A Rare Case of Methotrexate-Associated Lymphoproliferative Disease in the Orbit.

An 80-year-old Caucasian female with a history of rheumatoid arthritis presented with a 6-month history of progressive right upper eyelid ptosis, edema, erythema, and pain. MRI demonstrated a superior orbital mass. An incisional biopsy was performed, and pathologic analysis revealed an atypical lymphoid infiltrate, co-expressing both B and T-cell markers, with a low proliferation rate. Flow cytometry and IgH rearrangement study did not demonstrate any B- or T-cell monoclonal proliferation. Based on these findings, she was diagnosed with an iatrogenic immunodeficiency-associated lymphoproliferative disorder. Discontinuation of methotrexate resulted in the complete resolution of her symptoms, and she remains in remission 18 months later. Given the increased risk of lymphoproliferative disease in patients with rheumatoid arthritis, careful evaluation and close monitoring upon immunosuppressive medication withdrawal is necessary to confirm the diagnosis.

Chronic Lymphocytic Leukemia Presenting as Bilateral Periorbital Edema Treated With Low-dose Radiation Therapy.

Ocular manifestations in chronic lymphocytic leukemia (CLL) have been reported in 30% to 40% of patients and may be a result of direct tissue infiltration, concomitant blood dyscrasias, or a result of therapeutic intervention. Leukemia cutis, defined as infiltration of the epidermis or dermis by neoplastic lymphocytes, is rare. Herein, we present a case report of a patient with leukemia who presented with periorbital edema and ecchymosis. This is the first known case to date of periorbital CLL successfully treated with low-dose radiation therapy (4 Gy in 2 fractions). Clinicians should be aware of the possibility of ocular involvement from CLL, given the importance of prompt diagnosis and treatment.

NK/T-cell Lymphoma With Orbital Involvement: A Case Report and Systematic Review of the Literature.

PURPOSE: To present the clinical course of a patient with recurrent NK/T-cell lymphoma (NKTL) involving the orbit and to review the literature on patients with NKTL involving the orbit. METHODS: The PubMed database was searched for all cases of NKTL involving orbital, intraocular, or adnexal ocular structures. RESULTS: Ninety-six patients were included in the final analysis. The mean age of diagnosis was 48.1 ± 16.8 years. The patients were 53/96 (55.2%) male and 43/96 (44.8%) female. Tumor location varied and included the orbit in 80/96 (83.3%), nasosinus in 56/96 (58.3%), uvea in 11/96 (11.5%), lacrimal gland in 9/96 (9.4%), lacrimal drainage system in 11/96 (11.5%), and conjunctiva in 7/96 (7.3%) cases. Management included surgical debulking in 29/96 (30.2%) cases, radiotherapy in 52/96 (54.2%) cases, and chemotherapy in 82/96 (85.4%) cases. Median survival was 6 months (95% CI: 5-9). Chemotherapy (hazard ratio = 0.80, 95% CI: 0.67-0.95, p = 0.013), radiotherapy (hazard ratio = 0.75, 95% CI: 0.64-0.87, p < 0.001), and orbital involvement being a recurrence of disease (hazard ratio = 0.79, 95% CI: 0.67-0.95, p = 0.009) were associated with improved survival. Advanced Ann Arbor stage (III-IV) at diagnosis (hazard ratio = 1.22, 95% CI: 1.08-1.38, p = 0.001), vision loss (hazard ratio = 1.18, 95% CI: 1.04-1.34, p = 0.009), proptosis (hazard ratio = 1.15, 95% CI: 1.01-1.30, p = 0.035) and periorbital swelling (hazard ratio = 1.15, 95% CI: 1.00-1.33, p = 0.048) were associated with poor survival. CONCLUSIONS: NK/T-cell lymphoma involving the orbit, globe, or ocular adnexa heralds a poor prognosis where early diagnosis and therapy are critical. The use of radiotherapy and chemotherapy is associated with improved survival.

Septic Superior Ophthalmic Vein Thrombosis in a Prothrombotic Adolescent Patient.

A 14-year-old boy presented to the emergency room with 5 days of fever and periorbital edema and erythema refractory to 4 days of augmentin and clindamycin. Examination revealed normal visual acuity, mild left periorbital edema and erythema, and a (-)1 supraduction deficit, concerning for orbital cellulitis. CT imaging revealed pansinusitis, orbital cellulitis with subtle orbital fat stranding, and a dilated superior ophthalmic vein with concern for thrombosis. This was confirmed on subsequent magnetic resonance venography. He was treated with intravenous antibiotics and enoxaparin with significant improvement in 24 hours. Standard hypercoagulable workup revealed positive lupus anticoagulant and cardiolipin of unclear significance; on genetic sequencing, he was found to have a homozygous mutation of the 4G variant of plasminogen activator inhibitor-1. Plasminogen activator inhibitor-1 homozygosity is a rare predisposing hypercoagulable state. This case highlights the importance of hematologic and genetic studies in adolescent patients with superior ophthalmic vein thrombosis, particularly those with mild presentation.

Bilateral dacryoadenitis as the initial presentation of ANCA-associated vasculitis in a pediatric patient.

A 14-year-old female presented with 2 weeks of progressive right eye pain, erythema, and proptosis. Examination demonstrated an enlarged palpable mass along the right superior lateral orbit and bilateral conjunctival petechiae. Of note, she was asymptomatic on the left side, and the petechiae were present only on the superior bulbar conjunctiva with eyelid eversion. Imaging demonstrated bilateral lacrimal gland enhancement. Testing was significant for elevated inflammatory markers, but otherwise negative workup. Biopsy of the right lacrimal gland demonstrated acute-on-chronic inflammation without evidence of lymphoproliferative disease. On repeat testing, myeloperoxidase antibody levels (MPO/p-ANCA) were elevated, indicative of an underlying immune-mediated vasculitis. This case illustrates a rare presentation of ANCA-associated vasculitis in a pediatric patient. It further demonstrates the phenomenon of initial negative serology and subsequent auto-antibody seroconversion in a patient with localized granulomatosis with polyangiitis.

Spheno-Orbital Dermoid Masquerading as Recurrent Orbital Abscess.

A 10-month-old girl presented with eyelid edema and erythema that did not improve with systemic antibiotics. Due to a lack of improvement, MRI was performed to avoid ionizing radiation from CT. An orbital abscess was recognized and drained. However, the abscess recurred 2 times. CT scan was performed and a tract in the sphenoid bone helped to diagnose a congenital dural sinus tract with dermoid. Definitive surgery was performed with neurosurgery to remove the entire tract including cutaneous connection. CT scan proved critical to diagnosis and should be considered in infants in select cases despite the concern for ionizing radiation in this vulnerable age group.

Subperiosteal Masqueraders as Compared to Subperiosteal Abscess: Contrasting Clinical Presentation and Radiographic Densities.

PURPOSE: Subperiosteal orbital lesions are most commonly abscesses secondary to sinusitis but, in rare cases, may represent other processes. Here, the authors compare the clinical and radiographic presentation of subperiosteal abscesses and alternate subperiosteal processes ("masqueraders") in an effort to establish distinguishing preoperative diagnostic criteria. METHODS: A retrospective chart review of cases of subperiosteal orbital lesions that underwent surgical intervention over a 3-year period was performed. The medical records of 6 cases of subperiosteal masqueraders and 6 cases of abscesses were reviewed for the clinical course, imaging (including radiographic density of lesions), and pathology. Clinical and radiographic features of the 2 groups were compared. RESULTS: All cases presented with orbital signs on exam. Fever and leukocytosis were absent in the masquerader group and present in 3 patients from the abscess group. Common radiographic findings in both groups included a rim-enhancing convex mass along the orbital wall and adjacent sinus opacification, often with bony dehiscence. Of the masqueraders, the final diagnosis was hematoma in 3 cases, mucocele in 1, and malignancy in 2. The difference between the mean radiodensity of the subperiosteal abscesses, 38 ± 5 Hounsfield units (95% CI, 34-42), as compared with the average radiodensity of the masqueraders, 71 ± 5 Hounsfield units (95% CI, 67-75), was significant (p = 0.042). Comparing radiodensity of the orbital lesion to adjacent sinus lesions and metastatic lesions elsewhere was also informative in establishing the diagnosis. CONCLUSIONS: Radiographic features, particularly radiodensity, may help distinguish subperiosteal abscesses from other lesions and aid in preoperative diagnosis and management.

Post-traumatic enophthalmos secondary to orbital fat atrophy: a volumetric analysis.

PURPOSE: To investigate via volumetric analysis whether orbital fat atrophy occurs in late post-traumatic enophthalmos. METHODS: An IRB-approved retrospective cohort study identified patients with diagnoses of both orbital fracture and enophthalmos with a CT orbits >3 months after injury. Exclusion criteria were surgical repair, other orbital disease or surgery, adjacent sinus disease, and an abnormal contralateral orbit. Images were analyzed using OsiriX imaging software (v.9.0.2, Pixmeo, Switzerland). Total orbital volume and orbital fat volume for the fractured and normal contralateral orbits were measured via three-dimensional volume rendering assisted region-of-interest computation. Enophthalmos was measured radiographically. Paired samples t-tests were used to compare orbital fat and total orbital volumes between the fractured and normal contralateral orbits. RESULTS: Thirteen patients met the inclusion criteria. The numbers of patients with each fracture pattern were floor (4), medial wall (4), floor/medial wall (3), zygomaticomaxillary complex (floor+lateral wall) (1), zygomaticomaxillary complex+medial (inferior/medial/lateral walls) (1). Mean time from injury to CT scan was 21.8 ± 16.3 months. Comparing the fractured and normal contralateral orbits, there was a statistically significant decrease in orbital fat volume (mean difference 0.9 ml (14.2%), p = .0002) and increase in total orbital volume (mean difference 2.0 ml (7.0%), p = .0001). One ml orbital volume change was responsible for 0.83 mm enophthalmos. CONCLUSIONS: In addition to an increase in total orbital volume, orbital fat loss occurs with late post-traumatic enophthalmos due to unrepaired fractures. This suggests correction of bony change alone may be insufficient in some cases, and the use of custom implants may compensate for fat atrophy.

Orbital Nasal-Type Extranodal Natural Killer/T-Cell Lymphoma: An Ongoing Diagnostic Challenge Further Confounded by Small-Cell Predominance.

PURPOSE: To highlight the histopathologic diagnostic challenges of small-cell predominant extranodal nasal-type natural killer/T-cell lymphoma (ENTNKT) of the orbit. METHODS: Retrospective chart review and histopathologic study with immunohistochemistry and in situ hybridization of 3 cases. RESULTS: Three cases of ENTNKT presented to the Mass Eye and Ear emergency room as orbital cellulitis over 1 year. The first case was unusual in that there was a predominance of small cells, giving the ENTNKT the histopathologic appearance of a nonmalignant inflammatory process. This challenging case is juxtaposed alongside 2 other cases, which exhibited the more typical lymphomatous microscopic appearance. DISCUSSION: ENTNKT can extend into the orbit from the adjacent sinuses or rarely arise primarily in the orbit. A diagnosis is typically made with a biopsy. Occasionally, however, the histopathologic diagnosis can be elusive when a predominance of small lymphomatous cells that are virtually indistinguishable from non-neoplastic inflammatory cells is present. Demonstration of CD56 positivity by immunostaining and in situ hybridization for Epstein-Barr virus are essential in confirming the diagnosis. CONCLUSIONS: ENTNKT should be considered both in the clinical and histopathologic differential diagnoses of orbital infections and idiopathic inflammations (pseudotumor).

Association of Risk of Obstructive Sleep Apnea With Thyroid Eye Disease: Compressive Optic Neuropathy.

PURPOSE: To evaluate the association of risk of obstructive sleep apnea (OSA) and thyroid eye disease-compressive optic neuropathy (TED-CON). METHODS: The authors performed a retrospective observational study. All TED patients evaluated by the principal investigator over the past 5 years were screened with the snoring tired observed pressure (STOP)-Bang questionnaire to assess their risk for OSA. Patients were grouped into 2 age-matched cohorts based on the presence (TED-CON) or absence of CON. The groups were then compared using chi-square analysis for binary variables and Student t test for continuous variables. RESULTS: Three hundred twenty-six patients were identified to have TED. Of those, 109 were enrolled in the study. The prevalence of high risk of OSA was significantly higher in the TED-CON (59.2%) when compared with the noncompressive TED group (32.8%; p = 0.006). CONCLUSIONS: Obstructive sleep apnea and TED have each been independently associated with elevated serologic and tissue inflammatory mediators. The systemic inflammation associated with OSA has been implicated in the pathogenesis of disease states aggravated by untreated OSA. Effective treatment of OSA decreases the levels of circulating inflammatory mediators. Currently, smoking is the only known modifiable risk factor in TED. There is evidence to implicate the pathologic elevation of inflammatory cytokines in the mechanism of smoking on TED. This preliminary investigation reveals a significantly greater prevalence of OSA risk factors among patients with TED-CON, suggesting that this may be another modifiable risk factor associated with TED. Based on screening with the STOP-Bang questionnaire, there is a higher percentage of patients at high risk of OSA with TED with CON than with TED without CON.

Simultaneous ipsilateral transconjunctival repair of upper and lower eyelid retraction in thyroid-associated ophthalmopathy.

PURPOSE: To report a simple, highly effective technique of simultaneous transconjunctival repair of upper and lower eyelid retraction in patients with thyroid eye disease (TED). METHODS: A retrospective interventional case review was conducted on 22 eyes of 19 TED patients. The lower eyelid was recessed with placement of a tarsoconjunctival spacer graft harvested from the upper eyelid. The upper eyelid was then recessed through the conjunctival incision used to harvest the tarsal graft. A temporary tarsorrhaphy was placed for 5-7 days. The postoperative outcome was assessed by measuring the margin reflex distance of the upper eyelid (MRD1), inferior scleral show (ISS), and lagophthalmos. RESULTS: The absolute change in MRD1 ranged from 0 to 5 mm with an average of 1.86 ± 1.34 mm. The absolute change in ISS ranged from 0 to 2 mm with an average of 1.3 ± 0.49 mm. One patient had postoperative lagophthalmos and 17 of 19 had improvement in their ocular surface exposure symptoms. None of the patients' grafts were observed to undergo absorption during the postoperative course. CONCLUSIONS: This technique of harvesting a free tarsoconjunctival graft from the upper eyelid as a posterior spacer for the lower while simultaneously recessing the upper eyelid through the same incision is an effective and durable method of correcting eyelid retraction in TED.

Epibulbar Mass With Upper Eyelid Cleft and Focal Scalp Alopecia in a Neonate: A New Case of Oculoectodermal Syndrome.

A female neonate presented with a pedunculated left lateral epibulbar mass protruding through the eyelids that originated from the temporal cornea and superolateral bulbar and palpebral conjunctiva. She had a cleft in the ipsilateral central upper eyelid with horizontal kink of the tarsus lateral to the cleft and focal patches of alopecia on the scalp. Histopathology of the epibulbar mass revealed conjunctival epithelium with underlying connective tissue, cartilage, bone, adipose, and lacrimal gland consistent with epibulbar dermoid. Genetic testing of the surgical specimen was positive for a KRAS mutation at position 146. MRI showed subarachnoid asymmetry around the left temporal lobe and a C1-C2 enhancing lesion. These clinical and molecular findings suggest that this patient has a new clinical variant of oculoectodermal syndrome, a rare disorder associated with somatic KRAS gene mutations and characterized clinically by epibulbar dermoids, alopecia, aplasia cutis, brain anomalies, umbilical hernias, and congenital heart defects.

Clinical and Morphologic Characteristics of MEK Inhibitor-Associated Retinopathy: Differences from Central Serous Chorioretinopathy.

PURPOSE: To investigate the clinical and morphologic characteristics of serous retinal disturbances in patients taking mitogen-activated protein kinase kinase (MEK) inhibitors. PARTICIPANTS: A total of 313 fluid foci in 50 eyes of 25 patients receiving MEK inhibitors for treatment of their metastatic cancer, who had evidence of serous retinal detachments confirmed by optical coherence tomography (OCT). DESIGN: Single-center, retrospective cohort study. METHODS: Clinical examination and OCT were used to evaluate MEK inhibitor-associated subretinal fluid. The morphology, distribution, and location of fluid foci were serially evaluated for each eye. Choroidal thickness was measured at each time point (baseline, fluid accumulation, and fluid resolution). Two independent observers performed all measurements. Statistical analysis was used to correlate interobserver findings and compare choroidal thickness and visual acuity at each time point. MAIN OUTCOME MEASURES: Comparison of OCT characteristics of retinal abnormalities at baseline to fluid accumulation. RESULTS: The majority of patients had fluid foci that were bilateral (92%) and multifocal (77%) and at least 1 focus involving the fovea (83.3%). All fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. The 313 fluid foci were classified into 4 morphologies, as follows: 231 (73.8%) dome, 36 (11.5%) caterpillar, 31 (9.9%) wavy, and 15 (4.8%) splitting. Best-corrected visual acuity at fluid resolution was not statistically different from baseline; and no eye lost more than 2 Snellen lines from baseline at the time of fluid accumulation. There was no statistical difference in the choroidal thickness between the different time points (baseline, fluid accumulation, and fluid resolution). A strong positive interobserver correlation was obtained for choroidal thickness measurements (r = 0.97, P < 0.0001) and grading of foci morphology (r = 0.97, P < 0.0001). CONCLUSION: The subretinal fluid foci associated with MEK inhibitors have unique clinical and morphologic characteristics, which can be distinguished from the findings of central serous chorioretinopathy. In this series, MEK inhibitors did not cause irreversible loss of vision or serious eye damage.

Spontaneous regression of inflammatory myofibroblastic tumor of the orbit: A case report and review of literature.

Inflammatory myofibroblastic tumor is a rare entity characterized by the presence of myofibroblasts and inflammatory cells within a fibrous stroma. It typically occurs in the pediatric population. The most common site of occurrence is the lung though it has been reported throughout the body. Although rare, it has been reported in the orbit. The clinical course is ill defined in the literature; here we report a case of pediatric IMT with delayed spontaneous regression.

Medical comorbidities and orbital implant exposure.

PURPOSE: To investigate medical conditions and systemic therapies associated with orbital implant exposure in patients with anophthalmic sockets. METHODS: Retrospective review of patients who underwent enucleation or evisceration at a single centre between January 1, 2008 and March 1, 2018. Medical comorbidities, including peripheral or coronary artery disease, rheumatologic conditions, diabetes, malignancy and history of smoking were recorded. Use of immunomodulatory and anticoagulation therapy at the time of eye removal was noted. Patients were divided into two groups-those with implant exposure and those without. Univariate and multivariate analysis was used to compare groups. RESULTS: Two hundred and twenty-nine patients underwent eye removal surgery over a ten-year period. Implant exposure was seen in 20 (8.7%) patients. Univariate analysis revealed a statistically significant difference between groups in rates of smoking, malignancy, and immunomodulatory therapy at the time of surgery. A history of smoking (HR = 11.72; 95% CI: 2.95, 46.53; p = 0.0001) and immunomodulatory therapy (HR = 8.02; 95% CI: 1.96, 32.87; p = 0.004) were independent predictors of exposure. The probability of exposure was 81.2% when all three risk factors were present versus 4.4% when none were present (c-index = 0.737, 95% CI: 0.608, 0.865; p < 0.001). The model was a good fit to the data (Hosmer-Lemeshow goodness-of-fit test p = 0.475). CONCLUSIONS: Smoking and immunomodulatory therapy were associated with orbital implant exposure in patients with anophthalmic sockets. This is the first report examining medical comorbidities in patients with orbital implant exposure. Understanding the pathophysiology of implant exposure is crucial to preoperative planning and postoperative care.

Patient specific implants in orbital reconstruction: A pilot study.

PURPOSE: Successful repair of the orbital skeleton restores function and cosmesis by normalizing globe position and allowing full motility of the extraocular muscles. Routine repairs are successful with standard implants. However, defects that are irregular or cause volume deficiency can be challenging to repair. The development of patient specific implants (PSI) offers an additional tool in complex cases. Herein, we report our experience using PSI for orbital reconstruction. METHODS: An IRB-approved review was conducted of consecutive patients who received PSI from 8/2016-9/2018. Demographic and examination findings were recorded. PSI was designed using high-density porous polyethylene or polyetheretherketone (PEEK) and implanted for repair. The postoperative course was reviewed for outcomes and complications. RESULTS: Eight patients were identified. Two had silent sinus syndrome, 3 were complex facial fracture revisions, and 3 were post-oncologic reconstruction. Seven received porous polyethylene implants, and 1 had a PEEK implant. Mean follow up time was 10.2 months (3.3-28.3). All had an improved functional and aesthetic result. Diplopia and enophthalmos completely resolved in 60% of fracture and silent sinus patients. All fracture and silent sinus patients were orthotropic without diplopia in primary gaze at last follow up. Tumor patients had improvement in symmetry and functionality. There were no complications. CONCLUSION AND IMPORTANCE: Complex orbital skeleton derangements can be difficult to repair and standard implants may incompletely resolve the anatomic problem. In challenging cases, PSI may better achieve an aesthetically and anatomically successful outcome and improve functionality.