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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Changes in Intraocular Pressure with Use of Periocular Triamcinolone Cream.

Purpose: To evaluate the effect of periocular topical triamcinolone cream on intraocular pressure. Methods: A retrospective chart review identified 57 patients, 114 eyes using triamcinolone cream (0.1%, 0.025%) with subsequent intraocular pressure (IOP) checks at three follow-up visits. Descriptive, univariate, and multivariate analyses were performed to assess effects of age, therapy duration, consecutive weeks on steroid, prescription strength, time of day, and method of measurement on IOP levels. Generalized Estimating Equations were used in regression models to account for correlation of eyes within subjects and across visits. Results: We identified 57 patients using triamcinolone cream for allergic or eczematous dermatitis of the eyelid. Prescription strengths were 0.025% or 0.1% and patients were followed for a median of 4.9 months. Measurements of IOP at baseline did not change as compared to all IOP measurements at follow-ups and did not change with steroid strength. The mean change in IOP at all follow-up visits was 0.07 mm Hg (95% confidence interval [CI]: -0.36, 0.50). After adjustment for the method of tonometer and the patient's age, the mean change was 0.03 mm Hg (95% CI: -0.68, 0.73, P = 0.93). Prescription strength and consecutive weeks of therapy were not associated with IOP. Two patients experienced a significant elevation in IOP of > 10 mm Hg, one through the concomitant consequences of systemic corticosteroids usage and the other through prolonged topical application. Conclusion: In patients taking periocular triamcinolone cream, there was no clinically meaningful change in mean IOP between baseline and follow-up visits, and IOP measurements were not related to variances in prescription strength or duration of therapy.

Association Between Retinal Microanatomy in Preterm Infants and 9-Month Visual Acuity.

Importance: Preterm infants are at risk for poor visual acuity (VA) outcomes, even without retinal problems on ophthalmoscopy. Infant retinal microanatomy may provide insight as to potential causes. Objective: To evaluate the association between preterm infant retinal microanatomy and VA at 9 months' corrected age. Design, Setting, and Participants: This prospective observational study took place from November 2016 and December 2019 at a single academic medical center and included preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS). Infants were eligible for enrollment in BabySTEPS if they met criteria for retinopathy of prematurity (ROP) screening, were 35 weeks' postmenstrual age or older at the time of first OCT imaging, and a parent or guardian provided written informed consent. Of 118 infants enrolled in BabySTEPS, 61 were included in this analysis. Data were analyzed from March to April 2021. Exposures: Bedside optical coherence tomography (OCT) imaging at a mean (SD) 39.85 (0.79) weeks' postmenstrual age and monocular grating VA measurement at 9 months' corrected age. Main Outcomes and Measures: Presence and severity of macular edema and presence of ellipsoid zone at the fovea measured by extracting semiautomated thicknesses of inner nuclear layer, inner retina, and total retina at the foveal center; choroid across foveal 1 mm; and retinal nerve fiber layer (RNFL) across the papillomacular bundle (PMB). Pearson correlation coefficients were calculated and 95% CIs were bootstrapped for the association between retinal layer thicknesses and continuous logMAR VA. Associations were analyzed between retinal microanatomy and normal (3.70 cycles/degree or greater) vs subnormal grating VA at 9 months' corrected age using logistic regression and with logMAR VA using linear regression, adjusting for birth weight, gestational age, and ROP severity at the time of OCT imaging and accounting for intereye correlation using generalized estimating equations. Results: The mean (SD; range) gestational age of included infants was 27.6 (2.8; 23.0-34.6) weeks, and mean (SD; range) birth weight was 958.2 (293.7; 480-1580) g. In 122 eyes of 61 infants, the correlations between retinal layer thicknesses and logMAR VA were as follows: r, 0.01 (95% CI, -0.07 to -0.27) for inner nuclear layer; r, 0.19 (95% CI, 0.01 to 0.35) for inner retina; r, 0.15 (95% CI, -0.02 to 0.31) for total retina; r, -0.22 (95% CI, -0.38 to -0.03) for choroid; and r, -0.27 (95% CI, -0.45 to 0.10) for RNFL across the PMB. In multivariable analysis, thinner RNFL across the PMB (regression coefficient, -0.05 per 10-µm increase in RNFL thickness; 95% CI, -0.10 to -0.01; P = .046) and prior ROP treatment (regression coefficient, 0.33 for ROP treatment; 95% CI, 0.11 to 0.56; P = .003) were independently associated with poorer 9-month logMAR VA. Conclusions and Relevance: In preterm infants, RNFL thinning across the PMB was associated with poorer 9-month VA, independent of birth weight, gestational age, need for ROP treatment, and macular microanatomy. Evaluation of RNFL thickness using OCT may help identify preterm infants at risk for poor vision 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.

Comparison of Visual Acuity Results Between ATS-HOTV and E-ETDRS Testing Methods in Children With Optic Pathway Gliomas.

Purpose: To determine if visual acuity (VA) outcomes are comparable using the amblyopia treatment study HOTV protocol (ATS-HOTV) and electronic Early Treatment of Diabetic Retinopathy Study (E-ETDRS) protocol in children with optic pathway gliomas (OPGs). Methods: Children enrolled in a prospective study of OPGs were eligible if they completed both the ATS-HOTV and E-ETDRS during the same visit. The contribution of age, testing order, having neurofibromatosis type 1, visual field loss, and circumpapillary retinal nerve fiber layer thickness to VA difference were assessed using generalized estimating equations to account for the intereye correlation. Results: Forty-eight children (median age, 10.3 years; range, 5.2-17.1 years; 49% female) met inclusion criteria and contributed 93 study eyes at their initial visit. Eleven patients (22 eyes) had more than one study visit, permitting longitudinal evaluation. ATS-HOTV measures of VA were higher than E-ETDRS at the initial (0.13 ± 0.36 vs. 0.23 ± 0.39 logarithm of the minimum angle of resolution [logMAR], P < 0.001) and all visits (0.13 ± 0.34 vs. 0.21 ± 0.36 logMAR, P < 0.001). VA remained significantly higher with ATS-HOTV regardless of test order, but the mean difference between tests was most profound when tested with ATS-HOTV first compared to E-ETDRS first (P < 0.001). Conclusions: VA results differ significantly between the ATS-HOTV and E-ETDRS testing methods in children with OPGs. Given the wide range of ages and testing ability of children, one VA testing method should be used throughout longitudinal OPG clinical trials. Translational Relevance: It is imperative that age-appropriate VA testing methods are standardized across all pediatric OPG clinical trials.

Prevalence and Factors Associated with Optic Disc Tilt in the Primary Open-Angle African American Glaucoma Genetics Study.

PURPOSE: To investigate the prevalence and factors associated with optic disc tilt in the eyes of Black Americans with glaucoma. DESIGN: Cross-sectional. PARTICIPANTS: Subjects with glaucoma participating in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. METHODS: Stereo pairs of optic disc images were assessed independently by POAAGG-certified nonphysician graders for quantitative features including maximum and minimum linear disc diameters, and qualitative features including gradeability of images, shape of the cup, rim plane position, ß-peripapillary atrophy, sloping region adjacent to the outer disc margin, and rim pallor. Discrepancies were adjudicated by an ophthalmologist. Descriptive statistics and P values were generated for associations of tilt with demographic and ocular characteristics. Stepwise multivariable analysis was performed with logistic regression using Generalized Estimating Equations (GEEs) to account for inter-eye correlation within subjects. MAIN OUTCOME MEASURES: Tilt Ovality Index (TOI) of >1.30 and Stereoscopically Identified optic disc Tilt (SIT). RESULTS: Among 1251 subjects with data on both eyes, 104 (8.3%) had TOI. Subjects with TOI were less likely to be male (adjusted odds ratio [aOR], 0.46, 95% confidence interval [CI], 0.29-0.74, P < 0.001). Eyes with TOI were less likely to have large cup disc ratios (aOR, 0.18, 95% CI, 0.06-0.53, P < 0.001) and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.31, 95% CI, 0.19-0.49, P < 0.001). Among 1007 subjects with data on both eyes, 254 (25.2%) had SIT. Subjects with SIT were younger (aOR, 0.95, 95% CI, 0.93-0.96, P < 0.001), and eyes with SIT were more likely to have oval-shaped discs compared with round discs (aOR, 1.82, 95% CI, 1.32-2.52, P < 0.001), more likely to have a sloping region adjacent to the outer disc margin instead of being flat (aOR, 3.26, 95% CI, 2.32-4.59, P < 0.001), and less likely to have cylinder-shaped cups compared with conical-shaped cups (aOR, 0.59, 95% CI, 0.41-0.85, P < 0.001). Both TOI and SIT were not associated with myopia. CONCLUSIONS: There are substantial numbers of tilted optic discs in glaucoma patients with African ancestry. They occur more frequently in female subjects and younger subjects and are associated with several ocular features but not with myopia.

Tobacco counseling in the setting of thyroid eye disease / Aconselhamento sobre o uso de tabaco no contexto de doenças oculares associadas à tireoide

ABSTRACT 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.

RESUMO Objetivo: Fornecer informações sobre a ocorrência e a eficácia do aconselhamento sobre o uso de tabaco por oftalmologistas a pacientes com doenças oculares associadas à tireoide. Métodos: Analisamos os prontuários médicos eletrônicos de uma coorte digital de pacientes atendidos por oftalmologistas no Sistema de Saúde da Universidade da Pensilvânia entre o início de 2012 e o final de 2017 com os códigos da Classificação Internacional de Doenças (CID) para a doença de Graves, exoftalmia tireotóxica ou doença ocular associada à tireoide. Os históricos de uso de tabaco foram registrados na primeira e na última visita ao consultório de Oftalmologia, ou na visita mais próxima no tempo. A quantidade de maços/dia (mpd) e todas as anotações feitas nas visitas ao consultório de Oftalmologia foram analisadas para aconselhamento sobre o uso de tabaco. Resultados: Um total de 435 indivíduos preencheram os critérios de inclusão, dos quais 72 (16,6%) estavam fumando ativamente no momento do primeiro encontro. Apenas 57 (79,2%) desses indivíduos que fumam ativamente registraram queixas relacionadas ao tabagismo, sendo que 34 (59,6%) deles receberam alguma forma de aconselhamento sobre o uso de tabaco. Ao todo, 9 (26,5%) indivíduos dentre os que receberam aconselhamento sobre tabaco e 1 (4,3%) que não teve aconselhamento registrado pararam de fumar (diferença de risco de 22,1%; IC 95%, [1,7%, 39,1%]; p=0,04). Dentre aqueles que receberam aconselhamento, 17 (50,0%) reduziram seus mpd, além de 7 (30,4%) daqueles que não tiveram aconselhamento (diferença de risco de 19,6%; IC 95% [-6,3%, 41,3%]; p=0,18). No geral, 14 (25,5%) dos 55 oftalmologistas que tiveram um paciente fumante ativo registraram evidências de aconselhamento sobre o uso de tabaco. Conclusões: Os resultados deste estudo revelam tanto as oportunidades perdidas de aconselhamento sobre o uso do tabaco quanto a eficácia do aconselhamento no contexto de doenças oculares associadas à tireoide.

Elevated Intracranial Pressure in Patients with Craniosynostosis by Optical Coherence Tomography.

BACKGROUND: Craniosynostosis may lead to elevated intracranial pressure, which may be implicated with impaired neurocognitive development. However, accurately measuring intracranial pressure is challenging, and patterns in craniosynostosis patients are poorly characterized. Spectral-domain optical coherence tomography may enable noninvasive assessment of intracranial pressure in pediatric patients with craniosynostosis. METHODS: Pediatric patients with craniosynostosis undergoing surgical intervention between 2014 and 2019 prospectively underwent optical coherence tomographic evaluation. Intracranial pressure was directly measured intraoperatively in a subset of cases. Optical coherence tomographic parameters were compared to directly measured intracranial pressure and used for pattern assessment. RESULTS: Optical coherence tomography was performed in 158 subjects, among which 42 underwent direct intracranial pressure measurement during an initial cranial procedure. Maximal retinal nerve fiber layer thickness, maximal retinal thickness, and maximal anterior projection optical coherence tomographic parameters were positively correlated with intracranial pressure (p ≤ 0.001), with all parameters showing significantly higher values in patients with intracranial pressure thresholds of 15 mmHg (p < 0.001) and 20 mmHg (p ≤ 0.007). Patients with maximal retinal nerve fiber layer thickness and maximal anterior projection exceeding set thresholds in optical coherence tomography of either eye demonstrated 77.3 percent sensitivity and 95.0 percent specificity for detecting intracranial pressure above 15 mmHg, and 90.0 percent sensitivity and 81.3 percent specificity for detecting intracranial pressure above 20 mmHg. Patients with associated syndromes or multiple suture involvement and patients aged 9 months or older were significantly more likely to have elevated intracranial pressure above 15 mmHg (p ≤ 0.030) and above 20 mmHg (p ≤ 0.035). CONCLUSIONS: Spectral-domain optical coherence tomography can noninvasively detect elevated intracranial pressure in patients with craniosynostosis with reliable sensitivity and specificity. This technology may help guide decisions about the appropriate type and timing of surgical treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, I.

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.

Clinicopathologic Characteristics and Prognostic Factors Impacting Survival in Melanoma of the Eyelid.

PURPOSE: To examine prognostic factors for survival in patients with melanoma of the eyelid. DESIGN: Retrospective cohort study. METHODS: This population-based study reviewed patients with primary melanoma of the eyelid diagnosed in the Surveillance, Epidemiology and End Results database between 1975 and 2016. The primary outcomes included survival rates estimated by Kaplan-Meier analysis and mortality hazard ratios (HRs) for overall survival and disease-specific survival (DSS). RESULTS: The cohort consisted of 2257 patients with cutaneous melanoma of the eyelid, representing 1380 cases of melanoma in situ and 877 cases of invasive melanoma. For melanoma in situ and invasive melanoma respectively, at 5 years, the overall survival rates were 88.6% and 77.1%, while DSS rates were 99.4% and 91.0%. Cox regression analysis for eyelid melanoma indicated that for invasive melanoma, age at diagnosis ≥75 years (HR 2.17 [95% confidence interval {CI} 1.02-4.60]; P = .04), T4 staging (HR 8.45 [95% CI 2.96-25.31]; P < .001), lymph node involvement (HR 3.61 [95% CI 1.12-11.60]; P = .03), and nodular melanoma (HR 3.31 [95% CI 1.50-7.32]; P = .003) histologic subtype were associated with decreased rates of survival. Sex and tumor ulceration did not impact survival. CONCLUSIONS: This study is the largest analysis to date that focuses on DSS for cutaneous melanoma of the eyelid. The most significant predictors for invasive melanoma survival are age ≥75 years at diagnosis, T4 staging, lymph node involvement, and the nodular melanoma histologic subtype. Patients with these attributes are at higher risk and should be counseled regarding prognosis.