Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

Alcohol Consumption and the Diversity of the Oral Microbiome in Postmenopausal Women.

BACKGROUND: Alcohol reduces neutrophil function and decreases salivary flow, which could affect the composition of the oral microbiome. OBJECTIVE: We hypothesized that the α- and ß-diversity of the oral microbiome and the relative abundance of bacterial taxa would differ by frequency and type of alcohol consumption. METHODS: We used a food frequency questionnaire to assess the frequency of consumption of beer, wine, and liquor (drinks/week) in a sample of 1179 postmenopausal women in the Osteoporosis and Periodontal Disease Study. Women were categorized as nondrinkers, drinking <1 drink/wk, ≥1 to <7 drinks/wk, or ≥7 drinks/wk for total alcohol consumption and for beer, wine, and liquor consumption. The composition and diversity of the oral microbiome was assessed from subgingival plaque samples using 16S ribosomal RNA amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) was used to examine ß-diversity (between-sample diversity) in the microbiome between alcohol consumption categories. Analysis of covariance was used to examine the mean α-diversity (within-sample diversity), assessed by the Shannon index (species evenness), Chao1 index (species richness), and observed operational taxonomic unit (OTU) count and the mean relative abundance of 245 bacterial taxa across alcohol consumption categories. RESULTS: Over half of the participants (67%) consumed alcohol, with 14% reporting ≥1 drink/d. The ß-diversity across categories of total alcohol consumption, but not categories of alcohol type, was statistically significantly different (P for PERMANOVA = 0.016). Mean α-diversity measures were statistically significantly higher (P < 0.05) in the highest category of total alcohol and wine consumption compared to nondrinkers; no significant associations were found for beer or liquor consumption. The relative abundance of 1 OTU, Selenomonassp._oral_taxon_133, was significantly lower in the highest level of total alcohol consumption compared to nondrinkers after adjustment for multiple comparisons. CONCLUSIONS: Alcohol consumption was associated with the diversity and composition of the subgingival microbiome.

Association between Healthy Eating Index-2020 and Oral Microbiome among Postmenopausal Women.

BACKGROUND: Dietary intake has been suggested to be associated with the oral microbiome, but no study has examined the association between overall diet quality and the oral microbiome. OBJECTIVE: This study aims to investigate the cross-sectional association between the Healthy Eating Index-2020 (HEI-2020) and the diversity and composition of the oral microbiome among participants in the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study. METHODS: In 1,175 postmenopausal women (mean age 67±7.0 yrs), we estimated the HEI-2020 scores for each woman from a food frequency questionnaire administered from 1997-2000. Bacterial DNA was extracted from subgingival plaque samples and analyzed using 16S ribosomal RNA sequencing. The alpha-diversity (within-sample diversity) and beta-diversity (between-sample diversity) across HEI-2020 quartiles were examined using ANCOVA and PERMANOVA, respectively. The associations between the HEI-2020 score and the relative abundance of microbial taxa were examined by linear regression models. The analyses were further conducted for individual components of the HEI-2020. RESULTS: No statistically significant associations were observed between the HEI-2020 scores and the alpha- or beta-diversity. However, greater consumption of seafood and plant proteins, as well as total protein, and lower consumption of added sugars, were positively associated with alpha-diversity. After we applied a false detection rate (FDR) correction, higher HEI-2020 scores were significantly associated with decreased abundance of Lautropia, Streptococcus gordonii, Cardiobacterium valvarum, and Cardiobacterium hominis, and increased abundance of Selenomonas sp. oral taxon 133 and Selenomonas dianae (FDR adjusted p-values<0.10). Additionally, 28 other taxa were identified as being associated with HEI-2020 components. CONCLUSION: While the HEI-2020 was associated with the composition, but not the diversity, of the oral microbiome, individual HEI-2020 components were associated with both its diversity and composition. Specific dietary components may have more impact on the diversity and composition of oral microbiome than overall diet quality assessed by the HEI-2020.

Association between dietary patterns and periodontal disease: The OsteoPerio cohort study.

AIM: To examine the association of dietary patterns with periodontal disease (PD) and its progression over 5 years. MATERIALS AND METHODS: Analyses involved 1197 post-menopausal women from the OsteoPerio cohort. Dietary patterns assessed include Healthy Eating Index-2015 (HEI), Alternative HEI (AHEI), Dietary Approaches to Stop Hypertension (DASH) and alternate Mediterranean Diet (aMed) at baseline (the average of two food frequency questionnaires administered between 1993 and 2001). At baseline and the 5-year follow-up, periodontal assessments evaluated alveolar crestal height (ACH), probing pocket depth (PPD), clinical attachment loss (CAL), percentage of gingival sites bleeding on probing (%BOP) and missing teeth due to PD. Linear and logistic regression were used to examine the associations. RESULTS: Cross-sectionally, HEI and aMed were associated with smaller CAL and %BOP; along with DASH, they were associated with a decreased odds of teeth missing due to PD. AHEI and aMed were associated with a decreased odds of severe PD. Prospectively, AHEI was associated with greater ACH progression. This association was attenuated to the null after loss of ACH was imputed for teeth lost due to PD over follow-up, or after excluding participants with diabetes, osteoporosis, hypertension or heart disease at baseline. CONCLUSIONS: Better adherence to healthy dietary patterns was associated with better PD measures cross-sectionally but greater progression of ACH over 5 years. The latter might be explained by incident tooth loss due to PD and pre-existing comorbidities.

NO EFFECT OF REAL-WORLD UNIVERSAL FACE MASKING ON POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS RATE AT A SINGLE TERTIARY ACADEMIC CENTER.

PURPOSE: To determine whether universal masking during COVID-19 altered rate and outcomes of postinjection endophthalmitis. METHODS: Retrospective, single-site, comparative, cohort study. Eyes diagnosed with endophthalmitis within 4 weeks of intravitreal injection at the University of Michigan from August 1, 2012, to November 15, 2022, were identified. Cases were considered "masking" between March 15, 2020, and November 15, 2022. Endophthalmitis rate, visual acuity, and microbial spectrum were investigated. RESULTS: There were 20 postinjection endophthalmitis cases out of 72,194 injections (0.028%; one in 3,571 injections) premasking and 10 of 38,962 with universal masking (0.026%; one in 3,846 injections; odds ratio 0.9; 95% [confidence interval]: 0.4-2.0). Referral from the community was unchanged with 32 cases referred premasking (0.35 cases/month) and 10 cases with masking (0.31 cases/month). Presenting mean the logarithm of the minimum angle of resolution visual acuity with masking of all postinjection endophthalmitis cases trended worse (2.35 ± 0.40) compared with premasking (2.09 ± 0.48; P = 0.05) with light perception visual acuity more common with masking (31.6% vs. 10.9%, P = 0.06). There was no delay in time from procedure to initial treatment ( P = 0.36), no difference in the rate of initial treatment with tap and inject (T/I), and similar positive-culture rates ( P = 0.77) between the cohorts. Visual acuity after 30 days of follow-up was clinically unchanged (∼20/500 vs. 20/400; P = 0.59). CONCLUSION: Universal masking had no effect on postinjection endophthalmitis rate or on the rate of culture-positive cases. Although presenting visual acuity appeared worse with masking, this was not statistically significant, and current treatment paradigms resulted in similar visual outcomes.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Predictors of Long-Term Visual Acuity in a Modern Cohort of Patients With Acute Idiopathic and Multiple Sclerosis-Associated Optic Neuritis.

BACKGROUND: For patients with idiopathic or multiple sclerosis (MS)-associated optic neuritis (ON), the largest multicenter clinical trial (Optic Neuritis Treatment Trial [ONTT]) showed excellent visual outcomes and baseline high-contrast visual acuity (HCVA) was the only predictor of HCVA at 1 year. We aimed to evaluate predictors of long-term HCVA in a modern, real-world population of patients with ON and compare with previously published ONTT models. METHODS: We performed a retrospective, longitudinal, observational study at the University of Michigan and the University of Calgary evaluating 135 episodes of idiopathic or MS-associated ON in 118 patients diagnosed by a neuro-ophthalmologist within 30 days of onset (January 2011-June 2021). Primary outcome measured was HCVA (Snellen equivalents) at 6-18 months. Multiple linear regression models of 107 episodes from 93 patients assessed the association between HCVA at 6-18 months and age, sex, race, pain, optic disc swelling, symptoms (days), viral illness prodrome, MS status, high-dose glucocorticoid treatment, and baseline HCVA. RESULTS: Of the 135 acute episodes (109 Michigan and 26 Calgary), median age at presentation was 39 years (interquartile range [IQR], 31-49 years), 91 (67.4%) were women, 112 (83.0%) were non-Hispanic Caucasians, 101 (75.9%) had pain, 33 (24.4%) had disc edema, 8 (5.9%) had a viral prodrome, 66 (48.9%) had MS, and 62 (46.6%) were treated with glucocorticoids. The median (IQR) time between symptom onset and diagnosis was 6 days (range, 4-11 days). The median (IQR) HCVA at baseline and at 6-18 months were 20/50 (20/22, 20/200) and 20/20 (20/20, 20/27), respectively; 62 (45.9%) had better than 20/40 at baseline and 117 (86.7%) had better than 20/40 at 6-18 months. In linear regression models (n = 107 episodes in 93 patients with baseline HCVA better than CF), only baseline HCVA (ß = 0.076; P = 0.027) was associated with long-term HCVA. Regression coefficients were similar and within the 95% confidence interval of coefficients from published ONTT models. CONCLUSIONS: In a modern cohort of patients with idiopathic or MS-associated ON with baseline HCVA better than CF, long-term outcomes were good, and the only predictor was baseline HCVA. These findings were similar to prior analyses of ONTT data, and as a result, these are validated for use in conveying prognostic information about long-term HCVA outcomes.

Trends in Glaucoma Surgeries Performed by Glaucoma Subspecialists versus Nonsubspecialists on Medicare Beneficiaries from 2008 through 2016.

PURPOSE: To characterize the use of laser and incisional glaucoma surgeries among Medicare beneficiaries from 2008 through 2016 and to compare the use of these surgeries by glaucoma subspecialists versus nonsubspecialists. DESIGN: Retrospective, observational analysis. PARTICIPANTS: Medicare beneficiaries (n = 1 468 035) undergoing ≥1 laser or incisional glaucoma surgery procedure during 2008 through 2016. METHODS: Claims data from a 20% sample of enrollees in fee-for-service Medicare throughout the United States were analyzed to identify all laser and incisional glaucoma surgeries performed from 2008 through 2016. We assessed use of traditional incisional glaucoma surgery techniques (trabeculectomy and glaucoma drainage implant [GDI] procedure) and microinvasive glaucoma surgery (MIGS). Enrollee and procedure counts were multiplied by 5 to estimate use throughout all of Medicare. Linear regression was used to compare trends in use of glaucoma surgeries between ophthalmologists who could be characterized as glaucoma subspecialists versus nonsubspecialists. MAIN OUTCOME MEASURES: Numbers of laser and incisional glaucoma surgeries performed overall and stratified by glaucoma subspecialist status. RESULTS: The number of Medicare beneficiaries undergoing any glaucoma therapeutic procedure increased by 10.6%, from 218 375 in 2008 to 241 565 in 2016. The total number of traditional incisional glaucoma surgeries decreased by 11.7%, from 37 225 to 32 885 (P = 0.02). The total number of MIGS procedures increased by 426% from 13 705 in 2012 (the first year MIGS codes were available) to 58 345 in 2016 (P = 0.001). Throughout the study period, glaucoma subspecialists performed most of the trabeculectomies (76.7% in 2008, 83.1% in 2016) and GDI procedures (77.7% in 2008, 80.6% in 2016). Many MIGS procedures were performed by nonsubspecialists. The proportions of endocyclophotocoagulations, iStent (Glaukos; San Clemente, CA) insertions, goniotomies, and canaloplasties performed by glaucoma subspecialists in 2016 were 22.0%, 25.2%, 56.9%, and 62.8%, respectively. CONCLUSIONS: From 2008 through 2016, a large shift in practice from traditional incisional glaucoma surgeries to MIGS procedures was observed. Although glaucoma subspecialists continue to perform most traditional incisional glaucoma surgeries, many MIGS procedures are performed by nonsubspecialists. These results highlight the importance of training residents in performing MIGS procedures and managing these patients perioperatively. Future studies should explore the impact of this shift in care on outcomes and costs.

Vision impairment and depression among older adults in low- and middle-income countries.

OBJECTIVES: To investigate the association between visual impairment (VI) and depression in low- and middle-income countries (LMICs) and the mediating role of disability and social participation. METHODS/DESIGN: The World Health Organization Study on global AGEing and adult health (SAGE) provided data on objective and subjective visual function, depression, disability (WHODAS-12), and social participation for nationally representative samples of adults 50 years and older in China, India, Ghana, Mexico, Russia, and South Africa. Multivariable logistic and linear models were used to test the association between VI and depression and the indirect pathways through disability and social participation. Analyses were adjusted for sociodemographics, medical comorbidities, and complex survey design features. RESULTS: Visual acuity was worse in respondents with depression compared to those without depression in China (0.32 vs 0.23 logMAR; P < .001), Ghana (0.26 vs 0.18 logMAR; P < .001), and India (0.36 vs 0.30 logMAR; P < .001); self-reported vision was also significantly worse in these three countries, but not in Mexico, Russia, or South Africa. Greater disability significantly mediated the association of both objective and self-reported VI with depression in China and India. Social participation significantly mediated the association between subjective vision and depression in Ghana. CONCLUSIONS: There is variability in the association between VI and depression across LMICs and in the mediating role of disability and social participation. Culture-specific instruments may be needed to better characterize the association between VI and depression and further research is needed to assess causality.

Imaging Errors in Distinguishing Pituitary Adenomas From Other Sellar Lesions.

BACKGROUND: Pituitary adenomas and nonadenomatous lesions in the sellar region may be difficult to distinguish by imaging yet that distinction is critical in guiding management. The nature of the diagnostic errors in this setting has not been well documented. METHODS: Two neurosurgeons and 2 neuroradiologists of differing experience levels viewed deidentified MRIs of 18 nonadenomatous sellar lesions and 21 adenomas. They recorded their diagnoses, the imaging features they used to make those diagnoses, and their confidence in making those diagnoses. RESULTS: Among the 18 nonadenoma cases, 11 (61%) were incorrectly diagnosed as adenoma by at least 1 reader, including Rathke cleft cyst, plasmacytoma, aneurysm, craniopharyngioma, chordoma, Langerhans cell histiocytosis, metastasis, and undifferentiated sinonasal carcinoma. Among the 21 adenoma cases, 8 (38%) were incorrectly diagnosed by at least 1 reader as craniopharyngioma, Rathke cleft cyst, sinonasal carcinoma, hemangioblastoma, and pituitary hyperplasia. Incorrect imaging diagnoses were made with high confidence in 13% of readings. Avoidable errors among the nonadenomatous cases occurred when readers failed to appreciate that the lesion was separate from the pituitary gland. Unavoidable errors in those cases occurred when the lesions were so large that the pituitary gland had been obliterated or the imaging features of a nonadenomatous lesion resembled those of a cystic pituitary adenoma. Avoidable errors in misdiagnosis of adenomas as nonadenomas occurred when readers failed to appreciate features highly characteristic of adenomas. An unavoidable error occurred because a cystic adenoma had features correctly associated with craniopharyngioma. CONCLUSIONS: Errors in imaging differentiation of pituitary adenoma from nonadenomatous lesions occurred often and sometimes with high confidence among a small sample of neurosurgeons and neuroradiologists. In the misdiagnosis of nonadenomatous lesions as adenomas, errors occurred largely from failure to appreciate a separate pituitary gland, but unavoidable errors occurred when large lesions had obliterated this distinguishing feature. In the misdiagnosis of adenomas as nonadenomatous lesions, avoidable errors occurred because readers failed to recognize imaging features more characteristic of adenomas and because cystic adenomas share features with craniopharyngiomas and Rathke cleft cysts. Awareness of these errors should lead to improved management of sellar lesions.

Visual Outcomes in Surgically Treated Intracranial Meningiomas.

BACKGROUND: Intracranial meningiomas that arise from the medial sphenoid ridge, anterior clinoid process, tuberculum sellae, or planum sphenoidale often impair vision by compressing the optic nerves and optic chiasm. Although many studies have reported visual outcome following surgery for these tumors, documentation has often been incomplete and not validated by patient self-report. METHODS: Retrospective study of 40 patients drawn from a single, academic, medical center. We used a unique method of assessing visual outcome based on whether the change in visual function affected the preoperatively better-sighted or worse-sighted eye in the belief that this method would correlate with effects on activities of daily living (ADL). To elicit patient self-reports of those effects, we conducted telephone interviews of 25 patients with a standard questionnaire. We also assessed putative ophthalmic, imaging, and surgical predictors of visual outcome. RESULTS: Visual improvement occurred in 61% of patients with preoperative monocular visual dysfunction, but only 22% of patients reported improvement in their ability to conduct ADL, and 17% lost vision. Visual outcomes were better in patients with preoperative binocular visual dysfunction, where visual improvement occurred in 73% and no patient lost vision in the preoperatively better-sighted eye. However, only 27% of patients with preoperative binocular visual dysfunction reported improvement in their ability to conduct ADL. Long duration of vision impairment, presence of optic disc pallor, large tumor size, and imaging-based preoperative optic canal involvement did not preclude a favorable visual outcome. Aggressive surgical reduction in displacement of the optic nerves was not necessary to obtain a favorable visual outcome and sometimes led to an unfavorable visual outcome. CONCLUSIONS: In this study, surgery often improved vision, especially in patients with preoperative binocular visual dysfunction. But patients indicated that the effect on their ability to perform ADL was more modest. Moreover, 17% of patients with preoperative monocular visual dysfunction lost vision in the only affected eye, often to a considerable degree. In those patients, surgery would be justified primarily to relieve the concern of having a large brain tumor and to prevent tumor growth. Preoperative ophthalmic and imaging features poorly predicted visual outcomes. Favorable visual outcomes occurred without aggressive surgical debulking of the tumors.

Perceived Electrical Injury: Misleading Symptomology Due to Multisensory Stimuli.

BACKGROUND: An electrical accident victim's recollection is often distorted by Bayesian inference in multisensory integration. For example, hearing the sound and seeing the bright flash of an electrical arc can create the false impression that someone had experienced an electrical shock. These subjects will often present to an emergency department seeking either treatment or reassurance. CASE REPORTS: We present seven cases in which the subjects were startled by an electrical shock (real or perceived) and injury was reported. Calculations of the current and path were used to allocate causality between the shock and a history of chronic disease or previous trauma. In all seven cases, our analysis suggests that no current was passed through the body. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Symptomology seen as corroborating may actually be confounding. Witness and survivor descriptions of electrical shocks are fraught with subjectivity and misunderstanding. Available current is usually irrelevant and overemphasized, such as stress on a 100-ampere welding source, which is orders of magnitude beyond lethal limits. History can also be biased for a number of reasons. Bayesian inference in multisensory perception can lead to a subject sincerely believing they had experienced an electrical shock. Determination of the current pathway and calculations of the amplitude and duration of the shock can be critical for understanding the limits and potential causation of electrical injury.

Personalized Prediction of Glaucoma Progression Under Different Target Intraocular Pressure Levels Using Filtered Forecasting Methods.

PURPOSE: To generate personalized forecasts of how patients with open-angle glaucoma (OAG) experience disease progression at different intraocular pressure (IOP) levels to aid clinicians with setting personalized target IOPs. DESIGN: Secondary analyses using longitudinal data from 2 randomized controlled trials. PARTICIPANTS: Participants with moderate or advanced OAG from the Collaborative Initial Glaucoma Treatment Study (CIGTS) or the Advanced Glaucoma Intervention Study (AGIS). METHODS: By using perimetric and tonometric data from trial participants, we developed and validated Kalman Filter (KF) models for fast-, slow-, and nonprogressing patients with OAG. The KF can generate personalized and dynamically updated forecasts of OAG progression under different target IOP levels. For each participant, we determined how mean deviation (MD) would change if the patient maintains his/her IOP at 1 of 7 levels (6, 9, 12, 15, 18, 21, or 24 mmHg) over the next 5 years. We also model and predict changes to MD over the same time horizon if IOP is increased or decreased by 3, 6, and 9 mmHg from the level attained in the trials. MAIN OUTCOME MEASURES: Personalized estimates of the change in MD under different target IOP levels. RESULTS: A total of 571 participants (mean age, 64.2 years; standard deviation, 10.9) were followed for a mean of 6.5 years (standard deviation, 2.8). Our models predicted that, on average, fast progressors would lose 2.1, 6.7, and 11.2 decibels (dB) MD under target IOPs of 6, 15, and 24 mmHg, respectively, over 5 years. In contrast, on average, slow progressors would lose 0.8, 2.1, and 4.1 dB MD under the same target IOPs and time frame. When using our tool to quantify the OAG progression dynamics for all 571 patients, we found no statistically significant differences over 5 years between progression for black versus white, male versus female, and CIGTS versus AGIS participants under different target IOPs (P > 0.05 for all). CONCLUSIONS: To our knowledge, this is the first clinical decision-making tool that generates personalized forecasts of the trajectory of OAG progression at different target IOP levels. This approach can help clinicians determine appropriate, personalized target IOPs for patients with OAG.

Contrast sensitivity deficits in patients with mutation-proven inherited retinal degenerations.

BACKGROUND: Patients with retinal diseases frequently complain of poor visual function even when visual acuity is relatively unaffected. This clinical finding has been attributed to deficits in contrast sensitivity (CS). The purpose of our study was to evaluate the CS in patients with clinical and genetic diagnosis of inherited retinal degeneration (IRD) and relatively preserved visual acuity. METHODS: Seventeen patients (30 eyes) with IRD and visual acuity of 20/40 or better, and 18 controls (18 eyes) without any ocular condition underwent slit lamp examination, visual acuity testing via standard Snellen chart testing, CS testing via the Quick Contrast Sensitivity Function (QCSF), and Spectral Domain Optical Coherence Tomography (SD-OCT). CS were measured at 1.0, 1.5, 3.0, 6.0, 12.0, and 18.0 cycles per degree (cpd). T tests with general estimated equations were used to compare CS between groups. Wald chi square followed by pairwise comparisons was used to compare CS between multiple groups. RESULTS: We included 12 patients with rod-cone dystrophy (RCD), 3 patients with Stargardt disease (STGD) and 2 patients with Best disease. Patients with IRD had significantly worse CS than controls (p < 0.001) in all spatial frequencies. Patients with STGD had more marked deficits in CS than patients with Best disease (p < 0.001) and RCD (p < 0.001) despite having similar visual acuities. CONCLUSION: Patients with IRD, especially patients with STGD with relatively preserved visual acuity have marked deficits in CS when measured across a range of spatial frequencies. We recommend that clinical trials for STGD incorporate CS measured over a range of spatial frequencies as a secondary clinical endpoint for monitoring visual function. CS may provide an explanation for complaints of visual dysfunction when visual acuity is not significantly altered.

Testability Study of the Titmus V3 Test in Pre-school Children.

SIGNIFICANCE: Vision screening can identify people who have vision problems requiring a comprehensive examination. When children are screened, the most prevalent serious problem is amblyopia secondary to uncorrected ametropia. Screening also identifies strabismus, which can lead to loss of binocularity. Early diagnosis permits treatment with restoration of balanced vision and binocularity. PURPOSE: The study evaluated the testability of the Titmus V3 Vision Screener as a method to screen vision and strabismus in pre-school children. METHODS: Pre-school children between 36 and 66 months of age underwent vision screening in six Michigan counties. The State of Michigan screening consists of the LEA Symbols test for visual acuity and the stereo butterfly for near-strabismus testing. The proposed Titmus V3 screening tests were the LEA Symbols slide for vision and near-strabismus test slide. Primary and secondary objectives of this study were to evaluate the percentage of pre-school children who completed the Titmus V3 screening tests for vision and near strabismus and factors associated with an inability to complete the tests, contrasting the pass/fail results between the state and Titmus V3 results. RESULTS: Two-hundred sixty-three children were tested. The percentages of children unable to score on the Titmus V3 instrument versus the state's LEA Symbols test were 16.0% and 5.3%, respectively. The percentage of children unable to score on the Titmus V3 near-strabismus test slide was 6.9 versus 3.4% on the State of Michigan stereo butterfly test. Younger age at testing was the most important factor associated with the inability to complete testing. CONCLUSIONS: Because of testability limitations and higher failure rates relative to the State of Michigan testing methods, the Titmus V3 screening device is not a feasible alternative to the standard methods used by the State of Michigan for vision and near-strabismus screening among the pre-school subjects we tested.

Large Disparities in Receipt of Glaucoma Care between Enrollees in Medicaid and Those with Commercial Health Insurance.

PURPOSE: To determine whether the type of health insurance a patient possesses and a patient's race/ethnicity affect receipt of common tests to monitor open-angle glaucoma (OAG). DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: A total of 21 766 persons aged ≥40 years with newly diagnosed OAG between 2007 and 2011 enrolled in Medicaid or a large United States managed care network. METHODS: We determined the proportion of patients with newly diagnosed OAG who underwent visual field (VF) testing, fundus photography (FP), other ocular imaging (OOI), or none of these tests within the first 15 months after initial OAG diagnosis. Multivariable logistic regression was used to assess the extent by which health insurance type and race/ethnicity affected the odds of undergoing glaucoma testing. MAIN OUTCOME MEASURES: Odds ratios (OR) of undergoing VF testing, FP, OOI, or none of these tests in the 15 months after initial OAG diagnosis with 95% confidence intervals (CI). RESULTS: A total of 18 372 persons with commercial health insurance and 3394 Medicaid recipients met the study inclusion criteria. The proportions of persons with commercial health insurance with newly diagnosed OAG who underwent VF, FP, and OOI were 63%, 22%, and 54%, respectively, whereas the proportions were 35%, 19%, and 30%, respectively, for Medicaid recipients. Compared with those with commercial health insurance, Medicaid recipients were 234% more likely to not receive any glaucoma testing in the 15 months after initial diagnosis (OR = 3.34; 95% CI, 3.07-3.63). After adjustment for confounders, whites with OAG enrolled in Medicaid had 198% higher odds of receiving no glaucoma testing compared with whites possessing commercial health insurance (OR = 2.98; 95% CI, 2.66-3.33). Blacks with Medicaid insurance demonstrated 291% higher odds (OR = 3.91; 95% CI, 3.40-4.49) of not receiving any glaucoma testing compared with blacks with commercial health insurance. CONCLUSIONS: Irrespective of race/ethnicity, Medicaid recipients with OAG are receiving substantially less glaucoma testing compared with persons with commercial health insurance. Disparities in testing are observed across all races/ethnicities but were most notable for blacks. These findings are particularly disconcerting because blacks are more likely than whites to go blind from OAG and there are disproportionately more blacks in Medicaid. Efforts are needed to improve the quality of glaucoma care for Medicaid recipients, especially racial minorities.

Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.

PURPOSE: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR. DESIGN: Retrospective observational longitudinal cohort study. PARTICIPANTS: Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network. METHODS: In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A1c fraction (HbA1c). MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR. RESULTS: Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA1c, the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis. CONCLUSIONS: Youths with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease.

Assessing Geographic Variation in Strabismus Diagnosis among Children Enrolled in Medicaid.

PURPOSE: To determine how strabismus diagnosis varies within a given community and across communities among children with Medicaid health insurance. DESIGN: Retrospective cohort analysis. PARTICIPANTS: Children aged ≤10 years enrolled in Medicaid in Michigan or North Carolina during 2009. METHODS: Children who met the study inclusion criteria were identified from the Medicaid Analytic Extract database, which includes claims data for all children enrolled in Medicaid throughout the United States. Residential location was determined by the last known 5-digit ZIP code for each child, which was linked to the centroid of a ZIP Code Tabulation Area (ZCTA) for geo-referencing and spatial analyses. International Classification of Diseases, 9th Revision, Clinical Modification billing codes were used to identify children diagnosed with strabismus (code 378.xx). Bayesian hierarchical intrinsic conditional autoregressive spatial probit models were used to determine the risk of a child receiving a strabismus diagnosis in communities throughout Michigan and North Carolina. Maps display communities (ZCTAs) where the 95% credible intervals for the spatial random effects estimates do not cross zero, allowing for identification of locations with increased and decreased strabismus diagnosis risk relative to other communities in the states. MAIN OUTCOME MEASURES: Likelihood of receiving a diagnosis of strabismus. RESULTS: In 2009, among 519 212 eligible children in Michigan, 7535 (1.5%) received ≥1 strabismus diagnosis, and in North Carolina, 5827 of 523 886 eligible children (1.1%) were diagnosed with strabismus. In both states, the proportion receiving a strabismus diagnosis among black (0.9% in Michigan; 0.7% in North Carolina) and Hispanic (1.1% in Michigan; 0.8% in North Carolina) children was lower than the proportion for white children (1.8% in Michigan; 1.6% in North Carolina). Children living in poorer communities in both states were less likely to be diagnosed with strabismus independent of their race/ethnicity. CONCLUSIONS: A child's likelihood of being diagnosed with strabismus is associated with characteristics of the residential community where he or she resides. The findings of this study highlight the importance of ensuring that children who live in less affluent communities have access to the necessary services and eye care professionals to properly diagnose and treat them for this condition.

Evaluation of Screening for Retinopathy of Prematurity by ROPtool or a Lay Reader.

PURPOSE: To determine if (1) tortuosity assessment by a computer program (ROPtool, developed at the University of North Carolina, Chapel Hill, and Duke University, and licensed by FocusROP) that traces retinal blood vessels and (2) assessment by a lay reader are comparable with assessment by a panel of 3 retinopathy of prematurity (ROP) experts for remote clinical grading of vascular abnormalities such as plus disease. DESIGN: Validity and reliability analysis of diagnostic tools. PARTICIPANTS: Three hundred thirty-five fundus images of prematurely born infants. METHODS: Three hundred thirty-five fundus images of prematurely born infants were obtained by neonatal intensive care unit nurses. A panel of 3 ROP experts graded 84 images showing vascular dilatation, tortuosity, or both and 251 images showing no evidence of vascular abnormalities. These images were sent electronically to an experienced lay reader who independently graded them for vascular abnormalities. The images also were analyzed using the ROPtool, which assigns a numerical value to the level of vascular abnormality and tortuosity present in each of 4 quadrants or sectors. The ROPtool measurements of vascular abnormalities were graded and compared with expert panel grades with a receiver operating characteristic (ROC) curve. Grades between human readers were cross-tabulated. The area under the ROC curve was calculated for the ROPtool, and sensitivity and specificity were computed for the lay reader. MAIN OUTCOME MEASURES: Measurements of vascular abnormalities by ROPtool and grading of vascular abnormalities by 3 ROP experts and 1 experienced lay reader. RESULTS: The ROC curve for ROPtool's tortuosity assessment had an area under the ROC curve of 0.917. Using a threshold value of 4.97 for the second most tortuous quadrant, ROPtool's sensitivity was 91% and its specificity was 82%. Lay reader sensitivity and specificity were 99% and 73%, respectively, and had high reliability (κ, 0.87) in repeated measurements. CONCLUSIONS: ROPtool had very good accuracy for detection of vascular abnormalities suggestive of plus disease when compared with expert physician graders. The lay reader's results showed excellent sensitivity and good specificity when compared with those of the expert graders. These options for remote reading of images to detect vascular abnormalities deserve consideration in the quest to use telemedicine with remote reading for efficient delivery of high-quality care and to detect infants requiring bedside examination.

Response to ruxolitinib in patients with intermediate-1-, intermediate-2-, and high-risk myelofibrosis: results of the UK ROBUST Trial.

Myelofibrosis is characterized by splenomegaly and debilitating constitutional symptoms that negatively impact patients' quality of life. ROBUST, a UK, open-label, phase II study, evaluated the safety and efficacy of ruxolitinib in patients with myelofibrosis (N = 48), including intermediate-1 risk patients. The primary composite endpoint was the proportion of patients achieving treatment success [≥ 50% reduction in palpable spleen length and/or a ≥ 50% decrease in Myelofibrosis Symptom Assessment Form Total Symptom Score (MF-SAF TSS)] at 48 weeks. This was the first time that efficacy of ruxolitinib in myelofibrosis has been evaluated based on these criteria and the first time the MF-SAF was used in a population of patients solely from the United Kingdom. Overall, 50% of patients and 57% of intermediate-1 risk patients, achieved treatment success; reductions in spleen length and symptoms were observed in all risk groups. The majority of patients (66.7%) experienced ≥ 50% reductions from baseline in spleen length at any time. Improvements in MF-SAF TSS were seen in 80.0%, 72.7%, and 72.2% of intermediate-1, intermediate-2, and high-risk patients, respectively. Consistent with other studies of ruxolitinib, the most common haematological adverse events were anaemia and thrombocytopenia. Results indicate that most patients with myelofibrosis, including intermediate-1 risk patients, may benefit from ruxolitinib treatment.