Tocilizumab for the Management of Thyroid-Associated Orbitopathy.

PURPOSE: To describe the efficacy of tocilizumab in the treatment of a cohort of patients with active thyroid-associated orbitopathy. METHODS: Patients were identified with active thyroid-associated orbitopathy who were intolerant of or had progression of disease despite systemic corticosteroids and subsequently were treated with tocilizumab between January 2015 and December 2020. Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels were assessed prior to initiation of tocilizumab, following the first dose, and after the completion of treatment. RESULTS: Eleven patients were candidates for and underwent treatment with tocilizumab, 9 of which met criteria for analysis. Average age was 55.6 years. Average time between onset of active thyroid-associated orbitopathy and completion of tocilizumab was 6.5 months. Average number of infusions was 4.2. There was a statistically significant reduction in Clinical Activity Score, Thyroid-Associated Ophthalmopathy Scale score, and thyroid-stimulating immunoglobulin levels when comparing pre-treatment values (mean Clinical Activity Score 6.78 ± 1.09, mean Thyroid-Associated Ophthalmopathy Scale score 10.2 ± 1.92, mean thyroid-stimulating immunoglobulin level 440.6 [%]) to values immediately following completion of treatment (mean Clinical Activity Score 0.44 ± 0.53, mean difference 6.3 points, p < 0.001 [95% CI, 5.5-7.2]; mean Thyroid-Associated Ophthalmopathy Scale score 1.2 ± 1.09, mean difference 9.0 points, p < 0.001 [95% CI, 7.2-10.8]; mean thyroid-stimulating immunoglobulin level 200.7 [%], mean difference 239.9 [%], p = 0.001 [95% CI, 124.3-355.4]). One patient had elevation of cholesterol following therapy induction. Patients were followed for an average of 23.6 months after treatment. No patients had recurrence of active disease after completion of tocilizumab. CONCLUSIONS: This study supports the use of tocilizumab as a therapy for the inflammatory phase of thyroid-associated orbitopathy.

Delayed periorbital hemorrhage in oculoplastic surgery patients on oral anticoagulants.

Periorbital hemorrhage is a potentially sight threatening surgical complication. The effect of new oral anticoagulants (NOACs) on hemorrhagic events after periorbital surgery has not been investigated. We describe four cases of severe delayed postoperative hemorrhage associated with NOACs, in addition to three cases in patients on traditional antithrombotic agents. Time of delayed hemorrhage ranged from postoperative day 2 to 6. Six patients required surgical intervention to achieve control of bleeding, and two patients required transfusion of blood products. Risk factors and management of this rare complication are discussed.

Management of graves myopathy: Thyroid-associated orbitopathy: when should we operate?

Thyroid-associated orbitopathy (TAO) is an autoimmune disorder that affects multiple periocular tissues. In TAO, an active immunologic inflammatory phase is typically followed by a cicatrizing recovery phase. Management in the inflammatory phase is supportive, and surgical rehabilitation should generally be deferred until the patient is stable. We review current treatment concepts, with a focus on the timing and sequence of surgical procedures to address proptosis, motility restriction, and eyelid malposition in patients with TAO. A stepwise surgical approach maximizes the predictability of surgical outcomes and minimizes reoperations.

Tocilizumab as a steroid sparing agent for the treatment of Graves' orbitopathy.

PURPOSE: To describe the effect of tocilizumab in two patients with thyroid associated orbitopathy (TAO). OBSERVATIONS: We present two patients with TAO who could not tolerate corticosteroids and had a reduction in clinical and laboratory markers of inflammatory activity with subsequent tocilizumab therapy. CONCLUSIONS AND IMPORTANCE: The IL-6 receptor antibody tocilizumab is a promising candidate for the treatment of TAO because it selectively targets a key inflammatory mediator and has a favorable side effect profile. Our report demonstrates that tocilizumab can achieve further reduction in inflammatory activity after treatment with corticosteroids. Importantly, we and others have observed a decrease in the level of thyroid stimulating immunoglobulin (TSI) with tocilizumab treatment. This suggests an upstream effect in the inflammatory cascade. Although the impact of tocilizumab on long-term outcome is unknown at this time, we believe that early disruption of the inflammatory process may prevent late complications and decrease the need for rehabilitative surgery.

Assessing the Effectiveness of Arnica montana and Rhododendron tomentosum (Ledum palustre) in the Reduction of Ecchymosis and Edema After Oculofacial Surgery: Preliminary Results.

PURPOSE: The purpose of this study was to provide preliminary data on the potential effectiveness of the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) in reducing postoperative ecchymosis and edema in a select population of healthy volunteers after oculofacial surgery. METHODS: This retrospective review examined the postoperative course of healthy volunteers using topical Arnica and Ledum after undergoing common oculofacial procedures, including blepharoplasty, browpexy, and rhinoplasty, in the hands of 4 surgeons at tertiary referral centers from July 1, 2012 to December 31, 2012 using medical records review. Each patient included had used topical hydrogel pads (OcuMend, Cearna Inc., Chicago, IL) containing Arnica 50 M (10) 50% and Ledum 50 M (10). The pads were applied bilaterally after surgery through postoperative day 6. At each postoperative visit, the patients were evaluated by their respective surgeons and assigned a subjective physician-patient rating score comparing each patient's observed healing compared with expected healing if not using Arnica/Ledum. Photographs of patients undergoing equivalent procedures, but not using Arnica/Ledum were used as controls for comparison. Physician-patient rating scores were categorical: markedly accelerated healing defined as approximately 7 days ahead of expected, accelerated healing, defined as <7 days ahead of expected, and no appreciable difference from expected. The proportion of patients with each physician-patient rating score was calculated for postoperative days 1 to 2, 3 to 5, 6 to 8, and overall. Difference of proportions was calculated with 95% confidence intervals using Newcombe unpaired difference comparison of proportions. Photographs documenting the clinical progression of selected patients are provided. RESULTS: A total of 27 patients (16 females, 11 males) were included in the study. Age range was 18 to 70 years. The majority of patients were white (52.9%), and underwent blepharoplasty (78.9%). The median duration of follow-up was 7 days, range 1 to 14 days. The proportions of patients with markedly accelerated healing were 38.5% (5 of 13), 85.7% (6 of 7), 60.0% (12 of 20), and 51.9% (14 of 27) at POD 1 to 2, 3 to 5, 6 to 8, and overall, respectively. The proportions of patients with accelerated healing at the same time points were 15.4% (2 of 13), 14.3% (1 of 7), 30.0% (6 of 20), and 37.0% (10 of 27), respectively. The proportions of patients with no appreciable difference at the same time points were 46.2% (6 of 13), 0% (0 of 7), 10.0% (2 of 20), and 11.1% (3 of 27) of patients, respectively. The proportion of patients using Arnica/Ledum with markedly accelerated healing was significantly more than the proportion of those demonstrating no appreciable difference from expected at POD 3 to 5 (85.7% vs. 0%, p = 0.05), POD 6 to 8 (60.0% vs. 10.0%), and overall (51.9% vs. 11.1%, p = 0.05). No adverse effects were reported. CONCLUSIONS: The preliminary results from this study demonstrate that the combination of topical Arnica montana and Rhododendron tomentosum (Ledum palustre) may be effective in reducing postoperative ecchymosis and edema after oculofacial surgery.

Orbital Plasmacytoma Mimicking an Orbital Abscess.

An 83-year-old male with a 15-month history of multiple myeloma presented with acute onset of swelling, redness, and pain around his right eye. CT scan was consistent with an orbital abscess. The patient was taken to the operating room for drainage of the orbital abscess. Abnormal tissue was encountered intraoperatively so biopsies were taken. His cultures grew only one colony of coagulase-negative Staphylococcus aureus. The histopathology from the biopsies showed a CD-138 positive plasma cell neoplasia consistent with a plasmacytoma. Plasmacytomas have been reported to present as orbital cellulitis and as abscesses in other locations in the body, but to our knowledge, this is the first case of a plasmacytoma presenting as an orbital abscess.

Long-Term Results for Entropion Repair by Tarsal Margin Rotation With Posterior Lamella Superadvancement.

PURPOSE: To report the long-term stability of tarsal margin rotation and posterior lamellar superadvancement (TMR PLS) for the repair of upper eyelid cicatricial entropion. METHODS: A retrospective chart review was performed from January 2000 through December 2014 to identify all patients who had TMR PLS at the authors' institution. Charts were reviewed for demographic information, recurrence of entropion or trichiasis, and surgical complications. Failure was defined as return of entropion. Patients with greater than 24 months of follow up were included. RESULTS: A total of 30 TMR PLS procedures were performed during the review period. Nineteen cases from 14 patients were included in the final analysis. None of the 19 cases demonstrated recurrence of entropion over an average follow-up period of 78.3 months. Eight cases demonstrated trichiasis after TMR PLS, 5 of which required treatment. CONCLUSION: This case series suggests that TMR PLS for the treatment of upper eyelid cicatricial entropion has excellent long-term stability.

Eyelid margin basal cell carcinoma managed with full-thickness en-face frozen section histopathology.

PURPOSE: To determine the tumor control rate of basal cell carcinoma (BCC) of the eyelid margin managed by full-thickness eyelid resection with en-face frozen section-controlled margins and primary reconstruction of the defect. METHODS: This is a retrospective, consecutive, noncomparative, longitudinal interventional case series from a single institution. A review of medical records of all patients with BCC involving the eyelid margin treated by full-thickness en-face frozen section histopathology between June 1997 and June 2011 was conducted. All cases were managed with gross full-thickness resection of the eyelid margin tumor with subsequent reconstruction. Intraoperative frozen section histopathology was performed on additional 1-mm thick medial, lateral, and inferior/superior specimens in a full-thickness en-face fashion. The main outcome measure was rate of recurrence over the follow-up period. Additional data collected included patient demographics, lesion site and size, histopathology, reconstructive technique, and postoperative complications. RESULTS: The review resulted in a total of 74 patients with 77 lesions. Of these, 45 lesions had a minimum 5-year follow up. Those cases that involved the lacrimal system were excluded resulting in a total of 43 cases for analysis, which had a mean follow up of 6.4 years (range, 5.0-13.0). Three cases (6.9%) represented a recurrent BCC, while all other cases were primary BCCs. The histopathological subtypes included nodular (65.1%), infiltrative (18.6%), and superficial (16.3%). There were no cases of recurrence (100% cure rate) over the follow-up period. Most defects (88.4%) were reconstructed by direct closure or a temporal rotation flap. The only complication noted was the development of a hypertrophic scar in 1 patient that resolved with conservative management. In the total series of 77 lesions, the mean follow-up period was 4.5 years (range, 0.5-13.0). One recurrence (1.3%) was detected after 1.1 years for an infiltrative BCC measuring 10.0 mm in diameter that involved the lacrimal system. CONCLUSIONS: Eyelid margin BCC can be managed effectively with full-thickness en-face frozen section-controlled excision and primary reconstruction of the defect. The high cure rate compares favorably with other excision techniques such as Mohs micrographic surgery, with the advantages of a single operation and excellent reconstructive result.

A national survey of practice patterns: temporal artery biopsy.

OBJECTIVE: To assess current clinical practice patterns for temporal artery biopsy (TAB) among clinicians in establishing the diagnosis of giant cell arteritis. DESIGN: A survey was sent via e-mail using the Survey Monkey website (www.surveymonkey.com; accessed January 24, 2013). The survey initially was sent in July 2010 and continued through October 2010. PARTICIPANTS: The survey was sent via e-mail to the members and affiliates of the American Society of Ophthalmic Plastic and Reconstructive Surgery, the North American Neuro-Ophthalmology Society, and the American College of Rheumatology. METHODS: Data from the survey were collected via Survey Monkey and data analysis was performed using the Fisher exact test and Wilcoxon rank-sum test. MAIN OUTCOME MEASURES: Response to the survey questions on primary unilateral versus bilateral biopsy, performing second-side biopsy if first side results were negative, and the duration for which biopsy findings are reliable after initiating immunosuppressive therapy. RESULTS: The self-described primary subspecialty of the 1074 respondents was as follows: oculoplastic surgery (n = 127), neuro-ophthalmology (n = 119), rheumatology (n = 799), and other (n = 28). Overall, 66% of respondents advocated initial unilateral TAB, 18% advocated bilateral biopsy in all cases, and 16% recommended either unilateral or bilateral TAB depending on the degree of clinical suspicion. Rheumatologists were 4.5 times more likely to advocate initial bilateral biopsy than neuro-ophthalmologists or oculoplastic surgeons (P<0.0001, Fisher exact test). Most respondents believed that biopsy results were accurate for more than 14 days. These results were not affected by stratification of years in practice by the Kruskal-Wallis rank-sum test. CONCLUSIONS: Temporal artery biopsy practices vary greatly among treating physicians. This lack of consensus underscores the need for a systematic assessment of varying practice patterns. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

A new Cylindromatosis (CYLD) gene mutation in a case of Brooke-Spiegler syndrome masquerading as basal cell carcinoma of the eyelids.

A 70-year-old woman sought treatment for confluent flesh-colored papules on all 4 eyelids. Sixteen family members were reported to have similar lesions involving the face and scalp. Initial histopathologic examination of the lesions was interpreted as basal cell carcinoma, but on further review, the lesions were deemed to be consistent with trichoepitheliomas as seen in Brooke-Spiegler syndrome. Cylindromatosis gene mutation analysis confirmed this unique presentation of Brooke-Spiegler syndrome, and revealed a previously unidentified mutation in the cylindromatosis gene.

Silicone intubation for the treatment of epiphora in adults with presumed functional nasolacrimal duct obstruction.

PURPOSE: To evaluate the long-term efficacy of silicone intubation in adults with presumed functional nasolacrimal duct obstruction. METHODS: This retrospective cohort study reviewed adults with unilateral or bilateral epiphora and presumed functional nasolacrimal duct obstruction treated with silicone intubation and followed for signs of treatment failure (defined as persistent epiphora or need for a secondary procedure). Median time to event (failure) after silicone intubation was calculated using Kaplan-Meier survival analysis. Analysis was conducted at the level of the individual eye, with clustering by person taken in account. Cox proportional hazards models were used and adjusted for within-subject variance using a robust sandwich estimator. RESULTS: Forty-four eyes from 30 patients with isolated functional nasolacrimal duct obstruction underwent silicone intubation for epiphora. Mean time to stent removal in 40 of 44 eyes was 4.0 (±4.1) months. Mean duration from the time of stent placement to last follow-up was 2.6 (±2.0) years. Overall success after silicone intubation for resolution of symptoms was 77%. Kaplan-Meier survival analysis for time to event after silicone intubation yielded a median time of 5.7 years. Extrapolated data demonstrated a 96% success rate at 2 years and 85% success rate at 3 years and predicted approximately 50% of patients to have relief of epiphora between 5 and 6 years after silicone intubation. CONCLUSIONS: In this study, silicone intubation has good long-term success for relief of epiphora in patients with presumed functional nasolacrimal duct obstruction. This study provides important clinical information to guide management of epiphora in adults with functional nasolacrimal duct obstruction.

Human immunodeficiency virus-associated blepharoptosis.

PURPOSE: To better characterize an unusual blepharoptosis observed in HIV-positive patients and to evaluate histopathology. METHODS: This retrospective case series evaluated patients with HIV/AIDS and blepharoptosis with reduced levator excursion. Exclusion criteria included patients with identifiable causes of ptosis (e.g., aponeurotic dehiscences, prior eyelid trauma or surgery), known myopathic/neuropathic systemic disorders, congenital ptosis, cranial neuropathies, and systemic infiltrative processes. RESULTS: All 10 patients had bilateral symptomatic blepharoptosis. All patients (100%) were men with a mean age at presentation of 54 years (range, 42-77 years). Mean duration of HIV infection among 7 of 10 patients was 19 years (range, 13-24 years). Mean (±SD) MRD1 was 0.7 (±0.8) OD and 0.6 (±0.8) OS. Mean (±SD) levator excursion was 12 (±2.3) OD and 13 (±1.8) OS (normal levator excursion >15 mm). No patient was taking zidovudine (AZT) at the time of presentation. Nine patients (90%) underwent large bilateral levator resections for correction of blepharoptosis. Histopathologic specimens revealed abnormal levator muscle fibers with various degrees of atrophy, fibrosis, and regeneration without inflammation. CONCLUSIONS: The HIV-associated blepharoptosis observed among patients in this study is most consistent with a myopathy. Levator muscle histopathologic findings are virtually identical to muscle biopsies in individuals with HIV-associated myopathy, described before the advent of AZT or highly active antiretroviral therapy (HAART). Surgical management with levator resection provides optimal correction of HIV-associated blepharoptosis.

Long-term results for the use of gold eyelid load weights in the management of facial paralysis.

BACKGROUND: The placement of gold eyelid load weights to improve passive upper eyelid animation is integral to the management of patients with facial palsy, particularly for patients with long-term paralysis. METHODS: In a retrospective cohort review, outcomes after placement of 104 gold weights in 94 eyelids implanted by one surgeon from 1986 to 2000 were evaluated. The primary outcome measures were improvement in corneal exposure and visual acuity. Secondary outcome measures included time to removal and rates of adverse effects and complications. RESULTS: Mean time of follow-up was 43.37 +/- 41.40 months (range, 1 to 53 months). Visual acuity and corneal compensation improved after weight placement (p = 0.0001), while the necessary daily ocular care decreased. Overall, 91 (97 percent) of the 94 first-time weights implanted were successful in providing improved protection for the patient's eye and decreasing the daily care needs. Eleven weights (10.6 percent) became exposed and were removed. Kaplan-Meier survival curve analysis predicted a 3 percent exposure rate at 12 months, 5 percent at 24 months, and 10 percent at 5 years, which increased to 35 percent at 153 months. When needed, replacement weights were equally effective in maintaining ocular health. CONCLUSIONS: This study demonstrates that gold eyelid load weights help preserve vision and improve corneal compensation, while minimizing ocular nursing care. The complications are few, but after approximately 5 years, the incidence of weight exposure increases to approximately 10 percent. The exposure rate continues to increase with longer follow-up intervals. Extruded weights can be replaced multiple times with the expectation that they will continue to provide a good result.

Orbital metastasis from medullary thyroid carcinoma.

A 46-year-old woman with known multiple endocrine neoplasia type 2A was referred for evaluation of left-sided progressive diplopia and proptosis. She was given the presumptive diagnosis of progressive thyroid-associated orbitopathy. Clinical examination revealed significant proptosis and restricted motility of the left eye. Serial CT demonstrated a marked progression in size of the left inferior rectus muscle. This was postulated to be a rare case of metastasis of a medullary thyroid carcinoma to the left inferior rectus muscle, which was confirmed by lateral orbitotomy and excisional biopsy. The presence of unilateral proptosis raises the possibility of intraorbital or intracranial disease and warrants further investigation. Detection of metastases and subsequent surgical excision or debulking has palliative benefits, including prevention of compression or invasion of major structures and cooperative planning with oncology and participation in treatment regimens that may prove beneficial in patients with metastatic medullary thyroid carcinoma.

Müller muscle-conjunctiva resection to correct ptosis in high-risk patients.

PURPOSE: Müller muscle-conjunctiva resection could be seen as a relative contraindication in patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery. The concern centers around the theoretical risk of bleb-related complications or corneal damage from the palpebral conjunctival sutures. Our study aimed to determine whether any bleb- or cornea-related complications arose in patients who underwent Müller muscle-conjunctiva resection for ptosis correction. METHODS: A retrospective chart review was performed on 2 practices of oculofacial plastic surgeons from 2000 to 2006, including patients who had ptosis correction by Müller muscle-conjunctiva resection. Patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery were identified. Each case was reviewed to determine whether any bleb- or cornea-related complications occurred. The postoperative improvement of ptosis measured by interpalpebral distance or margin reflex distance-1 also was noted. RESULTS: Forty-three patients and 55 eyes with a history of a glaucoma filtering procedure (13 patients/15 eyes), corneal disease (1 patient/1 eye), or corneal surgery (29 patients/39 eyes) who underwent Müller muscle-conjunctiva resection were identified. The average follow-up time was 212.4 days. No bleb-related complications occurred. One patient with a history of Reis-Bücklers dystrophy experienced a corneal abrasion. Fifty-two of 55 patients had objective improvement of their ptosis. CONCLUSIONS: Müller muscle-conjunctiva resection can provide an effective means for ptosis repair in patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery. One temporary postoperative corneal complication occurred in our series.

Atypical presentations of pleomorphic adenoma of the lacrimal gland.

PURPOSE: To report 3 cases of pleomorphic adenoma of the lacrimal gland with atypical features. METHODS: The medical records, radiographic imaging, operative reports, and tumor histopathology of 3 patients with unusual presentations of pleomorphic adenoma of the lacrimal gland were reviewed. RESULTS: All 3 patients were females ranging in age from 18 to 64 years. The first patient presented with abrupt orbital inflammation mimicking orbital cellulitis. The second patient presented with a painful subcutaneous nodule. The last patient demonstrated calcification with bony erosion on orbital imaging. Orbitotomy was performed in all cases. Histopathologic evaluation of all specimens with light microscopy was consistent with pleomorphic adenoma of the lacrimal gland. CONCLUSIONS: Pleomorphic adenoma is the most common epithelial tumor of the lacrimal gland. A higher degree of suspicion must be present to make the correct diagnosis in cases with atypical features. Pleomorphic adenoma may present abruptly with orbital inflammation mimicking orbital cellulitis, as a painful subcutaneous nodule, or demonstrate calcification with bony erosion on orbital imaging. Complete surgical excision of the lesion within its pseudocapsule is recommended to prevent local recurrences and, although less likely, the possibility of malignant transformation.