Sensitivity and specificity of a point-of-care matrix metalloproteinase 9 immunoassay for diagnosing inflammation related to dry eye.

OBJECTIVES: To determine the clinical sensitivity, specificity, negative predictive value, and positive predictive value of a rapid point-of-care diagnostic test to detect elevated matrix metalloproteinase 9 levels (InflammaDry). METHODS: In a prospective, sequential, masked, multicenter clinical trial, InflammaDry was performed on 206 patients: 143 patients with clinical signs and symptoms of dysfunctional tear syndrome (dry eyes) and 63 healthy individuals serving as controls. Participants were assessed as healthy controls or for a clinical diagnosis of dry eye using the Ocular Surface Disease Index, Schirmer tear test, tear breakup time, and keratoconjunctival staining. MAIN OUTCOME MEASURES: The sensitivity and specificity of InflammaDry were compared with clinical assessment. RESULTS: InflammaDry showed sensitivity of 85% (in 121 of 143 patients), specificity of 94% (59 of 63), negative predictive value of 73% (59 of 81), and positive predictive value of 97% (121 of 125). CONCLUSION: Compared with clinical assessment, InflammaDry is sensitive and specific in diagnosing dry eye. APPLICATION TO CLINICAL PRACTICE: Dry eye is often underdiagnosed resulting from poor communication between the clinical assessment of dry eye severity between clinicians and patients. This often leads to a lack of effective treatment. Matrix metalloproteinase 9 is an inflammatory biomarker that has been shown to be elevated in the tears of patients with dry eyes. The ability to accurately detect elevated matrix metalloproteinase 9 levels may lead to earlier diagnosis, more appropriate treatment, and better management of ocular surface disease. Preoperative and perioperative management of inflammation related to dry eyes may reduce dry eyes that develop after laser in situ keratomileusis, improve wound healing, and reduce flap complications. Recognition of inflammation may allow for targeted perioperative therapeutic management of care for patients who undergo cataract and refractive surgery and improve outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01313351.

Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP.

A 3-month clinical trial comparing the IOP-lowering efficacy of bimatoprost and latanoprost in patients with normal-tension glaucoma.

This multicenter, randomized, double-blind clinical trial was undertaken to compare the intraocular pressure (IOP)-lowering efficacy and safety of topical bimatoprost 0.03% with that of latanoprost 0.005% for the treatment of patients with normal-tension glaucoma. After washout of all ocular hypotensive medications, patients with normal-tension glaucoma (n=60) were randomly assigned to oncedaily bimatoprost 0.03% or latanoprost 0.005% for 3 mo. Diurnal IOP measurements were taken at each study visit. Primary outcome measures consisted of mean change from baseline IOP (8 AM, Noon, 4 PM) and change in visual field. Secondary measures included mean IOP, ophthalmologic examination findings, results of clinical evaluation, and adverse events. Mean change from baseline IOP at each study visit was statistically significant at all diurnal measurements for patients taking bimatoprost and for those taking latanoprost (P<.001). The 8 AM mean change from baseline IOP measurement showed a significant between-group difference (P< or =.033) in favor of bimatoprost at both follow-up visits. After 3 mo of treatment, mean IOP reductions from baseline ranged from 2.8 to 3.8 mm Hg (17.5%-21.6%) with bimatoprost and from 2.1 to 2.6 mm Hg (12.7%-16.2%) with latanoprost. Overall mean reduction in IOP after 3 mo of treatment was 3.4 mm Hg (19.9% rpar; with bimatoprost and 2.3 mm Hg (14.6%) with latanoprost (P=.035). No significant between-group differences were observed in incidence of adverse events, clinical success, or demographic variables. Bimatoprost was found to be more effective than latanoprost in lowering IOP in the patient with normal-tension glaucoma. Both drugs were efficacious and well tolerated.

Bimatoprost versus latanoprost in lowering intraocular pressure in glaucoma and ocular hypertension: results from parallel-group comparison trials.

This review evaluated the clinical evidence of the comparative efficacy and safety of bimatoprost and latanoprost in lowering intraocular pressure (IOP) in patients with glaucoma and ocular hypertension. Four head-to-head, randomized, and controlled clinical trials of bimatoprost and latanoprost with treatment periods ranging from 1 to 6 months were identified from searches of the MEDLINE database through February 2004. According to a review and comparison of the results, bimatoprost, when compared with latanoprost, was associated with greater mean reductions in IOP, greater mean increases in the percentage of patients demonstrating target IOP, and greater response rates. The differences between drugs were not always statistically significant. Overall, the between-group differences in mean IOP ranged from 0 to 1.5 mm Hg. In 92% of the IOP measurements, the mean IOP was lower among patients given bimatoprost than among those given latanoprost; in the remaining 8%, the IOP reduction was equal. Transient, mild conjunctival hyperemia was the most frequently reported adverse effect associated with either drug, but it occurred more frequently with bimatoprost. Overall, both drugs were well tolerated. As a 1-mm Hg change in IOP has been shown to reduce the risk of progression in patients with glaucoma (according to the Early Manifest Glaucoma Trial), the greater efficacy demonstrated by bimatoprost in lowering IOP may be clinically significant.

Multicenter, open-label evaluation of hyperemia associated with use of bimatoprost in adults with open-angle glaucoma or ocular hypertension.

This month-long multicenter, open-label study evaluated the onset and progression of hyperemia associated with bimatoprost 0.03% once daily in 39 patients with open-angle glaucoma or ocular hypertension. Current glaucoma medication(s) was either replaced with or augmented by bimatoprost. Previous users of bimatoprost were excluded. Primary outcome measures were mean hyperemia scale scores (ciliary, conjunctival, and episcleral, graded on a seven-point scale) and incidence of hyperemia. Secondary outcome measures were fluorescein staining, patient assessment of ocular redness (take-home diary), and patient and investigator evaluations. Patients were asked how troubled they were by their ocular redness. Investigators were asked if they would continue the patient on bimatoprost despite the hyperemia. Overall, the frequency and severity of hyperemia peaked approximately 1 day after the first instillation of bimatoprost and decreased consistently throughout the study, returning to near-baseline levels by day 28. At day 1, 84.6% of patients were hardly troubled or not troubled by their ocular redness; only 15.4% were somewhat or moderately troubled. Investigators indicated that they would continue bimatoprost therapy in 92.3% of the patients. Hyperemia did not represent a significant safety concern.

A six-month randomized clinical trial comparing the intraocular pressure-lowering efficacy of bimatoprost and latanoprost in patients with ocular hypertension or glaucoma.

PURPOSE: To compare the intraocular pressure (IOP)-lowering efficacy and safety of topical bimatoprost 0.03% with latanoprost 0.005%. DESIGN: Multicenter, randomized, investigator-masked clinical trial. METHODS: After washout of glaucoma medications, ocular hypertension or glaucoma patients were randomly assigned to once-daily bimatoprost 0.03% (n = 133) or latanoprost 0.005% (n = 136) for 6 months. The primary outcome measure was mean change from baseline IOP (8 AM, 12 PM, 4 PM). Secondary measures included mean IOP, ophthalmologic examination, adverse events, and the percentage of patients reaching specific target IOPs. RESULTS: Mean change from baseline IOP was significantly greater for bimatoprost patients than for latanoprost patients at all measurements on each study visit; 1.5 mm Hg greater at 8 AM (P <.001), 2.2 mm Hg greater at 12 PM (P <.001), and 1.2 mm Hg greater at 4 PM (P =.004) at month 6. At the end of the study, the percentage of patients achieving a > or = 20% IOP decrease was 69% to 82% with bimatoprost and 50% to 62% with latanoprost (P < or = .003). In addition, the distribution of patients achieving target pressures in each range (< or = 13 to < or = 15 mm Hg, >15 to < or = 18 mm Hg, and > 18 mm Hg) showed that bimatoprost produced lower target pressures compared with latanoprost at all times measured (P < or = .026). Few patients were discontinued for adverse events (6 on bimatoprost; 5 on latanoprost). On ophthalmologic examination, conjunctival hyperemia (P <.001) and eyelash growth (P =.064) were more common in bimatoprost patients. CONCLUSIONS: Bimatoprost is more effective than latanoprost in lowering IOP. Both drugs were well tolerated, with few discontinuations for adverse events.

Comparison of the frequency doubling technology screening algorithm and the Humphrey 24-2 SITA-FAST in a large eye screening.

PURPOSE: To compare the Frequency Doubling Technology (FDT) C20-1 screening algorithm and the Humphrey Field Analyser II (HFA) 24-2 SITA-FAST in a large eye screening. METHODS: In a non-randomized, prospective, free eye screening, the FDT Screening Protocol (C20-1 Screening Algorithm) was administered to 574 attendees (422 men and 152 women, average age 64, range 17-89 years) of the 1998 Veterans of Foreign Wars (VFW) Convention in San Antonio, Texas. Individuals who failed the FDT (two or more misses out of 17 locations) immediately underwent white-on-white threshold visual field perimetry (HFA 24-2, SITA-FAST). Humphrey visual field analysis included STATPAC and masked evaluations by three glaucoma specialists. RESULTS: Approximately one-tenth of the VFW conference attendees voluntarily presented themselves for screening. Among these 574 volunteers, 69 (12%) failed the FDT and underwent HFA analysis. Eighty-one per cent (56/69) of these FDT failures had abnormal HFA Glaucoma Hemifield Tests. Eighty-eight per cent (61/69) were judged to have nerve fibre type visual field loss on HFA by at least two of three masked examiners. A positive correlation existed between the number of FDT locations missed and the HFA mean deviation (r = 0.5, P = 0.0001). A similar association was observed when FDT and HFA results were analysed by quadrant (r = 0.5, P < 0.0001). CONCLUSION: There was a low false positive rate and a good positive predictive value comparing the FDT screening algorithm to the HFA 24-2 SITA-FAST in this study. This supports the potential use of FDT as an economical screening device.