Predictors of Local Recurrence for Eyelid Sebaceous Carcinoma: Questionable Value of Routine Conjunctival Map Biopsies for Detection of Pagetoid Spread Purpose: To identify clinicopathologic factors associated with local recurrence of eyelid sebaceous carcinoma and determine whether routine conjunctival map biopsies are necessary to detect pagetoid spread. Methods: The authors searched PubMed for articles on eyelid sebaceous carcinoma and pagetoid spread published in English during 1982 to 2018, and they reviewed 99 consecutive patients with eyelid sebaceous carcinoma who underwent surgical excision with frozen section control of margins performed by 1 author (BE) during 1999 to 2017. Results: Local recurrence rates after surgery were 5% to 25% in the literature and 6% in the authors’ cohort. Risk factors for local recurrence included T3b (>20 mm) or worse disease according to the AJCC Cancer Staging Manual, eighth edition, pagetoid spread, diffuse growth pattern, and multicentric origin. Pagetoid spread was observed in 8.3% to 70% of patients in the literature and 31% of patients in the authors’ cohort. The literature review showed that surgical excision with frozen section control is the mainstay of management of eyelid sebaceous carcinoma, with topical chemotherapy and cryotherapy used in cases with pagetoid spread. The authors found no solid evidence for added value from routine 4-quadrant conjunctival map biopsies, and some studies called into question their accuracy and yield. Conclusions: In patients with eyelid sebaceous carcinoma, meticulous microscopic margin control is appropriate in all cases and particularly for tumors >20 mm and adjuvant topical chemotherapy should be considered for tumors with conjunctival pagetoid spread. Routine conjunctival map biopsies are not essential, but targeted map biopsies of areas with signs suggestive of pagetoid intraepithelial spread may be appropriate to guide future closer observation or adjuvant treatments.

Etiopathogenesis of Primary Acquired Nasolacrimal Duct Obstruction: What We Know and What We Need to Know Purpose: To provide a systematic review of the literature on the etiopathogenesis of primary acquired nasolacrimal duct obstruction (PANDO). Methods: The authors performed a PubMed search of all articles published in English with specific reference to etiopathogenesis of PANDO or associations of PANDO. Data captured include demographics, study techniques, hypothesis, presumed or confirmed interpretations with regards to pathogenesis, mechanisms, or pathways. Specific emphasis was laid on addressing the lacunae and potential directions for future research. Results: Numerous factors are believed to contribute to the etiopathogenesis of PANDO. The basic pathogenesis involves inflammation, vascular congestion, mucosal edema, fibrosis, obstruction, and stasis. Bony nasolacrimal duct diameter does not appear to play a significant role. There is no convincing data to substantiate nose as the site of disease origin and nasal factors appear to be comorbidities. Hormonal mechanisms are more evidence-based but can only partly explain the pathogenesis. Vascular theories are based on the behavior of perilacrimal cavernous bodies, their autonomic control, and additional structural changes in the helical patterns of connective tissue fiber arrangements. Repeated vascular malfunction leading to structural epithelial and subepithelial changes currently appears to be the most evidence-based and accepted theory. Tear proteomics holds a promise in decoding the etiopathogenesis of PANDO, at least in part. Conclusions: The etiopathogenesis of PANDO appears to be multifactorial. Hormonal microenvironments, vascular factors, and tear proteomics are promising candidates for further work. There is a need for focused work by Clinician-Scientists and the answers can have far reaching clinical implications.

Bony Orbital Volume Expansion in Thyroid Eye Disease Purpose: To quantify changes to the bony orbital volume (BOV) in patients with thyroid eye disease (TED) relative to normal controls. Methods: In this case–control study, all patients affected with TED seen over a 2-year period were screened for study entry. Eligible participants were adults with clinical evidence of TED and CT scans of their orbits obtained during the course of their routine care. Exclusion criteria included the history of decompression surgery and/or medical or other ophthalmic conditions that could alter the orbital anatomy. The primary outcome was the measurement of the BOV. Secondary outcome measures included the relationships between BOV and muscle volume, fat volume, Hertel measurements, duration of the disease, and the occurrence of dysthyroid optic neuropathy in patients with TED. Three-dimensional reconstructions of the orbits were created to measure BOV, muscle volume, and fat volume. Results: A total of 100 participants were included in the study, contributing 200 orbits. This sample was comprised of 50 patients with TED (37 female, 13 male) and 50 controls (37 female and 13 male). There were no differences between the control and patient groups in age or sex. Of the patients with TED, 14 were diagnosed with dysthyroid optic neuropathy (15 orbits, 1 case was bilateral). The mean (standard deviation [SD]) clinical activity score for males was 4.1 (2.29) and 4.35 (2.63) for females. The mean (SD) BOV for males in the TED group was 28.62 ml (3.47), while that of the control group was 24.59 ml (2.19). This difference was significant (p < 0.01). The mean (SD) BOV for females with TED was 24.33 ml (2.39), while that of the female control group was 20.97 ml (1.84). This was again significant (p < 0.01). There was a significant relationship between the BOV and fat volume (p <0.05). There were no significant relationships between BOV and: muscle volume, duration of disease (p = 0.705), Hertel measurements (p = 0.212), age (p = 0.9), and dysthyroid optic neuropathy (p = 0.12). Conclusions: This study found that the BOV is significantly greater in patients with TED, suggesting that TED is associated with widespread bony remodeling of the orbit.

Quality of CT Imaging of Periocular Metallic Foreign Bodies Using Artifact Reduction Software Purpose: CT is the standard of care for assessment of ocular and orbital trauma; however, artifacts from metallic foreign bodies can limit the utility of CT. The authors hypothesize that implementation of metal artifact reduction techniques can improve image quality and diagnostic confidence for a diverse group of interpreters. Methods: A case series of ten subjects with retained periocular metallic foreign bodies imaged with CT were identified retrospectively from a large urban trauma center. Postacquisition images were processed with an iterative-based metal streak artifact reduction software. The severity of the metal streak artifact was assessed by clinicians including radiologists (4), ophthalmologists (4), and oculoplastic specialists (3) using a numeric scale to grade images on seven clinically relevant criteria. Each image was also analyzed to measure the size of the artifact and degree of streaking. Results: Overall confidence in diagnosis and severity of metallic streak was improved with metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). Similarly, confidence in assessing specific features—including extra-ocular muscle, optic nerve, globe rupture, orbital fracture and identification of foreign bodies—was improved after metallic artifact reduction (p < 0.001, Wilcoxon signed-rank test). The standard deviation of pixel intensity for a path surrounding the foreign body as well as the area of the streak artifact decreased in the metallic artifact reduction-processed images (p < 0.001, paired t test). Conclusions: Metal artifact reduction in CT has potential benefits in improving image quality and reader confidence for periocular trauma cases in real-world settings.

Measurement of the Force Required by Blunt-Tipped Microcannulas to Perforate the Facial Artery Purpose: To measure the force required by blunt-tipped microcannulas of various sizes to penetrate the wall of the facial artery. Methods: Twenty hemifaces of 10 fresh frozen cadavers were dissected to reveal the facial artery from its origin at the external carotid artery until the angular artery was found. On the right side of each cadaver, the facial artery was removed at the nasolabial fold, while arteries on the left were kept in situ, preserved with their fascial attachments. A force-sensitive resistor (Tekscan, Boston, MA, U.S.A.) was used to measure the force required by a syringe attached to 18G, 22G, 23G, 25G, and 27G blunt-tipped microcannulas, to pierce the proximal wall of the facial arteries on the left hemiface at the nasolabial fold. The facial arteries from each right hemiface were pierced by cannulas that were attached to a horizontally mounted microtensile load cell, which included a linear motor (Ibex Engineering, Newbury Park, CA). The force required to perforate the proximal wall of the facial arteries was calculated for each cannula. A 2-tailed t test was used to compare the forces measured by the force-sensitive resistor and the microtensile load cell. Results: On force testing, the 18G and 22G cannulas were unable to penetrate the vessel wall in facial arteries that were both: removed from the cadavers and maintained in the cadavers. There was no statistically significant difference between the values obtained by the load motor and the force-sensitive resistor (p = 0.33). The force required to penetrate the proximal wall of the facial artery was: 0.72 kg to 0.81 kg for 23G, 0.43 kg to 0.54 kg for 25G, and 0.23 kg to 0.32 kg for 27G blunt-tipped microcannulas. There was a significant correlation between the gauge of the cannulas and the force required to penetrate the vessel walls (r = −0.970; p = <0.01). Conclusions: Blunt-tipped microcannulas smaller than 22G penetrate the facial artery with a low amount of force.

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 cm2. 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.

Bicanalicular Silicone Intubation for the Management of Punctal Stenosis and Obstruction in Patients With Allergic Conjunctivitis Purpose: To evaluate the use of bicanalicular silicone intubation for the management of punctal stenosis and obstruction in patients with allergic conjunctivitis. Methods: A retrospective interventional case series of patients with acquired epiphora due to stenotic or obstructed puncta as a result of allergic conjunctivitis was performed. Punctal dilation and bicanalicular silicone intubation were performed in all patients. Munk Scale for grading of epiphora along with grading of fluorescein dye disappearance test was used to evaluate the functional improvement. Grading of punctal stenosis using Kashkouli’s grading system was applied to evaluate the anatomical improvement. Patients having canalicular or nasolacrimal duct obstruction, punctal stenosis, and obstruction due to other causes were excluded. Results: Fifty-one patients met the inclusion criteria with male-female ratio of 1:1.55 and an average age of 46 years at presentation. High patient tolerances without complications with the use of tubes were reported. Significant improvement 6 months after tube removal in comparison to preoperative period was found with anatomical and functional success rate of 91.83% and 87.75%, respectively. Two patients had a recurrence of the punctal stenosis many months after stent removal because of the early tube prolapse and exacerbation of the allergic conjunctivitis. Conclusions: Bicanalicular silicone intubation seems to be a well-tolerated and effective tool in the management of acquired punctal stenosis or obstruction secondary to allergic conjunctivitis. Bicanalicular silicone intubation appears to be a good option as patients with allergic conjunctivitis typically present with bilateral involvement of both puncti.

Natural Course of Mild Graves Orbitopathy: Increase of Orbital Fat But Decrease of Muscle Volume With Increased Muscle Fatty Degeneration During a 4-Year Follow-Up Purpose: To describe the natural course of orbital fat volume and extraocular muscle volume in mild Graves orbitopathy during a 4-year follow-up. To describe fatty changes within the extraocular muscles. Patients: Twenty-five patients with mild Graves orbitopathy, who did not require any therapeutic intervention other than supportive therapy, were followed for 4 years. Methods: CT scans were performed in all patients at baseline and follow-up. A validated technique using Mimics (Materialise) was used to calculate fat and muscle volumes. Outcomes were compared with previously collected data. The amount of intramuscular fat was assessed on CT scans in a semi-quantitative way by two blinded observers according to a four-point scale. Results: After a median follow-up of 4.3 years, the median fat to orbital volume ratio increased with 0.08 from 0.57 to 0.65 (p = 0.000), whereas the median muscle volume to orbital volume ratio decreased with 0.03 from 0.17 to 0.14 (p = 0.000). In this control group in patients between 49 and 54 years old, the changes were 0.01 and −0.002, respectively. The Clinical Activity Score decreased to zero (p = 0.000), and the median eyelid aperture decreased from 12 to 10 mm (p = 0.007). A significant increase of intramuscular fat was found in patients with Graves orbitopathy. Conclusions: The natural course of mild Graves orbitopathy, as observed over 4 years, is characterized by an increase of orbital fat volume, a decrease in muscle volume, and an increased intramuscular fatty degeneration.

Noninflammatory Thyroid Eye Disease Purpose: Patients presenting with thyroid eye disease (TED) usually follow a well-defined self-remitting course characterized by an active inflammatory phase followed by an inactive fibrotic phase. We present 3 cases where patients presented primarily with signs of progressive fibrosis and no signs of prior active inflammation. Methods: We reviewed the clinical notes and investigations of 3 patients who presented to our center between January 2015 and August 2017. Results: All patients included in the study presented primarily with severe, progressive fibrosis without evidence of a previous active inflammatory condition. Although there were no signs of inflammation, each case was progressive, with 2 of the cases developing dysthyroid optic neuropathy that was relatively recalcitrant. We found that these patients were older than the general population of TED patients and that their disease course represents a departure from the common narrative. Conclusions: This subgroup of TED patients do not conform to the typical inflammatory natural history of TED. We propose that the heterogeneity of the orbital fibroblast pool and their function may be different in this subgroup. Further work will be required to reveal the pathophysiology of this atypical TED process, potentially revealing links between aging and the inflammatory mediators in TED.

Effect of Topical Periocular Steroid Use on Intraocular Pressure: A Retrospective Analysis Purpose: To study the effect of periocular steroid use on intraocular pressure (IOP). Methods: Charts of adult patients with atopic dermatitis or eczema treated with topical periocular steroid creams and ointments from January 1st, 2007 to October 1st, 2017 were reviewed. Patients with the following were excluded: glaucoma, ocular hypertension, known systemic/topical/injectable steroid history, and lack of documented IOP prior to or during treatment with periocular steroid ointment. Patient data were collected regarding gender, treatment regimen, as well as IOP prior to and during treatment. Steroid responders were identified. Statistical analysis was performed using linear mixed effects models adjusting for follow-up time to test the relationship between pre and posttreatment IOP change adjusting for intereye correlations. Results: Thirty-one patients were identified. Twenty-one were treated bilaterally and 10 unilaterally. Five patients were glaucoma suspects. The mean treatment period was 14.2 weeks with a range of 0.1–83.9 weeks. Patients were treated with fluorometholone (42%), loteprednol etabonate (23%), dexamethasone-neomycin-polymyxin B (13%), hydrocortisone 1% or 2.5% (3%), and tobramycin-dexamethasone (19%). In the combined sample, there was no significant IOP change even after adjusting for follow-up time (mean change: +0.44 mm Hg, p = 0.126). However, eyes with baseline IOP ≥ 14 mm Hg had a significant increase (+0.73 mm Hg/year, p = 0.032). Individual steroid responses included the following: 1 intermediate and 30 low responders, of which 19 patients had an IOP change of <1 mm Hg. One patient had a clinically significant intermediate steroid response of 7 mm Hg. Conclusions: Periocular steroid treatment causes a statistically significant rise in IOP in eyes with higher baseline IOP measurements, the risk of which increases with follow up. While this change is not always correlated with a clinically significant rise in IOP, clinicians should monitor more closely patients at greatest risk of steroid response.