Clinical efficacy of moxifloxacin in the treatment of bacterial keratitis: a randomized clinical trial.

PURPOSE: To determine the clinical efficacy and safety of moxifloxacin (1.0%) in patients with bacterial keratitis compared with patients treated with ofloxacin (0.3%) or fortified tobramycin (1.33%)/cephazolin (5%). DESIGN: Prospective randomized trial. PARTICIPANTS: A total of 229 patients diagnosed with bacterial keratitis were enrolled in the study; 78 patients were randomized to the fortified tobramycin/cephazolin group, 77 patients to the moxifloxacin group, and 74 patients to the ofloxacin group. A total of 225 patients were evaluable for safety and 198 patients were included in the efficacy analysis. INTERVENTION: After corneal specimens were obtained, the assigned study medication was instilled every hour, day and night, for 48 hours and on the third day, every hour by day and every 2 hours at night. For days 4 and 5, 1 drop every 2 hours by day and every 4 hours at night, and for days 6 and 7, 1 drop every 4 hours. After day 7, the antibiotic was tapered to every 6 hours and stopped when appropriate. MAIN OUTCOME MEASURES: Resolution of keratitis and healing of ulcer, time to cure, mean time to discharge, clinical sign score, adverse reactions to study medication, and treatment failures. RESULTS: Of the 186 nonexiting patients, resolution of the keratitis and healing of the ulcer occurred in 175 (94%) nonexiting patients. In the 175 patients in whom the corneal ulcer was cured, there were no statistically significant differences between the treatment groups for the mean time to cure (P = 0.25). There were no statistically significant differences between the 3 treatment groups in the various sign parameters including the sign score. A positive bacterial corneal culture was obtained in 190 (83%) of the 229 enrolled patients. The distribution of the species of bacterial organisms was similar in each treatment group and no significant difference in the percentage of isolates between the groups was observed. Twelve (5.2%) of the treated patients had serious complications (perforation or enucleation). No serious events attributable to therapy occurred during the study and all treatments were safe and well tolerated. CONCLUSION: No difference in healing rate, cure rate, or complications between fortified cephazolin and tobramycin, ofloxacin, or moxifloxacin was seen in this study.

Visual acuity thresholds for cataract surgery and the changing Australian population.

OBJECTIVE: To examine the relation between visual acuity thresholds for cataract surgery for the changing Australian population. METHODS: Population-based 5-year incidence data for 2594 people were used to calculate age-specific prevalence of incident cataract and existing cataract backlog. The cataract surgery rates (CSRs) per million people were estimated for different acuity thresholds for the Australian population at different times. RESULTS: In 2005, after adjusting by age, the estimated CSRs for Australia were 1470, 3110, 5080, and 6440 for visual acuities of less than 6/60, less than 6/18, less than 6/12, and less than 6/9, respectively, whereas the actual CSR was 9000. Although the acuity threshold had the greatest impact, the CSR for less than 6/12 increased 3-fold from 2300 in 1950 to 7210 in 2020 because of demographic changes. CONCLUSIONS: Demographic changes, with an increasing proportion of older people, will continue to increase the need for cataract surgery, as will a reduction in the visual impairment threshold. Plans for the future for eye care services should take these factors into account.

Rapid and cost-effective method to assess vision disorders in a population.

PURPOSE: The aim was to develop a means of rapidly assessing eye health in a cost- and time-effective way to monitor changes over time. METHODS: Key features of the five main eye diseases that cause vision loss in Australia were assessed. Participation was volunteer-based from randomly selected Melbourne suburbs. Recruitment was by mail. Anterior segments and fundi were photographed with a digital non-mydriatic fundus camera. Visual fields were tested with Frequency Doubling Technology. A questionnaire collected information about demographics, general health and lifestyle. Findings from this rapid assessment were compared with those from a population-based study. RESULTS: A total of 1695 people, aged between 70 and 79 years (mean 74), were recruited. The rates and causes of visual impairment were similar between the rapid assessment method and the population-based study. Among the 134 people (8%) with visual impairment at presentation, 98 (73%) had undercorrected refractive error, 17 (13%) had age-related macular degeneration, 11 (8%) had cataract, 2 (2%) had diabetic retinopathy and 2 (2%) had glaucoma. Screening costs per participant were only about AU$145, compared with AU$433 in the Melbourne Visual Impairment Project (VIP). The application of Frequency Doubling Technology as well as the use of a non-mydriatic digital camera for fundus and lens photography resulted in an average examination time of less than half the time needed in the VIP. Data collection took 3 months rather than 4 years in the VIP. CONCLUSION: The rapid assessment method was efficient in time and cost and produced results comparable to a normal population-based survey. Repeating the study design for a similarly sampled group every 2 years would allow the assessment of changes in the prevalence of undiagnosed eye disease.

Lutein and zeaxanthin and the risk of cataract: the Melbourne visual impairment project.

PURPOSE: To evaluate the association of cortical, nuclear, or posterior subcapsular (PSC) cataract with dietary intake of lutein-zeaxanthin (LZ) in a population-based sample. METHODS: For the study, 3271 (83% of the eligible residents) permanent residents aged > or =40 years were recruited in 1992 to 1994 via a cluster random sampling. In 1997 to 1999, 2594 (79%) attended the follow-up examination including lens photography, a life-style questionnaire, and a food-frequency questionnaire (FFQ). Cases were those with cortical opacity > or =4/16, nuclear opacity grade > or =2.0, or PSC opacity > or =1 mm2. Logistic regression was used to calculate the odds ratios for cataract by daily LZ intake, or its quintile indicator with the lowest quintile as the baseline category, controlling for energy-adjusted fat intake and variables previously found to be associated with the cataract outcomes. RESULTS: Of the 2322 participants who attended the follow-up survey and completed the FFQ, 1841 (79%), 1955 (84%), and 1950 (84%) were included in the analyses of cortical, nuclear, and PSC cataract, respectively. There were 182 (9.9%), 387 (19.8%), and 177 (9.1%) cases for cortical, nuclear, and PSC cataract, respectively. Cortical and PSC cataract were not significantly associated with LZ intake. For nuclear cataract the odds ratios were 0.67 (0.46-0.96) and 0.60 (0.40-0.90) for every 1-mg increase in crude and energy-adjusted daily LZ intake, respectively. The odds ratios (95% CI) for those in the top quintile of crude LZ intake was 0.58 (0.37-0.92; P = 0.023 for trend), and it was 0.64 (0.40-1.03) for energy adjusted LZ intake (P = 0.018 for trend). CONCLUSIONS: This study found an inverse association between high dietary LZ intake and prevalence of nuclear cataract.

Utilization of eye care services in Victoria.

PURPOSE: To determine baseline eye care utilization by older Victorians in order to assess change in 2 years after an eye health promotion campaign. METHODS: A letter of invitation to participate was sent to all people aged 70-79 years in randomly selected Melbourne postcode areas. A questionnaire was designed to allow gathering of eye health-related information. Eye exams included autorefraction, frequency doubling technology and non-mydriatic fundus photography. Results were compared with the Melbourne Vision Impairment Project . RESULTS: A total of 1695 people with a mean age of 74 years were recruited. The overall proportion with visual impairment was 8% (134/1695), of which 27% (36/134) was due to non-refractive causes. Only 31% (11/36) of visually impaired people knew about low-vision services, of whom 20% (7/36) had used them. Of all people with diabetes, only 52% (96/184) had a dilated eye exam within the recommended 2 years (Melbourne Vision Impairment Project 44%). CONCLUSIONS: Compliance rates with recommendations for 2-yearly eye exams for people with diabetes have not improved since the last major eye health study in Victoria 10 years ago. The same is true for the rate of undiagnosed glaucoma, suggesting that messages about eye examinations need to be promoted for older people at high risk of vision loss, for example, those with diabetes and at risk of vision loss from glaucoma.

Evaluation of an eye health program: the vision initiative.

PURPOSE: The aim of this study was to develop an innovative, rapid and economical assessment methodology to determine the knowledge, attitudes and behaviours regarding eye health and to determine the rates of the most common causes of visual impairment and undiagnosed eye disease. METHODS: Letters were posted to Seniors Card holders aged 70-79 in 18 randomly selected areas, stratified by socio-economic status. A questionnaire was developed to measure knowledge, attitudes and behaviours regarding eye health. Uncorrected refractive error was determined by measuring presenting and best-corrected visual acuity (VA). Diabetic retinopathy and age-related macular degeneration were assessed using digital non-mydriatic retinal photography. Glaucoma was assessed using Frequency Doubling Technology (FDT) and digital images of the optic nerve head. Cataract was determined using digital retro-illumination images of the lens taken with a non-mydriatic camera. The cost for recruiting, examining and grading images for each participant was calculated by dividing the total study cost by the number of participants examined. RESULTS: Of the 13,483 participants invited to participate in the study, appointments were made for 1860 (13.8%) people with 1,701 (91%) actually attending. Overall, missing data from the 1,695 questionnaires represented less than 1.0% and all participants attended the vision screening over a three-month period. Presenting and best-corrected visual acuity and FDT results on both eyes were obtained on 99% of the sample. The proportion of gradable digital images of the fundus in both eyes in the sample was 89%, while 90% of participants with bilateral presenting VA<6/12 had assessable lens images. The cost for recruiting, examining and grading images for each participant was approximately 150 AUS dollars. CONCLUSION: The recruitment from a mailing obtained the required sample size for the study, allowing a large sample of participants to be examined efficiently over a short period of time. It is important that the most common causes of visual impairment and undiagnosed eye disease can be determined using this rapid assessment methodology.

Vision loss in Australia.

OBJECTIVE: To assess the prevalence and causes of vision loss in Australia and to project these data into the future. DESIGN: Synthesis of data from two cross-sectional population-based cohort studies--the Melbourne Visual Impairment Project and the Blue Mountains Eye Study--and extrapolation to the entire Australian population. SETTING AND PARTICIPANTS: 8376 community and 533 nursing home residents recruited between 1992 and 1996 in urban and rural Victoria and New South Wales. MAIN OUTCOME MEASURES: Age-standardised prevalence of low vision (visual acuity < 6/12) and blindness (visual acuity < 6/60) (both measured in the best eye, with spectacles if usually worn for distance vision), and their causes for the Australian population for 2000 to 2024, projected from Australian Bureau of Statistics population data. RESULTS: In 2004, 480,300 Australians were estimated to have low vision, including 50,600 with blindness. The most common causes of low vision were undercorrected refractive error (62%), cataract (14%) and age-related macular degeneration (10%). The latter was responsible for almost half of all cases of blindness. The numbers of people with low vision and blindness are projected to almost double by 2024. CONCLUSIONS: Vision loss in Australia is a much bigger problem than is usually recognised; 76% of low vision is caused by uncorrected refractive error or cataract, both readily treatable. However, the prevention and treatment of macular degeneration poses a major challenge.

Association of the M55L and Q192R paraoxonase gene polymorphisms with age-related macular degeneration.

PURPOSE: To investigate the reported association of the two single-nucleotide polymorphisms (SNPs) of the paraoxonase gene (PON1), Met-Leu 55 (M55L) and Gln-Arg 192 (Q192R), in individuals of Anglo-Celtic descent who have age-related macular degeneration (AMD). DESIGN: Case-control association study. METHODS: Sixty-two individuals with late (end-stage) AMD and 115 control subjects (without AMD) were included in this study. The M55L and Q192R SNPs were amplified by polymerase chain reaction and genotyped, and statistical analysis was undertaken. RESULTS: No association of either SNP was detected in persons of Anglo-Celtic descent who had AMD, although there was a significant difference in SNP allele frequency between Anglo-Celtic and Japanese individuals. CONCLUSION: The M55L and Q192R SNPs of the PON1 gene do not appear to be associated with late AMD in individuals of Anglo-Celtic descent.

Detection of undiagnosed glaucoma by eye health professionals.

PURPOSE: To examine the clinical features of undiagnosed open-angle glaucoma (OAG) in people who have attended an eye care provider within the previous 12 months and to suggest strategies to assist in the early detection of glaucoma. DESIGN: Population based cross-sectional study. PARTICIPANTS: Permanent residents aged 40 years and older at recruitment during 1992 through 1996. METHODS: A cluster-stratified random sample of 4744 participants from the urban and rural cohorts was studied. Structured standardized interviews and dilated ocular examinations were conducted in all eligible participants. Data on demographic characteristics, prior knowledge of eye disease, use of eye care services, intraocular pressures, cup-to-disc ratios, visual fields, and photography of optic discs were obtained. All suspected glaucoma cases were submitted to a panel of 6 ophthalmologists to determine glaucoma diagnosis. MAIN OUTCOME MEASURES: Clinical features of participants seen by eye health professionals within the previous 12 months who have previously undiagnosed OAG, previously diagnosed OAG, and no glaucoma. RESULTS: Thirty-five previously undiagnosed and 43 previously diagnosed participants had visited an optometrist or ophthalmologist or both in the previous 12 months. Age and gender were not significantly different between the undiagnosed and diagnosed glaucoma cases. After logistic regression, the type of eye professional seen (odds ratio [OR], 45.17; 95% confidence interval [95% CI], 5.89-346.17; P = 0.0002) and the presence of visual field defects (OR, 0.06; 95% CI, 0.01-0.69, P = 0.020) were the only statistically significant variables between the diagnosed and undiagnosed glaucoma groups. CONCLUSIONS: Raised intraocular pressure should not be relied on as the only triggering factor in glaucoma investigations.

The need for routine eye examinations.

PURPOSE: To determine the incidence and causes of vision loss to assist in the objective determination of the preferred frequency of routine screening for those with normal vision. METHODS: A prospective, population-based study of people aged 40 or more years. Standardized examination protocols were used that included presenting and best corrected visual acuity, visual field testing, and comprehensive eye examination with dilation. RESULTS: There were 2529 people with a full data set, including 1590 with a normal baseline examination. The 5-year incidence of vision loss (<6/12 presenting acuity in the worse eye) was 2.39%. Overall, 24 (63%) of 38 of those with vision loss had noticed a change in their vision, and 18 (75%) of these 24 had attended an eye examination. This left only 14 (0.88%) people who had had normal baseline examination results and had asymptomatic vision loss develop over this 5-year period. CONCLUSIONS: Frequent routine eye examinations of those with normal examination results will have a low yield and may not be cost effective. Health promotion messages should target those who notice a change in vision and those at higher risk such as those with diabetes or a family history of eye disease.

The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration.

PURPOSE: To date, of all the genes studied in relation to age-related macular degeneration (AMD), the alleles of the apolipoprotein (apoE) gene have been the most consistently associated with disease. However, not all apoE studies have found an association, and among these the associations differ. The current study was conducted to investigate further the association of this gene in AMD. METHODS: Three hundred twenty-two unrelated individuals with diagnosed AMD and 123 unrelated but ethnically matched control subjects were analyzed. All subjects completed a standard questionnaire and were given a fundus examination. A blood sample was collected for DNA extraction. The common allelic variants of apoE were screened through the use of polymerase chain reaction (PCR) and restriction enzyme digestion followed by statistical analysis. RESULTS: Individuals with the epsilon3 epsilon4 genotype of apoE had an approximate halving of disease risk for late (end-stage) AMD (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.34-0.98) relative to the epsilon3 epsilon3 genotype at age of ascertainment. Stratification of late AMD into atrophic and neovascular disease revealed that the greatest protective effect for the epsilon3 epsilon4 genotype was in individuals with atrophic disease (OR 0.35, 95% CI 0.13-0.92). Men with the epsilon3 epsilon4 genotype also showed almost a threefold reduction in risk of disease in late AMD (OR 0.36, 95% CI 0.16-0.82). However, individuals with late AMD and the epsilon2 epsilon3 genotype had a significantly earlier mean age of diagnosis of disease (3.4 years, P = 0.015) compared with those with the epsilon3 epsilon3 genotype, and this was most evident in women (3.9 years, P = 0.011) and in individuals with neovascular disease (4.7 years, P = 0.003). CONCLUSIONS: The alleles of apoE appear to have a role in the etiology of AMD, with the epsilon4 allele being protective, or at the very least, delaying the age of diagnosis of disease, whereas the epsilon2 allele appears to have a modifier effect by bringing forward the mean age of disease diagnosis.

Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient.

Patients initiated on fluconazole and levofloxacin should be closely monitored for QTc-interval prolongation. While there have been published reports of fluconazole and levofloxacin causing QTc-interval prolongation when given alone, coadministration of these two agents may further increase this risk. This case describes an episode of TdP in which levofloxacin and fluconazole were likely significant factors. QT prolongation was present at baseline prior to drug initiation (QTc = 454-505 ms) and levofloxacin resulted in further prolongation (QTc = 480-536 ms). After two days of therapy with fluconazole, overlapping with levofloxacin, the patient had an episode of PMVT with syncope, and progressive QT prolongation was evident (QTc = 554 ms). Only mild hypokalemia (potassium concentration = 3.6 meq/L) was present, and not additional etiologies for TdP were identified. Levofloxacin and fluconazole were discontinued and no further PMVT was observed, but the QT interval did not return to normal until after an additional 11 days (QTc = 436 ms). As in many cases of TdP, multiple factors were involved. Renal failure, drug dosing, mild hypokalemia, and a baseline abnormal QT interval potentiated the role of levofloxacin and fluconazole in the development of TdP. We recommend that neither drug be used alone or in combination when there is baseline QT prolongation. We also recommend that concomitant use of these agents be avoided when possible. If combination therapy is required, caution is warranted, particularly in patients with risk factors for QT prolongation. Specific attention should be given to drug dosing, interactions, electrolytes, and ECG monitoring.

The impact of smoking on use of hospital services: the Busselton study.

OBJECTIVE: To use the Busselton study to estimate the impact of smoking on hospital use in Australia. METHODS: People on the electoral roll in Busselton in 1978 were invited to attend a survey where smoking habits were measured. 3,230 people aged 25 to 79 at the survey were followed until 1994 by record linkage to death records and to the Western Australian Hospital Morbidity Data System. Hyper Poisson regression was used to estimate ratios of hospital separation rates and mean bed day usage according to the 1978 smoking status. RESULTS: Compared with never smokers, current smokers had hospital separation rates that were 1.32 (95% confidence interval 1.16-1.49) times higher and used 1.40 (1.20-1.65) times as many hospital bed days. Former smokers had rates midway between never and current smokers. Separations due to neoplasms, circulatory disorders and respiratory disorders were all more frequent in current than in never smokers. Estimates of hospital use in Australia due to smoking were about two times higher than those previously published using different methods. CONCLUSIONS: Smoking is a major contributor to hospital use in Australia. People who stop smoking reduce their risk of hospitalisation. IMPLICATIONS: Smoking has a major impact on hospital use, which can be reduced by successful smoking cessation programs.