The antimalarial ferroquine: from bench to clinic.

Ferroquine (FQ, SSR97193) is currently the most advanced organo-metallic drug candidate and about to complete phase II clinical trials as a treatment for uncomplicated malaria. This ferrocene-containing compound is active against both chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P. vivax strains and/or isolates. This article focuses on the discovery of FQ, its antimalarial activity, the hypothesis of its mode of action, the current absence of resistance in vitro and recent clinical trials.

Risk factors for microbial keratitis with contemporary contact lenses: a case-control study.

OBJECTIVE: To assess the relative risks (RR) of microbial keratitis (MK) for contemporary contact lens (CL) types and wearing schedules. DESIGN: A 2-year prospective case-control study begun in December 2003. PARTICIPANTS: Cases were 367 CL wearers attending Moorfields Eye Hospital with proven or presumed MK. Controls were 1069 hospital controls, who were CL wearers with a disorder unrelated to CL wear, and 639 population-based controls who were CL wearers randomly selected from the Moorfields catchment area. Hospital patients completed a self-administered questionnaire; population-based controls were interviewed by telephone. TESTING: Multivariate analysis was done both for all cases of MK, and for the moderate and severe MK subgroups alone. MAIN OUTCOME MEASURES: The RR for developing MK, and vision loss, for all lens types compared with planned replacement soft lenses (the referent). RESULTS: Compared with planned replacement soft lenses (the referent), the RR of MK was significantly increased with daily disposable (DD) CLs (RR, 1.56x [95% confidence interval (CI), 1.1-2.1]; P = 0.009) and differed between different brands of DD lens, was reduced for rigid lenses (RR, 0.16x [95% CI, 0.06-0.4]; P<0.001), and no different for silicone hydrogel or other types of soft lens. Although the risk of MK was higher overall among DD lens users, the risk of vision loss was less than for planned replacement soft CL users (P = 0.05); no DD lens users lost vision to the level of >or=20/40. The RR for overnight wear, for any lens type, was 5.4 times higher (95% CI, 3.3-10.9; P<0.001). Comparison of the DD soft CL types with planned replacement soft lenses (the referent), showed significant differences between brands for the risk of MK. CONCLUSIONS: The risk of MK has not been reduced in users of DD and silicone hydrogel CLs. However, vision loss is less likely to occur in DD than in reusable soft CL users. Different brands of CL may be associated with significantly different risks of keratitis; understanding these differences should lead to the development of safer soft lenses. These findings suggest that lens/ocular surface interactions may be more important in the development of corneal infection than oxygen levels and CL case contamination.

Trends in serious ocular trauma in Scotland.

PURPOSE: To report trends in serious, sight-threatening ocular trauma in Scotland. METHODS: A prospective, population-based, observational study of patients with ocular trauma admitted to hospital in Scotland during a 12-month period (2008-2009), conducted through the British Ophthalmic Surveillance Unit. Data on circumstances of the injuries and visual outcomes were collected using protocols standardised to those from an earlier study (1991-1992) to allow direct comparisons over time. RESULTS: In all, 0.3% of all emergency admissions in Scotland were for ocular trauma. Significant differences were observed between the time periods in where an injury occurred (P=0.009): a reduction of those occurring in a sports/leisure facility (8.2%) and an increase in those occurring on the street (21.4%). Assaults remained the most common cause of injury (31%). Gender differences persisted with females more likely to have an injury from falls (OR=8.67; 95% CI: 2.41-31.49; P=0.002), or in the home (OR=5.40; 95% CI: 1.69-17.16; P=0.009 ), and less likely to have one in the workplace (P=0.06). Poor visual outcome was associated with injuries occurring in the home (OR=4.33, P=0.047), in a public place (OR=6.25, P=0.047), and those caused by a fall (OR 42.75, P<0.001); or assault (OR 7.29, P=0.019). Half of those with a poor outcome have no perception of light. CONCLUSION: Serious ocular trauma remains an infrequent, sight-threatening event, associated with significant monocular visual morbidity. The findings suggest a shift from corporate to personal responsibility for risk awareness, health, and safety.

Outcome of psychotherapy among early adolescents after trauma.

OBJECTIVE: The authors evaluated the effectiveness of brief trauma/grief-focused psychotherapy among early adolescents exposed to the 1988 earthquake in Armenia. METHOD: Posttraumatic stress and depressive reactions among treated and not treated subjects were evaluated pre- and postintervention, at 1 1/2 and 3 years after the earthquake, respectively. RESULTS: Severity of posttraumatic stress symptoms significantly decreased among the subjects given psychotherapy, while severity of these symptoms increased significantly among the subjects not treated with psychotherapy. The improvement in posttraumatic stress symptoms was attributable to improvement in all three symptom categories (intrusion, avoidance, and arousal) of posttraumatic stress disorder (PTSD). There was no change in severity of depressive symptoms among subjects given psychotherapy. However, depressive symptoms among subjects not treated with psychotherapy significantly worsened over time. The changes in severity of posttraumatic stress and depressive symptoms were positively correlated within both groups. CONCLUSIONS: The findings demonstrate the efficacy of trauma/grief-focused brief psychotherapy in alleviating PTSD symptoms and preventing the worsening of comorbid depression among early adolescents after a catastrophic disaster. The results support the broad use of such school-based interventions after major disasters and demonstrate the cross-cultural applicability of Western psychotherapeutic approaches.

Nonulcerative complications of contact lens wear. Relative risks for different lens types.

A case-control study was used to evaluate the relative risk (RR) of acute contact lens-related disorders. The study sample comprised new patients wearing contact lens presenting at the accident and emergency department at Moorfields Eye Hospital, London, England, in 12 months. Disorders were classified by pathogenesis. Compared with gas-permeable hard contact lenses (the referent), extended-wear soft contact lenses were related to the largest overall RR for any complication (2.7 [95% confidence limits, 1.73, 4.16]), whereas for daily wear soft contact lenses the overall RR was 1.3 (confidence limits, 1.0, 1.72). Relative risks were greatest for extended-wear soft contact lens wearers with metabolic disorders (2.1 [confidence limits, 1.28, 3.4]) and for such wearers with sterile infiltrates (2.4 [confidence limits, 1.22, 4.84]). Among those using daily wear contact lenses, RR was highest for those with toxic/hypersensitivity disorders (5.9 [95% confidence limits, 3.27, 10.49]). Severe complications involving greater morbidity occurred more frequently with extended-wear soft contact lenses. This could be reduced by selecting a more appropriate lens type to correct low refractive errors.

Risks of keratitis and patterns of use with disposable contact lenses.

Disposable soft contact lenses have been marketed as a safer alternative to conventional soft lenses. We undertook a case-control study of patients attending the casualty unit of an eye hospital to quantify the relative risk of keratitis in disposable lens wear and to establish associated patterns of use. All eligible contact lens users were identified and asked to complete a questionnaire (n=242). Keratitis, microbial or sterile, was the most common complication in disposable lens users, occurring in 16 of 41 subjects. The relative risks for all lens types were estimated by comparison with rigid lenses (the referent). Both extended- and daily-wear disposable lenses were associated with higher risks of keratitis than other lens types including conventional extended-wear lenses. Poor hygiene, disinfectant system failure, and lens type may all account for these statistically significant trends.

Decreasing stromal iris pigmentation as a risk factor for age-related macular degeneration.

To evaluate iris color, change of iris color, and iris pigment epithelial defects as risk factors in age-related macular degeneration, we compared 101 patients with age-related macular changes with 102 control subjects in a case-control study. Three of 101 patients (3%) and four of 102 control subjects (4%) had epithelial iris defects. Light iris color during youth was reported by 51 of 101 patients (50.5%) and 42 of 102 control subjects (41.2%) (odds ratio, 1.46; P = .184). Of the 101 patients, 26 (25.7%) noticed their iris color to have become lighter during life compared with six of 102 control subjects (5.9%) (odds ratio, 5.5; P = .0001). At present examination, 63 of 101 patients (62.4%) had light irides compared with 43 of 102 control subjects (42.2%) (odds ratio, 2.27; P = .004). These results suggest that initial light iris color and iris pigment epithelial defects are not associated with an increased risk of age-related macular degeneration, whereas decreased stromal iris pigmentation may indicate a higher risk.

Drusen as risk factors in age-related macular disease.

In a study of 150 consecutive patients with age-related macular disease and unilateral visual loss, the drusen in the better eye were analyzed for size, number, density, and fluorescein angiographic appearance, and these characteristics were compared with the type of the lesion causing visual loss in the contralateral eye. In the fellow eye of an eye with avascular detachment of the retinal pigment epithelium, the drusen were more densely packed, larger, and less fluorescent than in the fellow eye of an eye with primary neovascularization. The characteristics of drusen in fellow eyes of those eyes with pigment epithelial detachments and evidence of subpigment epithelial new vessels were intermediate between the other two groups. Because there is significant symmetry of drusen between fellow eyes, these data imply that the characteristics of drusen are important in the determination of the form of the lesion complicating age-related macular disease.

Evolution of age-related macular degeneration with choroidal perfusion abnormality.

Prolonged choroidal filling on fluorescein angiography in age-related macular degeneration is thought to indicate diffuse thickening of Bruch's membrane. To test the importance of this clinical sign, we reviewed the evolution of disease in eyes of patients with good visual acuity and a readable transit phase of fluorescein angiography at the time of recruitment into a longitudinal study of age-related macular degeneration. Ninety-six eyes satisfied these criteria. Of the 32 eyes with prolonged choroidal filling, 12 (38%) lost two or more lines, of visual acuity by two years, whereas only nine of 64 (14%) eyes with normal choroidal filling did so. The difference was caused by the higher incidence of geographic atrophy in the first group. The proportion of eyes that developed subretinal neovascularization was the same in the two groups, and no pigment epithelial detachments occurred. These findings indicate that this clinical sign has implications concerning visual prognosis in age-related macular degeneration.

Epidemiology and implications of ocular trauma admitted to hospital in Scotland.

OBJECTIVES: To describe the current epidemiology of serious ocular trauma which necessitates admission to hospital so that health and safety strategies for the prevention of ocular injuries and their role within the national health strategy, The Health of the Nation, can be better informed. DESIGN: A prospective observational study of all patients with ocular trauma admitted to hospital under the care of a consultant ophthalmologist between 1 November 1991 and 31 October 1992. SETTING: All ophthalmic department in Scotland. SUBJECTS: All patients with ocular trauma admitted to hospital in Scotland. The population of Scotland represented the population at risk of injury. MEASURES AND MAIN RESULTS: Measures included the type and cause of injury, the place where it occurred, and awareness of risk and safety. All ophthalmic departments in Scotland participated and 428 admissions were reported. The home was the most common place for a serious injury to occur (30.2%), followed by the workplace (19.6%) and a sports or leisure facility (15.8%). The home was the single most frequent place of injury for the 0-15 year and 65 year and over age groups. Tools or machinery, either at home (13.9%) or at work (10.3%), were collectively (24.2%) the most frequent cause of injury, followed by assault (21.8%) and sports-related activities (12.5%). The most frequent type of injury was a blunt injury (54.4%). Six per cent (n = 25) of all injuries were bilateral. Only 13.2% of patients were aware of any risk of injury, with 5.6% aware of any risk at home. When applicable, protective eye wear was only available to 48.6% of patients and only 19.4% of these used it. CONCLUSION: Serious ocular trauma frequently occurs at home and the young and the elderly are particularly at risk. This represents a significant change in the epidemiology of serious ocular trauma and has important implications for prevention. Health and safety strategies specifically aimed at preventing eye injury should now include the home as a high risk environment in addition to the work-place and sports/leisure facilities. The target groups for accident prevention in The Health of the Nation strategy include those at risk of serious ocular trauma with potentially sight threatening sequelae. Those involved in implementing the national accident prevention strategy should be aware of this, for in this process it is possible that some serious eye injuries may also be prevented.

Risk factors for treatment outcome of suspected microbial keratitis. Ofloxacin Study Group.

BACKGROUND: Primary treatment for suspected microbial keratitis is generally successful. Although risks such as contact lens use are well recognised as causative factors for microbial keratitis, little is known about the risk factors that influence treatment outcome. The present study evaluates the risk factors assessed at diagnosis as prognostic indicators of primary treatment failure. METHODS: Patients were prospectively enrolled in the ofloxacin treatment trial and data concerning symptoms, treatments, past and concurrent eye disease were collected along with the measurement of corneal ulcer size at the slit lamp. All patients were scraped for microbiological investigation, and treated with either ofloxacin (0. 3%) or standard therapy of fortified cefuroxime and gentamicin drops. Treatment success was complete healing of the ulcer with zero dimensions of the epithelial defect within 2 weeks of start of treatment. The important prognostic indicators were selected by comparison among those who failed treatment, had delayed healing, or were culture positive with other patients using univariate and stratified analysis. These were then used in a Poisson model for multiple regression analysis to estimate the relative risk of the main prognostic variables. RESULTS: Of the 118 patients enrolled in the study, 14 were identified as primary treatment failures, 17 had slow healing, and 15 indolent ulcers. There were 49 culture positive patients. The multivariate analysis identified that large culture positive ulcers in patients 60 years or older had 5.5 times the risk of primary treatment failure (p<0.001). Significant predictors of slow healing were previous ocular disease and a positive culture; significant predictors of indolent ulceration were previous ocular disease and steroid use at diagnosis; the main predictor of a culture positive result was ulcer size. CONCLUSIONS: Elderly patients with large ulcers were more likely to be culture positive, fail primary therapy, and require surgical intervention. A positive microbial culture provided prognostic information regardless of the organism isolated. However, this information was of less value for those with small ulcers and for younger patients.

3.8 million blinded by cataract each year: projections from the first epidemiological study of incidence of cataract blindness in India.

Data from a population based longitudinal study of randomly selected communities in Central India have for the first time provided direct estimates of age specific incidence of blindness from cataract. Person-time denominators have been used to compute age specific incidence rates (risk) of blindness from cataract for populations aged 35 and older. These age specific incidence measures have been applied to the 'population at risk' in each 5-year age class in order to estimate the total number of new cases of cataract blindness that occur in the country each year. The findings indicate that an estimated 3.8 million persons become blind from cataract each year in India (approximate 95% confidence limits: 3 to 4.5 million). The reasons why the estimates are considered as minima, and their implications concerning future national planning of ophthalmic services, are briefly discussed.

Visual outcome following posterior capsule rupture during cataract surgery.

AIM: To determine the relative risk of a poor visual outcome following posterior capsule rupture during cataract surgery. METHODS: Prospective data were collected on consecutive eyes undergoing cataract extraction. The patient's age, preoperative visual acuity, ocular comorbidity, grade of surgeon, and operative complications were documented. The best spectacle corrected visual acuity was recorded at discharge from the hospital service. RESULTS: From a total of 1533 cases, 1420 (92.6%) eyes had complete follow up data. Posterior capsule rupture occurred in 59 (4.1%) cases. Eyes with posterior capsule rupture were 3.8 times more likely to have a final best spectacle corrected visual acuity less than 6/12. CONCLUSIONS: Eyes having posterior capsule rupture during cataract surgery have a significant risk of reduced visual acuity.

A rapid method of grading cataract in epidemiological studies and eye surveys.

A rapid method of grading clinically important central lens opacities has been developed for use in eye surveys and in epidemiological studies of cataract and has been field-tested in a specifically designed observer agreement study in a survey of a rural community in Central India. The grading method is based on simple measurement of the area of lens opacity that obscures the red reflex relative to the area of clear red reflex, as visualised through the undilated normal pupil. Good to almost perfect agreements were attained between two ophthalmologists and two trained ophthalmic assistants for overall grades of central lens opacity. Most disagreements were trivial in nature and were concerned with difficulties in distinguishing grade 0 from grade 1, and with hazy appearance of the red reflex in high myopes and in cases of early nuclear sclerosis. Teaching materials including video tape and slides for training survey teams and other workers are in preparation.

Alterations of the anterior lens capsule associated with climatic keratopathy.

We describe changes in the anterior lens capsules of older people in Somalia, a country which is close to the equator and with large areas of sand, often highly reflective of sunlight. The capsule changes are confined to the central pupillary area. In order of apparently increasing severity they consist of a white opalescence ('frosting'), an elevation in front of the contour of the rest of the lens to form a plateau, and a 'bag' or herniation of the lens capsule through the pupil. Plateau and bagging taken together are strongly associated with climatic keratopathy (and by inference with reflected ultraviolet exposure), weakly associated with exfoliation syndrome, inversely related to the degree of cataract, and interfere severely with vision.

Outcome of cataract surgery in central India: a longitudinal follow-up study.

An epidemiological follow-up study of patients who had intracapsular cataract extraction in a voluntary hospital and its associated eye camps in Central India has for the first time evaluated the outcome one year after surgery in terms of visual acuity, use of spectacles, and improvement in income and mobility. The findings indicate that under these fairly typical conditions, 92% of the cases have adequate vision of 6/18 or better one year after surgery. Information on high usage of spectacles and on considerable improvements in income and mobility after cataract surgery is also reported. The outcome for patients operated upon in eye camps was almost as favourable as for those operated upon in hospital. Although the small differences are not statistically significant, the comparative findings require cautious interpretation and give rise to the epidemiological issues which are briefly discussed in this paper.

Childbearing and risk of cataract in young women: an epidemiological study in central India.

BACKGROUND/AIMS: Observations in central India, over a period of more than a decade, suggested that the frequency of sight restoring cataract surgery was substantially higher in women of childbearing age compared to men of the same age. Formal surveys in the subcontinent of India have confirmed a higher prevalence of cataract in women. The present study was conducted to explore possible effects of childbearing and associated adverse factors on cataract risk. METHODS: A case-control study design was used. Cases were mothers aged 35-45 with bilateral "senile" cataract. Controls were mothers of the same age but with clear lenses, attending the hospital services with other, mostly minor, complaints. RESULTS: A significant association was found between childbearing and risk of sight impairing cataract in mothers. Having more than three babies doubled the risk (adjusted odds ratio 2.0, p=0.012), and the risk increased by an estimated 20% for each additional birth. The birth effect was independent of age, socioeconomic status (occupation and income level), body mass index, and multiple episodes of severe dehydration, all regarded as putative risk factors for cataract. CONCLUSIONS: Having more than three babies may substantially increase the risk of sight impairing cataract in mothers of childbearing age in central India. The findings open new research challenges to identify cataract risk factors to which mothers may be exposed during pregnancy and childbirth, particularly under poor socioeconomic conditions.

Profile of patients presenting for cataract surgery in the UK: national data collection.

AIMS/METHODS: A national data collection exercise was carried out in more than 100 hospital eye service units within the UK to provide clinical and administrative information on patients undergoing cataract surgery. This included patient clinical data such as visual acuity at the time of wait listing and at the time of admission for surgery, presence of other eye disorders, other serious medical disorders, and data on waiting time and type of admission. RESULTS: The profiles of the 18 454 patients aged 50 years or older are reported. Findings of particular note were as follows. At the time of wait listing for cataract surgery 31% had visual acuity of 6/12 or better, 54% had visual acuity between 6/18 and 6/60, and 15% had less than 6/60 vision. Considering those who had visual acuity of 6/12 or better at the time of wait listing, by the time of admission for surgery, the vision deteriorated to 6/18-6/60 in 33% and in a further 3% the vision deteriorated to below 6/60. In patients with moderately poor visual acuity (<6/12-6/60) at the time of wait listing, 13% had less than 6/60 vision by the time of admission for surgery. CONCLUSION: This type of data collection and reporting exercise provides new material that can be used in the planning and provision of cataract surgery services in the UK.

The Arden grating test of visual function: a preliminary study of its practicability and application in a rural community in north-west Iran.

In a preliminary study involving 75 normal and 10 abnormal eyes the Arden grating acuity test was assessed under difficult conditions of rural field work. It was found to be adequately sensitive and specific for screening out individuals with visual impairment due to refractive errors or ocular disease, and to distinguish between these. Inexperienced paramedical personnel could carry out the test satisfactorily with no difficulty and with a minimum of training. In spite of the unusually distracting conditions under which the test was carried out 95% of the subjects tested performed satisfactorily. The results of this preliminary study suggest that the Arden grating test is a valuable tool for screening large populations in rural areas of developing countries.

National cataract surgery survey 1997-8: a report of the results of the clinical outcomes.

AIMS: A national survey of over 100 hospitals in the UK was carried out to collect routine clinical information on the outcomes of cataract surgery. The clinical outcomes of interest were: visual acuity at time of discharge from postoperative hospital follow up, visual acuity at time of final refraction; complications related to surgery occurring during the operation, within 48 hours of surgery, and within 3 months of surgery. In addition, information on age and comorbidity was obtained. This article reports on the findings of the experience of approximately 18 000 patients who had cataract surgery in the hospital eye service of the NHS. RESULTS: Of those with no ocular comorbidity, 85% achieved a visual acuity of 6/12 or better on discharge from postoperative hospital follow up, while 65% of patients with a serious co-existing eye disease achieved this level of acuity at this time. At final refraction, 92% of patients without ocular comorbidity and 77% of patients with ocular comorbidity achieved 6/12 or better visual acuity. The following main risk indicators were associated with visual outcomes and complications related to surgery: age, other eye diseases, diabetes and stroke, type of surgical procedure, and grade of surgeon. CONCLUSIONS: The acceptability of these findings could fruitfully be the subject of discussion within the ophthalmic community and hopefully issues arising out of the study can lead to research, especially in-depth studies of the outcomes of cataract surgery in those patients with co-existing serious eye conditions.