Eccrine poroma of the eyelid.

Clinical and histopathologic case of an eyelid eccrine poroma, a benign adnexal neoplasm rarely found on the periorbital skin.

Ophthalmic Plastic Surgery in Patients 100 Years and Older.

PURPOSE: The centenarian population is growing and ophthalmic plastic surgeons are providing care to an increasing number of elderly patients. Outcomes of centenarians have not been previously studied in the ophthalmic plastic surgery literature. The goal of the current review was to examine the baseline characteristics, surgical problems, and outcomes of this select group of patients. METHODS: A retrospective chart review was performed. Patients who underwent ophthalmic plastic surgery at age 100 or older between January 2000 and June 2016 by a member of the New England Oculoplastics Society were included in the study. RESULTS: Fifteen patients met inclusion criteria. The majority (66%) were female. More than half (60%) presented with a surgical problem of an urgent nature. Most disorders involved the lacrimal system or eyelids, and many were the result of trauma or infection. There were no cases of orbital tumor or thyroid eye disease. There were no surgical or anesthesia-related complications. Most patients (80%) had no documented history of dementia, and only 1 was diabetic. Notably, 33% of patients presented with no light perception vision in at least 1 eye. CONCLUSIONS: Ophthalmic plastic surgery can be performed safely in select patients 100 years of age and older. Formal prospective studies are needed to improve surgical care in this group.

A Common Procedure With an Uncommon Pathology: Triamcinolone Acetonide Eyelid Injection.

Local corticosteroid injections are frequently employed by ophthalmologists to treat a variety of ocular, periocular, and orbital inflammatory conditions. Triamcinolone acetonide is a slowly dissolving crystalline corticosteroid that is often used for this purpose because of its prolonged anti-inflammatory effect. On occasion, previously injected corticosteroid material persists in tissues longer than anticipated, creating nodules that may masquerade as other disease conditions, or appearing incidentally in excised lesions on histopathologic examination. The histopathologic features of corticosteroid residues are unfamiliar to most ophthalmic pathologists and general pathologists. These features are described herein. Triamcinolone acetonide deposits in the skin appear as pale eosinophilic lakes of acellular frothy material on hematoxylin-eosin staining and are occasionally surrounded by a mild inflammatory reaction.

Histopathologic Clues in Diagnosing Oral Mucosal Grafts to the Conjunctiva.

Excised redundant, forniceal "conjunctival" tissue from a 67-year-old man who experienced a chemical injury to his OS 25 years earlier was evaluated histopathologically with the hematoxylin-eosin, periodic acid Schiff (PAS) with and without diastase, mucicarmine, and Alcian blue methods. Additional immunoperoxidase testing for gross cystic disease fluid protein-15 (GCDFP-15) was undertaken. Non-keratinizing squamous epithelium composed of 8 to 10 layers of swollen keratinocytes without goblet cells surmounted a variably dense and well-vascularized collagenized lamina propria deep to which, in submucosal fibroadipose tissue, was embedded an accessory gland. The acini of the gland were composed of both GCDFP-15-positive serous cells and mucicarmine-positive goblet cells, indicating they were seromucinous rather than entirely serous, as is characteristic of normal lacrimal glandular tissue. Different features of the surface epithelium, the lamina propria, and the submucosa can separate the conjunctival and oral mucous membranes. A close analysis of the cytologic composition of associated accessory glands can reinforce the correct diagnosis of an oral mucous membrane graft when the past surgical history is unclear, because only serous cells but not mucocytes comprise the lacrimal glandular units.

Expression of extracellular matrix components in the meibomian gland.

Purpose: Extracellular matrix (ECM) is a key component of the stem cell local microenvironment. Our study aims to explore the periglandular distribution of major components of ECM in the Meibomian gland (MG). Methods: Human eyelids and mouse eyelids were collected and processed for immunofluorescence staining. Results: Human MG tissues stained positive for collagen IV α1, collagen IV α2, collagen IV α5, and collagen IV α6 around the acini and duct, but negative for collagen IV α3 and collagen IV α4. The mouse MG were stained positive for the same collagen IV subunits as early as postnatal day 15. Laminin α2, laminin ß1 and perlecan stained the regions surrounding the acini and the acinar/ductal junction in the human MG, but not the region around the duct. Tenascin-C was found specifically located at the junctions between the acini and the central ducts. Neither agrin nor endostatin was found in the human MG tissues. Conclusion: The ECM expresses specific components in different regions around the MG, which may play a role in MG stem cell regulation, renewal, and regeneration.

Eyelid basal cell carcinoma developing in an epidermoid cyst: a previously unreported event.

A 72-year-old woman presented with a 3 × 2 × 1-mm right lower eyelid micronodular, whitish solid lesion at the nasal eyelid margin that had caused madarosis. Local excision led to the microscopic discovery of 2 epidermoid cysts, one of which harbored a basal cell carcinoma arising from its orthokeratinizing squamous cell lining. Poral openings indicated that the cysts represented follicular infundibular ectasias. BER-EP4-positive immunostaining confirmed the basal cell nature of the neoplasm. This is the first example in the eyelid of an epidermoid cyst displaying malignant transformation. No matter how innocent they may appear, all small cystic or noncystic eyelid lesions should be submitted for pathologic evaluation.

The role of routine nasolacrimal sac biopsy during endoscopic dacryocystorhinostomy.

OBJECTIVES/HYPOTHESIS: Most patients who undergo endoscopic dacryocystorhinostomy (DCR) have a diagnosis of idiopathic nasolacrimal duct obstruction. The purpose of this study was to examine the impact of routine biopsy of the lacrimal sac performed at time of DCR on subsequent patient diagnosis and treatment. STUDY DESIGN: Retrospective review. METHODS: The histopathology of nasolacrimal specimens (n = 769), obtained from 654 consecutive patients undergoing endoscopic DCR by a single surgeon over a 30-year period, were reviewed. Specific focus included the identification of unanticipated pathologic findings as they related to pertinent patient demographics, clinical presentation, radiologic findings, and intraoperative observations. RESULTS: The study population was 69.6% female, with an average age of 56.1 ± 18.2 years. Pathological findings of tissue from the nasolacrimal sac, which was routinely sampled in all cases, showed inflammation (n = 566 [73.6%]), normal histology (n = 147 [19.1%]), granulomas (n = 8 [1.0%]), and neoplastic process (n = 7 [0.9%]). Patient history, preoperative CT scan, and/or intraoperative findings alerted the surgeon to the possibility of an unusual diagnosis in 12 of the 15 patients. An unsuspected neoplastic or granulomatous cause of lacrimal obstruction was identified on intraoperative biopsy in three patients (0.46%). CONCLUSIONS: Although neoplastic and granulomatous diseases are relatively rare causes of lacrimal obstruction necessitating DCR surgery, they may be identified by through patient evaluation in most cases and by routine intraoperative biopsy of the lacrimal sac in all cases. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:584-589, 2020.

In the eye of the beholder--skin rejuvenation using a light-emitting diode photomodulation device.

BACKGROUND: A light-emitting diode (LED) photomodulation system can produce pulses of amber light expected to induce structural skin changes and reverse the effects of photoaging. OBJECTIVE: To reproduce the encouraging results already published. METHODS AND MATERIALS: Facial skin was exposed to pulses of 588+/-10-nm-wavelength light from a photomodulation device for 40 seconds once a week for 8 weeks. Photographs, clinical assessment, and a subjective questionnaire were taken at baseline, at the last follow-up, and 1 month after that. Thirty-six patients' pre- and post-treatment photos were arbitrarily scrambled, and 30 independent blinded observers were asked to pick the post-treatment photo. Two time-point comparisons were evaluated. RESULTS: For every facial characteristic studied and for both time-point comparisons, patients reported highly statistically significant improvements. In extremely sharp contrast, neither the physician's assessment nor the independent observers' evaluation indicated any improvement. CONCLUSION: Although subjective findings are comparable between studies, we were unable to reproduce the objective results of efficacy previously reported. Patients genuinely believed that several of their facial features had improved, even though there was no detectable objective change. Our data therefore suggest that the LED photomodulation treatment from the device tested is a placebo.

The serpin saga; development of a new class of virus derived anti-inflammatory protein immunotherapeutics.

Serine proteinase inhibitors, also called serpins, are an ancient grouping of proteins found in primitive organisms from bacteria, protozoa and horseshoe crabs and thus likely present at the time of the dinosaurs, up to all mammals living today. The innate or inflammatory immune system is also an ancient metazoan regulatory system, providing the first line of defense against infection or injury. The innate inflammatory defense response evolved long before acquired, antibody dependent immunity. Viruses have developed highly effective stratagems that undermine and block a wide variety of host inflammatory and immune responses. Some of the most potent of these immune modifying strategies utilize serpins that have also been developed over millions of years, including the hijacking by some viruses for defense against host immune attacks. Serpins represent up to 2-10 percent of circulating plasma proteins, regulating actions as wide ranging as thrombosis, inflammation, blood pressure control and even hormone transport. Targeting serpin-regulated immune or inflammatory pathways makes evolutionary sense for viral defense and many of these virus-derived inhibitory proteins have proven to be highly effective, working at very low concentrations--even down to the femptomolar to picomolar range. We are studying these viral anti-inflammatory proteins as a new class of immunomodulatory therapeutic agents derived from their native viral source. One such viral serpin, Serp-1 is now in clinical trial (conducted by VIRON Therapeutics, Inc.) for acute unstable coronary syndromes (unstable angina and small heart attacks), representing a 'first in class' therapeutic study. Several other viral serpins are also currently under investigation as anti-inflammatory or anti-immune therapeutics. This chapter describes these original studies and the ongoing analysis of viral serpins as a new class of virus-derived immunotherapeutic.

Exaggerated postsurgical inflammation in a patient with insufficiently treated Addison disease.

A patient with Addison disease developed fever, pain, and marked orbital inflammation 3 days after evisceration in the setting of perforated corneal ulcer. He was treated for presumed orbital cellulitis without improvement. Increasing the corticosteroid dose for his Addison disease resulted in complete resolution of the inflammation.

Hypoxia: A breath of fresh air for the meibomian gland.

PURPOSE: Optimal meibomian gland (MG) function is critically important for the health and wellbeing of the ocular surface. We hypothesize that low oxygen (O2) conditions promote the function of human MG epithelial cells (HMGECs) and that human MGs exist in a relatively hypoxic environment. The purpose of this study was to test our hypotheses. METHODS: We used human and mouse eyelid segments, and immortalized human MG epithelial cells (IHMGECs) in our studies. To evaluate oxygen (O2) levels in the mouse MG and vicinity, we injected pimonidazole (pimo), a hypoxia marker, before sacrifice. Human eyelid samples were stained with the hypoxia marker glucose transporter 1 (Glut-1). To determine the effect of low O2 levels on IHMGECs, we cultured cells under proliferating and differentiating conditions in both normoxic (21% O2) and hypoxic (3% O2) conditions for 5-15 days. IHMGECs were evaluated for cell number, neutral lipid content, lysosome accumulation, expression of biomarker proteins and DNase II activity. RESULTS: Our results demonstrate that human and mouse MGs, but not the surrounding connective tissue, exist in a relatively hypoxic environment in vivo. In addition, our findings show that hypoxia does not influence IHMGEC numbers in basal or proliferating culture conditions, but does stimulate the expression of SREBP-1 in differentiating IHMGECs. Hypoxia also significantly increased DNase II activity, and apparently IHMGEC terminal differentiation. CONCLUSIONS: Our Results support our hypotheses, and indicate that relative hypoxia promotes MG function.

The role of genetics in Graves' disease and thyroid orbitopathy.

Graves' disease is a complex autoimmune disorder characterized by multiple systemic manifestations of overproduction of thyroid hormone, and in some cases, orbitopathy. The etiology of this disorder is multifactorial, involving heritable abnormalities of immune regulation as well as environmental triggers. The goal of this paper is to provide a review of recent research investigating candidate genes involved in the pathophysiology of both Graves' disease per se and of thyroid orbitopathy.

Recognizing the protruding eye.

UNLABELLED: It is currently unknown how much exophthalmos may be noticeable to an observer. The authors determined the threshold for detection of exophthalmos may be 4 millimeters. PURPOSE: To determine the threshold for detection of exophthalmos by an observer. METHODS: The Massachusetts Eye and Ear Infirmary Ophthalmic Plastics imaging database was used to select 28 photographs of patients with unilateral exophthalmos measuring between 1 to 11 mm for the study group and 28 photographs of patients without exophthalmos for the control group. One hundred ophthalmology attendings, residents, medical students, and technicians reviewed each photograph. Participants commented on whether the patient appeared "normal" or "abnormal." RESULTS: Eighty-one percent of the control patients were correctly identified as "normal." In comparison, 60% of patients with 1 mm of exophthalmos (p < 0.001), 53% of patients with 2 mm of exophthalmos (p < 0.001), 46% of patients with 3 mm of exophthalmos (p < 0.001), 35% of patients with 4 mm of exophthalmos (p < 0.001), and 40% of patients with 5 mm of exophthalmos (p < 0.001) were identified as "normal." The vast majority of patients (91.9%, p < 0.001) with 6 mm of exophthalmos were identified as "abnormal," and almost all patients (97.9%, p < 0.001) with more than 6 mm of exophthalmos were also described as having an "abnormal" appearance. CONCLUSIONS: Greater than half of the patients with 1-2 mm of exophthalmos appear as "normal" as the control patients. In comparison, the majority of patients with 4-5 mm of exophthalmos and nearly all the patients with 6 mm of exophthalmos and greater appear "abnormal." Our data suggests that the point at which exophthalmos becomes clinically perceptible to the majority of observers is 4 mm. There may be patients with 3 mm of exophthalmos and greater with orbital pathology being "missed" on cursory external examinations by general ophthalmologists, optometrists, and general practitioners.

Biomarkers for Progenitor and Differentiated Epithelial Cells in the Human Meibomian Gland.

The meibomian gland (MG) is a sebaceous gland that secretes through a holocrine process. Because such secretion requires the destruction of MG acinar epithelial cells, they need constant renewal and differentiation. The processes that promote these regenerative events in the human MG are unknown, nor is it known how to distinguish MG progenitor and differentiated cells. We discovered that Lrig1 and DNase2 serve as biomarkers for human MG progenitor and differentiated cells, respectively. Lrig1 is expressed in MG basal epithelial cells in the acinar periphery, a location where progenitor cells originate in sebaceous glands. DNase2 is expressed in the differentiated epithelial cells of the MG central acinus. Furthermore, proliferation stimulates, and differentiation suppresses, Lrig1 expression in human MG epithelial cells. The opposite is true for DNase2 expression. Our biomarker identification may have significant value in clinical efforts to restore MG function and to regenerate MGs after disease-induced dropout. Stem Cells Translational Medicine 2018;7:887-892.

Causes of dacryocystorhinostomy failure: External versus endoscopic approach.

OBJECTIVES: To compare the causes of failure between external and endoscopic dacryocystorhinostomy (DCR) techniques for the treatment of lacrimal obstruction. STUDY DESIGN: A retrospective cohort study. METHODS: The study population consisted of 53 consecutive patients who underwent revision endoscopic DCR from 2002 to 2013 for lacrimal duct obstruction. Identified causes of previous DCR failure were compared between patients whose initial surgery was performed through an external versus an endoscopic approach. RESULTS: Reasons for surgical failure after external (n = 21) versus endoscopic (n = 32) DCR included cicatricial closure of the internal lacrimal ostium (52.4 versus 53.1%; p = 0.96), inadequate removal of bone overlying the lacrimal sac (23.8 versus 9.4%; p = 0.15), sump syndrome (9.5 versus 9.4%; p = 0.99), and intranasal adhesions (65 versus 37.5%; p = 0.05). Adhesions that involved the middle turbinate were a particularly impactful cause of failure when the DCR was performed through an external versus the endoscopic approach (57.1 versus 28.1%; p = 0.04). Septoplasty was more likely to be needed at the time of revision surgery if the initial procedure was performed externally (71.1 versus 15.6%; p = 0.02). Surgical success rates for revision DCR were comparable between the groups (75.0% external versus 73.3% endoscopic; p = 0.90), with a mean follow-up of 12.7 months. CONCLUSION: DCR failure associated with intranasal adhesions was more likely to occur when the surgery was performed through an external rather than an endoscopic approach. Endoscopic instrumentation allowed for identification and correction of intranasal pathology at the time of DCR, including an enlarged middle turbinate or a deviated septum, which may improve surgical outcome.

Turnover and fate of fibrinogen and platelets at the rabbit aorta wall immediately after a balloon de-endothelializing injury in vivo.

A de-endothelializing injury to the artery wall in vivo results in a rapid procoagulant response at the surface of the exposed subendothelium. Activated tissue factor (TF)-bearing cells and hemostasis factors located at the site of injury respond by producing thrombin, and within minutes the principal thrombus-forming, blood-borne components (platelets, fibrinogen) accumulate at the site. To compare their behaviors, the rates of uptake and turnover of rabbit (51)Cr-platelets and rabbit (125)I-fibrinogen were quantified simultaneously during the initial 100-min interval after a balloon catheter injury to the rabbit aorta in vivo. Platelets ( approximately 70,000/mm(2)) and fibrin(ogen) ( approximately 2.8 pmol/cm(2)) saturated the ballooned aorta surface within five minutes after injury. Whereas the adherent platelet and fibrinogen concentrations remained steady at the aorta surface, fibrin(ogen)-related products continued to accumulate slowly in the tunica media (TM) for at least 100 minutes. A relatively small proportion (3.7%/min) of adhered platelets turned over at the ballooned aorta surface at 10 minutes, decreasing to 1.2%/min at 100 minutes. By contrast, a larger proportion of fibrin(ogen) ( approximately 20%/min) was turned over within the platelet layer at 10 minutes, decreasing to 6%/min at 100 minutes. As verified by immunostaining aorta sections and by protein analysis of TM extracts, the uptakes of platelets and fibrinogen at the site of injury contributed to an accumulation of products of platelet releasate and fibrin(ogen) degradation (FDPs) within the TM. These observations improve our understanding of the hemostatic processes and subsequent events that occur after an arterial injury in vivo.

Endocanalicular laser dacryocystorhinostomy analysis of 118 consecutive surgeries.

PURPOSE: To describe the outcomes of endocanalicular laser dacryocystorhinostomy (ECL DCR) for patients with nasolacrimal duct obstruction (NLDO). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: One hundred eight consecutive patients who underwent ECL DCR. METHODS: The records of the patients who underwent ECL DCR at 1 of 2 academic centers were reviewed and the data analyzed. MAIN OUTCOME MEASURES: Success was defined as the resolution of symptoms or unobstructed lacrimal irrigation. RESULTS: One hundred eighteen consecutive ECL DCR surgeries performed on 108 patients between June 1997 and June 2003 were reviewed, excluding 6 lost to follow-up. Endocanalicular laser DCR was the initial surgical intervention for all cases except 6 that had previously undergone surgery (external or endonasal DCR) at outside hospitals. Twenty-seven of the surgeries were considered failures on the basis of recurrent epiphora or discharge, or reflux on nasolacrimal irrigation. One of the failures was permanently corrected with balloon dacryoplasty. Nine of the other failures had a repeat procedure, with 7 remaining patent after one repeat procedure and an additional one remaining patent after a third procedure. All 6 ECL DCR procedures that were performed after external or endonasal DCR at an outside institution remained patent. Among the 102 initial lacrimal surgeries in this series, there was a 73.6% success rate. The overall success, including repeat procedures, was 81.5%. The success of this technique as a repeat procedure after previous external, endonasal, or ECL DCRs was 87.5%. CONCLUSIONS: Endocanalicular laser DCR offers a minimally invasive alternative procedure for the treatment of NLDO. In our series, the success rates are comparable to those previously reported. The technique had a high success rate when used to treat recurrent NLDO after previous lacrimal surgery.

Simplified repair of zygomatic fractures through a transconjunctival approach.

OBJECTIVE: To describe a simplified technique of zygomatic fracture repair. DESIGN: Retrospective, noncomparative case series with description of a surgical technique. PARTICIPANTS: Twenty consecutive patients with zygomatic fractures undergoing repair with the described technique. INTERVENTION: Fracture repair was accomplished with a technique that used a T-bar screw for reduction through a transconjunctival approach. MAIN OUTCOME MEASURE: Successful fracture reduction. RESULTS: Twenty patients with zygomatic fractures underwent successful reduction with the simplified technique. No complications were observed. CONCLUSIONS: The use of the T-bar through a transconjunctival approach is a simplified and effective technique for zygomatic fracture repair.

Successful treatment of idiopathic orbital inflammation with mycophenolate mofetil.

PURPOSE: To report our experience with the use of mycophenolate mofetil for treatment of idiopathic orbital inflammation (IOI). DESIGN: Noncomparative interventional case series. METHODS: We reviewed the records of five patients with IOI who were treated with mycophenolate mofetil. The indications for use included recurrent inflammation after other therapies (four patients) and to avoid corticosteroid-induced blood sugar elevation in poorly controlled diabetes mellitus (one patient). Treated patients were followed for a median of 8.5 months (range, 4-30 months) after mycophenolate mofetil therapy was begun. Main outcome measures were response to treatment, treatment-related side effects, drug dosage, previous and final treatment regimens, and discontinuation of systemic corticosteroids. RESULTS: Mycophenolate mofetil therapy was discontinued in one patient because of nausea. Each of the remaining four patients experienced complete resolution of orbital inflammation. Of these, only one patient remains on prednisone, but at a significantly reduced dose (1 mg/d). CONCLUSION: Mycophenolate mofetil therapy resulted in the resolution of inflammation in patients with refractory or corticosteroid-dependent IOI and was used successfully for a first episode of IOI in a patient for whom corticosteroids were contraindicated.