Fluorometholone inhibits high glucose-induced cellular senescence in human retinal endothelial cells.

Diabetic retinopathy (DR) is a common diabetic complication that severely impacts the life quality of diabetic patients. Recently, cellular senescence in human retinal endothelial cells (HRECs) induced by high glucose has been linked to the pathogenesis of DR. Fluorometholone (FML) is a glucocorticoid drug applied in the treatment of inflammatory and allergic disorders of the eye. The objective of the present study is to investigate the protective function of FML on high glucose-induced cellular senescence in HRECs. The in vitro injury model was established by stimulating HRECs with 30 mm glucose. After evaluating the cytotoxicity of FML in HRECs, 0.05% and 0.1% FML were used as the optimal concentration in the entire experiment. It was found that the excessive released inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8) in HRECs induced by high glucose were significantly suppressed by FML, accompanied by the inhibitory effects on the expression levels of vascular endothelial growth factor (VEGF) and tissue factor (TF). Declined telomerase activity and enhanced senescence-associated ß-galactosidase (SA-ß-gal) activity were found in high glucose-challenged HRECs, which were dramatically alleviated by FML, accompanied by the inactivation of the p53/p21 and retinoblastoma (Rb) signaling. Interestingly, FML ameliorated high glucose-induced dephosphorylation of Akt. Lastly, the protective effects of FML against high glucose-induced cellular senescence in HRECs were abolished by the co-treatment of the PI3K/Akt signaling inhibitor LY294002, suggesting the involvement of this pathway. Taken together, these data revealed that FML-inhibited high glucose-induced cellular senescence mediated by Akt in HERCs, suggesting a novel molecular mechanism of FML.

Ocular Physiologically Based Pharmacokinetic Modeling for Ointment Formulations.

PURPOSE: The purpose of this study is to show how the Ocular Compartmental Absorption & Transit (OCAT™) model in GastroPlus® can be used to characterize ocular drug pharmacokinetic performance in rabbits for ointment formulations. METHODS: A newly OCAT™ model developed for fluorometholone, as well as a previously verified model for dexamethasone, were used to characterize the aqueous humor (AH) concentration following the administration of multiple ointment formulations to rabbit. The model uses the following parameters: application surface area (SA), a fitted application time, and the fitted Higuchi release constant to characterize the rate of passage of the active pharmaceutical ingredient from the ointment formulations into the tears in vivo. RESULTS: Parameter sensitivity analysis was performed to understand the impact of ointment formulation changes on ocular exposure. While application time was found to have a significant impact on the time of maximal concentration in AH, both the application SA and the Higuchi release constant significantly influenced both the maximum concentration and the ocular exposure. CONCLUSIONS: This initial model for ointment ophthalmic formulations is a first step to better understand the interplay between physiological factors and ophthalmic formulation physicochemical properties and their impact on in vivo ocular drug pharmacokinetic performance in rabbits.

Long-term Outcomes on de novo Ocular Hypertensive Response to Topical Corticosteroids After Corneal Transplantation.

PURPOSE: To determine incidence, demographics, management, and outcomes of topical steroid-induced ocular hypertension after penetrating keratoplasty (PKP) and to establish effects on intraocular pressure (IOP) and graft rejection when alternate corticosteroids are used. METHODS: A single-center, retrospective review of 568 consecutive PKPs performed between 1997 and 2010 was conducted. Data were collected on demographics, best-corrected visual acuity, surgical indications, lens status, IOP, postoperative management, and incidence of rejection. RESULTS: Eighty eyes (14.1%) of 74 patients were included. The most common indication was keratoconus (28.8%). Twenty-seven eyes (33.8%) were phakic, 46 (57.4%) had a posterior chamber intraocular lens, and 7 (8.8%) had an anterior chamber intraocular lens. Mean postoperative IOP increase was only significant in the anterior chamber intraocular lens group (18.7 mm Hg, SD 10.4; P = 0.02). The average time for developing hypertension was 9.8 months (SD 14.8) postoperatively, with an average IOP increase of 13.3 mm Hg (SD 5.9). Prednisolone acetate 1% was switched to rimexolone 1% in 64 eyes (80%) and to fluorometholone 0.1% in 16 eyes (20%), which alone achieved IOP normalization in 26 eyes (32.5%) (P < 0.01). Fifty-four eyes (67.5%) required additional antiglaucoma medication. An average IOP reduction of 12.3 mm Hg (SD 6.9) was achieved at an average of 2.3 months (SD 5.2) after the switch. Seventeen eyes (21%) developed glaucoma and 13 eyes (16.3%) developed graft rejection after switching formulations, with no statistically significant differences between rimexolone and fluorometholone (P > 0.05). CONCLUSIONS: The use of alternate topical corticosteroids may be considered in cases of steroid-induced ocular hypertension after PKP because they offer good antiinflammatory prophylaxis with reduced hypertensive response.

Efficacy and Safety of Loteprednol 0.5% and Fluorometholone 0.1% After Strabismus Surgery in Children.

PURPOSE: To compare the effects of topical loteprednol and fluorometholone in children who underwent strabismus surgery. METHODS: This is a retrospective observational case series. A total of 60 Korean children who underwent strabismus surgery between January 2016 and September 2016 were included. Patients were prescribed topical loteprednol etabonate 0.5% or fluorometholone 0.1% until 3 weeks after surgery. Four parameters (intraocular pressure [IOP], conjunctival injection, conjunctival inflammation, and patient discomfort) were assessed every week for up to 4 weeks after surgery. Main outcome measures were comparison of parameters between the 2 groups at each following week after surgery. In addition, factors associated with clinically meaningful IOP elevation were evaluated. RESULTS: IOP was significantly elevated at the second and third postoperative week compared with baseline (P = 0.028 and 0.001) in the loteprednol group but not significantly in the fluorometholone group. The mean IOP of the loteprednol group at 1 and 3 weeks after surgery were significantly higher than that of the fluorometholone group (P = 0.032 and 0.017, respectively). Multivariate analysis revealed that age ≤8 years (odds ratio 14.52, 95% confidence interval 1.16-139.05) was associated with IOP >21 mmHg. There was no significant difference between the 2 groups in patient discomfort, conjunctival inflammation, and conjunctival injection. CONCLUSIONS: Loteprednol and fluorometholone showed similar anti-inflammatory effect after strabismus surgery in children. Loteprednol appeared to have more effect on IOP elevation than fluorometholone, especially in children ≤8 years of age. When treating young patients with loteprednol, clinicians should be aware of IOP elevation.

Development of fluorometholone-loaded PLGA nanoparticles for treatment of inflammatory disorders of anterior and posterior segments of the eye.

The main objective of this study was the development and optimization of fluorometholone-loaded PLGA nanoparticles for the treatment of inflammatory conditions of the eye. Design of experiments was used to obtain nanoparticles with the best physicochemical characteristics. The optimized nanoparticles containing 1.5 mg·mL-1 of fluorometholone showed a negative surface charge (-30 mV) and an average size below 200 nm being suitable for ocular administration. Drug-polymer interaction studies confirmed no new bonds were formed during the synthesis. Nanoparticles performance was assessed with biopharmaceutical behavior studies, ocular tolerance, anti-inflammatory efficacy and bioavailability. The biopharmaceutical behavior of the drug from nanoparticles was adjusted to hyperbola order showing a significantly greater permeation in the cornea than in the sclera. The optimized formulation had significantly greater anti-inflammatory effects than the commercial formulation. In addition, nanoparticles increased drug penetration toward the vitreous. Polymeric nanoparticles of fluorometholone could provide a suitable alternative for the treatment of inflammatory disorders of the anterior and posterior segments of the eye against of conventional topical formulations.

A Randomized Clinical Trial of Topical Diclofenac, Fluorometholone, and Dexamethasone for Control of Inflammation After Strabismus Surgery.

PURPOSE: To evaluate the comparative effects and safety of topical diclofenac sodium, fluorometholone, and dexamethasone for controlling inflammation after routine strabismus surgery. METHODS: This was a randomized clinical trial. Ninety-nine patients admitted for surgery to treat intermittent exotropia were randomly assigned to receive 1 of 3 postoperative eye drops between January 2015 and February 2016. The primary efficacy outcomes were pain and conjunctival injection. Pain score from 0 to 10 was evaluated in each patient at postoperative days 1, 2, 3, and 5, in addition to weeks 1, 2, and 4. Conjunctival injection was graded from 1 to 4 at postoperative weeks 1, 2, and 4. We also evaluated intraocular pressure (IOP), discomfort attributed to the drops, and development of any other side effects. RESULTS: Conjunctival injection grade was the lowest in the diclofenac sodium group at postoperative weeks 1 and 2 (P < 0.001 and P = 0.03). There was no significant difference in pain score among the 3 groups. Mean IOP was the highest in the dexamethasone group at postoperative weeks 1, 2, and 4 (P < 0.001, P < 0.001, and P = 0.02). Significant IOP elevation (≥10 mmHg relative to preoperative IOP) was observed in 6 patients in the dexamethasone group. There was no difference in discomfort upon administration of the drops among the 3 groups, and no other adverse events developed. CONCLUSION: Diclofenac sodium was more effective against conjunctival injection than the 2 topical corticosteroids tested, but had a similar effect on postoperative pain as them. IOP elevation developed only in the dexamethasone group.

Steroid-induced ocular hypertension in the pediatric age group.

PURPOSE: Comparing the effects of topical Rimexolone versus Dexamethasone and Rimexolone versus Fluorometholone on the intraocular pressure in children <13 years. METHODS: A total of 40 patients (80 eyes) undergoing bilateral recession strabismus surgery were divided into two groups. Group A included 20 children (40 eyes); for each, one eye was randomized to receive 1% Rimexolone and the fellow eye received 0.1% Dexamethasone. Group B included 20 children (40 eyes); for each, one eye was randomized to receive 1% Rimexolone and the fellow eye received 0.1% Fluorometholone. Patients received eye drops for two consecutive weeks. Preoperative and postoperative intraocular pressure values for weeks 1, 2, 3, 4, and 6 were measured. The ocular-hypertensive response of all patients was categorized as either high, intermediate or low (Armaly-Becker Classification). RESULTS: After a 2-week treatment for both groups, peak and maximal intraocular pressure changes were reached. Changes were significantly higher in the Dexamethasone-treated eyes than in the Rimexolone- and Fluorometholone-treated eyes, which had a comparable change. (Week 2 intraocular pressure Group A: 14.15 ± 3.23 mmHg vs 17.95 ± 4.27 mmHg; Group B: 15.1 ± 2.27 mmHg vs 15.2 ± 2.73 mmHg). In both groups, the increase was statistically significant compared to the baseline intraocular pressure (preoperative intraocular pressure Group A: 13.2 ± 3.53 mmHg vs 13.1 ± 3.43 mmHg; Group B: 12.55 ± 2.98 mmHg vs 12.15 ± 3.31 mmHg). Intraocular pressure returned to near preoperative values over the following four consecutive weeks (Week 6 intraocular pressure Group A: 12.25 ± 2.67 mmHg vs 12.55 ± 2.95 mmHg; Group B: 12.15 ± 2.8 mmHg vs 12.00 ± 2.75 mmHg). None of the patients were high responders. CONCLUSION: Dexamethasone caused a higher elevation in intraocular pressure than Rimexolone and Fluorometholone in children. The ocular-hypertensive response was transient after the 2-week course.

Ocular Inflammation Associated with Polymyalgia Rheumatica without Concomitant Giant-Cell Arteritis: A Report of Three Cases.

PURPOSE: We report three cases of ocular inflammation and polymyalgia rheumatica without concomitant giant-cell arteritis. METHODS: Report of three cases. RESULTS: Polymyalgia rheumatica onset was at a mean age of 66.7 years, and ocular inflammation, which developed 7-21 months later, was bilateral in all patients. Ocular inflammation presented as episcleritis, scleritis, or anterior uveitis, and it emerged during the tapering of low-dose prednisolone prescribed for polymyalgia rheumatica in all patients. Recurrence of ocular inflammation was observed in two patients. CONCLUSIONS: Ocular inflammation associated with polymyalgia rheumatica was often bilateral and occurred during steroid tapering. Although this presentation is relatively uncommon, polymyalgia rheumatica should be considered in the differential diagnosis of older patients presenting with ocular inflammation, especially those with proximal myalgia and elevated inflammatory markers.

Dose Uniformity of Topical Corticosteroids: A Simulated Trial of Fluorometholone Acetate 0.1% and Loteprednol Etabonate Gel 0.5.

PURPOSE: The purpose of the study was to determine the concentrations of Flarex® and Lotemax® when shaken and not shaken. Many patients fail to shake or inappropriately shake suspensions of corticosteroids before instillation as directed. This study was designed to help determine what concentration of corticosteroid these patients are receiving. In addition, independent confirmation of loteprednol etabonate ophthalmic gel dose uniformity was determined and compared as a possible alternative. METHODS: Drug concentrations of shaken versus unshaken Flarex and Lotemax were determined over a 20-day simulated tapered course in our institutional laboratory. Collected samples were analyzed by reversed-phase high-performance liquid chromatography with photodiode array detection at 240 nm. RESULTS: Flarex had a mean concentration of 93.7% of the declared concentration when shaken and 7.25% when not shaken. The difference between these groups was statistically significant (P = 0.0001). Lotemax had a mean concentration of 96.74% of the declared concentration when shaken and a mean concentration of 98.97% when not shaken. The difference between these groups was not statistically significant (P = 0.194). CONCLUSIONS: Flarex maintains dose uniformity when shaken. When not shaken, it has poor dose uniformity. Lotemax was consistent whether shaken or not in our study and can be considered to eliminate the variability of poor patient compliance with shaking. The manufacturers of both drugs recommend shaking before application.

Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases.

PURPOSE: To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases. DESIGN: Open cohort study. PARTICIPANTS: Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791). METHODS: The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics. MAIN OUTCOME MEASURES: Changes in the corneal epitheliopathy score. RESULTS: Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus. CONCLUSIONS: The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.

Long-term follow-up of transplantation of preserved limbal allograft and amniotic membrane for recurrent pterygium.

PURPOSE: To conduct a long-term follow-up study evaluating the efficacy and safety of transplantation of preserved limbal allograft and amniotic membrane for recurrent pterygium. METHODS: This was a retrospective, non-comparative, interventional case series conducted at a private eye hospital. Eighty-four eyes of 80 patients with recurrent pterygium were included in the study. The mean number of previous surgeries for pterygium was 1.36 ± 0.98 (range, 1-8). All subjects received transplantation of preserved limbal allograft and amniotic membrane. RESULTS: The mean follow-up period was 73.0 ± 38.1 months (range, 12-154 months). Pterygium recurred in 10 eyes (11.9 %). The mean period to recurrence was 16.3 ± 11.3 months (range, 5-33 months). Symblepharon was cured in 21 eyes, persisted in 2 eyes, and newly occurred in 3 eyes. Diplopia was cured in eight eyes, persisted in five eyes, and newly occurred in one eye. As for complications, intraocular pressure elevations over 21 mmHg were recognized in ten eyes of nine cases, in which the intraocular pressure was controlled by reduction of topical steroid in four eyes and by addition of topical prostaglandin derivatives in six eyes. Twenty-four eyes (28.6 %) gained two lines or more of Landolt best spectacle-corrected visual acuity (BSCVA), 56 eyes (66.7 %) stayed within one line from preoperation, and four eyes (4.8 %) lost two lines or more. There were no major complications and no graft rejection. CONCLUSIONS: Transplantation of preserved limbal allograft and amniotic membrane is a safe and effective procedure for recurrent pterygium.

General Pharmacokinetic Model for Topically Administered Ocular Drug Dosage Forms.

PURPOSE: In ocular drug development, an early estimate of drug behavior before any in vivo experiments is important. The pharmacokinetics (PK) and bioavailability depend not only on active compound and excipients but also on physicochemical properties of the ocular drug formulation. We propose to utilize PK modelling to predict how drug and formulational properties affect drug bioavailability and pharmacokinetics. METHODS: A physiologically relevant PK model based on the rabbit eye was built to simulate the effect of formulation and physicochemical properties on PK of pilocarpine solutions and fluorometholone suspensions. The model consists of four compartments: solid and dissolved drug in tear fluid, drug in corneal epithelium and aqueous humor. Parameter values and in vivo PK data in rabbits were taken from published literature. RESULTS: The model predicted the pilocarpine and fluorometholone concentrations in the corneal epithelium and aqueous humor with a reasonable accuracy for many different formulations. The model includes a graphical user interface that enables the user to modify parameters easily and thus simulate various formulations. CONCLUSIONS: The model is suitable for the development of ophthalmic formulations and the planning of bioequivalence studies.

Efficacy of Intraductal Meibomian Gland Probing on Tear Function in Patients With Obstructive Meibomian Gland Dysfunction.

PURPOSE: To assess the efficacy and safety of intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction who experienced little improvement with eyelid warming, massage, or artificial tears. METHODS: Forty-nine patients with obstructive meibomian gland dysfunction were randomly divided into 2 groups: intraductal meibomian gland probing with 0.1% fluorometholone (group I), and 0.1% fluorometholone alone (group II). Subjective symptom scores and objective signs, including lid margin abnormalities, meibum quality and expressibility, meibomian gland dropout, fluorescein staining, tear break-up time (TBUT), and Schirmer I test results, were recorded before treatment and after 1 day, 1 week, and 1 month posttreatment. RESULTS: Clinical subjective symptoms and objective signs including meibum grade, TBUT, lid margin abnormalities, and fluorescein staining demonstrated significant improvements in both groups after treatment over time (all P < 0.05), and group I was better than group II 1 month after treatment in meibum grade (6.1 ± 3.3 vs. 10.4 ± 4.9, respectively; P < 0.001), lid margin abnormalities (0.8 ± 0.1 vs. 1.3 ± 0.3, respectively; P < 0.001), and TBUT (8.2 ± 2.1 vs. 7.0 ± 3.0, respectively; P = 0.0293). Before applying any medications, 76% of patients obtained immediate symptom relief 1 day after probing. However, the Schirmer I test results and meibomian gland dropout were insignificant pre- and posttreatment in either group (P > 0.1, respectively). CONCLUSIONS: Intraductal meibomian gland probing demonstrated significant efficacy in symptom relief and tear film stabilization. Probing helped release accumulated meibum and could help increase the accessibility of diseased meibomian glands to topical corticosteroids.

Descemet's Membrane Endothelial Keratoplasty: Risk of Immunologic Rejection Episodes after Discontinuing Topical Corticosteroids.

PURPOSE: To assess the risk of immunologic rejection episodes if topical corticosteroids are discontinued 1 year after Descemet's membrane endothelial keratoplasty (DMEK) compared with continued once-per-day use. DESIGN: Prospective, longitudinal, parallel-group study. PARTICIPANTS: A total of 400 eyes of 259 DMEK recipients, aged 23 to 90 years. METHODS: Patients were enrolled 1 year after DMEK and allowed to choose whether to stop or continue once-daily topical corticosteroids to maximize compliance. Fellow eyes were eligible for enrollment because the donor grafts were independent. Participants were examined at 1, 3, 6, and 12 months during the second year after DMEK. Results were assessed using Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Incidence of immunologic rejection episodes. RESULTS: Steroids were discontinued in 277 eyes (no steroid group) and continued once per day in 123 eyes (steroid group). The subject demographics were well balanced across groups; 99% of the subjects were white, and 95% of the grafts were performed to treat Fuchs' dystrophy. The cumulative incidence of rejection episodes was significantly greater in the no steroid group (6% vs. 0% in the steroid group; P = 0.013). Thirteen of 14 rejection episodes (all in the no steroid group) resolved with resumption of topical corticosteroids. Overall, 1 of 277 grafts (0.4%) failed in the no steroid group, and none failed in the steroid group during the second year after DMEK (P = 0.49). The endothelial cell loss between 1 and 2 years was comparable in the no steroid and steroid groups (6.4%±12% vs. 5.6%±14%, respectively; P = 0.67). CONCLUSIONS: Continued once-per-day use of a topical corticosteroid, even a weak one, was protective against rejection episodes during the second year after DMEK, whereas 6% experienced a rejection episode when steroids were discontinued. Among the 364 eyes that completed 12 months' follow-up, only 1 graft (0.27%) failed.

Topical Fluorometholone Protects the Ocular Surface of Dry Eye Patients from Desiccating Stress: A Randomized Controlled Clinical Trial.

PURPOSE: To assess the efficacy of topical 0.1% fluorometholone in dry eye disease (DED) patients for ameliorating the worsening of the ocular surface when exposed to adverse environments. DESIGN: Single-center, double-masked, randomized, vehicle-controlled clinical trial. PARTICIPANTS: Forty-one patients showing moderate to severe DED. METHODS: Patients randomly received 1 drop 4 times daily of either topical 0.1% fluorometholone (FML group) or topical polyvinyl alcohol (PA group) for 22 days. Corneal and conjunctival staining, conjunctival hyperemia, tear film breakup time (TBUT), tear osmolarity, and the Symptom Assessment in Dry Eye (SANDE) questionnaire scores were determined at baseline. Variables were reassessed on day 21 before and after undergoing a 2-hour controlled adverse environment exposure and again on day 22. MAIN OUTCOMES MEASURES: Percentage of patients showing an increase 1 point or more in corneal staining and a reduction of 2 points or more (0-10 scale) in SANDE score, after the controlled adverse environment exposure and 24 hours later. RESULTS: After 21 days of treatment, the FML group showed greater improvements in corneal and conjunctival staining, hyperemia, and TBUT than the PA group (P≤0.03). After the adverse exposure, the percentage of patients having a 1-grade or more increase in corneal staining was significantly (P = 0.03) higher in the PA group (63.1% vs. 23.8%, respectively). Additionally, the FML group showed no significant changes in corneal staining (mean, 0.86; 95% confidence interval [CI], 0.47-1.25; vs. mean, 1.05; 95% CI, 0.59-1.51, for visit 2 and 3, respectively), conjunctival staining (mean, 0.95; 95% CI, 0.54-1.37 vs. mean, 1.19; 95% CI, 0.75-1.63), and hyperemia (mean, 0.71; 95% CI, 0.41-1.02 vs. 1.14; 95% CI, 0.71-1.58) after the exposure, whereas for the PA group, there was significant worsening (P≤0.009) in these variables (corneal staining: mean, 1.95; 95% CI, 1.57-2.33 vs. mean, 2.58; 95% CI, 2.17-2.98; conjunctival staining: mean, 1.68; 95% CI, 1.29-2.08 vs. mean, 2.47; 95% CI, 2.07-2.88; hyperemia: mean, 1.95; 95% CI, 1.63-2.26 vs. mean, 2.84; 95% CI, 2.62-3.07). CONCLUSIONS: Three-week topical 0.1% fluorometholone therapy is effective not only in reducing ocular surface signs in DED patients, but also especially in preventing exacerbation caused by exposure to a desiccating stress.

Lower Lid Laxity is Negatively Correlated with Improvement of the Ocular Surface Disease Index in Dry Eye Treatment.

PURPOSE: To compare the responses to dry eye treatment of patients sorted by the degree of lower lid laxity. METHODS: Sixty patients were grouped into three groups according to the degree of lower lid laxity. Tear break-up time (TBUT), Schirmer test (ST) scores, ocular surface disease index (OSDI) scores, and changes in OSDI score in each group were compared, before and at 3 months after treatment. RESULTS: TBUT, ST, and OSDI scores were not different among the three groups at baseline. TBUT improved in each group at 3 months after treatment, and no differences between groups were found. ST scores were not increased after treatment, while OSDI were improved to 22.57 ± 5.243, 31.16 ± 11.353, and 37.85 ± 13.342 in the no, moderate, and high laxity groups, respectively; these improvements were statistically significant (p = 0.003, <0.001, <0.001, respectively). Patients with greater than moderate lower lid laxity saw the smallest improvement in response to dry eye treatment, as assessed by change in OSDI score (p = 0.005 versus moderate laxity group, p = 0.005 versus no laxity group). CONCLUSIONS: Lower lid laxity is one of the factors contributing to the responses to dry eye treatment assessed by change in OSDI score, independent of TBUT and ST scores.

The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

Expert opinion in the management of aqueous Deficient Dry Eye Disease (DED).

BACKGROUND: Dry eye disease (DED) affects millions of people worldwide. There are a variety of new treatments beyond traditional therapies such as preservative free artificial tears. Here, we conduct a survey to identify the most common treatments used among specialists and assess their interest in newer therapies. METHODS: An international survey was distributed to dry eye researchers and expert practitioners via an internet survey. The survey data collected were analyzed with descriptive statistics. RESULTS: One hundred and fifteen respondents completed the survey; of these, 66 % were cornea specialists. The most commonly prescribed topical treatments included cyclosporine A (CSA) 0.05 % (71/104, 68 %), fluorometholone (FML) 0.1 % (59/99, 60 %), loteprednol etabonate 0.5 % (50/99, 51 %), and autologous serum eye drops (ASD; 48/97, 49 %). The most commonly prescribed non-topical medications included essential fatty acid supplements (72/104, 69 %), low-dose doxycycline (oral; 61/100, 61 %), and flaxseed supplements (32/96, 33 %) as well as punctal plugs (76/102, 75 %). Respondents reported treatment with topical corticosteroids for 2 to 8 weeks (46/86, 53 %), followed by less than 2 weeks (24/86, 28 %) and with topical CSA between 2 to 8 weeks (45/85, 53 %) followed by 2 to 6 months (24/85, 28 %). The top three signs and symptoms reported to indicate treatment response were, in order, fluorescein staining of the cornea, reduction in foreign body sensation, and reduction in burning sensation. CONCLUSION: This survey offers insight into current expert opinion in the treatment of DED. The results of this survey are hypothesis generating and will aid in the design of future clinical studies.