Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.

PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.

Microbial keratitis trends following refractive surgery: results of the ASCRS infectious keratitis survey and comparisons with prior ASCRS surveys of infectious keratitis following keratorefractive procedures.

In 2008, the American Society of Cataract and Refractive Surgery (ASCRS) surveyed its 9121 United States and international members to evaluate the changing trends and incidence, culture results, treatment, and visual outcomes of infectious keratitis following keratorefractive procedures worldwide. This paper presents and analyzes the results with comparisons to the data in surveys conducted in 2001 and 2004. Nineteen infections were reported by 14 surgeons who had performed an estimated 20,941 keratorefractive procedures, an incidence of 1 infection in every 1102 procedures. Sixteen cases presented in the first postoperative week, 1 case during the second week, 1 case between the second and fourth weeks, and 1 case at 1 month or later. The 16 cases that presented in the first week were diagnosed at initial presentation. The most common organism cultured was methicillin-resistant Staphylococcus aureus (MRSA). Microbial keratitis following refractive surgery is an increasingly recognized sight-threatening complication.

Topical loteprednol pretreatment reduces cyclosporine stinging in chronic dry eye disease.

PURPOSE: This retrospective, clinical comparative analysis describes differences in clinical signs and symptoms and medication tolerability between those patients who receive topical corticosteroids prior to initiation of topical cyclosporine 0.5% emulsion (tCSA) therapy for chronic dry eye disease (CDED) and those who received tCSA and were not first induced with corticosteroid drops. tCSA is the only approved medication for CDED. Stinging is the most common side effect of tCSA and reason for tCSA discontinuation. This analysis describes an effective pharmacologic means to reduce tCSA stinging and subsequent discontinuation. METHODS: Thirty-six consecutive patients were initially treated with loteprednol etabonate (LE) 0.5% (Lotemax; Bausch & Lomb) for a period ranging from 2 to 16 months prior to institution of concomitant tCSA (Restasis™; Allergan). Clinical parameters (fluorescein staining, conjunctival redness, tear meniscus) were compared over a period of 6 months to a second cohort of 36 consecutive patients who were initially prescribed continuous tCSA without concomitant LE pretreatment. Patients in the LE pretreatment group discontinued LE after 3-6 months of concomitant therapy while continuing tCSA therapy. RESULTS: Of the 36 LE pretreatment patients, only 2 developed significant stinging (5.5%) and 1 discontinued the use of tCSA because of stinging (2.8%). Of the patients without LE pretreatment, 8 developed stinging (22%) and 3 discontinued tCSA as a result (8.3%). The intergroup P value was significant for severe stinging (<0.02) and for tCSA discontinuation because of severe stinging (<0.04). Patients in the LE pretreatment group had no statistically significant differences in preenrollment disease severity or demographics (P range from 0.19 to 0.59) compared with the group without pretreatment. CONCLUSION: Topical corticosteroid preparation of the ocular surface in CDED with LE induction therapy may reduce discomfort from subsequent long-term maintenance topical medications, particularly tCSA. This analysis describes a readily available induction and maintenance pharmacologic strategy to reduce tCSA stinging and subsequent discontinuation.

Modalities to decrease stromal herpes simplex keratitis reactivation rates.

OBJECTIVE: To evaluate the efficacy of adjunctive treatments to decrease herpes simplex keratitis (HSK) recurrences in patients with simultaneous stromal HSK and dry eye disease. METHODS: This was a nonrandomized, single-center, retrospective, comparative analysis. Forty-two patients were diagnosed with unilateral HSK and dry eye disease. Of the 42 patients, 22 were treated with ipsilateral punctal occlusion by thermal cautery and 10 were treated with topical administration of cyclosporine, 0.05%, ophthalmic emulsion twice a day. Another group of 10 patients had previously undergone punctal occlusion and had cyclosporine ophthalmic emulsion twice a day added. All patients continued the use of oral acyclovir or valacyclovir hydrochloride and topical steroids. The frequency and duration of HSK recurrences were monitored for 1 year after initiation of treatment, and the rates were compared with those in the prior year. RESULTS: The thermal cautery and topical cyclosporine groups experienced HSK recurrences for mean durations of 7.1 and 5.8 mo/y before treatment, respectively, and these were reduced to 1.1 mo/y after treatment in both groups. Topical administration of cyclosporine further reduced the duration of HSK recurrences in patients with prior thermal cautery from an average of 1.3 mo/y before the addition of cyclosporine to 0.8 mo/y after the addition of cyclosporine. CONCLUSION: Permanent punctal occlusion by thermal cautery and the use of topical cyclosporine independently reduced recurrences of stromal HSK.

Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy.

INTRODUCTION: Beginning with second-generation ciprofloxacin 0.3% and ofloxacin 0.3%, fluoroquinolones have been widely used in the treatment and prophylaxis of ocular infections. However, their in-vitro potencies have been decreasing steadily since their introduction. Third-generation levofloxacin 0.5% produces higher ocular tissue penetration, thereby reducing the risk of selecting for decreased fluoroquinolone potency. Fourth-generation gatifloxacin 0.3% and moxifloxacin 0.5% have structural modifications that both reduce risk of resistance and improve potency against Gram-positive bacteria. A new third-generation formulation, levofloxacin 1.5%, was recently introduced, demonstrating increased ocular penetration compared with gatifloxacin 0.3% but clinical equivalence to its second-generation parent, ofloxacin 0.3%, in two randomized trials. METHODS: We investigated the therapeutic potential of levofloxacin 1.5% and compared it to that of existing fourth-generation fluoroquinolones. A MEDLINE search was conducted using the following search terms: moxifloxacin or gatifloxacin; levofloxacin; minimum inhibitory concentration or prevention or prophylaxis; keratitis or endophthalmitis. RESULTS: Nine eligible studies published between 2002 and 2008 were identified, eight of which are presented. The five in-vitro studies demonstrated that moxifloxacin and gatifloxacin are statistically more potent than levofloxacin against Gram-positive organisms and similar in potency in most cases of Gram-negative bacteria. In-vivo animal models testing moxifloxacin or gatifloxacin against levofloxacin 0.5% (no clinical trials testing the efficacy of levofloxacin 1.5% have yet been published) demonstrated that fourth-generation agents were superior to third-generation levofloxacin 0.5% for prophylaxis of Gram-positive bacteria-induced infections and were equal to, or better than, levofloxacin 0.5% for the treatment of Gram-negative infections. CONCLUSION: Fourth-generation agents have increased potency against Gram-positive bacteria compared with levofloxacin, while maintaining similar potency against Gram-negative bacteria. Although levofloxacin 1.5% has demonstrated superior ocular penetration relative to gatifloxacin, the limited available data do not suggest this translates into superior clinical activity compared with moxifloxacin, which has significantly greater ocular penetration and better Gram-positive potency than gatifloxacin.

Intraocular pressure-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination compared with brinzolamide 1% and timolol 0.5%.

PURPOSE: To compare the safety and intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination with brinzolamide 1% or timolol 0.5% alone in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Randomized, double-masked, parallel group, multicenter study. PARTICIPANTS: Five hundred twenty-three patients were randomized to the study treatments. METHODS: Patients with OAG or OHT were recruited to the study. Qualifying eyes had IOPs of 24 to 36 mmHg at 8 am and 21 to 36 mmHg at 10 am on 2 eligibility visits after an appropriate washout period from previous treatment. Patients were assigned randomly to either brinzolamide 1%/timolol 0.5%, brinzolamide 1% (Azopt; Alcon Laboratories, Fort Worth, TX), or timolol 0.5%, dosed twice daily and were followed up while receiving therapy for 6 months. At selected sites, additional IOP measurements were performed at 12 pm, 4 pm, and 8 pm during the 2 eligibility visits, at month 3, and at month 6. MAIN OUTCOME MEASURE: Mean IOP. RESULTS: Brinzolamide 1%/timolol 0.5% produced statistically significant and clinically relevant reductions from baseline ranging from 8.0 to 8.7 mmHg, which were statistically and clinically superior to that of either brinzolamide 1% (5.1-5.6 mmHg) or timolol 0.5% (5.7-6.9 mmHg). No safety concerns were identified based on an assessment of ocular and cardiovascular parameters and a review of adverse events. CONCLUSIONS: Brinzolamide 1%/timolol 05% is superior in IOP-lowering efficacy to either brinzolamide 1% or timolol 0.5%.

Ocular distribution, bactericidal activity and settling characteristics of TobraDex ST ophthalmic suspension compared with TobraDex ophthalmic suspension.

INTRODUCTION: TobraDex ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container. METHODS: A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose. RESULTS: Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST. CONCLUSION: TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.

Perception and quality of life associated with the use of olopatadine 0.2% (Pataday) in patients with active allergic conjunctivitis.

This 28-d, open-label, multicenter, single-arm clinical study was designed to evaluate perceptions of olopatadine 0.2% in patients with active ocular allergic signs and symptoms. The study enrolled 330 patients, 5 to 94 y of age, who had previously used olopatadine 0.1% for active allergic conjunctivitis. Most patients were white (n=230; 70.1%) and female (n=239; 72.9%). Of all enrolled patients, 328 were evaluable for analysis. Throughout the study, patients instilled 1 drop of olopatadine 0.2% into each eye once daily; adverse events were documented and ocular evaluations were conducted to ensure patient safety. Direct evaluations of efficacy were not performed. On days 1 and 7, patients completed the Rhinoconjunctivitis Quality of Life Questionnaire, recorded their perceptions of olopatadine 0.1% (day 1) or 0.2% (day 7), and had their ocular allergies assessed globally. On each of the first 6 d of treatment, patients also completed a telephone-based perception questionnaire. On day 28, patients returned to the study center, reported their treatment perceptions, had their ocular allergies assessed, and exited the trial. Overall, patients had a positive perception of olopatadine 0.2%. Patients were more satisfied with olopatadine 0.2% than they remembered being with olopatadine 0.1% (289 vs 257 patients; 87.6% vs 77.8%; P<.05). The majority of the 48 patients who wore contact lenses (n=42; 88%) believed that they could wear their contacts as desired. Significant improvement was noted in all categories of the Rhinoconjunctivitis Quality of Life Questionnaire (P<.0001). No unexpected safety findings were reported. Patients perceived olopatadine 0.2% to be effective and well tolerated.