Orbital Artifacts on MRI.

PURPOSE: To describe artifacts on orbital MRI, which led to an incorrect radiology report. METHODS: Retrospective chart review of patients identified from the orbital databases at the Royal Adelaide Hospital and University of Wisconsin Hospital. Patients who had artifacts on orbital MRI that led to an incorrect radiology report were included. Records were evaluated for age at imaging, gender, MRI sequence, laterality, and location of artifact, radiological characteristics and misdiagnosis, and cause of artifact. RESULTS: Data were collected from 7 patients (3 male) who had a median age of 61 years at the time of imaging. Five artifacts resulted from fat-suppression failure with 4 of these cases misdiagnosed as inflammatory changes and 1 misdiagnosed as neoplastic infiltration. The OD was involved in 4 cases. Six cases were in the inferior orbit region. CONCLUSIONS: Fat-suppression failure artifacts may arise in the inferior orbit region and can be mistaken for inflammatory or neoplastic orbital disease. This may prompt additional investigations such as orbital biopsy. Clinicians should be aware of artifacts which can affect orbital MRI and lead to potential misdiagnosis.

Outcomes of Patients With Thyroid Eye Disease Partially Treated With Teprotumumab.

PURPOSE: In response to the coronavirus (COVID-19) pandemic, teprotumumab production was temporarily halted with resources diverted toward vaccine production. Many patients who initiated treatment with teprotumumab for thyroid eye disease were forced to deviate from the standard protocol. This study investigates the response of teprotumumab when patients receive fewer than the standard 8-dose regimen. METHODS: This observational cross-sectional cohort study included patients from 15 institutions with active or minimal to no clinical activity thyroid eye disease treated with the standard teprotumumab infusion protocol. Patients were included if they had completed at least 1 teprotumumab infusion and had not yet completed all 8 planned infusions. Data were collected before teprotumumab initiation, within 3 weeks of last dose before interruption, and at the visit before teprotumumab reinitiation. The primary outcome measure was reduction in proptosis more than 2 mm. Secondary outcome measures included change in clinical activity score (CAS), extraocular motility restriction, margin reflex distance-1 (MRD1), and reported adverse events. RESULTS: The study included 74 patients. Mean age was 57.8 years, and 77% were female. There were 62 active and 12 minimal to no clinical activity patients. Patients completed an average of 4.2 teprotumumab infusions before interruption. A significant mean reduction in proptosis (-2.9 mm in active and -2.8 mm in minimal to no clinical activity patients, P < 0.01) was noted and maintained during interruption. For active patients, a 3.4-point reduction in CAS ( P < 0.01) and reduction in ocular motility restriction ( P < 0.01) were maintained during interruption. CONCLUSIONS: Patients partially treated with teprotumumab achieve significant reduction in proptosis, CAS, and extraocular muscle restriction and maintain these improvements through the period of interruption.

A Survey on the Management of Thyroid Eye Disease Among American and European Thyroid Association Members.

Background: The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. Methods: We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. Results: Two hundred fifty-two eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%, 114/227), white (79.7%, 181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%, 106/227), caring for 10 or more TED patients over the last 12 months (40.5%, 92/227), and reported not having a multidisciplinary TED clinic in their institution (52.8%, 120/227). The majority reported that new TED cases per annum have not changed in the past 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported a higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous (IV) steroids (73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%, 71/227), lack of effective TED treatments (19.8%, 45/227), and difficulty in predicting whether TED will develop (18.9%, 43/227). Conclusions: There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.

Predictive Modeling of New-Onset Postoperative Diplopia Following Orbital Decompression for Thyroid Eye Disease.

PURPOSE: To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques. METHODS: We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX). RESULTS: A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3-156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective. CONCLUSIONS: This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

The effect of visually significant dermatochalasis and blepharoptosis on driving safety.

OBJECTIVE: To evaluate the impact of visually significant blepharoptosis and dermatochalasis on driving safety and performance. Patients with visually significant blepharoptosis often complain of difficulty with driving, but the impact of blepharoptosis on driving has not been evaluated in a real-world setting. METHODS: Retrospective cohort study of 610 consecutive adult patients undergoing bilateral functional blepharoplasty or ptosis repair surgery at a single, University-based practice between 2014 and 2017. This cohort had a median age of 65 and was predominantly female. Pre-operative rates of motor vehicle collisions (MVCs) and moving violations (MVs) extracted from state Department of Transportation (DOT) records were compared with post-operative rates, using each patient as their own control. Poisson models were used for analysis. RESULTS: Subjects were included in the study for a median of 730 days before eyelid surgery (IQR 346 - 730) and 783 days after surgery (IQR 449 - 1176). There were 30 total MVCs before surgery (0.024 per subject, per year) and 48 after surgery (0.036 per subject, per year) (p = 0.08). There were 81 MVs before surgery (0.065 per subject, per year) and 66 after (0.049 per subject, per year) (p = 0.11). The multivariable model comparing MVCs pre- versus post-surgery adjusting for age, ptosis severity, gender, and comorbidities yields a rate ratio of 0.63 (p = 0.05). The multivariable model comparing MVs pre- versus post-surgery demonstrates a rate-ratio of 1.2 (p = 0.20). Older age was associated with lower rates of moving violations (coefficient of -0.03, p < 0.01). None of the other variables included in the final models had a significant association with MVCs or MVs. CONCLUSIONS: In this cohort, visually significant blepharoptosis and dermatochalasis were not associated with rates of MVCs or MVs. Further work is needed to study the impact of these common conditions on driving, for example adjusting MVC and MV rates by miles driven, which may influence decisions about when to operate on ptotic eyelids.

Simultaneous Orbital and Intracranial Abscesses in 17 Cases.

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

Necrotizing myositis in a rectus muscle arising in the setting of long-standing Langerhans cell histiocystosis and recent dabrafenib treatment.

PURPOSE: to describe an unusual case of necrotizing myositis in a rectus muscle, possibly related to BRAF inhibitor therapy. OBSERVATIONS: An 18-year old man with neurodegenerative Langerhans cell histiocytosis (LCH), recently started on the BRAF inhibitor dabrafenib, presented with right eye pain. Magnetic resonance imaging (MRI) orbits revealed a rectus muscle mass concerning for LCH recurrence or malignancy. Dabrafenib was stopped, and incisional biopsy of the mass was performed. The mass was absent on post-operative MRI, so no further treatment was pursued. Histopathologic evaluation was initially concerning for sarcoma, but on further analysis, appeared more consistent with necrotizing myositis. The mass did not recur, nor did the patient develop other signs or symptoms concerning for myositis or malignancy over a 24-month follow-up period. CONCLUSIONS: Necrotizing myositis has not been previously described in a rectus muscle or with BRAF inhibitor use, though myalgias and malignancies are established side effects. Necrotizing myositis may masquerade as sarcoma and should be on the differential diagnosis for a new mass in the setting of dabrafenib therapy.

An Update on Endocrine Mucin-producing Sweat Gland Carcinoma: Clinicopathologic Study of 63 Cases and Comparative Analysis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare, low-grade adnexal neoplasm with predilection for the periorbital skin of older women. Histologically and immunophenotypically, EMPSGC is analogous to another neoplasm with neuroendocrine differentiation, solid papillary carcinoma of the breast. Both lesions are spatially associated with neuroendocrine mucinous adenocarcinomas of the skin and breast, respectively. EMPSGC is ostensibly a precursor of neuroendocrine-type mucinous sweat gland adenocarcinoma (MSC), a lesion of uncertain prognosis. Non-neuroendocrine MSC has been deemed locally aggressive with metastatic potential, and previous works speculated that EMPSGC-associated (neuroendocrine-type) MSC had similar recurrence and metastatic potential with implications for patient follow-up. Only 96 cases of EMPSGC have been reported (12 cases in the largest case series). Herein, we present 63 cases diagnosed as "EMPSGC" in comparison with aggregated results from known published EMPSGC cases. We aim to clarify the clinicopathologic features and prognostic significance of the neuroendocrine differentiation of EMPSGC and its associated adenocarcinoma and to determine the nosological relevance of EMPSGC association in the spectrum of MSC histopathogenesis. Results established an overall female predominance (66.7%) and average presenting age of 64 years. EMPSGC lesions were associated with adjacent MSC in 33.3% of cases. The recurrence rate for neuroendocrine-type MSC was ~21%, less than the reported 30% for non-neuroendocrine MSC. There were no cases of metastasis. EMPSGC and neuroendocrine-type MSC are distinct entities with more indolent behavior than previously reported, supporting a favorable prognosis for patients.

Isolated Ophthalmoplegia Following Filler Injections to the Upper Face.

Ophthalmoplegia following cosmetic facial filler injections is a rare but serious complication. The authors report 2 cases of ophthalmoplegia following filler injection. In the first case, a 54-year-old female presented with acute onset headache, vomiting, and diplopia during malar and temporal injection of hyaluronic acid. In the second case, a 37-year-old female presented with binocular diplopia that developed following injection of an unknown filler to the upper face. Neither of the 2 patients had skin necrosis or ocular abnormalities other than motility deficits. To the authors' knowledge, there have been no other cases of isolated ophthalmoplegia without evidence of other ocular injuries following facial filler.

Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries.

PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.

The Programmed Death Pathway in Ocular Adnexal Sebaceous Carcinoma.

PURPOSE: Sebaceous carcinoma can be highly malignant and difficult to treat. Surgical excision followed by periocular reconstruction is the primary method of treatment. In aggressive cases, radiation, topical chemotherapy, and systemic chemotherapy have been explored as adjuvant therapy. Immunotherapy, through immune checkpoint inhibitors, has proven to have significant antitumor effect in many cancer types, including melanoma, non-small cell lung cancer, renal cell carcinoma, and cutaneous squamous cell carcinoma. Little is known about endogenous immune response directed against sebaceous carcinoma. In this study, we aim to characterize the expression pattern of PD-1 and its ligands PD-L1 and PD-L2 in both sebaceous carcinoma and in infiltrating immune cells to explore the potential use of checkpoint blockade as therapy. METHODS: We performed a retrospective chart and histology review of patients with sebaceous carcinoma between 1990 and 2017 at the University of Wisconsin. Tissue microarrays were made from paraffin blocks. Immunohistochemistry was performed for evaluation of tumor and immune cell infiltration for expression of PD-1, PD-L1, and PD-L2. Tumor or infiltrating immune cells were considered positive if ≥5% of cells had membranous (cell surface) expression. RESULTS: Twenty-eight patients were included. PD-L1 and PD-1 were not significantly expressed on tumor cells; however, PD-L1 and PD-1 were expressed on infiltrating immune cells in 46% and 25% of patients, respectively. In contrast, PD-L2 demonstrated positive expression on tumor cells in 46% of the cases along with positive expression on infiltrating immune cells in 38% of the cases. CONCLUSIONS: Sebaceous carcinoma currently has few effective adjuvant treatment options. The expression of PD-1, PD-L1, and PD-L2 on infiltrating immune cells and PD-L2 on tumor cells restrains T-cells from full activation and proliferation, therefore limiting the antitumor effect of T-cells, tipping the balance toward unopposed tumor progression. Consequently, PD-1 or PD-L1 inhibitors may have a role in sebaceous carcinoma treatment. Given the prevalence of PD-L2 expression in sebaceous carcinoma and the lack of PD-L2 blockade therapy available, PD-1 blockade may provide benefit over PD-L1 inhibitors. PD-1 blockade in combination with current methods may be a viable therapeutic option for patients with sebaceous carcinoma and deserves further study.Sebaceous carcinoma of the ocular and periocular regions showed expression of immune checkpoint ligands PD-1, PD-L1, and PD-L2, which suggests PD blockade may provide benefit as an adjuvant therapy for patients with sebaceous carcinoma.

Two cases of epidemic keratoconjunctivitis-associated dacryocystitis.

This report presents two cases of epidemic keratoconjunctivitis (EKC)-associated dacryocystitis. Both patients presented with preseptal edema. Orbital computed tomography (CT) scans were performed out of concern for orbital cellulitis and revealed soft tissue edema involving the preseptal aspect of the eyelids and also the lacrimal sac. Both patients were initially diagnosed with bacterial preseptal cellulitis with dacryocystitis and admitted for treatment with intravenous antibiotics. After no improvement on antibiotics, both patients were noted to have exam findings consistent with viral conjunctivitis, and one patient had a positive conjunctival swab for adenovirus. Both patients were subsequently treated with topical steroids, and symptoms improved. EKC has previously been identified as a cause of acquired nasolacrimal duct obstruction and canalicular stenosis, and acute inflammation of the lacrimal apparatus may explain this link. Dacryocystitis may also be contributory to the copious tearing seen in patients with epidemic keratoconjunctivitis.

Recurrent natural killer/T-cell lymphoma of the lacrimal sac and nasolacrimal duct in a 59-year-old Caucasian woman.

A 59-year-old Caucasian woman with past medical history significant for Natural Killer (NK)/T-cell lymphoma of the right nasal septum in remission for nine months presented after surveillance PET-CT imaging revealed increased metabolic activity in the right nasolacrimal duct. She also reported ipsilateral epiphora starting around this time. The lacrimal sac and nasolacrimal ductal mucosa were biopsied via an external approach. Pathologic evaluation revealed a proliferation of lymphoid cells with necrotic tissue. Immunohistochemical staining demonstrated predominantly CD3+, EBER+, and CD56+ cells indicating recurrent NK/T-cell lymphoma. This case describes an unusual presentation of recurrent NK/T-cell lymphoma involving the lacrimal excretory system in a Caucasian adult. Recurrent malignancy should be considered in the differential of any patient with a history of a lymphoproliferative disorder near the lacrimal drainage system who presents with new onset epiphora.

Physical therapy for facial nerve palsy: applications for the physician.

PURPOSE OF REVIEW: The aim of this study was to describe the current state of physical therapy for facial nerve palsy, the evidence basis for these interventions and how therapy can be integrated with other medical and surgical interventions for facial nerve palsy, as it applies to ophthalmologists, oculoplastic surgeons and other specialists. RECENT FINDINGS: Many studies indicate that physical therapy is effective for the rehabilitation of patients with facial nerve palsy and can be used synergistically with interventions administered by physicians, such as targeted botulinum toxin injections. The field is limited by a relative paucity of high-quality randomized controlled trials. Alternative therapies including Brief Electrical Stimulation continue to be studied; however, they lack a scientific rationale and, anecdotally, appear to cause more problems in cases of incomplete facial nerve recovery. SUMMARY: Physical therapy, specifically neuromuscular retraining, is a useful intervention for treating facial nerve palsy. Care for these patients is best delivered in a multidisciplinary setting in which physical therapy and medical or surgical interventions can be closely integrated. Further study aimed at standardizing physical therapy and optimizing the integration of this with other treatments for facial nerve palsy are needed.

Bilateral Primary Mucinous Carcinoma of the Eyelid.

The aim of this study is to report a case of bilateral primary mucinous carcinoma of the eyelids. This is a case report and literature review. A 71-year-old female presented with primary mucinous carcinoma of the left upper eyelid, which was excised with Mohs surgery. One year later, she developed primary mucinous carcinoma of the right upper eyelid, which was also treated Mohs surgery. Extensive workup was negative for evidence of an unknown primary carcinoma or metastasis. Primary mucinous carcinoma of the eyelids may occur as multifocal tumors, and bilateral disease is not necessarily indicative of metastatic disease.