PURPOSE:Lagophthalmos from facial nerve palsy is traditionally measured with patients in an upright position and may fail to identify positional variability. This study aims to assess the effects of body position, surgical technique, implant material, and patient demographics on lagophthalmos. METHODS:A multicenter prospective study was performed to evaluate positional changes in paralytic lagophthalmos and the effects of various patient and surgical factors. RESULTS:Sixty-four eyelids were included. Thirty-two (50%) of eyelids had upper eyelid weight implantation with a median post-operative follow-up of 67 weeks. The mean change in lagophthalmos from sitting to supine was a 1.4 mm increase (p < 0.001). There was a larger lagophthalmos variability in patients with eyelid weights compared to those without (p = 0.047), and in patients with gold compared to platinum weights (p = 0.026). Positional increase in lagophthalmos did not correlate with weight position (i.e. pretarsal vs. supratarsal) (p = 0.26), weight load (p = 0.70), House-Brackmann severity (p = 0.16), age (p = 0.14), or gender (p = 0.13). CONCLUSIONS:Surgeons should routinely measure lagophthalmos in the supine position, as nocturnal corneal exposure may warrant ocular lubrication, occlusion, or additional surgery. Platinum weights may be preferred over gold due to less positional lagophthalmos variability.

OBJECTIVE:Respiratory arrest plays an important role in sudden unexpected death in epilepsy (SUDEP). Adenosine is of interest in SUDEP pathophysiology due to its influence on seizures and breathing. The objective of this investigation was to examine the role of adenosine in seizure severity, seizure-induced respiratory disruption, and seizure-induced death using mouse models. Understanding adenosinergic contributions to seizure cessation and seizure-induced death may provide insights into how SUDEP can be prevented while avoiding increased seizure severity. METHODS:Our approach was to examine: (1) seizure severity and seizure-induced death after 15 mA electroshock seizures and during repeated pentylenetetrazol (PTZ) administration in wild-type mice (Adk +/+) and transgenic mice with reduced adenosine metabolism (Adk +/-); (2) the postictal hypercapnic ventilatory response (HCVR) in wild-type mice (the postictal HCVR could not be examined in Adk +/- mice due to their high mortality rate); and (3) the effects of adenosinergic drugs on seizure severity and seizure-induced death following maximal electroshock (MES). RESULTS:Adk +/- mice were more vulnerable to seizure-induced death in the 15 mA electroshock and repeated PTZ models. Despite increased mortality, Adk +/- mice had comparable seizure severity in the PTZ model and reduced seizure severity in the 15 mA electroshock model. Breathing and HCVR were suppressed by 15 mA electroshock seizures in wild-type mice. Pharmacological inhibition of adenosine metabolism decreased MES seizure severity but did not increase mortality. A1 selective and nonselective adenosine receptor antagonists increased seizure-induced death following MES. SIGNIFICANCE:Adenosine has opposing effects on seizure severity and seizure-induced death. On the one hand, our seizure severity data highlight the importance of adenosine in seizure suppression. On the other hand, our mortality data indicate that excessive extracellular adenosine signaling can increase the risk of seizure-induced respiratory arrest.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

We herein report four patients with periocular Merkel cell carcinoma treated with immune checkpoint inhibitors who experienced a dramatic response and, therefore, had less morbid surgery and/or avoided radiation therapy with its inherent ocular toxicity.

e18034 Background: Periocular squamous cell carcinoma can be of eyelid skin, ocular surface (bulbar) or palpebral conjunctival, or of lacrimal sac/nasolacrimal duct mucosal origin, is relatively rare, and presents unique anatomic considerations due to proximity to the eye and inherent risk to ocular structures associated with high dose radiation therapy. We herein report on 17 patients with orbital or periocular SCC who were treated with immunotherapy (IO) to decrease surgical morbidity or to avoid high dose radiation therapy. Methods: Retrospective review of all previously unreported patients with orbital, conjunctival, or periocular SCC who were treated with IO either in the neoadjuvant setting prior to surgery or for treatment of periocular SCC with perineural spread into the orbit and skull base. Results: 17 patients, 12 men and 5 women (Age range: 44-92; median=70 years old) with orbital (n=6), conjunctival (n=5), or lacrimal sac/duct (n=2) squamous cell carcinoma (SCC), or periocular SCC with perineural spread into the orbit and skull base (n=4) who were treated with IO either as single drug (n= 11) or in combination with chemotherapy (n= 6 ). In all patients either cemiplimab or pembolizumab was used. In 13 patients IO was used in the neoadjuvant setting prior to planned surgery. In 4 patients with perineural spread as they had non surgically resectable disease, IO was used to avoid high dose radiation therapy with its inherent significant risk of ocular toxicity. Overall, 3 patients achieved complete response, 10 patients achieved partial response, and 4 patients had stable disease, using RECIST criteria. One of 5 patients with conjunctival SCC also had nodal metastasis at presentation and achieved a dramatic complete response of both the conjunctival tumor and the nodal metastasis and managed to avoid surgery altogether. This patient had a very high tumor mutation burden (TMB). One patient developed diabetic ketoacidosis as a side effect of IO; otherwise the adverse effects were low grade. Conclusions: IO either as single drug or in combination with chemotherapy has a fairly high response rate in patients with ocular adnexal, conjunctival or orbital SCC and in patients with periocular SCC with perineural spread in the orbit and skull base. Future prospective trails using IO for orbital and ocular adnexal SCC should be planned and should aim to correlate molecular data such as TMB with response.

Mupirocin, an antibiotic produced by Pseudomonas fluorescens, is mainly used for the topical treatment of various skin and soft tissue infections caused by Staphylococcus (including methicillin-resistant Staphylococcus aureus) and Streptococcus around the world for decades. Nevertheless, the clinical application scope of mupirocin varies in different countries due to differences in their medical policies, prescription types, and drug resistance. According to the experience of Chinese doctors in the past few years, mupirocin presented low drug resistance rates, and could be used as a treatment option for various primary infections and secondary infections, with antibacterial effects in a broad application. In this review, we summarized the experience of mupirocin used in the Chinese population and discussed its clinical value to provide novel insights and inspiration for physicians.

Orbital plasmacytoma is a rare plasma cell tumor that may arise as an aggressive form of extramedullary multiple myeloma. Treatment modalities include surgical excision, radiation, and chemotherapy. Chimeric antigen receptor T cell therapy is currently reserved for refractory disease. The authors present a case of a 69-year-old woman with an extensive orbital plasmacytoma refractory to multimodal therapy who was treated with idecabtagene vicleucel chimeric antigen receptor T cell therapy. Four days after infusion, the patient exhibited grade 1 cytokine release syndrome, which resolved with tocilizumab. The orbital plasmacytoma significantly decreased in size 1 month after treatment and demonstrated complete serological response and sustained tumor burden reduction at 10-month follow-up. This case highlights the efficacy of chimeric antigen receptor T cell therapy for refractory orbital plasmacytoma and calls attention to potential inflammatory toxicities.

OBJECTIVE:Periocular squamous cell carcinoma (SCC) is relatively rare and presents unique anatomic considerations due to proximity to the eye and risk to ocular structures associated with high-dose radiation therapy or radical surgery. We present our observations in patients with periocular SCC treated with immune checkpoint inhibitor (ICI) therapy in an effort to decrease surgical morbidity or avoid high-dose radiation therapy. METHODS:Retrospective review of patients with orbital, conjunctival, or periocular SCC who were treated with ICI either in the neoadjuvant setting prior to surgery or for treatment of perineural spread in the orbit/skull base. RESULTS:Twelve men and 5 women with orbital (n = 6), conjunctival (n = 5), or lacrimal sac/duct (n = 2) SCC, or SCC with perineural spread (n = 4) were treated with ICI (cemiplimab or pembolizumab) either as single drug (n = 9) or combined with chemotherapy (n = 8). Overall, 5 patients achieved complete response, 8 patients achieved partial response, and 4 patients achieved stable disease, using the response evaluation criteria in solid tumors (RECIST) criteria. The objective response rate was 76.5%. In 12 patients ICI was used in the neoadjuvant setting prior to surgery. In 4 patients with perineural spread and unresectable disease, ICI was used to avoid high-dose radiation therapy. One additional patient with conjunctival SCC with nodal metastasis was treated with ICI alone and achieved a dramatic complete response and has thus far managed to avoid surgery altogether. CONCLUSIONS:ICI either as single drug or in combination with chemotherapy has a high response rate in patients with periocular SCC. Future prospective trials should aim to correlate molecular data with response.

Our primary objective was to estimate the overall response rate to immune checkpoint inhibitors (ICIs) in patients with locally advanced, multiply recurrent, or metastatic conjunctival melanoma treated with ICIs. A retrospective review of all consecutive conjunctival melanoma patients who were treated with ICI between October 2017 and January 2024 was carried out. The study included 16 patients with a median age of 66 years. The indications for ICI were locally extensive conjunctival melanoma in the eye/orbital area without nodal or distant metastasis in 10 patients, local recurrence of conjunctival melanoma and simultaneous nodal or distant metastasis in four patients, and metastatic conjunctival melanoma without local recurrence in two patients. Five patients received PD-1 inhibitor monotherapy with nivolumab or pembrolizumab; the other 11 received ipilimumab (CTLA-4 inhibitor) and nivolumab for several cycles and were then continued on nivolumab monotherapy (n = 6) or not given additional ICI therapy (n = 3). The number of cycles of ICI ranged from 2 to 25 (median, 13). Eight patients achieved a complete response. Six patients had progressive disease. The overall rate of objective response to ICI therapy was 63% (10 of 16), and for the subset of patients with local disease only, the objective response rate was 70% (7 of 10). In 14 patients (88%), orbital exenteration or additional extensive surgery was avoided; two patients had progression despite ICI and eventually needed an orbital exenteration. Future studies should aim to correlate biomarker data with response to ICI therapy in patients with conjunctival melanoma.

Teprotumumab is a novel insulin-like growth factor-1 receptor inhibitor approved for the treatment of thyroid eye disease, but growing reports of hearing loss require further investigation. To date, an effective protocol for managing hearing loss in this setting has not been determined. Here, we present the first report of the resolution of teprotumumab-related hearing loss with prompt oral prednisone. A 70-year-old woman on teprotumumab experienced sudden hearing loss and tinnitus after her first infusion. An audiogram demonstrated a mild down-sloping to moderately severe mixed conductive and sensorineural hearing loss that was promptly treated with prednisone 60 mg for 6 days with a 1-week gradual taper. An audiogram 3 weeks later demonstrated return of hearing to normal thresholds, and the whole teprotumumab treatment course was completed without further issue. This case highlights the importance of audiometric monitoring, prompt identification of hearing symptoms, and the potential for oral steroids to reverse teprotumumab-related hearing loss.

Teprotumumab has been shown to be effective in the treatment of thyroid eye disease, a potentially vision-threatening condition. Adverse events, including sensorineural hearing loss, have been associated with teprotumumab. The authors present the case of a 64-year-old female who discontinued teprotumumab due to significant sensorineural hearing loss after 4 infusions, along with other adverse events. The patient was unresponsive to a subsequent course of intravenous methylprednisolone and orbital radiation, during which she experienced worsening thyroid eye disease symptoms. Teprotumumab was restarted 1 year later, at a half dose of 10 mg/kg for 8 infusions. Three months post-treatment, she retains resolution of double vision and orbital inflammatory signs, and significant improvement in proptosis. She tolerated all infusions with an overall reduction in the severity of her adverse events and without return of significant sensorineural hearing loss. The authors conclude that a lower dose of teprotumumab can be effective for patients with active moderate-severe thyroid eye disease who experience significant or intolerable adverse events.

Purpose of Review To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON). Recent Findings Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care.

We present a case of herpes zoster keratitis reactivation shortly following the Shingrix vaccine. In our patient, reactivation of herpes zoster keratitis occurred a few weeks following the herpes zoster subunit (HZ/su) vaccine. The development of herpes zoster ophthalmicus following HZ/su is exceedingly rare, with only one prior reported case found in the literature. Reporting of this potential correlation is important in understanding the full risks of vaccines and can help elucidate the etiology of such responses.

Background: Upper and lower blepharoplasty are among the most common procedures in aesthetic surgery and are often emotionally laden due to the subjective nature of outcomes and implications with beauty and self-identity. This article capitalizes on the increasing wealth of patient-provided health information online and is the first to analyze the emotions surrounding blepharoplasty discussions in an open internet health forum, MedHelp. Methods: We used Python to scrape MedHelp for threads that contained “blepharoplasty” and then used IBM Watson Natural Language Understanding to perform sentiment analyses, calculating a general sentiment score (−1 to +1) as well as emotion scores for anger, sadness, joy, fear, and disgust (0 to 1) for posts and keywords contained within the posts. Keywords were then manually grouped into five distinct clinical categories: symptoms, doctor, treatment, medication, and body. Results: We collected 52 threads containing “blepharoplasty,” yielding 154 posts and 1365 keywords. The average sentiment score was negative among all posts (−0.15) and keywords (−0.30). Among all posts and keywords, sadness had the highest score and disgust had the lowest score. Conclusions: Fear and sadness are the predominant emotions for blepharoplasty patients online, and the most negative symptoms cited are not ones that surgeons typically expect.