Faculty Bibliography

PURPOSE:: The natural history of thyroid eye disease follows a biphasic course featuring an initial active stage followed by a durable quiescent stage. Reactivation of thyroid eye disease is defined by recurrence of inflammatory signs and symptoms after a period of stability lasting at least 6 months. It is thought to be rare and is poorly studied. The goal of this study was to define the incidence and characteristics of recurrent thyroid eye disease. METHODS:: A retrospective chart review of 415 visits of patients with thyroid eye disease was performed between 2006 and 2012. Recurrent cases were identified by subjective historical accounts of disease recurrence, review of prior orbital imaging, and photographic evidence. RESULTS:: Among 415 cases of thyroid eye disease, 65 cases of recurrence (15.7%) were identified. Most cases of reactivation occurred within the first 10 years after the initial episode of thyroid eye disease. The mean age of patients at the first event was 42.2 years and 52.6 years at the second event. Eighteen patients had identifiable events that may have triggered disease recurrence. The recurrence rate was higher among patients that had been smokers during their first episode of thyroid eye disease (22%) compared with the nonsmokers (14.6%). CONCLUSIONS:: Although uncommon, recurrence of thyroid eye disease does not appear to be as rare as previously believed. A better understanding of the natural history of thyroid eye disease is important as it impacts patient education and management.

BACKGROUND/AIMS: To clarify the pathogenesis of fibrosis in inflammatory orbital diseases, we analysed the gene expression in orbital biopsies and compared our results with those reported for idiopathic pulmonary fibrosis. METHODS: We collected 140 biopsies from 138 patients (58 lacrimal glands; 82 orbital fat). Diagnoses included healthy controls (n=27), non-specific orbital inflammation (NSOI) (n=61), thyroid eye disease (TED) (n=29), sarcoidosis (n=14) and granulomatosis with polyangiitis (GPA) (n=7). Fibrosis was scored on a 0-3 scale by two experts, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray. RESULTS: Within orbital fat, fibrosis was greatest among subjects with GPA (2.75+/-0.46) and significantly increased in tissue from subjects with GPA, NSOI or sarcoidosis (p<0.01), but not for TED, compared with healthy controls (1.13+/-0.69). For lacrimal gland, the average score among controls (1.36+/-0.48) did not differ statistically from any of the four disease groups. Seventy-three probe sets identified transcripts correlating with fibrosis in orbital fat (false discovery rate <0.05) after accounting for batch effects, disease type, age and sex. Transcripts with increased expression included fibronectin, lumican, thrombospondin and collagen types I and VIII, each of which has been reported upregulated in pulmonary fibrosis. CONCLUSIONS: A pathologist's recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts that are considered essential in fibrosis. Many transcripts implicated in orbital fibrosis have been previously implicated in pulmonary fibrosis. TED differs from other causes of orbital fat inflammation because fibrosis is not a major component. Marked fibrosis is less common in the lacrimal gland compared with orbital adipose tissue.

Importance: Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. Objective: To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. Design, Setting, and Participants: In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. Main Outcomes and Measures: Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05. Results: Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor kappaB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues. Conclusions and Relevance: Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

PURPOSE:: To describe a case series of ointment granuloma as a complication of sutureless transconjunctival blepharoplasty. METHODS:: A retrospective review of the medical records of 8 patients with this complication was conducted, including the histopathology of excised tissues. Institutional review board oversight was waived as this was not an institutional study but a Health Insurance Portability and Accountability Act-compliant retrospective chart review from the private medical practice of one of authors' coauthors. It adhered to the principles set forth in the Declaration of Helsinki. RESULTS:: Eight patients developed painless lower eyelid and anterior orbital masses following presumed successful blepharoplasty. Each had received intra- or immediate postoperative lubricating ointment. The mean time from surgery to appearance of the lesions was 50 days (range: 9 days-10 months). Three patients responded to intralesional injection of steroid with complete resolution. Five patients required surgical excision of the lesions without recurrence to date. Histopathological examination of the excised tissues revealed large, pleomorphic lipid-dropout pools bordered by attenuated histiocytes and giant cells. CONCLUSIONS:: The appearance of eyelid lumps or fullness in the early and mid-postoperative recovery should suggest ointment granuloma. If recognized early, management should commence with intralesional injection of steroids, although the definitive treatment is surgical excision. The authors recommend minimizing the access of topical ointments to the open inferior fornix, placing the medication sparingly onto the cornea at the close of surgery and instructing patients in avoiding overuse.

This case report describes a biopsy-proven metastasis of gestational choriocarcinoma to the medial rectus muscle. Patient evaluation and follow up included comprehensive ophthalmologic history and examination, external and fundus photography, immunohistochemistry preparations of the medial rectus muscle specimen, MRI, ultrasound of the abdomen and pelvis, comprehensive blood tests, and CT scans of the chest, abdomen, and pelvis. The tissue specimen was obtained via a medial perilimbal conjunctival peritomy. MRI revealed a mass intrinsic to the right medial rectus muscle. Immunohistochemical staining confirmed gestational choriocarcinoma metastasis in medial rectus muscle biopsy. The patient showed general and orbital improvement following 7 subsequent cycles of chemotherapy. In conclusion, gestational choriocarcinoma may metastasize to the orbit in addition to the previously reported ocular site, the choroid. A chemotherapy regimen of etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine can effectively treat the intraorbital component of the disease.

Purpose: To analyze the surgical management and outcomes of patients with canalicular lacerations and to report the epidemiological data and clinical characteristics of this group of patients. Methods: A retrospective review of medical records of all patients with canalicular lacerations from 1992 to the present at a single institution. Results: A total of 50 patients with injury to the canalicular system were identified, mean age 32 years (range 16 months - 88 years), 82% were male and 18% female. 82% were adult and 18% were pediatric patients. The most common mechanism of injury in adults was assault (50%) while in children it was accidents with objects (33%). 86% were found to have injury to one canaliculus while 14% had a bicanalicular laceration. 68% of the canaliculi injured were lower lid, 32% were upper lid. 78% of the lacerations were graded as mild or moderate and 22% were severe, with associated medial canthal avulsion or extensive globe or orbital injury. 94% proceeded to repair within 48 hours; in two patients, canalicular intubation could not be achieved intraoperatively. Of the 48 patients who underwent surgical repair, 22% had monocanalicular intubation with the Mini-Monoka and 78% percent had repair with the Crawford tube. All (100%) bicanalicular lacerations were repaired with the bicanalicular Crawford tube. The majority of monocanalicular lacerations (78%) were repaired with either the monocanalicular or bicanalicular Crawford tube; all (100%) of the lacerations repaired with the Mini-manoka were mild. Thirty patients had follow up beyond post-operative month 1, with an average follow-up of 6 months. The average length of intubation was 5.7 months. 93% of patients had successful functional and anatomic outcomes. The most common complication was tube extrusion requiring repositioning or repeat surgery, which occurred at the same rate (17%) with the Mini-Monoka and Crawford tube. In two such instances, one type of stent was replaced for another secondary to patient anatomy. Conclusions: In our experience, most canalicular lacerations are sustained by adult males and are related to assault. The majority of canalicular lacerations are repaired with bicanalicular Crawford tubes within 48 hours. Both methods of repair, Mini Monoka stent and Crawford tube, are effective in achieving good outcome and it is important to be familiar with the use of both

Abstract Purpose: To describe the location of the zygomatico-orbital foramen on the inferolateral orbital wall. Methods: This anatomic study examined 28 orbits of 14 dry human adult skulls. The zygomatico-orbital foramen was identified by passing a thin wire from the zygomatico-facial foramen to its orbital aspect and a thin flexible ruler was used to measure 1) the distance perpendicular to the closest point on the inferior orbital rim, 2) the distance from the inferior orbital fissure, and 3) the distance from the area used for retrobulbar injections. Results: The mean distance from the zygomatico-orbital foramen to the closest point on the inferior orbital rim was 4.7 mm (range from 1 to 7 mm). The mean distance from the inferior orbital fissure was 14.9 mm (range from 10 to 18 mm). The mean distance from the area of retrobulbar injection was 6.0 mm (range from 3 to 10 mm). Conclusions: The location of the zygomatico-orbital foramen within the inferolateral orbit is quite variable. This is the first study to attempt to quantify its proximity to the site of retrobulbar injection. We conclude that it is an important anatomical structure to consider when giving retrobulbar anesthesia, especially given the variability in technique among ophthalmologists.