Andrew R. Harrison

Blepharospasm (BSP) is characterized by excessive orbicularis oculi muscle activity leading to abnormal blinking and involuntary eyelid closure. Botulinum neurotoxin (BoNT) injections are the main treatment for BSP, but they only partially and transiently relieve symptoms, leading to a waxing and waning therapeutic response. A patient-centered outcome (PCO) tool that measures BSP symptoms in a simple and efficient way could inform the development of better treatments. Using a stepwise modified Delphi approach, potential PCO items were first identified using the Dystonia Coalition Database with data from over 200 individuals with BSP who had provided responses to existing clinical assessment scales. These items were then analyzed for contribution to overall severity using a Random Forests approach, and redundant items were merged and revised in a series of iterative meetings with a specialist panel along with input from patient advocacy group representatives and focus groups. An online survey was conducted with 330 individuals with BSP to validate and verify the items’ relevance. Finally, the specialist panel provided content validity ratio, which was repeated until it showed good agreement for relevance and clarity of all items. In the end, an easy-to-use PCO tool designed for smartphones and tablets containing 17 items covering three symptom domains (motor, disability, and psychosocial/quality of life) was created. This novel PCO tool for BSP may be used to characterize the cyclical response that an individual patient experiences from BoNT treatments and provide a vital tool for future investigations of longer-acting BoNT preparations or adjunctive therapies.

Purpose: The aim of this study was to investigate the medical accuracy of responses produced by Chat Generative Pretrained Transformer 4 (Chat GPT-4) and DALLE-2 in relation to common questions encountered during oculoplastic consultations. Methods: The 5 most frequently discussed oculoplastic procedures on social media were selected for evaluation using Chat GPT-4 and DALLE-2. Questions were formulated from common patient concerns and inputted into Chat GPT-4, and responses were assessed on a 3-point scale. For procedure imagery, descriptions were submitted to DALLE-2, and the resulted images were graded for anatomical and surgical accuracy. Grading was completed by 5 oculoplastic surgeons through a 110-question survey. Results: Overall, 87.3% of Chat GPT-4’s responses achieved a score of 2 or 3 points, denoting a good to high level of accuracy. Across all procedures, questions about pain, bruising, procedure risk, and adverse events garnered high scores. Conversely, responses regarding specific case scenarios, procedure longevity, and proceduredefinitions were less accurate. Images produced by DALLE-2-were notably subpar, often failing to accurately depict surgical outcomes and realistic details. Conclusions: Chat GPT-4 demonstrated a creditable level of accuracy in addressing common oculoplastic procedure concerns. However, its limitations in handling case-based scenarios suggests that it is best suited as a supplementary source of information rather than a primary diagnostic or consultative tool. The current state of medical imagery generated by means of artificial intelligence lacks anatomical accuracy. Significant technological advancements are necessary before such imagery can complement oculoplastic consultations effectively.

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.

Context Oxidative stress plays an indispensable role in pathogenesis of Graves’ orbitopathy (GO). Ferroptosis is a newly discovered form of cell death resulting from lipid peroxidation. Little is known about the role of ferroptosis in GO. Objective We aimed to identify the divergent role of ferroptosis in the GO and control orbital fibroblasts (OFs). Methods Orbital fat/connective tissues and serum immunoglobulins (Igs) were collected from GO and control subjects. Cell viability and lipid peroxidation were measured to evaluate ferroptosis sensitivity. Pyruvate dehydrogenase kinase 2 (PDK2) level and oxygen consumption rate were quantified to assess glycolysis status. Results Primary OFs were cultured from orbital tissues. Ferroptosis was induced by cystine deprivation and/or erastin treatment. The GO OFs possessed stronger resistance to ferroptosis than the control OFs. Selenium, a potential ferroptosis inhibitor, protected the control OFs from ferroptosis. Both transcriptomic and proteomic analyses indicated glycolytic shift in the GO OFs. Metabolic profiling, PDK2 quantification, and oxygen consumption assay confirmed enhanced glycolysis in the GO OFs. Inhibition of glycolysis by PDK2 knockdown and dichloroacetic acid (DCA) promoted ferroptosis sensitivity in the GO OFs. The ferroptosis-sensitizing effects of DCA were also observed when the GO OFs were treated with GO-Igs. IGF1R overexpression in the GO OFs contributed to glycolysis shift. IGF1R inhibitory antibodies facilitated ferroptosis induction in the GO OFs, but the effects were less remarkable under GO-Igs treatment. Conclusion These study findings establish that glycolysis facilitates ferroptosis resistance in the GO OFs, providing insights into the therapeutic role of glycolysis for GO treatment.

The authors describe a rare case of recurrent ectopic meningioma associated with sphenoid encephalocele in the medial anterior orbit of a 52-year-old man with a history of a resected intracranial meningioma. Typical features of ectopic meningioma are reviewed as well as potential etiologies of this very rare recurrence of intracranial meningioma in the orbit. Treatment is typically surgical excision. The authors report a rare case of recurrent orbital ectopic meningioma in the right medial canthus of a 52-year-old man.