Faculty Bibliography

OBJECTIVE: IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. METHODS: We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. RESULTS: None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. CONCLUSION: IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

PURPOSE: To evaluate the clinical and immunopathologic features of two patients with bilateral dacryoadenitis associated with regional enteritis. DESIGN: Retrospective clinicopathologic study. METHODS: Clinical records, photographs, and imaging studies were reviewed and microscopic sections of lacrimal gland biopsies were critically re-evaluated. The microscopic slides were stained with hematoxylin and eosin, special stains for organisms, and a range of immunohistochemical biomarkers including CD3, CD4, CD5, CD8, CD20, CD68, CD138, CD1a, IgG, IgG-4, and IgA. RESULTS: Both cases involved a young female patient with a well-established diagnosis of regional enteritis. Histopathologic examination of biopsies disclosed moderate intraparenchymal fibrosis and lymphoplasmacytic infiltrates without lymphoid follicles. Small to medium-sized intraparenchymal, non-caseating granulomas lacking multinucleated giant cells, and in one case, CD68-positive and CD1a-negative palisading granulomas in widened interlobular fibrous septa were detected. IgG4 plasma cells and vasculitis were not observed. Additional immunohistochemical studies revealed that CD8 T-lymphocytes (suppressor/cytotoxic subset) predominated over CD4-positive T-lymphocytes (helper cells) surrounding the necrobiotic foci and were intermixed with the CD68-positive histiocytes in the absence of CD20 B-lymphocytes. Special stains for organisms were negative. CONCLUSIONS: Dacryoadenitis is the rarest form of ocular adnexal involvement in regional enteritis, which affects the orbit far more frequently than ulcerative colitis. It is a granulomatous process with the possibility of palisading necrobiotic foci. In contrast, ulcerative colitis causes an interstitial lymphocytic and non-granulomatous myositis. Sarcoidosis, Wegener granulomatosis and pseudorheumatoid nodules must be ruled out. Treatment options entail a wide variety of agents with selection based upon empirical considerations and tailored to the patient's symptoms.

A 60-year-old man with stable bilateral thyroid eye disease (TED) underwent unilateral strabismus surgery. Within 1 month, he developed TED reactivation in only the contralateral orbit. At a later date, again after 6 months of inactive TED, he underwent bilateral strabismus surgery. Within 1 month of surgery, he developed bilateral TED reactivation. Surgical manipulation of orbital tissues may, in rare cases, provoke reactivation of TED.

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:: This study was designed to better understand the biologic nature of optic nerve gliomas (ONGs) and to investigate staining techniques that might improve the pathologic interpretation of surgical margins. METHODS:: In this retrospective case series, clinical data on patient presentation, MRI, surgical visualization, and initial pathologic interpretation were gathered. Specimens were then reexamined using analysis of p53, isocitrate dehydrogenase 1 (IDH1), MIB-1, and B-rapidly accelerated fibrosarcoma (BRAF) duplication. RESULTS:: Six patients were studied. All were diagnosed with World Health Organization grade 1 ONGs on original pathology. On reexamination, BRAF tandem duplication was found in 2 patients with neurofibromatosis Type 1 association. P53 immunoreactivity was noted in a third case. No cases had IDH1 immunoreactivity. Focal elevations of MIB-1 up to 7.5% were noted in 2 cases. CONCLUSIONS:: ONGs are neoplasms with variable degrees of aggressiveness. As more is understood regarding their varied genetic underpinnings, improved pathologic classification and individualized treatment regimens may be achieved. The authors hope that this study helps guide the oculoplastic community toward a multi-institutional, prospective study of ONG genomic sequencing.

PURPOSE: To determine the value of preoperative MRI in predicting the histopathologic margin of optic nerve glioma undergoing surgical resection. METHODS: Retrospective, noncomparative, multicenter case series of patients diagnosed with prechiasmal optic nerve glioma, using MRI, who underwent surgical resection. Clinical data were abstracted from patient medical records at 6 medical centers through a survey vehicle. Preoperative MRI findings were compared with intraoperative findings and postoperative histopathologic interpretations of the posterior margins of 13 surgically resected optic nerve gliomas. RESULTS: A total of 13 patient submissions qualified for study entry based on preoperative MRI having identified a unilateral optic glioma anterior to the optic chiasm. Of these, 2 cases (15%) demonstrated an abnormal macroscopic appearance of the chiasm intraoperatively and were surgically debulked rather than resected as planned preoperatively. The remaining 11 patients underwent resection posterior to the margins indicated by preoperative MRI. Of these, 3 (27%) demonstrated evidence of microscopically positive margins on histopathologic examination. Follow up ranged from 3 months to 21 years. One patient with involvement of the chiasm manifested tumor growth; no other recurrences or evidence of growth occurred in the remaining patients, including 1 other case with involvement of the chiasm and 3 cases with positive surgical margins. CONCLUSIONS: Unilateral optic nerve gliomas limited to the prechiasmatic nerve on MRI not infrequently extend beyond the MRI borders. This finding is of significance when considering management options, particularly surgical resection.

PURPOSE: Upper eyelid retraction is the most common sign of thyroid eye disease (TED). The results of traditional surgical procedures to correct upper eyelid retraction have been limited by unreliable postoperative eyelid height and contour. We investigate the outcome of the surgical correction of upper eyelid retraction using a modification of the full-thickness blepharotomy technique initially described by Elner et al. METHODS: Fifty-three patients (78 eyelids) underwent a modified full-thickness blepharotomy. RESULTS: Symmetry (within 1 mm) was achieved in 40 patients (75.5%) and symmetry (within 2 mm) was achieved in 43 cases (81.1%). Of the 53 patients, 8 (15.1%) required reoperation. CONCLUSIONS: Our surgical approach can be performed efficiently and produces predictably satisfactory eyelid height even in severely retracted eyelids.

PURPOSE: To evaluate the influence of saline irrigation on temperature rise in orbit bones and the optic canal during high-speed drilling. METHODS: An experimental study measuring temperature rise in an orbit during high-speed drilling was conducted. The orbital rims, sphenoid bone, and optic canals of 6 unpreserved caprine orbits were drilled with a 3.1-mm diamond drill bit at 35,000 rpm. Each orbit was divided into groups receiving no irrigation, continuous or intermittent external irrigation at 5-second intervals during the procedures. The temperature rise of each site was compared among the groups, along with the duration of drilling. RESULTS: The mean (+/- SD) temperature elevation in the optic canal without irrigation was 2.38 degrees C (+/- 0.30 degrees C). This was significantly higher than in the canals receiving intermittent irrigation (0.90 degrees C +/- 0.40 degrees C; p < 0.001) and continuous irrigation (0.66 degrees C +/- 0.40 degrees C; p < 0.001). Mean temperature rise in the orbital rim without irrigation was significantly higher (3.51 degrees C +/- 1.30 degrees C) than with intermittent (1.05 degrees C +/- 0.31 degrees C; p < 0.001) and continuous (0.98 degrees C +/- 0.61 degrees C; p < 0.001) irrigation. Mean temperature rise in the sphenoid was significantly higher (3.68 degrees C +/- 1.66 degrees C) without irrigation than with intermittent (1.36 degrees C +/- 1.17 degrees C; p = 0.005) and continuous (0.90 degrees C +/- 0.33 degrees C; p < 0.001) irrigation. There were no statistically significant differences between any of the intermittent and continuous irrigation groups. CONCLUSIONS: The presence of either continuous or intermittent irrigation during orbital drilling procedures significantly decreases the temperature rise in the region adjacent to the surgical site. This has important implications for surgical technique when operating near the optic canal. Further studies regarding potential effects on the optic nerve are warranted.

Subperiosteal orbital hemorrhage typically results from trauma. Spontaneous subperiosteal orbital hemorrhage (SSOH) is rare and has been reported with sudden elevation of cranial venous pressure, bleeding diathesis, and sinusitis. This article presents a series of 9 patients (11 orbits) with SSOH and review the associated systemic conditions. 10 out of 11 orbits (91%) underwent surgical intervention due to advanced orbital signs or poor vision.