Nidhi Talwar

The relationship between components of metabolic syndrome and open-angle glaucoma.

PURPOSE To determine whether an association exists between various components of metabolic syndrome (diabetes mellitus [DM], systemic arterial hypertension [HTN], hyperlipidemia, and obesity) and open-angle glaucoma (OAG) in a large, diverse group of individuals throughout the United States. DESIGN Longitudinal cohort study. PARTICIPANTS All beneficiaries aged ≥40 years continuously enrolled in a managed care network who had 1 or more visits to an eye care provider during 2001 to 2007 were identified. METHODS Billing codes were used to identify individuals with OAG and those with components of metabolic syndrome. Cox regression was used to determine the hazard of developing OAG in enrollees with individual components or combinations of components of metabolic syndrome, with adjustment for sociodemographic factors, systemic medical conditions, and other ocular diseases. MAIN OUTCOME MEASURES Hazard of developing OAG. RESULTS Of the 2 182 315 enrollees who met the inclusion criteria, 55090 (2.5%) had OAG. After adjustment for confounding factors, those with DM (hazard ratio [HR] = 1.35 [95% confidence interval [CI], 1.21-1.50]) or HTN (HR = 1.17 [95% CI, 1.13-1.22]) alone or in combination (HR = 1.48 [95% CI, 1.39-1.58]) had an increased hazard of developing OAG relative to persons with neither of these conditions. By contrast, persons with hyperlipidemia alone had a 5% decreased hazard of OAG (HR = 0.95 [95% CI, 0.91-0.98]). Comorbid hyperlipidemia attenuated the increased hazard between HTN (HR = 1.09 [95% CI, 1.05-1.12]) or DM (HR = 1.13 [95% CI, 1.05-1.21]) and OAG. CONCLUSIONS At a time when the prevalence of metabolic disorders in the United States, is increasing this study furthers our understanding of risk factors associated with OAG and helps identify persons who may be at increased risk for this condition.

The Association Between Glaucomatous and Other Causes of Optic Neuropathy and Sleep Apnea

PURPOSE To determine whether an association exists between sleep apnea and open-angle glaucoma, normal-tension glaucoma, nonarteritic ischemic optic neuropathy (NAION), papilledema, or idiopathic intracranial hypertension (IIH) and whether treatment with continuous positive airway pressure affects the development of these conditions. DESIGN Retrospective, longitudinal cohort study. METHODS Billing records for beneficiaries 40 years of age and older enrolled in a large United States managed care network from 2001 through 2007 were reviewed. Incidence of open-angle glaucoma, normal-tension glaucoma, NAION, papilledema, and IIH were determined for the beneficiaries and were stratified by sleep apnea status. Cox regression analyses determined the hazard of each of these conditions developing among individuals with and without sleep apnea, with adjustment for sociodemographic, ocular, and medical conditions. RESULTS Among the 2 259 061 individuals in the study, 156 336 (6.9%) had 1 or more sleep apnea diagnoses. The hazard of open-angle glaucoma was no different among persons with sleep apnea either treated (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.82 to 1.18) or untreated with continuous positive airway pressure (HR, 1.01; 95% CI, 0.98 to 1.05) and individuals without sleep apnea. Similar findings were observed when assessing the hazard of normal-tension glaucoma developing (P > .05 for both comparisons). A significantly increased hazard of NAION developing (HR, 1.16; 95% CI, 1.01 to 1.33) and IIH (HR, 2.03; 95% CI, 1.65 to 2.49) was observed among individuals with sleep apnea who were not receiving continuous positive airway pressure therapy as compared with individuals without sleep apnea, although similar increased risks could not be demonstrated among continuous positive airway pressure-treated sleep apnea patients for these conditions (P > .05 for both comparisons). CONCLUSIONS Patients with untreated sleep apnea are at increased risk for IIH and NAION. Clinicians should consider appropriate screening for these conditions in sleep apnea patients.

A Longitudinal Analysis of Risk Factors Associated with Central Retinal Vein Occlusion

PURPOSE To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States. DESIGN Longitudinal cohort study. PARTICIPANTS All beneficiaries aged ≥ 55 years who were continuously enrolled in a managed care network for at least 2 years and who had ≥ 2 visits to an eye care provider from 2001 to 2009. METHODS Insurance billing codes were used to identify individuals with a newly diagnosed CRVO. Multivariable Cox regression was performed to determine the factors associated with CRVO development. MAIN OUTCOME MEASURES Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO. RESULTS Of the 494 165 enrollees who met the study inclusion criteria, 1302 (0.26%) were diagnosed with CRVO over 5.4 (± 1.8) years. After adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25-1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66-0.85). A diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23-1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40-4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52-2.42) and 53% (HR, 1.53; 95% CI, 1.28-1.84) increased risk of CRVO, respectively, relative to those without these conditions. CONCLUSIONS This study confirms that HTN and vascular diseases are important risk factors for CRVO. We also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, we show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.

The Relationship Between Statin Use and Open-Angle Glaucoma

PURPOSE To determine whether 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) affect the risk of developing open-angle glaucoma (OAG) in persons with hyperlipidemia. DESIGN Retrospective, longitudinal cohort analysis. PARTICIPANTS Individuals aged ≥60 years with hyperlipidemia enrolled in a national United States managed care network between 2001 and 2009. METHODS Multivariable Cox regression analyses were performed to assess the relationship between statin use and the development of OAG (from no prior OAG diagnosis), progression from a prior diagnosis of glaucoma suspect to a diagnosis of OAG, and need for medical or operative interventions for OAG. Regression models were adjusted for sociodemographic factors and medical and ocular comorbidities. MAIN OUTCOME MEASURES Hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS Of the 524 109 individuals with hyperlipidemia, 316 182 (60%) had ≥1 outpatient prescription for statins. The hazard of developing OAG decreased 0.3% (adjusted HR, 0.997; 95% CI 0.994-0.999) for every additional month of statin consumption. Individuals with hyperlipidemia who took statins continuously for 2 years had an 8% (adjusted HR, 0.922; 95% CI, 0.870-0.976) decreased OAG risk relative to those who received no statin therapy. The hazard of progressing from a diagnosis of glaucoma suspect to OAG decreased 0.4% (adjusted HR, 0.996; 95% CI, 0.993-0.999) for every additional month of statin exposure. Individuals who took statins continuously for 2 years had a 9% (adjusted HR, 0.907; 95% CI, 0.846-0.973) decreased risk of progressing from glaucoma suspect to OAG relative to those who received no statin therapy. The hazard of requiring medical treatment for OAG decreased 0.4% (adjusted HR, 0.996; 95% CI, 0.993-0.998) for every additional month of statin exposure. No differences in need for glaucoma surgery were noted among those with OAG who were and were not taking statins (adjusted HR, 1.002; 95% CI, 0.994-1.010). CONCLUSIONS Statin use was associated with a significant reduction in the risk of OAG among persons with hyperlipidemia. Given the mounting evidence of statin protection against OAG including both basic science and observational clinical studies, an interventional prospective study might provide additional insights into the role of statins in the prevention of early OAG.

The Potential Association Between Postmenopausal Hormone Use and Primary Open-Angle Glaucoma

IMPORTANCE Retinal ganglion cells are known to express estrogen receptors and prior studies have suggested an association between postmenopausal hormone (PMH) use and decreased intraocular pressure, suggesting that PMH use may decrease the risk for primary open-angle glaucoma (POAG). OBJECTIVE To determine whether the use of 3 different classes of PMH affects the risk for POAG. DESIGN, SETTING, AND PARTICIPANTS Retrospective longitudinal cohort analysis of claims data from women 50 years or older enrolled in a US managed-care plan for at least 4 years in which enrollees had at least 2 visits to an eye care provider during the period 2001 through 2009. EXPOSURE Postmenopausal hormone medications containing estrogen only, estrogen + progesterone, and estrogen + androgen, as captured from outpatient pharmacy claims over a 4-year period. MAIN OUTCOMES AND MEASURES Hazard ratios (HRs) for developing incident POAG. RESULTS Of 152,163 eligible enrollees, 2925 (1.9%) developed POAG. After adjustment for confounding factors, each additional month of use of PMH containing estrogen only was associated with a 0.4% reduced risk for POAG (HR, 0.996 [95% CI, 0.993-0.999]; P = .02). The risk for POAG did not differ with each additional month of use of estrogen + progesterone (HR, 0.994 [95% CI, 0.987-1.001]; P = .08) or estrogen + androgen (HR, 0.999 [95% CI, 0.988-1.011]; P = .89). CONCLUSIONS AND RELEVANCE Use of PMH preparations containing estrogen may help reduce the risk for POAG. If prospective studies confirm the findings of this analysis, novel treatments for this sight-threatening condition may follow.

Racial differences in age-related macular degeneration rates in the United States: a longitudinal analysis of a managed care network.

PURPOSE To compare the incidence, prevalence, and hazard of nonexudative and exudative age-related macular degeneration (AMD) among different races throughout the United States. DESIGN Retrospective longitudinal cohort study. METHODS Billing records of all encounters for 2 259 061 beneficiaries aged ≥40 enrolled in a large, national US managed care network from 2001 through 2007 were reviewed and the incidence and prevalence of nonexudative and exudative AMD were determined and stratified by race. Cox regression analyses determined the hazard of nonexudative and exudative AMD for each race, with adjustment for confounders. RESULTS During the study, 113 234 individuals (5.0%) were diagnosed with nonexudative and 17 181 (0.76%) with exudative AMD. After adjustment for confounders, blacks had a significantly reduced hazard of nonexudative (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.71-0.79) and exudative AMD (HR=0.70, 95% CI: 0.59-0.83) at age 60 and a reduced hazard of nonexudative (HR=0.56, 95% CI: 0.52-0.60) and exudative AMD (HR=0.45, 95% CI: 0.37-0.54) at age 80 relative to whites. Similar comparisons for Latinos demonstrated an 18% reduced hazard for nonexudative AMD at age 80 (HR=0.82, 95% CI: 0.76-0.88) relative to whites. Asian Americans showed a 28% increased hazard for nonexudative AMD at age 60 (HR=1.28, 95% CI: 1.20-1.36) but a 46% decreased hazard for exudative AMD at age 80 (HR=0.54, 95% CI: 0.40-0.73). CONCLUSIONS Racial minorities, including Latinos and Asian Americans, do not appear to have similar risks of developing nonexudative and exudative AMD as whites. Additional studies using other sources should be conducted to determine the generalizability of this studys findings to other groups.

Predicting Development of Proliferative Diabetic Retinopathy

OBJECTIVE Identifying individuals most at risk for diabetic retinopathy progression and intervening early can limit vision loss and reduce the costs associated with managing more advanced disease. The purpose of this study was to identify factors associated with progression from nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR). RESEARCH DESIGN AND METHODS This was a retrospective cohort analysis using a claims database of all eye care recipients age ≥30 years enrolled in a large managed-care network from 2001 to 2009. Individuals with newly diagnosed NPDR were followed longitudinally. Multivariable Cox regression analyses identified factors associated with progression to PDR. Three- and five-year probabilities of retinopathy progression were determined. RESULTS Among the 4,617 enrollees with incident NPDR, 307 (6.6%) developed PDR. After adjustment for confounders, every 1-point increase in HbA1c was associated with a 14% (adjusted hazard ratio 1.14 [95% CI 1.07–1.21]) increased hazard of developing PDR. Those with nonhealing ulcers had a 54% (1.54 [1.15–2.07]) increased hazard of progressing to PDR, and enrollees with nephropathy had a marginally significant increased hazard of progressing to PDR (1.29 [0.99–1.67]) relative to those without these conditions. The 5-year probability of progression for low-risk individuals with NPDR was 5% (range 2–8) and for high-risk patients was 38% (14–55). CONCLUSIONS Along with glycemic control, nonophthalmologic manifestations of diabetes mellitus (e.g., nephropathy and nonhealing ulcers) are associated with an increased risk of diabetic retinopathy progression. Our retinopathy progression risk score can help clinicians stratify patients who are most at risk for disease progression.

Trends in Use of Ancillary Glaucoma Tests for Patients with Open-Angle Glaucoma from 2001 to 2009

PURPOSE To assess trends in the use of ancillary diagnostic tests in the evaluation of patients with open-angle glaucoma (OAG) and glaucoma suspects over the past decade. DESIGN Retrospective, longitudinal cohort analysis. PARTICIPANTS A total of 169 917 individuals with OAG and 395 721 individuals with suspected glaucoma aged ≥40 years enrolled in a national United States managed care network between 2001 and 2009. METHODS Claims data were analyzed to assess trends in visual field (VF) testing, fundus photography (FP), and other ocular imaging (OOI) testing for patients with OAG or suspected glaucoma between 2001 and 2009. Repeated-measures logistic regression was performed to identify differences in the odds of undergoing these procedures in 2001, 2005, and 2009 and whether differences exist for patients under the exclusive care of optometrists versus ophthalmologists. MAIN OUTCOME MEASURES Odds and annual probabilities of undergoing VF testing, FP, and OOI for OAG from 2001 to 2009. RESULTS For patients with OAG, the odds of undergoing VF testing decreased by 36% from 2001 to 2005, by 12% from 2005 to 2009, and by 44% from 2001 to 2009. By comparison, the odds of having OOI increased by 100% from 2001 to 2005, by 24% from 2005 to 2009, and by 147% from 2001 to 2009. Probabilities of undergoing FP were relatively low (13%-25%) for both provider types and remained fairly steady over the decade. For patients cared for exclusively by optometrists, the probability of VF testing decreased from 66% in 2001 to 44% in 2009. Among those seen exclusively by ophthalmologists, the probability of VF testing decreased from 65% in 2001 to 51% in 2009. The probability of undergoing OOI increased from 26% in 2001 to 47% in 2009 for patients of optometrists and from 30% in 2001 to 46% in 2009 for patients of ophthalmologists. By 2008, patients with OAG receiving care exclusively by optometrists had a higher probability of undergoing OOI than VF testing. CONCLUSIONS From 2001 to 2009, OOI increased dramatically whereas VF testing declined considerably. Because OOI has not been shown to be as effective at detecting OAG or disease progression compared with VF testing, increased reliance on OOI technology, in lieu of VF testing, may be detrimental to patient care.

Risk Factors for Developing Thyroid-Associated Ophthalmopathy Among Individuals With Graves Disease

IMPORTANCE Thyroid-associated ophthalmopathy (TAO) is a common and debilitating manifestation of Graves disease (GD). Presently little is known about factors that may increase the risk of developing TAO among patients with GD. OBJECTIVE To identify risk factors associated with the development of TAO among individuals with newly diagnosed GD. DESIGN, SETTING, AND PARTICIPANTS In this longitudinal cohort study, all beneficiaries 18 years of age or older with newly diagnosed GD who were continuously enrolled in a large nationwide US managed care network and who visited an eye care professional 1 or more times from 2001 to 2009 were identified. International Classification of Diseases, Ninth Revision, Clinical Modification billing codes were used to identify those who developed manifestations of TAO. Multivariable Cox regression was used to determine the hazard of developing TAO among persons with newly diagnosed GD, with adjustment for sociodemographic factors, systemic medical conditions, thyrotropin levels, and medical and surgical interventions for management of hyperthyroidism. MAIN OUTCOMES AND MEASURES Manifestations of TAO measured by hazard ratios (HRs) with 95% CIs. RESULTS Of 8404 patients with GD who met the inclusion criteria, 740 (8.8%) developed TAO (mean follow-up, 374 days since initial GD diagnosis). After adjustment for potential confounders, surgical thyroidectomy, alone or in combination with medical therapy, was associated with a 74% decreased hazard for TAO (adjusted HR, 0.26 [95% CI, 0.12-0.51]) compared with radioactive iodine therapy alone. Statin use (for ≥60 days in the past year vs <60 days or nonuse) was associated with a 40% decreased hazard (adjusted HR, 0.60 [CI, 0.37-0.93]). No significant association was found for the use of nonstatin cholesterol-lowering medications or cyclooxygenase 2 inhibitors and the development of TAO. CONCLUSIONS AND RELEVANCE If prospective studies can confirm our finding that a thyroidectomy and statin use are associated with substantially reduced hazards for TAO among patients with GD, preventive measures for this burdensome manifestation of GD may become a reality.

Risk Factors Associated with Developing Branch Retinal Vein Occlusion Among Enrollees in a United States Managed Care Plan

PURPOSE To determine risk factors associated with development of a branch retinal vein occlusion (BRVO) among a large group of managed-care plan beneficiaries in the United States. DESIGN Retrospective, longitudinal cohort study. PARTICIPANTS All beneficiaries age ≥55 years continuously enrolled for ≥2 years in a managed care network from 2001-2009 who had ≥2 visits to an eye care provider. METHODS Multivariable Cox regression analyses identified sociodemographic factors, ocular and nonocular conditions associated with incident BRVO. MAIN OUTCOME MEASURES Hazard of incident BRVO with 95% confidence interval (CI). RESULTS Of the 492,488 enrollees who met inclusion criteria, 2283 (0.5%) developed incident BRVO. After adjustment for confounding factors, blacks (adjusted hazard ratio [aHR], 1.43; CI, 1.19-1.73; P = 0.0001) had a 43% increased hazard of BRVO relative to non-Hispanic whites. Enrollees with hypertension (HTN) alone (aHR, 1.78; CI, 1.36-2.32; P < 0.0001) or HTN along with other metabolic syndrome components (diabetes mellitus [DM] and hyperlipidemia; aHR, 1.44; CI, 1.12-1.84; P = 0.005) had an increased hazard of developing a BRVO compared with those with none of these conditions. Disease severity was important; enrollees with end-organ damage caused by HTN had a 107% increased hazard of developing BRVO compared with enrollees without HTN (aHR, 2.07; CI, 1.75-2.45; P < 0.0001). Although there was no association between DM without end-organ damage and BRVO (aHR, 0.92; CI, 0.81-1.04; P = 0.2), individuals with end-organ damage from DM had a 36% increased hazard of BRVO (aHR, 1.36; CI, 1.18-1.57; P < 0.0001) compared with those without DM. Although cerebrovascular accident was associated with an increased hazard of developing BRVO (aHR, 1.34; CI, 1.19-1.52; P < 0.0001), other diseases of the vascular system (deep venous thrombosis/pulmonary embolism, peripheral vascular disease, hypercoagulable state, myocardial infarction) or anticoagulant use did not increase the risk of BRVO (P > 0.10 for all comparisons). CONCLUSIONS Both HTN and end-organ damage from DM contribute to arteriosclerosis, atherosclerosis, and endothelial dysfunction, which seem to be major risk factors for BRVO. Ophthalmologists should emphasize to patients and their primary physicians the importance of effectively managing systemic medical conditions associated with BRVO.