Pradeep G. Paul

Ocular biometry in occludable angles and angle closure glaucoma: a population based survey

Aim: To compare ocular biometric values in a population based sample of eyes with occludable angles, angle closure glaucoma, and normal subjects. Method: 2850 subjects from a population based glaucoma prevalence study underwent complete ocular examination including indentation gonioscopy. Ocular biometry was performed in all subjects classified to have occludable angles (n = 143); angle closure glaucoma (n = 22), and a random subgroup of 419 normal subjects. Ocular biometry readings between the groups were compared and statistically analysed using “t,” “z,” and Mann-Whitney U tests. Results: The mean age among subjects with occludable angles (54.43 (SD 9.53) years) and angle closure glaucoma (57.45 (8.5) years) was significantly higher (p<0.001) than normal subjects (49.95 (9.95) years). Axial length was shorter (p<0.001) in the occludable angle group (22.07 (0.69) mm) compared to the normal group (22.76 (0.78) mm). Anterior chamber depth (ACD) was shallower (p<0.001) among subjects with occludable angles (2.53 (0.26) mm) than normal subjects (3.00 (0.30) mm). Lens thickness (LT) was greater (p<0.001) in people with occludable angles (4.40 (0.53) mm) compared to normal subjects (4.31 (0.31) mm). No significant difference was noted in axial length, ACD (p = 0.451), and LT (p = 0.302) between angle closure glaucoma and occludable eyes. Conclusion: South Indian eyes with angle closure glaucoma and occludable angles seem to have significantly shorter axial lengths, shallower anterior chambers and greater lens thickness compared to the normal group.

Pseudoexfoliation in south India

Aim: To study the profile of pseudoexfoliation in a population based study. Method: 2850 consecutive subjects aged 40 years or older from a population based survey in a rural area of southern India underwent complete ophthalmic evaluation including history, visual acuity testing, refraction, slit lamp examination, applanation tonometry, gonioscopy, and dilated examination of the lens (including LOCS II grading of cataract), fundus, and optic disc. Patients with pseudoexfoliation syndrome were identified and their data were analysed with respect to age, sex, intraocular pressure, gonioscopic grading, cataract, and optic neuropathy. Results: 108 subjects had pseudoexfoliation syndrome (3.8 %). There was a significant increase in prevalence with age but no sex predilection. The condition was unilateral in 53 cases (49.1%) and bilateral in 55 cases (50.9%). 18 cases with pseudoexfoliation (16.7%) had high intraocular pressure (>21 mm Hg), 16 cases (14.8%) had occludable angles, and 14 cases (13%) had pseudoexfoliation glaucoma. There was a significantly higher prevalence of cataract among people with pseudoexfoliation compared to those without pseudoexfoliation (p = 0.014). Conclusion: The prevalence of pseudoexfoliation syndrome in the rural population of south India was 3.8%. Raised intraocular pressure was seen in 16.7% of people with pseudoexfoliation and glaucoma was present in 13%.

Association of Gly82Ser polymorphism in the RAGE gene with diabetic retinopathy in type II diabetic Asian Indian patients

AIM/HYPOTHESIS The binding of advanced glycation end products (AGE) to the receptor induces cellular oxidative stress and vascular dysfunction and this is implicated in the pathogenesis of diabetic retinopathy (DR). This study aims to investigate the frequency of Gly82Ser polymorphism in exon 3 of the receptor for AGE (RAGE) gene and its association with DR in Asian Indian patients who have type II diabetes. METHODS 200 Asian Indian patients with at least 15-year duration of type II diabetes were identified. This group included (1) 100 patients with retinopathy (DR) and (2) 100 patients without retinopathy (DNR). Fifty unrelated healthy controls (CT) were also included in the study. Genotype frequencies of Gly82Ser polymorphism were studied by polymerase chain reaction (PCR) amplification and restriction fragment length polymorphism analysis using AluI enzyme. Later, the nucleotide change was confirmed by DNA sequencing. RESULTS The frequency of the Ser82 allele was significantly higher, 18% in the DNR group compared to 7% in the DR group (P=.03). The same genotype was 2% in the CT group. CONCLUSION/INTERPRETATION Our result suggests that Ser82 allele in the receptor for AGE gene is a low-risk allele for developing DR in Asian Indian patients who have type II diabetes.

Sankara Nethralaya—Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN—DREAMS 1): Study Design and Research Methodology

Purpose: To describe the methodology of the Sankara Nethralaya—Diabetic Retinopathy Epidemiology and Molecular Genetic Study (SN—DREAMS 1), an ongoing population-based study to estimate the prevalence of diabetes and diabetic retinopathy in urban Chennai, Tamil Nadu, South India, and also to elucidate the clinical, anthropometric, biochemical and genetic risk factors associated with diabetic retinopathy. Methods: In this ongoing study, we anticipate recruiting a total of 5830 participants. Eligible patients, over the age of 40 years, are enumerated using the multistage random sampling method. Demographic data, socioeconomic status, physical activity, risk of sleep apnea, dietary habits, and anthropometric measurements are collected. A detailed medical and ocular history and a comprehensive eye examination, including stereo fundus photographs, are taken at the base hospital. Biochemical investigations (total serum cholesterol, high-density lipoproteins, serum triglycerides, hemoglobin, glycosylated hemoglobin HbA1c) and genetic studies of eligible subjects are conducted. A computerized database is created for the records. Conclusion: The study is expected to result in an estimate of the prevalence of diabetes and diabetic retinopathy and a better understanding of biochemical and genetic risk factors associated with diabetic retinopathy in an urban South Indian population. Worldwide, the prevalence of diabetes mellitus, in particular type II diabetes, is rising at an alarming rate. The World Health Organization (WHO) and International Diabetes Federation (IDF) have predicted that the number of cases of adult-onset diabetes would more than double by 2030 from the present level of 171 million to 366 million—an increase of 214%.1 In developed countries, this increase in diabetic population would be around 42% and in developing countries, particularly in India, it is even higher; i.e. 150%.1 In India, the prevalence of diabetes mellitus in the urban population is around 12.1%, as reported by the national urban diabetes study2 conducted in six major cities. Studies have shown the prevalence of diabetes to be higher among the high-income groups (25.5%) as compared to low-income groups (12.6%).345 The assessment of socioeconomic status was based on income,67 education,27 occupation2 or caste6—which are not representative of the actual socioeconomic status. In the present study, however, the sample was stratified on socioeconomic scoring. This scoring was calculated on the basis of several parameters such as the residence being rented or owned, the number of rooms in the house, the highest educational status, the highest salary, the highest occupation, material possessions (cycle, TV, audio, car, etc.) and house/land value. To the best of our knowledge, this kind of comprehensive socioeconomic scoring has not been done before for prevalence studies on diabetic retinopathy in the general population.

Association of VEGF Gene Polymorphisms with Diabetic Retinopathy in a South Indian Cohort

Background: Polymorphisms in vascular endothelial growth factor (VEGF) gene have been associated with diabetic retinopathy (DR) in various populations. A promoter polymorphism and a 3′UTR variation are studied for association with DR. Materials and Methods: Type 2 diabetic patients with and without retinopathy were recruited. The −634C/G and 936C/T polymorphisms were genotyped by direct sequencing and their frequencies were analyzed using relevant statistical tests. Results: No significant association was observed between genotypes, alleles and haplotypes of −634C/G and 936C/T polymorphisms and DR or its severity. However, C(−634)G genotype was found to increase the risk for DR in patients with microalbuminuria (OR: 8.9, 95% CI: 1.4, 58.3). Conclusion: Our study broadly suggests lack of association of VEGF gene polymorphisms with DR.

Determinants of glaucoma awareness and knowledge in urban Chennai.

Aim: To assess the awareness and knowledge levels about glaucoma and its determinants in an urban population of Chennai in south India. Materials and Methods: Chennai glaucoma study (CGS) was a population based prevalence study to estimate the prevalence of glaucoma in a rural and urban south Indian population. A total of 3850 subjects aged 40 years or above participated in the urban arm of CGS. A systematic random sample of 1926 (50.0%) subjects completed a questionnaire that assesses their awareness and knowledge level of glaucoma. Respondents “having heard of glaucoma” even before they were contacted/recruited for the study were defined as “aware” and respondents having some understanding of the eye disease were defined as “knowledgeable”. Results: Overall 13.5% were aware of glaucoma, the age-gender adjusted rate for awareness was 13.3% (95% CI: 11.57 to 15.03). Two clinicians graded knowledge on glaucoma, based on the subjects knowledge of risk factors, definitions and treatment aspects of glaucoma. Overall 8.7% had some knowledge about glaucoma. Among those who had knowledge 0.5% had good knowledge about glaucoma, 4% had fair knowledge and 4.2% had poor knowledge. We observed a very good agreement between the clinicians in grading knowledge (k =0.92). Determinants of glaucoma awareness and knowledge were higher levels of education, females, age, religion and family history of glaucoma. Conclusion: Awareness and knowledge about glaucoma was very low among the urban population of Chennai. We have found that younger subjects and men were less aware of glaucoma. Subjects with lower levels of education were less aware and knew less about glaucoma than their counterparts. The study findings stress the need for health education for effective prevention of blindness due to glaucoma.

Prevalence and causes of blindness in the rural population of the Chennai Glaucoma Study

Aim: To study the prevalence and causes of blindness in a rural south Indian population. Methods: 3924/4800 enumerated (81.75%) subjects, aged 40 years or more from rural Tamil Nadu, underwent comprehensive ophthalmic examination—visual acuity, refraction, intraocular pressure, gonioscopy, cataract grading (LOCS II), retinal examination, and SITA Standard where indicated. Blindness was defined using WHO criteria as best corrected visual acuity of less than 3/60 and/or visual field of less than 10 degrees in the better eye. The influence of age, sex, literacy, and occupation was assessed using multiple logistic regression. Results: 753 subjects (19.2%; 321 males, 432 females) presented with a visual acuity of <3/60; 132 subjects (3.36%, 95% CI: 2.80 to 3.93) were diagnosed to be blind. Cataract was responsible in 74.62% of eyes; glaucoma, cystoid macular oedema, optic atrophy, and corneal scars accounted for 3.79% each. Bilateral causes of blindness were cataract (78.63%), glaucoma (4.29%), optic atrophy (3.42%), cystoid macular oedema, and corneal scars (2.56% each). In 19 eyes (7.2%) the blindness was probably related to cataract surgery. Blindness was positively associated with increasing age (p<0.0001). Conclusion: 3.36% of the studied rural population was bilaterally blind, with cataract being the single most important cause.

Z-2 aldose reductase allele and diabetic retinopathy in India

Genetic factors have been identified that regulate the severity and the rapidity of onset of retinopathy in diabetic patients. Polymorphisms in (CA) n present upstream of the promoter of the aldose reductase ( ALR2 ) gene have been shown to be associated with retinopathy in different ethnic populations. We aimed to study the association between the (CA) n polymorphism and type 2 diabetic patients with and without retinopathy in the Asian Indian population. We screened 105 diabetic patients with retinopathy (DR) and 109 diabetic patients without retinopathy (DNR) for the (CA) n polymorphism and compared the results with those of an unrelated healthy control group (CT). We identified 13 alleles in our diabetic population. The Z–2 allele (136bp) showed an association with the DR group (13.81%) with a significant p value (p = 0.029) when compared with the DNR group (7.34%). The Z–2 allele also showed a significant association with those DR patients who had proliferative retinopathy (PDR) and maculopathy (MAC) (p = 0.004). The Z–2 allele is, therefore, a high-risk allele for diabetic retinopathy in the Asian Indian patients.

Methods and design of the Chennai Glaucoma Study.

PURPOSE To describe the methodology of a population-based study to estimate the prevalence of glaucoma in a rural and urban South Indian population and to study the genetics of glaucoma in this population. METHODS A sample size of 4758 each for rural and urban populations in the Indian state of Tamil Nadu was calculated. Eligible subjects aged 40 years and above from the rural study area covering 32 contiguous villages and the urban area comprising five random clusters in Chennai city are enumerated. Demographic data are collected in the field. A detailed clinical examination, including glaucoma diagnostic procedures, is conducted at the examination centre. Pedigree ascertainment and genetic studies are performed for subjects with occludable angles or glaucoma. Data are recorded in a computerised database. CONCLUSIONS This study is expected to result in an estimation of the prevalence and a better understanding of the genetics of glaucoma in this region.

Low frequency of myocilin mutations in Indian primary open-angle glaucoma patients.

Glaucoma is one of the major causes of blindness in the Indian population. Mutations in the myocilin (MYOC) gene have been reported in different populations. However, reports on MYOC mutations in Indian primary open‐angle glaucoma (POAG) patients and juvenile open‐angle glaucoma (JOAG) patients are sparse. We therefore screened 100 unrelated POAG/JOAG patients for MYOC mutations. Patients with POAG/JOAG were clinically diagnosed. Genomic DNA from such patients was collected and studied for MYOC mutations by direct sequencing. Nucleotide variations were compared with unrelated healthy controls by restriction enzyme digestion. Secondary structure prediction for the sequence variants was performed by Chou–Fasman method. A novel mutation in exon 1 (144 G→Α) resulting in Gln48His substitution was observed in 2% of the patients. Four other polymorphisms were also observed. The novel mutation was seen in four other affected family members of a JOAG patient. The novel mutation was found to alter the secondary structure in the glycosaminoglycan initiation site of the protein. MYOC mutations were found in 2% of the population studied. MYOC gene may not be playing a significant role in causing POAG in the Indian population.