Profile of ocular trauma in the Solomon Islands.

BACKGROUND: The objective of this study was to characterize the causes of ocular trauma and determine the risk factors for infection and vision loss following ocular trauma in the Solomon Islands. DESIGN: A prospective clinic-based study. PARTICIPANTS: A total of 507 patients with ocular trauma who were reviewed at the National Referral Hospital in Honiara or one of five provincial eye clinics were included. METHODS: An interview-based questionnaire to determine the circumstances of ocular trauma, and an ocular examination to elicit the trauma sustained,infectious sequelae and the visual outcome. MAIN OUTCOME MEASURE: Visual acuity. RESULTS: Males were significantly more likely to have ocular trauma than females (P = 0.01). The major cause of ocular trauma in young boys and girls was being poked by a stick, followed by lime burns in young boys. For both genders, physical violence resulted in most injuries across all adult age groups. Microbial keratitis complicated 4.4% of ocular trauma. Monocular vision impairment (<6/18) occurred in 5.5% of participants and was more likely to occur if female (P = 0.02). CONCLUSIONS: Ocular trauma is a significant cause of visual morbidity in the Solomon Islands. The results from this prospective study provide a basis for planning blindness prevention programmes in the Western Pacific.

Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0×10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0%-3.2% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61×10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25×10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15×10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32×10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

Is diabetic retinopathy related to subclinical cardiovascular disease?

OBJECTIVE: Persons with diabetic retinopathy (DR) have an increased risk of clinical cardiovascular events. This study aimed to determine whether DR is associated with a range of measures of subclinical cardiovascular disease (CVD) in persons without clinical CVD. DESIGN: Population-based, cross-sectional epidemiologic study. PARTICIPANTS: Nine hundred twenty-seven persons with diabetes without clinical CVD in the Multi-Ethnic Study of Atherosclerosis. METHODS: Diabetic retinopathy was ascertained from retinal photographs according to modification of the Airlie House Classification system. Vision-threatening DR (VTDR) was defined as severe nonproliferative DR, proliferative DR, or clinically significant macular edema. Subclinical CVD measures were assessed and defined as follows: high coronary artery calcium (CAC) score, defined as CAC score of 400 or more; low ankle-brachial index (ABI), defined as ABI of less than 0.9; high ABI, defined as ABI of 1.4 or more; high carotid intima-media thickness (IMT), defined as highest 25% of IMT; and carotid stenosis, defined as more than 25% stenosis or presence of carotid plaque. MAIN OUTCOME MEASURES: Associations between DR and subclinical CVD measures. RESULTS: The prevalence of DR and VTDR in this sample was 30.0% and 7.2%, respectively, and VTDR was associated with a high CAC score (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.15-4.73), low ABI (OR, 2.54; 95% CI, 1.08-5.99), and high ABI (OR, 12.6; 95% CI, 1.14-140.6) after adjusting for risk factors including hemoglobin A1c level and duration of diabetes. The association between VTDR and high CAC score remained significant after further adjustment for hypoglycemic, antihypertensive, and cholesterol-lowering medications. Diabetic retinopathy was not significantly associated with measures of carotid artery disease. CONCLUSIONS: In persons with diabetes without a history of clinical CVD, the presence of advanced-stage DR is associated with subclinical coronary artery disease. These findings emphasize the need to be careful about the use of anti-vascular endothelial growth factor for the treatment of DR.

Retinopathy signs in people without diabetes: the multi-ethnic study of atherosclerosis.

OBJECTIVE: To describe the prevalence of retinopathy and associations with cardiovascular risk factors in persons without diabetes in 4 racial/ethnic groups (white, black, Hispanic, and Chinese). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We included 6176 subjects aged 45-84 years without diabetes, selected from 6 United States communities. METHODS: Fundus images were taken using 45° digital camera through dark-adapted pupils and were graded for retinopathy as defined by the Early Treatment Diabetic Retinopathy Study severity scale: microaneurysms, hemorrhages, cotton wool spots, intraretinal microvascular abnormalities, hard exudates, venous beading, and new vessels. MAIN OUTCOME MEASURES: Retinopathy and the association with cardiovascular risk factors. RESULTS: Prevalence rates of retinopathy in persons without diabetes were 12.5% overall, varying from 11.9% (white), 13.9% (black), 12.6% (Hispanic), to 17.2% (Chinese). Hypertension was strongly associated with retinopathy (odds ratio [OR], 1.47; 95% confidence interval [CI], 1.23-1.75). After adjusting for age, gender, race, and other parameters, smoking (OR, 1.50; 95% CI, 1.09-2.06) and increased internal carotid intima media thickness (OR, 1.22; 95% CI, 1.05-1.41) were associated with retinopathy. A range of serum inflammatory factors were examined, but none were found to be significant. CONCLUSIONS: Retinopathy in persons without diabetes is common, varies with race/ethnicity, and associated with cardiovascular risk factors, including hypertension, smoking, and carotid artery intima media thickness.

Retinal vascular caliber and brachial flow-mediated dilation: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND PURPOSE: Retinal vascular caliber changes have been shown to predict stroke, but the underlying mechanism of this association is unknown. We examined the relationship between retinal vascular caliber with brachial flow-mediated dilation (FMD), a measure of systemic endothelial function. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of persons 45 to 84 years of age residing in 6 US communities free of clinical cardiovascular disease at baseline. Brachial FMD data were collected at baseline (July 2000 to June 2002), and retinal vascular caliber was measured from digital retinal photographs at the second examination, immediately after the first (August 2002 to January 2004). Data were available for 2851 participants for analysis. RESULTS: The mean brachial FMD was 4.39+/-2.79%. After adjusting for age and gender, brachial FMD was reduced in persons with wider retinal venular caliber (changes in FMD -0.25, 95% CI, -0.36, - 0.13; P<0.001, per SD increase in venular caliber). This relationship persists after adjusting for systolic blood pressure, serum total cholesterol, use of lipid-lowering and antihypertensive medication, body mass index, current smoking status, and hemoglobinA(1C) (-0.18; 95% CI -0.30, - 0.06; P=0.004, per SD increase in venular caliber). Brachial FMD was not associated with retinal arteriolar caliber. CONCLUSIONS: Persons with wider retinal venules have reduced brachial FMD, independent of other vascular risk factors. This suggests that retinal venular caliber, previously shown to predict stroke, may be a marker of underlying systemic endothelial dysfunction.

Evidence of early retinal microvascular changes in patients with type 2 diabetes and depression.

OBJECTIVE: To examine retinal vascular caliber, an indicator of early microvascular disease and depression in patients with Type 2 diabetes. METHODS: We conducted a clinic-based study, comparing participants with Type 2 diabetes with major depression (n = 43), without depression (n = 49), and healthy controls without diabetes or depression (n = 54). Retinal vascular caliber was measured from digital photographs. Depression status was determined, using standardized clinical assessment. RESULTS: After adjusting for age and gender, participants with diabetes and depression had larger arteriolar and venular calibers (147.7 microm for arteriolar and 215.7 microm for venular calibers) than participants with diabetes but without depression (143.3 microm and 213.9 microm) and healthy controls (135.8 microm and 202.5 microm, p for trend = .002 for arteriolar and p = .02 for venular caliber). In multivariate models adjusting for duration of diabetes, systolic blood pressure, cigarette smoking, serum glucose, Cerebrovascular Risk Factor Scale, Cumulative Illness Rating Scale, and retinopathy levels, this relationship remained significant for retinal arterioles (p = .02) but not for retinal venules (p = .10). CONCLUSIONS: These data show that patients with Type 2 diabetes with major depression have wider retinal arterioles, supporting the concept that depression is associated with early microvascular changes in Type 2 diabetes.

Analysis of glutathione S-transferase Pi isoform (GSTP1) single-nucleotide polymorphisms and macular telangiectasia type 2.

Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case-control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P=0.43) or the Ala114Val SNP (P=0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.

Relation of retinopathy to coronary artery calcification: the multi-ethnic study of atherosclerosis.

Microvascular disease, reflected by retinal vascular changes, has been shown to predict clinical coronary heart disease. Whether retinal vascular changes are associated with subclinical coronary artery disease is unclear and was examined in this study. The authors conducted a multiethnic, population-based study of 6,147 persons aged 45-84 years, sampled from six US communities in 2002-2004, who were free of clinical cardiovascular disease. Coronary artery calcification (CAC), a noninvasive measure of subclinical coronary artery disease, was assessed by cardiac computed tomography scanning and categorized into three groups of increasing severity: none (average CAC score = 0), mild (1-100), and moderate-to-severe (>100). Retinopathy signs and retinal vascular caliber were graded from retinal photographs following standardized protocols. After adjustment for age, gender, race/ethnicity, blood pressure, diabetes, lipid profile, smoking, and other risk factors, retinopathy was associated with having a moderate-to-severe CAC score (odds ratio = 1.43, 95% confidence interval: 1.18, 1.75). This association remained significant in both men and women and in persons with and without diabetes or hypertension. Variations in retinal vascular caliber were not significantly associated with CAC score. This study shows that retinopathy signs are independently associated with CAC, supporting the concept that common pathophysiologic processes may underlie both micro- and macrovascular disease.

Assessment of TGIF as a candidate gene for myopia.

PURPOSE: Transforming growth beta-induced factor (TGIF) has been identified as a candidate gene for high myopia through genetic linkage studies and through its role in ocular growth in animal studies. However, the association of single nucleotide polymorphisms (SNPs), based solely on myopia refraction, has so far been inconclusive. This is the first study conducted to investigate the association of TGIF with refraction and ocular biometric measurements. METHODS: Twelve tag SNPs (tSNPs) encompassing the TGIF gene and 2 kb upstream of its promoter region were used to evaluate the association between TGIF variants with both ocular biometric measures and refraction. A total of 257 cases of myopia (spherical equivalent [SE] worse than -0.50 D) and 294 control subjects (no myopia) were genotyped. Genotype frequencies were analyzed by chi(2) test and one-way ANOVA. RESULTS: Two tSNPs showed significant association with biometric measures, with the SNP rs8082866 being associated with both axial length (P = 0.013) and corneal curvature (P = 0.007) and the SNP rs2020436 being associated with corneal curvature (P = 0.022). However, these associations became nonsignificant after multiple testing (Bonferroni correction). CONCLUSIONS: Findings of this study suggest that the TGIF gene is unlikely to play a major role in either ocular biometric measures or refraction in a Caucasian population. Future studies should focus on other genes in the MYP2 linkage region or other linked regions to identify myopia-causing genes.

Relationships of retinal vessel diameters with optic disc, macular and retinal nerve fiber layer parameters in 6-year-old children.

PURPOSE: To describe the normal anatomic relationships of retinal vessel diameters with optic disc, macula, and retinal nerve fiber layer parameters in young children. METHODS: This was a population-based, cross-sectional study of 1204 healthy children 6 years of age who were participating in the Sydney Childhood Eye Study. Retinal arteriolar and venular diameters were measured from fundus photographs using standardized computer-based methods. Optical coherence tomography was performed to obtain measurements of the optic disc, macula, and retinal nerve fiber layer parameters. RESULTS: In multivariate analyses, each standard deviation (SD) decrease in optic disc area was associated with a 0.14-pixel decrease (P = 0.05) in arteriolar diameter and a 0.31-pixel decrease (P < 0.01) in venular diameter. Each SD decrease in optic cup area was associated with a 0.15-pixel decrease (P = 0.05) in arteriolar diameter and a 0.43-pixel decrease (P < 0.01) in venular diameter. Each SD decrease in macular (inner/outer) thickness or volume was associated with a 0.25- to 0.39-pixel decrease (P < 0.01) in arteriolar diameter and a 0.36- to 0.71-pixel decrease (P < 0.01) in venular diameter, and each SD decrease in retinal nerve fiber layer thickness was associated with a 0.62-pixel decrease (P < 0.01) in arteriolar diameter and a 0.99-pixel decrease (P < 0.01) in venular diameter. CONCLUSIONS: Children's eyes with a smaller optic disc, thinner macula, and thinner retinal nerve fiber layer have narrower retinal vessels. These anatomic relationships may provide new insights into the vascular etiology of various ocular diseases.

Retinal vessel caliber and the long-term incidence of age-related cataract: the Blue Mountains Eye Study.

OBJECTIVE: To determine whether local nutritional or ischemic factors are involved in cataract pathogenesis, we aimed to assess whether narrowed retinal vessel caliber predicted the long-term incidence of age-related cataract, as shown in 1 previous report. DESIGN: Population-based cohort study. PARTICIPANTS: The Blue Mountains Eye Study examined 3654 baseline participants (1992-1994), 2335 (75.1% of survivors) after 5 years, and 1952 (75.6% of survivors) after 10 years. METHODS: Retinal vessel caliber was measured from baseline retinal photographs using computer-assisted techniques. Mean arteriolar and venular diameters of each eye were summarized as central retinal arterial (CRAE) and venular (CRVE) equivalents. Cataract was assessed from lens photographs of both eyes using the Wisconsin grading system. MAIN OUTCOME MEASURES: Nuclear cataract was defined as opacity > Wisconsin standard photograph 3, cortical cataract defined as opacity >or=5% of the lens area, and posterior subcapsular (PSC) cataract as any present. Eye-specific data were analyzed using generalized estimating equations. Odds ratios (OR) and 95% confidence intervals (CI) are reported. RESULTS: After adjusting for age, gender, smoking, hypertension, diabetes, body mass index, and inhaled steroid use, reduced incidence of nuclear cataract was associated with the narrowest compared with the widest quintile of CRAE and CRVE (for CRAE: OR, 0.62; 95% CI 0.42-0.92; for CRVE: OR, 0.70; 95% CI, 0.47-1.05) but a higher incidence of PSC cataract (for CRAE: OR, 2.40; 95% CI, 1.34-4.29; for CRVE: OR, 3.17; 95% CI, 1.62-6.20) and cataract surgery (for CRAE: OR, 1.52; 95% CI, 1.06-2.17; for CRVE: OR, 1.58; 95% CI, 1.08-2.32). These associations were not maintained when both CRAE and CRVE were included simultaneously in the same models. Path analysis suggested that age was the most important contributor to nuclear cataract incidence, and CRAE and CRVE, as markers of a latent age-related variable, were only indirectly associated with its incidence (for CRAE: OR, 0.61; 95% CI, 0.41-0.91; for CRVE: OR, 0.62; 95% CI, 0.41-0.94). CONCLUSIONS: Retinal vessel narrowing predicted greater risk of long-term incidence of PSC cataract and cataract surgery, and was indirectly linked to a lower incidence of nuclear cataract. Retinal vessel narrowing could be a marker of age-related factors associated with risk of PSC and nuclear cataract.

Arterial compliance and retinal vascular caliber in cerebrovascular disease.

OBJECTIVE: Arterial stiffness is a newly recognized risk factor for stroke. Whether this is mediated by small- or large-artery disease is unknown. In this study, we examined the relationship between arterial stiffness and retinal vascular caliber. METHODS: A cross-sectional, population-based study of 5,731 participants (aged 45-84 years) who were free of clinical cardiovascular disease (the Multi-Ethnic Study of Atherosclerosis). Retinal arteriolar and venular calibers were measured from retinal photographs according to standardized protocols. Small- and large-artery compliance was determined from pulse contour analysis. RESULTS: After adjusting for age, sex, blood pressure, diabetes, smoking, lipid profile, and other risk factors, reduced large-artery compliance was associated with smaller retinal arteriolar caliber; each standard deviation decrease in large-artery compliance was associated with a 0.70 microm (p = 0.002) decrease in retinal arteriolar caliber. After adjusting for the same set of risk factors, reduced small-artery compliance was associated with wider retinal venular caliber; each standard deviation decrease in small artery compliance was associated with a 1.43 microm (p = 0.001) increase in retinal venular caliber. These associations remained significant after further adjustments for large-vessel atherosclerosis (carotid intima-media thickness, coronary artery calcium, and ankle-arm index). INTERPRETATION: Reduced arterial wall compliance in large arterial beds is associated with retinal arteriolar narrowing, whereas reduced arterial wall compliance in small arterial beds is associated with retinal venular widening. These data may provide further insights into the effects of altered arterial stiffness on the cerebral microcirculation.

Is depression associated with microvascular disease in patients with type 2 diabetes?

We hypothesize that late-life depression is a manifestation of microvascular disease in patients with type 2 diabetes. We conducted a clinic-based cross-sectional study, comparing retinal vascular caliber, a marker of microvascular disease, in participants with type 2 diabetes with major depression (n=34), without depression (n=27) and healthy non-diabetic controls (n=38). Retinal vascular caliber was measured from digital retinal photographs using a validated computer-assisted method. After adjusting for age and gender, there was a trend of increasing retinal arteriolar caliber from healthy controls (132.6 microm), to diabetic patients without depression (139.2 microm), and diabetic patients with major depression (145.3 microm, P=0.008). The trend in retinal arteriolar caliber remains significant after adjusting for duration of diabetes, but not after further adjusting for vascular risk factors. Our findings suggest that there is variation in the retinal vascular caliber between type 2 diabetic patients with and without major depression and non-diabetic controls. This variation was largely related to poorer diabetes control and a higher frequency of vascular risk factors in diabetic patients, particularly those with depression. Studies with larger sample size may provide further insights into this association.

Functional presbyopia in a rural Kenyan population: the unmet presbyopic need.

BACKGROUND: Presbyopia is the most common reason for requiring spectacles in low-income regions, although the unmet need for presbyopic spectacles in these regions is very high. The aim of this study was to estimate the prevalence of presbyopia, and the functional impairment and spectacle use among persons with presbyopia in a rural Kenyan population. METHODS: A cross-sectional study was carried out in the Rift Valley, Kenya. Clusters were selected through probability-proportionate to size sampling, and people aged >/=50 years within the clusters were identified through compact segment sampling. Within the context of this survey, 130 eligible participants were selected for interview and underwent near-vision testing. Functional presbyopia was defined as requiring at least +1.00 dioptre in order to read the N8 optotype at a distance of 40 cm in the participant's usual visual state. Participants were corrected to the nearest 0.25 dioptre in order to see N8. Unmet and met presbyopic need, and presbyopic correction coverage were calculated. RESULTS: Functional presbyopia was found in 111 participants (85.4%). Mean age was lower in those with presbyopia (64.1 years vs. 71.5 years, P = 0.004). Increasing degree of addition required to see N8 was significantly associated with increased difficulty with reading (P = 0.04), sewing (P = 0.03), recognizing small objects (P = 0.02) and harvesting grains (P = 0.05). Among participants with functional presbyopia, 5.4% wore reading glasses and 25.2% had prior contact with an eye care professional. The unmet presbyopic need was 80.0%, met presbyopic need was 5.4% and presbyopic correction coverage was 6.3%. Cost was cited as the main barrier to spectacle use in 62% of participants with presbyopia. CONCLUSION: In low-income regions, there is a high prevalence of uncorrected presbyopia, which is associated with near-vision functional impairment. Provision of spectacles for near vision remains a priority in low-income regions.

Distribution and associations of retinal vascular caliber with ethnicity, gender, and birth parameters in young children.

PURPOSE: To describe the distribution of retinal vascular calibers and their associations with ethnicity, gender, and birth parameters in children. METHODS: This was a school-based cross-sectional study of 768 children aged 7 to 9 years who participated in the Singapore Cohort Study of the Risk Factors for Myopia (SCORM). Participants had retinal photographs taken in 2001. Retinal vascular calibers were measured with computer-based program and summarized as average caliber of arterioles and venules in that eye. Associations of retinal vascular caliber with ethnicity, gender, and various birth factors were analyzed. RESULTS: In this population, the mean retinal arteriolar caliber was 156.4 microm (95% confidence interval [CI], 155.4-157.3) and venular caliber was 225.4 microm (95% CI, 224.1-226.8). The retinal arteriolar caliber was significantly narrower in Chinese (154.9 microm), compared with Malay (158.6 microm) and Indian (158.5 microm) children. Retinal venular caliber was also narrower in Chinese (223.3 microm) compared with Malay (230.8 microm) and Indian (229.0 microm) children. These differences were statistically significant, even after adjustments for age, gender, family income, parental education, body mass index, height, birth weight, axial length, and spherical equivalent (P = 0.05 for arteriolar caliber; P = 0.002 for venular caliber). In multivariate analysis, there were no significant gender differences in retinal vascular caliber. Birth factors, including birth weight, birth length, head circumference, and gestational age, were not significantly associated with changes in either retinal arteriolar or venular caliber. CONCLUSIONS: The results show ethnic variation in retinal vascular caliber in Singaporean children. No association of birth parameters with retinal vascular caliber was found. Because retinal vascular caliber is related to various cardiovascular and ocular diseases, it is possible that ethnic variations in retinal vascular caliber should be taken into consideration in future studies.

A tag-single nucleotide polymorphisms approach to the vascular endothelial growth factor-A gene in age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is the leading cause of poor vision in the developed world, and its pathogenesis remains unknown. The most devastating form of end stage disease is neovascular or wet AMD, where there is abnormal growth of new blood vessels under the retina. Vascular endothelial growth factor (VEGF) is thought to be a major player in the stimulus of this abnormal growth of blood vessels. We undertook a case-control association study to investigate the VEGF-A gene, a known angiogenic gene that has previously been associated with AMD. METHODS: We recruited 577 individuals with AMD (early, atrophic, and neovascular AMD) and 173 ethnically matched controls for our study. We employed a tag-single nucleotide polymorphisms (tSNP) approach to investigate this gene using a series of seven tSNPs that encompassed the coding region of the VEGF gene as well as its promoter. Alleles were determined by a MALDI-TOF based approach followed by statistical analysis. RESULTS: One SNP (rs3024997) showed evidence of departure from Hardy-Weinberg equilibrium in only the AMD cases. Therefore, it was retained for further analysis. All other SNPs in our study showed no departure from Hardy-Weinberg equilibrium. No association was found between any of the VEGF tSNPs analyzed in our study and AMD nor any of its sub-types. CONCLUSIONS: Using a tSNP approach, we found no evidence of an association of these SNPs within the VEGF-A gene being associated with either AMD or any of its subtypes in our population.

Influence of intraocular pressure on retinal vascular caliber measurements in children.

PURPOSE: To determine whether intraocular pressure (IOP) influences retinal vascular caliber in young children, in order to provide a better understanding of its physiological determinants. DESIGN: Cross-sectional study. METHODS: Three hundred and eighty-six Chinese children seven to nine years of age participated in the Singapore Cohort Study of the Risk factors for Myopia (SCORM). IOP was measured by noncontact tonometry. Retinal vascular calibers were measured from retinal photographs using a computer-based program following standardized protocols. RESULTS: After adjusting for age, gender, body mass index, corneal thickness, spherical equivalent refraction, axial length, and birth weight, mean retinal arteriolar and venular caliber were similar across the distribution of IOP (arteriolar caliber of 155.2 microm, 155.6 microm, 153.8 microm, 154.2 microm, P value for trends, 0.45; and venular caliber of 225.7 microm, 220.6 microm, 224.5 microm, 222.7 microm, P value for trends, 0.53; comparing increasing quartiles of IOP). CONCLUSIONS: Our study provides no evidence that IOP influences retinal vascular caliber in healthy young children.

Efficacy and safety of multiple intravitreal triamcinolone injections for refractory diabetic macular oedema.

AIM: The efficacy and safety of repeated injections of intravitreal triamcinolone (IVTA) for diabetic macular oedema is unclear, with results of previous reports conflicting. METHODS: This is a prospective, observational case series of 27 eyes receiving IVTA for diabetic macular oedema. LogMAR visual acuity (VA) and central macular thickness (CMT) were measured at baseline and in 3 to 6 monthly intervals for up to 24 months, then correlated with the number of IVTA injections given. RESULTS: One IVTA injection was required in 6 (18%) eyes, 2 in 8 (24%) eyes, 3 in 13 (39%) eyes and 4-5 in 6 (18%) eyes. VA improved in all patients, but neither the final improvement in VA nor the absolute improvement in CMT from baseline to 24 months correlated with the number of injections received (p = 0.44 and 0.84, respectively). Cataract surgery was more frequent in eyes receiving more injections (p = 0.01). CONCLUSIONS: This study suggests that repeated injections of IVTA continue to be as effective as the first over a 2-year period. The probability of cataract surgery increases with an increasing number of injections.

Is early age-related macular degeneration related to carotid artery stiffness? The Atherosclerosis Risk in Communities Study.

BACKGROUND/PURPOSE: Atherosclerosis and vascular stiffness have been implicated in the pathogenesis of age-related macular degeneration (AMD). The association of carotid artery stiffness, a measure of arterial elasticity reflecting early atherosclerosis, with early AMD, was examined in this study. METHODS: A population-based, cross-sectional study of 9954 middle-aged people (age range 51-72 years). The presence of AMD signs was determined from fundus photographs according to the Wisconsin grading protocol. Carotid arterial stiffness was measured from high-resolution ultrasonic echo tracking of the left common carotid artery, and was defined as an adjusted arterial diameter change (AADCmu). A smaller AADC reflects greater carotid artery stiffness. The associations of pulse pressure and carotid artery intima-media thickness (IMT) with early AMD signs were also analysed. RESULTS: In the study population, 454 (4.6%) had early AMD. The mean (SD) AADC was 403 (127) mu. After adjusting for age, sex, race/centre, education, cigarette smoking, fasting glucose, lipid profile and inflammatory markers, a smaller AADC was found to be not associated with early AMD (odds ratio 0.94; 95% confidence interval, 0.71 to 1.25) or its component lesions. Other measures of arterial stiffness (pulse pressure) and atherosclerosis (carotid IMT) were also not associated with early AMD. CONCLUSIONS: Carotid artery stiffness was not associated with signs of early AMD in this middle-aged population. These data provide no evidence of a link between age-related elastoid changes and early atherosclerotic processes in the carotid arteries and early AMD.

Analysis of the Y402H variant of the complement factor H gene in age-related macular degeneration.

PURPOSE: Recent studies in U.S. populations have indicated that the Y402H variant of the complement factor H (CFH) gene contains a major risk susceptibility allele for age-related macular degeneration (AMD). This study was conducted to ascertain whether this is also true in a non-U.S. population and also whether the at-risk allele is associated with the clinical phenotype of disease and the age at diagnosis. METHODS: Two hundred thirty-six unrelated individuals with AMD and 144 unrelated but ethnically matched control subjects were recruited and examined. All subjects completed a standard questionnaire, were given a fundus examination, and provided a blood sample for DNA extraction. Alleles of Y402H in the CFH gene were determined by use of a MALDI-TOF-based approach followed by statistical analysis. RESULTS: Individuals with AMD who had at least one copy of the C allele of Y402H had an increased risk of disease (odds ratio [OR] 2.98; 95% confidence interval [CI] 1.81-4.93) compared with cases with the T allele. On subgroup analysis, this risk was found to be most significant in individuals with neovascular disease (OR 4.34; 95% CI 1.94, 9.71). In addition, individuals with neovascular disease who were homozygous CC presented with a significant 7.0-year earlier age at diagnosis relative to those individuals who were homozygous TT. The population-attributable risk for the C allele ranged between 47% to 69%, depending on the AMD disease subtype. CONCLUSIONS: The C allele of Y402H represents a significant risk factor in individuals with AMD, and this effect is most pronounced in individuals with neovascular disease.