Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. INTRODUCTION: The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. METHODS: We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. RESULTS: Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. CONCLUSIONS: Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

In vivo MRI discrimination between live and lysed iron-labelled cells using balanced steady state free precession.

OBJECTIVES: The goal of this study was to evaluate the ability of balanced steady state free precession (b-SSFP) magnetic resonance imaging sequence to distinguish between live and lysed iron-labelled cells. METHODS: Human breast cancer cells were labelled with iron oxide nanoparticles. Cells were lysed using sonication. Imaging was performed at 3 T. The timing parameters for b-SSFP and the number of iron-labelled cells in samples were varied to optimise the b-SSFP signal difference between live and lysed iron-labelled cell samples. For in vivo experiments, cells were mixed with Matrigel and implanted into nude mice. Three mice implanted with live labelled cancer cells were irradiated to validate this method. RESULTS: Lysed iron-labelled cells have a significantly higher signal compared with live, intact iron-labelled cells in bSSFP images. The contrast between live and dead cells can be maximised by careful optimisation of timing parameters. A change in the b-SSFP signal was measured 6 days after irradiation, reflecting cell death in vivo. Histology confirmed the presence of dead cells in the implant. CONCLUSIONS: Our results show that the b-SSFP sequence can be optimised to allow for the discrimination of live iron-labelled cells and lysed iron-labelled cells in vitro and in vivo.

Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model.

PURPOSE: The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness. MATERIALS AND METHODS: Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC+ PBMC under both pre-clinical 9.4 Tesla (T) and clinical 3T conditions in a mouse model. RESULTS: A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC+ PBMC were in vivo migration-competent to draining and downstream lymph nodes. GM-CSF addition to culture increased PBMC migration to, and persistence within, secondary lymphoid organs. CONCLUSION: 19F cellular MRI is a non-invasive imaging technique capable of detecting and quantifying in vivo cell migration in conjunction with an established APC-based immunotherapy model. 19F cellular MRI can function as a surrogate marker for assessing and improving upon the therapeutic benefit that this immunotherapy provides.

Socioeconomic status, systolic blood pressure and intraocular pressure: the Tanjong Pagar Study.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher morbidity and mortality in many countries. Present evidence suggests that glaucoma has similar risk factors to major chronic diseases such as cardiovascular disease. This study investigates the association between SES and intraocular pressure (IOP), an important risk factor for glaucoma. METHODS: The Tanjong Pagar Study was a population-based cross-sectional survey of Chinese people aged 40-79 years, who were randomly selected from the Singapore electoral register. Of the 2000 people selected, 1717 were considered eligible and 1090 were examined in clinic and included in the present study. IOP was measured using applanation tonometry. SES was assessed using a standardised questionnaire; education and income were used as the main explanatory variables. The effect of systolic blood pressure (SBP) was also examined. RESULTS: Participants with lower levels of education and income had higher mean IOP (both p<0.01). These associations remained after adjusting for age and central corneal thickness, a strong independent predictor. SBP was strongly associated with both SES and IOP (both p<0.01). Adjusting for SBP attenuated the association between SES and IOP. CONCLUSION: Participants with lower education and income have a higher mean IOP. This effect may be mediated, in part, by an association of education and income with SBP. This is the first study to suggest that there is a social gradient in the distribution of the only major modifiable risk factor for glaucoma. Increasing similarities exist between the causation models of chronic diseases and that of glaucoma.

A technician-delivered 'virtual clinic' for triaging low-risk glaucoma referrals.

PurposeThe purpose of this study is to describe the outcomes of a technician-delivered glaucoma referral triaging service with 'virtual review' of resultant data by a consultant ophthalmologist.Patients and methodsThe Glaucoma Screening Clinic reviewed new optometrist or GP-initiated glaucoma suspect referrals into a specialist ophthalmic hospital. Patients underwent testing by three ophthalmic technicians in a dedicated clinical facility. Data were reviewed at a different time and date by a consultant glaucoma ophthalmologist. Approximately 10% of discharged patients were reviewed in a face-to-face consultant-led clinic to examine the false-negative rate of the service.ResultsBetween 1 March 2014 and 31 March 2016, 1380 patients were seen in the clinic. The number of patients discharged following consultant virtual review was 855 (62%). The positive predictive value of onward referrals was 84%. Three of the 82 patients brought back for face-to-face review were deemed to require treatment, equating to negative predictive value of 96%.ConclusionsOur technician-delivered glaucoma referral triaging clinic incorporates consultant 'virtual review' to provide a service model that significantly reduces the number of onward referrals into the glaucoma outpatient department. This model may be an alternative to departments where there are difficulties in implementing optometrist-led community-based referral refinement schemes.

Automated arteriole and venule classification using deep learning for retinal images from the UK Biobank cohort.

The morphometric characteristics of the retinal vasculature are associated with future risk of many systemic and vascular diseases. However, analysis of data from large population based studies is needed to help resolve uncertainties in some of these associations. This requires automated systems that extract quantitative measures of vessel morphology from large numbers of retinal images. Associations between retinal vessel morphology and disease precursors/outcomes may be similar or opposing for arterioles and venules. Therefore, the accurate detection of the vessel type is an important element in such automated systems. This paper presents a deep learning approach for the automatic classification of arterioles and venules across the entire retinal image, including vessels located at the optic disc. This comprises of a convolutional neural network whose architecture contains six learned layers: three convolutional and three fully-connected. Complex patterns are automatically learnt from the data, which avoids the use of hand crafted features. The method is developed and evaluated using 835,914 centreline pixels derived from 100 retinal images selected from the 135,867 retinal images obtained at the UK Biobank (large population-based cohort study of middle aged and older adults) baseline examination. This is a challenging dataset in respect to image quality and hence arteriole/venule classification is required to be highly robust. The method achieves a significant increase in accuracy of 8.1% when compared to the baseline method, resulting in an arteriole/venule classification accuracy of 86.97% (per pixel basis) over the entire retinal image.

Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies.

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost.

A pragmatic randomized trial comparing tablet computer informed consent to traditional paper-based methods for an osteoporosis study.

OBJECTIVE: Methods to improve informed consent efficiency and effectiveness are needed for pragmatic clinical trials. We compared informed consent using a tablet computer to a paper approach to assess comprehension and satisfaction of patients and clinic staff for a future osteoporosis clinical trial. METHODS: Nine community-based practices identified and recruited patients to compare the informed consent processes (tablet vs. paper) in a mock osteoporosis clinical trial. The tablet informed consent included an animation summarizing the trial, complete informed consent document, and questions to assess and reinforce comprehension of the study. Participants were women age ≥55 years with ≥1 year of alendronate use. We surveyed participants to assess comprehension and satisfaction and office staff for satisfaction and perceived time demands. RESULTS: The nine practices enrolled 33 participants. There was not a significant difference in comprehension between the tablet vs. paper informed consent [mean (SD) tablet: 12.2 (1.0) vs. paper: 11.4 (1.7)]. Office staff preferred the tablet to the paper informed consent for identifying potential study participants (two-sided t-test p = 0.02) despite an increased perceived time spent to complete the tablet process [tablet: 28.3 min (SD 16.3) vs. paper: 19.0 min (SD 6.9); p = 0.08]. CONCLUSIONS: Although, there were no significant differences in participant satisfaction and comprehension with the tablet informed consent compared to a paper informed consent, patients and office staff trended towards greater satisfaction with the tablet informed consent. Larger studies are needed to further evaluate the utility of electronic informed consent in pragmatic clinical trials.

A population based survey of the prevalence and types of glaucoma in rural West Bengal: the West Bengal Glaucoma Study.

AIM: To determine (i) the prevalence of glaucoma in people aged > or =50 years, (ii) the proportions of different types of glaucoma, (iii) the distributions of intraocular pressure and vertical cup disc ratio. METHOD: Population based prevalence survey in rural West Bengal. People aged > or =50 years in randomly selected villages in 24 Parganas South district. The main outcome measures were diagnosis of glaucoma, based on criteria described by the International Society for Geographic and Epidemiological Ophthalmology. RESULTS: 1594 people aged > or =50 years were enumerated in nine villages; 1324 (83.1%) were surveyed and 1269 people adequately examined. 42 definite cases of glaucoma were identified, with prevalence increasing from 2.7% (95% CI 1.7 to 3.7) in people aged 50-59 years to 6.5% (95% CI 0.0 to 14.1) in those aged > or =80 years. The age standardised estimate for the prevalence of all glaucoma in people aged > or =50 years was 3.4%. Only three cases of primary angle closure glaucoma (PACG) were identified, giving a crude ratio of primary open angle glaucoma (POAG) to PACG of more than 10:1. Three people with glaucoma were blind in one eye but none was blind in both eyes. CONCLUSION: Compared to other surveys of glaucoma in India, the age standardised prevalence observed was less than in Hyderabad, but similar to Tamil Nadu and Dhaka. The ratio of POAG to PACG was much higher than found previously, suggesting that PACG may be less prevalent in Bengalis than in Indian populations living in south India. The authors conclude that ophthalmic services in West Bengal should focus on detecting POAG. Since there is still no satisfactory method of screening for POAG, there is no alternative to case detection (opportunistic screening) in eye clinics.

Automated retinal vessel recognition and measurements on large datasets.

The characteristics of the retinal vascular network have been prospectively associated with many systemic and vascular diseases. QUARTZ is a fully automated software that has been developed to localize and quantify the morphological characteristics of blood vessels in retinal images for use in epidemiological studies. This software was used to analyse a dataset containing 16,000 retinal images from the EPIC-Norfolk cohort study. The objective of this paper is to both assess the suitability of this dataset for computational analysis and to further evaluate the QUARTZ software.

Measures of socioeconomic status and self-reported glaucoma in the U.K. Biobank cohort.

PURPOSE: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the U.K. Biobank. METHODS: Biobank is a study of U.K. residents aged 40-69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112,690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined. RESULTS: In all, 1916 (1.7%) people in U.K. Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs. 56.7 years, P<0.001) and male (2.1% vs. 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was -0.72 for those reporting glaucoma and -0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18,000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect. CONCLUSIONS: In a large U.K. cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions.

The relationship between ocular dimensions and refraction with adult stature: the Tanjong Pagar Survey.

PURPOSE: To describe the association of ocular dimensions and refraction with adult stature. METHODS: This was a population-based cross-sectional survey of adult Chinese aged 40 to 81 years residing in the Tanjong Pagar district in SINGAPORE: As part of the examination, ocular dimensions, including axial length, anterior chamber depth, lens thickness, and vitreous chamber depth, were measured using an A-mode ultrasound device. Corneal radius and refraction were determined with an autorefractor, with refraction further refined subjectively. Height (in meters) and weight (in kilograms) were measured using a standardized protocol, and body mass index (BMI) was calculated as weight divided by the square of the height (kilograms per square meter). RESULTS: Data on ocular biometry, refraction, height, and weight were available on 951 (55.4%) participants with phakic eyes. After controlling for age, sex, education, occupation, housing type, income, and weight, it was found that taller persons were more likely to have longer axial lengths (+0.23 mm longer axial length, for every 0.10 m difference in height), deeper anterior chambers (+0.07 mm), thinner lenses (-0.09 mm), longer vitreous chambers (+0.26 mm), and flatter corneas (+0.09 mm longer corneal radius), although refractions were similar. In contrast, heavier persons tended to have more hyperopic refractions (+0.22 D for every 10 kg difference in weight, +0.56 D for every 10 kg/m(2) difference in BMI) but similar ocular dimensions. CONCLUSIONS: Adult height is independently related to ocular dimensions, but does not appear to influence refraction. Thus, although taller persons are more likely to have longer globes, they also tend to have deeper anterior chambers, thinner lenses, and flatter corneas. Conversely, weight is independently related to refraction, although the exact biometric component responsible for this association is not apparent.

Variations in ocular biometry in an adult Chinese population in Singapore: the Tanjong Pagar Survey.

PURPOSE: To describe the variation in ocular biometry in adult Chinese individuals in Singapore. METHODS: This study was a population-based, cross-sectional survey of adult Chinese persons aged 40 to 81 years residing in Tanjong Pagar district, Singapore. Axial ocular dimensions, including axial length (AL), anterior chamber depth (ACD), lens thickness (LT), and vitreous chamber depth (VCD) were measured using an A-scan ultrasound device. Corneal curvature (CC) and noncycloplegic refraction were measured with an autorefractor, with refraction further refined subjectively. Lens nuclear opacity (NO) was graded clinically using the modified Lens Opacity Classification System III (LOCS III) score. RESULTS: A total of 1717 subjects were eligible for the survey, of whom 1232 (71.8%) participated. Biometric and refraction data were available for 1004 (58.5%) phakic subjects. The AL, ACD, LT, VCD, CC, and LOCS III scores were 23.23 +/- 1.17 mm, 2.90 +/- 0.44 mm, 4.75 +/- 0.47 mm, 15.58 +/- 1.11 mm, 7.65 +/- 0.27 mm, and 3.2 +/- 0.9 (mean +/- SD), respectively. On average, people aged 40 to 49 years, when compared with those 70 to 81 years, had longer ALs (mean difference, +0.58 mm), deeper ACDs (+0.52 mm), longer VCDs (+0.72 mm), but thinner lenses (-0.70 mm) and less severe NO (-1.7 LOCS III score). CCs did not vary significantly with age. After controlling for age, women had shorter ALs and VCDs, shallower ACDs, but thicker lenses and steeper CCs than men. The variation in noncycloplegic refraction with age was nonlinear. Among people aged 40 to 59 years, a higher prevalence of hyperopia was seen in older compared with younger persons (on average, a difference of +1.3 D for every 10-year difference in age, P: < 0.001), explained principally by shorter AL (and VCD) in older persons. Among those 60 to 81 years, this pattern was not obvious (a difference of -0.03 D for every 10-year difference in age, P: = 0.12), as NO became an additional determinant of refraction, with greater degrees of NO in older person's driving refraction in the "minus" direction. CONCLUSIONS: Ocular dimensions vary with age and gender in adult Chinese persons in Singapore. The variation in noncycloplegic refraction in people 40 years and older may be explained by differences in axial lengths (principally vitreous chamber depths) between older and younger persons and, from 60 years onwards, differences in lens nuclear opacification as well.

Prevalence and risk factors for refractive errors in adult Chinese in Singapore.

PURPOSE: To determine the epidemiology of refractive errors in an adult Chinese population in Singapore. METHODS: A disproportionate, stratified, clustered, random-sampling procedure was used to select names of 2000 Chinese people aged 40 to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar district in Singapore. These people were invited to a centralized clinic for a comprehensive eye examination, including refraction. Refraction was also performed on nonrespondents in their homes. Myopia, high myopia, and hyperopia were defined as a spherical equivalent (SE) in the right eye of less than -0.5 D, less than -5.0 D, and more than +0.5 D, respectively. Astigmatism was defined as less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of more than 1.0 D between the two eyes. Only phakic eyes were analyzed. RESULTS: From 1717 eligible people, 1232 (71.8%) were examined. Adjusted to the 1997 Singapore population, the overall prevalence of myopia, hyperopia, astigmatism, and anisometropia was 38.7% (95% confidence interval [CI]: 35.5, 42.1), 28.4% (95% CI: 25.3, 31.3), 37.8% (95% CI: 34.6, 41.1), and 15.9% (95% CI: 13.5, 18.4), respectively. The prevalence of high myopia was 9.1% (95% CI: 7.2, 11.2), with women having significantly higher rates than men. The age pattern of myopia was bimodal, with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower prevalence between those age ranges. Prevalence was reversed in hyperopia, with a higher prevalence in subjects aged 50 to 69. There was a monotonic increase in prevalence with age for both astigmatism and anisometropia. Increasing educational levels, higher individual income, professional or office-related occupations, better housing, and greater severity of nuclear opacity were all significantly associated with higher rates of myopia, after adjustment for age and sex. CONCLUSIONS: The results indicate that whereas myopia is 1.5 to 2.5 times more prevalent in adult Chinese residing in Singapore than in similarly aged European-derived populations in the United States and Australia, the sociodemographic associations are similar.

Glaucoma in Mongolia. A population-based survey in Hövsgöl province, northern Mongolia.

OBJECTIVES: To determine the prevalence of glaucoma and suspect glaucoma, and to classify the cases detected according to mechanism. DESIGN: A population-based prevalence study. SETTING: Rural and urban locations in Hövsgöl province, northern Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000 individuals 40 years of age and older were examined. MAIN OUTCOME MEASURE: Primary angle-closure glaucoma was diagnosed in subjects with previous acute or intermittent symptoms of angle closure and in individuals with an occludable angle and an intraocular pressure greater than 19 mm Hg or a glaucomatous visual field. RESULTS: The prevalence of manifest primary angle-closure glaucoma was 1.4% (14 subjects). The prevalence of gonioscopically occludable angles was 6.4% (64 subjects, including those with glaucoma). Primary open-angle glaucoma was diagnosed in 5 subjects (prevalence, 0.5%). As all these subjects were older than 60 years, the prevalence became 2.1% for this age group. Three cases (prevalence, 0.3%) of secondary open-angle glaucoma were detected. No cases of secondary angle-closure glaucoma were diagnosed. The prevalence of blindness was 1.2% (12 subjects), and primary glaucoma accounted for one third of these cases (4 subjects). CONCLUSIONS: We confirmed glaucoma as a major public health problem in northern Mongolia. Primary angle-closure glaucoma is more prevalent than primary open-angle glaucoma, supporting clinic-based data from other east Asian countries. Among the subjects examined, 97 (9.7%) had either manifest, latent, or suspect glaucoma. Neighboring populations may be similarly affected owing to a shared genetic heritage.

Anterior chamber depth measurement as a screening tool for primary angle-closure glaucoma in an East Asian population.

OBJECTIVE: To evaluate anterior chamber depth measurement as a method of screening for primary angle-closure glaucoma in an East Asian population. DESIGN: Two-phase, cross-sectional, community-based study. SETTING: Rural and urban locations in the Hovsgol and Omnogobi provinces, Mongolia. PARTICIPANTS: Nine hundred forty-two (94.2%) of 1000 individuals in Hovsgol(1995) and 775 (96.9%) of 1000 individuals in Omnogobi (1997) aged 40 years or older were examined. MAIN OUTCOME MEASURES: Anterior chamber depth was measured by optical pachymetry, slitlamp-mounted A-mode ultrasound, and handheld ultrasound. Gonioscopy was used to detect occludable angles, defined as one in which the trabecular meshwork was visible for less than 90 degrees of angle circumference. Primary open-angle glaucoma was diagnosed in subjects with an occludable angle and glaucomatous optic neuropathy with visual morbidity. The area under the curve in a receiver operating characteristic plot was used to compare test performance. RESULTS: Optical pachymetry outperformed the slitlamp-mounted ultrasound method of anterior chamber depth measurement (area under the curve, 0.93 and 0.90, respectively; z test, P = .001). Handheld ultrasound (area under the curve, 0.86) was inferior to optical measurement (z test, P = .001) but did not differ significantly from slitlamp ultrasound (z test, P = .06). The optical method gave sensitivity of 85% and specificity of 84% at a screening cutoff of less than 2.22 mm for detecting occludable angles. CONCLUSIONS: Measurement of axial anterior chamber depth can detect occludable angles in this Asian population and therefore may have a role in population screening for primary angle-closure glaucoma.

The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional population survey of the Tanjong Pagar district.

BACKGROUND: Data on prevalence of glaucoma in East Asia are scarce. OBJECTIVE: To determine the prevalence and clinical characteristics of glaucoma in adult Chinese Singaporeans. METHODS: A group of 2000 Chinese people, aged 40 to 79 years, were selected from the electoral register of Tanjong Pagar district in Singapore using a disproportionate, stratified, clustered, random-sampling procedure. Glaucoma was diagnosed in people with an excavated optic neuropathy and a reproducible visual field defect or on the basis of severe structural disc abnormality alone, if reliable field results could not be obtained. The diagnosis was also made in blind subjects with raised intraocular pressure or previous glaucoma surgery. RESULTS: Of 1717 eligible subjects, 1232 were examined, with a response rate of 71.8%. There were 45 cases of glaucoma: 27 were men and 18 were women. The main diagnoses were primary open-angle glaucoma (n = 22 [49%]), primary angle-closure glaucoma (n = 14 [31%]), and secondary glaucoma (n = 7 [16%]). It was not possible to determine the mechanism in 2 (4%). CONCLUSIONS: The age-standardized prevalence of glaucoma was 3.2% (95% confidence interval, 2.3-4.1) in the population 40 years and older. Glaucoma was the leading cause of blindness. Primary angle-closure glaucoma and secondary glaucoma were the most visually destructive forms of the disease. Our findings suggest current projections of glaucoma prevalence among ethnic Chinese are a substantial underestimate. Arch Ophthalmol. 2000;118:1105-1111

Incidence of acute primary angle-closure glaucoma in Singapore. An island-wide survey.

OBJECTIVES: To determine the incidence of acute primary angle-closure glaucoma (APACG) in Singapore and to identify demographic and meteorological risk factors. DESIGN: A prospective, island-wide incidence study. SETTING: All government and private ophthalmological practices in Singapore, from March 1, 1995, to February 29, 1996. METHODS: New cases of APACG were identified by all ophthalmologists in Singapore during a 1-year period. Demographic and clinical details were recorded. RESULTS: One hundred eighty-nine people (208 eyes) were seen with APACG for the first time during the 1-year period. These new cases represent an incidence of 12.2 per 100,000 per year (95% confidence interval, 10.5-13.9) in those aged 30 years and older. Major risk factors identified were female sex (relative risk, 2.4), Chinese ethnic origin (relative risk, 2.8), and age of 60 years or older (relative risk, 9.1). Half of those affected were seen 3 days or more after the onset of symptoms. Attacks were more frequent on hotter days. There also was a relationship between the number of attacks per day and the mean number of sunspots and mean solar radio flux during the previous 30 days. CONCLUSIONS: There is a high incidence of APACG in Singapore, with elderly women being the highest risk group. Chinese Singaporeans are at higher risk than other ethnic groups (Malay and Indian). There is often a substantial delay before these patients consult a physician. The onset of APACG seems to be associated with meteorological factors.

Regular fluctuations in growth hormone (GH) release determine normal human growth.

Growth hormone (GH) is the principal hormone associated with growth through childhood, but in a normal child the amount of GH secretion does not appear to be critical in the generation of normal growth rates. We have assessed the relationship between growth and urinary GH (uGH) output in a longitudinal study of 29 healthy prepubertal schoolchildren (13 male, 16 female; age 5.7-7.8 years) over 1 year. Height and uGH were measured three times a week. Individual height velocity curves were derived using non-linear regression. Growth was expressed in terms of the total increment over the year (DeltaHt, cm), height velocity standard deviation score (HVSDS) and the average size of individual growth spurts. Urinary GH data (ng) were expressed as a weekly average. Mean uGH did not correlate with stature or growth over the year. However, the coefficient of variation of uGH was correlated with height standard deviation score (HtSDS, r = 0.38, P< 0.05), while the relative constancy of short-term change in uGH (coefficient of incremental change, DeltaINC) was inversely correlated with DeltaHt (r = - 0.44) and HVSDS (r = - 0.42, both P< 0.05) but not with HtSDS. DeltaINC was also inversely correlated with the average size of individual growth spurts derived from the height velocity curves (r = - 0.45, P< 0.05). Using time series analysis to identify rhythms in uGH excretion, a positive correlation was found between the magnitude of rhythms of a period of 2 to 4 weeks and HtSDS (r = 0.40, P< 0.05). These data demonstrate that variability in GH is a more important determinant of normal childhood growth rate than the amount of GH alone. Stature is correlated to the overall variability in GH release, while increment in height and the magnitude of individual growth spurts are influenced by the constancy of the GH profile. This would imply that once the GH dose has been replaced in GH deficiency, optimal growth could only be achieved by varying the pattern of GH administration.