Papers by Pradeep Paul George
Telemedicine Journal and E-health, 2007
The purpose of this article was to study the influence of pupillary dilatation on the gradability... more The purpose of this article was to study the influence of pupillary dilatation on the gradability of a single-field 45 degrees digital fundus images taken in a telescreening model for diabetic retinopathy. Telescreening camps for diabetic retinopathy were organized in rural south India. Sixty-eight patients with type 2 diabetes were enrolled. Single-field 45 degrees digital fundus images were obtained before (group I) and after pupillary dilatation (group II). Digital fundus images were obtained using nonmydriatic fundus camera and transmitted in real time to the base hospital for grading by a retinal specialist. Various factors that could influence the gradability of images were studied, including patients' age and visual acuity, experience of the photographer, and interobserver variability. After pupillary dilatation, the nongradability of digital fundus images was reduced from 29.1% to 8.6%. With each line of improvement in Snellen's Visual acuity, the gradability improved by 12.1%; likewise, with each year of age, the gradability improved by 5.5% following mydriasis. Interobserver variation was excellent (k = 0.88). The learning curve of photographer had no effect on image gradability. Pupillary dilatation improves the gradability of a single-field 45 degrees digital fundus image during telescreening of diabetic retinopathy.
Eye, 2006
Purpose Exudative age-related macular degeneration (ARMD) is one of the debilitating ocular compl... more Purpose Exudative age-related macular degeneration (ARMD) is one of the debilitating ocular complications, which results in permanent blindness. Elevated homocysteine (Hcys) levels have been associated in the development of several vascular diseases. Vascular and oxidative stress theories have been implicated for the development of choroidal neovascularization in exudative ARMD. The aim of the present study was to investigate the possible role of plasma Hcys and thiol content (tSH) as a risk factor for the development of exudative ARMD. Method A total of 16 patients with exudative ARMD and 20 age-matched controls were recruited for the study. Plasma Hcys levels were analysed using Reverse Phase High Performance Liquid Chromatography. Plasma glutathione (GSH) content was determined using o-phthalaldehyde (OPA) derivatization and subsequent detection by fluorimeter. Plasma tSH levels were determined by using thiol-specific reagent dithionitrobenzoic acid (DTNB) spectrophotometrically. Results Plasma Hcys levels in exudative ARMD were elevated three-fold (1875.0 lM) when compared to healthy controls (6.771.8 lM). There was a two-fold decrease in the GSH and tSH in exudative ARMD when compared with controls. Negative correlation was observed between diminished tSH and Hcys levels (r ¼ À0.4837, P ¼ 0.05). Similarly plasma Hcys levels negatively correlated with GSH content (r ¼ À0.6620, Po0.05). Conclusion Results from our present study revealed that there is an elevated Hcys level and diminished thiol pool content in exudative ARMD that are significant.
Ophthalmic Research, 2007
Growth factors have been implicated in the pathogenesis of diabetic retinopathy (DR). IGF-1 is kn... more Growth factors have been implicated in the pathogenesis of diabetic retinopathy (DR). IGF-1 is known to trigger a critical cascade of molecular events that initiate retinal angiogenesis. Increased vitreous IGF-1 levels have been correlated with the severity of ischemia-associated diabetic retinal neovascularization. In the present study, a cytosine-adenine (CA)(n) repeat in the promoter of the IGF-1 gene is studied for association with DR. A total of 127 patients with retinopathy (cases: DR+) and 81 patients without retinopathy (controls: DR-) who had type 2 diabetes were recruited for the study. Patients underwent detailed clinical examination and DR was graded based on stereoscopic digital fundus photographs. Frequencies of alleles and genotypes between the two groups were analyzed for significance using relevant statistical tests. (CA)(17) and (CA)(18) repeats were the more frequent alleles. The frequency of the 18-repeat genotype was significantly higher in DR+ patients when compared to DR- patients and found to confer a 2.4 times (95% CI: 1.2-5.0) and 2.8 times (95% CI: 1.1-7.5) higher risk for developing DR and proliferative DR, respectively, when compared to <18-repeat genotypes. Our study suggests that the 18-repeat genotype is a susceptibility genotype for DR and its clinical severity in a Southern Indian cohort.
Introduction: The aim of this study was to compare the occurrence of diabetic retinopathy in targ... more Introduction: The aim of this study was to compare the occurrence of diabetic retinopathy in targeted screening diabetic patients (Group I) with newly diagnosed diabetic patients in general practice (Group II). Materials and Methods: This was an observational cross-sectional study. Data were obtained from 25,313 subjects who participated in the diabetic screening camps, and 128 newly diagnosed diabetes who presented to the diabetic retinopathy screening camps in general practice in rural and urban south India. The study variables were collected from all patients who underwent eye examination from the target screening detected diabetics [(n = 173) Group I] and those newly diagnosed in general practice [(n = 128) Group II]. The variations in prevalence of diabetic retinopathy and sight-threatening diabetic retinopathy in Group I and Group II and the factors affecting it were identified. Results: The occurrence of diabetic retinopathy was 6.35% (95% CI, 2.5-9.5) in Group I and 11.71% (95% CI, 5.6-16.4) in Group II. No significant difference was observed on occurrence of diabetic retinopathy, including sightthreatening retinopathy, in rural versus urban population and in Group I versus Group II. Patients diagnosed in general practice (Group II) with systolic blood pressure (BP) >140 were more likely to have retinopathy (P = 0.02). Conclusions: Diabetic retinopathy including sightthreatening complications was found at the time of diagnosis of diabetes in the targeted screening group as well as in newly diagnosed diabetics in the general practice group. Ann Acad Med Singapore 2006;35:531-5
Current Eye Research, 2005
Purpose: To study the effect of cataract surgery with intraocular lens (IOL) on frequency doublin... more Purpose: To study the effect of cataract surgery with intraocular lens (IOL) on frequency doubling perimetry (FDP). Methods: Patients aged 40 years or above seen at our outpatient clinic with no ocular pathology except for visually significant cataract and visual acuity 6/24 or better were eligible. They underwent FDP before and 4 to 6 weeks after cataract surgery with IOL. Results: Screening test: Mean scores by three different scoring methods were 1.82 (3.21), 2.80 (5.54), 4.18 (9.18) before and 0.22 (0.51), 0.26 (0.63), 0.26 (0.69) after surgery (p = 0.002 0.001, <0.0001). Threshold test: Mean deviation (MD) and pattern standard deviation (PSD) were −5.23 (3.08) and 5.15 (2.78) before and 2.94 (2.49) (p < 0.0001) and 5.21 (1.780) (p = 0.63) after surgery. Conclusions:
Ophthalmic Epidemiology, 2005
Purpose: To describe the methodology of the Sankara Nethralaya-Diabetic Retinopathy Epidemiology ... more 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 study 2 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
Ophthalmic Genetics, 2008
Background: Polymorphisms in vascular endothelial growth factor (VEGF) gene have been associated ... more 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.
Ophthalmic Epidemiology, 2005
Aim: To elucidate the rate of non-response among diabetics (recently diagnosed in rural diabetic ... more Aim: To elucidate the rate of non-response among diabetics (recently diagnosed in rural diabetic screening camps) who were referred for eye examination to detect diabetic retinopathy. Methods: At diabetic retinopathy screening camps, all patients underwent dilated fundus examination using binocular indirect ophthalmoscopy. Results: Of the 4,111 known diabetics, only 2231(55%) patients attended the diabetic retinopathy screening camps. Likewise, of the 1076 newly detected diabetics, only 125 (11.6%) attended the diabetic retinopathy screening camps. Conclusions: Non-response of such a magnitude calls for creating greater awareness among masses on diabetes and its microvascular complications. Second, conducting simultaneous diabetes screening and diabetic retinopathy screening camps could minimize the dropout rate.
Clinical Genetics, 2004
Glaucoma is one of the major causes of blindness in the Indian population. Mutations in the myoci... more 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.
Optometry and Vision Science, 2007
To compare the effect of uncorrected refractive error on threshold estimation using frequency dou... more To compare the effect of uncorrected refractive error on threshold estimation using frequency doubling perimetry (FDP) full-threshold N-30 with emmetropia among normal subjects. Methods. One thousand two hundred ninety-nine subjects were enrolled from the Chennai Glaucoma Study, a populationbased glaucoma prevalence study. Subjects underwent a comprehensive eye examination including the FDP full-threshold N-30 test. Normal subjects (with spherical equivalent refractive errors within Ϯ7 D) with no other ocular pathology were stratified into six groups based on the degree of myopia and hyperopia and compared with age-matched emmetropic controls. A subset of 22 subjects with higher refractive errors was assessed for within-subject effect on FDP parameters. The following FDP parameters were compared: mean deviation, pattern standard deviation, central threshold (CT), mean sensitivity (MS), paracentral points (PA), and peripheral threshold. Results. The one-way analysis of variance between all refractive error groups and emmetropes showed no statistically significant difference for the mean deviation (p ϭ 0.1002) and pattern standard deviation (p ϭ 0.4789). FDP parameters did not show a statistically significant difference for between and within-group comparisons. The variability of FDP sensitivity (derived from the 95% confidence interval range) as a proportion of the threshold range of the instrument was 31, 41, 46, and 41% for CT, MS, PA, and peripheral sensitivity, respectively, without spectacle correction and 29, 34, 36, and 35% for CT, MS, PA, and peripheral sensitivity, respectively, with correction. The mean CT, PA, and peripheral sensitivity show a decreasing trend from central to periphery in all the refractive error groups and a similar trend was noted in the emmetropic controls. Conclusion. Between-subject (uncorrected ammetropes and age-matched emmetropes) and within-subject comparisons showed no statistically significant differences in any of the FDP parameters or in the contrast sensitivity estimates between the central and peripheral test locations. This finding is likely due to the high within-subject variability of FDP. (Optom Vis Sci 2007;84:496-504)
Ophthalmic Genetics, 2003
Genetic factors have been identified that regulate the severity and the rapidity of onset of reti... more 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 (136 bp) 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.
Journal of Diabetes and Its Complications, 2002
Aim/hypothesis: The binding of advanced glycation end products (AGE) to the receptor induces cell... more 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. D
Journal of Telemedicine and Telecare, 2006
There is an urgent need to develop comprehensive screening strategies to prevent blindness due to... more There is an urgent need to develop comprehensive screening strategies to prevent blindness due to diabetes. Tele-ophthalmology is emerging as an important screening method for diabetic retinopathy with wide reach to remote and rural areas. In this form of telemedicine, retinal ...
British Journal of Ophthalmology, 2003
Annals of Surgical Oncology, 2008
Background This study aims to validate and compare the performance of the National Institute of H... more Background This study aims to validate and compare the performance of the National Institute of Health (NIH) criteria, Huang modified NIH criteria, and Armed Forces Institute of Pathology (AFIP) risk criteria for gastrointestinal stromal tumors (GISTs) in a large series of localized primary GISTs surgically treated at a single institution to determine the ideal risk stratification system for GIST. Methods The clinicopathological features of 171 consecutive patients who underwent surgical resection for GISTs were retrospectively reviewed. Statistical analyses were performed to compare the prognostic value of the three risk criteria by analyzing the discriminatory ability linear trend, homogeneity, monotonicity of gradients, and Akaike information criteria. Results The median actuarial recurrence-free survival (RFS) for all 171 patients was 70%. On multivariate analyses, size >10 cm, mitotic count >5/50 high-power field, tumor necrosis, and serosal involvement were independent prognostic factors of RFS. All three risk criteria demonstrated a statistically significant difference in the recurrence rate, median actuarial RFS, actuarial 5-year RFS, and tumor-specific death across the different stages. Comparison of the various risk-stratification systems demonstrated that our proposed modified AFIP criteria had the best independent predictive value of RFS when compared with the other systems. Conclusion The NIH, modified NIH, and AFIP criteria are useful in the prognostication of GIST, and the AFIP risk criteria provided the best prognostication among the three systems for primary localized GIST. However, remarkable prognostic heterogeneity exists in the AFIP high-risk category, and with our proposed modification, this system provides the most accurate prognostic information.
Ophthalmic Genetics, 2007
A 27-bp variable number tandem repeat (VNTR) in intron 4 of endothelial nitric oxide synthase (eN... more A 27-bp variable number tandem repeat (VNTR) in intron 4 of endothelial nitric oxide synthase (eNOS) gene has been associated with the risk for developing diabetic retinopathy (DR) in various ethnic populations. Hundred and eighty seven patients with retinopathy (cases; DR+) and 188 patients without retinopathy (controls: DR−) from southern India who had type 2 diabetes mellitus (T2DM) for more than 10 years, were included in the study. We could neither find significant allelic association with clinical severity of DR nor with macular edema. Our results suggest lack of association of intron 4 VNTR of eNOS gene with DR in southern India.
Ophthalmic Epidemiology, 2003
purpose To describe the methodology of a population-based study to estimate the prevalence of gla... more 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.
Ophthalmic Epidemiology, 2005
Purpose: To study whether the difference in the demographic characteristics of participants and n... more Purpose: To study whether the difference in the demographic characteristics of participants and non-participants could result in biased prevalence estimates and associations. Aim: To compare the non-participant & participant characteristics, and to ascertain if non-response bias is present in the rural population of the Chennai Glaucoma Study (CGS). Methods: Rural participants and non-participants were compared with regard to socio-demographic variables (age, gender, religion, mother tongue, literacy and employment). Results: 4800 subjects aged 40 years or over were enumerated, 82% (3934: 45% male and 55% female) responded. Gender did not influence participation (adjusted OR-1.11, CI: .91-1.36). Subjects in the 70-79 year age group were more likely to respond (OR-1.76; CI-1.31-2.38). Hindus had a higher participation rate than Christians or Muslims (adjusted OR-2.63, CI: 1.80-3.84). The other predictors of participation were illiteracy (adjusted OR-1.44, CI: 1.22-1.70), unemployment (OR-1.28, CI: 1.04-1.58), place of residence (main villages) (OR-1.89, 95% CI: 1.59-2.25) and cottage industry-based villages (OR-6.66, 95% CI: 4.6-9.64). Conclusion: Based on our study findings, it does not seem likely that participation bias will affect the study results. 10 15 20
To report the prevalence of refractive errors in a rural south Indian population. METHODS. Four t... more To report the prevalence of refractive errors in a rural south Indian population. METHODS. Four thousand eight hundred subjects (age, Ͼ39 years) from rural south India were enumerated for a population-based study. All participants underwent complete ophthalmic evaluation. Subjects who were phakic in the right eye with best corrected visual acuity of 20/40 or better were included for analysis. Association of refractive errors with age, sex, cataract, and diabetes mellitus were analyzed. RESULTS. Of the 3924 responders, 2508 were eligible. The unadjusted prevalence of emmetropia (spherical equivalent [SE], Ϫ0.50 to ϩ0.50 diopter sphere [DS]), myopia (SE Ͻ Ϫ0.50 DS), high myopia (SE Ͻ Ϫ5.00 DS), and hyperopia (SE Ͼ 0.50 DS) were 50.60%, 26.99%, 3.71%, and 18.70% and age and gender adjusted for the rural Tamil Nadu population were 46.77%, 30.97%, 4.32%, and 17.94%, respectively. The prevalence of emmetropia decreased significantly with age (P Ͻ 0.0001), and the prevalence of myopia and high myopia increased significantly with age (P Ͻ 0.001) and were significantly associated with nuclear sclerosis (P Ͻ 0.001). The prevalence of hyperopia increased until 60 years of age and then decreased. Hyperopia was more common among women than men (P Ͻ 0.001) and was negatively associated with nuclear sclerosis (P Ͻ 0.001) and positively with diabetes mellitus (P ϭ 0.008). Of the participants with astigmatism (cylindrical error greater than 0.50 DC), 9.80% had with-the-rule (WTR) and 77.44% against-the-rule (ATR) astigmatism. The prevalence of WTR and ATR astigmatism significantly decreased (P Ͻ 0.001) and increased (P ϭ 0.006) with age, respectively. CONCLUSIONS. The pattern of refractive errors in this rural south Indian population is similar to those reported in other tropical regions of the world. (Invest Ophthalmol Vis Sci. 2004;45: 4268 -4272)
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Papers by Pradeep Paul George