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1.  Prevalence of Cataract in an Older Population in India 
Ophthalmology  2011;118(2-19):272-278.e2.
To describe the prevalence of cataract in older people in 2 areas of north and south India.
Population-based, cross-sectional study.
Randomly sampled villages were enumerated to identify people aged ≥60 years. Of 7518 enumerated people, 78% participated in a hospital-based ophthalmic examination.
The examination included visual acuity measurement, dilatation, and anterior and posterior segment examination. Digital images of the lens were taken and graded by type and severity of opacity using the Lens Opacity Classification System III (LOCS III).
Main Outcome Measures
Age- and gender-standardized prevalence of cataract and 95% confidence intervals (CIs). We defined type of cataract based on the LOCS III grade in the worse eye of: ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any unoperated cataract was based on these criteria or ungradable dense opacities. Any cataract was defined as any unoperated or operated cataract.
The prevalence of unoperated cataract in people aged ≥60 was 58% in north India (95% CI, 56–60) and 53% (95% CI, 51–55) in south India (P = 0.01). Nuclear cataract was the most common type: 48% (95% CI, 46–50) in north India and 38% (95% CI, 37–40) in south India (P<0.0001); corresponding figures for PSC were 21% (95% CI, 20–23) and 17% (95% CI, 16–19; P = 0.003), respectively, and for cortical cataract 7.6% (95% CI, 7–9) and 10.2% (95% CI, 9–11; P<0.004). Bilateral aphakia/pseudophakia was slightly higher in the south (15.5%) than in the north (13.2%; P<0.03). The prevalence of any cataracts was similar in north (73.8%) and south India (71.8%). The prevalence of unoperated cataract increased with age and was higher in women than men (odds ratio [OR], 1.8). Aphakia/pseudophakia was also more common in women, either unilateral (OR, 1.2; P<0.02) or bilateral (OR, 1.3; P<0.002).
We found high rates of unoperated cataract in older people in north and south India. Posterior subcapsular cataract was more common than in western studies. Women had higher rates of cataract, which was not explained by differential access to surgery.
Financial Disclosure(s)
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
PMCID: PMC3146699  PMID: 20801514
2.  Inverse Association of Vitamin C with Cataract in Older People in India 
Ophthalmology  2011;118(10):1958-1965.e2.
To examine the association between vitamin C and cataract in the Indian setting.
Population-based cross-sectional analytic study.
A total of 5638 people aged ≥60 years.
Enumeration of randomly sampled villages in 2 areas of north and south India to identify people aged ≥60 years. Participants were interviewed for socioeconomic and lifestyle factors (tobacco, alcohol, household cooking fuel, work, and diet); attended a clinical examination, including lens photography; and provided a blood sample for antioxidant analysis. Plasma vitamin C was measured using an enzyme-based assay in plasma stabilized with metaphosphoric acid, and other antioxidants were measured by reverse-phase high-pressure liquid chromatography.
Main Outcome Measures
Cataract and type of cataract were graded from digital lens images using the Lens Opacity Classification System III (LOCS III), and cataract was classified from the grade in the worse eye of ≥4 for nuclear cataract, ≥3 for cortical cataract, and ≥2 for posterior subcapsular cataract (PSC). Any cataract was defined as any unoperated or operated cataract.
Of 7518 enumerated people, 5638 (75%) provided data on vitamin C, antioxidants, and potential confounders. Vitamin C was inversely associated with cataract (adjusted odds ratio [OR] for highest to lowest quartile = 0.61; 95% confidence interval (CI), 0.51–0.74; P=1.1×10−6). Inclusion of other antioxidants in the model (lutein, zeaxanthin, retinol, β-carotene, and α-tocopherol) made only a small attenuation to the result (OR 0.68; 95% CI, 0.57–0.82; P < 0.0001). Similar results were seen with vitamin C by type of cataract: nuclear cataract (adjusted OR 0.66; CI, 0.54–0.80; P < 0.0001), cortical cataract (adjusted OR 0.70; CI, 0.54–0.90; P < 0.002), and PSC (adjusted OR 0.58; CI, 0.45–0.74; P < 0.00003). Lutein, zeaxanthin, and retinol were significantly inversely associated with cataract, but the associations were weaker and not consistently observed by type of cataract. Inverse associations were also observed for dietary vitamin C and cataract.
We found a strong association with vitamin C and cataract in a vitamin C–depleted population.
Financial Disclosure(s)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
PMCID: PMC3185206  PMID: 21705085
3.  Risk factors for nuclear, cortical and posterior subcapsular cataracts in the Chinese population of Singapore: the Tanjong Pagar Survey 
The British Journal of Ophthalmology  2003;87(9):1112-1120.
Aim: To describe risk factors for nuclear, cortical, and posterior subcapsular (PSC) cataracts in Chinese Singaporeans.
Methods: A population based cross sectional study was carried out on ethnic Chinese men and women aged 40–81 years. A stratified, clustered, disproportionate (more weights to older people), random sampling procedure was used to initially select 2000 Chinese names of those aged 40–79 years from the 1996 electoral register in the Tanjong Pagar district in Singapore. Eligible subjects (n = 1717) were invited for a standardised ocular examination and interview at a centralised clinic, following which an abbreviated examination was conducted for non-respondents in their homes. Cataract was graded clinically using to the Lens Opacity Classification System (LOCS) III system. The main outcome measures were adjusted odds ratio for risk factors for specific cataract types (nuclear, cortical and PSC), any cataract and cataract surgery, examined in multiple logistic regression models.
Results: Out of the 1232 (71.8%) examined, 1206 (70.2%) provided lens data for this analysis. Increasing age was associated with all cataract types, any cataract, and cataract surgery. There was no significant sex difference in presence of any cataract, specific cataract types or cataract surgery. After controlling for age, sex, and other factors, diabetes was associated with cortical cataract (3.1; 95% CI: 1.6 to 6.1), PSC cataract (2.2; 95% CI 1.2 to 4.1), any cataract (2.0; 95% CI: 0.9 to 4.5), and cataract surgery (2.3; 95% CI: 1.3 to 4.1). Lower body mass index was associated with cortical cataract (1.8; 95% CI: 1.1 to 2.9; lowest versus highest quintile) and any cataract (2.3; 95% CI: 1.3 to 4.0). Current cigarette smoking was associated with nuclear cataract (1.7, 95% CI: 1.0 to 2.9; more than 10 cigarettes per day versus none). A non-professional occupation was associated with nuclear cataract (2.9; 95% CI: 1.5 to 5.8; for production or machine operators and 2.6; 95% CI: 1.2 to 5.5; for labourers or agricultural workers, both versus professionals). Lower education was associated with nuclear cataract (2.3; 95% CI: 1.0 to 5.2, none versus tertiary), while lower household income was associated with PSC cataract (4.7, 95% CI: 1.1 to 20.0; income S$4000).
Conclusions: Age related cataracts are associated with a variety of risk factors among Chinese people in Singapore, similar to those reported in European, Indian, and African derived populations. These data support common aetiological mechanisms for age related cataracts, irrespective of ethnic origin.
PMCID: PMC1771847  PMID: 12928278
cataracts; Chinese; Singapore
4.  Association of EPHA2 polymorphisms and age-related cortical cataract in a Han Chinese population 
Molecular Vision  2011;17:1553-1558.
The gene for Eph-receptor tyrosinekinase-type A2 (EPHA2) has been shown to be involved in the pathogenesis of age-related cataract (ARC). The aim of this study was to examine whether EPHA2 polymorphisms were associated with the susceptibility to age-related cortical cataract in a Han Chinese population.
Five single-nucleotide polymorphisms (SNPs)—rs3768293, rs3754334, rs7548209, rs707455, and rs477558—in the EPHA2 gene were genotyped in 422 Han Chinese patients with age-related cortical cataract and 317 age-, sex-, and ethnically matched healthy controls using a PCR restriction fragment length polymorphism (PCR-RFLP) assay. Data were analyzed by χ2 analysis.
The results showed that the five analyzed polymorphisms in EPHA2 were in Hardy–Weinberg equilibrium both in the patients and in the controls. The frequency of the rs477558 AA genotype was significantly increased in ARC patients compared with controls (χ2=8.649, pc=0.045, odds ratio [OR] 1.555, 95% CI 1.158 to 2.089). The frequency of the rs477558 AG genotype was significantly decreased in ARC patients compared with controls (χ2=9.281, pc=0.030, OR 0.626, 95% CI 0.463 to 0.847). Significantly higher frequencies of the GG genotype and the G allele of rs7548209 were observed in ARC patients compared with controls (χ2=10.430, pc=0.015, OR 1.660, 95% CI 1.219 to 2.261 and χ2=8.537, pc=0.015, OR 1.486, 95% CI 1.138 to 1.940, respectively). On the other hand, significantly decreased frequencies of the rs7548209 CG genotype and the C allele were observed in ARC patients compared with controls (χ2=9.999, pc=0.030, OR 0.603, 95% CI 0.440 to 0.826 and χ2=8.537, pc=0.015, OR 0.673, 95% CI 0.515 to 0.879, respectively). There was no difference in the frequencies of the genotype and allele of the rs3768293, rs3754334, and rs707455 SNPs between the patients with ARC and the controls.
Our study suggests that both SNP rs477558 and SNP rs7548209 of EPHA2 are associated with age-related cortical cataract in a Han Chinese population.
PMCID: PMC3115745  PMID: 21686326
5.  Risk factors for age related cataract in a rural population of southern India: the Aravind Comprehensive Eye Study 
Aim: To determine risk factors for lens opacities and age related cataract in an older rural population of southern India.
Methods: A cross sectional population based study of 5150 people aged 40 years and above from 50 clusters from three districts in southern India. The lens was graded and classified after dilation using LOCS III system at the slit lamp for cataract. Definite cataract was defined as nuclear opalescence ⩾3.0 and/or cortical cataract ⩾3.0 and/or PSC ⩾2.0.
Results: Definite cataracts were found in 2449 (47.5%) of 5150 subjects and the prevalence of cataract increased with age. The age adjusted prevalence of cataract was significantly lower in males (p = 0.0002). Demographic risk factors—increasing age and illiteracy—were common for the three subtypes of cataract; females were more likely to have cortical cataracts and nuclear cataracts. Additionally, nuclear cataracts were associated with moderate smoking (OR:1.28, 95% CI:1.01 to 1.64), lean body mass indices (OR: 1.37, 95% CI: 1.17 to 1.59) and higher waist to hip ratios (OR: 0.67, 95% CI: 0.54 to 0.82); cortical cataracts with hypertension (OR: 1.39 95% CI:1.11 to 1.72), pseudoexfoliation (OR:1.53,95% CI:1.17 to 2.01), and moderate to heavy smoking; and posterior subcapsular cataracts with diabetes (OR:1.55, 95% CI:1.12 to 2.15), lean body mass (OR:1.32, 95% CI:1.11 to 1.57), and high waist to hip ratios (OR: 0.77, 95% CI: 0.62 to 0.94).
Conclusions: Risk factors for age related cataract in this population do not appear to be different from those reported in other populations. Further studies are required to identify the reason for the high prevalence of age related cataract and to understand better the role of each risk factor for cataractogenesis in this population.
PMCID: PMC1772282  PMID: 15258010
age related cataract; India; Aravind Comprehensive Eye Study
6.  Association of the Ephreceptor Tyrosinekinase-Type A2 (EPHA2) Gene Polymorphism rs3754334 with Age-Related Cataract Risk: A Meta-Analysis 
PLoS ONE  2013;8(8):e71003.
Recent clinical studies have assessed the association of various polymorphisms on the ephreceptor tyrosinekinase-type A2 (EPHA2) with the risk for age-related cataract in populations of different ethnic/racial backgrounds, but inconsistent results have been obtained.
This meta-analysis aimed to identify if any polymorphism(s) might be commonly present in different ethnic/racial populations in association with the age-related cataract risk.
The PubMed and Web of Science databases (up to December 1, 2012) were searched for clinical studies on the association of EPHA2 polymorphisms with the risk for age-related cataract. The polymorphisms that were assessed in all eligible studies were analyzed for their association with the risk for age-related cataract using different models.
Three studies were identified, which were conducted, respectively, on white Americans in the Unites States and on Asians in Indian and China. The polymorphism, rs3754334, was the only one studied in all these three studies and was therefore the focus of this meta-analysis. No publication bias or heterogeneity was found. Our analysis results demonstrated that rs3754334 was associated with the risk of any cataracts in the recessive (OR = 1.202, 95% CI: 1.051–1.375, P = 0.007) and Codominant (OR = 1.194, 95% CI: 1.035–1.378, P = 0.015) models, but its association with cortical or nuclear phenotype of age-related cataract was not evident.
Polymorphism, rs3754334, might be a variant on the EPHA2 gene that is commonly associated with the risk for age-related cataract in different ethnical and geographical populations.
PMCID: PMC3745390  PMID: 23976972
7.  Risk factors associated with incident cataracts and cataract surgery in the Age Related Eye Disease Study (AREDS). AREDS Report Number 32 
Ophthalmology  2011;118(11):2113-2119.
To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS).
Clinic-based prospective cohort study.
Persons (N=4425), aged 60 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration (AMD) and cataract.
Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS System for Classifying Cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, with also a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type specific opacities and cataract surgery.
Main Outcome Measures
Moderate cataract was defined as a grade of ≥4.0 for nuclear opacity, ≥10% involvement within the full visible lens for cortical opacity, and ≥5% involvement of the central 5 mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs.
A clinic-based cohort of 4425 persons aged 55–80 years at baseline was followed for an average of 9.8 ± 2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; non-whites with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery.
Our findings are largely consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract.
PMCID: PMC3178670  PMID: 21684602
8.  The EPHA2 gene is associated with cataracts linked to chromosome 1p 
Molecular Vision  2008;14:2042-2055.
Cataracts are a clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of treatable vision loss and blindness worldwide. Here we identify a novel gene linked with a rare autosomal dominant form of childhood cataracts segregating in a four generation pedigree, and further show that this gene is likely associated with much more common forms of age-related cataracts in a case-control cohort.
Genomic DNA was prepared from blood leukocytes, and genotyping was performed by means of single nucleotide polymorphism (SNP) markers, and short tandem repeat (STR) markers. Linkage analyses were performed with the GeneHunter and MLINK programs, and association analyses were performed with the Haploview and Exemplar programs. Mutation detection was achieved by PCR amplification of exons and di-deoxy cycle-sequencing.
Genome-wide linkage analysis with SNP markers, identified a likely disease-haplotype interval on chromosome 1p (rs707455-[~10 Mb]-rs477558). Linkage to chromosome 1p was confirmed using STR markers D1S2672 (LOD score [Z]=3.56, recombination distance [θ]=0), and D1S2697 (Z=2.92, θ=0). Mutation profiling of positional-candidate genes detected a heterozygous transversion (c.2842G>T) in exon 17 of the gene coding for Eph-receptor type-A2 (EPHA2) that cosegregated with the disease. This missense change was predicted to result in the non-conservative substitution of a tryptophan residue for a phylogenetically conserved glycine residue at codon 948 (p.G948W), within a conserved cytoplasmic domain of the receptor. Candidate gene association analysis further identified SNPs in the EPHA2 region of chromosome 1p that were suggestively associated with age-related cataracts (p=0.007 for cortical cataracts, and p=0.01 for cortical and/or nuclear cataracts).
These data provide the first evidence that EPHA2, which functions in the Eph-ephrin bidirectional signaling pathway of mammalian cells, plays a vital role in maintaining lens transparency.
PMCID: PMC2582197  PMID: 19005574
9.  EPHA2 Is Associated with Age-Related Cortical Cataract in Mice and Humans 
PLoS Genetics  2009;5(7):e1000584.
Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27) before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.
Author Summary
Cataract is the leading cause of blindness. Cataract may form at any age, but the peak incidence is bimodal—in the perinatal period or later than 50 years of age. The early onset forms follow Mendelian inheritance patterns and are rare. Age-related cataract accounts for 18 million cases of blindness and 59 million cases of reduced vision worldwide. Among three types of age-related cataract, cortical cataract is known to be highly heritable, although few genes have been linked to its etiology. We report here that EPHA2 is associated with cortical cataract. EPHA2 is expressed in mouse and human cortical lens fiber cells, and homozygous deletion of Epha2 in two independent strains of mice led to development of cataract that progressed with age. Common and rare variants including a missense mutation in the EPHA2 gene were associated for cortical cataract in three different Caucasian populations. Our study identified EPHA2 as a gene for human age-related cataract and established Epha2 knockout mice as a model for progressive cortical cataract.
PMCID: PMC2712078  PMID: 19649315
10.  Cataract surgery and subtype in a defined, older population: the SEECAT Project 
The British Journal of Ophthalmology  2004;88(12):1512-1517.
Aim: To describe the distribution of cataract subtypes present before surgery among a defined population of older, bilaterally pseudophakic individuals.
Methods: This was a cohort study of bilaterally pseudophakic individuals participating in the Salisbury Eye Evaluation (SEE), and their locally resident siblings. Subjects underwent slit lamp and retroillumination photography and grading using the Wilmer Cataract Grading System. For all individuals determined to be bilaterally pseudophakic, an attempt was made to determine for each eye the type(s) of cataract present before surgery, based on previous SEE photographs (for SEE participants) and/or medical records obtained from the operating ophthalmologist (for both SEE participants and their siblings).
Results: The mean age of 223 participants providing data in this study was 78.7 (SD 5.2) years, 19.3% of subjects were black and 60.1% female. The most common surgically removed cataract subtype in this population was pure nuclear (43.5%), followed by nuclear combined with posterior subcapsular cataract (PSC) (20.6%), and nuclear combined with cortical (13.9%); less common types were pure cortical (4.9%), pure PSC (4.5%), and PSC combined with cortical (2.7%). Factors such as sex and source of lens data (study photograph versus clinical record) did not significantly affect the distribution of lens opacity types, while PSC was significantly (p = 0.01) more common among younger people and nuclear cataract was significantly (p = 0.001) more common among white compared to black people.
Conclusion: Epidemiological studies have suggested that the different subtypes of cataract are associated with different risk factors. As studies begin to identify new prevention strategies for cataract, it would appear likely that different strategies will be efficacious against different types of cataract. In this setting, it will be helpful to know which cataract types are most frequently associated with surgery. Among this older, majority white population, nuclear cataract showed a clear predominance among individuals having undergone surgery in both eyes. This may be contrasted with both clinic and population based studies of younger people, which have generally found PSC cataract to predominate.
PMCID: PMC1772435  PMID: 15548802
Cataract surgery; older people
11.  Topical Ocular Hypotensive Medication and Lens Opacification: Evidence from the Ocular Hypertension Treatment Study (OHTS) 
American journal of ophthalmology  2006;142(5):800-810.
To determine whether topical ocular hypotensive medication is associated with refractive changes, visual symptoms, decreased visual function, or increased lens opacification.
Multicenter clinical trial
We compared the medication and observation groups of OHTS during 6.3 years of follow-up with regard to the rate of cataract and combined cataract/filtering surgery, and change from baseline in visual function, refraction and visual symptoms. A one-time assessment of lens opacification was done using the Lens Opacities Classification System III (LOCS III) grading system.
An increased rate of cataract extraction and cataract/filtering surgery was found in the medication group (7.6%) compared to the observation group (5.6%) (HR 1.56; 95% CI 1.05–2.29). The medication and observation groups did not differ with regard to changes from baseline to June 2002 in Humphrey visual field mean deviation, Humphrey visual field foveal sensitivity, Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity, refraction and visual symptoms. For the medication and observation groups, LOCS III readings were similar for nuclear color, nuclear opalescence and cortical opacification. There was a borderline higher mean grade for posterior subcapsular opacity in the medication group (0.43 ± 0.6 SD) compared to the observation group (0.36 ± 0.6 SD) (p=0.07).
We noted an increased rate of cataract extraction and cataract/filtering surgery in the medication group as well as a borderline higher grade of posterior subcapsular opacification in the medication group on LOCS III readings. We found no evidence for a general effect of topical ocular hypotensive medication on lens opacification or visual function.
PMCID: PMC1976472  PMID: 17056362
12.  The Association Between Refractive Errors and Cataract: The Tehran Eye Study 
To determine the association between refractive errors and different types of cataract in Tehran, Iran.
Materials and Methods:
In a cross-sectional survey with a stratified cluster sampling approach, refractive errors were tested under cycloplegia. Myopia and hyperopia were defined as a spherical equivalent refractive error <-0.5 diopters (D) and more than +0.5 D, respectively. Cataract was graded according to the Lens Opacities Classification System III classification and the association between refractive errors and cataract was assessed. Of 1434 participants over the age of 40 years who participated in the study, data from 1313 right eyes were analyzed.
The mean age of the participants was 52.7 ± 10.0 years, and 58.3% (n = 767) were female. Overall, myopia was more prevalent among those with cataract (odds ratio [OR]: 2.00, 95% confidence interval [CI]: 1.38–2.89). Based on the type of cataract and refractive errors, the odds of myopia was significantly higher with nuclear cataracts (OR: 1.81, 95% CI: 1.14–2.87). The odds of myopia was higher for cases of nuclear cataract with some degrees of posterior subcapsular cataract (PSC) (OR: 3.33, 95% CI: 1.42–7.80). Of nine participants with cortical cataract, seven participants had hyperopia (OR: 3.77, 95% CI: 0.78–18.31).
Individuals with nuclear and PSC showed a significantly higher prevalence of myopia while the prevalence of hyperopia was lower in those with cataract. High myopia was seen in higher grades of nuclear cataract. The high percentage of hyperopia was also significant in patients with cortical cataract. More studies are necessary to clarify the correlation between cortical cataract and hyperopia.
PMCID: PMC3119285  PMID: 21731327
Cataract; Population-Based Study; Refractive Errors
13.  The locus for an inherited cataract in sheep maps to ovine chromosome 6 
Molecular Vision  2012;18:1384-1394.
Cataracts are an important cause of blindness in humans but there are few large animal models available. One of these animal models is Ovine Heritable Cataract, a bilateral cortical cataract which develops after birth. This cataract has been used as a model for human cataracts in drug trials, but the gene responsible for the cataract trait is unknown. A genetic test for cataract would improve the efficiency of the model by predicting which animals would develop cataracts. Identifying the genetic basis of the cataract would indicate its relevance to human cataract.
A genome scan was performed on 20 sheep chromosomes, representing 86% of the genome, to determine the position of the cataract locus. Additional microsatellite markers were tested on chromosome 6 using a larger pedigree. Fine mapping was performed using a breakpoint panel of 36 animals and novel microsatellite markers taken from the bovine genome assembly. All exons of the candidate gene nudix (nucleoside diphosphate linked moiety X)-type motif 9 (NUDT9) were sequenced in normal and affected sheep.
Significant linkage was found between cataract status and markers on chromosome 6. Linkage analysis on the larger pedigree showed the most likely position of the cataract locus was between 112.3 and 132.9 cM from the centromere. During fine mapping, NUDT9 was considered as a positional candidate for the cataract gene because it was located within the linked interval and is expressed in the lens. The gene was ruled out as the cataract gene after extensive genotype analysis, but a single nucleotide polymorphism (SNP) inside it provided a useful restriction fragment length polymorphism (RFLP) marker for further fine mapping. Twelve new markers were found and used to map the cataract locus to between 131.1 and 131.8 cM from the centromere.
A region of ovine chromosome 6 strongly linked to cataract has been identified, and a genetic test for cataract based on a SNP within this region has been developed. The best candidate gene within this region is AF4/FMR2 family, member 1 (AFF1), the mouse equivalent of which is associated with an inherited cataract.
PMCID: PMC3370893  PMID: 22690116
14.  Prevalence of Cataract Type in Relation to Axial Length in Subjects with High Myopia and Emmetropia in an Indian Population 
American journal of ophthalmology  2007;145(1):176-181.
To compare the prevalence of different types and densities of age-related cataract in subjects with high myopia and emmetropia in the Indian urban clinic-based population.
Prospective observational clinic-based case-control study.
An observational case-control study of 800 healthy eyes was undertaken at Iladevi Cataract & IOL Research Center, Ahmedabad, India. Subjects with high myopia (axial length [AXL] ≥ 26.0 mm) (n = 400 eyes) and those with emmetropia (AXL 21.0–23.99 mm) were examined (n = 400 eyes). The type of cataract was categorized as: nuclear, cortical, and posterior subcapsular cataract (PSC). Nuclear density was measured based on the Emery and Little classification.
In all the age groups (40+ years old), nuclear cataract was more often encountered in subjects with high myopia (Odds ratio: 3.8, 95% CI 2.9 – 5.2, P <0.001); PSC and mixed cataracts were frequently encountered in subjects with emmetropia (P <0.001). Prevalence of nuclear cataract was higher in subjects with high myopia with increasing AXL when compared with other types of cataract (P <0.001). In all the age groups, the nuclear density was significantly higher than grade 3 in subjects with high myopia when compared to those with emmetropia (P < 0.001 in <70 years of age, P = 0.003 in >70 years of age).
Nuclear cataract was strongly associated with high axial myopia. The density of the cataract was higher in the high myopia group. No association was observed between PSC or cortical cataract and high axial myopia.
PMCID: PMC2199267  PMID: 17936714
15.  Lens retrodots and vacuoles and their associations with the prevalence and incidence of age-related cataract 
Eye  2011;26(4):568-575.
To assess the prevalence of retrodots and vacuoles and their associations with the prevalence and long-term incidence of age-related cataract in an older Australian cohort.
Of 3654 baseline participants of the Blue Mountains Eye Study aged 49+ years (1992–1994), 2335 and 1952 were re-examined after 5 and 10 years, respectively. Lens photographs were graded for cataract, retrodots, and vacuoles. Eye-specific data were used to assess the associations between retrodots or vacuoles at baseline and the prevalence and 10-year incidence of nuclear, cortical, and posterior subcapsular (PSC) cataract and cataract surgery.
At baseline, retrodots were present in 142 persons (4%) and vacuoles in 1333 persons (40%). Prevalence of both lens features increased with increasing age (Pfor trend <0.0001). After adjusting for age and gender, vacuoles were associated with prevalent PSC cataract at baseline (odds ratio (OR), 1.60, 95% confidence interval (CI), 1.25–2.05). After adjusting for age, gender, smoking, hypertension, diabetes, education, and use of inhaled/oral steroids, baseline retrodots were associated with an increased incidence of cataract surgery (OR 2.90, 95% CI 1.71–4.91), while 3+ vacuoles at baseline were associated with an increased risk of PSC cataract (OR 3.56, 95% CI 2.13–5.95) and cataract surgery (OR 1.84, 95% CI 1.22–2.77).
Lens retrodots and vacuoles were found to be positively associated with 10-year incidence of cataract surgery, and vacuoles associated with PSC cataract, a finding suggestive of shared risk factors or pathogenesis between these two lens features and the development of PSC cataract.
PMCID: PMC3325569  PMID: 22193877
cataract; cataract surgery; lens opacities
16.  The influence of cortical, nuclear, subcortical posterior, and mixed cataract on the results of microperimetry 
Eye  2011;25(10):1317-1321.
Microperimetry is a useful instrument for evaluating sensitivity threshold due to retinal pathologies. The aim of the study is to assess the impact of different forms of cataract on microperimetry results.
In a prospective design, patients were recruited for cataract surgery at the Department of Ophthalmology, Medical University of Vienna. Exclusion criteria were any other ophthalmic disease except cataract, that is, macular pathology. Using the Lens Opacities Classification System III classification, patients were classified into four groups: nuclear, cortical, subcapsular posterior, and mixed cataract. Then patients underwent microperimetry: results were analyzed for magnitude of retinal sensitivity loss and correlated to the forms and density of the cataract.
Mean density of cataract was LOCS 3.2–3.5 in the four groups. Differences were not statistically significant. The best-corrected visual acuity (BCVA) was LogMAR 0.5±0.13 in nuclear, LogMAR 0.49±0.21 in cortical, and LogMAR 0.58±0.12 in mixed cataract patients, and significantly worse in patients with subcapsular posterior cataract (LogMAR 0.64±0.12). Microperimetry shows a mean sensitivity of 11.4–12.6 dB without significant group differences. The BCVA is correlated with microperimetry in patients with nuclear and cortical cataract. Density of cataract is highly correlated with microperimetry results in all groups.
The present study shows a good correlation of microperimetry results with the BCVA of patients with nuclear and cortical cataract. In patients with subcapsular posterior cataract, microperimetry results were better than estimated by BCVA. Density of cataract is highly correlated with macular sensitivity. A reduction of 1 dB in microperimetry per 1 posterior capsule opacification score increase can be estimated for these patients.
PMCID: PMC3194310  PMID: 21738231
microperimetry; retinal sensitivity; cataract; density of cataract; PCO score; best corrected visual acuity
17.  Comparison of age-specific cataract prevalence in two population-based surveys 6 years apart 
BMC Ophthalmology  2006;6:17.
In this study, we aimed to compare age-specific cortical, nuclear and posterior subcapsular (PSC) cataract prevalence in two surveys 6 years apart.
The Blue Mountains Eye Study examined 3654 participants (82.4% of those eligible) in cross-section I (1992–4) and 3509 participants (75.1% of survivors and 85.2% of newly eligible) in cross-section II (1997–2000, 66.5% overlap with cross-section I). Cataract was assessed from lens photographs following the Wisconsin Cataract Grading System. Cortical cataract was defined if cortical opacity comprised ≥ 5% of lens area. Nuclear cataract was defined if nuclear opacity ≥ Wisconsin standard 4. PSC was defined if any present. Any cataract was defined to include persons who had previous cataract surgery. Weighted kappa for inter-grader reliability was 0.82, 0.55 and 0.82 for cortical, nuclear and PSC cataract, respectively. We assessed age-specific prevalence using an interval of 5 years, so that participants within each age group were independent between the two surveys.
Age and gender distributions were similar between the two populations. The age-specific prevalence of cortical (23.8% in 1st, 23.7% in 2nd) and PSC cataract (6.3%, 6.0%) was similar. The prevalence of nuclear cataract increased slightly from 18.7% to 23.9%. After age standardization, the similar prevalence of cortical (23.8%, 23.5%) and PSC cataract (6.3%, 5.9%), and the increased prevalence of nuclear cataract (18.7%, 24.2%) remained.
In two surveys of two population-based samples with similar age and gender distributions, we found a relatively stable cortical and PSC cataract prevalence over a 6-year period. The increased prevalence of nuclear cataract deserves further study.
PMCID: PMC1524813  PMID: 16623958
18.  Association of IFN-g+874(T/A) polymorphism with female patients of age-related cataracts 
Oman Journal of Ophthalmology  2012;5(1):32-36.
Exposure to UV light is the major risk factor in the development of age-related cataract (ARC). UV filters produced during tryptophan catabolism maintain the transparency of the lens and protect retina from photo damage. Indoleamine 2, 3-dioxygenase (IDO), the first rate-limiting enzyme in the tryptophan catabolism, is up regulated by interferon-gamma (IFN-g) which harbors single nucleotide polymorphisms (SNPs). The T allele of SNP at +874 position of the IFN-g is known to be associated with the up regulation of IDO than the allele A. Hence, we attempted to study the IFN-g+874(T/A) polymorphism for its association with ARCs.
Materials and Methods:
A total of 680 cataract cases [199 nuclear (NC), 175 cortical (CC), 174 posterior subcapsular (PSC), and 132 mixed types (MT)] and 210 healthy controls were genotyped for +874(T/A) polymorphism using amplification refractory mutation system-polymerase chain reaction on 2% agarose gel stained with ethidium bromide.
There was increased risk for CC and PSC when the patients happened to be females, with low body mass index and with early onset. Considering the IFN-g polymorphism, a high risk was observed for CC and PSC in female patients of AA genotype with significant protection for those with TT genotypes.
Present results indicate that +874(T/A) polymorphism may be considered as one of the biomarkers to distinguish between the CC and PSC types of cataracts for risk estimations. The study appears to be the first of its kind reporting an association of IFN-g+874(T/A) polymorphism with ARCs.
PMCID: PMC3339672  PMID: 22557874
Age-related cataracts; indoleamine 2; 3-dioxygenase; interferon-gamma; tryptophan metabolism
19.  Five year incidence of cataract surgery: the Blue Mountains Eye Study 
Aims: To assess the 5 year incidence of cataract surgery in an older population based prospective cohort.
Methods: 5 Year prospective follow up of the population based Blue Mountains Eye Study (BMES) performed in 1992. The follow up study examined 2335 survivors (75.1%) of the 3654 baseline participants. Baseline and 5 year slit lamp and retroillumination lens photographs were graded for presence of cortical, nuclear, or posterior subcapsular cataract using the Wisconsin cataract grading method and cataract surgery was documented from the history and the clinical examination.
Results: An overall cataract surgery rate of 5.7% in first or both eyes was documented. The incidence was 0.3% in people aged 49–54 years at baseline, 1.7% for ages 55–64 years, 7.9% for ages 65 to 74 years, and 17.4% in people aged 75 years or older. The rate of surgery in first or both eyes was 6.0% in women and 5.2% in men, age adjusted p = 0.66. Bilateral cataract surgery was performed during follow up on 2.7% of participants, while 43.1% of unilateral phakic cases had second eye surgery. Presence of any posterior subcapsular (PSC) cataract, either alone or in combination with other cataract types, was the most likely type of cataract at baseline to be associated with incident cataract surgery. Baseline age was the most important non-ocular variable predicting incident cataract surgery.
Conclusions: This study has documented age specific rates for 5 year incident cataract surgery in an older community. The finding of relatively similar incidence rates and ocular predictors of cataract surgery to those reported by the Beaver Dam Eye Study, Wisconsin, United States, is of interest, given previous documented similarities between these two populations.
PMCID: PMC1771515  PMID: 12543745
cataract; cataract surgery; Blue Mountains Eye Study
20.  Cataract progression in India 
AIMS—The study was undertaken to test the feasibility of using the LOCS III cataract grading scale in the field and to determine the rate of cataract progression over a 1 year period of time.
METHODS—For 150 subjects between the ages of 33 and 55 who attended the refraction clinic at Aravind Eye Hospital in Madurai, India, lens abnormalities were graded at the slit lamp using the LOCS III scale. One year later, 99 of the subjects were re-evaluated by the same methodology to assess the amount of lens change.
RESULTS—Interrater reliability was high. A change of 0.5 or more in lens colour, cortical, nuclear, or posterior subcapsular cataract was observed in at least one eye of 54% of the subjects.
CONCLUSION—The LOCS III grading scale is a feasible method for measuring lens changes in the field with the slit lamp. Cataract progression in India is rapid enough to permit intervention studies to be performed with relatively small numbers of subjects over a short period of time (that is, 600 subjects for 2 years).

PMCID: PMC1722012  PMID: 9486033
21.  Prevalence of Visually Significant Cataract and Factors Associated with Unmet Need for Cataract Surgery: Los Angeles Latino Eye Study 
Ophthalmology  2009;116(12):2327-2335.
To estimate in a United States (U.S.) Latino population the prevalence of visually significant cataract, and to report predisposing, enabling, need, and health behavior characteristics associated with the unmet need for cataract surgery (UNCS).
Population-based, cross-sectional study.
6142 Latinos 40 years and older from 6 census tracts in Los Angeles County, California.
Participants completed an in-home interview and a comprehensive eye examination which included assessment of lens opacification, using the slit lamp-based Lens Opacities Classification System II (LOCS II), and best-corrected visual acuity (BCVA). Visually significant cataract was defined by: any LOCS II grading ≥2, BCVA <20/40, cataract as the primary cause of vision impairment, and self-reported vision of fair or worse. Because cataract surgery is not needed in all persons, participants with a visually significant cataract or prior cataract surgery in at least one eye composed the at-risk cohort needing cataract surgery. UNCS was defined as any person in the at-risk cohort who had at least one eye with a visually significant cataract. Univariate and stepwise logistic regression analyses were used to identify predisposing, enabling, need, and health behavior characteristics associated with UNCS.
Main Outcome Measure
Prevalence of visually significant cataract, and odds ratios for factors associated with UNCS.
Of 6142 participants who completed the interview and clinical examination, 118 (1.92%) had visually significant cataract in at least one eye. Of the 344 participants who have needed cataract surgery, 118 (29.9%) had UNCS. Independent factors associated with UNCS included health behavior - having last eye exam ≥5 years ago compared to <1 year ago (odds ratio; 95% confidence interval [OR], 3.76; 1.71-8.25)- and enabling factors - being uninsured (OR, 2.79; 1.30- 5.19), income less than $20,000 (OR, 2.60; 1.40-5.56), and self-reported barriers to eye care (OR 2.41; 1.14-5.13).
Latinos in our study had a substantial unmet need for cataract surgery. As Latinos with specific health behavior and enabling characteristics were more likely to have UNCS, interventions aimed at modifying these characteristics may be beneficial in reducing the unmet need and thus reducing the burden of visual impairment related to cataract in the U.S.
PMCID: PMC2787839  PMID: 19815276
22.  Cataract, Visual Impairment and Long-Term Mortality in a Rural Cohort in India: The Andhra Pradesh Eye Disease Study 
PLoS ONE  2013;8(10):e78002.
A large-scale prevalence survey of blindness and visual impairment (The Andhra Pradesh Eye Diseases Study [APEDS1]) was conducted between 1996-2000 on 10,293 individuals of all ages in three rural and one urban clusters in Andhra Pradesh, Southern India. More than a decade later (June 2009-March 2010), APEDS1 participants in rural clusters were traced (termed APEDS2) to determine ocular risk factors for mortality in this longitudinal cohort.
Methods and Findings
Mortality hazard ratio (HR) analysis was performed for those aged >30 years at APEDS1, using Cox proportional hazard regression models to identify associations between ocular exposures and risk of mortality. Blindness and visual impairment (VI) were defined using Indian definitions. 799/4,188 (19.1%) participants had died and 308 (7.3%) had migrated. Mortality was higher in males than females (p<0.001). In multivariable analysis, after adjusting for age, gender, diabetes, hypertension, body mass index, smoking and education status the mortality HR was 1.9 (95% CI: 1.5-2.5) for blindness; 1.4 (95% CI: 1.2-1.7) for VI; 1.8 (95% CI: 1.4-2.3) for pure nuclear cataract, 1.5 (95% CI: 1.1-2.1) for pure cortical cataract; 1.96 (95% CI: 1.6-2.4) for mixed cataract, 2.0 (95% CI: 1.4-2.9) for history of cataract surgery, and 1.58 (95% CI: 1.3-1.9) for any cataract. When all these factors were included in the model, the HRs were attenuated, being 1.5 (95% CI: 1.1-2.0) for blindness and 1.2 (95% CI: 0.9-1.5) for VI. For lens type, the HRs were as follows: pure nuclear cataract, 1.6 (95% CI: 1.3-2.1); pure cortical cataract, 1.5 (95% CI: 1.1-2.1); mixed cataract, 1.8 (95% CI: 1.4-2.2), and history of previous cataract surgery, 1.8 (95% CI: 1.3-2.6).
All types of cataract, history of cataract surgery and VI had an increased risk of mortality that further suggests that these could be potential markers of ageing.
PMCID: PMC3837009  PMID: 24282482
23.  Polymorphisms in two DNA repair genes (XPD and XRCC1) – association with age related cataracts 
Molecular Vision  2011;17:127-133.
Age related cataract is the leading cause of blindness in the world today. The association between DNA damage to the lens epithelium and the development of lens opacities has been reported in many studies. Polymorphisms of DNA repair enzymes may affect repair efficiency and thereby lead to the development of age related cataract.
In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, xeroderma pigmentosum complementation group (XPD) codon 312 and X-ray complementing group1 (XRCC1) codon 399, in a sample of 208 cataract patients (69 with cortical, 69 with nuclear and 70 with posterior sub capsular) and 151 sex and age matched healthy controls. XPD genotype was determined by Amplification Refractory Mutation System (ARMS) while XRCC1 was genotyped using the PCR-RFLP method.
There was a significant difference between frequencies for XPD-312 Asn/Asn genotype in cataract patients (21.6%) and healthy controls (13.2%; p=0.03, OR=1.97, 95% CI=1.06–3.63). Considering the types of cataract, XPD-312 Asn/Asn genotype was found to be significantly different in patients with cortical (29%) type in comparison to controls (13.2%; p=0.03, OR=2.39, 95% CI=1.11–5.12). No statistically significant difference was found for the genotypic and allelic distributions of the polymorphism in XRCC1. The MDR interaction analysis revealed weak synergism between the markers XPD-Asp312Asn and XRCC1-Arg399Gln contributing to cataract. It also showed that the AA genotype of XPD-Asp312Asn polymorphism when present in combination with the GA genotype of XRCC1-Arg399Gln had a fivefold and with AA had a fourfold risk for developing cataract.
The present study suggests that a polymorphism in XPD codon 312 may be associated with the development of maturity onset cataract. This is the first report on the association of XPD Asp312Asn polymorphism with maturity onset cataract.
PMCID: PMC3021570  PMID: 21245954
24.  Age-Related Cataract, Cataract Surgery and Subsequent Mortality: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(11):e112054.
Changes in lens may reflect the status of systemic health of human beings but the supporting evidences are not well summarized yet. We aimed to determine the relationship of age-related cataract, cataract surgery and long-term mortality by pooling the results of published population-based studies.
We searched PubMed and Embase from their inception till March, 2014 for population-based studies reporting the associations of any subtypes of age-related cataract, cataract surgery with all-cause mortality. We pooled the effect estimates (hazards ratios [HRs]) under a random effects model.
Totally, we identified 10 unique population-based studies including 39,659 individuals at baseline reporting the associations of any subtypes of cataract with all-cause mortality from 6 countries. The presence of any cataract including cataract surgery was significantly associated with a higher risk of death (pooled HR: 1.43, 95% CI, 1.21, 2.02; P<0.001; I2 = 64.2%). In the meta-analysis of 9 study findings, adults with nuclear cataract were at higher risks of mortality (pooled HR: 1.55, 95% CI, 1.17, 2.05; P = 0.002; I2 = 89.2%). In the meta-analysis of 8 study findings, cortical cataract was associated with higher risks of mortality (pooled HR: 1.26, 95% CI, 1.12, 1.42; P<0.001, I2 = 29.7%). In the meta-analysis of 6 study findings, PSC cataract was associated with higher risks of mortality (pooled HR: 1.37, 95% CI, 1.04, 1.80; P = 0.03; I2 = 67.3%). The association between cataract surgery and mortality was marginally non-significant by pooling 8 study findings (pooled HR: 1.27, 95% CI, 0.97, 1.66; P = 0.08; I2 = 76.6%).
All subtypes of age-related cataract were associated with an increased mortality with nuclear cataract having the strongest association among the 3 cataract subtypes. However, cataract surgery was not significantly related to mortality. These findings indicated that changes in lens may serve as markers for ageing and systemic health in general population.
PMCID: PMC4219834  PMID: 25369040
25.  Infant aphakia treatment study: Evaluation of cataract morphology in eyes with monocular cataracts 
Journal of Aapos  2011;15(5):421-426.
To describe a video-documented assessment of cataract type in eyes with monocular infantile cataract enrolled in the infant aphakia treatment study (IATS).
IATS is a randomized clinical trial comparing intraocular lens versus contact lens correction in 114 infants, aged 28 days to <7 months. A total of 83 videos were available for morphological analysis of cataract. Three examiners reviewed all surgical recordings and agreed on the cataract characteristics using a score sheet to record the lens layer or configuration of the opacity.
Nuclear cataract was present in 45 of 83 eyes (54%). Posterior capsule plaque was seen in 73 eyes (88%). All eyes with fetal nuclear cataract had associated posterior capsule plaque. Cortical cataract without nuclear involvement was seen in 21 eyes (25%). Posterior bowing of the posterior capsule was noted in 4 eyes (5%). Evidence of persistent fetal vasculature (PFV) was present in 18 eyes (22%). PFV was the only finding in 5 eyes but was also seen in combination with nuclear (7 eyes) and cortical cataracts (6 eyes). The entire lens was white in 3 eyes (4%), while the lens was partially resorbed in 7 (8%) eyes. Anterior capsule fibrosis was noted in 5 eyes with advanced cataract (1 with total cataract, 4 with partially resorbed lens).
Nuclear opacities were common, but many different cataract types presented in infancy. PFV occurred in isolation or in association with cataract. Posterior capsule plaque was frequently noted, especially when a nuclear cataract was present.
PMCID: PMC3345197  PMID: 22108352

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