The role of biopsy in lacrimal gland inflammation: A clinicopathologic study.

PURPOSE: To determine the causes of lacrimal gland inflammation based on histopathology and systemic evaluation. METHODS: This is a retrospective case series study. From the University of British Columbia Orbit Clinic between January 1976 and December 2008, we reviewed the medical records of 60 patients who presented with inflammatory features of the lacrimal gland (i.e., erythema, edema, or tenderness) in which the diagnoses were not possible clinically and on imaging alone. As was our routine practice, all these patients underwent lacrimal gland biopsy before starting any treatment. RESULTS: The histopathologic findings of the 60 patients showed that 37 (61.7%) had identifiable types of lacrimal inflammation including 10 with Sjogren's syndrome, seven with sarcoidal reaction, six with feature of granulomatosis with polyangiitis (formerly known as Wegener's granulomatosis), five with lymphoma, two with sclerosing inflammation, two with IgG4-related dacryoadenitis, and one patient each with infectious dacryoadenitis, myoepithelial carcinoma, xanthogranuloma, eosinophilic angiocentric fibrosis, and eosinophilic allergic granulomatous nodule. The histopathologic findings of the remaining 23 (38.3%) patients showed nonspecific inflammation of the lacrimal gland. 23 patients (38.3%) had associated systemic diseases. 48 patients (80%) were treated successfully and 10 (16.7%) had recurrence of inflammation. CONCLUSIONS: We recommend that in patients presenting with lacrimal gland inflammation (i.e., erythema, edema, tenderness) in which the specific diagnosis cannot be made clinically and on imaging, biopsy is warranted for accurate diagnosis and appropriate treatment. We found that the majority of these patients (61.7%) had specific histopathology, and 38% had systemic diseases.

Postoperative Changes in Strabismus, Ductions, Exophthalmometry, and Eyelid Retraction After Orbital Decompression for Thyroid Orbitopathy.

INTRODUCTION: Surgical rehabilitation of thyroid orbitopathy involves reducing proptosis, treating strabismus, lengthening the eyelids, and managing aesthetic changes. Not all are necessary in each patient; however, they often are. The current investigation intends to describe postdecompression changes that may influence the staging of these procedures. METHODS: In this retrospective cohort study, records of 169 patients who underwent orbital decompression between 1983 and 2001 were reviewed. A single orbital specialist confirmed all measurements. Time to follow up was defined as the most recent follow up after decompression and prior to any secondary procedures. No strabismus or eyelid surgery was performed at the time of decompression. Strabismus was measured with alternating prism cover test. Ductions were estimated utilizing Hirschberg's method. Exophthalmometry was measured with Hertel. Eyelid positions were defined relative to the pupillary light reflex. Strabismus data were analyzed within eye pairs. Ductions, exophthalmometry and eyelid position were analyzed for each eye. T-test for paired data was utilized to compare means pre- and postoperatively. RESULTS: The study population was on average 45 years old and 73.4% women. Average length of follow up was 1.2 years. Esotropia was significantly increased after decompression by an average of 8.1 prism diopters (p < 0.01). Exotropia and vertical deviations were not significantly altered. Ductions decreased by >5 degrees in at least one meridian for 68.1% of the population. Upper eyelid retraction remained unchanged; however, lower eyelid retraction improved by 50% from 1.4 mm to 0.7 mm (p < 0.01). Exophthalmometry improved from 23.5 mm to 19.7 mm (p < 0.01), and this result was correlated with the number of walls removed (Pearson r = -0.302, p < 0.01). CONCLUSIONS: On average, esotropia and ductions tend to worsen with decompression surgery. This result supports the clinical dictum to avoid strabismus surgery until after decompression. The improvement in lower eyelid retraction suggests that at least lower eyelid-lengthening surgery should be reserved for after decompression, as there may be significant spontaneous improvement, while the same may not be true for upper eyelid retraction, which does not tend to change with decompression.

Orbital Inflammation in Pregnant Women.

OBJECTIVE: To analyze overlaps between pregnancy and orbital inflammation (OI). DESIGN: Retrospective observational case series. METHODS: Eight new cases from 1997 to 2015 and 2 previously published cases were identified for inclusion in this investigation to provide the fullest clinical picture. Medical records, imaging studies, and the results of biopsies were reviewed. RESULTS: Three categories of association were discovered: (1) OI arising for the first time during pregnancy (5 cases); (2) OI arising within 3 months of delivery (2 cases); and (3) previously diagnosed OI reactivated or exacerbated by pregnancy (3 cases). One patient had a preexistent systemic autoimmune disease and another's was later diagnosed. One patient had attacks during sequential pregnancies. Findings included eyelid swelling and erythema, conjunctival chemosis, pain on eye movement, minimal diplopia, the usual absence of proptosis, and general preservation of visual acuity. Imaging studies disclosed extraocular muscle swelling (8 cases), most frequently of a single lateral rectus muscle. There were 2 cases of dacryoadenitis; 1 of these and an additional case displayed inflammation of the retrobulbar fat. Corticosteroids effected resolution of most symptoms. Singleton births were normal with the exceptions of an intrauterine fetal demise owing to acrania and a molar pregnancy. CONCLUSION: OI usually affects a single rectus muscle (typically the lateral) and, less often, the lacrimal gland and is often mild when it arises during or after pregnancy. Independent systemic autoimmune disease is an uncommon feature. Corticosteroids were efficacious except in 1 case with severe orbital scarring. No definitive causal relationships between pregnancy and OI could be established based on the clinical data.

Clinical Pearls and Management Recommendations for Strabismus due to Thyroid Orbitopathy.

Thyroid orbitopathy causes a unique form of strabismus with adult-onset diplopia. Prisms can be a temporizing measure, but many patients require strabismus surgery, which can be challenging. In this article, we highlight clinical guidelines for addressing strabismus due to thyroid orbitopathy and review our surgical experience.

Orbital lymphaticovenous malformations: Current and future treatments.

Orbital lymphaticovenous malformations consist of abnormal vascular channels lined by endothelial cells with a spectrum from venous to lymphatic characteristics. They may be venous-dominant or lymphatic-dominant. These lesions continue to present management challenges. Total excision or obliteration is not always achievable, recrudescence is common, and interventions carry a risk of damaging normal structures. Patients likely benefit most from a multidisciplinary approach, including both surgical and nonsurgical (e.g., sclerosants and liquid polymers) therapeutic modalities. Targeted biologic therapy would be ideal; nevertheless, this goal is complicated by the heterogeneous venous-lymphatic and stromal characteristics of these lesions. Ideally, antiangiogenic agents targeting both lymphatic and blood vascular endothelial cells will be developed to treat these lesions and reduce their regrowth. Further studies are warranted to enhance our understanding of these orbital lesions with regard to their angiogenic (proliferative) activities and profiles of marker expression, with a goal to produce effective medical therapies.

The association of lacrimal gland inflammation with alopecia areata.

PURPOSE: To describe the association of lacrimal gland inflammation with alopecia areata. METHODS: We reviewed the medical records of 4 patients diagnosed with lacrimal gland inflammation who had an antecedent or subsequent episode of alopecia. Data was collected on the presentation age, gender, medical history, disease onset, symptoms and signs, imaging, histopathology, systemic evaluation, management and outcome. Pathology and imaging results were correlated with clinical findings. RESULTS: Three patients were Asian and one Caucasian. Two developed alopecia after presentation for lacrimal inflammation. The remaining two had a history of alopecia totalis (2 years and 10 years). Three of the 4 patients presented or developed other systemic disorders, including seizures, thrombocytopenia, optic neuritis, ulcerative colitis, allergic rhinitis, lymphadenopathy, vasculitic rash and positive p-ANCA values. All received oral corticosteroids, with the addition of methotrexate therapy in one for relapsing inflammation. CONCLUSIONS: Lacrimal gland inflammation and alopecia areata are autoimmune processes that can be seen in association with each other.

Vascular malformations of the orbit: classification and the role of imaging in diagnosis and treatment strategies*.

PURPOSE: To describe the authors' experience with orbital vascular malformations using the International Society for the Study of Vascular Anomalies (ISSVA) classification and the preferred radiologic techniques. METHODS: Review of clinical and radiologic experience from 1976 to 2012. This article presents the findings from several studies conducted on vascular malformations of the orbit, all of which received institutional review board approval when needed. RESULTS: The orbital vascular malformations can be evaluated, classified, and managed according to the ISSVA classification to provide a common language of communication between specialties, which takes into account flow dynamics. CONCLUSIONS: The ISSVA can be applied for vascular malformations of the orbit.

Dynamic arterial and valsalva-augmented venous phase multidetector CT for orbital vascular lesions: a pictorial review*.

PURPOSE: To describe the value and purpose of a new method of dynamic arterial and Valsalva-augmented venous phase CT angiographic assessment of vascular orbital lesions. METHODS: Description of a dynamic arterial and Valsalva-augmented venous phase multidetector CT protocol currently being used at the institution of the authors for investigation of orbital vascular lesions. Research ethics approval was not required by the institution because this is a 1-case report, with a pictorial review of imaging findings in various representative orbital vascular lesions. RESULTS: One case of a distensible venous malformation depicts the clinical application of the imaging protocol. Key features of the malformation were demonstrated by arterial and venous phases of imaging. CONCLUSIONS: This technique is of value in diagnosis and management of vascular malformations of the orbit.

Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease.

PURPOSE: To compare the risk of developing compressive optic neuropathy in patients with active thyroid eye disease (TED) treated with corticosteroids with or without orbital radiotherapy. DESIGN: Retrospective single-center case-control study. METHODS: The clinical charts of 351 patients with active TED who received corticosteroids with or without orbital radiotherapy between 1999 and 2010 were reviewed. Patients with compressive optic neuropathy at the time of presentation were excluded. Group 1 received corticosteroids only and Group 2 received corticosteroids as well as orbital radiotherapy. The primary outcome measure was the development of compressive optic neuropathy. Secondary outcome measures were changes in other parameters indicating the activity of TED, including soft tissue inflammation, diplopia, ocular motility restriction, and appearance. RESULTS: There were 144 cases in Group 1 and 105 in Group 2. Both groups were matched for age, sex, and stability of thyroid function. The 2 groups differed only in the modality of treatment for active TED. The main indication for treatment in both groups was soft tissue inflammation. Corticosteroids were initiated an average of 2.6 months following symptom onset in Group 1 and 2.5 months in Group 2. Group 2 received orbital radiotherapy on average 4.2 months following the initiation of corticosteroid therapy and 8% (9/105) were intolerant to corticosteroids. At an average of 3.2 years follow-up, compressive optic neuropathy had developed in 17% (25/144) of Group 1 and 0% of Group 2 (P < .0001), on average 5.5 months following the initiation of corticosteroid therapy. Although both groups experienced a significant reduction in periocular inflammation, the radiotherapy-treated group demonstrated a significantly greater improvement in ocular motility. CONCLUSION: The rate of compressive optic neuropathy was significantly lower and improvement in ocular motility greater in patients receiving orbital radiotherapy in addition to corticosteroids. Patients with active TED appear to have an effective and sustained response to orbital radiotherapy combined with corticosteroids that is protective against disease progression and the development of compressive optic neuropathy.

Cavernous venous malformations of the orbit (so-called cavernous haemangioma): a comprehensive evaluation of their clinical, imaging and histologic nature.

PURPOSE: The purpose of this investigation is to describe the clinical, imaging, histologic and flow dynamic characteristics of orbital cavernous haemangioma. METHODS: In this clinicopathologic series, clinical features were obtained from patient records. All imaging studies were reviewed. All specimens were reviewed with haematoxylin and eosin, and 10 were subject to a staining protocol including: Movat Pantachrome, periodic acid Schiff, D2-40, CD31, GLUT-1, Ki-67, vascular endothelial growth factor receptor 1 (VEGF-r1) (flt-1), VEGF-r2 (Flk-1), VEGF, anti-smooth muscle actin (SMA), CD20, CD4, CD8 and CD68. Imaging and pathology were reviewed in a systematic fashion. RESULTS: Clinically, lesions were more common in middle-aged females presenting with axial proptosis and pain. One-third demonstrated signs of optic nerve dysfunction. Dynamic imaging revealed focal early and diffuse late enhancement. Lesions demonstrated slow growth at 0.2 cm3/year. Histologically, all lesions demonstrated large vascular channels with mature-appearing endothelium and abundant stroma. Three salient features were noted and characterised: thrombosis, nests of perivascular hypercellularity and expanded stromal elements. Acute thrombosis was a feature of each specimen (<10% of channels). Fibrin clots were lined by a layer of CD31+ endothelium. Perivascular hypercellular areas stained uniformly with CD31 and less so with VEGFr2. Additionally, focal areas of Ki67+ and CD68+ cells were found in these regions. Expanded stroma contained CD31+ microcapillary networks and stained diffusely with anti-SMA. CONCLUSIONS: Cavernous haemangioma demonstrate clinical features and growth characteristics of a benign mass. Dynamic imaging highlights their slow flow vascular nature. Histologically, the hypercellularity and stromal changes identified can be understood within the pathogenic context of thrombosis and recanalisation in an organised lesion.

Comparison of American Joint Committee on Cancer TNM-based staging system (7th edition) and Ann Arbor classification for predicting outcome in ocular adnexal lymphoma.

OBJECTIVE: To compare the TNM and Ann Arbor staging systems in predicting outcome in ocular adnexal lymphoma (OAL). METHODS: Retrospective review of the clinical, imaging and histopathologic records of OALs between 1986 and 2009. Outcome measures included local recurrence and progression. RESULTS: One hundred and sixty patients of OAL were included. Mean age was 65 ± 15 years (range 20-97) and 68 (43%) were male. The median follow-up of all OAL patients was 65 months (range 2.5-238). Histopathology identified low-grade, indolent B-cell lymphomas in 140 patients (87.5%) and rest had aggressive grades. Of 134 indolent OAL patients, those with unilateral disease had a 10-year progression free survival of 72% versus 48% in their bilateral counterparts (p = 0.001). Amongst unilateral OAL patients staged within the T1-2 group, a significantly better outcome was noted for patients without nodal or metastatic involvement compared to those with such involvement (p = 0.0001). The above observations helped to formulate a simple scoring system to prognosticate OALs based on their laterality and node/metastatic status. Amongst the 3 groups identified, group 1 with a score of 0 (unilateral OALs with no nodes or metastasis) had a 10-year progression free survival of 75%; group 2 with score 1 (either bilateral or positive nodes/metastasis) 50% and group 3 with score 2 (both bilateral OAL with positive nodes/metastasis) zero at 10 years (p < 0.00001). CONCLUSIONS: The TNM-based staging system better predicts outcome in OAL than the Ann Arbor system primarily by delineation of bilateral disease and nodal/metastatic involvement at presentation.

Accuracy of MRI in defining tumor-free margin in optic nerve glioma surgery.

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.

Combined radiological intervention and surgical excision of a periorbital arteriovenous fistula.

OBJECTIVE: To describe a case of periorbital arteriovenous fistula (AVF) treated with a combined approach of endovascular intervention and surgical excision. CASE REPORT: A 21-year-old lady presented with a vascular lump followed blunt trauma above the left medial brow area. Computed Tomography Angiogram (CTA) and Angiography of the internal and external carotid arteries showed presence of an AVF with main feeder vessel from a hypoplastic left ophthalmic artery. Pre-operative radiological embolization was performed but the patient defaulted planned surgery. She returned 4 months later complaining of pain and increased swelling of the lesion. Repeat CTA demonstrated residual shunt located below the supra-orbital rim medially supplied by the left supratrochlear artery. Excision was later performed without repeat embolization and was uncomplicated. Histological reported chronic inflammation with granulomatous foreign body giant cell reaction confirming pre-operative diagnosis of tissue reaction to glue cast. CONCLUSION: Treatments of Orbital AVFs are challenging and require multidisciplinary team management involving interventional radiologists and orbital surgeons. A foreign body reaction can develop followed embolization with tissue glue alone. Prompt surgical excision is therefore recommended to minimize post operation morbidity.

Quantitative computed tomographic predictors of compressive optic neuropathy in patients with thyroid orbitopathy: a volumetric analysis.

PURPOSE: To evaluate the relationship between orbital bony geometry and the volume of the intraorbital structures in predicting compressive dysthyroid optic neuropathy (DON). DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Images of 198 orbits from 99 patients suffering from thyroid-related orbitopathy were reviewed. METHODS: Clinical examination and computed tomography of the orbits, including volumetric analysis, were performed on all patients. MAIN OUTCOME MEASURES: Clinical and radiologic predictors of DON. RESULTS: Significant volumetric univariate predictors of compressive optic neuropathy included medial rectus volume (P = 0.005), lateral rectus volume (P = 0.011), superior muscle group volume (P = 0.04), and total rectus muscle volume (P = 0.015). Inferior rectus muscle volume, orbital volume, bony orbital apex angle, globe diameter, and bony medial wall contour were not associated with optic neuropathy. Multivariate modeling found medial rectus volume the only independently significant predictor. Univariate modeling of simple rectus diameter measurements found medial rectus axial diameter (P = 0.003) and total recti diameter (P = 0.016) predictive of optic neuropathy. Lateral rectus, superior rectus, and inferior rectus diameters were not predictive. Multivariate modeling found only medial rectus diameter to be a significant independent predictor of optic neuropathy. The area under the receiver operating characteristic curve was not different between the volumetric and rectus diameter curves. CONCLUSIONS: Medial rectus size was found to be the most important quantifiable predictor of compressive optic neuropathy in patients with optic neuropathy. In this study, simple maximum medial rectus diameter, as measured on axial scans, was equally predictive of compressive optic neuropathy as the more involved volumetric calculation. Assessment of orbital geometry, including bowing of the medial wall, orbital apex angle, globe diameter, and orbital volume, were not found to be predictive of DON.

Stereotactic fractionated radiotherapy for cavernous venous malformations (hemangioma) of the orbit.

PURPOSE: Cavernous malformations (hemangioma) of the orbit, when symptomatic, can often be treated successfully with complete surgical excision. However, when they involve local structures in their capsule, are situated in the orbital apex, or extend through the superior orbital fissure, the risks of surgery increase significantly. In such cases, alternative treatment modalities can be explored. In this study, the authors report on the use of fractionated stereotactic radiotherapy (SFRT) for the treatment of surgically complicated cavernous malformations. METHODS: In this retrospective cohort study, the authors reviewed the clinical and radiologic records of 5 patients treated with SFRT over the past 5 years. RESULTS: Patients ranged in age from 30 to 65 years, and 3 out of 5 were female. Two cases involved the cavernous sinus, one involved the ophthalmic artery, one involved the posterior ciliary artery, and the last traversed the superior orbital fissure. Four had significant visual field defects. Each was treated with SFRT. A total dose of 4000 cGy divided into 20,200 cGy fractions was applied for 3 cases, while 2 other cases were treated with total doses of 4563 and 4959 cGy divided into 28 × 162 cGy and 29 × 171 cGy fractions, respectively. Rapid resolution of visual field defect was noted by 3 months, and overall tumor shrinkage was on average 60% (range: 32-79%). Follow-up was on average 23.4 months (range: 5-50 months). No complications of treatment were noted. CONCLUSIONS: For symptomatic cavernous malformations demonstrating anatomical position that may increase risk of surgical excision, SFRT is an effective and safe method to control lesion size and improve visual function.

Sclerosing orbital inflammation and systemic disease.

PURPOSE: To determine the clinical differences between sclerosing orbital inflammation (SOI) isolated to the orbit and SOI manifesting as part of systemic inflammatory disease. METHODS: For the case series, the authors identified patients with SOI from their patient database and tabulated their clinical data. For the literature review, a search for case reports of SOI in the English literature was performed. The clinical data of each were tabulated and analyzed. RESULTS: For the case series, 13 cases of SOI were identified, 2 with multifocal fibrosclerosis (MFF) and 4 with other systemic inflammatory diseases. Of the 5 bilateral cases, 4 (80%) had some form of systemic inflammatory disease including 2 with MFF. Only 2 (25%) of the 8 unilateral cases had systemic inflammatory disease. The average ESR was 7 mm/hour for those without systemic disease and 41 mm/hour with evidence of systemic disease (p = 0.038). For the literature review, the authors identified 68 case reports of SOI not previously reported in large case series, 34 associated with MFF, 5 associated with other systemic disease, and 29 not associated with any systemic disease. Sixty-nine percent of cases with systemic disease had bilateral orbital involvement, whereas only 3.6% of those without systemic disease were bilateral (p = 1.15 × 10(-8)). Twenty of the cases with MFF noted ESR (83 mm/hour, mean), 95% of which were above normal. ESR was noted in only one non-MFF, nonsystemic disease case and was normal. CONCLUSIONS: SOI in the setting of MFF or other systemic inflammatory disease is often bilateral and associated with an elevated ESR.

Clinical and soft-tissue computed tomographic predictors of dysthyroid optic neuropathy: refinement of the constellation of findings at presentation.

OBJECTIVE: To evaluate the ability to predict the presence of dysthyroid optic neuropathy (DON) using computed tomography assessment of soft-tissue and clinical features. STUDY DESIGN: A retrospective consecutive case series of patients with thyroid-related orbitopathy. RESULTS: One hundred eighty-nine orbits from 99 patients were evaluated. Statistically significant clinical predictors of DON on univariate analysis included a difference in intraocular pressure from primary gaze to upgaze (P = .02), the presence of lagophthalmos (P = .04), and inflammation as measured by the VISA (vision, inflammation, strabismus, appearance/exposure) inflammatory scale (P = .004). Dysthyroid optic neuropathy was inversely related to the marginal reflex distance (P = .01), levator function (P = .02), total ductions (P = .003), and interpalpebral fissure (P = .04). Statistically significant radiologic predictors determined on univariate analysis included apical crowding (P < .001), presence of enlarged tendons (P = .004), increasing total rectus diameter (P = .02), and presence of small, low densities within the recti muscles (P = .04). Multivariate analysis found only total ductions (P = .02) and marginal reflex distance (P = .04) determined on clinical examination and apical crowding shown on computed tomography (P = .003) to be significantly associated with DON. Receiver operating characteristic curves were used to evaluate the ability of the clinical and radiologic assessment, as well as the combination of these assessments, to predict DON. All 3 models were strong predictors of DON, with no statistically significant differences in the area under the receiver operating characteristic curve among them (P = .14). CONCLUSIONS: Total ductions, marginal reflex distance, and apical crowding observed on computed tomography scans are able to predict the presence of DON with high sensitivity, specificity, positive predictive value, and negative predictive value. Eyelid ptosis is a novel predictor of DON.