Bickol N. Mukesh

Breast Cancer Subtypes Based on ER/PR and Her2 Expression: Comparison of Clinicopathologic Features and Survival

OBJECTIVE To compare the clinicopathologic features and survival in the four breast cancer subtypes defined by immunohistochemistry (IHC) expression of estrogen receptor (ER) or progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2): ER/PR+, Her2+; ER/PR+, Her2-; ER/PR-, Her2+; and ER/PR-, Her2-. METHODS A 7-year retrospective study of 1134 invasive breast cancer subjects. Clinical and pathologic features and survival of the four subtypes were compared. RESULTS Using ER/PR+ and Her2- as a reference, ER/PR-, Her2- had the worst overall survival (hazard ratio, 1.8; 95% confidence interval [CI], 1.06-3.2) and the worst disease-free survival (hazard ratio, 1.5; 95% CI, 0.8-3.0). In ER/PR+, Her2-, chemotherapy conferred significant overall and disease-free survival advantages. Subtype comparison revealed statistically significant differences in outcomes. CONCLUSION The triple negative subtype has the worst overall and disease free survival. Efforts should be directed at standardization of current testing methods and development of more reliable and reproducible testing.

The epidemiology of cataract in Australia

PURPOSE To describe the prevalence and risk factors for cataract in an Australian population aged 40 years and older. METHODS Participants were recruited by a household census and stratified, random cluster sampling to represent residents of Victoria, Australia, aged 40 years and older. The following information was collected: initial visual acuity and best-corrected visual acuity, demographic details, health history, dietary intake of antioxidants, lifetime ocular ultraviolet B exposure, and clinical eye examination, including lens photography. Cortical opacities were measured in sixteenths. Cortical cataract was defined as opacity greater than or equal to 4/16 of pupil circumference. Nuclear opacities were graded according to the Wilmer cataract grading scheme, and cataract was defined as greater than or equal to nuclear standard 2.0 of four standards. The height and width of any posterior subcapsular opacity was measured and recorded. Posterior subcapsular cataract was defined as posterior subcapsular opacity greater than or equal to 1 mm2. The worse eye was selected for analysis. Backward stepwise logistic regression was used to quantify independent risk factors for cataract. RESULTS A total of 3,271 (83% of eligible) of the urban residents, 403 (90% of eligible) nursing home residents, and 1,473 (92% of eligible) rural residents participated. The urban residents ranged in age from 40 to 98 years (mean, 59 years), and 1,511 (46%) were men. The nursing home residents ranged in age from 46 to 101 years (mean, 82 years), and 85 (21%) were men. The rural residents ranged in age from 40 to 103 years (mean, 60 years), and 701 (47.5%) were men. The overall weighted rate of cortical cataract was 11.3% (95% confidence limits, 9.68%, 13.0%) excluding cataract surgery and 12.1% (95% confidence limits, 10.5%, 13.8%) including cataract surgery. The risk factors for cortical cataract that remained in the multivariate logistic regression model were age, female gender, diabetes duration greater than 5 years, gout duration greater than 10 years, arthritis diagnosis, myopia, use of oral beta-blockers, and increased average annual ocular ultraviolet B exposure. Overall, 12.6% (95% confidence limits, 9.61%, 15.7%) of Victorians aged 40 years and older had nuclear cataract including previous cataract surgery, and 11.6% (95% confidence limits, 8.61%, 14.7%) had nuclear cataract excluding previous cataract surgery. In the urban and rural cohorts, age, female gender, rural residence, brown irides, diabetes diagnosed 5 or more years earlier, myopia, age-related maculopathy, having smoked for greater than 30 years, and an interaction between ocular ultraviolet B exposure and vitamin E were all risk factors for nuclear cataract. The rate of posterior subcapsular cataract excluding previous cataract surgery was 4.08% (95% confidence limits, 3.01%, 5.14%), whereas the overall rate of posterior subcapsular cataract including previous cataract surgery was 4.93% (95% confidence limits, 3.68%, 6.17%) . The independent risk factors for posterior subcapsular cataract in the urban and rural cohorts that remained were age in years, rural location, use of thiazide diuretics, vitamin E intake, and myopia. CONCLUSIONS The expected increase in the prevalence of cataract with the aging of the population highlights the need to plan appropriate medical services and public health interventions for primary and secondary prevention. Many of the identified risk factors for cataract in the population have the potential for being modified through public health interventions.

Five-year incidence of open-angle glaucoma: The visual impairment project

PURPOSE To determine the incidence of open-angle glaucoma (OAG) in Melbourne, Victoria, Australia. DESIGN Population-based cohort study. PARTICIPANTS Total of 3271 participants aged 40 years and older from Melbourne, Victoria, Australia. MAIN OUTCOME MEASURES Five-year incidence of OAG. METHODS Participants were recruited through a cluster random sampling from nine urban clusters. Baseline examination was conducted from 1992 through 1994, and the follow-up data were collected from 1997 through 1999. Each participant both at baseline and follow-up underwent a standardized ophthalmic examination including intraocular pressure measurement, visual field assessment, cup-to-disc ratio measurement, and paired stereo photographs of the optic disc. Glaucoma was assessed by a consensus group of six ophthalmologists that included two glaucoma specialists. Glaucoma was diagnosed as possible, probable, or definite. RESULTS The overall incidence of definite OAG was 0.5% (95% confidence limits [CL], 0.3, 0.7); probable and definite incidence of OAG was 1.1% (95% CL, 0.8,1.4); and possible, probable, and definite OAG incidence was 2.7% (95% CL, 1.8, 3.7). The incidence of possible, probable, and definite OAG increases significantly as age increases (P < 0.001). The incidence of definite OAG increases from 0% of participants aged 40 to 49 years to 4.1% of participants aged 80 years and older. The incidence of probable and definite OAG increases from 0.2% of participants aged 40 to 49 years to 5.4% of participants aged 80 years and older. The incidence of possible, probable, and definite OAG increases from 0.5% of participants aged 40 to 49 years to 11% of participants aged 80 years and older. A nonsignificant but higher incidence of definite OAG among men was observed in this study when compared with women (odds ratio, 2.2; 95% CL, 0.9, 5.9). Fifty percent of the definite OAG participants were undiagnosed. CONCLUSIONS The incidence of OAG increases significantly with age. The undiagnosed cases suggest the need to develop novel community screening strategies for glaucoma.

Reticular Drusen Associated With Geographic Atrophy in Age-Related Macular Degeneration

PURPOSE To characterize reticular drusen (RDR) in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in a prospective, multicenter, natural history study. METHODS Confocal scanning laser ophthalmoscopy (cSLO) three-field fundus autofluorescence (FAF; exc., 488; em., 500-700 nm), near-infrared reflectance (IR; 820 nm), and blue reflectance (BR; 488 nm) images as well as red-free (RF) and color fundus (CF) camera photographs were recorded in 458 GA patients. The digital images were evaluated by two independent readers with subsequent senior reader arbitration for prevalence and topographic distribution of RDR using a modified Early Treatment Diabetic Retinopathy Study grid. RESULTS RDR were detected with at least one cSLO modality in 286 of 458 (62%) patients in either eye (bilateral 207 [45%]) and were visible in fundus camera photographs in 66 of 371 (18%) patients (bilateral 48 [13%]). Prevalence of RDR by cSLO imaging was associated with increasing age (P = 0.007) and female sex (P = 0.007), but not with GA total lesion area (P = 0.38). Cohen kappa statistics showed good interobserver agreement for FAF (0.81) and IR (0.82) imaging modes, and moderate agreement was found for BR (0.48), RF (0.48), and CF (0.40). On three-field FAF images RDR were present most frequently superior to the fovea (99%). CONCLUSIONS RDR represent a common phenotypic hallmark in GA eyes. RDR are readily identified using cSLO imaging technology. These observations may explain the high prevalence determined herein, in contrast to previous reports based on fundus photographs. Incorporation of these novel imaging modalities in future natural history studies may facilitate efforts aimed at defining the role and predictive value of RDR in the progression of AMD. (ClinicalTrials.gov number, NCT00599846.)

Excessive daytime sleepiness and sleep complaints among children with epilepsy

OBJECTIVE Excessive daytime sleepiness (EDS) and sleep complaints are common among adults with epilepsy. We hypothesized that children with epilepsy have worse daytime sleepiness compared with controls. METHODS Children with and without epilepsy between ages 8 and 18 were recruited for the study. Parents and children were asked to fill out the Pediatric Sleep Questionnaire (PSQ) and Pediatric Daytime Sleepiness Scale (PDSS), respectively. The Mann-Whitney U test was used for group comparisons, with the Fischer exact or chi2 test for categorical variables. Regression analysis was used to identify predictors of EDS. RESULTS Twenty-six patients and matched controls were recruited for the study. Parents of children with epilepsy more often reported EDS (P < 0.001), symptoms of sleep-disordered breathing (P < 0.001), and parasomnias (P < 0.001) compared with controls. On the PDSS, children with epilepsy reported worse daytime sleepiness scores compared with controls (15.48 +/- 6.4 vs 11.88 +/- 5.25, P = 0.037). Based on conditional logistic regression modeling, symptoms of excessive daytime sleepiness [corrected] (OR = 15.3, 95% CI = 1.4-166.6) and parasomnias (OR = 12.4, 95% CI = 1.01-151.6) were significantly associated with having epilepsy when adjusted for duration of nightime sleep. Further, 10 children (38.5%) with epilepsy reported positive sleep-disordered breathing, whereas no one in the control group reported SDB (P < 0.001) [corrected] Epilepsy syndrome, anticonvulsants used, and presence or absence of seizure freedom, however, were not significant predictors of EDS among patients. CONCLUSIONS Daytime sleepiness appears to be common in children with epilepsy, and may be due to underlying sleep disorders. Further confirmatory studies are needed using screening questionnaires and formal sleep studies to systematically study the prevalence of sleep complaints and role of sleep disorders in these patients.

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.

Projected prevalence of age-related cataract and cataract surgery in Australia for the years 2001 and 2021: pooled data from two population-based surveys.

This study aimed to estimate the number of Australians over 50 with cataract in the years 2001 and 2021. Data from two population‐based studies were pooled: the Blue Mountains Eye Study and Melbourne Visual Impairment Project and Australian Bureau of Statistics population projections were used. Similar definitions for the three cataract types were used in the two studies (nuclear ≥ grade 4, posterior subcapsular ≥ 1 mm, cortical ≥ 10% lens area or ≥ 25% circumference). Combining the three types and prior surgery, it was estimated that in 2001, 1.7 million Australians had clinically significant cataract in either eye and 320 000 had previously undergone cataract surgery. It was estimated that the number of persons with cataract will rise to 2.7 million by 2021 (over 500 000 will have had cataract surgery). The number of Australians with cataract will grow by two‐thirds during the next 20 years, reflecting continued population ageing. Health care delivery systems will need to develop methods to handle this increased workload.

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.

Incidence and progression of cataract in the Melbourne Visual Impairment Project.

PURPOSE To determine the 5-year incidence and progression of cataract and cataract surgery in the Melbourne Visual Impairment Project. DESIGN Prospective cohort study. methods: Demographic information including race, sex, age, and education level was collected at baseline. Cortical cataract was defined as 4/16 or greater opacity; progression was defined as a more than 2/16 increase. Nuclear cataract was defined as Wilmer standard grade 2 or higher; progression was defined as more than 0.5 increase. Posterior subcapsular (PSC) cataract was defined as opacity 1 mm(2) or greater; progression was defined as greater than 1 mm(2) increase. results: Of the 3040 participants eligible to attend follow-up examinations, 2594 (85% of those eligible) participated. The mean age of participants at follow-up was 62.5 years, and 55% were female. The percentage of patients who had at least one lens extracted over 5 years increased from 0.5% of those aged 40 to 49 years at baseline to 35.7% of those aged 80 years or more at baseline. The overall incidence of the three types of cataract was as follows: cortical 7.7% (95% confidence limits [CL] = 5.8-9.8), nuclear 16.4% (95% CL = 12.1-20.8), and PSC 7% (95% CL = 5.3-8.7). The overall progression of cataract was cortical 14.3% (95% CL = 10.2-18.3), nuclear 19.3% (95% CL = 15.9-22.7), and PSC 20% (95% CL = 8.7-31.1). The incidence and progression rates increased significantly by age, but the rates were not significantly different by sex. CONCLUSION These cataract incidence data confirm the public health importance of cataract in Australia. The data also support the need to plan both primary prevention program and adequate surgical services to meet the anticipated increase in demand with the aging population.

Performance of Community-Based Glaucoma Screening Using Frequency Doubling Technology and Heidelberg Retinal Tomography

Purpose: To assess the performance of a community-based glaucoma screening algorithm in the general population. Methods: A total of 659 individuals aged 50–90 years were screened for glaucoma. Presenting visual acuity, family history of glaucoma, FDT perimetry, and HRT tests were assessed. Additional samples of participants served as control groups. Participants identified as glaucoma positive received a full ophthalmic examination. Based on this exam a consensus diagnosis was made which served as the gold standard. Results: The optimal screening strategy combining visual acuity and family history with FDT and HRT had sensitivities, specificities, positive predictive values and negative predictive values of 96.8%, 89.7%, 31.9%, and 99.8% respectively for detecting glaucoma. Conclusions: By combining assessments of presenting visual acuity and family history of glaucoma with Frequency Doubling Technology perimetry and Heidelberg Retina Tomography, we devised a community glaucoma-screening algorithm that showed a high sensitivity and specificity for detecting glaucoma in the general population.