Treatment Of Dry Eye Syndrome Research Articles

Improving the topical ocular pharmacokinetics of lyophilized cyclosporine A-loaded micelles: formulation, in vitro and in vivo studies

Dry eye syndrome (DES) is one of the most common disorders of the eye for which combined treatment includes modification of the ocular environment and pathogenic therapies. Cyclosporine A (CsA), a immunosuppressive agent, has been demonstrated to be effective for the treatment of DES but is limited clinically by its low ocular bioavailability due to poor water solubility. In this paper, methoxy poly (ethylene glycol)-poly (lactide) polymer (mPEG-PLA) micelles were investigated as alternative vehicles for the solubilization and delivery of CsA to the eye. The in vitro stability indicated that CsA-loaded micellar lyophilized powder was stable for at least 3 months and the release profile showed a sustained release manner of CsA from micelles physically. In vivo ocular distribution studies demonstrated that the micellar formulations exhibited a 4.5-fold increase in retention effect at eyes compared with 0.05% CsA emulsion. In addition, the in vivo pharmacokinetics profile showed that the CsA-loaded micelles could enhance the retention time, achieving longer effect toward the DES. These studies proposed an effective micelle formulation as a novel ocular drug delivery system to improve solubility and bioavailability of ophthalmic CsA-controlled delivery.

Особенности терапии синдрома «сухого глаза»

Особенности терапии синдрома «сухого глаза»

The effect of rebamipide ophthalmic suspension on ocular surface mucins in soft contact lens wearers.

To evaluate the changes in ocular surface mucins with 2%rebamipide ophthalmic suspension treatment in soft contact lens (SCL) wearers. Rebamipide suspension is a mucin secretagogue approved for the treatment of dry eye syndrome in Japan. In this study, the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) was used as a marker of membrane-associated mucins, and sialic acid concentration in tear fluids as a marker of secreted mucins. Thirty-two eyes of 16 SCL wearers with discomfort were treated with rebamipide suspension at a dose of one drop in each eye four times daily for two weeks. The parameters of clinical efficacy were tear break-up time, fluorescein staining scores for the cornea and conjunctiva, and Schirmer test values. Fluorescence intensities in the central cornea were measured by fluorophotometry after the application of 5% F-WGA solution. Tears collected by Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of sialic acid, total protein, and the four major tear proteins, namely secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured. Significant increases in F-WGA fluorescence intensities (p < 0.005) were seen in the corneal surfaces. Sialic acid concentrations increased over time; however, the differences were not statistically significant. Except for a slight increase in kerato-conjunctival staining scores (p < 0.05) and secretory IgA (p < 0.05), no other significant differences were seen among clinical parameters or tear proteins. Topical application of rebamipide suspension significantly increased F-WGA intensity, a marker of membrane-associated mucins in SCL wearers.

A Prospective, Randomized Trial of Two Mucin Secretogogues for the Treatment of Dry Eye Syndrome in Office Workers

The purpose of the study was to compare the two mucin secretogogues, diquafosol (DQS) and rebamipide (RBM), for the treatment of dry eye syndrome (DES) in office workers. Dry eye patients using computers for >4 h/day were randomly assigned treatment with either DQS or RBM. Main outcomes measures included changes in tear film break-up time (TBUT) and subjective symptoms assessed by the Dry Eye-Related Quality of Life Score (DEQS). The subjects had scheduled examinations at 0 and 4 weeks, and the examinations at 2 and 8 weeks were optional. Changes in keratoconjunctival fluorescein score and a patient satisfaction questionnaire were also recorded. Both groups showed significant improvements in the DEQS scores at 2, 4, and 8 weeks following the initiation of the study. Both groups showed significant increases in the TBUT at 2 and 4 weeks. No significant difference was found between the DQS and RBM groups at any time periods. Patients reported more comfort with the use of DQS compared with the use of RBM. No local or systemic side effects were noted. The results of the present study indicated that both DQS and RBM were effective for the treatment of DES in office workers.

Effect of pulsed laser light in patients with dry eye syndrome

Abstract Objectives The objective of this study was to determine the clinical benefits of pulsed light therapy for the treatment of Dry Eye Syndrome (DES) due to the decrease in aqueous tear production (aqueous deficient DES) and/or excessive tear evaporation (evaporative DES) due to Meibomian Gland Dysfunction (MGD). Methods A study was conducted on 72 eyes corresponding to 36 patients with DES. Out of these 72 eyes, 60 underwent refractive surgery (48 with femtosecond laser, 6 were operated with a mechanical microkeratome, and 6 with refractive photo-keratectomy[RPK], 6 treated with phacoemulsification, and 6 with no previous surgical treatment. Pulsed laser light (Intense Pulsed Light Regulated [IRPL®]) was use to stimulate the secretion of the Meibomian glands during 4 sessions, one every 15 days. Results Patients with aqueous deficient DES did not show any improvement. Eyes with no previous surgery and those treated with phacoemulsification and PRK had a favorable outcome. On the other hand, less conclusive results were observed in the eyes treated with excimer laser. Conclusions This treatment could be very helpful to treat evaporative DES produced by MGD. On the other hand, it is not helpful for those cases related to an isolated damage in the aqueous phase, or the mucin phase.

Autologous artificial tears used for treatment of dry eye syndrome in patients with chronic graft versus host disease.

Autologous artificial tears used for treatment of dry eye syndrome in patients with chronic graft versus host disease.

Evaluation of Decellularized Porcine Jejunum as a Matrix for Lacrimal Gland Reconstruction In Vitro for Treatment of Dry Eye Syndrome.

Dry eye syndrome (DES) can cause blindness in severe cases, but mainly palliative treatments exist. A tissue-engineered lacrimal gland (LG) could provide a curative treatment. We aimed to evaluate decellularized porcine jejunum (SIS-Muc) as a scaffold for porcine LG epithelial cells. To evaluate SIS-Muc as a potential scaffold, basement membrane proteins in SIS-Muc and native LG were compared (immunohistochemistry [IHC]). Porcine LG epithelial cells cultured on plastic were characterized (immunocytochemistry), and their culture supernatant was compared with porcine tears (proteomics). Epithelial cells were then seeded onto SIS-Muc in either a static (cell crown) or dynamic culture (within a perfusion chamber) and metabolic (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and secretory capacities (β-hexosaminidase assay), protein expression (IHC), and ultrastructure transmission electron microscopy (TEM) compared in each. Collagen IV and laminin were found in both native LG and SIS-Muc. When cultured on plastic, LG epithelial cells expressed pan-cytokeratin, Rab3D, HexA, and produced mucins, but lysozyme and lactoferrin expression was nearly absent. Some porcine tear proteins (lipocalin-2 and lactoferrin) were found in LG epithelial cell culture supernatants. When LG cells were cultured on SIS-Muc, metabolic and β-hexosaminidase activities were greater in dynamic cultures than static cultures (P < 0.05). In both static and dynamic cultures, cells expressed pan-cytokeratin, Rab3D, lysozyme, and lactoferrin and produced mucins, and TEM revealed cell polarization at the apical surface and cell-cell and cell-scaffold contacts. SIS-Muc is a suitable scaffold for LG cell expansion and may be useful toward reconstruction of LG tissue to provide a curative treatment for DES. Dynamic culture enhances cell metabolic and functional activities.

Experience in the Cationorm® use in the treatment of dry eye syndrome in patients after adenoviral keratoconjunctivitis

The dry eye syndrome ranges among widespread and persisting ophthalmic diseases. It is also called a disease of civilization. Among the causes particularly often leading to the dry eye syndrome adenoviral infection has to be listed. Over the last years, in Saint Petersburg, an increasing incidence rate of the epidemic adenoviral keratoconjunctivitis is noted, which is proceeding in severe membranous and infiltrative forms, involving the cornea. Occurring therewith secondary dry eye syndrome demands using effective medications. In the article, the experience in Cationorm (Santen, Japan) clinical use for secondary dry eye syndrome treatment is disclosed.

Protective effects of carbenoxolone, an 11β-HSD1 inhibitor, against chemical induced dry eye syndrome.

Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11β-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11β-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11β-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11β-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11β-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11β-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.

Omega-3 Supplement; A Comparison of Recommendations

Purpose: Research has shown Omega-3 supplementation can benefit dry eye patients. Our objective is to aid optometrists in the treatment of dry eye syndrome by summarizing the recommendations for oral Omega-3 supplements. Methods: We sent an online survey consisting of ten questions to optometrists affiliated with the Oklahoma Association of Optometric Physicians (OAOP) and the Facebook groups ODs on Facebook and Corporate Optometry to see if they are recommending Omega-3 supplements, which specific products, and at what dosage. Results: Ninety-five optometrists responded. 43.16% stated that their dry eye patients number between 26-50% of their practice. 60% responded they recommend Omega-3 supplements, and 37.89% said they tell their patients to increase their dietary fish intake and take Omega-3 supplements. 50% of eye care physicians responded that they sell dry eye supplements. When asked about how familiar optometrists are with the different forms of Omega-3 fatty acids, 30.85% stated they are very familiar, while 54.26% stated they are somewhat familiar and 14.89% stated they are not familiar at all with the differ-ent types. Conclusion: We found that the majority of optometrists who responded to our survey are recommending their patients consume between 1500-2000 milligrams of Omega-3’s per day for dry eye. Many health professionals uphold that at least 1,000 mg/day of EPA and DHA should be consumed to aid in improving systemic health. In the absence of stan-dards specifically for dry eye it is reasonable to base Omega-3 supplement recommenda-tions on those for systemic health.

Epigallocatechin Gallate-Loaded Gelatin-g-Poly(N-Isopropylacrylamide) as a New Ophthalmic Pharmaceutical Formulation for Topical Use in the Treatment of Dry Eye Syndrome

Given that biodegradable in situ gelling delivery systems may have potential applications in the design of ophthalmic pharmaceutical formulations, this study, for the first time, aims to develop gelatin-g-poly(N-isopropylacrylamide) (GN) carriers for topical epigallocatechin gallate (EGCG) administration in the treatment of dry eye disease (DED). By temperature triggered sol-gel phase transition of copolymers, EGCG-loaded GN was prepared at 32 °C and characterized by FTIR, NMR, and HPLC analyses. Results of WST-1 and live/dead assays showed that GN materials have good compatibility with corneal epithelial cells. Gradual biodegradation of delivery carriers allowed sustained release of EGCG without drug toxicity. Anti-inflammatory and antioxidant activity studies also indicated effective therapeutic drug levels at each time point within 3 days of release. In a rabbit dry eye model, corneal epithelial defects was ameliorated by treatment with single-dose administration of EGCG-containing GN. Furthermore, drug molecules released from carrier materials could prevent further tear evaporation and loss of mucin-secreting goblet cells in diseased animals. Our findings suggest that GN carrier is responsible for enhanced pharmacological efficacy of topically instilled EGCG, thereby demonstrating the benefits of using biodegradable in situ gelling delivery system to overcome the drawbacks of limited dry eye relief associated with eye drop dosage form.

Sodium Hyaluronate in the Treatment of Dry Eye Syndrome: A Systematic Review and Meta-Analysis

This systematic review and meta-analysis compares sodium hyaluronate (HY) with non-HY based artificial tears in the treatment of dry eye syndrome. A literature search for clinical trials comparing HY against non-HY preparations was conducted across PubMed, Cochrane Central Register of Controlled Trials and Scopus databases from inception up to May 2016. Majority of the 18 studies selected for review showed superiority of HY in improving ocular staining and symptoms. Randomized controlled trials (RCTs) examining Schirmer’s I (SH) and tear breakup time (TBUT) underwent further meta-analyses with calculation of pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs). 7 RCTs including 383 eyes randomized to HY and 596 eyes to non-HY preparations underwent meta-analysis for SH. 9 RCTs including 458 eyes randomized to HY and 651 eyes to non-HY preparations underwent meta-analysis for TBUT. By fixed-effects modelling, HY demonstrated greater improvement of SH compared to non-HY preparations (SMD, 0.238; 95% CI, 0.107 to 0.369; p < 0.001). By random-effects modelling, HY demonstrated less improvement of TBUT (SMD, −0.566; 95% CI, −1.099 to −0.0336; p = 0.037). In summary, neither preparation was shown to be consistently superior across all outcome measures. The difference in effect between preparations on SH and TBUT was not clinically significant.

Herbal Supplement in a Buffer for Dry Eye Syndrome Treatment.

Dry eye syndrome (DES) is one of the most common types of ocular diseases. There is a major need to treat DES in a simple yet efficient way. Artificial tears (AT) are the most commonly used agents for treating DES, but are not very effective. Herbal extractions of ferulic acid (FA), an anti-oxidant agent, and kaempferol (KM), an anti-inflammatory reagent, were added to buffer solution (BS) to replace ATs for DES treatment. The cytotoxicity and anti-inflammatory effects were examined in vitro by co-culture with human corneal epithelial cells (HCECs) to obtain the optimal concentration of KM and FA for treating HCECs. Physical properties of BS, such as pH value, osmolality, and refractive index were also examined. Then, rabbits with DES were used for therapeutic evaluation. Tear production, corneal damage, and ocular irritation in rabbits’ eyes were examined. The non-toxic concentrations of KM and FA for HCEC cultivation over 3 days were 1 µM and 100 µM, respectively. Live/dead stain results also show non-toxicity of KM and FA for treating HCECs. Lipopolysaccharide-stimulated HCECs in inflammatory conditions treated with 100 µM FA and 1 µM KM (FA100/KM1) showed lower IL-1B, IL-6, IL-8, and TNFα expression when examined by real-time PCR. The BS with FA100/KM1 had neutral pH, and a similar osmolality and refractive index to human tears. Topical delivery of BS + FA100/KM1 showed no irritation to rabbit eyes. The corneal thickness in the BS + FA100/KM1 treated group was comparable to normal eyes. Results of DES rabbits treated with BS + FA100/KM1 showed less corneal epithelial damage and higher tear volume than the normal group. In conclusion, we showed that the combination of FA (100 µM) and KM (1 µM) towards treating inflamed HCECs had an anti-inflammatory effect, and it is effective in treating DES rabbits when BS is added in combination with these two herbal supplements and used as a topical eye drop.

Evaluation of Clinical Efficacy and Safety of a Novel Cyclosporin A Nanoemulsion in the Treatment of Dry Eye Syndrome.

Topical administration of the anti-inflammatory agent cyclosporin A (CsA) is recommended for long-term management of dry eye syndrome (DES), yet standard ophthalmic CsA preparations have been reported to be unstable. In this trial, the efficacy and safety of Clacier™ (based on a phase 3 study developed by Huons Co. Ltd.), a novel 0.05% CsA nanoemulsion formulation, are compared with those of the conventional Restasis® emulsion. Patients with moderate-to-severe DES were randomly assigned to receive topical 0.05% CsA in the form of Clacier or Restasis, to be administered twice daily for 12 weeks. The primary efficacy outcome was the change from baseline in corneal fluorescein staining scores at week 12; changes at weeks 4 and 8 were secondary endpoints. Additional endpoints included score changes from baseline in nonanesthetic Schirmer's test I, tear breakup time, ocular surface disease index, and conjunctival staining. At week 12, corneal staining scores were improved in patients treated with Clacier and Restasis, with no significant difference between treatments (P = 0.41). Temporal conjunctival surface damage was significantly more ameliorated with Clacier treatment than with Restasis treatment (P = 0.034). Notably, tear film stability was improved more rapidly in Clacier patients at week 4 (P = 0.005) than in Restasis patients (P = 0.36). Improvements in tear production were comparable with both Clacier and Restasis treatments. Clacier did not increase the risk of adverse events as compared with Restasis. Treatment with Clacier alleviated clinical signs and symptoms of DES comparably to the commercially available Restasis, resulting in improved quality of life for patients. Clacier is an effective and safe therapeutic agent for DES.

Fingerprick autologous blood: a novel treatment for dry eye syndrome.

PurposeDry eye syndrome (DES) causes significant morbidity. Trials of blood-derived products in treatment of the condition show promising results. However, their production is expensive and time-consuming. We investigate fingerprick autologous blood (FAB) as an alternative low-cost, readily accessible treatment for DES.Patients and methodsProspective, non-comparative, interventional case series. In total, 29 eyes of 16 DES patients (2 males and 14 females) from two NHS sites in the United Kingdom. Patients instructed to clean a finger, prick with a blood lancet, and apply a drop of blood to the lower fornix of the affected eye(s), 4 times daily for 8 weeks then stop and review 4 weeks later. Follow-up visits occurred ~3 days, 2, 4, 8 weeks into therapy, and 4 weeks post-cessation. At each visit, visual acuity, corneal staining, Schirmer's test, tear break-up time (TBUT), and ocular comfort index (OCI) were measured, and photographs taken. Results were analysed using Student's paired t-test.ResultsAt 8 weeks, there was improvement in mean Oxford corneal staining grade (3.31 to 2.07 (P<0.0001)), TBUT (5.00 to 7.80 s (P<0.05)), visual acuity (0.08 to 0.01 LogMAR equivalent (P<0.05)), and OCI score (56.03 to 39.72 (P<0.0001)). There was no statistically significant change in Schirmer's test results. Four weeks post-cessation versus immediately after completion of FAB therapy, mean staining grade worsened from 2.07 to 2.86 (P<0.0001). OCI score worsened from 39.72 to 44.67 (P<0.05).ConclusionsIn our limited case series FAB appears to be a safe and effective treatment for DES.

THE CLINICAL CASES OF KERATOCONJUNCTIVITIS ENCOUNTERED IN THE PEDIATRIC PATIENTS PRESENTING WITH ATOPIC DERMATITIS

The eye damage in the children presenting with atopic dermatitis is known to occur in 20-40% of the cases. The nonspecific nature of the ophthalmological symptoms of this pathology markedly complicates differential diagnostics and the choice of the pathogenetically-based therapeutic modalities. This article describes the clinical cases that demonstrate the seriousness of this problem and illustrate the necessity of the comprehensive interdisciplinary approach to its solution. It is concluded that the use of the “Restasis” pharmaceutical for the treatment of dry eye syndrome associated with atopic dermatitis in the young patients is justified as contributing to a stable remission of the disorder and producing no undesirable side effects.

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.

This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES). This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17 patients were randomized to receive C-NAC eye drops once (QD) or twice (BID) daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution optical coherence tomography system. In Cohort I, mean TFT increased from 3.9 ± 0.5 μm predose to 4.8 ± 1.1 μm 10 min postdose after treatment with C-NAC. The increase was significantly different from placebo over time (P < 0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with QD and BID instillation, with no significant difference between regimens. In both groups, Ocular Surface Disease Index scores improved, fewer patients presented with corneal damage, and symptoms of ocular discomfort/conjunctival redness were reduced. A single instillation of C-NAC significantly increased mean TFT in patients with DES as early as 10 min after instillation and lasted for 24 h. The magnitude of the increase in TFT following a single instillation was comparable with that after instillation twice daily over 5 days. Corneal damage improved in >60% of patients. C-NAC could be a viable treatment option for DES.

Efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids in dry eye syndrome: a systematic review of randomized clinical trials.

To critically appraise scientific evidence regarding the efficacy of nutritional supplementation with omega-3 and omega-6 fatty acids for the treatment of dry eye syndrome (DES). A systematic review of randomized clinical trials was performed. Two independent reviewers selected and analysed the scientific papers that met inclusion and exclusion criteria. Objective and subjective efficacy outcomes were assessed. The trials involved a total of 2591 patients in fifteen independent studies. All studies were published between 2005 and 2015. The supplements used were mostly omega-3 and omega-6 in different proportions. Subjective improvement was measured using mainly Ocular Surface Disease Index (OSDI) test and Dry Eye Severity Score (DESS) test: significant differences in favour of the experimental group were found in seven of the studies. The objective amelioration was assessed by lacrimal function parameters: Tear break-up time (TBUT) significantly increased in nine studies and Schirmer's test in four studies. We observed a discrete improvement in the parameters of tear function. Scientific evidence is not strong enough to systematically recommend the use of omega-3 and omega-6 fatty acids as a standalone treatment of DES independently from its aetiology. However, they could be considered as an effective alternative to topical treatment in patients with DES secondary to certain pathologies.

Efecto del láser de luz pulsada en pacientes con síndrome de ojo seco

ObjectivesThe objective of this study was to determine the clinical benefits of pulsed light therapy for the treatment of Dry Eye Syndrome (DES) due to the decrease in aqueous tear production (aqueous deficient DES) and/or excessive tear evaporation (evaporative DES) due to Meibomian Gland Dysfunction (MGD). MethodsA study was conducted on 72 eyes corresponding to 36 patients with DES. Out of these 72 eyes, 60 underwent refractive surgery (48 with femtosecond laser, 6 were operated with a mechanical microkeratome, and 6 with refractive photo-keratectomy[RPK], 6 treated with phacoemulsification, and 6 with no previous surgical treatment. Pulsed laser light (Intense Pulsed Light Regulated [IRPL®]) was use to stimulate the secretion of the Meibomian glands during 4 sessions, one every 15 days. ResultsPatients with aqueous deficient DES did not show any improvement. Eyes with no previous surgery and those treated with phacoemulsification and PRK had a favourable outcome. On the other hand, less conclusive results were observed in the eyes treated with excimer laser. ConclusionsThis treatment could be very helpful to treat evaporative DES produced by MGD. On the other hand, it is not helpful for those cases related to an isolated damage in the aqueous phase, or the mucin phase.

Design and optimization of a novel implantation technology in contact lenses for the treatment of dry eye syndrome: In vitro and in vivo evaluation.

The limitation of contact lenses to be used as therapeutic device for controlled drug delivery is focused in this study. Incorporation of drug or formulation in the biomaterial affects the optical and physical property of contact lenses. The significance of project was to design a novel hyaluronic acid-laden ring implant contact lenses, to by-pass the changes in critical property of biomaterial.