Staged Excision Technique for Periocular Cutaneous Melanoma: Long-Term Outcomes of the Square Procedure.

PURPOSE: To examine the long-term outcome of the staged excision via the square procedure for the treatment of periocular thin cutaneous melanoma. METHODS: A retrospective chart review of 95 periocular cutaneous melanoma-in-situ and microinvasive melanoma tumors that were treated with the square procedure between April 1, 1994 and December 31, 2018 at the University of Michigan. Demographic and clinical data were evaluated. RESULTS: Of 95 cases, 19 (20%) were atypical junctional melanocytic proliferation with features of early melanoma-in-situ, 63 (66.3%) were melanoma-in-situ and 13 (13.7) were microinvasive melanoma with Breslow depth less than 1 mm. Tumor-free margins were achieved with a median margin of 10 mm (range 5-40 mm). Most cases (68.4%) required multiple excision stages. Surgical revision was necessary in 17.9% of cases and was associated with larger defect size. Local recurrence was noted in 8 patients (8.4%) at a median of 42 months postreconstruction. No tumor characteristics were found to predict recurrence. CONCLUSIONS: The square procedure for periocular melanoma offers an 8.4% recurrence rate, consistent with literature reports on similar staged excision approaches. The staged excision provides an excellent option for comprehensive margin review and tumor control with acceptable cosmetic results after reconstruction.

Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial.

BACKGROUND: Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision-related outcomes in patients with orbital and extensive periocular BCC (opBCC). MATERIALS AND METHODS: In this open-label, nonrandomized phase IV trial, we enrolled patients with globe- and lacrimal drainage system-threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists. RESULTS: In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1-15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2-4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1-91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins. CONCLUSION: Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number.NCT02436408. IMPLICATIONS FOR PRACTICE: Use of the antihedgehog inhibitor vismodegib resulted in preservation of end-organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end-organ preservation.

Primary venous aneurysms: A 20-year retrospective analysis.

OBJECTIVE: Primary venous aneurysms are unusual vascular occurrences. Our aim is to document our institution's experience with this pathology; describing frequency, diagnosis, outcomes and medical histories of patients with primary venous aneurysms within a 20-year time frame. METHODS: A retrospective study at our institution using its radiology database was conducted. Results were isolated to primary venous aneurysms diagnosed between 1997 and 2017. Basic demographics and medical history were collected. RESULTS: We identified 32 patients with primary venous aneurysms. Eighteen were male and 14 were female. The average age of presentation was 54 years old, with a range of 17-86. None of these patients reported a family history of aneurysmal disease. The majority were incidental. Of these aneurysms, 3 were of the head and neck, 1 was contained in the thorax, 17 were intra-abdominal and 11 were peripheral. Diagnosis was made by computed tomography, duplex ultrasound, or magnetic resonance imaging. Conservative management was most frequently employed, but four patients underwent surgical repair. Three aneurysms required operation for symptom management (external jugular, subclavian, inferior vena cava), whereas one aneurysm of the popliteal vein was prophylactically managed, given the high risk for pulmonary embolism. CONCLUSIONS: Primary venous aneurysms present infrequently. Despite their rarity, primary venous aneurysms have been reported to occur throughout the venous system. The majority of primary venous aneurysms in this series were found incidentally and can present both symptomatically or asymptomatically. The findings of our 20-year experience were consistent with the existing literature. Because the risk of rupture is negligible, the indications for surgical management remain for cosmesis, symptom management or high risk of thromboembolic events.

Suboptimal maternal and cord plasma pyridoxal 5' phosphate concentrations are uncommon in a cohort of Canadian pregnant women and newborn infants.

Vitamin B6 is important in fetal development, but little is known of the vitamin B6 status of pregnant women and newborns in North America and potential modifying factors. This prospective study determined maternal and cord plasma concentrations of pyridoxal 5' phosphate (PLP; an indicator of vitamin B6 status) in a convenience sample of 368 Canadian pregnant women and their newborns. The association of maternal intake of vitamin B6 and fetal genetic variants with cord plasma PLP and homocysteine concentrations was also examined. Dietary and supplemental intakes of vitamin B6 were assessed in early and mid to late pregnancy. PLP concentrations were measured in maternal plasma in early pregnancy and at delivery, and in cord plasma. Six fetal variants of the MTHFR and CßS genes were assessed for their association with cord plasma PLP and homocysteine concentrations. Geometric mean (95% CI) PLP concentrations were 107 (98, 116) nmol/L in early pregnancy and 58 (53, 62) nmol/L at delivery, respectively, and 296 (275, 319) nmol/L in cord blood (p < .0001). During early pregnancy and at delivery, 3.6% and 5.5% of women had plasma PLP concentrations <20 nmol/L, respectively. Ninety eight percent of the women with supplemental B6 intake of at least the recommended dietary allowance had PLP concentrations >20 nmol/L. Fetal genetic variants were not associated with cord PLP and homocysteine concentrations. Vitamin B6 deficiency is uncommon in a cohort of Canadian pregnant women due largely to prevalent vitamin B6 supplement use.

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.

Differences in rates of glaucoma among Asian Americans and other racial groups, and among various Asian ethnic groups.

PURPOSE: To determine the incidence and prevalence of different glaucoma types among Asian Americans and other races, and evaluate the hazard for glaucoma among different races and Asian ethnicities. DESIGN: Retrospective, longitudinal, cohort study. PARTICIPANTS: A group of 2,259,061 eye care recipients, aged ≥ 40, who were enrolled in a US managed-care network in 2001-2007. METHODS: Incidence and prevalence rates of open-angle glaucoma (OAG), narrow-angle glaucoma (NAG), and normal-tension glaucoma (NTG) were calculated and stratified by race and Asian ethnicity. Cox regression was performed to assess the hazard of developing OAG, NAG, and NTG for Asian Americans and other races, and among different Asian ethnicities, with adjustment for potentially confounding variables. MAIN OUTCOME MEASURES: Multivariable adjusted hazard of OAG, NAG, and NTG among different races and Asian ethnicities. RESULTS: The OAG prevalence rate for Asian Americans, 6.52%, was similar to that of Latinos (6.40%) and higher than that of non-Hispanic whites (5.59%). The NAG and NTG prevalence rates were considerably higher among Asian Americans (3.01% and 0.73%, respectively) relative to other races. After adjustment for potential confounding factors, Asian Americans had a 51% increased hazard of OAG (adjusted hazard ratio [HR], 1.51 [95% confidence interval (CI), 1.42-1.60]), a 123% increased hazard of NAG (adjusted HR, 2.23; CI, 2.07-2.41), and a 159% increased hazard of NTG (adjusted HR, 2.59; CI, 2.22-3.02) compared with non-Hispanic whites. Vietnamese Americans (adjusted HR, 3.78; CI, 3.19-4.48), Pakistani Americans (adjusted HR, 2.45, CI 1.50-4.01), and Chinese Americans (adjusted HR, 2.31, CI 2.06-2.59) had considerably higher hazards of NAG, whereas Japanese Americans (adjusted HR, 4.37, CI 3.24-5.89) had a substantially higher hazard of NTG, compared with non-Asian Americans. CONCLUSIONS: Given the rapid rise in the number of Asian Americans in the US population, resources should be devoted to identifying and treating glaucoma in these patients. Eye-care providers should be aware of the increased risk for OAG, NAG, and NTG among Asian Americans relative to other races. Knowing Asian-American patients' ancestral country of origin may permit more precise estimation of their risks for OAG, NAG, and NTG. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Digital Food Retail: Public Health Opportunities.

For over two decades, digital food retail services have been emerging alongside advances in mobile technology and improved access to wi-fi. Digitalization has driven changes within the food environment, complicating an already complex system that influences food-related behaviors and eating practices. Digital food retail services support an infrastructure that enhances commercial food systems by extending access to and availability of highly processed foods, further escalating poor dietary intakes. However, digital food retail services are heterogeneous-food delivery apps, online groceries, and meal kits-and can be feasibly adapted to nutrition interventions and personalized to individual needs. Although sparse, new evidence indicates great potential for digital food retail services to address food insecurity in urban areas and to support healthy eating by making it easier to select, plan, and prepare meals. Digital food retail services are a product of the digital transformation that reflect consumers' constant need for convenience, which must be addressed in future research and interventions. This paper will discuss public health opportunities that are emerging from the global uptake of digital food retail services, with a focus on online groceries, food delivery apps, and meal kits.

Change in Postoperative Opioid Prescribing Patterns for Oculoplastic and Orbital Procedures Associated With State Opioid Legislation.

Importance: Understanding whether statewide legislation, such as the Michigan Opioid Laws, is associated with reduction in postoperative opioid prescriptions is informative in guiding future legislation. Objective: To identify changes in opioid prescribing patterns for oculoplastic and orbital procedures associated with the enactment of the Michigan Opioid Laws in 2017 and 2018. Design, Setting, and Participants: This cross-sectional study included 3781 patients who underwent any of 10 common oculoplastic and orbital procedures between June 1, 2016, and November 30, 2019, at a tertiary care institution. Exposures: From 2017 to 2018, Michigan enacted a series of laws to address the state's worsening opioid epidemic. Two major components of this legislation enacted on June 1, 2018, required prescribers to review a report of patients' opioid use history and obtain signed consent after educating patients on the use and disposal of opioids prior to prescribing. Main Outcomes and Measures: Demographic information, type of surgery, type and amount of opioid prescriptions, and morphine milligram equivalent (MME) were analyzed. MME was calculated as the product of dose, quantity, and opioid-specific conversion factor for each prescription. Linear interpolation spline regression was used to evaluate the association of prescription MME with time. Results: Of 3781 patients, 1614 (42.7%) were male. The mean (SD) age at the time of surgery was 63.3 (16.6) years. Of 2026 patients undergoing surgery before June 1, 2018, 1782 (88.0%) were prescribed postoperative opioids; of 1755 patients undergoing surgery after June 1, 2018, 878 (50.0%) were prescribed postoperative opioids (P < .001). There was no difference in age, sex, race/ethnicity, surgery type, or opioids prescribed between these 2 cohorts. Linear interpolation spline regression showed a decrease of 26.025 MMEs (equivalent to a 36.2% reduction of mean MME) between June 1, 2017, and September 30, 2018 (ß, -1.735; 95% CI, -0.088 to -0.024; P < .001), stabilizing at a persistently reduced rate of MME prescribed through the end of the study period (October 1, 2018, to November 30, 2019; ß, -0.005; 95% CI, -0.039 to 0.016; P = .42). Changes in MME in the 12 months before or 12 months after the period of legislation enactment were not identified. Conclusions and Relevance: In this cross-sectional study, reduction in opioid prescriptions for oculoplastic and orbital procedures was observed during the enactment period of the Michigan Opioid Laws and appeared to be sustained through the end of the study period. Similar statewide or national legislations aimed at increasing prescriber awareness and patient education on opioid use may help curtail the prescription opioid epidemic.

Long-term results of thigh arteriovenous dialysis grafts.

INTRODUCTION:: A proportion of hemodialysis patients exhaust all options for arteriovenous access in upper extremities. Arteriovenous thigh grafts are a potential vascular access option in such patients. METHODS:: We performed a retrospective study of all thigh arteriovenous access grafts placed between 1995 and 2015. The clinical, demographic patient information and patency of each thigh graft was determined from the time of surgical creation placement until abandonment, transfer to other modality, or center or end of study, and the reason for access failure documented. RESULTS:: In total, 44 patients received 49 thigh arteriovenous accesses. The average age was 60 years (13-79 years); Half (53%) of the patients (n = 24) were female and 61% of the patients (n = 30) of arteriovenous accesses were left-sided. The cumulative proportion surviving (primary patency rates) at 12, 24, and 28 months were 43% (standard error = 9%), 33% (standard error = 9%), and 13% (standard error = 9%), respectively. The cumulative proportion of surviving grafts at 12, 24, and 48 months were 61% (standard error = 8%), 58% (standard error = 9%), and 31% (standard error = 13%), respectively. In total, 37 revisions were performed in 22 patients to maintain patency or eradicate infection. Infection occurred in 20 patients (39%) of thigh grafts requiring 16 patients (80% of those affected) to be removed; 14 patients had grafts (33.3%) that served as the lone hemodialysis arteriovenous access during the patients' lifetime on dialysis. CONCLUSION:: Arteriovenous thigh graft access is used infrequently, but they have an acceptable patency. Some accesses require revisions and they have a high infection rate. Despite this, an acceptable proportion of leg grafts provide durable access for the dialysis lifetime of the patient.

Axillary artery aneurysm combined with brachial plexus palsy due to Takayasu arteritis.

We report the case of a young female patient who presented with a right axillary artery aneurysm with neurological symptoms due to Takayasuarteritis (TA). Decompression of the aneurysm and arterial repair with an interposition vein bypass resulted in a full recovery. The case emphasises that peripheral aneurysms can occur due to TA and that there may be neurological complications.

The Role of Intraoperative Cerebral Angiography in Transorbital Intracranial Penetrating Trauma: A Case Report and Literature Review.

BACKGROUND: Transorbital intracranial penetrating trauma with a retained intracranial foreign body is a rare event lacking a widely accepted diagnostic and therapeutic algorithm. Intraoperative catheter angiography (IOA) has been advocated by some authorities to rule out cerebrovascular injury before and/or after removal of the object, but no standard of care currently exists. CASE DESCRIPTION: A 19-year-old man was involved in a construction site accident whereby a framing nail penetrated the left globe, traversed the lateral bony orbit, and terminated in the midtemporal lobe. No hematoma or injury to the middle cerebral arteries (MCAs) was apparent on noncontrast head computed tomography (CT) or CT angiography, respectively. The foreign body was removed in the operating room under direct visualization after a frontotemporal craniotomy without incident. No significant venous or arterial bleeding was encountered. All visualized MCA branches appeared intact. Indocyanine green videoangiography performed immediately after object removal showed adequate filling of the MCA branches. Given these uneventful clinical and radiographic findings, IOA was not performed. Postoperative head CT and CT angiography showed no obvious neurovascular injury. On postoperative day 2, the patient was noted to have an expressive aphasia. Cerebral angiography showed absent antegrade filling of the angular artery with some retrograde perfusion. Magnetic resonance imaging confirmed an ischemic infarction in the midtemporal lobe. The patient's expressive aphasia improved to near baseline during his hospitalization and he made an excellent clinical recovery. CONCLUSIONS: In transorbital intracranial penetrating trauma with a retained intracranial object, we advocate microsurgical removal of the object under direct visualization followed immediately by IOA. IOA should be strongly considered even in the setting of minimal intraoperative bleeding and normal findings on videoangiography (a course of action that was not followed in the present case). Given that CT angiography and intraoperative videoangiography may miss a potentially treatable traumatic arterial injury, IOA can help determine whether cerebral revascularization may be necessary.

Maternal folic acid supplementation modulates DNA methylation and gene expression in the rat offspring in a gestation period-dependent and organ-specific manner.

Maternal folic acid supplementation can alter DNA methylation and gene expression in the developing fetus, which may confer disease susceptibility later in life. We determined which gestation period and organ were most sensitive to the modifying effect of folic acid supplementation during pregnancy on DNA methylation and gene expression in the offspring. Pregnant rats were randomized to a control diet throughout pregnancy; folic acid supplementation at 2.5× the control during the 1st, 2nd or 3rd week of gestation only; or folic acid supplementation throughout pregnancy. The brain, liver, kidney and colon from newborn pups were analyzed for folate concentrations, global DNA methylation and gene expression of the Igf2, Er-α, Gr, Ppar-α and Ppar-γ genes. Folic acid supplementation during the 2nd or 3rd week gestation or throughout pregnancy significantly increased brain folate concentrations (P<.001), while only folic acid supplementation throughout pregnancy significantly increased liver folate concentrations (P=.005), in newborn pups. Brain global DNA methylation incrementally decreased from early to late gestational folic acid supplementation and was the lowest with folic acid supplementation throughout pregnancy (P=.026). Folic acid supplementation in late gestation or throughout pregnancy significantly decreased Er-α, Gr and Ppar-α gene expression in the liver (P<.05). The kidney and colon were resistant to the effect of folic acid supplementation. Maternal folic acid supplementation affects tissue folate concentrations, DNA methylation and gene expression in the offspring in a gestation-period-dependent and organ-specific manner.

Thyrotropin receptor and CD40 mediate interleukin-8 expression in fibrocytes: implications for thyroid-associated ophthalmopathy (an American Ophthalmological Society thesis).

PURPOSE: To better understand the pathogenesis of thyroid-associated orbitopathy (TAO) through elucidating the role of thyrotropin receptor (TSHR) and CD40 in the expression of interleukin-8 (IL-8) in peripheral blood fibrocytes. Fibrocytes infiltrate the orbit of patients with TAO, where they differentiate into fibroblasts. Fibrocyte precursors occur with increased frequency in the peripheral blood expressing TSHR and CD40 in TAO patients. We hypothesize that in vitro derived fibrocytes and peripheral blood fibrocyte precursors express proinflammatory chemoattractant molecules including IL-8 initiated by TSHR and CD40 signaling. Since nearly all TAO patients express activating antibodies to TSHR, this is particularly relevant for activation of peripheral blood fibrocytes. METHODS: TSHR and CD40 expression on peripheral blood fibrocytes was determined by flow cytometry. IL-8 RNA was quantitated by real-time polymerase chain reaction. IL-8 protein production was measured by Luminex and flow cytometry. Thyroid-stimulating hormone and CD40 ligand-stimulated phosphorylation of Akt in peripheral blood fibrocytes was studied by flow cytometry. RESULTS: Both TSHR- and CD40-mediated signaling lead to IL-8 expression in mature fibrocytes. Fibrocyte precursors assayed directly from circulating peripheral blood demonstrate intracellular IL-8 expression with addition of thyroid-stimulating hormone or CD40 ligand. TSHR- and CD40-induced IL-8 production is mediated by Akt phosphorylation. CONCLUSIONS: Peripheral blood TSHR(+) and CD40(+) fibrocytes express IL-8 and may promote the recruitment of inflammatory cells, mitogenesis, and tissue remodeling in TAO. TSHR- and CD40-mediated IL-8 signaling is mediated by Akt. Delineating the molecular mechanisms of fibrocyte immune function may provide potential therapeutic targets for TAO.

Rituximab (Rituxan) therapy for severe thyroid-associated ophthalmopathy diminishes IGF-1R(+) T cells.

CONTEXT: Rituximab depletes CD20(+) B cells and has shown potential benefit in thyroid-associated ophthalmopathy (TAO). The impact of rituximab on T cell phenotype in TAO is unexplored. OBJECTIVE: The objective of the study was to quantify the abundance of IGF-I receptor-positive (IGF-1R(+)) CD4 and CD8 T cells in active TAO before and after treatment with rituximab. DESIGN: This was a retrospective case series assessing IGF-1R(+) T cells before and after treatment with rituximab with an 18-month follow-up. SETTING: The study was conducted at a tertiary care medical center. PATIENTS: Study participants included eight patients with severe TAO. INTERVENTIONS: Two infusions of rituximab (1 g or 500 mg each) were administered 2 weeks apart. MAIN OUTCOME MEASURES: Quantification of IGF-1R(+) T cells using flow cytometry was measured. RESULTS: Eight patients with moderate to severe TAO [mean pretreatment clinical activity score (CAS) 5.1 ± 0.2 (SEM)] were treated. Four to 6 weeks after treatment, CAS improved to 1.5 ± 0.3, whereas the proportion of IGF-1R(+) CD3(+) T cells declined from 41.9% to 28.3% (P = .004). The proportion of IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) T cells declined 4-6 weeks after treatment (from 45.6% to 21.5% and from 32.0% to 15.8%, P = .003 and P = .001, respectively). In two patients, IGF-1R(+) CD4(+) and IGF-1R(+) CD8(+) subsets approximated pretreatment levels after 16 weeks. CONCLUSIONS: Frequency of IGF-1R(+) T cells in patients with TAO declines within 4-6 weeks after rituximab treatment. This phenotypic shift coincides with clinical improvement. Thus, assessment of the abundance of IGF-1R(+) T cells in response to rituximab may provide a biomarker of clinical response. Our current findings further implicate the IGF-1R pathway in the pathogenesis of TAO.

The association between glaucomatous and other causes of optic neuropathy and sleep apnea.

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

Geographic and climatic factors associated with exfoliation syndrome.

OBJECTIVE: To identify geographic and climatic risk factors associated with exfoliation syndrome (ES). METHODS: A retrospective study of 626 901 eye care recipients, dating from 2001 to 2007 from 47 US states in a managed care network. Incident ES cases-patients (N = 3367) were identified by using billing codes. We assessed the risk of ES by geographic latitude tier in the continental United States and assigned state-level climatic data (eg, ambient temperature, elevation, and sun exposure) according to patients' residential location. The hazard of ES was calculated by using multivariable-adjusted Cox proportional hazards regression models. RESULTS: Compared with middle-tier residence, northern-tier residence (above 42°N) was associated with an increased hazard of ES (adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.94-2.35). Southern-tier (below 37°N) was associated with a reduced hazard of ES (HR, 0.83; 95% CI, 0.75-0.93). Excluding whites did not change these associations. After adjustment for joint environmental effects, for every 1° increase in July high temperature, the hazard of ES decreased by 9% (HR, 0.91; 95% CI, 0.89-0.93); for every 1° increase in January low temperature, the hazard decreased 3% (0.97; 0.96-0.98). For each additional sunny day annually, the hazard increased by 1.5% (HR, 1.02; 95% CI, 1.01-1.02) in locations with average levels of other climatic factors. CONCLUSION: Ambient temperature and sun exposure may be important environmental triggers of ES.