Factors That Influence Clinician Prescribing of Corticosteroids for Acute Idiopathic and Multiple Sclerosis-Associated Optic Neuritis: A Qualitative Study.

BACKGROUND: Treatment with corticosteroids is common for patients with idiopathic and multiple sclerosis-associated optic neuritis (I/MS-ON). Yet, the Optic Neuritis Treatment Trial and meta-analyses confirm that few patients benefit and that visual benefit is of questionable clinical significance, short-lived, and comes with potential harms. The purpose of this study was to uncover the breadth of factors that underlie clinicians' treatment decisions and determine how these factors may influence corticosteroid use for I/MS-ON. METHODS: We performed semistructured, one-on-one, qualitative interviews with neurologists, neuro-ophthalmologists, and emergency department clinicians at 15 academic and private practices across the United States. The interview guide used the Theoretical Domain Framework and a vignette to explore numerous factors that might influence decision making for definite I/MS-ON. We analyzed transcripts using inductive thematic analysis to generate themes. RESULTS: A total of 22 clinicians were interviewed before thematic saturation was reached: 8 neuro-ophthalmologists, 8 neurologists, and 6 emergency medicine (EM) clinicians (2 physician assistants, 4 physicians). All neuro-ophthalmologists and nearly all neurologists (7 of 8) were aware of risks/benefits of corticosteroid treatment for I/MS-ON. However, neuro-ophthalmologists varied in their corticosteroid treatment recommendation (n = 3 recommended treatment, n = 2 recommended observation, n = 3 recommended shared decision making), whereas all neurologists recommended corticosteroids, indicating that knowledge of corticosteroid risk/benefit alone does not drive decision making. EM clinicians were not aware of risk/benefits of corticosteroid treatment for I/MS-ON and relied on the treatment recommendations of neurologists. Clinicians recommending corticosteroids held personal beliefs that corticosteroids benefit those with worse vision loss, relieve pain, allow earlier return to work, or have easily mitigated side effects. They also perceived that prescribing steroid was the principal method of "doing something," which fit a key provider role. Clinicians who did not recommend corticosteroids or were neutral perceived the risks as nontrivial, considered discussing treatment trade-offs as "doing something" and incorporated patient preferences. CONCLUSIONS: Knowledge of risk/benefits of corticosteroids are necessary but not sufficient for evidence-based I/MS-ON practice. Variation in how clinicians treat patients with acute I/MS-ON is influenced largely by psychosocial factors, such as beliefs about corticosteroid risk/benefit trade-offs and the role of the clinician to provide treatment. Interventions to support evidence-based decision making for I/MS-ON treatment will need to provide risk/benefit information to support clinicians with varying levels of expertise, incorporate patient preference, and normalize the option to observe.

The Role of Artificial Intelligence in Predicting Optic Neuritis Subtypes From Ocular Fundus Photographs.

BACKGROUND: Optic neuritis (ON) is a complex clinical syndrome that has diverse etiologies and treatments based on its subtypes. Notably, ON associated with multiple sclerosis (MS ON) has a good prognosis for recovery irrespective of treatment, whereas ON associated with other conditions including neuromyelitis optica spectrum disorders or myelin oligodendrocyte glycoprotein antibody-associated disease is often associated with less favorable outcomes. Delay in treatment of these non-MS ON subtypes can lead to irreversible vision loss. It is important to distinguish MS ON from other ON subtypes early, to guide appropriate management. Yet, identifying ON and differentiating subtypes can be challenging as MRI and serological antibody test results are not always readily available in the acute setting. The purpose of this study is to develop a deep learning artificial intelligence (AI) algorithm to predict subtype based on fundus photographs, to aid the diagnostic evaluation of patients with suspected ON. METHODS: This was a retrospective study of patients with ON seen at our institution between 2007 and 2022. Fundus photographs (1,599) were retrospectively collected from a total of 321 patients classified into 2 groups: MS ON (262 patients; 1,114 photographs) and non-MS ON (59 patients; 485 photographs). The dataset was divided into training and holdout test sets with an 80%/20% ratio, using stratified sampling to ensure equal representation of MS ON and non-MS ON patients in both sets. Model hyperparameters were tuned using 5-fold cross-validation on the training dataset. The overall performance and generalizability of the model was subsequently evaluated on the holdout test set. RESULTS: The receiver operating characteristic (ROC) curve for the developed model, evaluated on the holdout test dataset, yielded an area under the ROC curve of 0.83 (95% confidence interval [CI], 0.72-0.92). The model attained an accuracy of 76.2% (95% CI, 68.4-83.1), a sensitivity of 74.2% (95% CI, 55.9-87.4) and a specificity of 76.9% (95% CI, 67.6-85.0) in classifying images as non-MS-related ON. CONCLUSION: This study provides preliminary evidence supporting a role for AI in differentiating non-MS ON subtypes from MS ON. Future work will aim to increase the size of the dataset and explore the role of combining clinical and paraclinical measures to refine deep learning models over time.

Facilitators and Barriers to Weight Loss Among Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: Little is known about motivation for weight loss and barriers to weight loss among patients with idiopathic intracranial hypertension (IIH). Such information is crucial for developing tailored weight management recommendations and novel interventions. METHODS: We administered a survey to patients with IIH presenting to neuro-ophthalmology clinics at The University of Michigan Kellogg Eye Center (Michigan, USA) and St. Thomas' Hospital (London, England). Participants rated importance and motivation to lose weight (1-10 scale; 10 = extremely important/motivated). Facilitators and barriers to weight loss were assessed using open-ended survey questions informed by motivational interviewing methodology. Open-ended responses were coded by 2 team members independently using a modified grounded theory approach. Demographic data were extracted from medical records. Descriptive statistics were used to analyze quantitative responses. RESULTS: Of the 221 (43 Michigan and 178 London) patients with IIH (Table 1), most were female (n = 40 [93.0%] Michigan and n = 167 [94.9%] London). The majority of patients in the United States were White (n = 35 [81.4%] Michigan), and the plurality were Black in the United Kingdom (n = 67 [37.6%] London]) with a mean (SD) BMI of 38.9 kg/m2 (10.6 kg/m2) Michigan and 37.5 kg/m2 (7.7 kg/m2) London. Participants' mean (SD) level of importance to lose weight was 8.5 (2.2) (8.1 [2.3] Michigan and 8.8 [2.1] London), but their mean (SD) level of motivation to lose weight was 7.2 (2.2) (6.8 [2.4] Michigan and 7.4 [2.1] London). Nine themes emerged from the 992 open-ended coded survey responses grouped into 3 actionable categories: self-efficacy, professional resources (weight loss tools, diet, physical activity level, mental health, and physical health), and external factors (physical/environmental conditions, social influences, and time constraints). Most responses (55.6%; n = 551) were about barriers to weight loss. Lack of self-efficacy was the most discussed single barrier (N = 126; 22.9% total, 28.9% Michigan, and 20.4% London) and facilitator (N = 77; 17.5% total, 15.9% Michigan, and 18.7% London) to weight loss. Other common barriers were related to physical activity level (N = 79; 14.3% total, 13.2% Michigan, and 14.8% London) and diet (N = 79; 14.3% total, 9.4% Michigan, and 16.3% London). Commonly reported facilitators included improvements in physical activity level (N = 73; 16.6% total, 18.5% Michigan, and 15.1% London) and dietary changes (N = 76; 17.2% total, 16.4% Michigan, and 17.9% London). CONCLUSIONS: Patients with IIH believe weight loss is important. Self-efficacy was the single most mentioned important patient-identified barrier or facilitator of weight loss, but professional resource needs and external factors vary widely at the individual level. These factors should be assessed to guide selection of weight loss interventions that are tailored to individual patients with IIH.

A Validated Method to Identify Neuro-Ophthalmologists in a Large Administrative Claims Database.

BACKGROUND: Validated methods to identify neuro-ophthalmologists in administrative data do not exist. The development of such method will facilitate research on the quality of neuro-ophthalmic care and health care utilization for patients with neuro-ophthalmic conditions in the United States. METHODS: Using nationally representative, 20% sample from Medicare carrier files from 2018, we identified all neurologists and ophthalmologists billing at least 1 office-based evaluation and management (E/M) outpatient visit claim in 2018. To isolate neuro-ophthalmologists, the National Provider Identifier numbers of neuro-ophthalmologists in the North American Neuro-Ophthalmology Society (NANOS) directory were collected and linked to Medicare files. The proportion of E/M visits with International Classification of Diseases-10 diagnosis codes that best distinguished neuro-ophthalmic care ("neuro-ophthalmology-specific codes" or NSC) was calculated for each physician. Multiple logistic regression models assessed predictors of neuro-ophthalmology specialty designation after accounting for proportion of ophthalmology, neurology, and NSC claims and primary specialty designation. Sensitivity, specificity, and positive predictive value (PPV) for varying proportions of E/M visits with NSC were calculated. RESULTS: We identified 32,293 neurologists and ophthalmologists who billed at least 1 outpatient E/M visit claim in 2018 in Medicare. Of the 472 NANOS members with a valid individual National Provider Identifier, 399 (84.5%) had a Medicare outpatient E/M visit in 2018. The model containing only the proportion of E/M visits with NSC best predicted neuro-ophthalmology specialty designation (odds ratio 1.05 [95% confidence interval 1.04, 1.05]; P < 0.001; area under the receiver operating characteristic [AUROC] = 0.91). Model predictiveness for neuro-ophthalmology designation was maximized when 6% of all billed claims were for NSC (AUROC = 0.89; sensitivity: 84.0%; specificity: 93.9%), but PPV was low (14.9%). The threshold was unchanged when limited only to neurologists billing ≥1% ophthalmology claims or ophthalmologists billing ≥1% neurology claims, but PPV increased (33.3%). CONCLUSIONS: Our study provides a validated method to identify neuro-ophthalmologists who can be further adapted for use in other administrative databases to facilitate future research of neuro-ophthalmic care delivery in the United States.

Sociodemographic and Geographic Variation in Access to Neuro-Ophthalmologists in the United States.

BACKGROUND: Neuro-ophthalmologists have expertise in rare and complex disorders, but the ability of patients to access neuro-ophthalmic care has not been examined at a nationwide level. METHODS: Using the 2020 directory of all 502 members of the North American Neuro-Ophthalmology Society as a reference, we found the practice locations of 461 confirmed practicing members and converted each street address to latitude and longitude coordinates. We calculated the travel distance and time from each census tract to the nearest practice location and calculated population-weighted averages by state, region, and other prespecified factors. Choropleth maps were used to visualize the distribution of travel distances and times across the United States. RESULTS: California had the most practicing neuro-ophthalmologists out of any state (50), whereas 4 states (DE, MT, SD, and WY) had none. Washington, DC and MA had the most neuro-ophthalmologists per capita. The average travel distance and time to the nearest neuro-ophthalmologists were found to be 40.90 miles and 46.50 minutes, respectively, although a large portion of western plains and mountain regions had travel times of over 120 minutes. Patients in rural areas had longer travel times than those in urban areas, and Native American patients had the longest travel times of any racial or ethnic group. CONCLUSION: The travel time to see a neuro-ophthalmologist varies widely by state, region, and rurality, with Native American patients and rural patients being disproportionately affected. By identifying the areas with the greatest travel burdens, future policies can work to alleviate these potential barriers to care.

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.

Evaluation of Diplopia by Emergency Medicine Physicians and Consulting Neurologists.

BACKGROUND: Appropriate evaluation of diplopia requires separating serious from benign causes. If providers are not adept in this task, diagnosis of critical conditions may be delayed and unnecessary testing may result. METHODS: We studied the records of 100 consecutive patients who presented to an emergency department between 2010 and 2020 with diplopia as a prominent symptom. We rated the performance of emergency medicine physicians (EMPs) and consulting neurologists (CNs) in the examination, diagnosis, and ordering of diagnostic tests according to standards based on neuro-ophthalmologic consultation and the neuro-ophthalmologic literature. RESULTS: EMPs made no diagnosis or an incorrect diagnosis in 88 (88%) of 100 encounters. They ordered 14 unindicated and 12 incorrect studies, mostly noncontrast computed tomography scans. CNs made an incorrect diagnosis in 13 (31%) encounters. They ordered 6 unindicated and 2 incorrect studies. The total charge for unindicated and incorrect studies ordered by EMPs and CNs was $119,950. CONCLUSIONS: EMPs and CNs made frequent errors in the examination, diagnosis, and ordering of diagnostic studies, leading to inefficient care and unnecessary testing. EMPs largely delegated the evaluation of diplopia to their consultants. If such consultative support were not available, the care of diplopic patients would be delayed. CNs performed more complete examinations, but rarely enough to allow appreciation of the pattern of ocular misalignment, contributing to misdiagnoses and ordering errors. The identification of these provider errors allows for more targeted teaching in the evaluation of diplopia.

Change in Ophthalmic Clinicians' Attitudes Toward Telemedicine During the Coronavirus 2019 Pandemic.

Background: Ophthalmic clinicians report low confidence in telemedicine-based eye care delivery, but it may have changed given its rapid expansion during the coronavirus 2019 (COVID-19) pandemic. Introduction: The purpose of this study was to determine clinician confidence in telemedicine-based eye care services during COVID-19. Materials and Methods: An electronic survey was sent to clinicians at University of Michigan Kellogg Eye Center (April 17, 2020-May 6, 2020) when nonemergent in-person visits and procedures were restricted. The primary outcome was clinician confidence in using telemedicine-based eye care during COVID-19. Secondary outcomes included telemedicine utilization and its association with clinician confidence using Fisher's exact test. Results: Of the 88 respondents (90.7% response rate; n = 97 total), 83.0% (n = 73) were ophthalmologists and 17.0% (n = 15) were optometrists. Telemedicine utilization increased from 30.7% (n = 27) before the pandemic to 86.2% (n = 75) after the pandemic. Clinicians' confidence in their ability to use telemedicine varied with 28.6% (24/84) feeling confident/extremely confident, 38.1% (32/84) somewhat confident, and 33.3% (28/84) not-at-all confident. Most felt that telemedicine was underutilized (62.1%; 54/87) and planned continued use over the next year (59.8%; 52/87). Confident respondents were more likely to have performed three or more telemedicine visits (p = 0.003), to believe telemedicine was underutilized (p < 0.001), and to anticipate continued use of telemedicine (p = 0.009). Discussion: The majority of clinicians were at least somewhat confident about using telemedicine during the pandemic. Clinician confidence was associated with telemedicine visit volume and intention to continue using telemedicine. Conclusions: Policies that foster clinician confidence will be important to sustain telemedicine-based eye care delivery.

Multiple sclerosis relapse risk in the postoperative period: Effects of invasive surgery and anesthesia.

BACKGROUND: Postoperative multiple sclerosis (MS) relapses are a concern among patients and providers. OBJECTIVE: To determine whether MS relapse risk is higher postoperatively. METHODS: Data were extracted from medical records of MS patients undergoing surgery at a tertiary center (2000-2016). Conditional logistic regression estimated within-patient unadjusted and age-adjusted odds of postoperative versus preoperative relapse. RESULTS: Among 281 patients and 609 surgeries, 12 postoperative relapses were identified. The odds of postoperative versus preoperative relapse in unadjusted (odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.18-1.79; p = 0.33) or age-adjusted models (OR = 0.66, 95% CI = 0.20-2.16; p = 0.49) were not increased. CONCLUSIONS: Surgery/anesthesia exposure did not increase postoperative relapse risk. These findings require confirmation in larger studies.

Causes of Horner Syndrome: A Study of 318 Patients.

BACKGROUND: Some reports have indicated that when a cause for Horner syndrome can be determined, it is most often chest and neck tumors and stroke. Others have suggested that Horner syndrome is more frequently caused by surgical procedures in the neck and chest. These differences may be explained by disparate accrual methods. Therefore, we decided to compare the cause of Horner syndrome in cases where the diagnosis was confirmed by apraclonidine testing conducted by ophthalmologists to cases in which the diagnosis was made entirely on clinical grounds mostly by nonophthalmologists. METHODS: We applied a new search engine to the inpatient and outpatient electronic medical records text at the University of Michigan Medical Center from 1996 to 2018 for Horner syndrome with and without pharmacologic confirmation through ocular instillation of apraclonidine 0.5%. Among apraclonidine-confirmed cases, 159 met inclusion criteria. Among apraclonidine-unconfirmed cases, more than 2,000 cases were identified, so that we included only the first 159 cases that met inclusion criteria. In these 318 cases, we documented patient demographics, ophthalmologic features, imaging, underlying cause, and whether the cause was discovered before or after the diagnosis of Horner syndrome. RESULTS: In the cohort of 159 apraclonidine-confirmed cases of Horner syndrome, a cause was identified in 97 (61%). Procedures in the neck, chest, skull base, and paraspinal region accounted for most of the identified causes, with cervical carotid dissection the next most common cause. In a cohort of 159 cases of Horner syndrome not tested with apraclonidine because the clinical diagnosis appeared firm, procedures again accounted for the largest percentage, but tumor was the next most common cause. In both groups, when a cause for Horner syndrome could be identified, that cause was nearly always known before Horner syndrome was identified. However, in an important minority of cases, mostly involving carotid dissection or tumor, the identification of Horner syndrome was critical to the discovery of those conditions. CONCLUSIONS: The prevalence of causes of Horner syndrome depends on the accrual method. Among pharmacologically-confirmed cases, the cause was often undetermined or due to a preceding neck or chest procedure. Among pharmacologically-unconfirmed cases, a substantial proportion had also been caused by neck and chest procedures, but tumors in that region were also common. When a cause of Horner syndrome was found in both cohorts, it was usually known before Horner syndrome was discovered, making Horner syndrome an afterthought. However, in an important minority of cases where the cause was not yet known, the identification of Horner syndrome was valuable in leading to important diagnoses such as carotid dissection and tumor.

Validity of International Classification of Diseases Codes for Identifying Neuro-Ophthalmic Disease in Large Data Sets: A Systematic Review.

BACKGROUND: Administrative health claims data have been used for research in neuro-ophthalmology, but the validity of International Classification of Diseases (ICD) codes for identifying neuro-ophthalmic conditions is unclear. EVIDENCE ACQUISITION: We performed a systematic literature review to assess the validity of administrative claims data for identifying patients with neuro-ophthalmic disorders. Two reviewers independently reviewed all eligible full-length articles and used a standardized abstraction form to identify ICD code-based definitions for 9 neuro-ophthalmic conditions and their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A quality assessment of eligible studies was also performed. RESULTS: Eleven articles that met criteria for inclusion are as follows: 3 studies of idiopathic intracranial hypertension (PPV 54%-91% and NPV 74%-85%), 2 studies of giant cell arteritis (sensitivity 30%-96% and PPV 94%), 3 studies of optic neuritis (sensitivity 76%-99%, specificity 83%-100%, PPV 25%-100%, and NPV 98%-100%), 1 study of neuromyelitis optica (sensitivity 60%, specificity 100%, PPV 43%-100%, and NPV 98%-100%), 1 study of ocular motor cranial neuropathies (PPV 98%-99%), and 2 studies of myasthenia gravis (sensitivity 53%-97%, specificity 99%-100%, PPV 5%-90%, and NPV 100%). No studies met eligibility criteria for nonarteritic ischemic optic neuropathy, thyroid eye disease, and blepharospasm. Approximately 45.5% provided only one measure of diagnostic accuracy. Complete information about the validation cohorts, inclusion/exclusion criteria, data collection methods, and expertise of those reviewing charts for diagnostic accuracy was missing in 90.9%, 72.7%, 81.8%, and 36.4% of studies, respectively. CONCLUSIONS: Few studies have reported the validity of ICD codes for neuro-ophthalmic conditions. The range of diagnostic accuracy for some disorders and study quality varied widely. This should be taken into consideration when interpreting studies of neuro-ophthalmic conditions using administrative claims data.

Acute Isolated Sixth Nerve Palsy Caused by Unruptured Intradural Saccular Aneurysm.

BACKGROUND: Unruptured intracranial aneurysms that cause isolated sixth nerve palsies are usually located extradurally in the cavernous sinus or intradurally as part of fusiform enlargement of the parent artery. Intradural saccular aneurysms of the vertebrobasilar circulation are a rare but life-threatening cause of isolated sixth nerve palsy. We provide documentation of 2 such cases. METHODS: Case records of the Neuro-ophthalmology Clinics at the University of Michigan. RESULTS: A 56-year-old woman with an arteriosclerotic risk profile reported new diplopia and had an isolated left sixth nerve palsy caused by an unruptured saccular aneurysm of the anterior inferior cerebellar artery. It was successfully coiled, and the sixth nerve palsy markedly improved. A 62-year-old woman with an arteriosclerotic risk profile and new diplopia had an isolated right sixth nerve palsy caused by a large unruptured vertebral artery aneurysm. It was coiled and later stented and recoiled. These procedures isolated the aneurysm and relieved the sixth nerve palsy. CONCLUSIONS: Isolated sixth nerve palsies in these 2 older adult patients with arteriosclerotic risk profiles were caused by unruptured intradural vertebrobasilar aneurysms. This report adds documentation to a rare phenomenon that must be taken into consideration in deciding whether brain imaging is needed in isolated sixth nerve palsy.

Brand Medications and Medicare Part D: How Eye Care Providers' Prescribing Patterns Influence Costs.

PURPOSE: To quantify costs of eye care providers' Medicare Part D prescribing patterns for ophthalmic medications and to estimate the potential savings of generic or therapeutic drug substitutions and price negotiation. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Eye care providers prescribing medications through Medicare Part D in 2013. METHODS: Medicare Part D 2013 prescriber public use file and summary file were used to calculate medication costs by physician specialty and drug. Savings from generic or therapeutic drug substitutions were estimated for brand drugs. The potential savings from price negotiation was estimated using drug prices negotiated by the United States Veterans Administration (USVA). MAIN OUTCOME MEASURES: Total cost of brand and generic medications prescribed by eye care providers. RESULTS: Eye care providers accounted for $2.4 billion in total Medicare part D prescription drug costs and generated the highest percentage of brand name medication claims compared with all other providers. Brand medications accounted for a significantly higher proportion of monthly supplies by volume, and therefore, also by total cost for eye care providers compared with all other providers (38% vs. 23% by volume, P < 0.001; 79% vs. 56% by total cost, P < 0.001). The total cost attributable to eye care providers is driven by glaucoma medications, accounting for $1.2 billion (54% of total cost; 72% of total volume). The second costliest category, dry eye medications, was attributable mostly to a single medication, cyclosporine ophthalmic emulsion (Restasis, Allergan, Irvine, CA), which has no generic alternative, accounting for $371 million (17% of total cost; 4% of total volume). If generic medications were substituted for brand medications when available, $148 million would be saved (7% savings); if generic and therapeutic substitutions were made, $882 million would be saved (42% savings). If Medicare negotiated the prices for ophthalmic medications at USVA rates, $1.09 billion would be saved (53% savings). CONCLUSIONS: Eye care providers prescribe more brand medications by volume than any other provider group. Efforts to reduce prescription expenditures by eye care providers should focus on increasing the use of generic medications, primarily through therapeutic substitutions. Policy changes enabling Medicare to negotiate prescription drug prices could decrease costs to Medicare.

Accuracy and Reliability of a Handheld, Nonmydriatic Fundus Camera for the Remote Detection of Optic Disc Edema.

BACKGROUND: Optic disc edema can be an important indicator of serious neurological disease, but is poorly detected using the direct ophthalmoscope. Portable fundus photography may overcome this difficulty. INTRODUCTION: The purpose of this study was to determine the sensitivity and specificity of a handheld, nonmydriatic fundus camera for the detection of optic disc edema. MATERIALS AND METHODS: Retrospective review of nonmydriatic optic disc photographs taken with a portable fundus camera (Pictor Plus; Volk Optical, Mentor, OH) from the University of Michigan Neuro-Ophthalmology Clinics. We included 103 consecutive eyes with optic disc edema and 103 consecutive eyes without optic disc edema of 109 patients. Four masked neuro-ophthalmologists graded a single photograph of each optic disc presented in randomized order and documented the presence of optic disc edema. Sensitivity and specificity of graders' photographic interpretation was compared with clinical examinations. Reliability of assessments within and between graders was determined using kappa statistics. RESULTS: The sensitivity and specificity for detection of optic disc edema were 71.8-92.2% and 81.6-95.2%, respectively. Photos were found to be ungradable in 0-8.3% of cases. The intergrader reliabilities ranged from 0.60 [95% confidence interval (CI): 0.52-0.67] to 0.72 (95% CI: 0.66-0.77). Intragrader reliability ranged from 0.76 (95% CI: 0.63-0.92) to 0.82 (95% CI: 0.69-0.95). DISCUSSION: Photographs taken with portable, nonmydriatic technology met threshold sensitivity and specificity for remote screening for optic disc edema when performed by most, but not all graders. Reliability between graders was moderate-strong and strong within individual providers. CONCLUSIONS: Portable photography holds promise for use in remote screening of optic disc edema.

DNA methylation analysis of the temporal artery microenvironment in giant cell arteritis.

OBJECTIVE: To investigate the inflammatory response in giant cell arteritis (GCA) by characterising the DNA methylation pattern within the temporal artery microenvironment. METHODS: Twelve patients with non-equivocal histological evidence for GCA and 12 age-matched, sex-matched and ethnicity-matched controls with normal biopsies were studied. DNA was extracted from the affected portions of temporal artery tissue in patients with GCA and from histologically confirmed normal arteries in controls. Genome-wide DNA methylation status was evaluated using the Illumina Infinium HumanMethylation450 BeadChip Array. Differentially methylated loci between affected and unaffected arterial tissues were identified, and subsequent bioinformatic analysis performed. Immunohistochemistry was used to examine tissue expression patterns in temporal artery biopsies. RESULTS: We identified 1555 hypomethylated CG sites (853 genes) in affected temporal artery tissue from patients with GCA compared with normal controls. Gene ontology enrichment analysis of hypomethylated genes revealed significant representation in T cell activation and differentiation pathways, including both TH1 and TH17 signatures. Our DNA methylation data suggest a role for increased activity of the calcineurin/nuclear factor of activated T cells (NFAT) signalling pathway in GCA, confirmed by immunohistochemistry showing increased expression and nuclear localisation of NFAT1. NFAT signalling downstream targets such as interleukin (IL)-21/IL-21R and CD40L were overexpressed in GCA-affected arteries. Further, proinflammatory genes including TNF, LTA, LTB, CCR7, RUNX3, CD6, CD40LG, IL2, IL6, NLRP1, IL1B, IL18, IL21, IL23R and IFNG were hypomethylated in the cellular milieu of GCA arteries. CONCLUSIONS: We characterised the inflammatory response in GCA-affected arteries using 'epigenetic immunophenotyping' and identified molecules and pathways relevant to disease pathogenesis in GCA.

Demographic, Systemic, and Ocular Factors Associated with Nonarteritic Anterior Ischemic Optic Neuropathy.

OBJECTIVE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a devastating ocular condition causing permanent vision loss. Little is known about risk factors for developing this disease. We assessed demographic, systemic, and ocular factors associated with NAION. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Beneficiaries between 40 and 75 years old without NAION at baseline enrolled in a large U.S. managed care network. METHODS: Enrollees were monitored continuously for ≥2 years between 2001 and 2014 to identify those newly diagnosed with NAION (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code 377.41). All persons were under ophthalmic surveillance and all cases had ≥1 confirmatory ICD-9-CM code for NAION during follow-up. MAIN OUTCOME MEASURES: Multivariable Cox regression modeling was used to generate hazard ratios (HRs) with 95% confidence intervals (CIs) to describe the statistical relationship between selected demographic characteristics, systemic and ocular conditions, and the hazard of developing NAION. RESULTS: Of 1 381 477 eligible enrollees, 977 (0.1%) developed NAION during a mean ± standard deviation (SD) follow-up of 7.8±3.1 years. The mean ± SD age for NAION cases at the index date was 64.0±9.2 years vs. 58.4±9.4 years for the remainder of the beneficiaries. After adjustment for confounding factors, each additional year older was associated with a 2% increased hazard of NAION (HR = 1.02; 95% CI: 1.01-1.03). Female subjects had a 36% decreased hazard of developing NAION (HR = 0.64; 95% CI: 0.55-0.74) compared with male subjects. Compared with whites, Latinos had a 46% decreased hazard of developing NAION (HR = 0.54; 95% CI: 0.36-0.82), whereas African ancestry was not significantly associated with NAION (HR = 0.91; 95% CI: 0.72-1.15). Systemic diseases associated with NAION included hypertension (HR = 1.62; 95% CI: 1.26-2.07) and hypercoagulable states (HR = 2.46; 95% CI: 1.51-4.00). Although diabetes mellitus (DM) was not significantly associated with NAION compared with those without DM (P = 0.45), patients with end-organ involvement from DM had a 27% increased hazard of NAION relative to those with uncomplicated DM (HR = 1.27; 95% CI: 1.01-1.59). Ocular diseases associated with NAION were age-related macular degeneration (HR = 1.29; 95% CI: 1.08-1.54) and retinal vein occlusion (HR = 3.94; 95% CI: 3.11-4.99). CONCLUSIONS: Our study identified several modifiable risk factors that may be associated with NAION. Should future studies confirm these findings, they may offer opportunities to prevent or treat this debilitating condition.