Anatomic Variations of the Infraorbital Foramen in Caucasian Versus African American Skulls.

PURPOSE: The infraorbital foramen (IOF) represents a highly conserved structure but demonstrates morphologic variability. The purpose of this study is to describe the IOF location, size, and supernumerary foramina in an African American population and compare it with a Caucasian population. METHODS: Sixty African American and 60 Caucasian skulls from the Hamann-Todd collection of the Cleveland Museum of Natural History were studied. The primary outcome was the number of accessory IOF and measurements of the location, size, shape, and direction of each foramen. Pearson chi-square, t tests, Fisher exact test, and Wilcoxon rank sum tests were used to analyze the data. RESULTS: The African American population had a smaller vertical IOF diameter (mean = 2.81 mm) compared with the Caucasian population (mean = 3.08 mm) on the right side (p < 0.01). The distance from the IOF to the anterior nasal spine on the left side was greater in the African American population (mean = 33.93 mm) compared with the Caucasian population (Caucasian mean = 32.84 mm, p = 0.03). The distance from the IOF to the zygomaticomaxillary suture was significantly shorter in the African American population (mean = 11.85 mm) compared with the Caucasian population (mean = 13.21 mm) on the left side (p = 0.01). Accessory foramina were found in 13 Caucasian skulls (21.7%) and 6 African American skulls (10%; p = 0.08). Two distinct types of IOF existed in each population, one close to the main foramen and one within the sutura notha. CONCLUSIONS: The IOF is smaller and exits more laterally, with a lower proportion of accessory foramina in an African American population compared with a Caucasian population. Both groups exhibit 2 distinct types of IOF. These morphologic differences should be noted during surgeries and anesthetic planning to avoid neurovascular complications.

Age-related Changes in Globe Position.

PURPOSE: To longitudinally evaluate for changes in globe position as part of the natural aging process. METHODS: A Cleveland Clinic Foundation imaging database of all head imaging scans performed from 1995 to 2017 was used to identify adults with normal orbits undergoing imaging studies at least 20 years apart. A total of 100 patients (200 globes) who had CT or MRI scans were studied. Globe position was determined by measuring the distance from the anterior aspect of the cornea to the zygomaticofrontal processes baseline. Clinically significant changes in globe position were defined as changes of ≥2 mm posteriorly (enophthalmos) or anteriorly (exophthalmos). RESULTS: On average, globe projection decreased by 0.25 ± 2.3 and 0.26 ± 2.2 mm in the right and left eyes, respectively. Clinically significant enophthalmos with age was measured in 55 (27.5%) globes in 35 (35%) individuals, while clinically significant exophthalmos with age was measured in 43 (21.5%) globes in 26 (26%) individuals. The proportion of cases that developed enophthalmos, exophthalmos, or experienced no change were not significantly different from each other (p = 0.26). No patients developed clinically significant enophthalmos in one eye and exophthalmos in the other. CONCLUSIONS: Adults may develop clinically significant enophthalmos, exophthalmos, or no change in globe position over a 20-year period. This lack of uniform change in globe position with age impacts surgical considerations for treatment of the aging periocular region.

Dimensions and Morphologic Variability of the Retro-Orbicularis Oculi and Frontalis Muscle Fat Pad.

PURPOSE: To quantify the complete dimensions of the retro-orbicularis oculi fat (ROOF) pad and to determine its relationship to other fat compartments of the forehead. METHODS: The entire forehead of 14 hemifaces of seven fresh frozen human cadavers (four female, three male) was dissected in the subcutaneous and submuscular planes. For each plane, a ruler was placed at the facial midline, and images of the dissection plane were taken at 90° and 45°. Images were analyzed for vertical height, horizontal length, the distance to midline from the point of maximal height, and area for each hemiface of the ROOF and for the entire fat compartment contiguous with the ROOF. A two-tailed t test was conducted between ROOF and ROOF plus the extended fat plane across all measurements. A Wilcoxon nonparametric signed rank test was performed to determine equivalent fat distribution of the extended fat plane over each cadaver's respective eye. RESULTS: The deep fat originating from the ROOF consistently extended laterally and superiorly in each specimen, distinctly separated via septae from the deep central, deep lateral, and the deep temporal fat compartments. The color, composition, and distribution of this contiguous deep fat did not differ phenotypically from the traditional ROOF. The extended deep fat plane possessed an average vertical height of 3.09 ± 0.68 cm, average distance to midline from point of maximal height of 3.56 ± 0.53 cm, an average horizontal length of 5.37 ± 0.82 cm, and an average area of 13.40 ± 2.69 cm. The extended deep fat demonstrated a statistically significant increase in maximal height, length, and total area compared with the ROOF. A Wilcoxon nonparametric signed rank test was nonsignificant (α = 0.01) across all measurements, demonstrating that the extended fat plane was similarly distributed over each eye. CONCLUSIONS: A layer of deep fat originating from the traditionally defined ROOF extends superiorly and laterally beneath the frontalis muscle, separate from the deep lateral, deep central, and deep temporal fat pads. This is the first study to clearly demonstrate a contiguous superficial musculoaponeurotic system layer of fat extending under both the orbicularis oculi and frontalis muscles. This plane of fat is more appropriately described as the retro-orbicularis oculi and frontalis fat.

Collagenoma of the Eyelid.

The rare case of an eyelid lesion comprised of hamartomatous dermal collagen, known as a collagenoma, is presented. Collagenomas may be sporadically acquired, or inherited as part of numerous autosomal dominant syndromes. In the appropriate clinical context, their diagnosis should prompt a thorough review of systems, systemic examination, and inquiry into family history, to assess for underlying autosomal dominant syndromes. Recognition of collagenomas may thus allow diagnosis of inherited syndromes, allowing patients to obtain appropriate genetic counseling, as well as screening and treatment of associated systemic pathology.

Anatomical Description of Zygomatic Foramina in African American Skulls.

PURPOSE: The zygomaticofacial/temporal/orbital nerve is a terminal branch of the zygomatic nerve and exits the orbit through zygomatic foramina. The nomenclature in the literature varies with some studies identifying all 3 foramina on the malar surface of the zygoma, while others describe each along different aspects of the zygoma. In this study, foramen on the malar surface of the zygoma is termed zygomatic foramen, and the authors describe anatomical variations in the position and number of these foramina in an African American population. METHODS: Sixty-two African American skulls from the Hamann-Todd collection of the Cleveland Museum of Natural History were studied. The primary outcome was the number of zygomatic foramina on the malar surface of the zygomatic bone. Secondary outcomes included the location of foramina relative to the orbital rim and the frontozygomatic suture. Mean and standard deviation were used to describe measurements. Chi-squared and Wilcoxon signed rank tests were used to analyze measurements between left and right hemicrania. RESULTS: The average number of foramina was 1.98 ± 0.93. More foramina were found on the right (2.13 ± 0.98) when compared with the left (1.68 ± 0.79; p = 0.001). The average distance between the lateral-most and medial-most foramina was 9.7 ± 5.0 mm. The distance from the orbital rim to the lateral foramen was 8.4 ± 4.2 mm, and distance from the orbital rim to the medial foramen was 7.7 ± 2.1 mm. The frontozygomatic suture was 22.9 ± 3.9 mm from the lateral foramen and 27.9 ± 3.6 mm from the medial foramen. CONCLUSION: The locations of the foramina in relation to the frontozygomatic suture and orbital rim were consistent with other populations. However, in this African American population, more zygomatic foramina were noted compared with previously published results in Korean, Indian, Brazilian, and West Anatolian populations. Surgeons should be cognizant of zygomatic foramina in this population to reduce potential neurovascular complications.

Paracanthal "One-Snip" Decompression in a Cadaver Model of Retrobulbar Hemorrhage.

PURPOSE: The authors assess the effectiveness of a modified paracanthal or "one-snip" procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage. METHODS: This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or "one-snip" procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques. RESULTS: Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11-18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the "one-snip" procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups. CONCLUSIONS: Compared with traditional lateral canthotomy xand inferior cantholysis, the modified paracanthal or "one-snip" procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression.

Microanatomical Location of Hyaluronic Acid Gel Following Injection of the Upper Lip Vermillion Border: Comparison of Needle and Microcannula Injection Technique.

PURPOSE: To compare needle and microcannula injection techniques in regards to the microanatomical location of hyaluronic acid (HA) gel injected in the upper lip vermillion border of cadaver specimens. METHODS: The upper lip vermillion border was injected transcutaneously with HA gel in 8 fresh hemifaces of 4 female human cadavers. Each hemiface was injected by a single experienced injector, the right side using a 27-gauge microcannula and the left side using a 30-gauge needle. A 2-cm region of each lip was excised lateral to a point 1-cm lateral to the philtrum. Specimens were fixed in 95% alcohol, embedded in paraffin, and stained with hematoxylin-eosin for histologic examination. RESULTS: Most HA injected with either a needle or a microcannula was located within the orbicularis oris muscle, and the remaining HA resided within the subcutaneous fat. In 3/4 right (microcannula) hemifaces, 100% of the HA was located within the muscle. Only 2/4 left (needle) hemifaces had at least 95% of the HA located within the muscle. Overall, in right (microcannula) hemifaces, 93% of the filler was located within the muscle, and in left (needle) hemifaces, 79% of the filler was located within the muscle (p =0.14). CONCLUSIONS: Most HA filler injected into the vermillion border after either microcannula or needle injection resides within the orbicularis oris muscle rather than in a subcutaneous/submucosal location. Injection with a microcannula shows a trend for more uniform intramuscular location compared with needle injection.

Continuous Positive Airway Pressure Thresholds for Nasolacrimal Air Regurgitation in a Cadaveric Model.

PURPOSE: To elucidate the mechanisms underlying nasolacrimal air regurgitation (AR) in the setting of continuous positive airway pressure therapy. METHODS: Twelve nasolacrimal systems of 6 fresh female human cadavers were evaluated individually for AR using continuous positive airway pressure therapy before any nasolacrimal procedure. Cadavers were then randomly assigned to undergo nasolacrimal duct probing or endoscopic dacryocystorhinostomy and then each hemisystem was again evaluated for AR. The pressure where AR was first observed (discovery pressure) or maximum possible pressure in systems without AR was recorded. In systems that demonstrated AR, the pressure was then gradually decreased to the lowest pressure where regurgitation persisted. This pressure was recorded as the secondary threshold pressure. RESULTS: None of the 12 unoperated nasolacrimal systems or the 6 systems that underwent nasolacrimal duct probing demonstrated AR through the maximum continuous positive airway pressure therapy (30 cm H2O). After endoscopic dacryocystorhinostomy, all 6 nasolacrimal systems demonstrated AR. The mean discovery pressure was 16.0 cm H2O (range, 14.0-18.0 cm H2O) and mean secondary threshold pressure was 7.25 cm H2O (range, 6.5-8.0 cm H2O). CONCLUSIONS: Air regurgitation during continuous positive airway pressure therapy in the setting of prior endoscopic dacryocystorhinostomy can be replicated in a cadaver model. The secondary threshold pressures required for AR in this model were similar to AR pressures reported clinically. Prior to dacryocystorhinostomy, patients using continuous positive airway pressure therapy should be counseled on AR, and physicians should consider this phenomenon when evaluating ophthalmic complaints in postoperative patients on positive airway pressure therapy.

Deoxycholic Acid and the Marginal Mandibular Nerve: A Cadaver Study.

BACKGROUND: One of the rare but serious complications observed with deoxycholic acid administration is damage to the marginal mandibular nerve. In this study, we evaluated if deoxycholic acid directly induces histologic damage to fresh cadaveric marginal mandibular nerve. METHODS: A segment of marginal mandibular nerve was harvested from 12 hemifaces of 6 fresh cadavers. The nerve specimen was exposed to either 0.9% sterile saline for 24 h, deoxycholic acid (10 mg/ml) for 20 min, or deoxycholic acid (10 mg/ml) for 24 h. The nerve specimens were then fixed in glutaraldehyde for a minimum of 24 h. Toluidine blue stained sections were evaluated for stain intensity using light microscopy and color deconvolution image analysis. Supraplatysmal fat was harvested as a positive control and exposed to the same treatments as the marginal mandibular nerve specimens, then evaluated using transmission electron microscopy. RESULTS: Toluidine blue staining was less in the marginal mandibular nerve exposed to deoxycholic acid when compared to saline. The specimen exposed to deoxycholic acid for 24 h showed less toluidine blue staining than that of the nerve exposed to deoxycholic acid for 20 min. Transmission electron microscopy of submental fat exposed to deoxycholic acid revealed disruption of adipocyte cell membrane integrity and loss of cellular organelles when compared to specimens only exposed to saline. CONCLUSIONS: Deoxycholic acid (10 mg/ml) damages the marginal mandibular nerve myelin sheath in fresh human cadaver specimens. Direct deoxycholic acid neurotoxicity may cause marginal mandibular nerve injury clinically. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration.

Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.

Short-interfering RNAs induce retinal degeneration via TLR3 and IRF3.

The discovery of sequence-specific gene silencing by endogenous double-stranded RNAs (dsRNA) has propelled synthetic short-interfering RNAs (siRNAs) to the forefront of targeted pharmaceutical engineering. The first clinical trials utilized 21-nucleotide (nt) siRNAs for the treatment of neovascular age-related macular degeneration (AMD). Surprisingly, these compounds were not formulated for cell permeation, which is required for bona fide RNA interference (RNAi). We showed that these "naked" siRNAs suppress neovascularization in mice not via RNAi but via sequence-independent activation of cell surface Toll-like receptor-3 (TLR3). Here, we demonstrate that noninternalized siRNAs induce retinal degeneration in mice by activating surface TLR3 on retinal pigmented epithelial cells. Cholesterol conjugated siRNAs capable of cell permeation and triggering RNAi also induce the same phenotype. Retinal degeneration was not observed after treatment with siRNAs shorter than 21-nts. Other cytosolic dsRNA sensors are not critical to this response. TLR3 activation triggers caspase-3-mediated apoptotic death of the retinal pigment epithelium (RPE) via nuclear translocation of interferon regulatory factor-3. While this unexpected adverse effect of siRNAs has implications for future clinical trials, these findings also introduce a new preclinical model of geographic atrophy (GA), a late stage of dry AMD that causes blindness in millions worldwide.

Cautery selection for oculofacial plastic surgery in patients with implantable electronic devices.

PURPOSE: To discover oculofacial plastic surgeon practice patterns for cautery selection in the setting of implantable electronic devices and present guidelines based on a review of current literature. METHODS: A 10-Question web-based survey was sent to the email list serve of the American Society of Ophthalmic Plastic and Reconstructive Surgery to determine surgeon cautery preference in the setting of various implantable electronic devices and comfort level with the guidelines for cautery selection in their practice or institution. The relationship between survey questions was assessed for statistical significance using Pearson's Chi-square tests. RESULTS: Two hundred ninety-three (41% response rate) surveys were completed and included for analysis. Greater than half of respondents either had no policy (36%) or were unaware of a policy (19%) in their practice or institution regarding cautery selection in patients with a cardiac implantable electronic device. Bipolar cautery was favored for use in patients with a cardiac implantable electronic device (79%-80%) and this number dropped in patients with implantable neurostimulators (30%). Overall, one-third of respondents did not feel comfortable with their practice/institution policy. CONCLUSION: Choices and comfort level among oculofacial plastic surgeons for cautery selection in patients with implantable electronic devices vary considerably, and some choices may increase the risk for interference-related complications. Practice patterns vary significantly in the setting of a neurostimulator or cochlear implant, where interference can cause thermal injury to the brain and implant damage, respectively. Guidelines are proposed for cautery selection in patients with implantable electronic devices undergoing oculofacial plastic surgery.

Case Report: Primary Orbital Squamous Cell Carcinoma.

Squamous cell carcinoma (SCC) of the orbit is almost uniformly the result of local invasion from a cutaneous primary, extension by perineural invasion, or the result of metastasis. This is owed to the lack of native squamous epithelium in the orbit. After review of the literature, to date, only 6 reports of 8 patients with primary orbital SCC exist. Of those cases, only 2 reported non-apical orbital SCC. There are 2 reports of orbital SCC after retina surgery with proposed transplanted conjunctival epithelium and subsequent malignant transformation of a conjunctival cyst. The initial signs and symptoms can be vague and lead to delay in diagnosis. We present a case of primary orbital SCC and discuss the workup, imaging, and multidisciplinary management of this rare condition.

Effect of mannitol on globe and orbital volumes in humans.

PURPOSE: To determine the effect of intravenous mannitol on globe and orbital volumes. METHODS: Retrospective chart review of a consecutive series of Cleveland Clinic Neurosurgical Intensive Care Unit patients who underwent computed tomographic imaging before and after intravenous mannitol administration. Volume measurements were performed according to a previously described technique by averaging axial image areas. Measurements before and after mannitol administration were compared using paired t-test. RESULTS: Fourteen patients (28 eyes) met inclusion criteria. Average globe volume decreased 186 mm3 (-2.5%, p = 0.02) after mannitol administration, while average orbital volume increased 353 mm3 (+3.5%, p = 0.04). Average globe volume change for subjects with follow-up scan less than 4.7 hours (mean 1.9 hours; range 0.2-4.5 hours) after mannitol administration was -125 mm3 (-1.7%, p = 0.24) and average orbital volume change was +458 mm3 (+5.1%, p = 0.11). Average globe volume change after mannitol administration for those with follow-up more than 4.7 hours (average 13.9 hours, range 4.9-24.7 hours) was -246 mm3 (-3.3%, p = 0.05) and orbital volume change was +248 mm3 (+2.2%, p = 0.24). Dividing the study population into groups based on mannitol dose did not yield any statistically significant change. CONCLUSIONS: Human globe volume decreases after intravenous mannitol administration, while orbital volume increases. These volume changes occur during the time period when intraocular pressure normalizes, after the pressure-lowering effects of the drug. This novel volumetric information improves our understanding of mannitol's mechanism of action and its effects on human ocular and periocular tissues.

Ocular Adnexal Amyloidosis: A Mass Spectrometric Analysis.

PURPOSE: Ocular adnexal amyloidosis (OAA) may represent localized manifestation of an underlying systemic process. Accurate identification of the amyloid fibrils can guide the systemic evaluation and treatment. The aim of this study was to characterize subtypes of OAA using immunohistochemistry and mass spectrometric analysis and to correlate with ocular involvement and systemic association. DESIGN: Retrospective case series. METHODS: Review of patients with OAA subtyped by immunohistochemistry and mass spectrometric analysis at the Cleveland Clinic from June 1995 to June 2017. RESULTS: While immunohistochemistry identified AL amyloid protein in 67% (4/6) of specimens tested, mass spectrometry identified AL amyloid protein in all specimens (10/10). AL lambda was identified in 5 (50%) samples, kappa in 3 (30%), and both kappa and lambda light chains in 2 (20%). The 5 cases of conjunctival amyloidosis were either AL lambda only (3 cases) or both lambda and kappa (2 cases). There were 3 cases that had associated systemic involvement. Two of these had eyelid skin involvement and AL kappa amyloidosis and the other patient had uveal involvement and AL lambda amyloidosis. CONCLUSIONS: Primary amyloidosis-AL is the most common form diagnosed by mass spectrometric analysis in patients with OAA. Immunohistochemistry is ineffective in the characterization of the amyloid deposits in a significant number of cases. Evaluation to exclude systemic involvement or associated underlying lymphoproliferative disorder is warranted.

Cicatricial ectropion in a patient treated with dupilumab.

PURPOSE: To describe a case of bilateral conjunctivitis and cicatricial ectropion associated with dupilumab therapy for atopic dermatitis. OBSERVATIONS: Severe hyperemia of the conjunctiva and eyelid margins, as well as cicatricial ectropion, began two months after starting weekly dupilumab injections for atopic dermatitis. The findings worsened over the next several months and improved after discontinuing dupilumab. CONCLUSIONS AND IMPORTANCE: Dupilumab is a promising intervention in the management of atopic dermatitis and asthma, however, little is known about its potential ocular adverse effects. We report the first case of dupilumab-associated ocular inflammation leading to cicatricial ectropion.

Dysthyroid optic neuropathy: update on pathogenesis, diagnosis, and management.

INTRODUCTION: Dysthyroid optic neuropathy (DON) is a severe manifestation of thyroid eye disease (TED) that can result in permanent vision loss. Management is complex, multidisciplinary, and involves medical and/or surgical therapies. This review describes current concepts in the epidemiology, pathophysiology, diagnosis, and treatment of DON. AREAS COVERED: An extensive review of the literature was performed to detail current concepts on the diagnosis and management of DON. This includes utilization of various medical and surgical modalities for disease management. EXPERT COMMENTARY: DON can result in permanent blindness and often requires the use of corticosteroids and surgical decompression. We favor the use of intravenous corticosteroids and a transcaruncular approach when surgical decompression is indicated. The use of orbital radiation for DON is often reserved for patients that are poor surgical candidates and/or patients with refractory disease.

Recurrent Orbital Solitary Fibrous Tumor in a 12-Year-Old.

PURPOSE: To report the clinical features and pathology of orbital solitary fibrous tumors and present a case of a recurrence in a 12-year-old boy. METHODS: Case Report. RESULTS: A 12-year-old boy presented to our institution with double vision in upgaze for 6 months. Examination revealed 3 mm of left-sided proptosis, hypoglobus, and -3 impairment of supraduction. Magnetic resonance imaging of the orbits showed an avidly enhancing mass within the superolateral aspect of the orbit. Biopsy revealed a solitary fibrous tumor with STAT6 and CD34 positivity. Positron emission tomography-computed tomography was negative for metastatic disease. The tumor underwent excision. However, 4 months postoperatively, imaging revealed changes consistent with recurrence. A repeat lateral orbitotomy with orbital rim marginotomy was performed with complete gross excision of the tumor. The patient remains tumor-free 22 months after reoperation. CONCLUSION: Orbital solitary fibrous tumor rarely occurs in the pediatric population. Despite initial complete gross tumor excision, this case represents the youngest individual with a recurrence to the authors' knowledge. This case of rapid recurrence may have been due to tumor seeding at the time of initial biopsy or other factors. This case increases the known spectrum of orbital solitary fibrous tumors.