HIF signalling: The eyes have it.

The hypoxia inducible factors (HIFs) promote changes in gene expression in response to hypoxia, and mediate key physiological responses such as angiogenesis. They play important roles in development and normal physiology, as well as in ischaemic and other pathologies. The human eye is a complex organ, with tight regulation of vascularisation and oxygen delivery, with the highly specialised retina containing both highly vascularised and avascular regions. This review, written to honour the significant contribution of Lorenz Poellinger to this field, covers the role of the HIFs in normal development of the eye, specifically the vasculature, as well as their roles in numerous retinal pathologies, including ischaemic retinopathies, and age-related macular degeneration (AMD). The characterisation of the HIFs in the eye has improved our understanding of the development, function, and numerous pathologies of the eye, and should inform future therapeutic approaches.

Relationships among biomarkers of one-carbon metabolism.

One-carbon metabolism is a network of metabolic pathways, disruption of which has been associated with cancer and other pathological conditions. Biomarkers of these pathways include homocysteine (HCY), S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). A better understanding of the relationships between these biomarkers is needed for their utilization in research. This study investigated the relationships between fasting concentrations of plasma HCY, SAM, SAH and the ratio of SAM:SAH, and serum folate, vitamin B(12) and creatinine in a healthy adult population. A cross-sectional study recruited 678 volunteers; only subjects with complete data (n = 581) were included in this analysis. Correlations were used to examine bivariate relationships among the biomarkers and multivariate linear regression determined independent relationships with HCY, SAM and SAH treated as dependent variables in separate models. Multivariate logistic regression examined determinants of a low SAM:SAH ratio (defined as having a SAM:SAH ratio in the bottom quartile and SAH value in the top quartile). HCY correlated inversely with folate and vitamin B(12) and weakly correlated with SAH and creatinine. Both SAM and SAH correlated with creatinine but were independent of serum folate and vitamin B(12). In multivariate analyses, folate, vitamin B(12), creatinine, sex and age were associated with HCY; age and creatinine were determinants of SAM, and sex and creatinine determinants of SAH. Finally, male sex and increasing creatinine levels were associated with having a low SAM:SAH ratio. Findings suggest that HCY, SAM and SAH are relatively independent parameters and reflect distinct aspects of one-carbon metabolism.

Cataract in central Sri Lanka: prevalence and risk factors from the Kandy Eye Study.

PURPOSE: To estimate the prevalence of and risk factors for cataracts in the Kandy District of central Sri Lanka. METHODS: A population-based, cross-sectional ophthalmic survey of the inhabitants of rural villages in central Sri Lanka was conducted; 1375 individuals participated (79.9%; age > or = 40 years, average age 57) and 1318 (95.9%) had an examinable lens in at least one eye. Data collection included district, age, occupation, education level, smoking history, height, weight and dilated lens assessment using Lens Opacities Classification System III grading: nuclear (> or =4), cortical (> or =2) and posterior subcapsular (> or =2) cataracts. Aphakic and pseudophakic eyes were included as operated cataracts for statistical analysis. RESULTS: The prevalence of any cataract including operated eyes was 33.1% (95% Confidence Interval (CI), 22.4-43.7%): 26.0% cortical; 7.9% posterior sub-capsular and 4.5% nuclear cataracts. No significant association was found between cataract and gender, smoking or outdoor occupation. Low level of education (secondary or higher vs no education: Odds Ratio (OR) 0.6, CI 0.4-0.9, P = 0.04) and shorter stature were associated with a higher likelihood of any cataract (OR 1.7, CI 1.1-2.7, P = 0.02). CONCLUSIONS: The overall prevalence of cataract in central Sri Lanka is similar to that in other developing Asian regions except for the unusually low prevalence of nuclear cataract. Illiteracy and height appear to be significant predictors for cataract in this population and further investigation is required to explore their influence.

Prevalence and determinants of age-related macular degeneration in central Sri Lanka: the Kandy Eye Study.

AIMS: To determine the prevalence, associations and risk factors for age-related macular degeneration (ARMD) in central Sri Lanka. METHODS: The study was a population-based, cross-sectional survey of residents aged > or = 40 years in rural Sri Lanka. ARMD was assessed on dilated fundoscopy using the International Age-Related Maculopathy Epidemiology Study Group classification system. RESULTS: Of the 1721 subjects identified, 1375 participated (79.9%). Of the participants, 1013 were aged > or = 50 years (73.6%). The prevalence of any ARMD (adjusted for study design) was 4.72 (95% CI 2.22 to 7.20)% with 3.82 (95% CI 1.60 to 6.04)% early ARMD and 1.70 (95% CI 0.14 to 3.27)% late ARMD. Age (p<0.001) and Sinhalese ethnicity (p = 0.016) were significantly associated with ARMD. Men had a tendency toward a higher prevalence of ARMD than women, although this was not statistically significant (p = 0.081). Ocular risk factors such as cortical cataract (p = 0.024) and pseudophakia (p = 0.003) were associated with ARMD on the univariate but not multivariate analyses. Illiteracy and the identification of social supports were significantly associated with ARMD on univariate analyses. However, only social support was statistically significant after multivariate analysis (p = 0.024). CONCLUSIONS: Although the prevalence of ARMD is slightly lower in Sri Lanka than surrounding regions, it contributes to a higher proportion of visual impairment, including blindness. Risk factors include age and Sinhalese ethnicity.

Risk factors for early angle-closure disease in a Burmese population: the Meiktila Eye Study.

PURPOSE: To determine risk factors for early angle-closure disease (AD) in a Burmese population. METHODS: A cross-sectional, population-based survey of the inhabitants, 40 years of age and over, from villages in the Meiktila District was performed; 2481 eligible participants were identified, 2076 participated in the study, and 2050 could be categorized as having early AD (defined by the presence of so-called occludable angles (<90 degrees of posterior trabecular meshwork visible on gonioscopy), but without glaucomatous optic neuropathy). The ophthalmic examination included Snellen visual acuity, slit-lamp examination, tonometry, gonioscopy, biometry, and dilated stereoscopic fundus examination. RESULTS: The mean axial length (AL) and anterior chamber depth (ACD) in those with occludable angles were 21.9 and 2.60 mm, respectively; in those with non-occludable angles, the corresponding lengths were 22.74 and 2.84 mm, respectively (P<0.001 for both comparisons). In the univariate analyses, age, female gender, nuclear and cortical cataract, steeper corneal curvature, more anterior lens position, and myopia were also significantly associated with occludability. In the multivariate analysis, age, AL, ACD, and nuclear cataract were significantly associated with occludability. CONCLUSION: In this Burmese population, those with occludable angles had significantly shorter ALs, ACDs, and thicker lenses than those without occludable angles. In multivariate analysis, increasing age, decreasing AL, decreasing ACD, and nuclear cataract were significant predictors of early AD. The presence of nuclear cataract per se should raise clinical suspicion of the possibility of AD in this population.

Ocular biometry and determinants of refractive error in rural Myanmar: the Meiktila Eye Study.

OBJECTIVE: To describe the ocular biometry and determinants of refractive error in an adult population in Myanmar. METHODS: A cross-sectional, population-based survey of the inhabitants 40 years of age and over from villages in the Meiktila District was performed; 2481 eligible participants were identified, and 2076 participated in the study. Biometric components including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), lens thickness (LT) and corneal curvature (CC) were measured. Lens opalescence was measured using the Lens Opacity Grading System III. Non-cycloplegic refraction was measured with an autorefractor. RESULTS: Complete biometric, refractive and lenticular data were available on 1498 participants. Men had longer ALs, ACDs, VCDs and steeper CCs than women. There was an increase in LT, nuclear opalescence (NO) and myopic shift with increasing age, with no significant change in AL with age. In the 40-59 year age group, VCD was a significant predictor of refractive error, but LT (p<0.001) and NO (p<0.001) were stronger predictors. In the 60+ age group, NO (p<0.001) was also the dominant predictor of refractive error. CONCLUSION: This Burmese population, particularly women, has a relatively short AL and ACD. NO is the strongest predictor of refractive error across all age groups in this population.

Prevalence of exfoliation syndrome in central Sri Lanka: the Kandy Eye Study.

AIMS: To report the prevalence and correlates of exfoliation syndrome (XFS) in central, rural Sri Lanka. METHODS: A population-based, cross-sectional ophthalmic survey of inhabitants 40 years of age and over from villages in the Kandy District was conducted. Selection was randomised using a cluster sampling process. 1721 eligible participants were identified, 1375 participated. A detailed ophthalmic history and examination including ocular biometry was made of each participant. RESULTS: The prevalence of XFS was estimated to be 1.1% (95% CI 0.5 to 1.5%; 22 eyes). XFS was bilateral in eight subjects, unilateral in six subjects. Univariate analysis demonstrated a significant association between XFS and increasing age (p<0.001), increasing intraocular pressure (odds ratio 1.2; 95% CI 1.09 to 1.27; p<0.001), nuclear cataracts (odds ratio 1.92; 95% CI 1.47 to 2.51; p<0.001), visual impairment (odds ratio 9.72; 95% CI 3.01 to 31.44; p<0.001) and a history of hypertension (odds ratio 3.89; 95% CI 1.14 to 13.16; p = 0.030). CONCLUSION: XFS in this Sri Lankan population was associated with advanced age, raised intraocular pressure, nuclear cataracts, hypertension and visual impairment.

Cataract in rural Myanmar: prevalence and risk factors from the Meiktila Eye Study.

AIMS: To determine the prevalence of and risk factors for cataracts in a rural region of central Myanmar. METHODS: A cross-sectional, population-based survey of inhabitants >or=40 years of age from villages of central Myanmar; 2076 participated, and 2044 (82.3%) had an examinable lens in at least one eye. Data recording included smoking history, occupation, education level, betel-nut chewing, height and weight, and dilated lens assessment using Lens Opacities Classification System III grading: nuclear (>or=4), cortical (>or=2) and posterior subcapsular (>or=2) cataracts. Aphakic and pseudophakic eyes were included as operated cataracts for statistical analysis. RESULTS: The prevalence of any cataract including operated eyes was 40.39% (95% CI 37.30 to 43.48%): 27.35% nuclear, 20.91% cortical and 11.34% posterior subcapsular cataracts. No significant association was found between cataract and betel-nut use, gender, smoking or outdoor occupation. The likelihood of all cataract types increased with age (multivariate analysis including operated eyes: OR 1.154, CI 1.13 to 1.18, p<0.001). Low level of education and low body mass index were associated with nuclear cataracts. Large village size was associated with increased risk for nuclear cataract (OR 3.23, CI 1.989 to 5.250, p<0.001) and decreased risk for cortical cataract (OR 0.20, CI 0.08 to 0.47, p<0.001). CONCLUSIONS: The prevalence of cataract in rural Myanmar is similar to that in other developing Asian regions. Cataracts are strongly associated with increasing age, and are more common in those with lower education and lower body mass index.

Pseudoexfoliation in a rural Burmese population: the Meiktila Eye Study.

AIMS: The aim of this study was to report on the prevalence and correlates of pseudoexfoliation syndrome (PXF) in a rural Burmese population. METHODS: The study was a cross-sectional, population-based survey of the inhabitants > or =40 years in the Meiktila District. Ophthalmic examination included Snellen visual acuity, slit lamp examination, tonometry, gonioscopy, dilated fundus examination and frequency doubling perimetry. RESULTS: In a population of 2076 subjects (4016 eyes) the prevalence of PXF was 3.4% (95% CI 2.14 to 4.67%; 78 eyes). Twelve eyes with PXF were blind. In the univariate analysis, PXF was associated with: increasing age, blindness (odds ratio (OR) 4, 95% CI 1.84 to 8.68; p<0.0004), increasing intraocular pressure (IOP) (OR 1.08, 95% CI 1.04 to 1.11; p<0.00001), nuclear cataract (OR 6.92, 95% CI 2.89 to 16.59; p<0.00001), cortical cataract (OR 4.78, 95% CI 2.37 to 9.65; p<0.00001) and the presence of an occludable angle (OR 3.05, 95% CI 1.52 to 6.13; p<0.002). In the multivariate analysis, only increasing age and IOP remained significantly associated with PXF. CONCLUSIONS: The prevalence of PXF in the Burmese population is greater than previously reported in other East Asian populations. Increasing age and IOP are the strongest predictors of PXF, and it is associated with cataract, occludable angles and blindness.

Anisometropia in an adult population in rural myanmar: the Meiktila Eye Study.

PURPOSE: To determine the prevalence and risk factors for anisometropia in a rural adult population in central Myanmar. METHODS: A population-based ophthalmic survey was conducted in rural villages in central Myanmar. Ansiometropia was assessed in subjects with phakic eyes. The severity of anisometropia was defined as the absolute difference of the spherical equivalent between the two eyes. RESULTS: Prevalence of anisometropia (> or =1.0 D) in all participants was 35.3% (95% CI 32.7-37.9%); severe anisometropia (> or =2.0 D) was present in 18.9 % (95% CI 16.8-21.0%). There was no significant gender difference in anisometropia prevalence or severity. Prevalence and severity of anisometropia were significantly associated with age. Multiple logistic regression analysis revealed that cataract, myopia, but not age, were associated with anisometropia. The between-eye differences in axial length (r = 0.15, p < 0.001) and corneal curvature (r = 0.19, p < 0.001) were significantly correlated with the severity of anisometropia. CONCLUSIONS: Prevalence of anisometropia is relatively high in this rural adult population in Myanmar. Myopia and cataract, but not increasing age, are the potential risk factors of anisometropia in this population.

The spatiotemporal pattern of somal and axonal pathology after perikaryal excitotoxic injury to retinal ganglion cells: a histological and morphometric study.

OBJECTIVE: To describe the spatiotemporal pattern of somal and axonal pathologic changes after perikaryal excitotoxic injury to retinal ganglion cells in-vivo. METHODS: 40 male Sprague-Dawley rats were killed at 0 h, 24 h, 72 h and 7 days after injecting 20 nM N-methyl-D-aspartate (NMDA) into the vitreous chamber of left eye. Saline-injected right eyes served as control. After perfusion fixation, the eyes and retrobulbar optic nerves from half of the animals in each group were embedded in paraffin and tissues from the other half embedded in resin. Paraffin-embedded eyes and resin-embedded proximal (intraorbital) and distal (intracranial) optic nerve segments were evaluated by light microscopy. Light microscopic photographs of proximal and distal optic nerve segments were compared using the following parameters: axon counts, axonal swellings and myelin changes. RESULTS: Retinas showed cell loss in ganglion cell layer (GCL) and reduction in inner retinal thickness at 72 h after NMDA injection (p<0.05), with changes becoming more advanced after 7 days (p<0.001). The cell count in GCL correlated strongly with the axonal counts (R=0.929, p<0.001). Axon loss, axon swellings and myelin damage were seen in both proximal and distal segments of optic nerves 72 h post-NMDA exposure (p<0.05), with changes increasing further at 7 days (p<0.001). Pathological changes were more prominent in the distal segments (p<0.05). CONCLUSION: Excitotoxic perikaryal injury causes an axonopathy, which is synchronous with the somal degeneration and which is most prominent in the distal portions of the axon, consistent with "dying-back like neuropathy".

Prevalence of refractive error in rural Myanmar: the Meiktila Eye Study.

OBJECTIVE: To determine the prevalence of refractive error and associated risk factors in the Meiktila District of central rural Myanmar. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Randomized stratified cluster sampling of the inhabitants 40 years or older from villages in Meiktila was performed; 2481 eligible participants were identified, 2076 participated in the study, and adequate refractive data were obtained on 1863 individuals (75.1%). METHODS: Demographic data including age, gender, and education level were obtained from all participants. The ophthalmic examination included autorefraction, nuclear opalescence (NO) grading at the slit lamp, and applanation tonometry. MAIN OUTCOME MEASURES: Refractive errors were classified by type of ametropia and their prevalence was determined. Univariate and multivariate analyses were performed and odds ratios were calculated for the predictors of refractive error within the statistical models. RESULTS: Mean refractive error measured -1.3 diopters (D) (standard deviation [SD], 2.9) and mean cylindrical error measured 1.1 D (SD, 1.5). Myopia of >-1.0 and >-6.0 D occurred in 42.7% (95% confidence interval [CI], 40.4%-44.9%) and 6.5% (95% CI, 5.4%-7.6%) of subjects, respectively. Myopic refractive error was associated significantly with a higher degree of NO (P<0.001) and age. Hypermetropia of >+1.0 D occurred in 15% (95% CI, 5.4%-7.6%) of the population and was associated with higher education levels (P<0.001). Astigmatism worse than 1.0 D occurred in 30.6% (95% CI, 28.5%-32.7%) of the population and was associated with age (P<0.001) and NO (P<0.001). CONCLUSION: Myopia was more prevalent in older subjects and in those with increased NO. The prevalence rates of myopia in the > or =40 age group are higher than those found in other Asian regions and are likely to contribute to visual impairment.

South Australian adolescent ophthalmic sun protective behaviours.

AIMS: To study student's knowledge of the effects of sunlight on the eyes, as well as their sun protective behaviours. METHODS: In total, 640 [corrected] students aged 13-18 years were surveyed in South Australia, during August-September 2004, using a standardized previously used survey. Scores were calculated regarding knowledge about ultraviolet light, sunlight effects on eyes, as well as eye and body protection. Risk factor scores were produced for each student. The data were analysed by the analysis of variance (ANOVA), as well as the Cochran-Mantel-Haenszel methods. Results were compared to the same survey conducted in 1995 in Queensland Australia. RESULTS: This group demonstrated a moderate level of knowledge, similar to the 1995 survey. Students in the older age groups demonstrated significantly higher knowledge. The majority of students (74%) owned a pair of sunglasses; however, 44.5% almost never wore their glasses. The reported frequency of wearing sunglasses was significantly related to advertising, believing sunglasses protect the eyes, as well as personal, family, and peer attitudes towards wearing sunglasses. CONCLUSION: The results of our survey suggest no significant change in knowledge and behaviours of students, compared to the 1995 survey. We feel it is imperative that adolescents be made more aware of the damaging effects of sunlight and the benefits of eye protection. Health promotion campaigns should target the youth and consider that as a group, they are significantly influenced by the media, peers, and family attitudes.

Comparison of the ICare rebound tonometer with the Goldmann applanation tonometer by experienced and inexperienced tonometrists.

PURPOSE: To assess the agreement between ICare rebound tonometer and Goldmann applanation tonometer in the hands of experienced and inexperienced tonometrists. PATIENTS AND METHODS: Two tonometrists, experienced with both Goldmann applanation tonometry (GAT) and ICare Tonometry (ICT) measured intraocular pressure (IOP), in a masked fashion, in 100 patients. In another series of 58 patients, ICT was performed by an inexperienced tonometrist and GAT by an experienced tonometrist. RESULTS: In approximately 80% of patients, the difference in IOP between GAT and ICT was

The prevalence, severity and risk factors for pterygium in central Myanmar: the Meiktila Eye Study.

AIMS: To determine the prevalence, severity and risk factors associated with pterygium in adults in central Myanmar. METHODS: Population-based, cross-sectional survey of the people 40 years and over residing in rural Myanmar. Pterygium was graded for severity (T1 to T3) by visibility of episcleral vessels, and the apical extent was recorded. An autorefractor was used to measure refractive error. RESULTS: There were 2481 subjects identified, and 2076 (83.7%) participated. The prevalence of pterygium in either eye was 19.6% (95% confidence interval (CI) 16.9 to 22.2) and of bilateral pterygium 8.0% (95% CI 7.7 to 8.3). Outdoor occupation was an independent predictor of pterygium (p<0.01). The mean apical extent from the limbus was 2.2 mm (95% CI 2.05 to 2.35). Higher-grade pterygia did not have a significantly greater apical extent (p = 0.35). The presence of pterygium was associated with astigmatism, (p = 0.01), and the amount of astigmatism increased as both the severity (p<0.01) and apical extent increased (p<0.01). Two people of the 84 people blinded in both eyes were bilaterally blind from pterygium (1.7%; 95% CI 0.2 to 6.1), and pterygium accounted for 2.2% (95% CI 0.7 to 5.0) of blindness in at least one eye. No participant had low vision in both eyes due to pterygium, but pterygium led to 0.8% (95% CI 0.3 to 1.6) of low vision in at least one eye. Pterygium was therefore associated with 0.4% (95% CI 0.04 to 1.3) of binocular visual impairment and 1.0% (95% CI 0.6 to 1.8) of visual impairment in a least one eye. CONCLUSIONS: There is a high prevalence of pterygium in central Myanmar, and the risk of developing this condition increases with outdoor occupation. Pterygium in this population is associated with considerable visual morbidity, including blindness.

Gonioscopy findings and prevalence of occludable angles in a Burmese population: the Meiktila Eye Study.

AIM: To determine the prevalence of preglaucomatous angle-closure disease in central Myanmar. METHODS: A population-based survey of inhabitants >or=40 years in the Meiktila District was carried out; 2481 subjects were identified, 2076 participated and 2060 underwent gonioscopy of at least one eye. Eyes with angles traditionally described as "occludable" were recorded as primary angle-closure suspects (PACS); eyes with PACS and peripheral anterior synechiae (PAS), or an increased intraocular pressure but without primary angle-closure glaucoma, were recorded as primary angle closure (PAC). RESULTS: The prevalence of PACS in at least one eye was 5.7% (95% CI 4.72 to 6.62); prevalence increased with age and was more common in women (p<0.001). The prevalence of PAC in at least one eye was 1.50% (95% CI 1.47 to 1.53). All participants with PAS had at least 90 degrees of closure (range 90-360 degrees). CONCLUSION: The prevalence of preglaucomatous angle-closure disease (PACS and PAC) in this population was 5.7% and 1.5%, respectively. PACS was more common in women, and its prevalence increased with age.

Prevalence of glaucoma in rural Myanmar: the Meiktila Eye Study.

AIM: To determine the prevalence of glaucoma in the Meiktila district of central, rural Myanmar. METHODS: A cross-sectional, population-based survey of inhabitants > or =40 years of age from villages in Meiktila district, Myanmar, was performed; 2481 eligible participants were identified and 2076 participated in the study. The ophthalmic examination included Snellen visual acuity, slit-lamp examination, tonometry, gonioscopy, dilated stereoscopic fundus examination and full-threshold perimetry. Glaucoma was classified into clinical subtypes and categorised into three levels according to diagnostic evidence. RESULTS: Glaucoma was diagnosed in 1997 (80.5%) participants. The prevalence of glaucoma of any category in at least one eye was 4.9% (95% CI 4.1 to 5.7; n = 101). The overall prevalence of primary angle-closure glaucoma (PACG) was 2.5% (95% CI 1.5 to 3.5) and of primary open-angle glaucoma (POAG) was 2.0% (95% CI 0.9 to 3.1). PACG accounted for 84% of all blindness due to glaucoma, with the majority due to acute angle-closure glaucoma (AACG). CONCLUSION: The prevalence of glaucoma in the population aged > or =40 years in rural, central Myanmar was 4.9%. The ratio of PACG to POAG was approximately 1.25:1. PACG has a high visual morbidity and AACG is visually devastating in this community. Screening programmes should be directed at PACG, and further study of the underlying mechanisms of PACG is needed in this population.

Madarosis.

Madarosis may be a presenting feature of a number of vision and life-threatening conditions, including herpes zoster, leprosy, HIV/AIDS, trachoma, malignant eyelid tumors, discoid lupus, scleroderma, and hypothyroidism. It may occur via two broad pathogenic pathways: scarring and non-scarring, which indicates the potential for lash re-growth. Madarosis may occur as an isolated finding or together with loss of other body and scalp hair. The etiology of madarosis can be further divided into dermatological, infection, endocrine, neoplastic, drug-related, congenital, and trauma. This report includes salient points in the clinical history and examination of patients with madarosis, with an emphasis on excluding or diagnosing visual or life threatening disorders associated with madarosis.