Disease Modulation Versus Modification: A Call for Revised Outcome Metrics in the Treatment of Thyroid Eye Disease.

PURPOSE: This perspective introduces the concepts of disease-modulating and -modifying therapy for thyroid eye disease and offers novel metrics for therapeutic outcomes. METHODS: A focused literature review was performed. RESULTS: Modulators are treatments that suppress disease symptoms whereas modifiers alter the natural history of a disease. Though many drugs are capable of exhibiting both effects, consideration of a drug's primary effect is useful when considering therapeutic options. For thyroid eye disease, corticosteroids and teprotumumab are effective at modulating many signs and symptoms of the disease, particularly those related to soft tissue inflammation. Orbital radiotherapy and rituximab have demonstrated effectiveness at durably modifying the natural history of thyroid eye disease. CONCLUSIONS: Outcome metrics should reflect the unique therapeutic objectives associated with disease modulation and modification. This conceptual framework should guide treatment of thyroid eye disease.

Ophthalmologic Involvement in Adults with Histiocytic Disorders: Clinical Presentation and Treatment Outcomes.

PURPOSE: To evaluate the clinical presentation, treatment, and outcomes in adult patients with histiocytic disorders with ocular, orbital, optic nerve, or cavernous sinus involvement. DESIGN: Observational, retrospective chart review. PARTICIPANTS: Adult patients (age ≥ 18 years) at Mayo Clinic from January 1, 1996, to July 1, 2021, with histiocytic disorders. Inclusion criteria were (1) histiocytic disorder by biopsy and appropriate clinical phenotype; (2) available medical records; and (3) ocular, orbital, optic nerve, or cavernous sinus involvement. METHODS: Retrospective chart review. MAIN OUTCOME MEASURES: Response to therapy, measured in clinical and radiographic impact. RESULTS: Thirty-two patients were identified: 7 with Langerhans cell histiocytosis (LCH); 15 with Erdheim-Chester disease (ECD); 1 with mixed LCH/ECD phenotype; 8 with Rosai-Dorfman disease (RDD); and 1 with mixed RDD/ECD phenotype. Ophthalmologic involvement was part of the initial presentation in 69% of patients (22/32). Eyelid edema (13/32, 41%) and proptosis (12/32, 38%) were the most frequent presentations. Isolated orbital or cavernous sinus involvement was present in 3 of 7 patients with LCH and 1 of 8 patients with RDD. Optic nerve sheath involvement was present in 2 of 7 LCH patients, 14 of 15 ECD patients, and 1 RDD/ECD patient. Diffuse (> 75%) orbital involvement was seen in 12 of 15 ECD patients and 1 of 7 LCH patients. Ocular involvement was seen in 1 of 15 ECD patients, 6 of 8 RDD patients, and 1 of 1 mixed RDD/ECD patient. The cavernous sinuses were involved in 1 of 7 LCH patients, 5 of 15 ECD patients, and both mixed phenotype patients. Visual acuity was affected in 14 patients (14/24, 58%) with a median logarithm of the minimum angle of resolution visual acuity of 0.1 (range, -0.12 to 3). BRAF V600E mutations were found in 75% (3/4) of LCH patients and 91% (10/11) of ECD patients. Patients received a variety of treatment, and response was variable across disease types. CONCLUSIONS: Orbital involvement was more commonly seen in LCH and ECD, whereas ocular involvement was more common in RDD. Visual acuity may be impacted from ocular involvement or compression of the optic nerve with diffuse orbital involvement.

Predictive Modeling of New-Onset Postoperative Diplopia Following Orbital Decompression for Thyroid Eye Disease.

PURPOSE: To identify risk factors for the development of new-onset, postoperative diplopia following orbital decompression surgery based on patient demographics, clinical exam characteristics, radiographic parameters, and surgical techniques. METHODS: We conducted a multi-center retrospective chart review of patients who underwent orbital decompression for thyroid eye disease (TED). Patient demographics, including age, gender, smoking history, preoperative exophthalmometry, clinical activity score (CAS), use of peribulbar and/or systemic steroids, and type of orbital decompression were reviewed. Postoperative diplopia was determined at a minimum of 3 months postoperatively and before any further surgeries. Cross-sectional area ratios of each extraocular muscle to orbit and total fat to orbit were calculated from coronal imaging in a standard fashion. All measurements were carried out using PACS imaging software. Multivariable logistic regression modeling was performed using Stata 14.2 (StataCorp, College Station, TX). RESULTS: A total of 331 patients without preoperative diplopia were identified. At 3 months postoperatively, 249 patients had no diplopia whereas 82 patients developed diplopia. The average postoperative follow-up was 22 months (range 3-156) months. Significant preoperative clinical risk factors for postoperative diplopia included older age at surgery, proptosis, use of peribulbar or systemic steroids, elevated clinical activity score, and presence of preoperative compressive optic neuropathy. Imaging findings of enlarged cross-sectional areas of each rectus muscle to the overall orbital area also conferred a significant risk of postoperative diplopia. Regarding surgical factors, postoperative diplopia was more common among those undergoing medial wall decompression, bilateral orbital surgery, and balanced decompression, whereas endoscopic medial wall decompression was found to be relatively protective. CONCLUSIONS: This study identifies risk factors associated with the development of diplopia following orbital decompression using multivariable data. This study demonstrates that several characteristics including age, clinical activity score, the cross-sectional muscle to orbit ratios, in addition to the type of orbital decompression surgery, are predictive factors for the development of new-onset postoperative diplopia.

Incidence of Ischemic Optic Neuropathy After Cardiopulmonary Bypass: 20-Year Experience.

OBJECTIVE: This study evaluated the incidence and risk factors for ischemic optic neuropathy (ION) as a complication of cardiac surgery requiring cardiopulmonary bypass (CPB). DESIGN: Retrospective chart review of prospectively collected data at a tertiary care center. SETTING: Single tertiary academic referral center. PARTICIPANTS: This study comprised 44,568 cardiac surgery patients who underwent CPB between January 1, 1995, and January 5, 2017, using the Society of Thoracic Surgeons database and cross-matching it with International Classification of Diseases codes for visual changes. INTERVENTIONS: None; this was a retrospective chart review. MEASUREMENTS AND MAIN RESULTS: Six patients initially were identified as experiencing visual changes. Only 1 patient from 44,568 cardiac surgeries with CPB between January 1, 1995, and January 5, 2017, experienced ION, for an incidence 0.22 per 10,000. Because only 1 patient experienced ION, the authors were unable to determine risk factors for this complication; however, the nadir perioperative hemoglobin in the affected patient was 7.3 g/dL (postoperative). CONCLUSION: The incidence of ION decreased from 6 per 10,000 in the authors' previous study from 1976-1994 to 0.22 per 10,000 in the present study. Because of the low incidence of this dreaded complication, the authors were not able to identify risk factors for ION. Practice improvements (eg, transition to membrane oxygenators, blood transfusion guidelines, less- invasive surgical options for high-risk patients) during the time between the authors' studies likely affected the incidence reduction.

Trochleaectomy: An Effective Treatment of Trochlear Pain in Monocular Patients.

BACKGROUND: Conventional treatment options for trochlear pain arising from trochleitis or primary trochlear headache include oral anti-inflammatory medications and/or local injection of corticosteroids and local anesthetic. Trochleaectomy is an additional option to consider for monocular patients with intractable trochlear pain. METHODS: We report 3 patients undergoing trochleaectomy for refractory trochlear pain syndromes. RESULTS: Trochleaectomy resulted in resolution of their periocular discomfort. CONCLUSIONS: Trochleaectomy is an effective procedure to treat trochlear pain syndrome in functionally monocular patients.

The "Quiet TED"-A Special Subgroup of Thyroid Eye Disease.

PURPOSE: Thyroid eye disease (TED) or Graves' orbitopathy starts with an active inflammatory stage (active disease) followed by resolution of inflammation and progression to a fibrotic, inactive stage. In our practice, we have encountered cases that have not had active disease despite presence of fibrotic sequelae and disease progression. We aim to delineate the clinical characteristic of this unique group of patients. METHODS: We conducted a single-center (Mayo Clinic Rochester) retrospective chart review of TED patients who throughout the course of their disease had only evidence for inactive TED, defined as clinical activity score <3. RESULTS: Median age in the cohort (n = 19) was 54 years (IQR 47-61). 58% had a prior diagnosis of Graves' disease (GD) before referral. 80% (n = 15) were euthyroid at the time of TED onset (median thyroid-stimulating hormone 1.7 mIU/L). The most common finding was diplopia (100%, n = 19) followed by proptosis (63%, n = 12). Interestingly the disease was asymmetric in 42% of cases. Overall median clinical activity score on presentation was 1 (IQR 0-1). Severity wise, 85% (n = 16) of patients were classified as moderate-to-severe during follow up. Orbital decompression was performed in only 1 case, while extraocular muscle surgery was performed in 13 cases. CONCLUSIONS: Quiet TED is a subgroup of TED patients that defies the classic disease paradigm. It presents primarily with diplopia and proptosis. Further evaluation of this group might identify useful insights in TED pathophysiology and help optimize therapeutic choices.

Carcinoid Tumors of the Orbit and Ocular Adnexa.

PURPOSE: Well-differentiated neuroendocrine or carcinoid tumors are found most commonly in the gastrointestinal tract. When metastatic to the orbit, they tend to have a propensity for the extraocular muscles. The purpose of this study was to better understand the diversity in presentation of orbital carcinoid disease and to determine predictors for survival. METHODS: In this observational cross-sectional cohort study, data from 8 tertiary orbital practices were compiled. Demographic, clinical, pathologic, American Joint Committee on Cancer stage and grade, imaging, and management data were extracted for all the patients. Descriptive statistics were calculated. Subgroups were compared utilizing analysis of variance analyses and Kaplan-Meier curves. Time to progression and disease-specific and overall mortality were calculated. Comparisons were performed for the following a priori pairs: unknown versus known primary tumor, single versus multiple extraocular muscle involvement, unilateral versus bilateral orbital disease, extraocular muscle versus other orbital involvement, and excisional versus incisional surgery. RESULTS: A total of 28 patients with carcinoid tumors of the orbit were identified. Of these, 57.1% of patients were female, the mean age at diagnosis of the primary tumor was 58.8 years and the mean age at diagnosis of orbital disease was 62.6 years. At primary presentation, all patients were American Joint Committee on Cancer stage III or IV and 21.4% demonstrated carcinoid syndrome. Muscle involvement was noted in 78.6% of patients, and of these, 72% were noted to have single muscle disease. Eight patients had no primary tumor identified; 3 of these 8 demonstrated disseminated disease at the time of diagnosis. The overall 5-year survival rate was 81.8% from diagnosis of primary tumor and 50% from diagnosis of orbital disease. Subgroup analysis revealed that patients with unilateral orbital disease when compared with bilateral orbital disease had a longer progression-free survival and time to death from all causes (p = 0.025). Patients with disease localized to the orbit at presentation had longer time to death than those with disseminated disease. Treatment with surgery, radiation, or octreotide did not appear to affect survival. Patients managed with systemic chemotherapy had a shorter time of survival than the rest of the group. All other subgroup comparisons were not found to be statistically significant. CONCLUSIONS: Neuroendocrine tumors of the orbit represent a wide spectrum of disease, with some cases being part of disseminated disease, while others being localized presentations. This heterogeneity may be responsible for the slightly higher overall survival in these patients than others with metastatic carcinoid tumors in other locations.

A Prospective, Randomized, Double-blind, Placebo-controlled Study of Orbital Radiotherapy for Graves' Ophthalmopathy.

CONTEXT: Although widely used for more than 85 years, the efficacy of radiotherapy for Graves' ophthalmopathy (GO) has not been established convincingly. OBJECTIVE: To evaluate the efficacy of radiotherapy for GO. DESIGN: Prospective, randomized, internally controlled, double-blind clinical trial in a tertiary care academic medical center. PARTICIPANTS: The patients were ethnically diverse males and females over age 30 seen in a referral practice. The patients had moderate, symptomatic Graves' ophthalmopathy (mean clinical activity score, 6.2) but no optic neuropathy, diabetes, recent steroid treatment, previous decompression, or muscle surgery. Forty-two of 53 consecutive patients were enrolled after giving informed consent and fulfilling study entry criteria. Eleven eligible patients declined to participate because of inconvenience, desire for alternative therapy, or concern about radiation. INTERVENTION: One randomly selected orbit was treated with 20 Gy of external beam therapy; sham therapy was given to the other side. Six months later, the therapies were reversed. MAIN OUTCOME MEASURES: Every 3 months for 1 year, we measured the volume of extraocular muscle and fat, proptosis, range of extraocular muscle motion, area of diplopia fields, and lid fissure width. Effective treatment for GO will modify one or more of these parameters. RESULTS: No clinically or statistically significant difference between the treated and untreated orbit was observed in any of the main outcome measures at 6 months. At 12 months, muscle volume and proptosis improved slightly more in the orbit that was treated first. CONCLUSIONS: In this group of patients, representative of those for whom radiotherapy is frequently recommended, we were unable to demonstrate any beneficial therapeutic effect. The slight improvement noted in both orbits at 12 months may be the result of natural remission or of radiotherapy, but the changes are of marginal clinical significance.

Intracranial Pure Germinoma With Optic Nerve Infiltration.

A 19-year-old man presented with a 3-year history of episodic headaches, right hemiparesis, and progressive vision loss in both eyes. Initially, extensive laboratory testing was unrevealing. MRI later demonstrated progressive enlargement and enhancement of the left optic nerve poorly correlated with the timing of his clinical manifestations. There was no clinical or radiological response to treatment with corticosteroids, mycophenolate mofetil, or rituximab administered empirically for possible inflammatory processes. Later in the disease course, he developed diabetes insipidus (DI), worsening vision to light perception bilaterally, severe cognitive decline, and spastic quadriparesis. Cerebrospinal fluid (CSF) beta human chorionic gonadotropin (ß-hCG) was elevated. Eventually, a left optic nerve biopsy was performed, which was consistent with an intracranial pure germinoma with infiltration of the optic nerve and disseminated leptomeningeal disease. Although rare, intracranial germ cell tumors can primarily involve the anterior visual pathways and should be considered in the setting of DI and elevated CSF ß-hCG.

Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit.

PURPOSE: To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit. METHODS: Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis. RESULTS: The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device's ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location. CONCLUSIONS: The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.

Thyroid eye disease presenting with superior rectus/levator complex enlargement.

Purpose: To describe the demographic and clinical characteristics of patients with thyroid eye disease (TED) who present with predominate superior rectus/levator complex involvement.Methods: A multi-institutional retrospective review was performed to identify patients with TED who presented with superior isolated or predominate rectus/levator involvement. Baseline and subsequent visits were reviewed to characterize the clinical course.Results: Nineteen patients were identified. All patients had imaging demonstrating an enlarged levator/superior rectus complex. At presentation, the mean clinical activity score (CAS) was 2.1 (range: 0-5). Nineteen (100%) patients had proptosis on the affected side. Lid abnormalities, including upper/lower eyelid retraction and ptosis were higher on affected side compared to the unaffected side. Eleven (58%) patients had vertical misalignment. Mean thyroid stimulating immunoglobulin (TSI) was 3.7 (range: 1-7.1). Mean follow-up time was 18 months (range: 0-60 months). At last follow-up, the mean CAS was 1.3 (range 0-5). Ten (53%) patients had proptosis. Eleven (58%) patients had vertical misalignment. Repeat imaging in eight patients showed interval enlargement of other extraocular muscles.Conclusions: The presentation of TED with superior rectus/levator complex enlargement may be under-appreciated. Orbital imaging, as well as laboratory evaluation, may help support a diagnosis of TED. In the setting of abnormal TSI and/or thyrotropin receptor antibody, presence of upper eyelid retraction, and an otherwise unremarkable laboratory and systemic evaluation, a presumptive diagnosis of TED may be made, and the patient can be followed closely, as he/she is likely to develop involvement of other extraocular muscles, consistent with a more typical presentation of TED.

Incipient Syphilitic Papillitis.

Patients with syphilis can present with optic disc oedema (ODE) without visual compromise, which has been primarily attributed to papilloedema from raised intracranial pressure or optic perineuritis from optic nerve sheath inflammation. We report four cases of ODE in the setting of syphilis with preserved visual function, normal intracranial pressure, and no enhancement of the optic nerve or sheath on magnetic resonance imaging. We propose the term "incipient syphilitic papillitis" for cases presenting with ODE, preserved vision and absence of optic nerve sheath enhancement, which is likely a more common presentation than syphilitic optic perineuritis.

Lower Eyelid Reconstruction Using a Nasolabial, Perforator-based V-Y Advancement Flap: Expanding the Utility of Facial Perforator Flaps.

BACKGROUND: Reconstruction of the lower eyelid represents a unique challenge to the reconstructive surgeon. Studies evaluating the utility of the nasolabial V-Y advancement flap in lower eyelid reconstruction are limited and techniques to optimize outcomes following eyelid reconstruction with this technique are not well described. We seek to evaluate our experience and outcomes with lower eyelid reconstruction using the nasolabial perforator-based V-Y advancement flap. METHODS: After institutional review board approval, medical charts of all patients who underwent lower eyelid reconstruction using the nasolabial perforator-based V-Y advancement flap between February 2013 and October 2017 were reviewed. Data regarding etiology, location of the lesion, lower eyelid defect, methods of reconstruction, postoperative complications, and follow up duration were collected and analyzed. RESULTS: Over the study period, 5 patients (3 male) underwent lower eyelid reconstruction after oncologic resection of melanoma (n = 1) and nonmelanoma (n = 4) skin cancer using the nasolabial perforator-based V-Y advancement flap at a mean age of 69 years (range, 56-82 years). Median follow-up duration was 5.9 months (interquartile range, 2.25-25.9). A mean of 5.4 (range, 2-10) perforators were included in the initial flap design. After completion of flap dissection and perforator division, a mean of 4.4 (range, 2-7) perforators were preserved and included in the flap. All flaps demonstrated clinical viability with no cases of partial or total flap loss. One patient developed an asymptomatic ectropion during the follow-up period. CONCLUSIONS: The nasolabial, perforator-based V-Y advancement flap is a reliable reconstructive method for lower eyelid defects.

Distinguishing IgG4-Related Ophthalmic Disease From Graves Orbitopathy.

PURPOSE: The authors aimed to determine key features of IgG4-related ophthalmic disease (IgG4-ROD) and Graves orbitopathy (GO) to aid in diagnosis. METHODS: The authors retrospectively identified ophthalmology patients seen between June 2009 and November 2013 with clinical overlap of GO and IgG4-ROD. Patient findings were reviewed to characterize the 2 conditions. RESULTS: Among 8 patients (7 male and 1 female), the mean age was 45.8 years. Time between diagnoses of GO and IgG4-ROD ranged from 1 month to 8 years. Imaging showed enlarged extraocular muscles in all patients. Enlarged infraorbital nerves were seen in 4 patients. Tissue biopsy showed CD20+ lymphocytes with a large proportion of IgG4 plasma cells in 7 of 8 orbital specimens. Six patients had a ratio of IgG4:IgG cells >40%. DISCUSSION: No pathognomonic clinical findings for GO or IgG4-ROD have been reported, but some key features can help distinguish the conditions. GO is likely if findings include increased thyrotropin receptor antibodies, lid retraction/lid lag, and enlarged extraocular muscles with typical tendon-sparing morphology. Findings suggestive of IgG4-ROD include history of asthma and progressive orbital disease in patients with previous diagnosis of GO, disproportionately large lateral rectus muscle, and enlarged infraorbital nerves. Increased serum IgG4 level and biopsy showing >10 IgG4+ plasma cells/high-power field and IgG4:IgG ratio >40% will support the diagnosis of IgG4-ROD. CONCLUSIONS: GO and IgG4-ROD are complicated inflammatory processes affecting the orbit and present diagnostic challenges. The authors recommend biopsy for patients who do not follow the usual clinical course of GO or have clinical characteristics of IgG4-ROD.

Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study.

Objective: To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV). Methods: Medical records of potential cases of AAV seen at Mayo Clinic from 2003 to 2013, inclusive, were reviewed to identify confirmed cases meeting the diagnosis of AAV using the Chapel Hill Consensus Conference 2012 descriptors. Records of confirmed cases of AAV were then further reviewed for IOD, and clinical characteristics, treatment and outcomes abstracted. Results: A total of 1171 confirmed cases of AAV were identified of which 183 patients (mean age 49.0 years; 51% female; 95% Caucasian) had IOD. The most common manifestation of IOD was injection of the eye (57%) followed by eye pain (46%) and visual acuity loss (18%). Scleritis was the most common type of IOD (22%) followed by episcleritis (21%), orbital inflammation (18%), lacrimal duct stenosis (10%) and uveitis (9%). Oral glucocorticoids were used to treat IOD in the majority of patients (96%). CYC and rituximab were the most frequently used immunosuppressive agents (54 and 36%, respectively). Of those with orbital inflammation, 52% underwent therapeutic surgical intervention. Clinical remission of IOD was achieved in 91% of patients but relapses were seen in 23%. Significant visual acuity loss was observed in only six patients. Conclusion: IOD is a common manifestation of AAV and seen in about 16% of patients with AAV. Scleritis, episcleritis and orbital inflammation are the most common subtypes. Most patients respond well to glucocorticoids and immunosuppression, but relapse of IOD is common.

Dacryocystorhinostomy for Acquired Nasolacrimal Duct Stenosis in the Elderly (≥80 Years of Age).

PURPOSE: The incidence of acquired nasolacrimal duct obstruction (NLDO) increases with age. Dacryocystorhinostomy, the definitive treatment for NLDO, has a high success rate (80%-100%) with a low complication rate (1%-6%), but surgical outcomes have not been reported previously specifically for an elderly population, in which there may be increased risk for intraoperative and postoperative complications. The purpose of this study was to examine surgical outcomes and complication rates of dacryocystorhinostomy in an elderly population. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients 80 years of age or older undergoing external dacryocystorhinostomy at the Mayo Clinic between January 1, 1990, and December 31, 2010, were compared with a matched control group of younger patients (40-79 years of age) undergoing external dacryocystorhinostomy by the same surgeons. METHODS: We reviewed the medical charts for patients as described above. Data abstracted from patient medical records included symptomatic relief and complications such as tube protrusion, infection, persistent bleeding, and return to operating room. Statistical analysis included a 2-sample t test to compare continuous variables, chi-square testing for categorical comparisons, and the generalized estimating equation model to control for nonindependence. MAIN OUTCOME MEASURES: Primary end point was symptomatic improvement at last follow-up. Secondary end points included anatomic patency, adverse event rate, and return to operating room within 1 month of surgery. RESULTS: Forty-two dacryocystorhinostomies (32 patients) were performed in the elderly group. The control group comprised 73 dacryocystorhinostomies in 63 patients. Resolution of symptom rate at last follow-up was 64% in the elderly group versus 86% in the younger cohort (P = 0.02). Although there was no difference between groups with respect to common postoperative complications, there was a higher rate of predefined serious complications in the elderly group (5 events vs. 1 event; P = 0.01). There was no difference between groups regarding need for additional eyelid surgery (P = 0.30). CONCLUSIONS: Although most elderly patients experience symptom resolution after dacryocystorhinostomy, the rate of symptom resolution was lower than that of younger patients. The risk of routine complications was similar between the groups. The risk of serious complications was higher in the elderly group.

Low-Flow Arterialized Venous Malformations of the Orbit.

PURPOSE: Orbital vascular malformations are classified by their hemodynamic properties, either high or low flow. Low-flow lesions may be simple venous, lymphatic, or combined lymphaticovenous malformations. The authors report a series of cases in which predominantly low flow, venous lesions were unexpectedly noted to have arterial feeders. METHODS: A retrospective chart review of patients identified by the authors as having orbital varices with arterial components was conducted. The authors identified 7 such cases. After careful review, 2 cases were excluded due to inconclusive neuroradiographic findings. The authors review the clinical, radiologic, histopathologic, and surgical information from the remaining 5 cases and discuss their clinical significance. RESULTS: All 5 cases were most consistent with variceal lesions: 3 as clinically distensible lesions and 2 as thrombosed lesions. Additional arterial feeder vessels were noted by angiography (3) or intraoperative visualization (2). The arterial contribution varied from faint vessels to distinct branches of the ophthalmic artery. Ages ranged from 13 to 61 years without predilection for gender. Treatments consisted of excision, embolization, and observation. Two poignant cases are highlighted: the first illustrating that an angiogram in isolation of its clinical picture can be misleading and result in treatment intervention with undue risk, and the second illustrating that inadequate treatment of unrecognized arterial components may contribute to recurrences. CONCLUSIONS: Low-flow orbital variceal lesions may have less prominent, arterial components. This type of combined arterialized venous malformation is largely unrecognized in the ophthalmic literature. Correct identification of these lesions is critical in providing safe, effective, and durable treatment.

Expression of Vascular Endothelial Growth Factor Receptors in Benign Vascular Lesions of the Orbit: A Case Series.

PURPOSE: Vascular lesions of the orbit, although not malignant, can cause morbidity because of their location near critical structures in the orbit. For the same reason, they can be challenging to remove surgically. Anti-vascular endothelial growth factor (VEGF) drugs are increasingly being used to treat diseases with prominent angiogenesis. Our study aimed to determine to what extent VEGF receptors and their subtypes are expressed on selected vascular lesions of the orbit. DESIGN: Retrospective case series of all orbital vascular lesions removed by one of the authors (JAG) at the Mayo Clinic. PARTICIPANTS: A total of 52 patients who underwent removal of vascular orbital lesions. METHODS: The pathology specimens from the patients were retrieved, their pathologic diagnosis was confirmed, demographic and clinical information were gathered, and sections from vascular tumors were stained with vascular endothelial growth factor receptor (VEGFR), vascular endothelial growth factor receptor type 1 (VEGFR1), vascular endothelial growth factor receptor type 2 (VEGFR2), and vascular endothelial growth factor receptor type 3 (VEGFR3). MAIN OUTCOME MEASURES: The existence and pattern of staining with VEGF and its subtypes on these lesions. RESULTS: There were 28 specimens of venous malformations, 4 capillary hemangiomas, 7 lymphatic malformations, and 6 lymphaticovenous malformations. All samples stained with VEGF, 55% stained with VEGFR1, 98% stained with VEGFR2, and 96% stained with VEGFR3. Most (94%) of the VEGFR2 staining was diffuse. CONCLUSIONS: Most orbital vascular lesions express VEGF receptors, which may suggest a future target for nonsurgical treatment.