. By activating the natural tear film, OC-01 VNS may provide benefits over topical medications.Trial registrationClinicalTrials.gov, NCT03688802.

Dataset Information

The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

Publications

The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

Similar Datasets

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