Oculoplastics

ABSTRACT: Conjunctival melanocytic proliferations are diagnostically challenging, often complicated by small specimen size, and are separated into 3 broad categories. The first group includes benign nevi and primary acquired melanosis (PAM) without atypia. The second group includes junctional melanocytic proliferations with a risk of progression to invasive melanoma (PAM with atypia). The last category is conjunctival melanoma, of which 65% of tumors arise in the setting of PAM with atypia. Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry has been widely adopted to differentiate cutaneous nevi and melanoma. However, there are limited studies on its utility in the evaluation of conjunctival melanocytic proliferations with little data regarding its potential utility in stratifying PAM. Twenty-eight clinically annotated cases (14 PAM without atypia and 14 PAM with atypia) were retrospectively evaluated with PRAME/MART-1 duplex immunohistochemistry and were assigned the commonly used PRAME immunoreactivity score: 0 for no staining, 1+ for 1%-25% of cells positive, 2+ for 26%-50%, 3+ for 51%-75%, and 4+ for >75%. PAM without atypia showed low (0-3+) PRAME expression in 14 of 14 cases (100%). PAM with atypia showed strong and diffuse (4+) PRAME expression in 12 of 14 cases (86.7%). Seven of eight (87.5%) PAM with severe atypia, 4 of 4 PAM (100%) with moderate atypia, and 1 of 2 PAM (50%) with mild atypia showed 4+ PRAME expression. In addition, all 5 cases that recurred or progressed (all classified as PAM with atypia) showed 4+ PRAME expression. Although additional larger studies are needed, PRAME seems to be a useful adjunct in evaluating junctional melanocytic proliferations of the conjunctiva.

Rho guanine nucleotide exchange factor 10 (ARHGEF-10) is a RHO GTPase that has a role for neural morphogenesis, however its effect on the eyes remains unknown. Here, we report a 44-year-old man who presented with eyelid swelling along with a history of bilateral hand contractures, high-arched feet and muscle wasting, who was found to have an ARHGEF-10 mutation. Neuroimaging was significant for numerous nerve-based cystic abnormalities in the bilateral orbits and throughout the neuraxis, and an orbital biopsy revealed S-100 and SOX-10 positive lesion consistent with pseudocysts. While the role of ARHGEF-10 remains unclear, further research is warranted to further describe its clinical manifestations.

Three patients presented with periorbital swelling, pain with extraocular movements, and binocular diplopia 1-4 days after receiving an mRNA Coronavirus Infectious Disease-19 (COVID-19) vaccine (BNT162b2, Pfizer/BioNTech; mRNA-1273, Moderna). All patients had a normal afferent function, unilateral limitation of extraocular motility, proptosis, and periorbital inflammation. Neuroimaging of the orbits with contrast revealed inflammation and enlargement of extraocular muscles in 2 cases and the lacrimal gland in 1 case. In all 3 cases, an extensive infectious and inflammatory laboratory work-up was unremarkable and signs and symptoms of orbital inflammation rapidly improved to complete resolution after treatment with high-dose oral prednisone. This is the first reported series of orbital inflammation occurring shortly after administration of the COVID-19 vaccine. Clinicians may consider an inflammatory postvaccine etiology as an alternative to presumed idiopathic diagnosis in such cases.

A 13-year-old boy presented with 3 days of left-sided periorbital pain, swelling, mucoid discharge, and fever to 103°F, with onset 1 day after swimming in the ocean. Within 12 hours, he experienced rapid clinical deterioration with formation of a superomedial subperiosteal abscess and an epidural abscess with leptomeningitis despite treatment with broad-spectrum intravenous antibiotics. The patient underwent urgent left orbitotomy with abscess drainage and functional endoscopic sinus surgery. Intraoperative cultures grew Shewanella algae and Escherichia coli . The patient showed marked clinical improvement following surgical intervention and tailored antibiotic therapy. This is the first reported case of orbital abscess with acute bacterial rhinosinusitis due to infection with Shewanella algae .

BACKGROUND: To present 2 patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease with unilateral orbital inflammation, optic nerve head edema, and abnormalities of the optic nerve and nerve sheath on imaging. We review the most current literature on this important and uncommon clinical phenotype. METHODS: A case report of 2 patients and a comprehensive review of the relevant literature on orbital inflammation in MOG antibody-associated disease (MOG-AD). RESULTS: Two patients presented with decreased vision and unilateral orbital inflammation. Both had optic nerve head edema and abnormalities of the optic nerve and nerve sheath on imaging. The patients were treated with immunosuppressants and had improvement of vision changes as well as their orbital inflammatory signs. MOG antibody was positive in high titers in both patients. Only 3 other cases of orbital inflammation associated with MOG antibody have been described. In all cases, orbital signs responded rapidly to intravenous methylprednisolone, but the improvement in visual acuity was variable and less robust. CONCLUSION: Orbital inflammation is a unique and underrecognized phenotype of MOG-AD with only a few reports in the literature. In patients who present with vision loss and orbital inflammation, MOG-AD should be considered in the differential.

PURPOSE: To document a unique case of granular cell tumor of the orbit, located lateral to and abutting the optic nerve, that benefited from treatment with proton beam irradiation, with a comprehensive review of the literature on granular cell tumor of the orbit. METHODS: Clinicopathologic case report with detailed imaging features and histopathologic and immunohistochemical evaluation for cytoplasmic tumor biomarkers differentiating granular cell tumor (GCT) from it mimicking lesions with relevant literature citations. The authors reviewed 20 cases of orbital GCT from 2011 to 2020 in addition to 40 cases from 1948 to 2011 and included a summary of imaging and clinical features, outcomes, and recommended treatment modalities. RESULTS: A 32-year-old man with 1-year history of left retrobulbar pain and diplopia on lateral gaze, intermittent left eyelid swelling, and a tonic left pupil was found to have a fusiform intraconal mass extending toward the orbital apex and abutting the optic nerve. Histopathologic and immunohistochemical investigations collectively supplied data diagnostic of a GCT with an initial low proliferation rate. GCT is a soft tissue neoplasm that originates in the nervous system and can occur anywhere in the body. This enhancing tumor is isointense to gray matter on T1-weighted MRI, hypointense on T2. After an incisional biopsy, the patient's symptoms persisted, and follow-up imaging several months later revealed further growth of the mass. The impossibility of complete surgical removal prompted the decision to treat with proton beam radiation therapy, which resulted in substantial regression in the size of the residual tumor. Most frequently involving the inferior rectus muscle (42%), orbital GCT is usually benign with only 4 reported cases of malignant orbital GCT (7%). Wide surgical resection with complete removal is usually curative for benign orbital GCT, and proton beam radiation therapy can aid in tumor shrinkage. CONCLUSIONS: GCT should be considered in the differential diagnosis when encountering patients with mass lesions involving the extraocular muscles, peripheral nerves, or less frequently, the optic nerve or orbital apex. Immunohistochemical analysis of biopsied tissue is required for the definitive diagnosis of GCT. Consideration of adjuvant therapies such as proton beam radiation therapy may be appropriate in cases of incomplete surgical resection of benign GCT. Proton beam radiation therapy can be an excellent therapeutic option for symptomatic relief and residual tumor size reduction with an acceptable toxicity profile.

CONTEXT.—: Conjunctival melanocytic lesions consist of a variety of neoplastic and nonneoplastic conditions. These include benign processes such as primary intraepithelial hypermelanosis and melanocytic hyperplasia, secondary forms of intraepithelial hypermelanosis and melanocytic hyperplasia, melanocytic nevi, melanocytic proliferations with malignant potential, and melanoma. OBJECTIVE.—: To provide a concise yet comprehensive resource regarding the histopathologic diagnosis of conjunctival melanocytic lesions. We aim to detail and clarify the numerous classification schemes that exist for junctional melanocytic proliferations of the conjunctiva (known as primary acquired melanosis or PAM; also termed conjunctival melanocytic intraepithelial neoplasia or C-MIN). Although not uniformly adopted, C-MIN is classified by using a numeric system based on a defined set of criteria. A less complex scheme (conjunctival melanocytic intraepithelial lesion or CMIL) has recently been proposed by the World Health Organization. Additionally, we aim to update the reader regarding molecular features and prognostic indicators. DATA SOURCES.—: Peer-reviewed literature and archived cases for illustration. CONCLUSIONS.—: Accurate histologic classification is essential, as PAM/C-MIN/CMILs that have a significant potential to progress to invasive melanoma may be clinically indistinguishable from low-risk lesions. Conjunctival melanoma (CM) more closely resembles cutaneous melanoma in terms of its pathogenesis and molecular features, compared to melanoma arising at other mucosal sites or to uveal melanoma. Depth of invasion and ulceration status, among other factors, have emerged as important prognostic indicators in CM. Sentinel lymph node biopsy may provide further prognostic information. Lastly, integration of pathologic and clinical findings is essential at this anatomically sensitive location to determine appropriate clinical management.

PURPOSE: To review the clinical features, microbiology, management, and incidence of bacterial dacryoadenitis at our institution. METHODS: This was a case series examining patients with bacterial dacryoadenitis from 2004 to 2020. Charts were reviewed for demographics, comorbidities, presenting symptoms and signs, radiology, microbiology, and management. Main outcomes included need for surgical intervention or inpatient admission. RESULTS: Forty-five patients with bacterial dacryoadenitis had a mean age of 46.1 years. Presenting symptoms included eyelid edema (100%), extraocular motility restriction (53.3%), and purulent discharge (75.5%). Based on computed tomography or magnetic resonance imaging, 9 (20.5%) patients presented with definite abscess and 15 (34%) presented with a phlegmon or early abscess. Eleven patients (24.4%) required surgical drainage. Twenty patients (44.4%) required admission, for an average stay of 4 days (range 2-8 days). Common organisms included Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. Presence of an early abscess or phlegmon correlated with need for drainage (p < 0.01). Extraocular motility restriction correlated with need for drainage (p = 0.02) and admission (p = 0.05). The incidence of bacterial dacryoadenitis at our institution increased as a percentage of confirmed dacryoadenitis cases; from 2004 to 2010 the incidence was 0 to 9.1% per year, while from 2010 to 2019 the incidence ranged from 7.7 to 36.2%. In 2019, our institution had 17 cases (incidence 36.2%) of bacterial dacryoadenitis. CONCLUSIONS: Bacterial dacryoadenitis is a major cause of dacryoadenitis, and its incidence may be increasing. It can resolve with minimal complications if managed appropriately, although some patients may require surgical drainage or admission for intravenous antibiotics.

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.

PURPOSE: To present a protocol for audiologic monitoring in the setting of teprotumumab treatment of thyroid eye disease, motivated by 4 cases of significant hearing loss, and review the relevant literature. METHODS: Cases of hearing loss in the setting of teprotumumab were retrospectively elicited as part of a multi-institutional focus group, including oculoplastic surgeons, a neurotologist and an endocrinologist. A literature review was performed. RESULTS: An aggregate of 4 cases of teprotumumab-associated hearing loss documented by formal audiologic testing were identified among 3 clinicians who had treated 28 patients. CONCLUSIONS: Teprotumumab may cause a spectrum of potentially irreversible hearing loss ranging from mild to severe, likely resulting from the inhibition of the insulin-like growth factor-1 and the insulin-like growth factor-1 receptor pathway. Due to the novelty of teprotumumab and the lack of a comprehensive understanding of its effect on hearing, the authors endorse prospective investigations of hearing loss in the setting of teprotumumab treatment. Until the results of such studies are available, the authors think it prudent to adopt a surveillance protocol to include an audiogram and tympanometry before, during and after infusion, and when prompted by new symptoms of hearing dysfunction.

PURPOSE: To review the published literature to determine the efficacy and safety of homeopathic agents or vitamins in reducing ecchymosis after oculofacial surgery or laser surgery. METHODS: A literature search was conducted in the PubMed database initially in December 2019 and updated in March 2020 to identify all studies in the English language literature on the use of homeopathic agents or vitamins in oculofacial procedures, including laser surgery. The search yielded 124 citations, and 11 articles met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Eleven studies met inclusion criteria; 9 were rated level I, and 2 were rated level III. RESULTS: The agents studied in the articles identified included oral or topical Arnica montana (AM), oral Melilotus extract, topical vitamin K oxide, and topical AM combined with Rhododendron tomentosum. Metrics to describe ecchymosis varied. In 7 controlled studies, perioperative AM provided no or negligible benefit versus placebo. In 2 studies, vitamin K cream was equivalent to placebo. One study of oral Melilotus extract had less ecchymosis compared with controls in paranasal and eyelid ecchymosis at postoperative day (POD) 7, but not at PODs 1 and 4. A lone cohort study of combined topical AM and R. tomentosum lacked objective metrics and adequate controls. No serious side effects from administration of homeopathic agents or vitamins were identified. CONCLUSIONS: The current literature does not support the use of AM, vitamin K oxide, R. tomentosum, or Melilotus extract for reducing ecchymosis after oculofacial surgery or pulsed dye laser surgery.

Clinicopathologic correlation of a pinguecula with spheroidal degeneration: a benign entity occasionally encountered in clinical practice.

PURPOSE: To compare the incidence of lower eyelid malposition following repair of isolated orbital floor fractures with that of complex orbitofacial fractures (defined as multi-wall fractures or prior orbital fracture repairs requiring revision) by oculofacial plastic surgeons via a transconjunctival or swinging eyelid approach. METHODS: Retrospective review of 175 patients who underwent surgical repair of orbital fractures at our institution. The primary outcomes were the occurrence of lower eyelid malposition (ectropion, entropion, and eyelid retraction) and the need for subsequent surgical correction. RESULTS: Of 95 patients with isolated orbital floor fractures, 4 developed eyelid malposition (4.2%), 1 of which required surgical repair (1.1%). Of 80 patients with complex orbitofacial fractures (48 multi-wall fractures, 32 secondary revisions), 10 had pre-operative eyelid malposition and were excluded from further analysis. Fourteen of the remaining 70 patients developed postoperative eyelid malposition (20%), 3 of which required surgical repair (4.3%). The difference in the occurrence of eyelid malposition between groups was statistically significant (p = .001), but the difference in rates of those requiring subsequent repair was not (p = .182). There was no statistically significant difference in the occurrence of eyelid malposition when considering other surgical factors including lateral canthotomy, conjunctival closure, implant material, or anterior rim screws. CONCLUSIONS: The incidence of lower eyelid malposition following orbital fracture repair via a fornix-based approach was significantly higher for the repair of complex orbitofacial fractures than for isolated floor fractures. However, very few patients in either group required surgical repair for eyelid malposition. Surgical factors including implant material did not affect outcomes.

PURPOSE: Fatty infiltration of the extraocular muscles has been described radiographically in patients with thyroid eye disease (TED), yet it has not been studied on a large scale nor quantified. Our purpose was to define and characterize this entity in patients with TED. METHODS: An IRB-approved cross-sectional retrospective review of medical records identified patients with a clinical diagnosis of TED and at least one CT of the orbits. A 2:1 age and sex-matched control population consisted of patients without a history nor radiographic evidence of orbital disease or systemic thyroid abnormality. The presence of fatty infiltration in each extraocular rectus muscle was defined using Hounsfield units (HU). Laterality, muscles involved, and pattern of fatty infiltration were also evaluated. Student's t-tests, Chi-square, and Fisher's exact tests were used to compare TED and control groups. RESULTS: The study population consisted of 252 patients with TED and 504 age and sex-matched controls. Fatty infiltration was significantly more prevalent in TED patients (36/252, 14.3%) compared to controls (11/504, 2.2%) (p < .001). The mean density of fat infiltration was significantly lower in TED patients (-40.4 HU) than controls (-34.8 HU) (p = .048). In TED patients, the frequency of muscle involvement was inferior rectus (61.8%), lateral rectus (19.7%), superior rectus (11.8%) and medial rectus (6.6%), which was not significantly different than controls (p > .05). Most muscles (88.2%) in the TED group exhibited a heterogeneous pattern of infiltration, which did not differ from controls (p = .34). CONCLUSIONS: This study characterizes fatty infiltration of the extraocular muscles in patients with TED.