Oculoplastics Publications

Singer MC, Marchal F, Angelos P, Bernet V, Boucai L, Buchholzer S, Burkey B, Eisele D, Erkul E, Faure F, Freitag SK, Gillespie MB, Harrell RM, Hartl D, Haymart M, Leffert J, Mandel S, Miller BS, Morris J, Pearce EN, Rahmati R, Ryan WR, Schaitkin B, Schlumberger M, Stack BC, Van Nostrand D, Wong KK, Randolph G. Salivary and lacrimal dysfunction after radioactive iodine for differentiated thyroid cancer: American Head and Neck Society Endocrine Surgery Section and Salivary Gland Section joint multidisciplinary clinical consensus statement of otolaryngology, ophth. Head Neck 2020;Abstract
BACKGROUND: Postoperative radioactive iodine (RAI) administration is widely utilized in patients with differentiated thyroid cancer. While beneficial in select patients, it is critical to recognize the potential negative sequelae of this treatment. The prevention, diagnosis, and management of the salivary and lacrimal complications of RAI exposure are addressed in this consensus statement. METHODS: A multidisciplinary panel of experts was convened under the auspices of the American Head and Neck Society Endocrine Surgery and Salivary Gland Sections. Following a comprehensive literature review to assess the current best evidence, this group developed six relevant consensus recommendations. RESULTS: Consensus recommendations on RAI were made in the areas of patient assessment, optimal utilization, complication prevention, and complication management. CONCLUSION: Salivary and lacrimal complications secondary to RAI exposure are common and need to be weighed when considering its use. The recommendations included in this statement provide direction for approaches to minimize and manage these complications.
Freitag SK, Aakalu VK, Tao JP, Wladis EJ, Foster JA, Sobel RK, Yen MT. Ophthalmic Technology Assessment - Sentinel Lymph Node Biopsy for Eyelid and Conjunctival Malignancy: A report by the American Academy of Ophthalmology. Ophthalmology 2020;Abstract
PURPOSE: To determine the efficacy and safety of sentinel lymph node biopsy (SLNB) in the management of eyelid and conjunctival malignancy. METHODS: A literature search was performed in August 2019 and January 2020 for articles published in English in the PubMed and Cochrane Library databases. This search yielded 151 articles that were reviewed for relevancy, of which 27 were deemed to have met the inclusion criteria for this assessment. The data from these articles were abstracted and the articles were rated for strength of evidence by the panel methodologist. RESULTS: All 27 studies were rated level III, and a total of 197 SLNBs were reported. Diagnoses included conjunctival and eyelid cutaneous melanoma (85 and 42 patients, respectively), sebaceous gland carcinoma (35), squamous cell carcinoma (26), Merkel cell carcinoma (6), pigmented epithelioid melanocytoid tumor (1), mucoepidermoid carcinoma (1), and signet ring carcinoma (1). Tracer was found in regional lymph nodes in 100% of patients in 21 of 27 articles and in 191 of 197 patients overall. The number of lymph nodes removed ranged from 1 to 16, with the majority ranging from 1 to 5. Tumor-positive lymph nodes were found in 33 of 197 (16.8%) patients, prompting recommendations for adjuvant treatments. Survival data were reported for 16 of these patients, with follow-up periods ranging from 3 to 36 (average 12.7) months. Fourteen of 16 patients received adjuvant treatments. Nine were alive and well, 1 was alive with metastases, and 6 died from metastatic disease (including 2 patients who refused additional treatment). False-negative SLNB was reported in 5 articles involving 9 of 197 (4.6%) procedures. Complications were documented in 7 of 27 articles and included transient facial nerve weakness, persistent blue-dye staining of the conjunctiva, neck hematoma, and suture abscess. CONCLUSIONS: Sentinel lymph node biopsy is a promising procedure in patients with eyelid and conjunctival malignancy, and it is useful in identifying sentinel lymph nodes. However, at present, there exists insufficient evidence that SLNB improves patient outcomes and survival. Recognition of microscopic metastatic disease may prove beneficial in staging and guiding adjuvant therapy.
Liou VD, Yoon MK. Advances in steroid sparing medical management of active thyroid eye disease. Semin Ophthalmol 2020;:1-8.Abstract
Thyroid eye disease (TED) is an autoimmune inflammatory disease of the orbit and the most common extrathyroidal manifestation of Graves disease. The release of pro-inflammatory cytokines is associated with inflammation of the ocular surface and lacrimal gland along with periorbital skin erythema and edema. Resultant tissue remodeling, fibrosis, and fat deposition can impart permanent physical changes to the ocular adnexa with effects on function and cosmesis. These changes occur in the active phase of disease, and it is during this time that steroids are often relied on to help alleviate symptoms. Due to the common and predictable side effects of long-term and high-dose steroid use, there has been a continuous effort to find alternative steroid-sparing medical management options for TED. This review highlights the various research studies that support the use of these medications.
Jakobiec FA, Hanbazazh M, Barrantes PC, Chodosh J. Adult Primary Capillary Hemangioma of the Sclera: A Previously Undescribed Entity With a Review of Epibulbar Vascular Lesions. Ophthalmic Plast Reconstr Surg 2020;36(4):327-333.Abstract
PURPOSE: The objective of this article is to document a unique case of a primary hemangioma and review epibulbar vascular tumors of the conjunctiva and episclera. METHODS: A case report with detailed histopathologic, histochemical, and immunohistochemical studies coupled with a comprehensive review of the relevant literature with a tabulation of previously reported epibulbar vascular lesions was performed. RESULTS: A vascular tumor developed in a 46-year-old woman over 2-3 months that histopathologically was located in the superficial third of the normally avascular sclera and was composed of capillary caliber vessels. CD31 and CD34 positivity established the vascular nature of the lesion. Despite its adult onset, the tumor was also glut-1 positive, a vascular characteristic of childhood capillary hemangiomas that will ultimately involute. Smooth muscle actin was positive in the endothelial cells and associated pericytes. An ectatic muscular vessel identified in the midst of the lesion was interpreted as an anomalous intrascleral branch of an epibulbar anterior ciliary artery, where it perforated the sclera in the vicinity of the insertion of an extraocular rectus muscle. It was deduced to be the source of the capillary proliferation. A literature review failed to identify any previously reported epibulbar vascular tumor that originated primarily in the sclera or secondarily infiltrated this ocular tunic. CONCLUSION: An adult primary capillary intrascleral neoplasm is described as the rarest of all epibulbar vascular tumors and in keeping with the exceptional status of the ocular endothelium was glut-1 positive. This lesion must be distinguished from an array of other common and esoteric epibulbar vascular conditions.
Tao JP, Aakalu VK, Wladis EJ, Sobel RK, Freitag SK, Foster JA, Yen MT. Bioengineered Acellular Dermal Matrix Spacer Grafts for Lower Eyelid Retraction Repair: A Report by the American Academy of Ophthalmology. Ophthalmology 2020;127(5):689-695.Abstract
PURPOSE: To review the literature on the efficacy and safety of bioengineered acellular dermal matrix (BADM) grafts for lower eyelid retraction repair. METHODS: A literature search was conducted in the PubMed database initially in January 2018 and updated in July 2019 to identify all studies in the English language literature on the use of BADM grafts in eyelid reconstruction. The searches yielded 193 citations, and 15 of the 34 articles selected for full review met all inclusion criteria for this assessment. A panel methodologist then assigned a level of evidence rating for each study. Two of the 15 studies included were rated level II and 13 were rated level III. RESULTS: The definition of success varied, but lower eyelid position improvement using lower lid margin-to-pupillary reflex distance was the most common outcome measure. Other end points were the amount of lagophthalmos, cosmesis, exposure, reoperation, or complications, as well as prosthesis retention in anophthalmic socket cases. The surgeon-reported success rate of these outcomes ranged from 75% to 100%. Minor complications included cyst formation, infection, chemosis, pyogenic granuloma, and corneal abrasion. No serious complications such as blindness, anaphylactic reaction, or terminal disease transmission occurred. Of the 526 implants included for assessment in these disparate studies, 27 cases (5%) required reoperation. CONCLUSIONS: No level I evidence was available, and the existing level II and level III studies have variable primary end points, study design limitations, and only short-term follow-up data. The current literature suggests that BADM grafts represent an implantation option for lower eyelid retraction repair. Short-term results are favorable, and the materials used may fill an important gap in care for patients for whom no acceptable alternatives exist, but long-term safety and efficacy remain unknown.
Shoji MK, Shishido S, Freitag SK. The Use of Sirolimus for Treatment of Orbital Lymphatic Malformations: A Systematic Review. Ophthalmic Plast Reconstr Surg 2020;36(3):215-221.Abstract
PURPOSE: Orbital lymphatic malformations are rare congenital choristomas associated with pain, proptosis, exposure keratopathy, and vision loss. Current treatments of surgery, drainage, and sclerotherapy may have adverse effects including risk of damage to surrounding structures, swelling, and malformation persistence or recrudescence. Sirolimus, which inhibits mammalian target of rapamycin, a regulator of cell growth and vascular endothelial growth factor expression, has successfully treated systemic vascular malformations. However, its efficacy and safety have not yet been well established for orbital lymphatic malformations. METHODS: Systematic review and analysis of relevant published literature were performed. PubMed, Embase, and World of Science searches were conducted for studies involving sirolimus treatment of orbital lymphatic malformations through July 2019. RESULTS: Nine case series and reports with 10 total patients who received sirolimus for treatment of orbital lymphatic malformations were included. The age at sirolimus initiation ranged from 1 week to 23 years. The malformation was lymphatic in 6 patients, lymphaticovenous in 3 patients, and lymphatic-arteriovenous in 1 patient. Six patients underwent ineffective prior therapy including sclerotherapy, surgery, or medical therapy. Initial sirolimus dosage ranged from 0.05 mg/kg twice a day to 1 mg twice a day, and duration ranged from 6 months to 53 months. Seven patients had partial response, and 3 patients, all of whom had a microcystic malformation component, experienced complete response. Adverse effects included mild reversible leukopenia, hypertriglyceridemia, hypercholesterolemia, and transaminitis with adverse effects denied or not specified for 6 patients. CONCLUSIONS: Sirolimus may be a safe and effective treatment for orbital lymphatic malformations, especially microcystic malformations.
Jakobiec FA, Eagle RC, Selig M, Ma L, Shields C. Clinical Implications of Goblet Cells in Dacryoadenosis and Normal Human Lacrimal Glands. Am J Ophthalmol 2020;213:267-282.Abstract
PURPOSE: The purpose of this study was to investigate an enlarged dacryoadenotic lacrimal gland and normal lacrimal glands for the presence of goblet cells (mucocytes). DESIGN: Retrospective clinicopathologic series. METHODS: An enlarged lacrimal gland (dacryoadenosis) without obvious histopathologic alterations was extensively evaluated histochemically, immunohistochemically, and ultrastructurally to detect the presence of goblet cells and to compare the findings with those in five normal lacrimal glands. RESULTS: Granular, zymogen-rich pyramidal acinar cells in normal glands predominated over a previously not reported subpopulation of nongranular, pale-staining cells in both dacryoadenotic and normal lacrimal glands. These cells histochemically stained positively with mucicarmine and Alcian blue. Immunohistochemical and electron microscopic evaluations established that there was a displacement or replacement of cytoplasmic gross cystic disease fluid protein-15 and CK 7-positive tonofilaments in the pale acinar cells by myriad mucus granules. The goblet cells constituted approximately 2% of the normal acinar cells and 5% of dacryoadenotic acinar cells. A depletion of myoepithelial cells and ectopic intra-acinar ductular cells were also observed in dacryoadenosis. CONCLUSION: Dacryoadenosis is caused by an increase in the number of acini without individual acinar cell hyperplasia. A normal cytologic feature of the lacrimal gland is the presence of acinar goblet cells that had been long overlooked; they are increased in number in dacryoadenosis. Intra-acinar ductular cells and the scattered loss of myoepithelial cells are other abnormalities in dacryoadenosis. The presence of lacrimal gland goblet cells may have physiologic implications for the precorneal tear film and its derangements as well as for the histogenesis of mucus-producing carcinomas.
Wladis EJ, Aakalu VK, Foster JA, Freitag SK, Sobel RK, Tao JP, Yen MT. Intense Pulsed Light for Meibomian Gland Disease: A Report by the American Academy of Ophthalmology. Ophthalmology 2020;Abstract
PURPOSE: To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease. METHODS: A literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results. RESULTS: All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited. CONCLUSIONS: Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.
Dohlman JC, Habib LA, Cunnane ME, Yoon MK. Subperiosteal Masqueraders As Compared to Subperiosteal Abscess: Contrasting Clinical Presentation and Radiographic Densities. Ophthalmic Plast Reconstr Surg 2020;Abstract
PURPOSE: Subperiosteal orbital lesions are most commonly abscesses secondary to sinusitis but, in rare cases, may represent other processes. Here, the authors compare the clinical and radiographic presentation of subperiosteal abscesses and alternate subperiosteal processes ("masqueraders") in an effort to establish distinguishing preoperative diagnostic criteria. METHODS: A retrospective chart review of cases of subperiosteal orbital lesions that underwent surgical intervention over a 3-year period was performed. The medical records of 6 cases of subperiosteal masqueraders and 6 cases of abscesses were reviewed for the clinical course, imaging (including radiographic density of lesions), and pathology. Clinical and radiographic features of the 2 groups were compared. RESULTS: All cases presented with orbital signs on exam. Fever and leukocytosis were absent in the masquerader group and present in 3 patients from the abscess group. Common radiographic findings in both groups included a rim-enhancing convex mass along the orbital wall and adjacent sinus opacification, often with bony dehiscence. Of the masqueraders, the final diagnosis was hematoma in 3 cases, mucocele in 1, and malignancy in 2. The difference between the mean radiodensity of the subperiosteal abscesses, 38 ± 5 Hounsfield units (95% CI, 34-42), as compared with the average radiodensity of the masqueraders, 71 ± 5 Hounsfield units (95% CI, 67-75), was significant (p = 0.042). Comparing radiodensity of the orbital lesion to adjacent sinus lesions and metastatic lesions elsewhere was also informative in establishing the diagnosis. CONCLUSIONS: Radiographic features, particularly radiodensity, may help distinguish subperiosteal abscesses from other lesions and aid in preoperative diagnosis and management.
Jakobiec FA, Hanbazazh M, Barrantes PC, Yoon MK. Conjunctival Implantation Cyst in the Orbicularis Oculi Muscle: Review of a Possible Origin From Displaced Stem Cells With a Differential Diagnosis. Ophthalmic Plast Reconstr Surg 2020;Abstract
PURPOSE: To document a unique case of a corneal/conjunctival epithelial inclusion cyst located in the orbicularis oculi muscle with a comprehensive review of variant conjunctival cysts and simulating conditions. METHODS: Clinicopathologic case report with detailed histopathologic and immunohistochemical evaluation for cytokeratins combined with a tabulation of mimicking lesions and relevant literature citations. RESULTS: A 59-year-old man experienced severe blunt left periorbital trauma that resulted in a limbal partial-thickness corneal wound with an associated epithelial abrasion and a full-thickness eyelid laceration extending from the superior fornix to the margin. Several months after surgical repair of the eyelid a cyst appeared in the superior pretarsal skin. Histopathologic and immunohistochemical investigations supplied data suggesting that the cyst had a high probability of a corneoscleral limbal stem cell origin. Distinctive features of the lesion are contrasted with those of allied or simulating cysts. CONCLUSIONS: Stem cells are now believed to be located at the corneoscleral limbus, in the inferior fornix, in the medial canthal region, and at the eyelid margin where transitions from conjunctival epithelium to epidermal epithelium occur. Due to their replicative, hardy and robust nature, stem cells displaced to alien environments are most likely to survive and produce cysts. The cyst's corneal-type cytologic characteristics, the absence of goblet cells, and the expression of a broad spectrum of cytokeratin biomarkers in the current case give support to the proposal that limbal stem cells in the region of the corneal laceration were displaced to the eyelid orbicularis muscle and were responsible for this most extraordinary cyst. Comparison with other epithelial cystic linings lends further evidence for this conclusion.
Habib LA, Wolkow N, Cohen L, Ma L, Yoon MK, Lee NG. Pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease. Am J Ophthalmol Case Rep 2020;18:100623.Abstract
Purpose: Pyoderma gangrenosum (PG) of the eyelid can be difficult to diagnosis and may mimic other, more common pathologies, thereby delaying proper treatment and management. PG may be associated with systemic disorders that have significant comorbidities. Observations: The authors present two cases of pyoderma gangrenosum of the eyelid associated with inflammatory bowel disease. Conclusions and importance: This case series highlights the importance of early recognition of eyelid pyoderma gangrenosum to avoid local and systemic comorbidities with timely and appropriate management.
Wolkow N, Jakobiec FA, Afrogheh AH, Kidd M, Eagle RC, Pai SI, Faquin WC. PD-L1 and PD-L2 Expression Levels Are Low in Primary and Secondary Adenoid Cystic Carcinomas of the Orbit: Therapeutic Implications. Ophthalmic Plast Reconstr Surg 2020;Abstract
PURPOSE: To determine if there is a biologic rationale for using checkpoint inhibitor drugs targeting programmed cell death ligand 1 (PD-L1) and PD-L2 in the treatment of adenoid cystic carcinoma of the orbit. METHODS: Twenty-three cases of adenoid cystic carcinoma involving the orbit (13 primary lacrimal gland, 5 secondarily extending into the orbit, and 5 unspecified) were examined histopathologically. Immunohistochemistry for PD-L1, PD-L2, and CD8 was performed. Charts were reviewed for clinical correlations. RESULTS: Expression of PD-L1 and of PD-L2 was overall low in adenoid cystic carcinoma (mean expression 1.4 ± 0.9 of 5 for PD-L1, mean 0.83 ± 1.1 of 5 for PD-L2), and tumor-infiltrating CD8-positive T-lymphocytes were sparse (mean 1.1 ± 0.51 of 3). Only 13 of the 23 (57%) cases expressed PD-L1 as a combined positive score ≥1 of cells. No associations were found between expression levels of these markers and patient sex, tumor site of origin, Tumor, Node, Metastasis stage, or patient outcome. A significant association was observed between stromal PD-L1 expression and tumor histopathologic subtype (p = 0.05), and between tumor PD-L1 expression and prior exposure to radiation (p = 0.03). CONCLUSIONS: Checkpoint inhibitor drugs may have limited impact in the treatment and clinical course of orbital adenoid cystic carcinoma based on the low frequency of CD8 infiltrate and low expression of PD-L1 and PD-L2. Pretreatment with radiation, however, may improve tumor response to checkpoint inhibitor drugs.