A remnant planetary core in the hot-Neptune desert.

The interiors of giant planets remain poorly understood. Even for the planets in the Solar System, difficulties in observation lead to large uncertainties in the properties of planetary cores. Exoplanets that have undergone rare evolutionary processes provide a route to understanding planetary interiors. Planets found in and near the typically barren hot-Neptune 'desert'1,2 (a region in mass-radius space that contains few planets) have proved to be particularly valuable in this regard. These planets include HD149026b3, which is thought to have an unusually massive core, and recent discoveries such as LTT9779b4 and NGTS-4b5, on which photoevaporation has removed a substantial part of their outer atmospheres. Here we report observations of the planet TOI-849b, which has a radius smaller than Neptune's but an anomalously large mass of [Formula: see text] Earth masses and a density of [Formula: see text] grams per cubic centimetre, similar to Earth's. Interior-structure models suggest that any gaseous envelope of pure hydrogen and helium consists of no more than [Formula: see text] per cent of the total planetary mass. The planet could have been a gas giant before undergoing extreme mass loss via thermal self-disruption or giant planet collisions, or it could have avoided substantial gas accretion, perhaps through gap opening or late formation6. Although photoevaporation rates cannot account for the mass loss required to reduce a Jupiter-like gas giant, they can remove a small (a few Earth masses) hydrogen and helium envelope on timescales of several billion years, implying that any remaining atmosphere on TOI-849b is likely to be enriched by water or other volatiles from the planetary interior. We conclude that TOI-849b is the remnant core of a giant planet.

Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Frozen Section Histoanatomy of the Peritarsal Eyelid.

BACKGROUND: Mohs surgery of eyelid skin cancers requires detailed knowledge of anatomy for precise surgery and accurate evaluation of histology. OBJECTIVE: To review the histology of the peritarsal eyelid using frozen sections as encountered intraoperatively by Mohs surgeons. METHODS: The authors review the literature describing the anatomy and histology of the peritarsal eyelid from the lens of a Mohs surgeon. Histology from select Mohs cases is used to frame the discussion of the microanatomy of this region. RESULTS: The peritarsal eyelids contain a unique mixture of skin, muscle, tarsus, glandular tissue, and conjunctiva. The histologic appearance of many of these structures differs from skin found outside of this anatomic region. Tumors of the eyelid and periocular region may mimic normal histologic structures found within the peritarsal eyelid. CONCLUSION: The peritarsal eyelids have unique anatomy and associated histologic structures. Knowledge of the detailed histoanatomy is required for confident execution of Mohs surgery in this anatomic region.

Real-World Experience With Teprotumumab in Patients With Dysthyroid Optic Neuropathy.

BACKGROUND: Teprotumumab, an insulin-like growth factor I receptor inhibitory antibody, improved proptosis, diplopia, inflammatory signs/symptoms, and quality of life in patients with active thyroid eye disease (TED) in clinical trials. The trials excluded patients with dysthyroid optic neuropathy (DON). Recently, many case reports and case series have reported the successful use of teprotumumab to treat DON. Here, we review the data from published cases and our clinical experience in treating patients having DON with teprotumumab. METHODS: A literature search was conducted of patients with DON treated with teprotumumab from January 2020 through September 2022. Data from DON patients from the authors' (M.A.T. and C.A.B.) clinical practice were included. Primary outcome measure was mean (SD) improvements for visual acuity, color vision, and visual fields. Improvements in proptosis and clinical activity score (CAS) and diplopia were compared before and after teprotumumab administration. RESULTS: Ten observational studies/case reports were identified along with 2 patients in our practice. In all, there were 24 active TED patients with DON (37 eyes) who were treated with teprotumumab. Mean (SD) age was 66.5 (13.6) years and 13 (54%) were females, disease duration ranged from 2 months to >15 years. 22/24 patients had none, minimal improvement or progression of visual loss with intravenous/oral corticosteroids, orbital decompression (n = 9), and orbital radiation (n = 2). There were 2 patients who received teprotumumab as the only therapy. Overall, 88% (21/24) reported improvement in visual acuity after teprotumumab and in 75% (18/24), improvement in vision was observed after just 2 infusions of teprotumumab. Three eyes had decompression surgery in close proximity to teprotumumab infusions and were excluded from analyses. Mean (SD) improvement in visual acuity was 3.73 lines (SD 3.74), range 2-15 lines in 33 eyes. The mean (SD) improvement in the mean deviation on visual field testing in 15 eyes was 5.6 db (3.0 db). Mean (SD) improvement in proptosis was 4.37 mm (SD: 2.11) (20 patients, 32 eyes); and clinical activity score: mean reduction of 5.1 (1.3) for 18 patients. Teprotumumab was well tolerated in all but one patient. Adverse events reported included fatigue, dysgeusia, hearing loss, nausea, hyperglycemia, and muscle spasms. CONCLUSIONS: Teprotumumab is an effective treatment for DON in our experience and in published cases in whom treatment with steroids, surgery, or orbital radiation was unsuccessful.

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 follicular lymphoma in a patient with a history of thyroid eye disease: a case report.

The most common cause of both unilateral and bilateral proptosis in adults is thyroid eye disease (TED), and the diagnosis in typical cases is made without imaging. However, many other orbital diseases, including inflammatory, infectious, and neoplastic processes, can mimic the symptoms of thyroid eye disease, highlighting the importance of imaging and biopsy in challenging cases. There are limited reports in the literature of orbital lymphoma being diagnosed in patients with a history of thyroid eye disease. Here, we present the case of a patient with long-standing TED who developed new asymmetric proptosis and was subsequently diagnosed with systemic follicular lymphoma.

The Importance of Health Literacy in Addressing Eye Health and Eye Care Disparities.

Disparities in eye health and eye care frequently result from a lack of understanding of ocular diseases and limited use of ophthalmic health services by various populations. The purpose of this article is to describe the principle of health literacy and its central role in enhancing health, and how its absence can result in poorer health outcomes. The article evaluates the current status of health literacy in visual health and disparities that exist among populations. It also explores ways to improve health literacy as a means of reducing disparities in visual health and eye care. Advancing dissemination of health information and enhancing health literacy may help not only to reduce healthcare barriers in the underserved populations but also to lessen visual health disparities.

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.

Expert Consensus on the Use of Teprotumumab for the Management of Thyroid Eye Disease Using a Modified-Delphi Approach.

BACKGROUND: Teprotumumab is the first treatment for thyroid eye disease (TED), a debilitating autoinflammatory condition, approved by the Food and Drug Administration in the United States, which reduces proptosis and improves quality of life. In the absence of guidelines, clinical recommendations were developed for using teprotumumab in patients with TED in the United States. METHODS: A 3-round modified-Delphi panel was conducted between October 2020 and February 2021 with experts in the management of patients with TED. Key areas regarding the use of teprotumumab were investigated, including eligible patient populations, concomitant treatments, and assessment of response and adverse events. This used 2 survey rounds via an online questionnaire, where statements were scored using 9-point Likert scales. Statements with conflict were included in the third round, involving a consensus meeting via videoconference. RESULTS: Consensus was obtained for all statements (n = 75); of which, 56% were revised to enable agreement of the group. The consensus meeting provided agreement regarding which populations should receive teprotumumab therapy, including all adult patients with TED with a clinical activity score of ≥4. Treatment with teprotumumab can also be considered for TED patients displaying the following characteristics: a CAS of <3, lid retraction of ≥2, and mild or early optic neuropathy with close clinical observation. Further recommendations included suitability of treatment for those beyond 16 months following the initial diagnosis of TED, low CAS concomitant treatment with steroids in some cases, retreatment for those who have relapses, and finally a recommendation to continue therapy for all 8 infusions despite the lack of response by the fourth infusion. CONCLUSIONS: This work constitutes the first consensus on guidelines for the use of teprotumumab. The modified Delphi approach involved physicians with significant experience with the clinical use of teprotumumab, and recommendations were based on current evidence.

Epidemiology of Product-Related Ocular Injuries in the United States From 2001 to 2020.

BACKGROUND: Although ocular injuries are a major cause of ocular morbidity, ocular trauma secondary to consumer-related products is often preventable, and epidemiologic data can highlight potential avenues for intervention. OBJECTIVE: Our aim was to characterize epidemiologic trends in product-related ocular injuries presenting to the emergency department (ED) from 2001 to 2020 based on the National Electronic Injury Surveillance System (NEISS) database. METHODS: The NEISS database was reviewed for all ED visits for ocular injuries between 2001 and 2020. Trends in incidences were determined by calculating average annual percent change. RESULTS: There were 106,533 ocular injuries reported to the NEISS database, which represented an estimated 4 million national cases. Most injuries occurred during the summer in men (69.2% of cases) younger than 40 years (66.2%). The incidence rates decreased for patients younger than 60 years, but remained steady in those 60 years and older. Although the most common overall cause was home workshop equipment-related products (23.5%), patients younger than 20 years were most likely injured from sports (27.2%), and those 80 years and older experienced injuries due to furniture (24.0%). CONCLUSIONS: Although the overall incidence of product-related ocular injuries has decreased over the past 2 decades, not all age groups are affected equally. The data showed that the trends in frequency and cause of eye-related ED visits differ depending on the age of the patient and indicated avenues for age-specific interventions.

Changes in choroidal thickness and choroidal vascularity index in thyroid eye disease: a systematic review.

PURPOSE: To evaluate the evidence for changes in choroidal thickness and choroidal vascularity index (CVI) in people with thyroid eye disease (TED), stratified by severity, as measured by optical coherence tomography (OCT). METHODS: Systematic review, including quality assessment, of published studies investigating choroidal thickness in TED. Outcomes of interest included CVI, subfoveal choroidal thickness, mean choroidal thickness, and peripheral choroidal thickness in four quadrants (superior, inferior, medial, lateral). RESULTS: Nineteen studies were included which contained measurements from 1067 eyes in 798 patients with TED. Most studies found an increased CVI and increased choroidal thickness in patients with TED compared to normal controls, especially in the subfoveal region. In addition, several studies reported an increased thickness in patients with active vs. inactive TED, although the results are equivocal. Finally, many studies reported associations between increased choroidal thickness and worsened clinical measurements of disease activity, such as Clinical Activity Score (CAS). CONCLUSIONS: This systematic review provided evidence for an association between increased CVI/choroidal thickness and TED, suggesting a potential for OCT-measured CVI/choroidal thickness as an objective clinical marker. Given heterogeneity, future studies are needed to assess the role of measuring the choroidal changes in diagnosis and management of TED.

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.

Lupus Miliaris Disseminatus Faciei of the Posterior Eyelids: A Case Report.

A 70-year-old woman with a history of Demodex blepharitis presented with a 1-year history of red-yellow nodules in the tarsus of her eyelids. Excisional biopsy revealed robust caseating granulomatous inflammation, consistent with the diagnosis of lupus miliaris disseminatus faciei. Lupus miliaris disseminatus faciei is a rare granulomatous dermatosis of unknown etiology. Estimated 200 cases have been reported to date, but none have been reported affecting the posterior lamellae of the eyelids. Lupus miliaris disseminatus faciei classically presents as symmetric yellow or brown papules on the central face and eyelid skin. Infectious etiologies and systemic granulomatous disease need to be ruled out with histologic staining and serologies.

Warfarin-associated delayed orbital hemorrhage after orbital fracture repair with smooth nylon foil implant.

The authors describe the first report in the literature of delayed orbital hemorrhage that may be partly caused by supratherapeutic anticoagulation. A 52-year-old man with supratherapeutic international normalized ratio (INR) presented with acute proptosis, orbital pain and diplopia 9 months after the floor and medial orbital wall fracture repair using nylon foil implant. He was found to have hemorrhaged into the capsule surrounding the orbital implant. Three weeks later, the patient underwent implant removal after warfarin was discontinued for 5 days and INR was normalized. His symptoms resolved postoperatively. This case describes a unique risk factor of delayed orbital hemorrhage in patients with previous orbital fracture repair, and highlights that coagulopathy should be investigated in patients presenting with acute proptosis with a history of orbital fracture repair. The authors also provide a comprehensive and up-to-date literature review on previously reported cases with delayed hemorrhagic complications from alloplastic orbital implants.

Comprehensive genomic profiling of orbital and ocular adnexal lymphomas identifies frequent alterations in MYD88 and chromatin modifiers: new routes to targeted therapies.

Non-Hodgkin lymphoma of the orbit and ocular adnexa is the most common primary orbital malignancy. Treatments for low- (extra-nodal marginal zone and follicular lymphomas) and high-grade (diffuse large B-cell lymphoma) are associated with local and vision-threatening toxicities. High-grade lymphomas relapse frequently and exhibit poor survival rates. Despite advances in genomic profiling and precision medicine, orbital and ocular adnexal lymphomas remain poorly characterized molecularly. We performed targeted next-generation sequencing (NGS) profiling of 38 formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas obtained from a single-center using a panel targeting near-term, clinically relevant genes. Potentially actionable mutations and copy number alterations were prioritized based on gain- and loss-of-function analyses, and catalogued, approved, and investigational therapies. Of 36 informative samples, including marginal zone lymphomas (n=20), follicular lymphomas (n=9), and diffuse large B-cell lymphomas (n=7), 53% harbored a prioritized alteration (median=1, range 0-5/sample). MYD88 was the most frequently altered gene in our cohort, with potentially clinically relevant hotspot gain-of-function mutations identified in 71% of diffuse large B-cell lymphomas and 25% of marginal zone lymphomas. Prioritized alterations in epigenetic modulators were common and included gain-of-function EZH2 and loss-of-function ARID1A mutations (14% of diffuse large B-cell lymphomas and 22% of follicular lymphomas contained alterations in each of these two genes). Single prioritized alterations were also identified in the histone methyltransferases KMT2B (follicular lymphoma) and KMT3B (diffuse large B-cell lymphoma). Loss-of-function mutations and copy number alterations in the tumor suppressors TP53 (diffuse large B-cell and follicular lymphoma), CDKN2A (diffuse large B-cell and marginal zone lymphoma), PTEN (diffuse large B-cell lymphoma), ATM (diffuse large B-cell lymphoma), and NF1 (diffuse large B-cell lymphoma), and gain-of-function mutations in the oncogenes HRAS (follicular lymphoma) and NRAS (diffuse large B-cell lymphoma) were also observed. Together, our study demonstrates that NGS can be used to profile routine formalin-fixed, paraffin-embedded orbital and ocular adnexal lymphomas for identification of somatic-driving alterations and nomination of potential therapeutic strategies.

Lymphangiogenic and Chemotactic Factors in Conjunctival Melanoma.

PURPOSE: The aim of this study was to evaluate expression patterns of known lymphangiogenic growth factors and chemokines in conjunctival melanoma, and to describe patterns of lymphatic vessel growth in these tumors. METHODS: This was a retrospective chart review comprising 5 participants (6 tumor specimens) and the main outcome measures were expression of growth factors, chemokines, and their receptors known to be important in tumor lymphangiogenesis as well as patterns of lymphatic vessel growth on immunohistochemical sections. RESULTS: Tumor cells in all specimens expressed lymphangiogenic growth factors VEGFC, VEGFD, and their receptor VEGFR3. Chemotactic factors CXCL12 and CCL21 and their receptors, CXCR4 and CCL21, were also expressed in tumor cells and lymphatic endothelial cells. Staining was most intense for these proteins at the invasive tumor edge, suggesting increased lymphangiogenic activity at this location. In addition, lymphatic vessels clustered near the invasive edge of the tumors. CONCLUSIONS: VEGFC, VEGFD, and VEGR3 are diffusely expressed by conjunctival melanoma cells, most intensely at the invasive tumor edge. CXCL12, CXCR4, CCL21, and CCR7 were also most intensely expressed at the invasive edge, where the highest density of lymphatic vessels was also observed. These expression patterns suggest that these mediators of tumor-associated lymphangiogenesis warrant further investigation as potential therapeutic targets in conjunctival melanoma.

Quantified Incision Placement for Postseptal Approach Transconjunctival Blepharoplasty.

PURPOSE: This study quantifies the incision location in transconjunctival lower eyelid blepharoplasty to optimize postspetal (direct) access to the eyelid/orbital fat. METHODS: A retrospective chart review of patients undergoing transconjunctival blepharoplasty by one surgeon (GGM) from January 2013 to January 2014 was performed. Simultaneous globe retropulsion and lower eyelid inferior displacement was used to balloon the conjunctiva forward to maximally visualize the transconjunctival surface anatomical landmarks of importance. A caliper was used to measure the distance in millimeters from the inferior tarsus to the most superior projection of visible fat. The conjunctival incision was made 0.5 mm posterior to this measured distance. For each procedure it was noted whether the preseptal or postseptal plane was entered. RESULTS: Sixty-six patients were assessed. Fifty patients were women, and the mean patient age was 54 years (range 36-71 years). The mean distance from the inferior tarsus to the visualized superior tip of fat was 6.03 mm (range 5-7 mm) and the mean incision placement was 6.53 mm (range 5.5-7.5 mm). The postseptal space (direct access to fat) was entered in 54 cases (82%). The inferior vascular arcade was identified in 23 cases (35%) cases. In this instance, the incision was placed below this landmark in 16 cases (70%). There were 5 cases (7.6%) of postoperative chemosis which all resolved within 2 months with conservative measures. There were no other complications related to the conjunctival incision. CONCLUSION: Placing the conjunctival incision for postseptal approach transconjunctival blepharoplasty 0.5 mm posterior to the most superior projection of clinically visible fat (with adjunctive globe retropulsion and lower eyelid infraplacement) accesses the postspetal space directly in 82% of cases. Previously suggested incision placements: between 2 and 5 mm below the tarsus, at the fornix, or at the inferior vascular arcade are subjective/anecdotal at best and without similar quantitative validation.