Long-Term Follow-Up of a Case of Severe Hyperglycemia Requiring Hospitalization after Third Dose of Teprotumumab: A Case Report.

Introduction: In 2020, teprotumumab became the first FDA-approved treatment for thyroid eye disease (TED). In clinical trials, hyperglycemia had been described as mild and controlled with medication. We present a case that occurred in 2020 of a 67-year-old male with TED and pre-existing glucose intolerance, who was hospitalized with severe hyperglycemia (1,059 mg/dL) after three doses of teprotumumab. Case Presentation: This patient's HbA1c was in the pre-diabetic range (6.3%) 6 months prior to initiating teprotumumab. After three doses, the patient was hospitalized with hyperosmolar hyperglycemic nonketotic syndrome and an HbA1c of 11.7%. He was diagnosed with type 2 diabetes mellitus and treated with insulin aspart mixed 70/30. He remained on this regimen for 14 months with an A1c of 6.0%. He then self-discontinued the insulin, with an A1c 4 months later measuring 5.5%. The patient's latest HbA1c approximately two and a half years after hospitalization was 6.1% on no medications. Conclusion: It appears that teprotumumab was a trigger for this transient case of diabetes, and detecting those that have underlying glucose intolerance ahead of time is important. We recommend blood glucose levels for patients with pre-diabetes prior to and ideally in the first few days after each infusion, to help determine patients at a greater risk for adverse hyperglycemic outcomes. A glucometer may be valuable for patients to self-monitor while on teprotumumab. If fasting blood glucose is ≥126 mg/dL or non-fasting glucose is >200 mg/dL, patients should be referred for further diabetes assessment and possible treatment initiation.

Repeatability and Reproducibility of 4.5 by 4.5 mm Peripapillary Optical Coherence Tomography Angiography Scans in Glaucoma and Non-Glaucoma Eyes.

PRCIS: Peripapillary vessel parameters from optical coherence tomography angiography (OCTA) 4.5×4.5 mm scans in nonglaucomatous and glaucomatous eyes showed high repeatability and reproducibility, with higher reliability for commercially developed OCTA parameters compared with custom OCTA parameters. PURPOSE: The purpose of this study was to assess intrasession repeatability versus intersession reproducibility of peripapillary vessel parameters from 4.5×4.5 mm OCTA scans in nonglaucomatous eyes and glaucomatous eyes. MATERIALS AND METHODS: In a longitudinal study, peripapillary OCTA scans were quantified using research-oriented custom quantification software that calculated vessel area density (VAD) and flux and clinic-oriented commercially developed software (Cirrus 11.0) that calculated perfusion density (PD) and flux index (FI). Intrasession repeatability and intersession reproducibility were evaluated using within-eye coefficient of variation (CV W ) and intraclass correlation coefficient (ICC). RESULTS: With 127 nonglaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were 1.900%, 1.174%, 2.787%, and 1.425%, respectively. The intersession CV W were 2.039%, 1.606%, 4.053%, and 2.798%, respectively. Intrasession ICC ranged from 0.903 to 0.956, and intersession ICC ranged from 0.850 to 0.896. Among 144 glaucomatous eyes, intrasession CV W for VAD, PD, flux, and FI were: 3.841%, 1.493%, 5.009%, and 2.432%, respectively. The intersession CV W were 4.991%, 2.155%, 6.360%, and 3.458%, respectively. Intrasession ICC ranged from 0.956 to 0.969, and intersession ICC ranged from 0.918 to 0.964. CONCLUSIONS: Among nonglaucomatous and glaucomatous eyes, the majority of peripapillary OCTA vessel parameters from 4.5×4.5 mm scans had greater intrasession repeatability than intersession reproducibility. There was a greater agreement for the commercially developed quantification parameters than for their custom quantification counterparts.

Intrasession Repeatability and Intersession Reproducibility of Macular Vessel Parameters on Optical Coherence Tomography Angiography in Glaucomatous and Non-Glaucomatous Eyes.

PURPOSE: Using optical coherence tomography angiography (OCTA), this study compared intrasession repeatability versus intersession reproducibility of macular vessel parameters in glaucoma and non-glaucoma subjects. METHODS: 6 × 6 mm2 macular OCTA scans (Cirrus HD-OCT 5000) were acquired from glaucomatous and non-glaucomatous subjects as part of an observational, longitudinal study. Vessel area density (VAD) and vessel skeleton density (VSD) were calculated using research-based quantification software while perfusion density (PDZ) and vessel density (VDZ) were calculated using commercially developed software (Cirrus 11.0, Carl Zeiss Meditec). Intrasession repeatability and intersession reproducibility were determined using within-eye standard deviation (SW), within-eye coefficient of repeatability (CRW), within-eye coefficient of variation (CVW), and intraclass correlation coefficients (ICC). RESULTS: The intrasession repeatability and intersession reproducibility for macular OCTA parameters were similar to one another for both non-glaucomatous and glaucomatous eyes. Intrasession CVW from the non-glaucoma group (n = 73) was 1.097% for VAD, 1.007% for VSD, 2.980% for PDZ, and 2.714% for VDZ. Intersession CVW from the non-glaucoma group (n = 55) was 1.389% for VAD, 1.279% for VSD, 2.935% for PDZ, and 2.695% for VDZ. Intrasession CVW from the glaucoma group (n = 59) was 1.189% for VAD, 0.970% for VSD, 3.827% for PDZ, and 3.542% for VDZ. Intersession CVW from the glaucoma group (n = 45) was 1.412% for VAD, 1.132% for VSD, 3.915% for PDZ, and 3.654% for VDZ. Non-glaucomatous intrasession ICC ranged from 0.711 to 0.824, non-glaucomatous intersession ICC ranged from 0.649 to 0.762, glaucomatous intrasession ICC ranged from 0.710 to 0.853, and glaucomatous intersession ICC ranged from 0.661 to 0.827. CONCLUSIONS: Macular OCTA scans can be a useful tool in monitoring the longitudinal progression of glaucoma due to their high repeatability and reproducibility.

Wedge Defects on Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma: Prevalence and Associated Clinical Factors.

PRCIS: Among subjects with glaucoma, wedge-shaped defects on optical coherence tomography angiography (OCTA) were associated with disc hemorrhages (DH), paracentral visual field (VF) defects, increased cup-to-disc ratio (CDR), and thinner retinal nerve fiber layer (RNFL). PURPOSE: To examine determinants of wedge defects on peripapillary OCTA in glaucoma. MATERIALS AND METHODS: A total of 278 eyes of 186 subjects with mild to severe primary open-angle glaucoma underwent 6×6 spectral-domain OCTA imaging of the superficial peripapillary retina from 2016 to 2020 at an academic practice. Wedge defects were defined as focal microvasculature loss that extends outward from the optic nerve in an arcuate, wedge shape. Logistic regression models controlling for intereye correlation identified variables significantly associated with wedge defects. Eyes with profound microvasculature loss in both hemispheres were excluded. Candidate variables included: age, sex, race or ethnicity, diabetes, hypertension, follow-up duration, baseline untreated intraocular pressure, intraocular pressure at time of imaging, DH history, paracentral VF defects, CDR, central corneal thickness, spherical equivalent, VF mean deviation, RNFL thickness, and glaucoma stage. RESULTS: Of 278 eyes, 126 (45.3%) had wedge defects in at least 1 hemisphere. In our multivariable logistic regression model, wedge defects were associated with DH history [odds ratio (OR): 3.19, 95% confidence interval (CI): 1.05-9.69, P=0.041], paracentral VF defects [OR: 4.38 (95% CI: 2.11-9.11), P<0.0001], larger CDR [OR: 1.27 (95% CI: 1.03-1.56), P=0.024, per 0.1 increase], and thinner RNFL [OR: 1.71 (95% CI: 1.25-2.34), P=0.0009, per 10 µm decrease]. CONCLUSION: DH history and paracentral VF defects were independently associated with wedge defects on OCTA, which was present in 45.3% of primary open-angle glaucoma patients. These findings may provide insight into glaucoma pathogenesis.

Health Within Reach-a Patient-Centered Intervention to Increase Hepatitis B Screening Among Asian Americans: a Randomized Clinical Trial.

BACKGROUND: There are few studies to date of interventions to increase viral hepatitis screening among Asian Americans, who have high rates of chronic hepatitis B (HBV) infection. OBJECTIVE: To develop, implement, and test the efficacy of a mobile application (Hepatitis App) delivered in four languages to increase HBV screening among Asian Americans. DESIGN: Cluster-randomized clinical trial. PARTICIPANTS: Four hundred fifty-two Asian American patients ≥ 18 years of age, who had no prior HBV testing, and received primary care within two healthcare systems in San Francisco, CA. INTERVENTIONS: The intervention group received the Hepatitis App, delivering interactive video education on viral hepatitis in English, Cantonese, Mandarin, or Vietnamese and a provider printout (Provider Alert) and Provider Panel Notification. The comparison group received a mobile application delivering nutrition and physical activity education and Provider Panel Notification. MAIN MEASURES: Primary outcomes were patient-provider discussion about HBV and documentation of a HBV screening test within 3 months post-intervention. Secondary outcome was documentation of an order for a HBV screening test. KEY RESULTS: Participants had a mean age of 57 years and were 64% female, 80% foreign-born, and 44% with limited English fluency. At post-visit, over 80% of intervention participants reported they liked using the Hepatitis App. At 3-month follow-up, the intervention group was more likely than the comparison group (all P < 0.001) to have discussed HBV with their provider (70% vs.16%), have a HBV test ordered (44% vs.10%), and receive a HBV test (38% vs.8%). In multivariable analyses, the intervention odds ratio for HBV test ordering was 7.6 (95% CI: 3.9, 14.8) and test receipt was 7.5 (95% CI: 3.6, 15.5). CONCLUSIONS: A multi-lingual educational intervention using a mobile application in primary care clinics was well received by Asian American patients, enhanced patient-provider communication about HBV, and increased HBV screening. Technology can improve healthcare quality among Asian Americans. TRIAL REGISTRATION: ClinicalTrials.gov NCT02139722 ( https://clinicaltrials.gov/ct2/show/NCT02139722 ).

Longer Axial Length Potentiates Relationship of Intraocular Pressure and Peripapillary Vessel Density in Glaucoma Patients.

Purpose: The purpose of this study was to investigate how axial length (AL) changes the relationship of intraocular pressure (IOP) with peripapillary vessel density (pVD) in glaucoma versus non-glaucomatous eyes. Methods: A population-based, cross-sectional study of 2127 African Americans aged 40 years and older in Inglewood, California, were imaged with 6 × 6-mm optic disc optical coherence tomography angiography scans. There were 1028 healthy subjects (1539 eyes) and 65 subjects with glaucoma (86 eyes) who met inclusion criteria. A multivariable linear mixed effects regression model investigated the relationship of IOP on pVD after controlling for signal strength, retinal nerve fiber layer thickness, and age. These results were stratified by AL groups. Results: Higher IOP was a significant predictor of lower pVD among subjects with glaucoma (P = 0.009), but not among healthy subjects (P = 0.26). After stratifying by the sample median AL (23.46 mm), higher IOP was associated with lower pVD among subjects with glaucoma with longer AL (≥ 23.46 mm, P = 0.005), but not among those in the shorter AL (< 23.46 mm, P = 0.45). IOP was not significantly associated with pVD among healthy subjects in either AL stratum. Conclusions: Among subjects with glaucoma with longer AL, IOP was significantly associated with pVD. This relationship was not seen among subjects with glaucoma with shorter AL or non-glaucomatous subjects in either AL group. These findings support the hypothesis that disturbed retinal autoregulation may be present in subjects with glaucoma with longer AL. Longitudinal studies are needed to further investigate whether axial elongation increases glaucoma risk by compromising retinal autoregulation.

Hemiretinal Asymmetry in Peripapillary Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PURPOSE: To investigate hemiretinal asymmetry in radial peripapillary capillary vessel area density (VAD) of healthy, glaucoma suspect, and glaucoma eyes of varying severity and its diagnostic utility for glaucoma. DESIGN: Population-based, cross-sectional study. METHODS: Optic disc scans (6 × 6 mm) were collected on optical coherence tomography angiography (OCTA) to obtain VAD and on optical coherence tomography (OCT) to measure circumpapillary retinal nerve fiber layer (RNFL) thickness. Hemiretinal difference in VAD (hdVAD) was defined as the absolute difference between superior and inferior hemiretinal VAD. Age-adjusted multivariable linear regression of hdVAD on glaucoma severity was performed. Areas under curves (AUCs) were calculated from predicted probabilities generated by multiple logistic regression of glaucoma severity on age-adjusted single and combined parameters. RESULTS: A total of 1,043 eyes of 1,043 participants (587 healthy, 270 suspect, 67 mild, 54 moderate, 65 severe glaucoma) were included. After age adjustment, mean hdVAD was similar between healthy and suspect (P = .225), higher in mild vs suspect (P < .001), and higher in moderate vs mild (P = .018), but lower in severe vs moderate (P = .001). AUCs of hdVAD were highest for discriminating mild (0.685) and moderate (0.681) glaucoma from healthy. Combining hdVAD and global RNFL (gRNFL) yielded the highest AUCs of all parameters for mild (0.818) and any POAG (0.859) and resulted in significantly better diagnostic accuracy than either hdVAD or gRNFL alone (P < .05 for all comparisons). CONCLUSIONS: hdVAD is higher in early glaucoma and may help with early detection when damage is focal, but its diagnostic ability appears less robust in advanced glaucoma when damage is diffuse.

Steps to Measurement Floor of an Optical Microangiography Device in Glaucoma.

PURPOSE: To compare dynamic ranges and steps to measurement floors of peripapillary and macular metrics from a complex signal-based optical microangiography (OMAGC) optical coherence tomography angiography (OCTA) device for glaucoma with those of OCT measurements. DESIGN: Cross-sectional study. METHODS: Imaging of 252 eyes from 173 patients with glaucoma and 123 eyes from 92 subjects without glaucoma from a glaucoma clinic was quantified using custom and commercial software. Metrics from OCT (retinal nerve fiber layer [RNFL], ganglion cell/inner plexiform layer [GCIPL]) and OCTA (custom: peripapillary vessel area density [pVAD], macular vessel area density [mVAD], and macular vessel skeleton density [mVSD]; commercial: peripapillary perfusion density [pPDZ], macular perfusion density [mPDZ], and macular vessel density [mVDZ]) were plotted against visual field mean deviation (MD) with linear change-point analyses, measurement floors, and steps to floors. RESULTS: Mean MD (dB) for glaucomatous eyes was -5.77 (-6.45 to -5.10). The number of eyes with mild glaucoma (MD >-6), moderate glaucoma (MD -6 to -12), and severe glaucoma (MD <-12) were 164, 50, and 38, respectively. pPDZ yielded the lowest estimated floor at -26.6 dB (standard error [SE] 1.53), followed by OCTA macular metrics (-25 to -21 dB; SE 1.03) and pVAD (-17.6 dB, SE 1.06). RNFL and GCIPL produced floors at -17.8 (SE 0.927) and -23.6 dB (SE 1.14). The highest number of steps to measurement floor belonged to RNFL (7.20) and GCIPL (7.33), followed by pPDZ (4.25), mVAD (3.87), and mVSD (3.81), with 2.5 or fewer steps for pVAD, mPDZ, and mVDZ. CONCLUSIONS: pPDZ, mVAD, and mVSD had approximately 4 steps within their dynamic ranges, without true measurement floors, and thus may be useful in evaluating advanced glaucomatous progression. Improving OCTA test-retest repeatability could augment number of steps for OCTA metrics, increasing their clinical utility.

Ankyloglossia: Last three-years of outpatient care at a tertiary referral center.

INTRODUCTION: Ankyloglossia is an oral anomaly characterized by a shortened, thickened lingual frenulum that may cause reduced tongue mobility. However, the diagnosis and management of this condition has long been a debated topic. Given the paucity of high level evidence, management can be frustrating for both families and clinicians. Our study aims to examine differences in the management of ankyloglossia and investigate influencing factors at a single tertiary pediatric referral center. METHODS: A retrospective chart review was completed of children less than one year of age seen in the outpatient otolaryngology clinic. Billing records were searched for ICD-9 code 750.0 (ankyloglossia) between January 2, 2015 and October 9, 2017 and data extracted from the charts of those meeting inclusion criteria. RESULTS: A total of 266 charts were reviewed that met the inclusion criteria during the study period. 100 (38%) were female with a mean age of 2.9 months. In the final multivariate regression model, children seen by providers in Group 1 (providers with high rates of frenotomies) had 4.4 times the odds of having a frenotomy as those seen by a provider in Group 2 (providers with low rates of frenotomies) (p < 0.001, 95%CI: 2.2, 8.9), and male children had 2.5 times the odds of having a frenotomy as female children (p = 0.002, 95%CI: 1.4, 4.5). CONCLUSION: In this study we identify additional variables that may influence the decision to perform a frenotomy in children with ankyloglossia. The significant impact of clinician biases in the management of ankyloglossia suggests arbitrary differences in the way these patients are managed, highlighting the lack of consensus amongst otolaryngologists and the need for clear indications and diagnostic criteria.

Systemic Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

PURPOSE: To determine the relationship between systemic factors and radial peripapillary capillary (RPC) vessel density (VD) in healthy African American (AA) participants of the African American Eye Disease Study. DESIGN: A population-based, cross-sectional study. METHODS: A total of 4135 eyes from 2127 AA participants aged 40 years and older in Inglewood, California, were imaged for 6×6-mm optic disc scans on a spectral-domain optical coherence tomography angiography (OCTA) device. Of these, 1029 eyes from 1029 participants who met the inclusion and exclusion criteria were analyzed, including only 1 eye per participant. Custom software was used to quantify RPC VD. Multivariate linear regression was used to identify systemic factors associated with RPC VD with a significance level set at 0.05. The contribution of each variable to the final model was estimated with the magnitude of standardized regression coefficients (SRCs). The fit of the final model was measured by R2. RESULTS: The average RPC VD was 0.346±0.045. Controlling for signal strength, the systemic variables in the final multivariate model associated with reduced RPC VD were older age (ß = -0.0123 per decade; SRC = -0.2733; P < .0001), male sex (ß = -0.0067; SRC = -0.0716; P = .0060), and longer diabetes duration (ß = -0.0022 per 5 years; SRC = -0.0527; P = .0427). The model R2 was 0.3689. CONCLUSIONS: Age, sex, and systemic influences, such as diabetes duration, need to be considered when assessing changes in RPC VD in glaucoma and other ocular diseases. Longitudinal studies are needed to investigate whether reduced RPC VD and the factors that affect it are associated with an increased risk of developing glaucomatous nerve damage.

Ocular Determinants of Peripapillary Vessel Density in Healthy African Americans: The African American Eye Disease Study.

Purpose: The African American (AA) population has unique ocular anatomic characteristics and a disproportionately high incidence of glaucoma, which is associated with lower peripapillary vessel density (VD). This study aimed to identify ocular determinants of peripapillary VD in healthy AAs. Methods: This was a cross-sectional, population-based study of 1029 AAs, ages 40 and older. Participants underwent examination to obtain axial length (AL), IOP, central corneal thickness (CCT), mean retinal nerve fiber layer (RNFL) thickness, visual field mean deviation (MD), and 6 × 6-mm optical coherence tomography angiography scans of the optic nerve. Participants with glaucoma, vision-threatening diabetic retinopathy, or other relevant ocular disease were excluded. Prototype software was used to quantify VD. A multivariable regression model, controlling for age and signal strength, identified the ocular variables that predicted peripapillary VD. The contribution of each variable was assessed with the magnitude of standardized regression coefficients (SRC). Results: Based on univariate regressions, AL, RNFL thickness, and MD had significant associations with peripapillary VD (all P < 0.001). In the final multivariate model, lower mean RNFL thickness (ß = 0.0022, P < 0.001, SRC = 0.542) and longer AL (ß = -0.0055, P < 0.001, SRC = -0.118) were associated with lower peripapillary VD, controlling for age and signal strength, with model R2 of 0.69. Conclusions: Thinner RNFL and longer AL were the most influential ocular determinants of lower peripapillary perfusion in healthy AA eyes. Additional research is needed to clarify whether longer AL increases risk of glaucoma by affecting capillary perfusion.