Inherited retinal disorders: a genotype-phenotype correlation in an Indian cohort and the importance of genetic testing and genetic counselling.

PURPOSE: Recent advances in sequencing technologies have enabled radical and rapid progress in the genetic diagnosis of inherited retinal disorders (IRDs). Although the list of gene variations continues to grow, it lacks the genetic etiology of ethnic groups like South Asians. Differences in racial backgrounds and consanguinity add to genetic heterogeneity and phenotypic overlaps. METHODS: This retrospective study includes documented data from the Gen-Eye clinic from years 2014 to 2019. Medical records and pedigrees of 591 IRD patients of Indian origin and genetic reports of 117 probands were reviewed. Genotype-phenotype correlations were performed to classify as correlating, non-correlating and unsolved cases. RESULTS: Among the 591 patients, we observed a higher prevalence of clinically diagnosed retinitis pigmentosa (38.9%) followed by unspecified diagnoses (28.5%). Consanguinity was reported to be high (55.6%) in this cohort. Among the variants identified in 117 probands, 36.4% of variants were pathogenic, 19.2% were likely pathogenic, and 44.4% were of uncertain significance. Among the pathogenic and likely pathogenic variants, autosomal recessive inheritance showed higher prevalence. About 35% (41/117) of cases showed genotype-phenotype correlation. Within the correlating cases, retinitis pigmentosa and Stargardt disease were predominant. Novel variants identified in RP, Stargardt, and LCA are reported here. CONCLUSION: This first-of-a-kind report on an Indian cohort contributes to existing knowledge and expansion of variant databases, presenting relevant and plausible novel variants. Phenotypic overlap and variability lead to a differential diagnosis and hence a clear genotype-phenotype correlation helps in precise clinical confirmation. The study also emphasizes the importance of genetic counselling and testing for personalized vision care in a tertiary eye hospital.

Ex vivo model for studying endothelial tip cells: Revisiting the classical aortic-ring assay.

A drug undergoes several in silico, in vitro, ex vivo and in vivo assays before entering into the clinical trials. In 2014, it was reported that only 32% of drugs are likely to make it to Phase-3 trials, and overall, only one in 10 drugs makes it to the market. Therefore, enhancing the precision of pre-clinical trial models could reduce the number of failed clinical trials and eventually time and financial burden in health sciences. In order to attempt the above, in the present study, we have shown that aortic ex-plants isolated from different stages of chick embryo and different regions of the aorta (pulmonary and systemic) have differential sprouting potential and response to angiogenesis modulatory drugs. Aorta isolated from HH37 staged chick embryo showed 16% (p < 0.001) and 11% (p < 0.001) increase in the number of tip cells at 72 h of culture compared to that of HH35 and HH29 respectively. The ascending order of the number of tip cells was found as central (Gen II), proximal (Gen I) and distal (Gen III) in a virtual zonal segmentation of endothelial sprouting. The HH37 staged aortas displayed differential responses to pro- and anti-angiogenic drugs like Vascular endothelial growth factor (VEGF), nitric oxide donor (spNO), and bevacizumab (avastin), thalidomide respectively. The human placenta tissue-culture however evinced endothelial sprouting only on day 12, with a gradual decrease in the number of tip cells until 21 days. In summary, this study provides an avant-garde angiogenic model emphasized on tip cells that would enhance the precision to test next-generation angiogenic drugs.

Ophthatome™: an integrated knowledgebase of ophthalmic diseases for translating vision research into the clinic.

BACKGROUND: Medical big data analytics has revolutionized the human healthcare system by introducing processes that facilitate rationale clinical decision making, predictive or prognostic modelling of the disease progression and management, disease surveillance, overall impact on public health and research. Although, the electronic medical records (EMR) system is the digital storehouse of rich medical data of a large patient cohort collected over many years, the data lack sufficient structure to be of clinical value for applying deep learning methods and advanced analytics to improve disease management at an individual patient level or for the discipline in general. Ophthatome™ captures data contained in retrospective electronic medical records between September 2012 and January 2018 to facilitate translational vision research through a knowledgebase of ophthalmic diseases. METHODS: The electronic medical records data from Narayana Nethralaya ophthalmic hospital recorded in the MS-SQL database was mapped and programmatically transferred to MySQL. The captured data was manually curated to preserve data integrity and accuracy. The data was stored in MySQL database management system for ease of visualization, advanced search functions and other knowledgebase applications. RESULTS: Ophthatome™ is a comprehensive and accurate knowledgebase of ophthalmic diseases containing curated clinical, treatment and imaging data of 581,466 ophthalmic subjects from the Indian population, recorded between September 2012 and January 2018. Ophthatome™ provides filters and Boolean searches with operators and modifiers that allow selection of specific cohorts covering 524 distinct ophthalmic disease types and 1800 disease sub-types across 35 different anatomical regions of the eye. The availability of longitudinal data for about 300,000 subjects provides additional opportunity to perform clinical research on disease progression and management including drug responses and management outcomes. The knowledgebase captures ophthalmic diseases in a genetically diverse population providing opportunity to study genetic and environmental factors contributing to or influencing ophthalmic diseases. CONCLUSION: Ophthatome™ will accelerate clinical, genomic, pharmacogenomic and advanced translational research in ophthalmology and vision sciences.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Recessive mutations in SLC38A8 cause foveal hypoplasia and optic nerve misrouting without albinism.

Foveal hypoplasia and optic nerve misrouting are developmental defects of the visual pathway and only co-occur in connection with albinism; to date, they have only been associated with defects in the melanin-biosynthesis pathway. Here, we report that these defects can occur independently of albinism in people with recessive mutations in the putative glutamine transporter gene SLC38A8. Nine different mutations were identified in seven Asian and European families. Using morpholino-mediated ablation of Slc38a8 in medaka fish, we confirmed that pigmentation is unaffected by loss of SLC38A8. Furthermore, by undertaking an association study with SNPs at the SLC38A8 locus, we showed that common variants within this gene modestly affect foveal thickness in the general population. This study reveals a melanin-independent component underpinning the development of the visual pathway that requires a functional role for SLC38A8.

Two novel missense substitutions in the VSX1 gene: clinical and genetic analysis of families with Keratoconus from India.

BACKGROUND: Visual system homeobox gene (VSX1) plays a major role in the early development of craniofacial and ocular tissues including cone opsin gene in the human retina. To date, few disease-causing mutations of VSX1 have been linked to familial and sporadic keratoconus (KC) in humans. In this study, we describe the clinical features and screening for VSX1 gene in families with KC from India. METHODS: Clinical data and genomic DNA were collected from patients with clinically diagnosed KC and their family members. The study was conducted on 20 subjects of eight families from India. The coding exons of VSX1 gene were amplified using PCR and amplicons were analyzed by direct sequencing. Predictive effect of the mutations was performed using Polyphen-2, SIFT and mutation assessor algorithms. Additionally, haplotypes of VSX1 gene were constructed for affected and unaffected individuals using SNPs. RESULTS: In the coding region of VSX1, one novel missense heterozygous change (p.Leu268His) was identified in five KC patients from two unrelated families. Another family of three members had a novel heterozygous change (p.Ser251Thr). These variants co-segregated with the disease phenotype in all affected individuals but not in the unaffected family members and 105 normal controls. In silico analysis suggested that p.Leu268His could have a deleterious effect on the protein coded by VSX1, while p.Ser251Thr has a neutral effect on the functional properties of VSX1. Haplotype examination revealed common SNPs around the missense change (p.Leu268His) in two unrelated KC families. CONCLUSIONS: In this study, we add p.Leu268His, a novel missense variation in the coding region of VSX1 to the existing repertoire of VSX1 coding variations observed in Indian patients with the characteristic phenotype of KC. The variant p.Ser251Thr might be a benign polymorphism, but further biophysical studies are necessary to evaluate its molecular mechanism. The shared haplotype by two families with the same variant suggests the possibility of a founder effect, which requires further elucidation. We suggest that p.Leu268His might be involved in the pathogenesis of KC, which may help in the genetic counselling of patients and their family.

Association of Genetic Variants with Polypoidal Choroidal Vasculopathy: A Systematic Review and Updated Meta-analysis.

TOPIC: A systematic review and meta-analysis of the genetic association with polypoidal choroidal vasculopathy (PCV) and the genetic difference between PCV and neovascular age-related macular degeneration (nAMD). CLINICAL RELEVANCE: To identify genetic biomarkers that are potentially useful for genetic diagnosis of PCV and for differentiating PCV from nAMD. METHODS: We performed a literature search in EMBASE, PubMed, Web of Science, and the Chinese Biomedical Database for PCV genetic studies published before February 6, 2015. We then conducted a meta-analysis of all polymorphisms that had sufficient genotype/allele data reported in ≥2 studies and estimated the summary odds ratio (OR) and 95% confidence intervals (CIs) for PCV. We also compared the association profiles between PCV and nAMD, and performed a sensitivity analysis. RESULTS: A total of 66 studies were included in the meta-analysis, involving 56 polymorphisms in 19 genes/loci. In total, 31 polymorphisms in 10 genes/loci (age-related maculopathy susceptibility 2 [ARMS2], high-temperature requirement factor A1 [HTRA1], complement factor H [CFH], complement component 2 [C2], CFB, RDBP, SKIV2L, CETP, 8p21, and 4q12) were significantly associated with PCV. Another 25 polymorphisms in 13 genes (ARMS2, HTRA1, C2, CFB, ELN, LIPC, LPL, ABCA1, VEGF-A, TLR3, LOXL1, SERPING1, and PEDF) had no significant association. Twelve polymorphisms at the ARMS2-HTRA1 locus showed significant differences between PCV and nAMD. The sensitivity analysis validated the significance of our analysis. CONCLUSIONS: This study revealed 31 polymorphisms in 10 genes/loci that contribute to PCV susceptibility. Among them, ARMS2-HTRA1 also showed allelic diversity between PCV and nAMD. Our results confirm the gene variants that could affect the phenotypic expressions of PCV and nAMD.

Biosynthetic and functional defects in newly identified SLC4A11 mutants and absence of COL8A2 mutations in Fuchs endothelial corneal dystrophy.

Late-onset Fuchs endothelial corneal dystrophy (FECD) shows genetic heterogeneity. Identification of SLC4A11 as a candidate gene for congenital hereditary endothelial dystrophy with similar corneal endothelial defects as FECD and reduced mRNA expression of SLC4A11 in the endothelium of FECD cases suggested that this gene may also be involved in pathogenesis of FECD. Mutations in SLC4A11 give rise to SLC4A11 protein marked by retention in the endoplasmic reticulum as a result of mis-folding. We screened 45 sporadic late-onset, 4 early-onset FECD patients and an early-onset autosomal dominant FECD family. We identified three previously unreported missense mutations: c.719G>C (p.W240S), c.1519G>A (p.V507I) and c.1304C>T (p.T434I) in unrelated individuals. These SLC4A11 mutants, expressed in HEK293 cells, had defects in either their cell surface expression or functional activity (rate of osmotically driven water flux). SLC4A11 mutations contribute to 11% (5/45) of sporadic late-onset FECD in the cohort studied. COL8A2, which causes some cases of early-onset FECD, was also screened in this cohort. No mutations were identified in COL8A2, in neither the late-onset cohort nor the early-onset family, suggesting genetic heterogeneity in this FECD family.

Nonsense mutations in FAM161A cause RP28-associated recessive retinitis pigmentosa.

Retinitis pigmentosa (RP) is a degenerative disease of the retina leading to progressive loss of vision and, in many instances, to legal blindness at the end stage. The RP28 locus was assigned in 1999 to the short arm of chromosome 2 by homozygosity mapping in a large Indian family segregating autosomal-recessive RP (arRP). Following a combined approach of chromatin immunoprecipitation and parallel sequencing of genomic DNA, we identified a gene, FAM161A, which was shown to carry a homozygous nonsense mutation (p.Arg229X) in patients from the original RP28 pedigree. Another homozygous FAM161A stop mutation (p.Arg437X) was detected in three subjects from a cohort of 118 apparently unrelated German RP patients. Age at disease onset in these patients was in the second to third decade, with severe visual handicap in the fifth decade and legal blindness in the sixth to seventh decades. FAM161A is a phylogenetically conserved gene, expressed in the retina at relatively high levels and encoding a putative 76 kDa protein of unknown function. In the mouse retina, Fam161a mRNA is developmentally regulated and controlled by the transcription factor Crx, as demonstrated by chromatin immunoprecipitation and organotypic reporter assays on explanted retinas. Fam161a protein localizes to photoreceptor cells during development, and in adult animals it is present in the inner segment as well as the outer plexiform layer of the retina, the synaptic interface between photoreceptors and their efferent neurons. Taken together, our data indicate that null mutations in FAM161A are responsible for the RP28-associated arRP.

Ophthalmic genetic counselling: emerging trends in practice perspectives in Asia.

Genetic counselling (GC) provides information to the patient and the family to make informed choices. Among the advanced Western countries and a few Asian countries, there are certified or trained professionals who perform GC. The Human Genome Project and next-generation sequencing diagnostics have provided an opportunity for increased genetic testing in the field of ophthalmology. The recent interventional therapeutic research strategies have also generated additional interest to seek GC globally, including in Asia. However, GC has several barriers to practise in the developing countries in Asia, namely, (a) shortage of qualified or trained genetic counsellors, (b) poor knowledge and reluctance in clinical adoption of genomics among the physicians in clinical practice, (c) overstretched public health services, and (d) negligible ophthalmic GC-related research and publications. The GC inadequacy in Asia is glaring in the most populous countries like China and India. Cultural differences, religious beliefs, misogyny, genetic discrimination, and a multitude of languages in Asia create unique challenges that counsellors in the West may only encounter with the immigrant minorities. Since there are currently 500 or more specific Mendelian genetic eye disorders, it is important for genetic counsellors to translate the genetic results at a level that the patient and family understand. There is therefore a need for governmental and healthcare organisations to train genetic counsellors in Asia and especially this practice must be included in the routine comprehensive ophthalmic care practice.

Correlation between tear levels of vascular endothelial growth factor and vitamin D at retinopathy of prematurity stages in preterm infants.

Deregulation of vascular endothelial growth factor (VEGF) levels leads to retinopathy of prematurity (ROP). Vitamin D (VIT-D) is known to regulate VEGF in an oxygen dependent manner. The purpose of this study was to correlate tear levels of VEGF and VIT-D with different ROP stages in preterm infants. In this prospective cross-sectional study, we enrolled 104 pre-term infants. They were grouped into: Group-1 (Classical ROP) and Group-2 (Aggressive ROP), which were further subdivided into Group-1A (progressing), Group-1B (regressing), Group-2A (pre-treatment), and Group-2B (post-treatment). Tear VEGF and VIT-D levels and their association with different ROP stages were assessed. Stage 1 and stage 2 had higher whereas stage 3 had lower VEGF levels in Group-1B compared to Group-1A. Stage 1 and stage 3 showed higher levels of VIT-D with no difference in stage 2 in Group-1B compared to Group-1A., Group-2B showed higher VEGF and lower VIT-D levels compared to Group-2A. Presence of a positive correlation at an early stage (stage 1) of ROP and a negative correlation at a more advanced stage (stage 3) of ROP with VIT-D and VEGF implies stage-specific distinct signaling crosstalk. These findings suggest that VIT-D supplementation may have the potential to modify the course and outcome of ROP.

Current concepts and molecular mechanisms in pharmacogenetics of essential hypertension.

Hypertension is a leading age-related disease in our society and if left untreated, leads to fatal cardiovascular complications. The prevalence of hypertension has increased and becomes a significant global health economic burden, particularly in lower-income societies. Many loci associated with blood pressure and hypertension have been reported by genome-wide association studies that provided potential targets for pharmacotherapy. Pharmacogenetic research had shown interindividual variations in drug efficacy, safety, and tolerability. This could be due to genetic polymorphisms in the pharmacokinetics (genes involved in a transporter, plasma protein binding, and metabolism) or pharmacodynamic pathway (receptors, ion channels, enzymes). Pharmacogenetics promises great hope toward targeted therapy, but challenges remain in implementing pharmacogenetic aided antihypertensive therapy in clinical practice. Using various databases, we analyzed the underlying mechanisms between the candidate gene polymorphisms and antihypertensive drug interactions and the challenges of implementing precision medicine. We review the emergence of pharmacogenetics and its relevance to clinical pharmacological practice.

Impact of Literacy on Hypertension Knowledge and Control of Blood Pressure in a Southern Indian Tertiary Hospital.

BACKGROUND: Hypertension is a global public health concern. Awareness and knowledge about the disease in a community collectively would allow adequate prevention, promote self-care practices, adherence to medication and ultimately effective management of hypertension. AIMS: To ascertain the level of education associated with the knowledge of hypertension and control of blood pressure. METHODS: A cross-sectional questionnaire survey consisting of item questions about awareness and knowledge of hypertension. Hypertensive patients (n = 424) of both genders and more than 20 years of age were included in the study. Hypertensive patients were divided into two groups (school group and school pass-out group) to assess the level of knowledge. Chi-square test was performed to determine the assessment, and p-value < 0.05 was considered significant. RESULTS: Out of 424 participants, 71.2% were school group and 28.7% school pass-out group. School pass-out group had significant knowledge about dangerous natural course of hypertension (p = 0.00069), hypertension can lead to death if untreated (p = 0.015), benefits of cessation of smoking (p = 0.03), advantage of limiting alcohol (p = 0.019) and performing regular exercise (p = 0.013) reduces blood pressure. School pass-out group had significant (p = 0.04) hypertension control compared to the school group. CONCLUSION: Educational status plays a vital role in increasing knowledge and improving the management of hypertension through better self-care practices and strict adherence to medication. Community- based health education interventional programs targeting the lower socioeconomic group of a population would help to reduce the gap in awareness and effective control of hypertension.

Retinoblastoma genetics screening and clinical management.

BACKGROUND: India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored. METHODS: Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence. RESULTS: Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy. CONCLUSIONS: We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.

Prevalence of refractive errors and associated risk factors in subjects with type 2 diabetes mellitus SN-DREAMS, report 18.

PURPOSE: To report the prevalence of refractive errors and the associated risk factors in subjects with type 2 diabetes mellitus from an urban Indian population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: One thousand eighty participants selected from a pool of 1414 subjects with diabetes. METHODS: A population-based sample of 1414 persons (age >40 years) with diabetes (identified as per the World Health Organization criteria) underwent a comprehensive eye examination, including objective and subjective refractions. MAIN OUTCOME MEASURES: One thousand eighty subjects who were phakic in the right eye with best corrected visual acuity of > or =20/40 were included in the analysis for prevalence of refractive errors. Univariate and multivariate analyses were done to find out the independent risk factors associated with the refractive errors. RESULTS: The mean refraction was +0.20+/-1.72, and the Median, +0.25 diopters. The prevalence of emmetropia (spherical equivalent [SE], -0.50 to +0.50 diopter sphere [DS]) was 39.26%. The prevalence of myopia (SE <-0.50 DS), high myopia (SE <-5.00 DS), hyperopia (SE >+0.50 DS), and astigmatism (SE <-0.50 cyl) was 19.4%, 1.6%, 39.7%, and 47.4%, respectively. The advancing age was an important risk factor for the three refractive errors: for myopia, odds ratio (OR; 95% confidence interval [CI] 4.06 [1.74-9.50]; for hyperopia, OR [95% CI] 5.85 [2.56-13.39]; and for astigmatism, OR [95% CI] 2.51 [1.34-4.71]). Poor glycemic control was associated with myopia (OR [95% CI] 4.15 [1.44-11.92]) and astigmatism (OR [95% CI] 2.01 [1.04-3.88]). Female gender was associated with hyperopia alone) OR [95% CI] 2.00 [1.42-2.82]. CONCLUSIONS: The present population-based study from urban India noted a high prevalence of refractive errors (60%) among diabetic subjects >40 years old; the prevalence of astigmatism (47%) was higher than hyperopia (40%) or myopia (20%).

Influence of serum lipids on clinically significant versus nonclinically significant macular edema: SN-DREAMS Report number 13.

PURPOSE: To estimate the prevalence of diabetic macular edema, both clinically significant macular edema (CSME) and nonclinically significant macular edema (non-CSME), and report the associations of dyslipidemia on them. DESIGN: A population-based cross-sectional study in India. PARTICIPANTS: After all exclusions, 1414 subjects with diabetes underwent an examination. METHODS: The CSME was defined according to the Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines; stereo digital fundus pairs were studied. The dyslipidemia cases were classified according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). MAIN OUTCOME MEASURES: Prevalence of CSME and non-CSME and association of serum lipids with them. RESULTS: The prevalence was 31.76% (95% confidence interval [CI], 26.04-37.47) for overall diabetic macular edema, 25.49% (95% Ci, 20.14-30.84) for non-CSME, and 6.27% (95% Ci, 3.29-9.24) for CSME. Univariate analysis identified macroalbuminuria and microalbuminuria, poor glycemic control, high total serum cholesterol, high serum low-density lipoprotein (LDL) cholesterol, and high serum non-high-density lipoprotein (HDL) cholesterol related to non-CSME and CSME (trend chi-square test, P<0.05). Logistic regression analysis (after adjusting variables such as age, gender, body mass index, duration, smoking, hypertension, glycosylated hemoglobin, macroalbuminuria and microalbuminuria, and insulin use) revealed high serum LDL cholesterol (odds ratio [OR], 2.72], high serum non-HDL cholesterol (OR, 1.99), and high cholesterol ratio (OR, 3.08) related to non-CSME, and poor glycemic control (OR, 8.06), microalbuminuria (OR, 14.23), and high serum total cholesterol (OR, 9.09) related to CSME. CONCLUSIONS: One third of the subjects had diabetic macular edema, and 6% of them showed evidence of CSME necessitating laser photocoagulation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Anemia and diabetic retinopathy in type 2 diabetes mellitus.

OBJECTIVES: To estimate the prevalence of anemia in persons with type 2 diabetes mellitus and its role as a risk factor for the presence and the severity of diabetic retinopathy, in a population based study. METHODS: In all 5999 subjects from the general population aged > or =40 years were enumerated for the study. A total of 1414 persons identified with diabetes underwent comprehensive eye examination, and stereoscopic digital fundus photography was used for diabetic retinopathy grading. All patients underwent hemoglobin estimation for detection of anemia. Univariate and multivariate analyses were done to determine the independent risk factors for anemia. RESULTS: The prevalence of anemia (Hb <12 g/dl in women and <13 g/dl in men) was 12.3%. Between 40 and 49 years of age, prevalence of anemia was higher in women than in men (26.4 % vs 10.3%). Men with anemia, and not women, had 2 times the risk of developing diabetic retinopathy. Multivariate analysis revealed independent predictors for anemia: age group more than 69 years OR 2.49 (95% CI 1.44-4.30), duration of diabetes of more than 5 years OR 1.56 (1.09-2.69) and the presence of diabetic retinopathy OR 1.82 (95% CI 1.22-2.69). CONCLUSION: Every tenth individual in a population of diabetes mellitus could be anemic. Identifying and treating anemia would make a great impact in managing microvascular complications such as diabetic retinopathy.

KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association.

PURPOSE: We quantified mRNA expression of candidate genes for proliferation (KIF14 and E2F3) in a large retinoblastoma tumor cohort and associated with disease phenotype. METHODS: KIF14 and E2F3 mRNA expression was quantified by real time PCR in 57 retinoblastoma (RB) tumors, 3 RB cell lines, and control samples that included 4 each fetal, age-matched, adult retinas. Immunohistochemistry was done to confirm KIF14 and E2F3 protein expression in tumor cells. The mRNA expression levels were correlated with disease phenotypes including the significance of chemotherapy on tumors. RESULTS: There was statistically significant overexpression of KIF14 and E2F3 mRNA in tumors compared with control retinas (p<0.0001). Further, E2F3 also showed a significant overexpression compared to RB cell lines (p=0.01). Immunohistochemistry confirmed KIF14 and E2F3 protein overexpression in tumor cells. KIF14 had significant mRNA overexpression with older age (p=0.01) in presenting patients and in unilateral RB patients (p=0.04). Chemotherapy-treated tumors showed a significant decrease in KIF14 and E2F3 expression compared to untreated tumors (p<0.01 and 0.001, respectively). CONCLUSIONS: This report confirms significant mRNA overexpression of KIF14 and E2F3 together in a large cohort of RB tumors. The decreased expression in chemotherapy treated cases needs further validation in a large chemotherapy-treated cohort.

Prevalence of diabetic retinopathy in India: Sankara Nethralaya Diabetic Retinopathy Epidemiology and Molecular Genetics Study report 2.

OBJECTIVE: The aim of the study was to estimate the prevalence of diabetic retinopathy in an urban Indian population older than 40 years. DESIGN: A population-based cross-sectional study. PARTICIPANTS: Five thousand nine hundred ninety-nine subjects residing in Chennai, India, were enumerated. METHODS: A multistage random sampling, based on socioeconomic criteria, was followed. Identified subjects with diabetes mellitus (based on the World Health Organization criteria) underwent detailed examination at the base hospital. The fundi of all patients were photographed using 45 degrees , 4-field stereoscopic digital photography. The diagnosis of diabetic retinopathy was based on Klein's classification of the Early Treatment Diabetic Retinopathy Study scale. MAIN OUTCOME MEASURES: These included age- and gender-adjusted prevalence of diabetes and diabetic retinopathy, and correlation of prevalence with history-based risk factors. RESULTS: The age- and gender-adjusted prevalence rate of diabetes in an urban Chennai population was 28.2% (95% confidence interval [CI], 27.0-29.3), and the prevalence of diabetic retinopathy in general population was 3.5% (95% CI, 3.49-3.54). The prevalence of diabetic retinopathy in the population with diabetes mellitus was 18.0% (95% CI, 16.0-20.1). History-based variables that were significantly associated with increased risk of diabetic retinopathy included gender (men at greater risk; odds ratio [OR], 1.41; 95% CI, 1.04-1.91); use of insulin (OR, 3.52; 95% CI, 2.05-6.02); longer duration of diabetes (>15 years; OR, 6.43; 95% CI, 3.18-12.90); and subjects with known diabetes mellitus (OR, 2.98; 95% CI, 1.72-5.17). Differences in the socioeconomic status did not influence the occurrence of diabetic retinopathy. CONCLUSIONS: The prevalence of diabetic retinopathy was 18% in an urban population with diabetes mellitus in India. The duration of diabetes is the strongest predictor for diabetic retinopathy. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Consanguinity and its association with visual impairment in southern India: the Pavagada Pediatric Eye Disease Study 2.

To determine the association of consanguinity with the occurrence of genetically transmitted eye diseases in rural and urban populations in Pavagada and Madhugiri taluks, Karnataka state, south India. This study was part of a population based cross-sectional prevalence survey, "The Pavagada pediatric eye disease study 2." As a part of the demographic data, trained investigators collected information on consanguinity from the parents of children identified for the study. The children underwent visual acuity measurements and were examined by an ophthalmologist. Children with minor eye diseases were treated and those with major eye diseases were seen by a pediatric ophthalmologist. Eight thousand five hundred and fifty-three children were examined. The prevalence of ocular morbidity was 6.54% and blindness was 0.09%. The percentage of consanguineously married couples in the screened population was 34.33%. Among the blind children, 75% were blind with a disease with potential genetic etiology. Out of that, 66.67% were born out of consanguineous marriage (uncle-niece). Among children with diseases with a potential genetic etiology 54.29% of the children were born out of consanguineous union. Most of these children (71.43%) were born out of uncle-niece marriages. Further analysis showed that consanguineous parents were more likely to have children with disease with a potential genetic etiology as compared to nonconsanguineous parents (odds ratio: 2.551, p = 0.012). It is evident that consanguineous marriages, especially uncle-niece unions are common in the study area. Consanguinity is more likely to result in children with eye diseases with potential genetic etiology.