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.

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.

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.

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.

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.

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.

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.

Topical Fluorometholone Versus Diclofenac Sodium in Cases With Perennial Allergic Conjunctivitis.

PURPOSE: To compare the efficacy of diclofenac sodium (DS) 0.1% and fluorometholone (FL) 0.1% in patients with perennial allergic conjunctivitis. METHODS: Fluorometholone 0.1% or DS 0.1% eye drops were topically administrated 4 times daily for 4 weeks in patients with perennial allergic conjunctivitis. Assessment was conducted with a 4-point rating scale (0=none, 1=mild, 2=moderate, and 3=severe) for 4 signs and 5 symptoms. RESULTS: Two hundred sixty-one patients were recruited. The demographics and baseline skin prick scores between both groups were comparable. Mean baseline scores in DS and FL group were 6.77 ± 2.24 and 6.34 ± 2.10, respectively. The scores rapidly decreased to 3.28 ± 1.47 and 2.69 ± 1.44 on day 7. Diclofenac sodium expressed a slower effect compared with FL within the first 3 days of treatment (P=0.01). CONCLUSIONS: The efficacy of topical FL and DS was comparable for the management of cases with perennial allergic conjunctivitis. However, FL led to a more rapid alleviation of signs and symptoms as compared with DS in early days after the initiation of treatment.

[Comparison of clinical effects of bromfenac sodium ophthalmic solution 0.1% versus glucocorticoids for post-LASEK usage].

OBJECTIVE: To evaluate the safety, effectiveness and compliance of Bronuck (bromfenac sodium ophthalmic solution 0.1%) following LASEK in comparison with glucocorticoids. METHODS: In this prospective trial, 60 patients (120 eyes) undergoing LASEK were randomized into the bromfenac sodium group (60 eyes) and control group (60 eyes). Patients in both groups initially received dexamethasone 0.1% four times a day after LASEK for 7 days, and then the patients in the bromfenac sodium group were given Bronuck twice a day for the next 11 weeks, while the patients from the control group were given fluorometholone 0.1% with gradually decreased doses during the same period. Results of the routine examinations done before and 3, 10, 30, 90 and 180 days after LASEK were recorded, including uncorrected visual acuity, best corrected visual acuity, intraocular pressure (IOP), corneal topography, ocular symptoms and signs, which were used for comparison between the two groups. All data of right eyes were analyzed for their independence, normality and homogeneity of variance. Independent samples t-test or non-parametric Mann-Whitney test was performed accordingly. RESULTS: There was no statistically significant difference in IOP and corneal topography (K1, K2, SAI, SRI and CY) between the two groups postoperatively. The IOP was (16.33 ± 6.21) mmHg(1 mmHg = 0.133 kPa), (15.67 ± 2.82) mmHg, (15.35 ± 2.22) mmHg and (13.10 ± 3.41) mmHg in the bromfenac sodium group, and (16.87 ± 3.68) mmHg, (14.05 ± 2.23) mmHg, (14.39 ± 2.22) mmHg and (13.18 ± 2.49) mmHg in the control group at 10, 30, 90 and 180 days, respectively. The bromfenac sodium group showed significantly better uncorrected visual acuity (5.16 ± 0.08) than the control group (5.02 ± 0.09) on day 30 (t = 2.32, P < 0.05). In the bromfenac sodium group, four eyes had visual fatigue, and four eyes had dry eye symptoms on day 180. Epithelial flaps were all well positioned with satisfying healing process. Each group had one case (two eyes) of haze on day 30, and the bromfenac sodium group had another case (2 eyes) of new-onset haze on day 60. But all the cases of haze were graded 0.5 according to the Fantes Standard, too mild to compromise their visual acuities, and were resolved after frequent topical medication for 1 month. Four patients from the control group were prescribed antiglaucoma medications due to elevated IOP. The refractive status remained stable for patients from both groups. CONCLUSIONS: Administration of Bronuck can reduce the amount of or partially substitute for corticosteroids. Mild haze early after LASEK may disappear after intensive treatment.

Bromfenac sodium 0.1%, fluorometholone 0.1% and dexamethasone 0.1% for control of ocular inflammation and prevention of cystoid macular edema after phacoemulsification.

PURPOSE: To compare bromfenac sodium 0.1%, fluorometholone 0.1% and dexamethasone 0.1% for the control of postoperative inflammation and prevention of cystoid macular edema (CME) after phacoemulsification. METHODS: Patients were randomized to receive bromfenac sodium 0.1% for 1 month (OBS1) or 2 months (OBS2), or fluorometholone 0.1% for 1 month (OFM) or dexamethasone 0.1% for 1 month (ODM). Best-corrected visual acuity, intraocular pressure, endothelial cell density, photon count value and retinal foveal thickness were measured. RESULTS: Mean photon count values were lower in the OBS1 and OBS2 groups compared with the ODM group during the first week. Bromfenac sodium cleared the ocular inflammation more rapidly than fluorometholone and dexamethasone. The foveal thickness was thinner in the second month and the incidence of CME was lower in the OBS1 and OBS2 groups compared with the OFM and ODM groups. CONCLUSION: Bromfenac sodium was more effective and safer than fluorometholone and dexamethasone as an anti-inflammatory, decreasing macular thickness and preventing CME in age-related cataract patients after cataract surgery.

[The clinical efficacy of 0.1% bromfenac sodium hydrate ophthalmic solution after excimer laser in situ keratomileusis].

OBJECTIVE: To investigate the clinical efficacy and safety of 0.1% bromfenac sodium hydrate ophthalmic solution in myopia and astigmatism eyes after sub-Bowman keratomileusis (SBK) METHODS: A case control study. Number of patients with low to moderate myopia (-6.00 D ≤ spherical equivalent < -2.00 D) in the test and control groups was 17 cases (32 eyes) and 20 cases (40 eyes), respectively. Number of patients with high myopia (-11.00 D ≤ spherical equivalent < -6.00 D) in the test and control groups was 22 cases (42 eyes) and 15 cases (26 eyes) respectively. The first day after SBK, 0.1% bromfenac sodium hydrate eye drops was administrated 2 times/day in patients in the test group and continued for 10 and 14 days in low and high myopia, respectively. In the control group, 0.1% fluorometholone eye drops was used 4 times/day, then reduced gradually and continuously for 16 days. Visual acuity, computer refraction, intraocular pressure (IOP) and corneal topography examination were conducted at different postoperative period. Symptoms and related complications were recorded. Ranked data were statistically analyzed using the Wilcoxon rank sum test and quantitative data were analyzed using independent samples t-test. RESULTS: For low to moderate myopic patients, average postoperative IOP and corneal curvature K2 after one and three months in the test group were (7.84 ± 1.35) and (8.13 ± 1.75) mm Hg(1 mm Hg = 0.133 kPa), and (38.66 ± 1.68) and (38.75 ± 1.45) D, respectively; in the control group, these parameters were (9.37 ± 1.28) and (9.47 ± 1.58) mm Hg and (39.56 ± 1.58), and (39.51 ± 1.50) D, respectively. All of these data in the test group were lower than those in the control group, the differences were statistically significant (t = -2.299, -2.112, P < 0.05). There were no significant differences (P < 0.05) in postoperative uncorrected visual acuity, spherical equivalent, corneal curvature K1, astigmatism CY, IOP (after 6 months) and corneal curvature K2 (after 6 months) between the test and control group. For the high myopic patients, mean postoperative uncorrected visual acuity in the test group and control group after 3 months were 5.14 ± 0.06 and 5.09 ± 0.07, respectively. The difference was statistically significant (t = 2.517, P = 0.015). There were no significant differences in symptoms between these two groups (two-sided test P > 0.1). High IOP and obvious myopia regression were not found in all patients. CONCLUSIONS: Bromfenac sodium hydrate eye drops (0.1%) can achieve the same therapeutic effect as fluorometholone eye drops after SBK and the former is better than the later in postoperative IOP control.

Topical steroid and non-steroidal anti-inflammatory drugs inhibit inflammatory cytokine expression on the ocular surface in the botulinum toxin B-induced murine dry eye model.

PURPOSE: To evaluate the effect of the topical steroid, fluorometholone, and the non-steroidal anti-inflammatory drugs (NSAIDs), nepafenac and ketorolac, on inflammatory cytokine expression of the ocular surface in the botulium toxin B-induced murine dry eye model. METHODS: Topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, and 0.4% ketorolac were applied 3 times per day in a dry eye mouse model 1 week after intralacrimal botulium toxin B (BTX-B) or saline (sham) injection. Tear production and corneal fluorescein staining were evaluated in all groups before injection at baseline and at 3 time points up to 4 weeks after injection. The pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were evaluated by immunohistochemistry. RESULTS: BTX-B-injected mice showed significantly decreased aqueous tear production and increased corneal fluorescein staining at the 1 and 2 week time points compared with normal control and saline-injected mice. In the BTX-B-injected mice, immunofluorescent staining for TNF-α and IL-1ß in corneal and conjunctival epithelial cells increased significantly at the 2 and 4 week time points compared to that of normal and saline-injected mice, and returned to normal levels at the 4 week time point. Topical fluorometholone significantly improved corneal surface staining in the BTX-B-injected mice after 1 week of treatment, and increased the tear production within 2 weeks, but without statistical significant difference. Topical fluorometholone significantly decreased the staining of TNF-α and IL-1ß in corneal and conjunctival epithelia after 1-week treatment. Topical artificial tears, 0.1% nepafenac, and 0.4% ketorolac did not show obvious effects on tear production, corneal surface staining, and levels of IL-1ß and TNF-α expression in normal, and BTX-B-injected dry eye mice. CONCLUSIONS: Topical fluorometholone caused suppression of inflammatory cytokine expression on the ocular surface in the Botulium toxin B-induced murine dry eye model, while topical NSAIDs demonstrated no clearly beneficial effects.

Efficacy and safety of long-term corticosteroid eye drops after penetrating keratoplasty: a prospective, randomized, clinical trial.

PURPOSE: Endothelial rejection remains a major cause of graft failure after penetrating keratoplasty (PKP). Topical corticosteroids are the gold standard for preventing rejection; however, protocols for corticosteroid treatment have been diverse. The aim of the present study was to examine the efficacy and safety of long-term use of corticosteroid eye drops after PKP in a randomized, clinical trial. DESIGN: Randomized, nonblinded, clinical trial. PARTICIPANTS: We enrolled 42 patients (21 males and 21 females) with a mean age of 65.3 years who underwent PKP and maintained graft clarity for >1 year with topical steroid eye drops. INTERVENTION: Patients were randomly assigned to 1 of 2 groups: Administration of 0.1% fluorometholone 3 times a day (steroid group) or discontinuation of steroid eye drops (no steroid group). All patients were followed for 12 months. MAIN OUTCOME MEASURES: Proportion of eyes without endothelial rejection and the proportion of eyes with clear grafts and the incidence of local or systemic side effects. RESULTS: Of the initial 42 patients, 4 in the steroid group and 6 in the no steroid group did not complete the trial. Of the patients who completed the trial, 1 patient in the steroid group and 6 in the no steroid group developed endothelial rejection at an average of 5.2±4.5 (mean ± standard deviation) months after study enrollment. The difference in the incidence of rejection between groups was found to be significant by both chi-square (P = 0.027) and Kaplan-Meier analyses (log-rank test, P = 0.032). No difference was observed between the 2 groups in visual acuity, intraocular pressure, epithelial damage, tear-film break-up time, cataract progression, infection, or incidence of systemic side effects. CONCLUSIONS: Prolonged use of 0.1% fluorometholone was beneficial for the prevention of rejection after PKP. Because no adverse consequences were noted, we recommend continuing use of the low-dose corticosteroids, even in non-high-risk cases.

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.

Growth suppression caused by corticosteroid eye drops.

Scarce data on systemic activity of corticosteroid eye drops are available in children. Two weeks treatment with fluorometholone eye drops in a case series of five children caused growth suppression detected by knemometry. The suppression had no impact on height growth during the following year.

Preoperative nonsteroidal anti-inflammatory drug or steroid and outcomes after trabeculectomy: a randomized controlled trial.

PURPOSE: To investigate the benefit of preoperative treatment with either topical nonsteroidal anti-inflammatory drug (NSAID) or steroid in terms of clinical outcomes following trabeculectomy. DESIGN: Prospective, randomized placebo-controlled trial. PARTICIPANTS: Sixty-one patients. METHODS: Between July 2005 and October 2007, 61 consecutive medically uncontrolled glaucoma patients scheduled for first-time trabeculectomy were randomized to 1 of 3 study topical medication groups: nonsteroidal anti-inflammatory drugs (ketorolac), steroids (fluorometholone), or placebo (artificial tears). Patients instilled 1 drop 4 times daily for 1 month before the procedure and were examined on days 1 and 2, at weeks 1, 2, and 4, and at months 3, 6, 12, 18, and 24 after trabeculectomy. MAIN OUTCOME MEASURES: Incidence of postoperative surgical or medical interventions (needling, laser suture lysis, needling revision, and intraocular pressure [IOP]-lowering medication). RESULTS: Fifty-four patients (54 eyes) were entered for analysis. The mean number of preoperative medications was 2.3+/-0.9. The mean baseline IOP was 21.0+/-6.0 mmHg. The mean postoperative target IOP was 16.5+/-1.8 mmHg. The mean follow-up was 23.6+/-4.0 months. The percentage of patients requiring needling within the first year was 41% in the placebo group, 6% in the NSAID, and 5% in the steroid group (P = 0.006). The percentage of patients requiring IOP-lowering medication to reach the target IOP at 1 year was 24% in the placebo group, 18% in the NSAID group, and 0% in the steroid group (P = 0.054 overall; P = 0.038 for steroids vs. others). The log-rank test showed a significant (P = 0.019) difference in medication-free survival curves between the different groups. More specifically, patients in the steroid group needed significantly less medication over the total follow-up (P = 0.007). CONCLUSIONS: Topical ketorolac or fluorometholone for 1 month before surgery was associated with improved trabeculectomy outcomes in terms of likelihood of postoperative needling. In the steroid group, there was a significantly reduced need for additional postoperative IOP-lowering medication compared with the other groups. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comparison of olopatadine and fluorometholone in contact lens-induced papillary conjunctivitis.

PURPOSE: The purpose of this study was to compare the efficacy of olopatadine with fluorometholone in contact lens-induced mild to moderate papillary conjunctivitis. METHODS: A randomized, double-masked study was conducted. Eighty-five (n = 170 eyes) soft contact lens users with mild to moderate papillary conjunctivitis were enrolled. Patients were randomly assigned to three groups to receive olopatadine 0.1%, fluorometholone 0.1%, or both. All drugs were instilled twice daily for 8 weeks. Contact lens use was discontinued during initial 4 weeks of therapy and subsequently patients were prescribed monthly disposable lenses. Patients were followed up every 2 weeks, and variables assessed were symptoms and signs, tear film status, and intraocular pressures. RESULTS: Decrease in ocular redness, itching, and tearing along with improvement in contact lens tolerance was comparable in all the three groups. Olopatadine was more effective in reducing redness than fluorometholone at 8 weeks (P=0.01). Improvement in congestion and papillary reaction was comparable in all groups. There was a significant increase in tear break up time of more than 2 sec for fluorometholone and no significant increase for olopatadine. The olopatadine and fluorometholone groups had significant increase of more than 2 mm in Schirmer test and more than 3 sec in tear break up time. In patients with subnormal and borderline tear functions, significant improvement was observed with both drugs. After 8 weeks of use of fluorometholone, there was a significant increase in intraocular pressure (P=0.003). CONCLUSIONS: Olopatadine and fluorometholone were the most effective for papillary conjunctivitis followed by olopatadine monotherapy and then fluorometholone monotherapy. Olopatadine is effective in alleviating signs and symptoms of contact lens-induced mild to moderate papillary conjunctivitis and is comparable with fluorometholone in efficacy.

Pediatric ocular rosacea.

A case of severe pediatric ocular rosacea was effectively treated after 2.5 years of misdiagnosis. A high index of suspicion should be maintained in children with ocular surface disease, with or without dermatologic rosacea, to correctly diagnose ocular rosacea and avoid morbidity and complications.

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.