Inflammation and Fibrosis in Orbital Inflammatory Disease: A Histopathologic Analysis.

PURPOSE: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens. METHODS: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls. RESULTS: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048). CONCLUSIONS: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease.

Acellular cadaveric dermal matrix grafts for orbital wall reconstruction in patients with sinonasal malignancies.

PURPOSE: To describe the utilization of acellular cadaveric dermal matrix (ACDM) in patients undergoing orbital wall reconstruction after orbital preservation surgery for sinonasal malignancy. METHODS: Retrospective case series of seven patients with sinonasal malignancy who had orbital reconstruction with ACDM implants from January 2012 to August 2020. Orbital preservation was performed in all patients with tumor extension up to and including periorbital. The main outcome measures were implant exposure, orbital infection, diplopia in primary gaze, enophthalmos, and eyelid malposition. RESULTS: Patients ranged 37-78 years old (median: 66 years) and included 4 females and 3 males. The median follow-up time was 9 months (range 6-43 months) from the date of surgery. Squamous cell carcinoma comprised the majority of tumors with all patients needing medial wall reconstruction. Three patients received postoperative radiation therapy. No patients had any implant exposure, orbital infection, enophthalmos, or eyelid malposition. CONCLUSIONS: ACDM grafts can be used safely in orbital wall reconstruction in patients with sinonasal malignancies.

Microbiology of orbital cellulitis with subperiosteal abscess in children: Prevalence and characteristics of Streptococcus anginosus group infection.

PURPOSE: To evaluate the predominant pathogens and clinical course in pediatric patients with orbital cellulitis (OC) complicated by subperiosteal abscess (SPA). METHODS: This is a single-center retrospective chart review evaluating pediatric patients with OC complicated by SPA treated at a tertiary care center in the Pacific Northwest. Data were analyzed for characteristics, rates of infection, and antibiotic resistance of the predominant pathogens in pediatric patients. RESULTS: Twenty-seven children were identified with OC complicated by SPA and bacterial cultures drawn. The average age (SD) of the patients was 9.2 years (4.8), median 9.6; 15 range 5 months to 17.2 years. Seventeen (63.0%) were male. Sinusitis was present in all patients. Streptococcus species were the most common pathogen accounting for 52% (17/33) of isolates. Streptococcus anginosus group (SAG) was the predominant species and were isolated in 10 out of 27 (37%) children in the study. Twenty-one (78%) patients required surgery for the treatment of SPA. Among surgically treated patients, females tended to be younger than males (p = .068). Pediatric patients with SAG infections required more surgery than children without this isolate, 100% and 65%, respectively (p = .030). Female patients tended to have SAG infections more often than males (p = .063). CONCLUSIONS: Orbital infections caused by SAG require surgical management more often than those caused by other pathogens. Our results suggest a difference in pathogenic organisms in male and female patients with SPA. SAG is one of the most common pathogens isolated in orbital cellulitis complicated by SPA in children.

Simultaneous Orbital and Intracranial Abscesses in 17 Cases.

PURPOSE: To describe the demographics, clinical presentation, treatment, and outcomes of a rare cohort with simultaneous orbital and intracranial abscesses. METHODS: A historical cohort study of 17 patients with simultaneous orbital and intracranial abscesses between 2010 and 2018 was performed. The demographics, location of abscesses, treatment, and outcomes of these patients were analyzed. RESULTS: The mean age was 26.9 years (range 5-83 years). Fourteen patients (82%) were male. In this cohort, the most common orbital abscess location was the superior orbit, involved in 14 patients (82%). The most common site of intracranial abscess was the frontal lobe, involved in 16 patients (94%). Concurrent sinus disease was present in 16 patients (94%). Surgical evacuation was the standard of treatment, with 94% of patients undergoing at least one surgical procedure. Streptococcus species were the most common, isolated from 6 sinus cultures (43%), 3 orbitotomy cultures (21%), and 4 craniectomy cultures (36%). Staphylococcus species were also common. Most patients (94%) had stable or improved mental status and visual function at the conclusion of their treatment. CONCLUSIONS: Simultaneous orbital and intracranial abscesses are rare. Local invasion from the orbit into the intracranial space may occur from direct spread, thus superior orbital abscesses pose the greatest risk for intracranial spread. Additional factors such as infection with Streptococcus and Staphylococcus species as well as male sex appear to be risk factors for intracranial spread. For those who develop intracranial abscesses, young age and absence of seizures or altered mental status at presentation may be associated with favorable outcomes.

Surgical Intervention of Periocular Infantile Hemangiomas in the Era of ß-Blockers.

PURPOSE: To examine the role of adjuvant surgical resection of infantile hemangiomas after systemic ß-blocker therapy. METHODS: This is a multicentered retrospective study. Standard protocol for oral propranolol was employed by the referring physicians. Ocular indications for surgery included ptosis obstructing the visual axis, high degrees of astigmatism causing amblyopia, or disfigurement from residual tumor. Patients underwent complete excision or debulking. RESULTS: Eleven girls and 4 boys were surgically treated with mean operative age of 34.4 months. Patients were followed for a mean of 19.6 months after surgery. Four patients required surgical treatment due to an inability to tolerate medical therapy secondary to drug-related side effects (including bradycardia). The other 11 patients proceeded to surgery due to residual eyelid and orbital lesions despite medical treatment. All 15 patients underwent orbitotomy for residual hemangioma excision. Four patients also underwent simultaneous levator advancement at the time of excision. In all cases, there was resolution of ptosis with clearing of the visual axis. No complications were incurred during the surgical treatment and there were no hemangioma recurrences. CONCLUSIONS: This is the first study to report surgical management of periocular infantile hemangiomas recalcitrant to standard therapy in the ß-blocker era. In patients with infantile hemangioma who have failed medical therapy, adjuvant surgical treatment still plays an important role. For patients with persistent tumor causing ocular sequelae, surgical intervention aimed at soft tissue debulking and ptosis repair can be successful in achieving excellent functional and aesthetic outcomes with minimal side effects.For patients with periocular infantile hemangiomas with residual soft tissue deformity following propranolol therapy, surgical treatment plays an important role in improving functional and cosmetic outcomes with minimal side effects.

The Narrow-Lumen Jones Tube: A Novel Approach to Dry Eye Following Conjunctivodacryocystorhinostomy.

Conjunctivodacryocystorhinostomy with placement of a Jones tube (JT) is the gold standard for upper lacrimal system dysfunction. However, traditional JT have been associated with various complications. In their practice, the authors have encountered challenges with postoperative dry eye in a select group of patients, with recurrence of epiphora following tube occlusion, suggesting a need for decreasing the rate of tear drainage while maintaining a patent JT. To address this issue, the senior author (J.D.N.) introduced a modified JT with a narrow lumen (reduced-flow JT) for patients who experience significant dry eye symptoms after placement of a JT. The authors describe 3 patients who experienced improvement in dry eye symptoms after the placement of reduced-flow JT.

Clinical Presentation and Anatomical Location of Orbital Plasmacytomas.

PURPOSE: To evaluate the clinical and anatomical location of orbital plasmacytomas and assess local control following therapy. METHODS: The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried to identify patients diagnosed with orbital plasmacytoma. These patients' records were reviewed for demographic characteristics, clinical and radiologic findings, treatments, and outcomes. RESULTS: Thirty patients from 4 institutions (24 from MD Anderson Cancer Center, 3 from SUNY Downstate Medical Center, 2 from University of California, Los Angeles, and 1 from Oregon Health and Science University) were identified. Eighteen patients (60%) were diagnosed with multiple myeloma (MM) before and 11 (37%) were diagnosed with MM immediately after orbital plasmacytoma. Based on imaging, 4 distinct anatomical patterns were identified: 1) bony plasmacytoma affecting the superotemporal orbit, epidural space, and temporal fossa (15 patients; 50%); 2) discrete orbital plasmacytoma (7 patients; 23%); 3) infiltrative plasmacytoma either originating from a sinus (4 patients; 13%); or 4) originating from the orbital floor and infiltrating facial soft tissue (4 patients; 13%). Of the 29 patients with available treatment data, 2 had radiation only, 3 had chemotherapy only, 6 had chemoradiation, and 18 had stem cell transplant following chemoradiation (n = 17) or only chemotherapy (n = 1). Following treatment, 10 patients achieved complete and 11 achieved partial responses. CONCLUSION: Orbital plasmacytomas were found exclusively in patients with MM diagnosed before or immediately after orbital plasmacytoma. Plasmacytomas can have 4 distinct anatomical patterns of origin. Following treatment, all patients had good to excellent local control of their orbital lesions.

Proptosis Caused by Rhabdomyomatous Mesenchymal Hamartomata Occurring in the Orbit.

Two infants were referred for progressive orbital proptosis. MRI in both cases demonstrated a homogenous mass in the orbit adherent to and isointense with a rectus muscle. Histopathology in both cases demonstrated a bland proliferation of spindle cells with entrapped skeletal muscle. Immunochemistry demonstrated that the abnormal tissue was of skeletal muscle origin, consistent with rhabdomyomatous mesenchymal hamartoma (RMH). Observation was elected due to the reported benign nature of RMH. In contrast to RMH of the cutaneous tissues that typically follows a benign course, RMH of the orbit may present with rapid growth.

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.

Review of AlloDerm Acellular Human Dermis Regenerative Tissue Matrix in Multiple Types of Oculofacial Plastic and Reconstructive Surgery.

PURPOSE: AlloDerm acellular human dermis is used for repair or replacement of damaged or inadequate skin tissue. It has been used successfully in multiple types of surgeries, including abdominal wall reconstruction, breast reconstruction, and head and neck reconstruction. Its application to ophthalmic plastic and reconstructive surgery is less well described. This study seeks to evaluate the efficacy and factors influencing surgical outcomes using Alloderm in multiple types of oculofacial plastic surgery. METHODS: Institutional Review Board-approved retrospective review of 84 patients who underwent surgical procedures using Alloderm. Preoperative demographic data, comorbidities, smoking, clinical etiology, surgical methods, Alloderm type, and outcome (cosmetic and functional) were evaluated. RESULTS: This study included 84 patients, accounting for a total of 98 procedures. Mean age was 52.5 years (3-93 years). Etiologies necessitating surgery included malignancy in 26 patients (31.0%), trauma in 19 patients (22.6%), congenital lesions in 15 patients (17.9%), and senile change in 11 patients (13.1%). Surgical procedures included lower eyelid posterior lamella elongation, socket and fornix reconstruction, scar repair, patch grafts, and filler. Mean duration of follow up was 530 days. Overall, 92.8% of patients had favorable outcomes. Factors associated with significantly worse outcomes included smoking, congenital anomaly etiologies, and previous graft/flaps in the same area (p = 0.03, p = 0.029, and p = 0.007, respectively). CONCLUSIONS: This study suggests that Alloderm acellular human dermis can be used safely and effectively in multiple types of oculofacial procedures. Smoking, congenital anomaly etiologies, and previous graft/flap were associated with poor cosmetic and functional outcomes.

Inflammatory myofibroblastic tumor of the orbit: a case report.

Inflammatory myofibroblastic tumor (IMT) is a neoplasm most commonly found in the abdominal-pelvic region, lung, and retroperitoneum. The tumor tends to affect soft tissues of children and young adults and can locally recur but rarely metastasizes. Histologically, the appearance is one of bland spindle cell proliferation with a prominent, chronic inflammatory infiltrate. This article describes 1 case of IMT found in the orbit that is presented with rapidly progressive painless proptosis. In the authors' review of the literature, they have only found 2 other case reports involving the orbit.

Blepharophimosis syndrome with absent tear production.

The purpose of this report was to present a case of congenital alacrima in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). A 9-month-old boy presented with characteristic clinical findings of BPES confirmed by genetic testing. On further history taking and evaluation, the patient was noted to have no tear production, despite clinically present palpebral lobes of the lacrimal glands. BPES is an autosomal dominant condition characterized by narrowed horizontal palpebral fissures, severe bilateral symmetric ptosis, epicanthus inversus, and telecanthus. To the authors' knowledge, this represents the second reported case of congenital alacrima in this syndrome. The first case described in the literature was in a 9-month-old girl who had congenital absence of the lacrimal glands. BPES may present with alacrima requiring vigilant lifelong lubrication and careful consideration in decisions for eyelid surgery including ptosis repair.

Changes in Intraocular Pressure During Orbital Floor Fracture Repair.

PURPOSE: To evaluate changes in intraocular pressure (IOP) during orbital floor fracture repair. METHODS: Retrospective chart review of patients undergoing isolated orbital floor fracture repair with implant placement at a level 1 trauma center and tertiary care center. Patients with combined zygomaticomaxillary or medial wall fracture repair, or other significant ocular injuries were excluded. IOP measurements using a handheld applanation tonometer were recorded immediately after induction of anesthesia, immediately after orbital floor implant placement, and on postoperative day 1. RESULTS: Nine patients who underwent isolated orbital floor fracture repair were examined. There was a statistically significant mean decrease of 4.66 mmHg (p < 0.05) in IOP from prior to surgical to immediately after implant placement. There was also a significant mean increase in IOP of 7.44 mmHg (p < 0.05) at postoperative day 1 compared with immediately after implant placement. There was no statistically significant difference in IOP between prior to surgical incision and postoperative day 1. CONCLUSIONS: All patients who underwent orbital floor fracture repair in this study had a significant decrease in IOP during orbital floor fracture repair that returned to immediately preoperative levels by postoperative day 1. This initial decrease in IOP may be because of intraoperative manipulation of the globe.

Carbon dioxide laser-induced combustion of extravasated intraocular silicone oil in the eyelid mimicking xanthelasma.

A 48-year-old woman with a history of retinal detachment repair with vitrectomy, scleral buckling, and silicone oil with subsequent oil removal was referred for unilateral upper eyelid ptosis with edema and overlying skin changes simulating xanthelasma. During surgical excision, a white flare-like plume was noted when the carbon dioxide (CO2) laser was used to make the incisions. The pathology report confirmed silicone oil intrusion in the conjunctiva and upper eyelid. A postoperative in vitro experiment showed that silicone oil was readily ignited by the CO2 laser.

The porous polyethylene/bioglass spherical orbital implant: a retrospective study of 170 cases.

PURPOSE: To report patient outcomes after placement of porous polyethylene (PPE)/bioglass (BG) orbital implants for primary enucleation or secondary implantation. DESIGN: Retrospective chart review in one surgeon's practice (J.D.N.). METHODS: A chart review of all patients who underwent placement of PPE/BG orbital implants was performed. Data included patient's age, gender, surgical indication, prior ocular surgery, medical history, procedure performed, implant size, and postoperative complications. RESULTS: PPE/BG implants were placed in 170 sockets. Seventy-seven patients were women, and 85 were men. One hundred forty patients underwent primary enucleation and placement of an implant, and 22 patients underwent secondary implantation. One hundred sixty-one patients did well after orbital implantation with a comfortable socket, quiet conjunctiva, and motility. Complications occurred in 9 patients (5.3%). Excessive discharge alone occurred in 2 patients (1.2%). Seven sockets undergoing primary enucleation and implant placement had implant exposure. One patient had an early exposure, and 6 had late exposures. All exposures were successfully treated with antibiotics or additional surgery. Secondary surgeries were required by some patients, but not due to implant complications, included ectropion repair in 5 patients (2.9%) and volume augmentation in 3 patients (1.7%). CONCLUSIONS: The PPE/BG orbital implant may be a useful implant for orbital reconstruction after primary enucleation or as a secondary implant.

Primitive neuroectodermal tumor of the orbit in adults: a case series.

PURPOSE: To present the clinical, radiologic, and histopathologic features of orbital primitive neuroectodermal tumor (PNET) in 5 adult patients. METHODS: Retrospective case series of 5 adult patients with orbital PNET. Orbitotomy was performed in all cases. The authors report clinical findings, radiologic features, histopathology, immunohistochemical analysis, management, and outcomes for 5 patients with orbital PNET. RESULTS: Five adult patients presented with progressive unilateral proptosis and visual impairment. Common radiographic findings included a heterogeneous mass without associated destructive features, located in the superior and/or lateral orbit. Four cases demonstrated strong immunohistochemical staining for CD99 in a membranous pattern. One case required chromosomal analysis with fluorescence in situ hybridization to confirm the diagnosis. All patients received chemotherapy and/or orbital radiation with resolution of proptosis but no improvement of vision. One patient died of disease. CONCLUSIONS: To the authors' knowledge, this is the largest series of orbital PNET in adults. This tumor has an age demographic wider than previously believed and should be considered in the differential diagnosis of a hypercellular small round cell orbital tumor in both children and adults. Current treatment regimens are not standardized but typically use a similar approach to the treatment of Ewing sarcoma. Orbital PNET appears to have less propensity for metastasis compared with PNET in other locations. However, long-term aggressiveness remains to be proven.

Non-specific orbital inflammation: Current understanding and unmet needs.

Non-specific orbital inflammation (NSOI) is a noninfectious inflammatory condition of the orbit. Although it is generally considered the most common diagnosis derived from an orbital biopsy, it is a diagnosis of exclusion, meaning that the diagnosis requires exclusion of a systemic process or another identifiable etiology of orbital inflammation. The clinical diagnosis of NSOI is ill-defined, but it is typically characterized by acute orbital signs and symptoms, including pain, proptosis, periorbital edema, chemosis, diplopia, and less commonly visual disturbance. NSOI poses a diagnostic and therapeutic challenge: The clinical presentations and histological findings are heterogeneous, and there are no specific diagnostic criteria or treatment guidelines. The etiology and pathogenesis of NSOI are poorly understood. Here we recapitulate our current clinical understanding of NSOI, with an emphasis on the most recent findings on clinical characteristics, imaging findings, and treatment outcomes. Furthermore, gene expression profiling of NSOI and its implications are presented and discussed.

Inferolateral migration of hydrogel orbital implants in microphthalmia.

PURPOSE: Hydrogel spheres may be useful in treating orbital hypoplasia associated with congenital microphthalmia. The authors describe migration associated with the use of these devices. METHODS: The authors retrospectively reviewed 5 cases in which a hydrogel orbital expander (Osmed) was implanted to treat orbital hypoplasia in pediatric patients with congenital microphthalmia (with or without previous surgery). RESULTS: In all 5 cases, a lateral orbitotomy, conjunctiva-sparing approach was used to insert the hydrogel spheres. Two cases involved previously unoperated orbits; 3 patients had prior orbit or socket surgery. Inferolateral movement outside the desired central, deep orbital position occurred in all 5 cases. Four of 5 cases required further procedures to achieve an adequate orbital implant position. CONCLUSIONS: Inferolateral migration may occur with hydrogel spheres implanted via a lateral orbitotomy approach in microphthalmia.

Radiologic imaging shows variable accuracy in diagnosing orbital inflammatory disease and assessing its activity.

Radiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.