A Review of the Categorizations of Mild, Moderate, and Severe Bacterial Keratitis Ulcers and Day-1 Treatment Regimen When Using the Topical Fluoroquinolones 0.3% Ciprofloxacin and 0.3% Ofloxacin.

Background: There are published suggestions that bacterial keratitis (BK) can be classified as mild, moderate, or severe and that the day-1 antibiotic drop regimen may differ for each category using the topical second-generation fluoroquinolones 0.3% ciprofloxacin and 0.3% ofloxacin (2FQ). The classification criteria are not consistently defined and the suggested regimens are often unreferenced and so here, the evidence base for applying such regimens in clinical practice is examined. Objective: To examine the evidence base regarding the categorization criteria used for BK and determine whether any evidence exists to support suggestions that different day-1 treatment regimen using the 2FQ may be applied based on any assigned categorization. Methods: The literature on BK treatment was reviewed, as were the clinical studies involving the commercially available 2FQ. All statements pertaining to classification and treatment paradigms involving BK were then collated and reviewed, as were the methodologies employed in the 2FQ clinical studies. Results: There have been no clinical trials using the 2FQ, or indeed any other topical antibiotics, which have used different day-1 drop regimen depending on the size, depth, and location of the ulcer or for ulcers classified as mild, moderate, or severe. Thus, there is no evidence to support the suggestion that a lower number of drops on day 1 is as effective as a higher number on categorized BK ulcers. Conclusions: No standardized method of categorizing BK was found, and there is no evidence to support the contention that mild, moderate, or smaller BK ulcers should be treated any differently to larger or severe ulcers on day 1. The manufacturers of 2FQ do not supply different treatment regimens for different ulcer sizes and severity categories. When using the 2FQ, all BK ulcers should be treated equally in line with the manufacturers' recommended day-1 treatment regimen.

Inter-visit Test-Retest Variability of OCT in Glaucoma.

PURPOSE: To determine the inter-visit test-retest variability (TRV) of a spectral domain optical coherence tomograph, the Topcon 3D OCT-2000, in the measurement of optic nerve head topography, peripapillary retinal nerve fiber layer (pRNFL), and macular ganglion cell complex (GCC) parameters in glaucoma patients. We also examine whether TRV with this instrument varies with the extent of glaucomatous damage. METHODS: Twenty-four subjects with varying degrees of glaucoma severity provided 41 eyes with usable results for the study. 3D Disc Retinal Nerve Fiber Layer Analysis and Macula V (GCC) scans were repeated 1 week apart, at the same time of day, to determine the inter-visit TRV. TRV was determined using Bland-Altman limits of agreement (LoA) and the resulting coefficients of repeatability (CR). RESULTS: The overall horizontal and vertical cup/disc ratio CRs were 0.05 and 0.07, respectively. The GCC CR was 2.9 µm. In contrast, average pRNFL TRV expanded with increasing damage, with the LoA being well fitted by ±(34.67 - 0.294(d)), where d is the pRNFL thickness. A more complex model, with constant LoA of ±5.61 µm at d >82 µm, and linearly expanding TRV below that, achieved marginal significance (P < .06). CONCLUSIONS: The repeatability of GCC measurements with this instrument was excellent. The determination of statistically significant change in average pRNFL should take into account average pRNFL thickness.

Retest Variability in the Medmont M700 Automated Perimeter.

PURPOSE: To investigate the level of test-retest variability in the Medmont M700 automated perimeter. We compare the retest variability of the outer 20° test points of one test method to test points in the inner 10° of two test methods to determine whether test points from different tests and regions exhibit different retest variability. We also generate some clinically applicable coefficient of repeatability (CoR) values for M700 Overall Defect (OD) and Pattern Defect (PD) indices. METHODS: Twenty-four glaucoma patients with varying degrees of field loss were enrolled, and 21 patients (40 eyes) had usable results. The Central (30°) test and the Macula (10°) test were performed on each eye on the same day. To determine retest variability, the tests were repeated 1 week later at the same time of day. RESULTS: Test points from 5 to 20 dB in the outer 20° of the 30° test showed lower retest variance than points of equal decibel value in the central 10° of the same test. For the 30° test, the OD CoR was 2.4 dB. The PD retest CoR varied with glaucoma severity, ranging from 1.24 dB for PD less than or equal to 2.8 to 3.1 dB for PD more than 5.7. The 10° test CoR for OD was 2.1 dB, and PD retest CoR ranged from 1.58 for PD less than or equal to 2.8 to 2.4 for PD more than 5.7. CONCLUSIONS: In glaucoma patients, retest variance for some decibel values does not seem to increase with increasing eccentricity in the M700. The OD values as graded by the M700 do not appear to correspond well with the amount of visual field loss and are not directly comparable to mean deviation results reported by other perimeters. Pattern defect values in the M700 seem to correlate well with the degree of field loss.

A Literature-Based Review and Analysis of the Pharmacodynamics of the Dose Frequency of Topical 0.3% Ciprofloxacin and 0.3% Ofloxacin in the Day-1 Treatment of Bacterial Keratitis.

Purpose: To determine the appropriate dose frequency for the second-generation fluoroquinolones (2FQs), ciprofloxacin 0.3% and ofloxacin 0.3%, in the day-1 treatment of bacterial keratitis (BK) based on the corneal concentrations achievable and required Minimum Inhibitory Concentration90 (MIC90) of common BK isolates. Methods: Literature-based ocular MIC90 required to treat bacterial isolates of BK patients were determined for each fluoroquinolone. Published corneal concentrations for each 2FQ, and the drop regimens used to reach these concentrations, were then analyzed to determine the relationship between the corneal 2FQ concentration and the amount of drug applied per hour and the total amount applied. Results: Significant relationships were found to exist for corneal concentrations of both ciprofloxacin and ofloxacin and the amount of drug applied per hour (both P = 0.005), and the total amount of drug applied (P = 0.003 and P = 0.0004, respectively). Derived ciprofloxacin drops/hour corneal concentrations agreed well with both a literature-based regimen and the manufacturers' day-1 drop regimen for various MIC90. Derived ofloxacin drops per hour indicated a higher rate than that suggested by the manufacturer. Conclusions: Both a literature-based and the manufacturers' drop regimens for the day-1 treatment of BK using 0.3% ciprofloxacin have a pharmacodynamic basis, which is related to the required MIC90 of commonly encountered isolates in BK. Dose frequency for 0.3% ofloxacin should be in line with the manufacturers' maximum suggested drop regimen. Commonly suggested drop regimens below these recommendations for either FQ may need to be revised in view of these findings.