Assessing patient perception of risk in ocular stem cell therapies.

A wide variety of stem cell-derived therapies are under development for the treatment of retinal degeneration. In order to better understand patient perspectives about these therapies, we assessed risk tolerance using an in-person survey of 178 patients at an academic eye center. Risk of malignancy served as a hypothetical, readily understood, and serious adverse event to be considered in trade for potential visual improvement from a stem cell-derived treatment. The results indicate that patients were willing to trade visual improvement against a risk of malignancy that far exceeds actual risk. Two novel findings were that older patients and those with an intermediate level of visual loss were particularly risk tolerant. The quantitative survey results provide a step toward understanding patient perspectives that will, over the long term, guide the development of ocular stem cell-derived therapies.

Reduced Mammography Screening for Breast Cancer among Women with Visual Impairment.

PURPOSE: Timely mammography to screen for breast cancer in accordance with the United States Preventive Services Task Force (USPSTF) recommendations can reduce morbidity and mortality substantially. This study assessed whether the odds of undergoing screening mammography are similar for women with and without visual impairment (VI). DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: Women aged 65 to 72 years enrolled in fee-for-service Medicare from January 1, 2008, through December 31, 2015. METHODS: Patients with no vision loss (NVL), partial vision loss (PVL), and severe vision loss (SVL) were matched 1:1:1 based on age, race, time in Medicare, urbanicity of residence, and overall health. Women with pre-existing breast cancer were excluded. Multivariable conditional logistic regression modeling compared the odds of undergoing screening mammography within a 2-year follow-up period among the 3 groups. MAIN OUTCOMES MEASURES: Proportion of participants undergoing mammography and adjusted odds ratios (ORs) of undergoing mammography within 2 years of follow-up. RESULTS: A total of 1044 patients were matched (348 in each group). The mean ± standard deviation age at the index date was 69.0 ± 1.5 years for all 3 groups. The proportion of women undergoing 1 mammography screening or more within the 2-year follow-up was 69.0% (n = 240), 56.9% (n = 198), and 56.0% (n = 195) for the NVL, PVL, and SVL groups, respectively (P = 0.0005). The mean ± standard deviation number of mammography screenings undergone per patient during the 5-year period (3-year look-back plus 2-year follow-up) was 3.1 ± 2.0, 2.5 ± 2.0, and 2.3 ± 2.1 for the NVL, PVL, and SVL groups, respectively (P < 0.0001). Women with SVL had 42% decreased odds (OR, 0.58; 95% CI, 0.37-0.90; P = 0.01), and those with PVL had 44% decreased odds (OR, 0.56; CI, 0.36-0.87; P = 0.009) of undergoing mammography during follow-up compared with those with NVL. CONCLUSIONS: Women with VI were significantly less likely to undergo mammography screening for breast cancer than women without VI. Clinicians should look for ways to help ensure that patients with VI undergo mammography and other preventive screenings as recommended by the USPSTF.

Association of Co-occurring Dementia and Self-reported Visual Impairment With Activity Limitations in Older Adults.

Importance: The number of older adults with visual impairment (VI) and dementia is projected to increase in the US because of the aging of the population. Dementia and VI commonly co-occur and are each independently associated with disability. To care for an aging population, it may be important to characterize the association of coexisting dementia and self-reported VI on daily functioning. Objective: To evaluate the association of co-occurring dementia and self-reported VI on daily functioning. Design, Setting, and Participants: This cross-sectional analysis of a nationally representative cohort study used data from the National Health and Aging Trends Study (NHATS), an annual study of US adults 65 years and older. Participants in the 2015 survey with complete data on outcomes, associated factors, and covariates were included in this study. Data analysis took place from January 2019 to November 2019. Main Outcomes and Measures: Multivariable Poisson regression was used to model the independent associations and interaction of dementia and self-reported VI status on 3 functional activity scales (self-care, mobility, and household activities). Marginal predicted proportions were calculated. Analyses were adjusted for sociodemographic and medical factors and accounted for the complex survey design. Results: A total of 7124 participants were included. The weighted proportion of female respondents was 55.3% (95% CI, 54.0%-56.6%), and 56.1% (95% CI, 54.1%-58.1%) were between 65 and 74 years old. Self-reported VI was present in 8.6% (95% CI, 7.8%-9.3%) of participants, while 8.3% (95% CI, 7.8%-8.9%) had possible dementia and 6.3% (95% CI, 5.7%-6.9%) had probable dementia. Self-reported VI was associated with an expected decrease in mobility score of 14.7% (functional scale scores: no VI, 10.82 vs VI, 9.23), self-care score of 9.5% (no VI, 14.54 vs VI, 13.16), and household activity score of 15.2% (no VI, 18.23 vs VI, 15.45), while probable dementia was associated with expected decreases of 27.8% (no dementia, 10.82 vs probable dementia, 7.81), 22.9% (no dementia, 14.54 vs probable dementia, 11.20), and 34.7% (no dementia, 18.23 vs probable dementia, 11.90), respectively. Among those with probable dementia and self-reported VI, there was an expected decrease in mobility score of 50.1% (functional ability scores: no VI and no dementia, 10.82 vs VI and probable dementia, 5.40), self-care score of 42.4% (no VI and no dementia, 14.54 vs VI and probable dementia, 8.38), and household activity score of 52.4% (no VI and no dementia, 18.23 vs VI and probable dementia, 8.68), suggesting that respondents with co-occurring dementia and self-reported VI had lower functional activity scores than would be associated with the independent contributions of these conditions. Conclusions and Relevance: Older adults with both dementia and self-reported VI may be at high risk for disability, and their co-occurrence may potentiate this risk. These findings suggest that the growing population of older adults with both visual impairment and dementia may benefit from interventions to maximize vision and cognition and promote functioning and independence.

Use of Bevacizumab and Ranibizumab for Wet Age-Related Macular Degeneration: Influence of CATT Results and Introduction of Aflibercept.

PURPOSE: To assess whether publication of Comparison of Age-related macular degeneration Treatment Trial (CATT) results and introduction of aflibercept to the marketplace affected intravitreal bevacizumab and ranibizumab utilization. DESIGN: Retrospective analysis of treatment patterns. METHODS: We calculated weekly bevacizumab and ranibizumab utilization during 3 timeframes: (1) before CATT publication, (2) between CATT publication (April 28, 2011) and assignment of a unique aflibercept billing code (January 1, 2013), and (3) afterward for 164,188 Medicare beneficiaries with neovascular macular degeneration receiving ≥1 anti-vascular endothelial growth factor injection(s) from January 1, 2008 to December 31, 2014. We identified ophthalmologists who predominantly (≥80%) administered bevacizumab or ranibizumab and evaluated changes in preferences over the 3 periods. We replicated analyses on 881,381 commercially insured beneficiaries. RESULTS: Among 317 ophthalmologists administering predominantly ranibizumab to Medicare beneficiaries pre-CATT, 221 (69.7%) reduced ranibizumab use post-CATT, whereas 96 (30.3%) continued using ranibizumab ≥80% of the time. Findings were reversed among 1041 ophthalmologists who predominantly administered bevacizumab pre-CATT-777 (74.6%) continued bevacizumab-predominant use while 264 (25.4%) reduced bevacizumab use post-CATT. Among the 145 ophthalmologists who predominantly administered ranibizumab before aflibercept's availability, 77 (53.1%) reduced ranibizumab utilization and 68 (46.9%) continued using ranibizumab ≥80% of the time after aflibercept became available. Corresponding numbers among the 909 ophthalmologists who predominantly administered bevacizumab pre-aflibercept were 381 (41.9%) reducing and 528 (58.1%) continuing bevacizumab-predominant use. Similar results were observed for commercially insured patients. CONCLUSIONS: Many ophthalmologists who favored ranibizumab switched to bevacizumab after CATT publication, while most who favored bevacizumab before CATT publication continued favoring it afterward. Aflibercept's introduction had little impact on preferences for ranibizumab or bevacizumab.

Association of Vision Loss With Hospital Use and Costs Among Older Adults.

Importance: Patients with vision loss who are hospitalized for common illnesses are often not identified as requiring special attention. This perception, however, may affect the outcomes, resource use, and costs for these individuals. Objective: To assess whether the mean hospitalization lengths of stay, readmission rates, and costs of hospitalization differed between individuals with vision loss and those without when they are hospitalized for similar medical conditions. Design, Setting, and Participants: This analysis of health care claims data used 2 sources: Medicare database and Clinformatics DataMart. Individuals with vision loss were matched 1:1 to those with no vision loss (NVL), on the basis of age, years from initial hospitalization, sex, race/ethnicity, urbanicity of residence, and overall health. Both groups had the same health insurance (Medicare or a commercial health plan), and all had been hospitalized for common illnesses. Vision loss was categorized as either partial vision loss (PVL) or severe vision loss (SVL). Data were analyzed from April 2015 through April 2018. Main Outcomes and Measures: The outcomes were lengths of stay, readmission rates, and health care costs during hospitalization and 90 days after discharge. Multivariable logistic and linear regression models were built to identify factors associated with these outcomes among the NVL, PVL, and SVL groups. Results: Among Medicare beneficiaries, 6165 individuals with NVL (with a mean [SD] age of 82.0 [8.3] years, and 3833 [62.2%] of whom were female) were matched to 6165 with vision loss. Of those with vision loss, 3401 (55.2%) had PVL and 2764 (44.8%) had SVL. In the Clinformatics DataMart database, 5929 individuals with NVL (with a mean [SD] age of 73.7 [15.1] years, and 3587 [60.5%] of whom were female) were matched to 5929 individuals with vision loss. Of the commercially insured enrollees with vision loss, 3515 (59.3%) had PVL and 2414 (40.7%) had SVL. Medicare enrollees with SVL, compared with those with NVL, had longer mean lengths of stay (6.48 vs 5.26 days), higher readmission rates (23.1% vs 18.7%), and higher hospitalization and 90-day postdischarge costs ($64 711 vs $61 060). Compared with those with NVL, Medicare beneficiaries with SVL had 4% longer length of stay (estimated ratio, 1.04; 95% CI, 1.01-1.07; P = .02), 22% higher odds of readmission (odds ratio, 1.22; 95% CI, 1.06-1.41; P = .007), and 12% higher costs (estimated cost ratio, 1.12; 95% CI, 1.06-1.18; P < .001). Similar findings were obtained for those with commercial health insurance. When these findings were extrapolated to hospitalizations of patients with vision loss nationwide, an estimated amount of more than $500 million in additional costs annually were spent caring for these patients. Conclusions and Relevance: These findings suggest that opportunities for improving outcomes and reducing costs exist in addressing patients' vision loss and concomitant functional difficulties during hospitalization and thereafter.

Trends in Use of Ambulatory Surgery Centers for Cataract Surgery in the United States, 2001-2014.

Importance: Cataract surgery is commonly performed at ambulatory surgery centers (ASCs) and hospital outpatient departments (HOPDs). These venues differ in many ways, including surgical efficiency, patient throughput, patient safety, and costs per surgery. Objective: To determine trends in use of ASCs and HOPDs for cataract surgery from 2001 to 2014 and factors affecting the site of surgery. Design, Setting, and Participants: This retrospective longitudinal cohort analysis involved individuals 40 years and older who underwent cataract surgery between January 2001 and December 2014 from a nationwide US managed care network. Data were analyzed from February 2016 to February 2017. Main Outcomes and Measures: We identified all enrollees who underwent cataract surgery and determined whether the surgery was performed at an ASC or HOPD. We calculated the proportion of surgeries performed at each site each year from 2001 to 2014. Multivariable logistic regression identified characteristics of enrollees who had cataract surgery at an ASC vs a HOPD. We also assessed geographic variation in the proportion of cataract surgeries performed at ASCs in 306 communities throughout the United States. Results: Of the 369 320 enrollees included in this study, 208 319 (56.4%) were female, and the mean (SD) age was 66.3 (10.4) years. All enrollees underwent cataract surgery (531 325 surgeries) from 2001 to 2014. Of these, 237 046 (64.2%) underwent cataract surgery at an ASC. The proportion of cataract surgeries performed at ASCs increased from 43.6% in 2001 to 73.0% in 2014. Compared with enrollees with incomes less than $40 000, those with incomes greater than $100 000 were 20% more likely to undergo cataract surgery at an ASC (odds ratio, 1.20; 95% CI, 1.12-1.29). Enrollees with better overall health were no more likely to undergo cataract surgery at an ASC (odds ratio, 1.00; 95% CI, 0.99-1.00) than at an HOPD. Enrollees who lived in communities without certificate of need laws were more than twice as likely to have surgery at an ASC (odds ratio, 2.49; 95% CI, 2.35-2.63). The proportion of cataract surgeries performed at ASCs from 2012 to 2014 varied considerably, from 1.6% in La Crosse, Wisconsin, to 98.8% in Pueblo, Colorado. Conclusions and Relevance: We observed a large shift in the site of cataract surgery from HOPDs to ASCs from 2001 to 2014. Future research is needed to assess the effect of this transition in site of surgical care on patient access to surgery, surgical outcomes, patient safety, and societal costs.

Factors Affecting Visits to the Emergency Department for Urgent and Nonurgent Ocular Conditions.

PURPOSE: To determine the frequency of emergency department (ED) visits for nonurgent and urgent ocular conditions and risk factors associated with ED use for nonurgent and urgent ocular problems. DESIGN: Retrospective, longitudinal cohort analysis. PARTICIPANTS: All enrollees aged 21 years or older in a United States managed care network during 2001-2014. METHODS: We identified all enrollees visiting an ED for ocular conditions identified by International Classification of Diseases, billing codes. Diagnosis is well-described as urgent, nonurgent, or other. We assessed the frequency of ED visits for urgent and nonurgent ocular conditions and how they changed over time. Next, we performed multivariable Cox regression modeling to determine factors associated with visiting an ED for urgent or nonurgent ocular conditions. MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence intervals (CIs) of visiting an ED for urgent or nonurgent ocular conditions. RESULTS: Of the 11 160 833 enrollees eligible for this study, 376 680 (3.4%) had 1 or more ED visit for an eye-related problem over a mean ± standard deviation of 5.4±3.3 years' follow-up. Among these enrolled, 86 473 (23.0%) had 1 or more ED visits with a nonurgent ocular condition and 25 289 (6.7%) had at least 1 ED visit with an urgent ocular condition. Use of the ED for nonurgent ocular problems was associated with younger age (P < 0.0001 for all comparisons), black race or Latino ethnicity (P < 0.0001 for both), male sex (P < 0.0001), lower income (P < 0.0001 for all comparisons), and those who frequently sought treatment at an ED for nonophthalmologic medical problems in a given year (P < 0.0001). Enrollees with established eye care professionals had a 10% reduced hazard of visiting the ED for nonurgent ocular conditions (adjusted HR, 0.90; 95% CI, 0.88-0.92; P < 0.0001). CONCLUSIONS: Nearly one-quarter of enrollees who visited the ED for an ocular problem received a diagnosis of a nonurgent condition. Better educating and incentivizing patients to seek care for nonurgent ocular diseases in an office-based setting could yield considerable cost savings without adversely affecting health outcomes and could allow EDs to better serve patients with more severe conditions.

Association of Daily Dosage and Type of Statin Agent With Risk of Open-Angle Glaucoma.

IMPORTANCE: There is growing evidence that statins may protect against the development or worsening of open-angle glaucoma (OAG). As researchers plan clinical trials to more definitively study whether statins indeed protect against OAG, it would be helpful to know whether specific daily dosages or types of statin confer a greater protective effect than others. OBJECTIVE: To assess whether the protective effect of statins on the risk of glaucoma varies depending on the daily dosage or type of statin taken. DESIGN, SETTING, AND PARTICIPANTS: Using claims data from January 2001 to December 2009, we observed 25 420 patients with no preexisting glaucoma and quantified exposure to statins and other cholesterol-lowering medications. Using multivariable regression modeling, we assessed the hazard of developing OAG and how it varied by the daily dosage or type of statin and whether any protective effect persists after accounting for baseline low-density lipoprotein level. EXPOSURES: Different daily dosages and types of statins. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for developing OAG with 95% CIs. RESULTS: Of the 25 420 patients who met the eligibility criteria for study inclusion, the mean (SD) age was 66.1 (5.8) years, and 14 112 (55.5%) were female. Additionally, 19 232 patients (84.1%) were white, 1252 (5.5%) were black, and 1558 (6.8%) were Latino. After accounting for baseline low-density lipoprotein levels, persons who filled prescriptions for statins continuously for 2 years had a 21% reduced risk of glaucoma compared with nonusers (adjusted HR, 0.79; 95% CI, 0.66-0.96; P = .02). There was no additional protective effect associated with taking the highest dosage of statins (80 mg) compared with a lower dosage (40 mg) (HR, 1.03; 95% CI, 0.59-1.80; P = .91). The protective effect of the following statins on OAG risk did not differ compared with atorvastatin, an inexpensive generic statin: lovastatin (HR, 1.09; 95% CI, 0.71-1.68; P = .69), cerivastatin (HR, 0.61; 95% CI, 0.09-4.41; P = .63), rosuvastatin (HR, 0.83; 95% CI, 0.48-1.44; P = .51), fluvastatin (HR, 0.89; 95% CI, 0.39-2.02; P = .78), pravastatin (HR, 1.29; 95% CI, 0.93-1.79; P = .13), and simvastatin (HR, 1.03; 95% CI, 0.83-1.29; P = .78). CONCLUSIONS AND RELEVANCE: Even after accounting for baseline low-density lipoprotein level, statin exposure continued to be associated with a reduction in OAG risk. Our study helps inform researchers of a reasonable daily dosage and type of statin to use when designing randomized clinical trials to assess the association between statin use and glaucoma.

Rates of Vitrectomy among Enrollees in a United States Managed Care Network, 2001-2012.

PURPOSE: To determine whether vitrectomy surgery rates have changed over the past decade and factors affecting the odds of undergoing this procedure. DESIGN: Retrospective, longitudinal cohort study. PARTICIPANTS: All enrollees 21 years of age or older between 2001 and 2012 in a United States managed care network. METHODS: Claims data from a managed care network were analyzed to identify all enrollees who underwent 1 vitrectomy or more each year from 2001 through 2012. Rates of vitrectomy per 1000 enrollees were computed each year from 2001 through 2012 for the entire group and separately for patients with and without diabetes mellitus. Multivariate logistic regression assessed factors affecting the odds of undergoing vitrectomy surgery. MAIN OUTCOME MEASURES: Annual rates of vitrectomy surgery from 2001 through 2012 and odds ratios (ORs) of undergoing a vitrectomy with 95% confidence intervals (CIs). RESULTS: Among the 11 161 907 eligible enrollees, 40 892 (0.4%) underwent vitrectomy over the 12-year period. The average age of those undergoing vitrectomy was 57±13 years. Overall vitrectomy rates increased 31% from 2001 to 2012 (from 1.47 to 1.92 per 1000 patients). During this same period, the vitrectomy rate among persons with diabetes mellitus decreased by 43% (from 5.84 to 3.31 per 1000 patients with diabetes). Women had 24% decreased odds of undergoing vitrectomy (adjusted odds ratio [OR], 0.76; 95% confidence interval [CI], 0.72-0.79). The odds of undergoing a vitrectomy were 17% greater for black persons (adjusted OR, 1.17; 95% CI, 1.07-1.27) and 7% higher for persons with diabetes (adjusted OR, 1.07; 95% CI, 1.01-1.14). CONCLUSIONS: Overall, we observed an increase in the vitrectomy rates per 1000 enrollees in this large managed care network over the course of the past decade. However, among persons with diabetes mellitus, vitrectomy rates declined substantially over this period. These changes may be explained, in part, by advances in surgical instrumentation and imaging methods to detect retinal diseases changing indications for surgery, improvements in diabetes care, and alternative treatment options for managing retinal conditions. These results may be useful for future planning of manpower needs and highlight the need for aggressive prevention of complications in black persons with diabetes.

Bupropion use and risk of open-angle glaucoma among enrollees in a large U.S. managed care network.

OBJECTIVE: Tumor Necrosis Factor (TNF) mediates retinal ganglion cell death in glaucoma. Anti-TNF drugs are neuroprotective in an animal model of glaucoma. It is unclear whether medications with anti-TNF properties such as bupropion have an impact on the risk of developing open-angle glaucoma (OAG) in humans. The purpose of this study is to determine whether bupropion use alters the risk of developing OAG. METHODS: Claims data for beneficiaries age ≥35 years with no pre-existing OAG enrolled in a large nationwide U.S. managed care network continuously for ≥4 years between 2001-2011 was analyzed to identify patients who had been newly-diagnosed with OAG. The amount of bupropion use as captured from outpatient pharmacy claims over a four-year period was also quantified for each beneficiary. Multivariable Cox regression modeling assessed the impact of bupropion and other antidepressant medications on the risk of developing OAG with adjustment for sociodemographic characteristics of the enrollees along with medical and ocular comorbidities. RESULTS: Of 638,481 eligible enrollees, 15,292 (2.4%) developed OAG. After adjustment for confounding factors including use of other antidepressant medication classes, each additional month of bupropion use was associated with a 0.6% reduced risk of OAG (HR = 0.994, (95% CI: 0.989-0.998), p = 0.007). Compared to nonusers, those with 24-48 months of bupropion use had a 21% reduced hazard (HR=0.79, (CI: 0.65-0.94), p = 0.0099) of OAG. This association did not differ among persons taking bupropion for depression or for other reasons (p-interaction = 0.82). There was no significant association between use of tricyclic antidepressants (HR = 1.000, (CI: 0.997-1.004), p = 0.95) or selective serotonin reuptake inhibitors (HR = 0.999, (CI: 0.997-1.001), p = 0.39) and development of OAG. CONCLUSION: These findings suggest bupropion use may be beneficial in reducing the risk of OAG. If prospective studies confirm the findings of this analysis, this may identify a novel therapeutic target for OAG.

Impact of the introduction of generic latanoprost on glaucoma medication adherence.

PURPOSE: To assess possible changes in medication adherence to prostaglandin analog (PGA) regimens among patients with open-angle glaucoma (OAG) after the initial introduction of generic PGAs. DESIGN: Longitudinal cohort analysis. PARTICIPANTS: Patients older than 40 years with OAG continuously enrolled in a nationwide managed-care network during 2009-2012 who used PGAs. METHODS: Mean adherence rates were calculated for topical PGA use during the 18 months before the introduction of generic latanoprost (September 2009-February 2011) and the 18 months after generic latanoprost became available (July 2011-December 2012). The rates were compared between persons who continued to use brand-name PGAs once generic latanoprost became available and others who switched to generic latanoprost. Multivariable logistic regression identified variables associated with an improvement or worsening of adherence of ≥25%. MAIN OUTCOME MEASURES: Mean adherence rates and odds of 25% or more improved or worsened adherence (with 95% confidence intervals [CIs]). RESULTS: A total of 8427 patients met the study eligibility criteria. Compared with persons switching to generic latanoprost, patients who continued taking brand name PGAs were 28% less likely to have improved adherence (odds ratio [OR], 0.72; 95% CI, 0.55-0.94) and 39% more likely to have reduced adherence (OR, 1.39; 1.04-1.86) of ≥25%. Improved adherence after the generic drug's introduction was also associated with higher monthly medication copay in the pregeneric period (P = 0.02), lower copay after introduction of the generic drug (P < 0.0001), and black race (OR, 1.25; 95% CI, 1.04-1.50). Six-hundred twelve patients (7.3%) discontinued all antiglaucoma interventions when generic latanoprost became available. CONCLUSIONS: Given that cost can significantly deter adherence, switching patients to generic medications may help improve patients' drug-regimen adherence. A considerable number of patients discontinued glaucoma drug use altogether when generic latanoprost became available. Ophthalmologists should work with insurers and pharmacists to prevent such discontinuation of use as generic forms of other PGA agents become available.

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.

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.

Reduced fluorescein angiography and fundus photography use in the management of neovascular macular degeneration and macular edema during the past decade.

PURPOSE: We assessed recent trends in the use of diagnostic testing for neovascular age-related macular degeneration (NVAMD) and macular edema (ME). METHODS: Claims data from a managed-care network were analyzed on patients with NVAMD (n = 22,954) or ME (n = 31,810) to assess the use of fluorescein angiography (FA), fundus photography (FP), and optical coherence tomography (OCT) from 2001 to 2009. Repeated-measures logistic regression was performed to compare patients' odds of undergoing these procedures in 2001, 2005, and 2009. In addition, the proportions of patients with an incident NVAMD or ME diagnosis in 2003 or 2008 who underwent FA, FP, and OCT were compared. RESULTS: From 2001 to 2009, among patients with NVAMD, the odds of undergoing OCT increased 23-fold, whereas the odds of receiving FA and FP decreased by 68% and 79%, respectively. Similar trends were observed for ME. From 2003 to 2008, the proportion of patients undergoing OCT within 1 year of initial diagnosis increased by 315% for NVAMD and by 143% for ME; the proportion undergoing OCT without FA within 1 year increased by 463% for NVAMD and by 216% for ME. CONCLUSIONS: Use of OCT increased dramatically during the past decade, whereas use of FA and FP declined considerably, suggesting that OCT may be replacing more traditional diagnostic testing in patients with NVAMD or ME. Future studies should evaluate whether this increased reliance on OCT instead of FA and FP affects patient outcomes.

Role of statins in the development and progression of age-related macular degeneration.

PURPOSE: To determine if statins are associated with the development or progression of age-related macular degeneration (AMD). METHODS: A large, national insurance claims database was reviewed to identify individuals aged 60 years or older who were enrolled for ≥2 years and had ≥1 visits to an eye provider. Prescription claims for statins within a 24-month look-back period and outpatient lipid laboratory values were also reviewed. Cox regression analysis was used to determine whether statin use was associated with the development of nonexudative or exudative AMD or progressing from nonexudative to exudative AMD. RESULTS: Of the 107,007 beneficiaries eligible for the nonexudative AMD analysis, 4,647 incident cases of nonexudative AMD occurred. Seven hundred and ninety-two incident cases of exudative AMD were found among the 113,111 beneficiaries eligible for the exudative AMD analysis. Of the 10,743 beneficiaries with known nonexudative AMD eligible for the progression model, 404 progressed to exudative AMD during their time in the plan. After multivariable analysis, statin use was not associated with the development of nonexudative AMD (P > 0.05). Statin use of >12 months was associated with an increased hazard for developing exudative AMD (P < 0.005). Among those taking statins, only enrollees with the highest lipid levels had an increased hazard of developing exudative AMD (P < 0.05). CONCLUSION: In those with elevated lipid levels, >1 year of statin use was associated with an increased hazard for exudative AMD. Lipid status influences the relationship between statins and the risk of AMD. Because of a number of limitations in study design, these observations warrant further study and should not be the rationale for any changes in the use of statins to treat dyslipidemias.

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.

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.

Racial disparities in the use of ancillary testing to evaluate individuals with open-angle glaucoma.

OBJECTIVE: To determine whether racial disparities exist in the use of ancillary testing to evaluate individuals with open-angle glaucoma. METHODS: We identified all enrollees aged 40 years and older in a large US managed care network with retinal or optic nerve conditions that could warrant the use of ancillary testing. Among persons with open-angle glaucoma or glaucoma suspects, we performed repeated-measures multivariable logistic regression to determine the odds and probabilities each year of undergoing visual field testing, fundus photography, and other ocular imaging for black, white, Hispanic, and Asian American men and women and compared the groups. RESULTS: Among the 797 879 eligible enrollees, 149 018 individuals had open-angle glaucoma. The odds of undergoing visual field testing decreased for all groups from 2001 through 2009, decreasing most for Hispanic men and women (63% and 57%, respectively) (adjusted odds ratio [AOR], 0.37; 95% CI, 0.31-0.43 and AOR, 0.43; 95% CI, 0.37-0.50, respectively) and least (36%) for Asian American men (AOR, 0.64; 95% CI, 0.51-0.80). By comparison, the odds of undergoing other ocular imaging increased for all groups from 2001 through 2009, increasing most (173%) for black men and women (AOR, 2.73; 95% CI, 2.34-3.18 for men and AOR, 2.73; 95% CI, 2.40-3.09 for women) and least (77%) for Hispanic women (AOR, 1.77; 95% CI, 1.49-2.09). CONCLUSION: Hispanic men and women had considerably reduced odds of undergoing visual field testing and other ocular imaging compared with other groups during the decade. Although increases in glaucoma testing have been noted in recent years among Hispanic men and women for some types of ancillary tests, efforts should be made to better understand and overcome some of the persistent barriers to monitoring for glaucoma in this group.

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.