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.

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 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.

Developmental anatomy of the nasolacrimal duct: implications for congenital obstruction.

OBJECTIVE: To measure the height, anteroposterior, and transverse diameters of the nasolacrimal duct (NLD) in normal children between 2 weeks and 34 months of age and to compare the development of the NLD with the maxilla. DESIGN: Retrospective case series. PARTICIPANTS: Thirty-eight children with no history of NLD abnormalities who underwent prior axial computed tomography (CT) facial scans of 0.50 to 0.625 mm resolution. METHODS: Consecutive cases of CT facial series over a 16-month period at a single institution were studied. MAIN OUTCOME MEASURES: Height, anteroposterior and transverse diameters, and volume of the NLD; height of the maxillary sinus. RESULTS: The height of the bony NLD increases 1.8-fold, the average diameter increases 1.4-fold, and the volume increases 4.6-fold between 2 weeks and 34 months of age. The dimensional increases of the NLD are nonlinear, with most of the increase occurring in the first 6 months of life. The increase in height of the NLD is highly correlated with postnatal growth of the maxilla. CONCLUSIONS: Spontaneous resolution of NLD obstruction in normal infants is coincident with elongation, limited radial extension, and the resulting volume expansion of the NLD. We propose that increases in hydrostatic pressure within the fluid column of the NLD combined with central cavitation of the epithelial core can account for the patency of the NLD in normal infants. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Vismodegib for periocular and orbital basal cell carcinoma.

IMPORTANCE: Basal cell carcinoma (BCC) represents 90% of malignant eyelid tumors and is locally invasive and destructive, if left untreated. OBJECTIVE: To assess the feasibility of using vismodegib for periocular and orbital BCC based on its efficacy and tolerability. DESIGN, SETTING, AND PARTICIPANTS: In this prospective observational case series, consecutive patients with periocular or orbital BCC who met criteria for treatment with vismodegib were recruited prospectively during an 8-month period from February through September 2012 from 2 academic hospitals. Seven patients received oral vismodegib, 150 mg daily, until maximum clinical response was achieved, the tumor progressed, or the patient could no longer tolerate adverse effects. Clinical response and adverse effects related to treatment were recorded. The primary endpoint was reduction in lesion size, measured as percentage change in the externally visible dimension. EXPOSURE: Oral vismodegib. RESULTS: All 7 patients had locally advanced, biopsy-proven, infiltrative BCC that was not amenable to surgical resection or radiation. No patients had metastatic disease at presentation. The mean patient age was 71 years (range, 43-100 years), and 4 patients (57%) had secondary orbital involvement. The mean lesion size was 3.4 cm (range, 1.0-6.0 cm), and all 7 cases (100%) represented recurrent tumors excised previously with controlled margins by frozen section or Mohs micrographic surgery. The mean treatment duration was 11 weeks (range, 4-16 weeks), and the mean duration of follow-up was 7.3 months (range, 5-10 months). Two patients (29%) demonstrated complete clinical regression, 2 (29%) demonstrated greater than 80% partial clinical regression, 2 (29%) demonstrated less than 35% partial clinical regression, and 1 (14%) progressed. Adverse reactions occurred in 6 patients (86%) and included alopecia (29%), dysgeusia (29%), muscle cramps (29%), and anorexia (14%). Two patients (29%) developed new squamous cell carcinomas (well-differentiated, keratoacanthoma type) at uninvolved sites including the eyebrow and forearm. CONCLUSIONS AND RELEVANCE: Vismodegib seems to be well-tolerated and effective for treating periocular and orbital BCC in about half of all cases. Patients receiving treatment should be monitored for new squamous cell carcinomas at uninvolved sites.

Atypical canaliculitis.

A 34-year-old immunocompetent woman sought treatment for a 6-week history of right inferior medial canthal swelling and discharge consistent with canaliculitis. Symptoms persisted after conservative medical therapy. After canaliculotomy and removal of a dacryolith, the patient experienced resolution of signs and symptoms. Although Actinomyces has been a frequently reported cause of canaliculitis, we report a unique case of canaliculitis caused by Mycobacterium chelonae.

Floppy eyelid syndrome.

In this review, we define characteristics of floppy eyelid syndrome, as well as related syndromes, such as lax eyelid syndrome. Presenting symptoms, ocular signs, and important clinical examination techniques are described, and associated ocular and systemic conditions, as well as corresponding pathophysiology are discussed. Significant new histopathologic findings in floppy eyelid syndrome and recent surgical developments are summarized. This review provides a critical update of floppy eyelid syndrome and aids the ophthalmologist in new methods of assessment and management.