Association of Somatic TET2 Mutations With Giant Cell Arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is an age-related vasculitis. Prior studies have identified an association between GCA and hematologic malignancies (HMs). How the presence of somatic mutations that drive the development of HMs, or clonal hematopoiesis (CH), may influence clinical outcomes in GCA is not well understood. METHODS: To examine an association between CH and GCA, we analyzed sequenced exomes of 470,960 UK Biobank (UKB) participants for the presence of CH and used multivariable Cox regression. To examine the clinical phenotype of GCA in patients with and without somatic mutations across the spectrum of CH to HM, we performed targeted sequencing of blood samples and electronic health record review on 114 patients with GCA seen at our institution. We then examined associations between specific clonal mutations and GCA disease manifestations. RESULTS: UKB participants with CH had a 1.48-fold increased risk of incident GCA compared to UKB participants without CH. GCA risk was highest among individuals with cytopenia (hazard ratio [HR] 2.98, P = 0.00178) and with TET2 mutation (HR 2.02, P = 0.00116). Mutations were detected in 27.2% of our institutional GCA cohort, three of whom had HM at GCA diagnosis. TET2 mutations were associated with vision loss in patients with GCA (odds ratio 4.33, P = 0.047). CONCLUSIONS: CH increases risk for development of GCA in a genotype-specific manner, with the greatest risk being conferred by the presence of mutations in TET2. Somatic TET2 mutations likewise increase the risk of GCA-associated vision loss. Integration of somatic genetic testing in GCA diagnostics may be warranted in the future.

Eosinophilic Angiocentric Fibrosis of the Orbit: A Clinicopathologic Review of 6 Novel Cases With Review of the Literature.

PURPOSE: To describe 6 cases and review the current state of knowledge of eosinophilic angiocentric fibrosis (EAF) involving the orbit. DESIGN: Retrospective clinicopathologic case series and review of the current literature METHODS: Clinical records and histopathologic data of orbit-involving EAF were gathered between 2004 and 2022 from a single academic institution. The patients' presenting clinical symptoms and signs, laboratory data, radiographic studies, and management documentation were collected. RESULTS: Retrospective review identified 6 novel cases, totaling 31 cases of EAF involving the orbit described as of this writing. Fourteen patients were male, and the average age of presentation was 49.8 years (range 25-78 years). Eighteen patients had concurrent sinonasal involvement, whereas 13 had primary orbital involvement. The median duration of symptoms prior to evaluation was 24 months, with nasal symptoms, proptosis, periorbital swelling, and pain being the most common presenting symptoms. The majority of patients underwent surgical debulking, as well as treatment with glucocorticoids and steroid-sparing agents, such as rituximab, with varied results. CONCLUSION: EAF involving the orbit is uncommon. The histopathologic findings include a perivascular, eosinophil-rich infiltrate and a pauci-inflammatory storiform type of fibrosis concentrated around small vessels. Orbital involvement usually results from local extension from adjacent sinuses, but primary orbital involvement has been described. Surgical debulking and immunosuppressive agents such as rituximab have been shown to stabilize disease.

Safety of Botulinum Toxin A Injections for Facial Rejuvenation: A Meta-Analysis of 9,669 Patients.

PURPOSE: To quantitatively evaluate safety profile for botulinum toxin A (BTX-A) injections among patients undergoing treatment for cosmetic indications is produced, with special attention to clinically relevant covariates and their relative impact on safety. METHODS: A systematic literature search was performed using PubMed (1996-January 2020) and Embase (1947-January 2020) to identify all randomized controlled trials (RCTs) that reported safety data for patients receiving BTX-A for cosmetic indications compared to placebo. A meta-analysis was performed to determine pooled risk ratios (RR) for treatment-related adverse events (TRAEs) and for specific adverse events. Meta-regression and additional analyses were performed for significant and/or clinically relevant covariates. RESULTS: Following the review of 8,690 studies, 32 RCTs involving 9,669 patients were included. The pooled RR of any TRAE occurring after BTX-A injection compared to placebo injection was 1.53 (95% CI, 1.33-1.77; p < 0.001). Statistically significant covariates included individual injection volume and total injection volume. The type of BTX-A formulation, treatment site, total BTX-A units, and BTX-A units per injection were not significant. Specific adverse events more likely to occur following BTX-A injection rather than placebo injection included eyelid/eyebrow malposition (RR 3.55; p < 0.001), facial paresis (RR 2.42; p = 0.316), and headache (RR 1.45; p = 0.003). Injection site reactions and injection site bruising occurred at similar rates in both groups. CONCLUSIONS: The overall safety profile of BTX-A is acceptable and consistent with previous publications. The authors' additional analyses provide a relative comparison of the impact of various treatment parameters on safety.

Orbital Inflammation in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: A Case Report and Review of the Literature.

BACKGROUND: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype. METHODS: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD). RESULTS: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust. CONCLUSION: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.

Radiographic analysis of fatty infiltration of the extraocular muscles in thyroid eye disease.

PURPOSE: Fatty infiltration of the extraocular muscles has been described radiographically in patients with thyroid eye disease (TED), yet it has not been studied on a large scale nor quantified. Our purpose was to define and characterize this entity in patients with TED. METHODS: An IRB-approved cross-sectional retrospective review of medical records identified patients with a clinical diagnosis of TED and at least one CT of the orbits. A 2:1 age and sex-matched control population consisted of patients without a history nor radiographic evidence of orbital disease or systemic thyroid abnormality. The presence of fatty infiltration in each extraocular rectus muscle was defined using Hounsfield units (HU). Laterality, muscles involved, and pattern of fatty infiltration were also evaluated. Student's t-tests, Chi-square, and Fisher's exact tests were used to compare TED and control groups. RESULTS: The study population consisted of 252 patients with TED and 504 age and sex-matched controls. Fatty infiltration was significantly more prevalent in TED patients (36/252, 14.3%) compared to controls (11/504, 2.2%) (p < .001). The mean density of fat infiltration was significantly lower in TED patients (-40.4 HU) than controls (-34.8 HU) (p = .048). In TED patients, the frequency of muscle involvement was inferior rectus (61.8%), lateral rectus (19.7%), superior rectus (11.8%) and medial rectus (6.6%), which was not significantly different than controls (p > .05). Most muscles (88.2%) in the TED group exhibited a heterogeneous pattern of infiltration, which did not differ from controls (p = .34). CONCLUSIONS: This study characterizes fatty infiltration of the extraocular muscles in patients with TED.

Comparative Incidence of Periocular Surgical Site Infections with Increased Surgical Mask Use during the COVID-19 Pandemic.

PURPOSE: To evaluate the effect of surgical mask use on infection rates for office-based periocular surgeries during the pandemic. METHODS: An Institutional Review Board-approved retrospective review of medical records identified patients who had an office-based oculofacial plastic surgery procedure during the pandemic between March and December 2020. Statistical analysis was used to compare this group to patients that underwent procedures between March and December 2019, prior to the pandemic when neither surgeon nor patient wore a surgical mask. RESULTS: The study consisted of 680 patients. Thirty-one different types of procedures were encountered. The incidence of infections in 2020 compared to 2019 was not statistically significant (1.12% (n = 3) versus 1.21% (n = 5), p = 1). All patients with infections were treated with oral antibiotics and improved without long-term complications. CONCLUSIONS: Periocular surgical site infections are uncommon, and the wearing of surgical masks by patient and surgeon during our office-based oculofacial procedures did not change the incidence of SSIs.

Advances in Telemedicine in Ophthalmology.

Telemedicine is the provision of healthcare-related services from a distance and is poised to move healthcare from the physician's office back into the patient's home. The field of ophthalmology is often at the forefront of technological advances in medicine including telemedicine and the use of artificial intelligence. Multiple studies have demonstrated the reliability of tele-ophthalmology for use in screening and diagnostics and have demonstrated benefits to patients, physicians, as well as payors. There remain obstacles to widespread implementation, but recent legislation and regulation passed due to the devastating COVID-19 pandemic have helped to reduce some of these barriers. This review describes the current status of tele-ophthalmology in the United States including benefits, hurdles, current programs, technology, and developments in artificial intelligence. With ongoing advances patients may benefit from improved detection and earlier treatment of eye diseases, resulting in better care and improved visual outcomes.

Advances in steroid sparing medical management of active thyroid eye disease.

Thyroid eye disease (TED) is an autoimmune inflammatory disease of the orbit and the most common extrathyroidal manifestation of Graves disease. The release of pro-inflammatory cytokines is associated with inflammation of the ocular surface and lacrimal gland along with periorbital skin erythema and edema. Resultant tissue remodeling, fibrosis, and fat deposition can impart permanent physical changes to the ocular adnexa with effects on function and cosmesis. These changes occur in the active phase of disease, and it is during this time that steroids are often relied on to help alleviate symptoms. Due to the common and predictable side effects of long-term and high-dose steroid use, there has been a continuous effort to find alternative steroid-sparing medical management options for TED. This review highlights the various research studies that support the use of these medications.

Giant Dermatofibrosarcoma Protuberans With Bilateral Orbital Involvement.

Dermatofibroma sarcoma protuberans (DFSP) is a rare, locally aggressive soft tissue sarcoma with a tendency for recurrence after excision. Although reports of unilateral orbital and bilateral eyelid disease exist, there have been no prior reports of DFSP with bilateral orbital involvement and no previously described cases of DFSP associated with transient optic neuropathy. The authors present a case report of a 34-year-old woman with a giant scalp DFSP involving the bilateral orbits. Despite radical resection with 5 cm margins where possible, multiple positive margins remained including deep positive margins at the bilateral superomedial retroseptal soft tissue. The patient completed adjuvant radiation for surgically unresectable disease. This case highlights the challenge of achieving local control given the disease extent and infiltration of the bilateral eyelids and orbits. This is the first reported case of DFSP with bilateral orbital involvement and associated transient optic neuropathy.

Sarcomatoid Renal Cell Carcinoma Metastasis to the Penis.

Secondary cancers of the penis are extremely uncommon with less than 300 cases reported in the past 100 years. These cancers are most frequently a result of an aggressive or poorly managed primary prostate or bladder cancer and rarely a metastasis from a primary kidney tumor. Currently, there is no published literature which describes the spread of sarcomatoid renal cell carcinoma (SRCC) to the penis. In this report, we present a 55-year-old-man who presented with a large right-sided SRCC which metastasized to the base of his penis within 1 month of symptom onset. We also discuss the possible route of metastasis based on primary tumor size and location within the retroperitoneum.

Validating hyperbilirubinemia and gut mucosal atrophy with a novel ultramobile ambulatory total parenteral nutrition piglet model.

Total parenteral nutrition (TPN) provides all nutrition intravenously. Although TPN therapy has grown enormously, it causes significant complications, including gut and hepatic dysfunction. Current models use animal tethering which is unlike ambulatory human TPN delivery and is cost prohibitive. We hypothesize that using ultramobile infusion pumps, TPN can be delivered cost-effectively, resulting in classical gut and hepatic injury, and we thus aim to establish a new model system. Neonatal pigs (n=8) were implanted with jugular vein and duodenal catheters. Animals were fitted in dual-pocket jackets. An ultramobile ambulatory pump was placed in one pocket and connected to the jugular vein or duodenal catheter. Isocaloric TPN or swine formula was placed in the other pocket. Rigorous Wifi-based video and scheduled monitoring was performed. After 14days, the animals were euthanized. The mean (±SD) daily weight gain (in grams) for enteral-fed control (EN) vs TPN animals was 102.4±10.8 and 91.03±12.1 respectively (P<.05). Total parenteral nutrition resulted in significant conjugated bilirubin elevation and hepatomegaly. Mean (±SD) serum conjugated bilirubin (in µmol/L) was 1.5±0.7 for EN and 6.3±2.8 for TPN (P<.05). Marked gut atrophy was noted with TPN. The mean (±SD) gut weight as a percent of body weight was 4.30±0.26 for EN and 2.62±0.48 for TPN (P<.05). Surgical sites healed well. All animals remained completely mobile. We thus established that TPN can be successfully delivered using ultramobile pumps and believe that this remains the first such description of an ambulatory piglet TPN model system. In addition to cholestasis and gut atrophy, classical TPN-induced injury was documented.

Racial differences in beliefs of physician prescribing practices for low-cost pharmacy options.

BACKGROUND: Previous studies have reported that certain populations are sensitive to high out-of-pocket drug costs, and drug noncompliance leads to poorer health outcomes. OBJECTIVE: Our aim was to measure patient awareness of discount pharmacy options, cost barriers to medication access, and beliefs about health care provider's use of low-cost medications. METHODS: This cross-sectional 17-item survey was administered to patients in the emergency department of an urban trauma center in February 2011. Differences in responses by sex and race groups were assessed. A logistic regression model was created to estimate the association of sociodemographic factors and medication use with awareness of discount pharmacy options. RESULTS: Five hundred and fifty-two surveys were analyzed. Among respondents who were prescribed medications within the past year, three fourths of patients felt comfortable asking physicians for cheaper medicines. Slightly more than half were aware of low-cost pharmacy options, and 78% of these respondents correctly listed at least one of these pharmacies. Caucasian patients were more comfortable than African American patients asking for cheaper medicines (82.5% vs. 72.2%; p < 0.05) and were more aware of low-cost prescription programs (63.9% vs. 43.5%; p < 0.001). When adjusted for insurance status and current medication use, Caucasian patients were 2.7 times more likely to name a valid discount pharmacy option compared to African Americans (95% confidence interval 1.85-4.07). CONCLUSIONS: This study suggests populations may be more uncomfortable initiating a discussion about medication costs and selection of lower-cost alternatives. Health care providers may need to develop communication strategies in which medication cost is addressed with sensitivity and consistency.