SGLT2 inhibitors and diabetic retinopathy progression.

PURPOSE: To evaluate whether sodium-glucose co-transporter 2 (SGLT2) inhibitors affect progression of non-proliferative diabetic retinopathy (NPDR) compared to standard of care. METHODS: A retrospective cohort study compared subjects enrolled in a commercial and Medicare Advantage medical claims database who filled a prescription for a SGLT2 inhibitor between 2013 and 2020 to unexposed controls, matched up to a 1:3 ratio. Patients were excluded if they were enrolled for less than 2 years in the plan, had no prior ophthalmologic exam, had no diagnosis of NPDR, had a diagnosis of diabetic macular edema (DME) or proliferative diabetic retinopathy (PDR), had received treatment for vision-threatening diabetic retinopathy (VTDR), or were younger than 18 years. To balance covariates of interest between the cohorts, an inverse probability treatment weighting (IPTW) propensity score for SGLT2 inhibitor exposure was used. Multivariate Cox proportional hazard regression modeling was employed to assess the hazard ratio (HR) for VTDR, PDR, or DME relative to SGLT2 exposure. RESULTS: A total of 6065 patients who initiated an SGLT2 inhibitor were matched to 12,890 controls. There were 734 (12%), 657 (10.8%), and 72 (1.18%) cases of VTDR, DME, and PDR, respectively, in the SGLT2 inhibitor cohort. Conversely, there were 1479 (11.4%), 1331 (10.3%), and 128 (0.99%) cases of VTDR, DME, and PDR, respectively, among controls. After IPTW, Cox regression analysis showed no difference in hazard for VTDR, PDR, or DME in the SGLT2 inhibitor-exposed cohort relative to the unexposed group [HR = 1.04, 95% CI 0.94 to 1.15 for VTDR; HR = 1.03, 95% CI 0.93 to 1.14 for DME; HR = 1.22, 95% CI 0.89 to 1.67 for PDR]. CONCLUSION: Exposure to SGLT2 inhibitor therapy was not associated with progression of NPDR compared to patients receiving other diabetic therapies.

Mohs Micrographic Surgery for Facial Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor with frequent metastases. They often appear in the face where cosmetic and functional outcome is critical. Mohs micrographic surgery (MMS) is a controlled intervention that optimizes negative margins without sacrificing tissue. OBJECTIVE: A comprehensive assessment of outcomes of MMS-treated facial MCC will help guide clinicians in surgical and medical management. METHODS & MATERIALS: Retrospective review identified facial MCC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded and descriptive and predictive analyses were performed. RESULTS: 34 cases were reviewed with a mean followup of 34.4 months. The most common sites were the forehead, cheek-jaw region, and nasal ala. 2 (5.9%) patients had local recurrence by a mean of 4.3 months. No documented variables were significantly associated with local recurrence. 8 (23.5%) patients had progression to metastasis by a mean of 9.4 months. Younger age at biopsy and surgery, male sex, and intraoperative detection of in-transit disease were significantly associated with progression to metastasis. CONCLUSIONS: In summary, the tissue-sparing approach of MMS may be beneficial for MCC in cosmetically and functionally sensitive facial locations as it preserves tissue without compromising outcomes.

Statin use and the risk of progression to vision threatening diabetic retinopathy.

PURPOSE: This study aims to assess the effect of statins on progression from nonproliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR) or diabetic macular edema (DME). METHODS: Two cohort studies using a U.S. medical claims database from 2002 to 2019 including NPDR patients 18 years or older. A risk factor analysis performed a time-updating cox regression model assessing statin usage. A second new-user active comparator design analysis replicating a previously published study. Main outcomes included a new diagnosis of VTDR (composite of either PDR or DME) or DME and PDR individually for the risk factor study and included additional outcomes of new DR, NPDR, vitreous hemorrhage (VH) and tractional retinal detachment (TRD) for the new user study. RESULTS: Risk factor analysis included 66 617 statin users with NPDR at baseline and 83 365 nonstatin users. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After multivariable analysis, no protective effect of statin use was found for progression to VTDR, PDR, or DME (HR = 1.01-3, p >0.33 for all comparisons). Replicated new user design analysis also showed no protective effect for statins on risk of development of DR (HR = 1.03, 95% CI: 0.99-1.07, p = 0.13), PDR (HR = 0.89, 95% CI: 0.79-1.02, p = 0.09), DME (HR = 0.94, 95% CI: 0.86-1.03, p = 0.21), VH (HR = 1.00, 95% CI: 0.86-1.16, p = 0.99), and TRD (HR = 1.11, 95% CI: 0.89-1.38, p = 0.36). CONCLUSION: Statin use was found not to be protective for progression of DR regardless of study methodology. These results suggest that the specifics of the population studied rather than differing study methodology are important in assessing the effect of statins on DR progression.

Sebaceous Carcinoma of the Face Treated With Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) for sebaceous carcinoma (SC) may reduce local recurrence rates, but published case series have small cohorts and limited follow-up. Mohs micrographic surgery is particularly suitable for sensitive functional and cosmetic locations, such as the face, because it facilitates tissue conservation using complete peripheral and deep margin assessment before reconstruction. Coordinated care between Mohs and oculoplastic surgeons has not been described. OBJECTIVE: To assess rates of local recurrence and metastasis after MMS of facial SC and to describe coordinated care between Mohs and oculoplastic surgeons. MATERIALS AND METHODS: Retrospective review identified facial SC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded. Descriptive and predictive analyses were performed. RESULTS: Forty-nine cases were reviewed with a mean follow-up of 51 months. The most common sites were periorbital, infraorbital cheek, and nasal ala. No patients experienced regional recurrence after MMS. One patient with Muir-Torre syndrome developed metastatic recurrence (at 82.9 months). All patients underwent 2-stage reconstruction with dermatology-performed MMS and oculoplastic reconstruction. CONCLUSION: Collaboration between Mohs and oculoplastic surgeons with a tissue-sparing approach of MMS can reduce recurrence and optimize cosmesis and function for central facial SC.

Evaluating the association of clinical factors and optical coherence tomography retinal imaging with axial length and axial length growth among preterm infants.

PURPOSE: To study the association of clinical factors and optical coherence tomography (OCT) retinal imaging with axial length (AL) and AL growth in preterm infants METHODS: Among a subgroup of infants from the prospective BabySTEPS study who were screened for retinopathy of prematurity (ROP) and had both AL measured and OCT imaging performed, we analyzed data collected prior to 42 weeks postmenstrual age (PMA) and prior to ROP treatment. Using linear mixed effects models, we evaluated associations between AL and AL growth with gestational age (GA), birthweight, PMA, sex, race, multiparity, maximum ROP stage, and OCT features. RESULTS: We included 66 infants (132 eyes), mean GA = 27.6 weeks (SD = 2.3; range: 23.0-34.4) and mean birthweight = 961 g (SD = 269, range: 490-1580). In the final predictive model, longer AL was associated with earlier GA, higher birthweight, later PMA, non-White race, and thicker subfoveal choroid (all p values ≤ 0.01). AL increased linearly up to 42 weeks PMA. There was no difference in AL growth rate by GA, sex, race, multiparity, maximum ROP severity, central foveal thickness, or subfoveal choroidal thickness (all p values > 0.05); but AL growth rate was slower in infants with lower birthweight (p = 0.01). CONCLUSIONS: Among preterm infants, those with earlier GA, higher birthweight, later PMA, non-White race, and thicker subfoveal choroid had the longest AL. AL increased linearly up to 42 weeks PMA and lower birthweight was associated with slower AL growth. These findings may improve the accuracy of measurements taken on preterm infants using imaging techniques affected by AL (e.g., measuring lateral dimensions on OCT). TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02887157 , date of registration: August 25, 2016.

Primary orbital melanoma: A report of a case and comprehensive review of the literature.

Purpose: To review the clinical features and treatment-associated outcomes of primary orbital melanoma among cases reported in the literature and to present a case treated with orbital exenteration and post-operative radiotherapy.Methods: Case reports and case series on primary orbital melanoma published in the literature between 1980 and 2020 were reviewed. Data collected included patient demographics, presenting ocular symptoms, diagnostic imaging, histology, management, and outcomes.Results: Eighty-eight cases of primary orbital melanoma were reviewed. The average age at presentation was 45 years and 58% of patients were male. The most common presenting symptoms and signs were proptosis (73%), decreased visual acuity (32%), pain (14%), diplopia (15%), and palpable mass (9%). Imaging frequently showed a well-circumscribed enhancing lesion. Diagnosis was made by histology in all cases, and orbital blue nevus was identified in 42%. In the majority of cases, treatment consisted of orbital exenteration (54%) or excision (38%). Adjuvant radiotherapy was given in 47% of cases. For the 72 patients with reported outcomes, 36% had metastases, 15% had local recurrence, and 32% died of metastatic disease. Patients who received surgery and radiotherapy had improved survival compared to those who received surgery alone (p = .01). There was no difference in survival between those who underwent orbital exenteration or excision (p = .16).Conclusions: Primary orbital melanoma is a rare malignancy and should be considered in patients with a history of unilateral proptosis and a well-defined orbital mass on imaging. Surgery remains the mainstay of treatment. Adjuvant radiotherapy may improve patient survival.

Childhood adversity impact on gut microbiota and inflammatory response to stress during pregnancy.

BACKGROUND: Adverse childhood experiences (ACEs), such as abuse or chronic stress, program an exaggerated adult inflammatory response to stress. Emerging rodent research suggests that the gut microbiome may be a key mediator in the association between early life stress and dysregulated glucocorticoid-immune response. However, ACE impact on inflammatory response to stress, or on the gut microbiome, have not been studied in human pregnancy, when inflammation increases risk of poor outcomes. The aim of this study was to assess the relationships among ACE, the gut microbiome, and cytokine response to stress in pregnant women. METHODS: Physically and psychiatrically healthy adult pregnant women completed the Adverse Childhood Experiences Questionnaire (ACE-Q) and gave a single stool sample between 20 and 26 weeks gestation. Stool DNA was isolated and 16S sequencing was performed. Three 24-hour food recalls were administered to assess dietary nutrient intake. A subset of women completed the Trier Social Stress Test (TSST) at 22-34 weeks gestation; plasma interleukin-6 (IL-6), interleukin-1ß (IL-1ß), high sensitivity C-reactive protein (hsCRP), tumor necrosis factor α (TNF-α), and cortisol were measured at four timepoints pre and post stressor, and area under the curve (AUC) was calculated. RESULTS: Forty-eight women completed the ACE-Q and provided stool; 19 women completed the TSST. Women reporting 2 or more ACEs (high ACE) had greater differential abundance of gut Prevotella than low ACE participants (q = 5.7 × 10^-13). Abundance of several gut taxa were significantly associated with cortisol, IL-6, TNF-α and CRP AUCs regardless of ACE status. IL-6 response to stress was buffered among high ACE women with high intake of docosahexaenoic acid (DHA) (p = 0.03) and eicosapentaenoic acid (EPA) (p = 0.05). DISCUSSION: Our findings suggest that multiple childhood adversities are associated with changes in gut microbiota composition during pregnancy, and such changes may contribute to altered inflammatory and glucocorticoid response to stress. While preliminary, this is the first study to demonstrate an association between gut microbiota and acute glucocorticoid-immune response to stress in a clinical sample. Finally, exploratory analyses suggested that high ACE women with high dietary intake of ω-3 polyunsaturated fatty acids (PUFAs) had a dampened inflammatory response to acute stress, suggesting potentially protective effects of ω-3s in this high-risk population. Given the adverse effects of inflammation on pregnancy and the developing fetus, mechanisms by which childhood adversity influence the gut-brain axis and potential protective factors such as diet should be further explored.

Reproducibility of 2D GluCEST in healthy human volunteers at 7 T.

PURPOSE: To investigate the reproducibility of gray and white matter glutamate contrast of a brain slice among a small group of healthy volunteers by using the 2D single-slice glutamate CEST (GluCEST) imaging technique. METHODS: Six healthy volunteers were scanned multiple times for within-day and between-day reproducibility. One more volunteer was scanned for within-day reproducibility at 7T MRI. Glutamate CEST contrast measurements were calculated for within subjects and among the subjects and the coefficient of variations are reported. RESULTS: The GluCEST measurements were highly reproducible in the gray and white matter area of the brain slice, whether it was within-day or between-day with a coefficient of variation of less than 5%. CONCLUSION: This preliminary study in a small group of healthy volunteers shows a high degree of reproducibility of GluCEST MRI in brain and holds promise for implementation in studying age-dependent changes in the brain.

Risk Factors for Chalazion Diagnosis and Subsequent Surgical Excision.

PURPOSE: To identify factors associated with chalazion diagnosis and surgical excision. METHODS: Patients with an incident chalazion diagnosis from 2002 to 2019 were compared 1:5 with matched controls. Multivariable logistic regression was performed to identify variables associated with diagnosis and surgical excision. RESULTS: Chalazion patients (n = 134,959) and controls (678,160) were analyzed. Risk factors for diagnosis included female sex, non-white race, northeast location, conditions affecting periocular skin and tear film (blepharitis, meibomian gland dysfunction, rosacea, pterygium), non-ocular inflammatory conditions (gastritis, inflammatory bowel disease, sarcoidosis, seborrheic dermatitis, Graves' disease), and smoking (p < .001 for all comparisons). Thirteen percent of patients with chalazion underwent subsequent surgical excision. Diabetes and systemic sclerosis diagnoses decreased odds of diagnosis (p < .001). Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use increased odds of surgery (p < .001). CONCLUSION: Female sex, non-white race, conditions affecting periocular skin and the tear film, several non-ocular inflammatory conditions, and smoking were risk factors for chalazion diagnosis. Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use were risk factors for surgical intervention for chalazion. Our results prompt further study of these variables and their relationship to chalazion diagnosis to understand physiology and improve clinical outcomes. Furthermore, the results of this study suggest early recognition and treatment of concomitant rosacea may serve an important role in the management of chalazion and in the prevention of surgical intervention.

Stimulus type and duration affect magnitude and evolution of flicker-induced hyperemia measured by laser speckle flowgraphy at the optic disc and peripapillary vessels.

Neurovascular coupling is a vital mechanism employed by the cerebrovascular system, including the eye, to regulate blood flow in periods of neuronal activation. This study aims to investigate if laser speckle flowgraphy (LSFG) can detect coupling response elicited by flickering light stimuli and how variations in stimulus type and duration can affect the magnitude and evolution of blood flow in the optic nerve head (ONH) and peripapillary vessels. Healthy adults were exposed to two types of 10-Hz flicker stimuli: a photopic negative response-like stimulus (PhNR-S) or a visual evoked potential-like stimulus (VEP-S)-each presented in separate 10- and 60-s epochs. Both PhNR-S and VEP-S significantly increased ONH blood flow (p < 0.001) immediately after flicker cessation, with a trend of 60-s stimuli (PhNR-S = 11.6%; VEP-S = 10.4%) producing a larger response than 10-s stimuli (PhNR-S = 7.5%; VEP-S = 6.2%). Moreover, exposure to 60-s stimuli elicited a significantly prolonged ONH hyperemic response, especially with PhNR-S. Lastly, stimulation with either 60-s stimuli elicited a robust increase in blood flow within the peripapillary arterioles (p < 0.01) and venules (p < 0.01) as well. Flicker stimulation with common visual electrophysiology stimuli (PhNR-S and VEP-S) induced a demonstrable increase in ONH and peripapillary vessel blood flow, which varied with flicker duration. Our results validate that LSFG is a robust method to quantify flicker-induced hyperemic responses and to study neurovascular coupling in humans.

Systemic disease associations with angioid streaks in a large healthcare claims database.

BACKGROUND/OBJECTIVES: To assess systemic associations of angioid streaks (AS) using a large US healthcare database. SUBJECTS/METHODS: A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV). RESULTS: One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis. CONCLUSIONS: In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation.

Long-Term Burden of Pain and Reduced Visual Acuity after Gunshot Wounds to the Orbit.

PURPOSE: To characterize the clinical presentation, surgical management, long-term complications and outcomes of Gunshot Wounds(GSW) to the orbit. METHODS: An extended case series with retrospective chart-review was conducted on all cases (1985-2020) of traumatic ocular injuries secondary to GSWs at an academic institution with a level 1 trauma center. Predictors included demographic information, clinical and radiologic examination findings, and surgical intervention at time of presentation. Outcomes included long-term lid malposition, visual acuity, pain, and secondary surgery. Descriptive statistics and tests of association were performed, including Fishers exact tests for categorical data, Kruskal-Wallis rank sum tests, analysis of variance, and, in the case of repeated measures, generalized estimating equations. RESULTS: 88 patients with GSW involving the orbit were included with average age of 32.6 years (sd = 15.7). Patients were 85.2% male, 75% African-American, 25.0% Caucasian, and 5.7% Hispanic. Median follow up was 43.3 months (4.6, 136.4). The injuries at presentation were 53.4% intracranial, 21.6% open globe, 80.7% orbital fracture, 89.8% lid laceration. Visual acuity did not significantly improve over time. Long-term complications included abnormal lid or globe position in 26.1% of patients, reduced visual acuity in 55.2%, and persistent pain in 50.6%. CONCLUSION: To our knowledge, this represents the first and largest clinical epidemiologic study with insight into the clinical presentation, surgical intervention, and long-term outcomes of GSW to the orbit. The results demonstrate a long-term burden of persistent pain and reduced visual acuity in patients who suffer from GSW to the globe and orbit. This study may guide patient management and communications.

Biphasic change in retinal nerve fibre layer thickness from 30 to 60 weeks postmenstrual age in preterm infants.

BACKGROUND/AIMS: The optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants. METHODS: We used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA. RESULTS: From 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 µm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at -0.3 µm/week (95% CI: -0.5 to -0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 µm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at -0.8 µm/week (95% CI: -0.9 to -0.6). CONCLUSION: We demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

Associations between systemic health and retinal nerve fibre layer thickness in preterm infants at 36 weeks postmenstrual age.

BACKGROUND/AIMS: Neonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants. METHODS: We prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models. RESULTS: 83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI -15.9 to -4.9) lower in infants with than without sepsis/NEC in the univariable analysis (p<0.001). This difference remained statistically significant after adjustment for confounding variables in various combinations (birth weight, birthweight percentile, gestational age, infant weight at imaging and growth velocity). A 250 g increase in infant weight at imaging was associated with a 3.1 µm (95% CI 2.1 to 4.2) increase in RNFL thickness in the univariable analysis (p<0.001). CONCLUSIONS: Low infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. Future longitudinal studies are needed to investigate this relationship further.

The association of stroke with central and branch retinal arterial occlusion.

OBJECTIVES: To determine the near-term risk of stroke following a retinal artery occlusion (RAO). METHODS: The risk of stroke was assessed in two manners; with a self-controlled case series (SCCS) and a propensity score (PS) matched cohort study using a US medical claims database. The date of RAO diagnosis was assigned as the index date. In the SCCS, incidence of stroke was compared in 30- and 7-day periods pre- and post-index date. In PS analysis, matched cohorts were created from patients with RAO or hip fracture. Cox proportional hazard regression assessed the hazard for stroke. Patients were censored at 1 year, upon leaving the insurance plan or if they had a qualifying event for the comparison group. RESULTS: The SCCS included 16,193 patients with RAO. The incidence rate ratio (IRR) of new stroke in the month after RAO was increased compared to all periods >2 months before and all months after the index date (IRRs: 1.68-6.40, p < 0.012). Risk was increased in the week immediately following the index date compared to most weeks starting 2 weeks prior to and all weeks immediately after the index date (IRRs: 1.93-29.00, p < 0.026). The PS study analysed 18,213 propensity-matched patients with RAO vs. hip fracture. The HR for having a stroke after RAO compared to a hip fracture was elevated in all analyses (All RAO HR: 2.97, 95% CI: 2.71-3.26, p < 0.001; CRAO HR: 3.24, 95% CI: 2.83-3.70, p < 0.001; BRAO HR: 2.76, 95% CI: 2.43-3.13, p < 0.001). CONCLUSIONS: The highest risk for stroke occurs in the days following a CRAO or BRAO, supporting guidelines suggesting immediate referral to a stroke centre upon diagnosis.

Hypercoagulability Testing and Hypercoagulable Disorders in Young Central Retinal Vein Occlusion Patients.

PURPOSE: To determine frequency of hypercoagulability testing and hypercoagulable states in patients with central retinal vein occlusion (CRVO) younger than 50 years. DESIGN: Retrospective cohort study. PARTICIPANTS: Deidentified patients younger than 50 years with newly diagnosed CRVO from a national insurance claims database. METHODS: The de-identified Clinformatics Data Mart Database (Optum) containing medical claims from a commercial and Medicare Advantage insurance database was used. All outpatient medical claims (office visits, associated diagnoses, and laboratory testing) and demographic data for each beneficiary during their enrollment were accessible. MAIN OUTCOME MEASURES: Prevalence of (1) laboratory hypercoagulable workup within 90 days of CRVO diagnosis, (2) new diagnosis of a hypercoagulable state within 1 year of CRVO diagnosis, and (3) diagnosis of hypertension, diabetes mellitus (DM), and hyperlipidemia. RESULTS: One thousand one hundred eighty-one patients met inclusion criteria. Six hundred seventy-one patients (56.8%) were men, 450 patients (38.1%) had undergone hypercoagulable testing within 90 days, and 136 patients (11.5%) were diagnosed with a hypercoagulable state within 1 year after CRVO diagnosis. This proportion was similar between those patients with DM, hypertension, or hyperlipidemia (10.5% [65/620]) and those without (12.7% [71/561]; P = 0.28). Of the 136 patients diagnosed with a hypercoagulability state, 68.4% (93/136) had undergone testing within 90 days of CRVO diagnosis and 31.6% (43/136) did not. Of those who had not undergone hypercoagulability testing, 5.9% (43/731) were diagnosed with a hypercoagulable state within 1 year compared with 20.7% (93/450) in those who were tested (P < 0.001). CONCLUSIONS: The prevalence of a hypercoagulable state within 1 year of CRVO diagnosis in patients younger than 50 years was 11.5%, and the prevalence was similar between patients with atherosclerotic risk factors and those without. Rate of testing was only 38.1%. Future research should examine the usefulness of uniform hypercoagulable testing in young CRVO patients.

Recent Practice Patterns in Acute Retinal Artery Occlusions in the United States.

PURPOSE: To determine how to practice patterns for work-up of incident retinal artery occlusion (RAO) compare to the American Academy of Ophthalmology (AAO) guidelines. METHODS: In this cohort study, patients receiving a new diagnosis of RAO, either central (CRAO) or branch (BRAO), were identified between 2002 and 2020 from a large US medical claims database. Claims were reviewed for diagnostic tests specified by the AAO as essential components of an RAO work-up including carotid ultrasound, echocardiogram, magnetic resonance imaging (MRI) and emergency department (ED) referral. Outcomes included rates of and time to completion of work-up. RESULTS: 18697 new outpatient diagnoses of RAO (11348 BRAO, 7349 CRAO) were analyzed. 15.9% and 30.4% of patients received carotid ultrasounds within 7 and 30 days, respectively. 9.4% and 21.1% of patients received echocardiograms within 7 and 30 days, respectively. 4.9% and 8.1% of patients received a brain MRIs within 7 and 30 days, respectively. Only 4.1% of patients were referred to the ED within a day of diagnosis. Ophthalmologists diagnosed the majority (78.7%) of RAOs compared to neurologists (0.6%). Patients diagnosed by ophthalmologists were significantly more likely to have carotid ultrasound within 7 days, but those diagnosed by neurologists were more likely to have echocardiogram, MRI, and ED referral (p < .01 for all comparisons). The rates of adherence to the AAO care guidelines increased significantly between 2002 and 2020 (p < .01). CONCLUSIONS: The referral and work-up practices demonstrated in this new RAO diagnosis patient cohort have improved with time but are still far below the standard recommended by the AAO.

Risk of non-infectious uveitis or myasthenia gravis in patients on checkpoint inhibitors in a large healthcare claims database.

AIM: To determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy. METHODS: A retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed. RESULTS: For evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis. CONCLUSIONS: Exposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.

Effect of teprotumumab on intraocular pressure in thyroid-associated ophthalmopathy.

PURPOSE: To examine changes in intraocular pressure (IOP) in patients with thyroid eye disease (TED) following teprotumumab. MATERIALS AND METHODS: A retrospective review of 17 patients with TED who received teprotumumab between January 2020 and September 2021 was conducted. IOP, extent of proptosis, and clinical activity score were reviewed at baseline and at 6 weeks, 12 weeks, and 24 weeks for patients undergoing teprotumumab treatment. The primary outcome measure was change in IOP, while secondary outcome measures included changes in proptosis and clinical activity score. RESULTS: Of the 17 patients (34 eyes) with TED who were treated with teprotumumab, the mean age was 50.5 years, and 15 (88%) were female. The mean baseline IOP was 20 mm Hg (range 13-28), and the mean baseline clinical activity score was 3.8 (range 0-6). Of the 34 eyes examined at baseline, examinations were repeated in 16 at 6 weeks, 26 at 12 weeks, and 8 at 24 weeks. At week 6 of treatment, mean IOP decreased by 4.9 mm Hg (P < 0.0001). At week 12 of treatment, mean IOP decreased by 4.6 mm Hg (P < 0.0001). Mean IOP was decreased at last record of follow-up by 4.9 mm Hg (P < 0.0001). CONCLUSION: Among patients with TED, teprotumumab treatment was associated with a reduction in IOP.

Tobacco counseling in the setting of thyroid eye disease.

PURPOSE: To collect data on the rate and efficacy of tobacco counseling sessions delivered by ophthalmologists under the setting of patients with thyroid eye disease. METHODS: We analyzed the electronic medical records of a digital cohort of patients who visited ophthalmologists at the University of Pennsylvania Health System from 2012 to 2017 with reference to the International Classification of Disease (ICD) codes for Graves' disease, thyrotoxic exophthalmos, and/or thyroid eye disease. Tobacco histories were recorded at the first and last ophthalmology office visits or the most temporally proximal encounter in packs/day (ppd), and each ophthalmology visit note was analyzed to validate the occurrence of tobacco counseling. RESULTS: A total of 435 patients met our study inclusion criteria, of which 72 (16.6%) were active smokers at the time of their first visit. Only 57 (79.2%) of these active smokers had recorded smoking burdens, 34 (59.6%) of which received at least one form of recorded tobacco counseling session. Nine (26.5%) of the subjects who received tobacco counseling and 1 (4.3%) of those who did not have a recorded counseling, quit smoking (risk difference of 22.1%; 95% CI, [1.7%, 39.1%]; p=0.04). In addition, 17 (50.0%) of the subjects who received counseling and 7 (30.4%) of those who did not have a recorded counseling, reduced their ppd consumption (risk difference of 19.6%; 95% CI [-6.3%, 41.3%]; p=0.18). Overall, 14 (25.5%) out of the 55 ophthalmologists who were active smokers had recorded evidence of tobacco counseling. CONCLUSIONS: Our cumulative results provide the consequence of both missed opportunities for tobacco counseling as well as its efficacy in the setting of thyroid eye disease.