scholarly journals Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1366
Author(s):  
Tzu-Yang Chen ◽  
Ching-Li Tseng ◽  
Chih-An Lin ◽  
Hua-Yang Lin ◽  
Parthiban Venkatesan ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Dry Eye ◽  
Goblet Cell ◽  
Corneal Epithelium ◽  
Benzalkonium Chloride ◽  
Immunofluorescent Staining ◽  
Prolonged Treatment ◽  
Eye Drops ◽  
Cell Recovery ◽  
Anti Inflammatory

Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompatibility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis®, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Importantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical application. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E2 (PGE2) in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES.

scholarly journals A Meta-Analysis of the Efficacy of Hyaluronic Acid Eye Drops for the Treatment of Dry Eye Syndrome

2021 ◽  
Vol 18 (5) ◽  
pp. 2383
Author(s):  
Yun-Jung Yang ◽  
Won-Young Lee ◽  
Young-jin Kim ◽  
Yeon-pyo Hong
Keyword(s):  
Hyaluronic Acid ◽  
Confidence Interval ◽  
Dry Eye ◽  
Test Scores ◽  
Meta Analysis ◽  
Mean Difference ◽  
Dry Eye Syndrome ◽  
Eye Drops ◽  
Cochrane Central Register ◽  
Standard Mean Difference

Hyaluronic acid (HA) is commonly used for treating dry eye syndrome (DES). This meta-analysis was performed to compare the efficacies of HA- and non-HA-based eye drops, including saline and conventional artificial tears (ATs), for the treatment of dry eye disease. Eight databases (PubMed, EMBASE, Cochrane Central Register of Controlled Trials, DBpia, KoreaMed, KMBASE, RISS, KISS) were searched for studies comparing the efficacies of HA- and non-HA-based ATs in patients with DES published up to September 2020. Two independent reviewers assessed the quality and extracted the relevant data. The mean differences of Schirmer’s (SH) test scores, tear breakup times (TBUT), corneal fluorescein staining scores (Oxford scale, 0–4), and ocular surface disease indexes were calculated. The standard mean difference and 95% confidence interval were calculated using a random effect model. Nineteen studies, including 2078 cases, were included. HA eye drops significantly improved tear production compared with non-HA-based eye drops (standard mean difference (SMD) 0.18; 95% confidence interval (CI) 0.03, 0.33). In a subgroup analysis, the SH test scores and TBUT values after using HA significantly increased compared to those measured after using saline (SMD 0.27; 95% CI 0.05, 0.49 and SMD 0.28; 95% CI 0.03, 0.52, respectively). Based on these results, HA eye drops may be superior to non-HA eye drops including normal saline and ATs. Further research is needed to assess the efficacies stratified by age, treatment duration, the severity of dry eye, and optimal dosages.

scholarly journals The Effects of High Molecular Weight Hyaluronic Acid Eye Drop Application in Environmental Dry Eye Stress Model Mice

2020 ◽  
Vol 21 (10) ◽  
pp. 3516 ◽  
Author(s):  
Takashi Kojima ◽  
Taeko Nagata ◽  
Haruka Kudo ◽  
Wolfgang G. K. Müller-Lierheim ◽  
Gysbert-Botho van Setten ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Hyaluronic Acid ◽  
High Molecular Weight ◽  
Dry Eye ◽  
Ophthalmic Solution ◽  
Low Molecular Weight ◽  
Eye Drops ◽  
Office Work ◽  
Lissamine Green ◽  
Inflammatory Effect

Hyaluronic acid (HA) ophthalmic solution is widely used in dry eye treatment worldwide. However, there are no reports comparing the dry eye treatment effects of high molecular weight HA with low molecular weight HA. Sixty eight-week-old C57BL/6 mice were assigned to the following 6 groups and exposed to environmental dry eye stress (EDES) that mimics office work environment: (1) 0.1% low molecular weight HA (LMWHA) eye drops, (2) 0.3% LMWHA eye drops, (3) 3% diquafosol sodium (DQ) eye drops, (4) 0.15% high molecular weight HA (HMWHA) eye drops, (5) no treatment with exposure to EDES (EDES+/Treatment−), and (6) no treatment without exposure to EDES (EDES−/Treatment−). After EDES, the HMWHA group had significantly longer break-up time (BUT) than the 0.1%, 0.3% LMWHA groups and the DQ group. After EDES, the HMWHA group had significantly lower lissamine green staining scores than the LMWHA and DQ groups. Subepithelial presumed dendritic cell density in the HMWHA group was significantly lower than the EDES+/Treatment− group. After EDES exposure, Conjunctival Muc5AC mRNA expression in the HMWHA group was significantly higher than the 0.1 and 0.3% LMWHA groups. Ophthalmic HMWHA solution may have a better dry eye treatment effect than LMWHA or DQ solution, owing to its anti-inflammatory effect.

scholarly journals Efficacy of the Mineral Oil and Hyaluronic Acid Mixture Eye Drops in Murine Dry Eye

2015 ◽  
Vol 29 (2) ◽  
pp. 131 ◽  
Author(s):  
Jung Han Choi ◽  
Jung Han Kim ◽  
Zhengri Li ◽  
Han Jin Oh ◽  
Kyu Youn Ahn ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Dry Eye ◽  
Mineral Oil ◽  
Acid Mixture ◽  
Eye Drops

scholarly journals Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro

2021 ◽  
pp. 69-75
Author(s):  
Anne Hedengran ◽  
Xenia Begun ◽  
Olivia Müllertz ◽  
Zaynab Mouhammad ◽  
Rupali Vohra ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Goblet Cell ◽  
Benzalkonium Chloride ◽  
Goblet Cells ◽  
Eye Drops ◽  
Dependent Manner ◽  
The Impact ◽  
Conjunctival Goblet Cells

<b><i>Introduction:</i></b> Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. <b><i>Methods:</i></b> Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol<sup>®</sup> (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. <b><i>Results:</i></b> All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; <i>p</i> = 0.93), 71% for DS (0.0075% BAK; <i>p</i> = 0.067), 70% for OP (0.01% BAK; <i>p</i> = 0.054), and 69% for LT (0.02% BAK; <i>p</i> = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (<i>p</i> = 0.217), 52% for DS (<i>p</i> = 0.011), 34% for OP (<i>p</i> = 0.017), and 31% for LT (<i>p</i> = 0.0007). <b><i>Conclusion:</i></b> LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.

scholarly journals Efficacy of hyaluronic acid 0.3%, cyanocobalamin, electrolytes, and P-Plus in menopause patients with moderate dry eye disease

2021 ◽  
Author(s):  
Concepción De-Hita-Cantalejo ◽  
María Carmen Sánchez-González ◽  
Carmen Silva-Viguera ◽  
Marta C. García-Romera ◽  
Ricardo Feria-Mantero ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Vitamin B12 ◽  
Dry Eye ◽  
Meibomian Gland ◽  
Dry Eye Disease ◽  
Eye Disease ◽  
Eye Drops ◽  
Phenol Red ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

Abstract Purpose To study the treatment efficacy of hyaluronic acid 0.3%, cyanocobalamin (vitamin B12), electrolytes, and P-Plus in menopausal patients with moderate dry eye disease. Methods Thirty female patients of mean age 53.06 ± 5.20 years (45–65) were enrolled in this prospective longitudinal study. Meibomian gland loss assessment was determined using a scale with four levels. The Ocular Surface Disease Index (OSDI) questionnaire, phenol red thread (PRT) test, and tear film break-up time (TFBUT) were also completed by the patients. Tear eye drops were formulated with 0.3 g of sodium hyaluronate, P-Plus ™, vitamin B12, sodium chloride, potassium chloride, calcium chloride, magnesium chloride, and SCO® (stabilized complex oxychloride). After 30 days, the patients were re-evaluated. Results The mean meibomian gland loss percentage was 37.97 ± 19.02 % (7.20 to 88.30%). Before treatment, the OSDI was 22.53 ± 14.03 score points (6.25 to 77.08). Posterior OSDI decreased to 16.26 ± 13.69 score points (0.00 to 70.83) (W = 58.00, P < 0.01). Before treatment, PRT was 10.31 ± 4.48 mm (4.00 to 21.00). Posterior PRT increased to 15.41 ± 6.27 mm (4.00 to 21.00) (W = 1520.50, P < 0.01). Before treatment, TFBUT was 6.23 ± 1.75 s (3.00 to 9.00). The posterior TFBUT increased to 8.10 ± 2.06 s (4.00 to 14.00) (W= 1382.50, P < 0.01). Conclusion The hyaluronic acid 0.3% and vitamin B12 eye drops effectively decreased dry eye symptoms in menopausal women and improved tear stability and volume.

scholarly journals Anti‑inflammatory effects of glycine thymosin�β4 eye drops in experimental dry eye

2020 ◽  
Author(s):  
Rujun Jin ◽  
Ying Li ◽  
Lan Li ◽  
Dong Hwan Kim ◽  
Che Dong Yang ◽  
...  
Keyword(s):  
Dry Eye ◽  
Eye Drops ◽  
Thymosin Β4 ◽  
Anti Inflammatory

scholarly journals Current treatment modalities for dry eye disease

2021 ◽  
Vol 21 (1) ◽  
pp. 18-23
Author(s):  
E.B. Tatarnikova ◽  
◽  
O.I. Krivosheina ◽  
Keyword(s):  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Current Treatment ◽  
Dry Eye Disease ◽  
Treatment Modalities ◽  
Eye Disease ◽  
Published Data ◽  
Eye Drops ◽  
Anti Inflammatory

For many years, dry eye disease (DED) is a common ophthalmic condition associated with ocular surface damage and loss of homeostasis of the tear film. The key pathogenic factors of DED are tear film instability and tear hyperosmolarity, ocular surface inflammation and damage, and neurosensory alterations. Current treatment for DED consists of non-medical therapies, tear substitutes, anti-inflammatory agents, and surgical procedures. These treatments improve disease course and quality of life. However, these treatments are largely palliative as long-term (and even life-long) installation of eye drops is required. Modern and effective treatments for DED are needed. This paper reviews domestic and foreign published data on the important therapies for DED and novel tools to promote symptom relief. These data are required for the understanding of the pharmacological effects of various drug classes prescribed for DED and early treatment initiation. Keywords: dry eye disease, tear replacement therapy, anti-inflammatory treatment, surgery, hyaluronic acid, preservatives. For citation: Tatarnikova E.B., Krivosheina O.I. Current treatment modalities for dry eye disease. Russian Journal of Clinical Ophthalmology. 2021;21(1):18–23. DOI: 10.32364/2311-7729-2021-21-1-18-23.

scholarly journals Astragalus Ⅳ ameliorates the dry eye injury in rabbit model via MUC1-ErbB1 pathway

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Li Chu ◽  
Suhong Ma ◽  
Zhiwei Chen ◽  
Wenfu Cao
Keyword(s):  
Dry Eye ◽  
Rabbit Model ◽  
Immunofluorescent Staining ◽  
Bulbar Conjunctiva ◽  
Therapeutic Effects ◽  
Eye Drops ◽  
Protective Agent ◽  
Model Group ◽  
Astragaloside Iv ◽  
Schirmer Tear Test

The therapeutic effects and potential mechanisms of astragaloside IV on a rabbits dry eye model induced by benzalkonium chloride (BAC) was examined. In our study, a BAC-induced dry eye rabbit model was treated with eye drops containing astragaloside IV (5, 10 μM) or solvent four times a day. The clinical evaluations, such as tear break-up time (BUT) and Schirmer tear test (STT), were performed on days 0, 7, 14, 21, and 28. On day 28, the cornea and bulbar conjunctiva tissues (left eye and right eye) were collected with histology, and immunofluorescent staining conducted. The levels of MUC1 and ErbB1in the corneas were determined by real-time quantitative PCR (qRT-PCR) and the proteins levels of MUC1 and ErbB1 were detected by Western blot. It was demonstrated that both astragaloside IV (5, 10 μM) treatments resulted in an increased STT and BUT on days 7, 14, 21 and 28. Additionally, the astragaloside IV (5, 10 μM)-treated group showed increasing PAS-positive goblet cells than model group (0 μM). Moreover, the MUC1 in model group (0 μM) was decreased, while the expression of MUC1 in astragaloside IV (5, 10 μM) group was increased. Furthermore, astragaloside IV had a protective effect on BAC-induced rabbits’ dry eye and demonstrated clinical improvements, which indicated that astragaloside IV served as a potential protective agent in the clinical treatment of dry eye.

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