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Background: Streptococcus pneumoniae (Spn) infection remains common worldwide despite recent vaccine efforts. Invasive pneumococcal disease (IPD) is the most severe form of Spn infection. Known individual risk factors for IPD include male gender and African American race. However, area-level socioeconomic factors have not been assessed. We examined the association of neighborhood-level disadvantages and risk of IPD in a tertiary medical center located in a socioeconomic diverse urban area in the Southeastern United States., Methods: Patients hospitalized with culture-confirmed Streptococcus pneumoniae (Spn) infection from 01/01/2010 - 12/31/2019 were identified from electronic health record (EHR). The cohort's demographic and clinical information were obtained from EHR. Patients' residential address was geocoded and matched to 2015 area deprivation index (ADI). The association of ADI and IPD was evaluated using logistic regression after controlling for the demographic information (age, sex, race) and clinical factors (BMI, smoking status, alcoholism, immunosuppressive status, vaccination status, comorbidities)., Results: A total of 268 patients were hospitalized with culture-positive Streptococcus pneumoniae infection and 92 (34.3%) of them had IPD. The analysis showed that higher neighborhood deprivation (ADI in 79-100) was associated with increased risk of developing IPD in younger patients with age less than 65 (p = 0.007) after controlling for the individual demographic information and clinical factors., Conclusions: ADI is a risk factor for IPD in younger adults. Community-level socioeconomic risk factors should be considered when developing prevention strategies such as increasing vaccine uptake in high risk population to reduce the disease burden of IPD., Competing Interests: Declaration of competing interest The authors declared no conflict of interests in this work., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess whether a panel of serum pemphigoid autoantibody tests could be used to confirm an immunopathologic diagnosis of mucous membrane pemphigoid (MMP) in direct immunofluorescent negative (DIF-) MMP patients., Design: Prospective cross-sectional study., Participants: Seventy-six patients with multisite MMP with 45 matched control participants., Methods: Enzyme-linked immunosorbent assays (ELISAs) for BP180 and BP230 (MBL International), immunoglobulin A (IgA) A and immunoglobulin G indirect immunofluorescence (IIF) on human salt-split skin and the keratinocyte footprint assay for anti-laminin 332 antibodies., Main Outcome Measures: Sensitivity and specificity of autoantibody detection and significant differences for individual tests and test combinations for MMP involving different sites., Results: All DIF- patients (24/73 [31.8%]) had either ocular-only disease or ocular involvement in multisite disease. Serum pemphigoid autoantibodies were detected in 29 of 76 MMP patients (38.2%) compared with 3 of 45 control participants (6.7%). Autoantibody reactivity detected by any 1 or more of the tests was present in 6 of 24 DIF- patients (25%) compared with 22 of 49 DIF positive (DIF+) patients (44.9%). Ocular-only MMP serum reactivity was not significantly different for any test or test combination compared with control participants, whereas DIF- multisite ocular MMP differed for 1 ELISA and 3 of 7 test combinations. By contrast, for DIF+ nonocular MMP patients, all the individual tests, apart from IgA IIF, and all test combinations were significantly different compared with those for control participants. For the entire MMP cohort, the sensitivity of all individual tests was low, having a maximum of 21.05% for BP180 reactivity but increasing to 38.16% for an optimal test combination. Disease activity was associated strongly with positive serologic findings., Conclusions: Pemphigoid serum autoantibody tests did not provide immunopathologic evidence of MMP in ocular-only MMP patients but showed limited value in DIF- multisite ocular MMP patients. The requirement for immunopathologic confirmation of MMP by autoantibody detection is inappropriate for DIF- ocular-only MMP patients, resulting in missed diagnoses, delayed therapy, and poor outcomes. Alternative diagnostic criteria for ocular-only MMP are required to exclude the other causes of scarring conjunctivitis until more sensitive and specific immunopathologic tests become available., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: This study was designed to validate a semi-quantitative clinical assessment tool for cicatrising conjunctivitis (CC)., Methods: Fifty-five patients (109 eyes) with mucous membrane pemphigoid (MMP) and 31 patients (61 eyes) with Stevens-Johnson syndrome (SJS) were included. Three methods were used for validation: (1) comparison of inter- and intra-observer reproducibility for the components selected for the initial version of the tool, (2) quantitative measurement of the scarring component with a fornix depth measurer, compared with qualitative Tauber grading methodology, (3) the final version of the tool was compared with the published Sotozono SJS grading system. Main outcome measures included: inter- and intra-observer reproducibility, calculation of composite measures of scarring and morbidity, component redundancy, and correlation with other grading systems., Results: Inter- and intra-observer agreement was moderate-to-excellent for graded components of conjunctival hyperaemia, upper and lower symblepharon, upper and lower fornix depth, corneal vascularisation, and corneal opacity. There was poor-to-good agreement for limitation of motility which was rejected from inclusion in the final tool. Composite scores for scarring components and morbidity components showed good-to-excellent agreement and distribution of ocular disease severity. Analysis of the composite components showed no redundancy - all components contributed independently. Comparison with both Tauber and Sotozono grading methodologies showed good concordance., Conclusions: This study has developed the first validated assessment tool applicable to causes of CC. The tool is concise and discriminates patients with varying disease severity. It measures both disease activity and severity and is suitable for clinical and research applications., Competing Interests: Declaration of competing interest None Declared., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Mucous membrane pemphigoid (MMP) is a rare, chronic and often aggressive subepidermal autoimmune blistering disease potentially affecting several mucous membranes with blisters and secondary erosions and scars. The pathogenesis of MMP is poorly understood, and the contribution of genetic predispositions, other than HLA class II allele variants to MMP, is unknown. The objective of this study is to identify susceptibility genes for MMP in a British cohort of MMP patients. A GWAS was conducted in a British cohort of 106 MMP patients. Publicly available genotypes of 2900 blood donors of the UK Blood Service and of 6740 individuals of the 1958 British Birth Cohort served as control. Subsequently, putative susceptibility genes were independently replicated in a German cohort of 42 MMP patients. The GWAS found 38 SNPs in 28 haploblocks with an odds ratio >2 reaching genomewide significance (P < 5.7 × 10 -7 ). Replication confirmed an association of MMP with SNPs in rs17203398 (OR: 3.9), located intronically in the β-galactocerebrosidase gene (GALC) on chromosome 14 and with recessive polymorphisms in rs9936045 (OR: 3.1) in the intergenic region between CASC16 and CHD9 on chromosome 16. The risk of developing MMP is partially genetically determined. SNPs in GALC enhance the risk for MMP, indicating that β-galactocerebrosidase may be involved in the pathogenesis of MMP. Likewise, impacts of polymorphisms in the intergenic region between CASC16 and CHD9 on the activity of neighbouring genes may facilitate the emergence of MMP. The putative role of both polymorphisms requires functional studies in the future., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose: This study investigated independent risk factors and causative organisms in microbial keratitis in daily disposable contact lens (CL)-wearers., Methods: A multisite prospective case-control study was undertaken. Cases were daily disposable CL-wearers attending Moorfields Eye Hospital with microbial keratitis and those reported through a one-year surveillance study in Australia and in New Zealand. A population-based telephone survey identified daily disposable CL-wearing controls. Subjects completed a questionnaire describing CL-wear history, hygiene and demographics. The sample used for risk factor analysis was weighted in proportion to the CL-wearing population at each location. Corneal scrape results were accessed. Independent risk factors were determined using multiple binary logistic regression. Causative organisms in different CL-wear modalities were compared using a chi-squared test., Results: 963 daily disposable CL-wearers were identified, from which 67 cases and 374 controls were sampled. Independent risk factors were; wearing CLs every day compared with less frequent use (OR 10.4x; 95% CI 2.9-56.4), any overnight wear (OR 1.8x; 95% CI 1.6-2.1), less frequent hand washing (OR 1.8x; 95% CI 1.6-2.0), and smoking (OR 1.3x; 95% CI 1.1-1.6). Certain daily disposable CLs (OR 0.2x; 95% CI 0.1-0.2) had protective effects. Environmental organisms were less frequently recovered with daily disposable CLs (20%), compared with other modalities (36%; p<0.02)., Conclusion: Overnight wear, increased exposure in daily wear, smoking and poor hand hygiene are significant risk factors for microbial keratitis with daily disposable CLs. Risk varied with daily disposable CL type. The profile of causative organisms is consistent with less severe disease.

Background: Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers., Methods: Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study., Results: Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects that may have played a role in the elevated transaminases levels. No clinically significant ECG abnormalities were observed., Conclusions: The parameters and PK/PD model derived from this study pave the way to the further rational development of ferroquine as an anti-malarial partner drug. The safety of ferroquine has to be further explored in controlled human trials. Trial registration anzctr.org.au (registration number: ACTRN12613001040752), registered 18/09/2013.

Background: Artemisinin-based combination therapies (ACTs) are the recommended first-line treatment for uncomplicated Plasmodium falciparum malaria. Ferroquine is a new combination partner for fast-acting ACTs such as artesunate. We aimed to assess different doses of ferroquine in combination with artesunate against uncomplicated P falciparum malaria in a heterogeneous population in Africa., Methods: We did a phase 2, multicentre, parallel-group, double-blind, randomised, dose-ranging non-inferiority trial at eight African hospitals (two in Gabon, three in Burkina Faso, one in Benin, and two in Kenya). We recruited patients presenting with acute P falciparum monoinfection (1000-200,000 parasites per μL), and a central body temperature of at least 37·5°C or history of fever in the past 24 h. We assessed patients in two sequential cohorts: cohort 1 contained adults (bodyweight >50 kg) and adolescents (aged ≥14 years, >30 kg), and cohort 2 contained children (aged 2-13 years, 15-30 kg). We randomly assigned patients (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day for 3 days, or ferroquine monotherapy 4 mg/kg per day given single-blind (ie, allocation was only masked from the patient) once per day for 3 days. We did 14 patient visits (screening, 3 treatment days and 48 h post-treatment surveillance, a visit on day 7, then one follow-up visit per week until day 63). The primary endpoint was non-inferiority of treatment in terms of PCR-corrected cure rate against a reference value of 90%, with a 10% non-inferiority margin, assessed in patients treated without major protocol deviations for parasitologically confirmed malaria. We assessed safety in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00988507, and is closed., Findings: Between Oct 16, 2009, and Sept 22, 2010, we randomly assigned 326 eligible patients to treatment groups, with last follow-up visit on Dec 1, 2010. 284 patients (87%) were available for per-protocol analyses. At day 28, PCR-confirmed cure was noted in 68 (97%, 95% CI 90-100) of 70 patients treated with ferroquine 2 mg/kg plus artesunate, 73 (99%, 93-100) of 74 with ferroquine 4 mg/kg plus artesunate, 71 (99%, 93-100) of 72 with ferroquine 6 mg/kg plus artesunate, and 54 (79%, 68-88) of 68 with ferroquine 4 mg/kg monotherapy. The three dose groups of ferroquine plus artesunate met the non-inferiority hypothesis. The most common adverse events were headache in cohort 1 (30 [19%] of 162 patients) and worsening malaria in cohort 2 (23 [14%] of 164 patients); occurrences were similar between treatment groups., Interpretation: Ferroquine combined with artesunate was associated with high cure rates and was safe at all doses tested, and could be a promising new drug combination for the treatment of P falciparum malaria. Ferroquine could also partner other drugs to establish a new generation of antimalarial combinations, especially in regions that have developed resistance to ACTs., Funding: Sanofi., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

Purpose: Ocular trauma remains an important cause of visual morbidity worldwide. A previous population-based study in Scotland reported a 1-year cumulative incidence of 8.14 per 100 000 population. The purpose of this study was to identify any change in the incidence and pattern of serious ocular trauma in Scotland., Methods: This study was a 1-year prospective observational study using the British Ophthalmological Surveillance Unit reporting scheme among Scottish ophthalmologists. Serious ocular trauma was defined as requiring hospital admission. Data were collected using two questionnaires for each patient 1 year apart., Results: The response rate from ophthalmologists was 77.1%. There were 102 patients reported with complete data giving an incidence of 1.96 per 100 000 population, four times less than in 1992. In patients younger than 65 years, the age-adjusted incidence ratio (males/females) indicated a ninefold higher risk of trauma in males. In 25 patients (27.2%), the injured eye was blind (final visual acuities (FVA) <6/60), 24 being attributable to the eye injury. Standardised morbidity ratios suggested a threefold decrease in risk of poor visual outcome in 2009 compared with 1992., Conclusions: The incidence of serious ocular trauma has fallen; this study has shown hospital admission for serious eye injury in Scotland has decreased fourfold in 17 years. Young adult males continue to be at highest risk, which needs to be specifically addressed in future health-prevention strategies. This study also observed a reduction in visual loss from serious ocular injuries, although the reasons for this require further exploration.

Ferroquine (SSR97193), a ferrocene-quinoline conjugate, is a promising novel antimalarial currently undergoing clinical evaluation. This study characterizes its pharmacokinetic properties. Young male African volunteers with asymptomatic Plasmodium falciparum infection were administered a single oral dose (n = 40) or a repeated oral dose (n = 26) given over 3 days of ferroquine in two dose-escalation, double-blind, randomized, placebo-controlled clinical trials. In addition, a food interaction study was performed in a subsample of participants (n = 16). The studies were carried out in Lambaréné, Gabon. After single-dose administration of ferroquine, dose linearity was demonstrated in a dose range of 400 to 1,200 mg for maximum mean blood concentrations ([C(max)] 82 to 270 ng/ml) and in a dose range of 400 to 1,600 mg for overall exposure to ferroquine (area under the concentration-time curve [AUC], 13,100 to 49,200 ng · h/ml). Overall mean estimate for blood apparent terminal half-life of ferroquine was 16 days and 31 days for its active and major metabolite desmethylferroquine (SSR97213). In the 3-day repeated-dose study, C(max) and overall cumulated exposure to ferroquine (AUC(cum)) increased in proportion with the dose from day 1 to day 3 between 400 and 800 mg. No major food effect on ferroquine pharmacokinetics was observed after single administration of 100 mg of ferroquine except for a slight delay of time to maximum blood concentration (t(max)) by approximately 3 h. The pharmacokinetics of ferroquine and its active main metabolite are characterized by sustained levels in blood, and the properties of ferroquine as a partner drug in antimalarial combination therapy should be evaluated.

Aims: To address the absence from the public health ophthalmology literature of age- and sex-specific prevalence and related resource use for diabetic macular oedema (DMO) in England, UK., Methods: Calculation of age- and sex-specific rates from primary source clinical data, and application to the demographic structure of England to estimate the number of cases affected by DMO. A public health commissioner and provider of social care perspective was adopted in a standard cost of illness study., Results: The number of people with diabetes in England in 2010 was estimated at 2,342,951 of which 2,334,550 were aged ≥ 12 years. An estimated 166,325 (7.12%) had DMO in one or both eyes, and of these, 64,725 individuals had clinically significant DMO reducing the visual acuity to poorer than 6/6 in at least one eye. The overall health and social care costs in 2010, on the pathway from screening to rehabilitation and care in the home, are estimated at £116,296,038., Conclusions: The outcomes of this study should alert public health commissioners and clinical providers to the burden of DMO. The methods employed should also encourage the use of clinical ophthalmic data at the interface between local population and hospital-based recording systems.

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.

Background: The development and spread of drug resistant Plasmodium falciparum strains is a major concern and novel anti-malarial drugs are, therefore, needed. Ferroquine is a ferrocenic derivative of chloroquine with proven anti-malarial activity against chloroquine-resistant and -sensitive P. falciparum laboratory strains., Methods: Adult young male aged 18 to 45 years, asymptomatic carriers of P. falciparum, were included in two-dose escalation, double-blind, randomized, placebo-controlled Phase I trials, a single dose study and a multiple dose study aiming to evaluate oral doses of ferroquine from 400 to 1,600 mg., Results: Overall, 54/66 patients (40 and 26 treated in the single and multiple dose studies, respectively) experienced at least one adverse event, 15 were under placebo. Adverse events were mainly gastrointestinal symptoms such as abdominal pain (16), diarrhoea (5), nausea (13), and vomiting (9), but also headache (11), and dizziness (5). A few patients had slightly elevated liver parameters (10/66) including two patients under placebo. Moderate changes in QTc and morphological changes in T waves were observed in the course of the study. However, no adverse cardiac effects with clinical relevance were observed., Conclusions: These phase I trials showed that clinically, ferroquine was generally well-tolerated up to 1,600 mg as single dose and up to 800 mg as repeated dose in asymptomatic young male with P. falciparum infection. Further clinical development of ferroquine, either alone or in combination with another anti-malarial, is highly warranted and currently underway.

Purpose: To assess the relative risks of acute, nonulcerative complications with recently introduced contact lens (CL) wear modalities (compared with the previously most common soft lens wear schedule), and to identify any other associated factors., Design: A 2-year prospective case-control study commencing in December 2003., Participants: Cases were 877 CL wearers attending Moorfields Eye Hospital with CL-related disorders other than microbial keratitis. Controls were 1069 hospital controls who were CL wearers presenting 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 controls were interviewed by telephone., Testing: The relative risks of developing the CL-related disorders with different CL types were evaluated. For the more common disorders, multivariable analysis was undertaken., Main Outcome Measures: The relative risk of developing an acute, nonulcerative, CL-related disorder., Results: Compared with planned replacement soft CL, daily disposable lenses significantly reduced the risk of toxic/hypersensitivity (odds ratios for CL solution disorders and papillary conjunctivitis 0.1 and 0.5; P<0.001 and P = 0.05, respectively) and metabolic disorders (0.4; P=0.04), but the most commonly used brand was associated with increased risks of sterile keratitis (2.7x; 95% confidence interval [CI], 1.7-4.1; P<0.001), mechanical disorders (2.2x; 95% CI, 1.5-3.2; P<0.001), and a tendency for patients to have lens removal difficulties (P<0.001). Silicone hydrogel CL wear was free from hypoxic complications but associated with an increased risk of sterile keratitis (2.0x; 95% CI, 1.2-3.3; P=0.005), mechanical disorders (1.8x; 95% CI, 1.1-2.8; P=0.015), and attendance with any nonulcerative complication (1.9x; 95% CI, 1.5-2.6; P<0.001) when compared with other reusable soft lenses. Significant additional risk factors were identified for sterile keratitis (overnight wear [ON], more days per week of lens wear, poor hand hygiene, smoking, and less CL experience) and mechanical disorders (ON and less CL experience)., Conclusions: Neither of the 2 recently introduced CL modalities-daily disposable and silicone hydrogel lenses-reduced the overall risk of acute nonulcerative disorders.

Purpose: To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery., Design: Prospective, randomized, double-blinded treatment trial., Participants: Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy., Methods: One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy., Main Outcome Measures: Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery., Results: Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032)., Conclusions: This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients., Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.

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.

Aims: Despite the increase in cataract surgery rates, the volume of unmet needs for this type of surgery in the population is substantial due to ageing and widening of the indication criteria. Our objective was to assess future trends in needs for cataract surgery according to different scenarios of indication criteria., Methods: A discrete-event simulation model was built for the population aged 50 years or older in five regions of Spain (45.7% of the population). Different scenarios of worse eye visual acuity thresholds for indication criteria were compared. Data from the North London Eye Study were used to project the baseline needs for surgery onto the study population. The surgery rate of each region was calculated using the Minimum Data Set. The model used data for the year 2003 and the simulation horizon was 5 years., Results: The volume of need predicted for the year 2008 when scenarios of 0.5 (20/40) and 0.4 (20/50) visual acuity thresholds were used was 69,214 and 51,315 surgeries needed per million inhabitants, respectively. However, unmet needs decreased when a 0.3 (20/70) threshold was used. The increment in the cataract surgery rate needed to prevent the cataract backlog from increasing was 60% for a 0.5 threshold and 50% for a 0.4 threshold., Conclusion: Application of indication criteria following current guidelines would substantially increase unmet needs for surgery in the next 5 years.

Background: Amniotic membrane transplantation (AMT), as a new tool in the armamentarium of therapies available for ocular surface problems, became widely available in the UK in 1998. This study evaluates the indications for treatment, the surgical procedures used, and the results of a subset of the first AMT cases carried out by the group using this nationally available supply. This user group model provides data which is different from that obtained from uncontrolled case series, or clinical trials, and may be more representative of the outcomes that can be expected when a procedure becomes widely available., Methods: The first 233 AMTs, performed by the UK user group, were evaluated by audit and outcomes were assessed at 3 months., Results: Of the 233 transplants, there were 126 (54.1%) valid outcome returns: the outcome for persistent epithelial defects was a healed and stable surface in 11/35 (31.4%, 95% CI 16.9 to 49.3); for chemical/thermal injuries, a healed uninflamed eye with clear cornea in 5/18 (27.8%, 95% CI 9.7 to 53.4); for bullous keratopathy a pain-free, stable surface without bullae in 4/18 (22.2%, 95% CI 6.4 to 47.6); for ocular surface reconstruction, an epithelialised uninflamed conjunctiva without scarring in 12/23 (52.2%, 95% CI 30.6 to 73.2); and for limbal stem cell deficiency, a corneal phenotype in 4/7 (57.1%). The operative technique least associated with failure was use of a bandage contact lens at the end of the procedure (OR 0.19, 95% CI 0.06 to 0.59, p = 0.004). Previous treatment with topical steroids was significantly associated with failure (OR 5.70, 95% CI 1.77 to 18.43, p = 0.004)., Conclusion: Although the outcome criteria used in this study were stringent, and the follow-up duration was short, the results of AMT by this user group were generally less favourable than those of previously reported case series. Controlled clinical trials would improve the quality of evidence for use of amniotic membrane in ocular disease.

Purpose: To determine whether square-edged polymethyl methacrylate (PMMA) intraocular lenses (IOLs) reduce posterior capsule opacification (PCO) in the context of extracapsular cataract surgery in a developing country., Setting: A rural hospital in India., Methods: This was a prospective randomized double-masked fellow-eye controlled study. Over a 4-month period, 118 patients with normal eyes apart from age-related cataract were randomized to receive a square-edged or round-edged PMMA IOL in the first eye. The IOLs were identical apart from the edge profile. The fellow-eye had implantation of the alternative IOL within 1 month. Retroillumination images of the posterior capsule were taken using a dedicated camera system and analyzed to quantify the PCO area using POCO software 1 and 2 years postoperatively and the PCO area and severity using POCOman semiqualitative software at 2 years. Visual acuity was measured using a Gujarati logMAR chart., Results: One hundred fifteen patients were available for examination at 1 year and 107 at 2 years. With POCO software, the PCO area was reduced in the square-edged IOL group at 1 year (median 30% versus 20%, P=.001) and at 2 years (median 45% versus 35%, P=.006). With POCOman, the PCO area and severity were reduced in the square-edged group at 2 years (median 41.5% versus 33.2%, P=.019 and 0.59 versus 0.46, P=.037, respectively). There was no significant difference in visual acuity between the 2 groups at 1 or 2 years., Conclusions: Sophisticated image analysis techniques can be used in developing countries to quantify PCO. Using extracapsular surgery, square-edged PMMA IOLs reduced the PCO area and severity compared with an identical round-edged IOL; however, the differences were not as marked as those reported with phacoemulsification. This may be due to the difficulty of performing a capsulorhexis that lies on the IOL surface in this situation. Nevertheless, square-edged IOLs offer a potential benefit for extracapsular surgery in the developing world.

Background: To determine the efficacy and safety of optic nerve sheath fenestration, and to identify factors predicting visual field (VF) and visual acuity (VA) in patients with progressive pseudotumour cerebri syndrome., Methods: This retrospective observational case series studied 51 eyes of 32 patients with pseudotumour cerebri syndrome, by chart review and comparison of preoperative and postoperative examinations. Main outcome measures included VF, VA and complications., Results: Postoperative VF mean deviation scores improved (P = 0.03) within 6 months when compared with preoperative VF. Multiple regression analysis demonstrated that eyes with mean deviation > or = -20 dB were associated with improved or stabilized VA at 6 months, odds ratio 7.5 and confidence interval (1.2, 46.1), P = 0.03. Eyes with VF defects outside 10 degrees of fixation were associated with improved or stabilized VF at 6 months odds ratio 9.7, 95% confidence interval 1.1, 85.9, P = 0.04. Five patients developed self-limiting complications from surgery., Conclusions: Optic nerve sheath fenestration is safe and effective in stabilizing or improving VF and VA in the short to medium term. Patients with mild VF loss improved following surgery, and patients with severe VF loss stabilized following surgery.

Purpose: To determine risk factors for rhegmatogenous retinal detachment after cataract surgery., Design: Retrospective case-control study., Participants and Controls: A consecutive series of 63298 cataract surgery procedures in 45520 patients performed between August 1994 and March 2003 was identified. After exclusions for incomplete data, 249 cases of pseudophakic retinal detachment were matched with 845 controls that had cataract surgery on the same day, but without subsequent retinal detachment., Methods: Details were extracted from the clinical records. A conditional logistic regression model for matched case-control groups was used. Multiple regression analysis was performed to estimate the odds ratio for each variable, with adjustment for the effects of other variables selected from the candidate pool., Main Outcome Measures: Occurrence of rhegmatogenous retinal detachment., Results: The major risk factors (odds ratio [OR], 95% confidence interval [CI], P value) for detachment were posterior capsule tear (OR, 19.9; CI, 10.8-36.7; P<0.001), zonule dehiscence (OR, 12.4; CI, 3.8-41.2; P<0.001), retinal detachment in fellow eye (OR, 12.3; CI, 5.2-29.1; P<0.001), axial length >23 mm (OR, 3.2; CI, 2.0-5.0; P<0.001), and male gender (OR, 2.2; CI, 1.4-3.3; P<0.001). For patients aged >64 years, the odds ratio was linearly reduced for each subsequent decade. Differences in the surgical technique (i.e., phacoemulsification vs. extracapsular extraction), type of anesthetic, prior glaucoma, or subsequent neodymium:yttrium-aluminum-garnet laser posterior capsulotomy were not significantly related to retinal detachment. Approximately 37% (CI, 35%-38%) of retinal detachment was attributable to posterior capsule tear., Conclusions: Patient characteristics rather than surgical complications constitute the major risks factors for retinal detachment after cataract surgery.

Purpose: To assess the visual acuity outcome after treatment, in patients with differing types of uveitis associated with sarcoidosis, and to determine the types of sight-threatening complications., Methods: This was an retrospective, non-comparative, interventional study of patients who had uveitis with a confirmed diagnosis of sarcoidosis and a minimum follow-up duration of 6 months from presentation. The worst affected eye at presentation was selected for the study. Complications causing impaired vision were documented, changes in visual acuity after completion of treatment were measured, and the risk of 'poor outcome' (visual acuity 6/12 and less) was compared in the various types of uveitis, using 'exact' multiple logistic regression to control confounding by other prognostic factors., Results: Seventy-five patients were studied. The spectrum of ocular inflammation in sarcoidosis is wide. Presentation may be acute and non-granulomatous or chronic and granulomatous with posterior segment involvement being varied. Poor visual outcome was significantly more frequent in multifocal choroiditis (5/7, 71.4%), and in panuveitis without multifocal choroiditis (13/28, 46.4%), compared to only 3/24 (12.5%) patients with anterior uveitis. The excess risks remained significant after adjustment for confounding effects of other prognostic factors including age, sex and manifest systemic sarcoidosis. Causes of visual loss were cataract, glaucoma, macular oedema, vitreous haemorrhage and retinal detachment., Conclusion: Multifocal choroiditis is a less common manifestation of uveitis associated with sarcoidosis but appears to be associated with a worse visual prognosis despite immunosuppressive therapy.

Objective: To test the applicability of lot quality assurance sampling (LQAS) for the rapid assessment of the prevalence of active trachoma., Methods: Prevalence of active trachoma in six communities was found by examining all children aged 2-5 years. Trial surveys were conducted in these communities. A sampling plan appropriate for classifying communities with prevalences < or =20% and > or =40% was applied to the survey data. Operating characteristic and average sample number curves were plotted, and screening test indices were calculated. The ability of LQAS to provide a three-class classification system was investigated., Findings: Ninety-six trial surveys were conducted. All communities with prevalences < or =20% and > or =40% were identified correctly. The method discriminated between communities with prevalences < or =30% and >30%, with sensitivity of 98% (95% confidence interval (CI)=88.2-99.9%), specificity of 84.4% (CI=69.9-93.0%), positive predictive value of 87.7% (CI=75.7-94.5%), negative predictive value of 97.4% (CI=84.9-99.9%), and accuracy of 91.7% (CI=83.8-96.1%). Agreement between the three prevalence classes and survey classifications was 84.4% (CI=75.2-90.7%). The time needed to complete the surveys was consistent with the need to complete a survey in one day., Conclusion: Lot quality assurance sampling provides a method of classifying communities according to the prevalence of active trachoma. It merits serious consideration as a replacement for the assessment of the prevalence of active trachoma with the currently used trachoma rapid assessment method. It may be extended to provide a multi-class classification method.

Aim: To determine the incidence, regional variation in frequency, outcome, and risk factors for acanthamoeba keratitis (AK) in England and Wales., Methods: AK cases presenting from 1 October 1997 to 30 September 1999 were identified by the British Ophthalmic Surveillance Unit active reporting system. Clinical and patient postal questionnaire data were analysed., Results: 106 reported cases met study criteria. The annual incidence for the 2 years was 1.26 and 1.13 per million adults and, for contact lens (CL) wearers, 21.14 and 17.53 per million. There was marked regional variation in incidence (0 to 85.13 per million adult CL wearers), with CL wearers in the south having a ninefold increased risk of AK compared with those resident in the north (95% confidence limits: 2.2-38.9, p<0.0001), and a threefold increased risk with hard as opposed to soft domestic water (95% confidence limits: 1.73 to 6.58, p<0.001). Treatment and outcome data were similar to those previously reported. 93/106 (88%) patients were CL wearers. Among these, 46/77 (60%) were disinfecting irregularly, and 20/63 (32%) had been swimming in CLs. One step hydrogen peroxide and chlorine release soft CL (SCL) disinfection systems were significantly over-represented among the cases. Among SCL users, one or more previously established risk factors for AK were identified in 50/55 (91%) patients., Conclusions: The incidence was considerably higher than most previous estimates, and was static. The geographical variation in incidence may be partly related to the increase in risk associated with hard water. The fact that water quality can have such an effect on the risk of AK suggests that many CL wearers must be letting tapwater come into contact with their lenses or storage cases. Improved education for CL wearers and practitioners about hygiene practice and the variable efficacy of contact lens systems could be expected to reduce the incidence of this disease.

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.

Background/aims: In diabetics, cataract is associated with higher risk of death. In non-diabetics the data are conflicting, but some indicate an association between one type of cataract (nuclear) and increased mortality. The aim of this study was to estimate and compare age and sex specific mortality for elderly people with and without cataract in a population based cohort., Methods: A random sample drawn from a defined population of elderly people (age 65 and older) registered with 17 general practice groups in north London formed the study cohort and were followed up for 4 years. The age and sex specific mortality from various causes was estimated and compared in those with and without cataract., Results: In non-diabetics (n=1318), cataract (lens opacity at baseline) was significantly associated with higher mortality in women. The age standardised death rate per 1000 was 39.8 and 24.8 in women with and without cataract, respectively (age adjusted hazard ratio 1.7, confidence limits 1.1 to 2.7, p=0.032). This was not the case in non-diabetic men (hazard ratio 0.9, confidence limits 0.6 to 1.5, p=0.782). The excess mortality in women with cataract was consistent for cardiovascular, respiratory, and other non-cancer causes of death. There was no association between cataract and mortality from cancer., Conclusions: This study has shown, for the first time, that cataract is associated with higher mortality in women but not in men, among the non-diabetic population. This sex effect suggests that women may be exposed to risk factors that increase both the risk of cataract and mortality, and that men may have little or no exposure to these "sex specific" factors. Possible risk factors that warrant further investigation may be those associated with some pregnancy and childbearing experience.

Background: In California, from 1996 through 1998, more than 50% of multicounty outbreaks with confirmed food vehicles were related to alfalfa or clover sprouts., Objective: To summarize investigations of sprout-associated outbreaks., Design: Matched case-control studies., Setting: California., Patients: Outbreak-associated patients and matched population controls., Measurements: Matched odds ratios and 95% CIs; traceback and environmental investigations of sprout and seed growers; and pulsed-field gel electrophoresis of isolates from patients, sprouts, and seeds., Results: Five sprout-associated outbreaks of salmonellosis and one outbreak of infection with nonmotile Shiga toxin-producing Escherichia coli O157 occurred. Six hundred patients had culture-confirmed disease, and two died. It is estimated that these outbreaks caused 22 800 cases of gastrointestinal illness or urinary tract infection. In the case-control studies, odds ratios for the association between illness and alfalfa sprout consumption ranged from 5.0 to infinity (all were statistically significant). Three sprout growers were implicated, and each was associated with two outbreaks. Outbreak strains of Salmonella were isolated from sprouts supplied by two sprout growers and from seeds used by the third sprout grower., Conclusions: As currently produced, sprouts can be a hazardous food. Seeds can be contaminated before sprouting, and no method can eliminate all pathogens from seeds. Seed and sprout growers should implement measures to decrease contamination. The general public should recognize the risks of eating sprouts, and populations at high risk for complications from salmonellosis or E. coli O157 infection should avoid sprout consumption.

Background: Cataract extraction constitutes the largest surgical workload in ophthalmic units throughout the world. Extracapsular cataract extraction (ECCE), through a large incision, with insertion of an intraocular lens has been the most widely used method from 1982 until recently. Technological advances have led to the increasing use of phacoemulsification (Phako) to emulsify and remove the lens The technique requires a smaller incision, but requires substantial capital investment in theatre equipment. In this randomised trial we assessed the clinical outcomes and carried out an economic evaluation of the two procedures., Methods: In this two centre randomised trial, 232 patients with age related cataract received ECCE, and 244 received small incision surgery by Phako. The main comparative outcomes were visual acuity, refraction, and complication rates. Resource use was monitored in the two trial centres and in an independent comparator centre. Costs calculated included average cost per procedure, at each stage of follow up., Results: Phako was found to be clinically superior. Surgical complications and capsule opacity within 1 year after surgery were significantly less frequent, and a higher proportion achieved an unaided visual acuity of 6/9 or better (<0.2 logMAR) in the Phako group. Postoperative astigmatism was more stable in Phako. The average cost of a cataract operation and postoperative care within the trial was similar for the two procedures. With the input of additional spectacles for corrected vision at 6 months after surgery, the average cost per procedure was pound359.89 for Phako and pound367.57 for ECCE., Conclusion: Phako is clinically superior to ECCE and is cost effective.

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.

Aim: To determine the effect of age on final corrected visual acuity following cataract extraction., Methods: A case series of 880 patients aged 60 years and older undergoing cataract extraction between 1996 and 1999 was studied. The best corrected visual acuity was assessed at discharge from the service and the proportion of patients who achieved a postoperative acuity of > or = 6/12 was determined for different age groups. Analysis was also performed after exclusion of patients identified preoperatively as having ocular comorbidity that was thought to limit their final corrected acuity. The odds ratios for visual outcome were calculated for age using multiple logistic regression analysis to adjust for other prognostic factors., Results: A significant age effect was observed, with the proportion of patients who had no ocular comorbidity identified preoperatively and who achieved a visual acuity of > or = 6/12 at discharge decreasing with age (p<0.001). In patients with no comorbidity the odds of achieving an acuity of > or = 6/12 were 4.6 times higher in the 60-69 year age group than in the oldest age group (80+ years)., Conclusions: Age is a significant determinant of visual outcome. This has implications if a points system incorporating an assessment of visual acuity or if visual acuity alone is used to determine the threshold for eligibility for cataract surgery.

Aims: To assess the Tuck-Crick and the Quigley-Vitale predictive regression equations against fresh independent real world data for estimating the prevalence of primary open angle glaucoma (POAG) in the UK. To apply the equations to the elderly population of England and Wales, for which there is sample survey data on glaucoma, and demographic data., Methods: Directly measured actual prevalence of POAG in a population sample of 1530 people was compared with the predicted prevalence derived by applying the Tuck-Crick and the Quigley-Vitale equations to the sample data. The two equations were applied to the demographic data of the population to project POAG prevalence and to derive 5 year cumulative incidence for the elderly population. These were compared with estimates derived from the local survey data., Results: The actual directly measured prevalence of POAG in the local sample was 3.01%. The Tuck-Crick estimate was 2. 74% (difference 0.27%), and the Quigley-Vitale was 3.50% (difference -0.49%). The three methods-projection from local survey data, Tuck-Crick, and Quigley-Vitale-gave point estimates of 2.85% (228 526 cases), 2.71% (217 375 cases), and 3.50% (280 364 cases) respectively for the prevalence of POAG in the elderly population of England and Wales (8 008 705 people aged 65 or older). Calculation of incidence from age specific prevalence gave the following results: the numbers of new cases of POAG expected (5 year cumulative incidence) in the elderly population were 71 146 and 94 485 for methods 2 and 3 respectively., Conclusions: The Tuck-Crick predictive equation performed well when applied to fresh (independent) actual data from a local sample survey using a particular definition for POAG, and its usefulness for estimation of prevalence of POAG in England and Wales has been demonstrated. The work on development of predictive equations has been very promising and further refinements could be made when more fresh survey data become available.

Aim: To re-survey the Gambia after an interval of 10 years to assess the impact of a national eye care programme (NECP) on the prevalence of blindness and low vision., Method: Comparison of two multistage cluster random sample surveys taking into account the marked increase in population in the Gambia, west Africa. Samples of the whole population in 1986 and 1996 were taken. The definition of blindness is presenting vision less than 3/60 in the better eye, or visual fields constricted to less than 10 degrees from fixation. Low vision is less than 6/18 but 3/60 or better. Causes of blindness were determined clinically by three ophthalmologists., Results: The crude prevalence of blindness fell from 0.70% to 0.42%, a relative reduction of 40%. During the same 10 year period, the population increased by 51% from 775 000 to 1 169 000. When the results were standardised for age, a west to east gradient was found for changes in risk of blindness over the 10 year period. This matched the phased west to east introduction of the NECP interventions. There was a modest but significant increase in the risk of low vision across the whole country., Conclusions: The overall reduction in risk of blindness, in those areas where the NECP has been active, appears to justify the programme and the support of donor organisations. The low vision cases due to cataract must now be addressed.

Aims: To evaluate and compare prospectively the anterior chamber inflammatory response after phacoemulsification cataract surgery and after trabeculectomy with peripheral iridectomy., Methods: Anterior chamber inflammation was measured using the Kowa FM-500 laser flare meter in 131 patients undergoing trabeculectomy and 148 patients undergoing phacoemulsification cataract extraction with intraocular lens implantation. Flare was measured before surgery and on each postoperative visit up to 12 months., Results: Before surgery there was no significant difference in flare readings between the two groups. Following trabeculectomy flare returned to baseline levels 4 weeks after surgery, while following phacoemulsification cataract extraction it remained significantly higher at week 6 (p<0.006) and month 3 (p<0.05)., Conclusions: Anterior chamber inflammation is more prolonged after cataract surgery than after trabeculectomy. This may have implications for the timing of trabeculectomy in relation to cataract surgery.

Background: The pool of old cases of cataract, the expected new cases, and the shortfall in cataract surgery and consequently the numbers dying with poor vision without the benefit of cataract surgery are regarded as escalating problems worldwide. Successive governments and the professional ophthalmic bodies have not had the wherewithal to estimate the magnitude or interaction of these elements in the population of the UK. This study has collected and applied the best available epidemiological data on cataract prevalence, incidence and service utilisation, and demography to address the problem of control of the cataract pool in the population of England and Wales., Methods: Data from recent surveys undertaken by the authors, both on prevalence of vision impairing cataract and on patterns of cataract surgery, were used together with demographic and service utilisation information obtained from government departments. These were integrated within a holistic model, which was run under varied assumed levels and patterns of service provision., Results: The study shows that there is a serious pool of unoperated vision impairing cataract in the population aged 65 and older, reflecting a shortfall in cataract surgery. Continuing with the present level and pattern of service provision, the pool will increase to over 2.5 million by the year 2001. In addition, more than 700 000 will die with unoperated impaired vision., Conclusions: Targeting of existing or new additional operations to those below the visual acuity of 6/12 will have relatively little effect on numbers dying without surgery, but should have a substantial controlling effect on the pool of vision impairing cataract in the population.

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.

Aim: To determine whether the addition of systemic corticosteroid to local intensive corticosteroid therapy of endothelial corneal allograft rejection improves outcome., Methods: A prospective randomised treatment trial was carried out at a tertiary referral centre. 36 consecutive corneal graft recipients, presenting with a first episode of endothelial graft rejection, received either (i) one intravenous pulse of methylprednisolone 500 mg in addition to local corticosteroid treatment, or (ii) local treatment only. The regimen of local treatment standardised in all cases for the first 24 hours consisted of one subconjunctival betamethasone 2 mg injection and dexamethasone 0.1% drops in the affected eye every hour for 24 hours., Results: Failure to reverse the graft rejection episode was found in 3/36 (8%) patients. Each of these had been treated with local steroid only. Graft failure from any cause occurred in 9/36 (25%) within 2 years of follow up. No statistically significant difference was found between the two groups with regard to reversal of the graft rejection episode, later recurrence of graft rejection, or graft failure., Conclusions: In treatment of graft rejection, additional systemic treatment with 500 mg methylprednisolone yields no significant benefit over intensive local corticosteroid alone. Graft survival following treatment of a rejection episode with local corticosteroid treatment alone is good in those patients without other risk factors for graft failure and much higher than reported previously.

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.

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.

Aims: A case-control study was performed to evaluate soft contact lens (SCL) wear modality as a risk factor for microbial keratitis., Methods: Contact lens wearers presenting as new patients to Moorfields Eye Hospital accident and emergency department during a 12 month period completed a self administered questionnaire detailing demographic data and contact lens use habits. Cases were patients with a clinical diagnosis of SCL related microbial keratitis. Controls were SCL users attending with disorders unrelated to contact lens wear. Odds ratios (estimates of relative risks) and 95% confidence limits (CL) were calculated through multivariable logistic regression analysis., Results: There were 89 cases and 566 controls. A substantially increased risk with 1-4 weekly disposable SCL compared with non-disposable SCL was identified among both daily wear (DW) (odds ratio = 3.51, 95% CL 1.60-7.66, p = 0.002) and extended wear (odds ratio 4.76, 95% CL 1.52-14.87, p = 0.007) users after adjustment for demographic, lens use and hygiene variables. Other significant factors among DW users were "occasional" overnight use, use of chlorine based (as opposed to other chemical) systems in combination with poor storage case hygiene, and irregular disinfection., Conclusion: Properties of some disposable SCL may be partly responsible for these excess risks. It is also possible, however, that this finding is largely a reflection of widespread complacency among patients and practitioners with respect to disposable SCL fitting and use.

Aim: The management of suppurative keratitis due to filamentous fungi presents severe problems in tropical countries. The aim was to demonstrate the efficacy of chlorhexidine 0.2% drops as an inexpensive antimicrobial agent, which could be widely distributed for fungal keratitis., Methods: Successive patients presenting to the Chittagong Eye Institute and Training Complex with corneal ulcers were admitted to the trial when fungal hyphae had been seen on microscopy. They were randomised to drop treatment with chlorhexidine gluconate 0.2% or the standard local treatment natamycin 2.5%. The diameters, depths, and other features of the ulcers were measured and photographed at regular intervals. The outcome measures were healing at 21 days and presence or absence of toxicity. If there was not a favourable response at 5 days, "treatment failure" was recorded and the treatment was changed to one or more of three options, which included econazole 1% in the latter part of the trial., Results: 71 patients were recruited to the trial, of which 35 were randomised to chlorhexidine and 36 to natamycin. One allocated to natamycin grew bacteria and therefore was excluded from the analysis. None of the severe ulcers was fully healed at 21 days of treatment, but three of those allocated to chlorhexidine eventually healed in times up to 60 days. Of the nonsevere ulcers, 66.7% were healed at 21 days with chlorhexidine and 36.0% with natamycin, a relative efficacy (RE) of 1.85 (CL 1.01-3.39, p = 0.04). If those ulcers were excluded where fungi were seen in the scraping but did not grow on culture, the estimated efficacy ratio does not change but becomes less precise because of smaller numbers. Equal numbers of Aspergillus (22) and Fusarium (22) were grown. The Aspergillus were the most resistant to either primary treatment., Conclusions: Chlorhexidine may have potential as an inexpensive topical agent for fungal keratitis and warrants further assessment as a first line treatment in situations where microbiological facilities and a range of antifungal agents are not available.

Objective: To estimate the magnitude of serious eye disorders and of visual impairment in a defined elderly population of a typical metropolitan area in England, and to assess the frequency they were in touch with, or known to, the eye care services., Design: Cross sectional survey using two stage cluster random sampling., Setting: General practices in north London., Subjects: Random sample of people aged 65 and older, drawn from a defined population of elderly people registered with 17 general practice groups., Main Outcome Measures: Proportions and population prevalence estimates were determined for visual acuity, assessed with the person's own spectacles (if any), classified into four categories: prevalence of cataract, age related macular degeneration, and refractive error causing visual impairment and of definite primary open angle glaucoma; and status of contact with eye services., Results: 1547 of 1840 (84%) eligible people were examined. The population prevalence of bilateral visual impairment (visual acuity <6/12) was 30%, of which 72% was potentially remediable. 92 of these 448 cases (21%) had visual acuity <6/60 ("blindness") in one or both eyes. Prevalence of cataract causing visual impairment was 30%; 88% of these people were not in touch with the eye services. The prevalence of vision impairing, age related macular degeneration was 8% and of glaucoma (definite cases) was 3%. Three quarters of the people with definite glaucoma were not known to the eye services., Conclusions: Untreated visual impairment and eye disorders affect a substantial proportion of people aged 65 years and older. These findings should contribute to the setting up of future strategies for preservation of sight and eye health services in general.

Aims: Suppurative corneal ulcers due to filamentous fungi are a serious and intractable problem in many tropical developing countries. In vitro studies and a small pilot study have shown that chlorhexidine gluconate is effective. The aim was to establish the optimum concentration which would be appropriate to use in a larger randomized clinical trial., Methods: A masked randomized clinical trial of three concentrations of chlorhexidine compared with natamycin 5% was carried out in consecutive patients with established corneal ulcers shown by microscopy to contain fungal hyphae and later proven to be culture positive. Topical treatments were applied 1/2-hourly to 2-hourly for up to 5 days, with reduced frequency thereafter, and all patients were re-assessed at 21 days., Results: Of 60 patients entered in the trial, 2 were lost to follow-up, and 12 were classified as 'severe' with little prospect of recovery. At 5 days the response was related to the concentration of chlorhexidine, with 0.2% giving the best results. Compared with the response to natamycin as the referent, the relative efficacy was 1.17 with chlorhexidine 0.05%, 1.43 with 0.1%, and 2.00 with 0.2%. The superiority of 0.2% chlorhexidine over natamycin was statistically significant (relative efficacy 2.20, p = 0.043) in patients not having had prior antifungal treatment., Conclusions: This preliminary study justifies further trials of chlorhexidine as a primary treatment for fungal corneal ulcers in circumstances where specific antifungal agents are not available.

Background: Trachoma is a leading cause of blindness in the developing world and is most prevalent among people who live in poor rural communities in arid locations., Methods: We analysed the results of surveys of trachoma prevalence in Marakissa, a rural village in The Gambia. These surveys were undertaken in 1959, by the Medical Research Council, and in 1987 and 1996 by the Gambian National Eye Care Programme., Findings: During this 37-year period, the prevalence of active inflammatory trachoma among children aged 0-9 years fell from 65.7 cases per 100 children in 1959 to 2.4 cases per 100 children in 1996. The prevalence also fell dramatically among people of 10-19 years (52.5 to 1.4 per 100) and among people of 20 years and older (36.7 to 0 cases per 100)., Interpretation: The dramatic fall in disease occurrence was paralleled by improvements in sanitation, water supply, education, and access to health care in the village. Of particular importance is that the decline in trachoma occurred without any trachoma-specific intervention.

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.

In preparation for the planning of a regional prevention of blindness programme, a population-based survey of blindness and eye disease was conducted in two provinces (Diyarbakir and Mardin) of southeast Turkey. A stratified cluster random sampling procedure was used to select 8,571 persons. The main objectives of the survey were to assess the population need for basic ophthalmic services, both in rural and in rapidly growing urban communities, and to secure baseline data for subsequent evaluation of the programme. The prevalence of visual impairment (best binocular vision poorer than 6/ 18) was estimated at 1.9% with 95% confidence limits of 1.6% and 2.1%, amounting to 29,400 +/- 4500 visually imparied persons in the regional population of 1.6 million. The prevalence of blindness (best vision poorer than 3/60) was 0.4%, and an estimated 1.5% had low vision (best vision poorer than 6/18, but not blind). Compared to the blindness prevalence of 0.2% in the European Economic Community (EEC), the age-standardised prevalence of blindness in southeast Turkey was 8 times as high. The main causes of blindness in the sample were cataract (50%), corneal opacity (15%), glaucoma (12%), phthisis (6%) and optic atrophy (6%). Cataract and refractive errors were responsible for 52% and 26% of the low vision, respectively. Acute inflammatory trachoma was prevalent in a number of rural and urban communities, affecting an estimated 25,900 people in the region. The need for basic ophthalmic services was estimated for the two provinces. Some 26,600 were in need of cataract surgery, 4,400 needed eyelid surgery for trachoma-induced entropion, and 28,600 required spectacles to improve their visual acuity to 6/18 or better. More than half of the current burden of severe visual loss in the two provinces of southeast Turkey is potentially remediable through the provision of cataract surgery and of spectacles to correct aphakia. The survey findings suggest that as the age structure of the regional population approaches that of the EEC through the "ageing trend', a four-fold increase in the burden of blindness might be expected, unless improvements are made in curative and preventive ophthalmic services in parallel with the general development that improves survival.

Aims: To describe the impact of cataract surgery in terms of visual function (functioning in everyday life with respect to vision dependent activities) and health related quality of life., Methods: An observational, longitudinal study of patients undergoing cataract surgery was carried out at three district general hospitals in outer London districts of North Thames Region with follow up at 4 and 12 months postoperatively for a clinical assessment and a standardised administered interview. Patients were admitted for surgery to the first eye for age-related cataract between 1 May 1993 and 31 August 1994. Visual functioning was assessed by the VF-14, health related quality of life was assessed by the sickness impact profile (SIP), and vision related quality of life was assessed by VR-SIP (a modification of the generic SIP)., Results: Significant gains in all the outcome measures were demonstrated at 4 months postoperatively. No significant change (gain or loss) was observed between 4 and 12 months after surgery to the first eye. Postoperatively, the mean visual function (VF-14) scores, and health related (SIP) and vision related (VR-SIP) quality of life scores, indicated less reported trouble with vision dependent activities and better perceived quality of life, respectively. The average gains in visual function and quality of life (health and vision related) were apparent in groups with good visual outcome and poor visual outcome. Significant additional gains were seen at 1 year in patients who had second eye surgery in the interval between the postoperative assessments., Conclusions: Gains in visual functioning and quality of life (health and vision related) have been demonstrated following cataract surgery. These gains were sustained at 1 year after surgery to the first eye, with additional gains being conferred if second eye surgery had been performed. Assessment of the outcomes of cataract surgery by clinical indicators alone may underestimate the overall benefits of surgery, particularly in patients with poor visual outcome.