Study design and baseline findings from the progression of ocular findings (PROOF) natural history study of dry eye.

BACKGROUND: The aim of this research is to initiate a 5-year natural history study of dry eye disease (DED) using objectively assessed and patient-reported outcomes, to explore the hypothesis that DED is a progressive condition that has substantive and measurable impacts not only on the ocular surface, but on quality of life and visual functioning. Our objective for this report is to examine the baseline data. METHODS: A multicenter, prospective, controlled, observational study of Level 2 (mild-to-moderate) DED patients based on International Task Force Delphi Panel severity grading, and controls, documented baseline measures (including tear film biomarkers and quality of life). Tear cytokine concentrations were also measured in the tear film. Patients were using artificial tears as needed. RESULTS: Two hundred seventeen DED patients and 67 gender- and age-matched controls were enrolled. A majority were females and Caucasian and groups did not differ significantly in terms of gender, race, or age. Differences between DED and matched controls, at baseline, included mean scores for Ocular Surface Disease Index (31.7 vs 4.1, P < 0.0001), Schirmer test (5.7 vs 15.3 mm, P < 0.0001), corneal staining (1.4 vs 0.2, P < 0.0001), conjunctival staining (1.4 vs 0.3, P < 0.0001), and tear break-up time (5.7 vs 8.5 s, P < 0.0001). Tear cytokines levels were determined and included interferon-γ, interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor-α, epidermal growth factor, IL-13, IL-17, IL-1α, and inducible protein-10. The mean levels of IL-8 and IL-6 were slightly higher in the DED group at baseline. Blurred vision was reported as moderate/severe/very severe at baseline in 57.6% of DED patients vs.10.5% of normal controls (P < 0.0001). DED patients reported greater reductions in work and non-work productivity, as well as greater need for visits to ophthalmologists during the prior year. CONCLUSIONS: In this report of the baseline findings of a 5-year natural history study of DED, a striking disease burden is observed with regard to blurred vision, productivity, and visits to eye care practitioners in mild to moderate DED patients compared to normal subjects of similar ages and genders. TRIAL REGISTRATION: ClinicalTrials.gov NCT00833235 on January 30, 2009.

PERSIST: Physician's Evaluation of Restasis(®) Satisfaction in Second Trial of topical cyclosporine ophthalmic emulsion 0.05% for dry eye: a retrospective review.

BACKGROUND: Chronic dry eye disease often requires long-term therapy. Tear film alterations in the setting of dry eye may include reduced tear volume as well as an increase in inflammatory cytokines and osmolarity. Topical cyclosporine ophthalmic emulsion 0.05% (Restasis(®); Allergan Inc, Irvine, CA) is indicated to increase tear production in patients with dry eye and reduced tear production presumed to be due to ocular inflammation. This study was designed to evaluate the efficacy of a second trial of topical cyclosporine in patients with dry eye who were previously considered treatment failures. MATERIALS AND METHODS: This multicenter (three cornea practices) retrospective chart review evaluated clinical outcomes in patients with dry eye who received a second trial of cyclosporine after a prior treatment failure, defined as prior discontinuation of topical cyclosporine after less than 12 weeks. RESULTS: Thirty-five patients, most of whom were female (71.4%) and Caucasian (62.9%), were identified. Prior discontinuation was most commonly due to burning/stinging (60%). The median duration of second treatment was 10 months (range 1 week to 45 months). Physician education was provided in the second trial in 97.1% of cases. At initiation of the second trial of cyclosporine, 10 (28.6%) patients received courses of topical corticosteroids. Physicians reported on a questionnaire that 80% of patients achieved clinical benefit with a second trial of cyclosporine. CONCLUSION: A repeat trial with topical cyclosporine can achieve clinical success. Direct patient education via the physician and staff may be key to success. Proper patient education may overcome adherence issues, particularly with respect to the need for long-term treatment of chronic dry eye. This study has the usual limitations associated with a retrospective chart review, and future prospective studies are warranted.

Intraocular pressure elevations with loteprednol etabonate: a retrospective chart review.

PURPOSE: Ocular corticosteroids can cause elevations in intraocular pressure (IOP). The purpose of this study was to characterize the timing and severity of IOP elevations in patients receiving loteprednol etabonate 0.5% or loteprednol etabonate 0.5%/tobramycin 0.3%. METHODS: A retrospective chart review was conducted at 5 academic and private practices. Any patient who experienced an elevation in IOP ≥5 mm Hg while using loteprednol etabonate or loteprednol etabonate/tobramycin was eligible for inclusion in the study. Data collected included patient demographics, medical and ophthalmic history, concomitant medications, reason for treatment, IOP, and medical and surgical interventions. RESULTS: Fifty patients experienced IOP elevations after use of topical loteprednol etabonate and were included in the study. The mean (standard deviation [SD]) patient age was 58.8 (20.3) years and 66% were women. The most common reasons for prescribing loteprednol etabonate were dry eye (30%), postoperative therapy (22%), and allergic conjunctivitis (16%). Before treatment, 28% of patients had a history of open-angle glaucoma or ocular hypertension. Mean (SD) IOP before treatment was 15.5 (3.2) mm Hg and increased to a mean (SD) of 24.7 (6.5) mm Hg, a statistically significant increase of 9.2 (SD: 5.8; range: 5-29) mm Hg (P<0.0001). The median duration of treatment with loteprednol etabonate at the time of observed IOP elevation was 55 days (range: 3 days to 3 years). Twenty-four percent of patients required IOP-lowering medications and 8% required surgery to control the elevated IOP. CONCLUSIONS: Alternatives to corticosteroids should be considered when long-term treatment is required for an ocular surface condition.

Methicillin resistance of Staphylococcus species among health care and nonhealth care workers undergoing cataract surgery.

PURPOSE: The purpose of this study is to characterize the bacterial flora of the ocular and periocular surface in cataract surgery patients and to determine the prevalence of methicillin resistance among staphylococcal isolates obtained from health care workers (HCWs) and non-HCWs. METHODS: In this prospective, multicenter, case series study, eyelid and conjunctival cultures were obtained from the nonoperative eye of 399 consecutive cataract patients on the day of surgery prior to application of topical anesthetics, antibiotics, or antiseptics. Speciation and susceptibility testing were performed at the Dean A. McGee Eye Institute. Logistic regression was utilized to evaluate whether any factors were significant in predicting the presence of methicillin-resistant staphylococcal isolates. RESULTS: Staphylococcus epidermidis (62.9%), followed by S. aureus (14.0%), was the most frequently isolated organism. Methicillin-resistant S. epidermidis accounted for 47.1% (178/378) of S. epidermidis isolates, and methicillin-resistant S. aureus accounted for 29.5% (26/88) of S. aureus isolates. Methicillin-resistant staphylococcal isolates were found in 157 of 399 (39.3%) patients, the majority (89.2%) of whom were non-HCWs. The likelihood of being colonized with methicillin-resistant organisms increased with age (odds ratio [OR], 1.27; 95% confidence interval [CI]: 1.02-1.58; P = 0.04) but decreased with diabetes (OR, 0.51; 95% CI: 0.29-0.89; P = 0.02). Being a HCW (OR, 1.25; 95% CI: 0.61-2.58; P = 0.54) was not a risk factor for colonization with methicillin-resistant organisms. CONCLUSION: Patients without exposure to health care environments are as likely as HCWs to be colonized with methicillin-resistant organisms. Increasing methicillin resistance with age may partially explain the increased risk of endophthalmitis reported with older age.