p16INK4A expression is frequently increased in periorbital and ocular squamous lesions

Backgroundp16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied.MethodsWe retrospectively surveyed 13 ocular surface and 16 orbital squamous lesions biopsied at UC San Diego Healthcare System and VA San Diego Healthcare System for p16 expression by immunohistochemistry. These cases included ocular surface lesions with diagnoses of conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma in situ. Peri-orbital eyelid biopsies included lesions with diagnoses of SCCis and invasive squamous cell carcinoma. We performed multivariate logistic regression, followed by student's T-test or Fisher's exact test to determine if there were statistically significant associations between p16 immunoreactivity and patient age, gender, diagnosis, and ethnicity. Statistical significance was defined as p < 0.05.ResultsWe found an unexpectedly large prevalence of strong nuclear and cytoplasmic p16 immunoreactivity in our cases. Almost all of the ocular surface squamous lesions were diffusely positive for p16 expression (12/13). All of the periorbital lesions showed diffuse p16 immunoreactivity (16/16). Altogether, 28/29 lesions tested showed strong and diffuse p16 expression. We found no statistically significant correlation between p16 expression and patient age, gender, ethnicity, or diagnosis. In 6 of the peri-orbital biopsies, we had sufficient tissue to assess high-risk HPV expression by in situ hybridization. Interestingly, all of these cases were negative for HPV, despite strong p16 expression.ConclusionStrong p16 expression was observed in virtually all of the ocular surface and peri-orbital squamous neoplasms in our study. The relationship between p16 expression and HPV infection in ocular surface and peri-orbital sites requires further investigation

Phospholipase C-γ as a Potential Therapeutic Target for Graves’ Orbitopathy

Background Phospholipase C-γ (PLC-γ) plays a crucial role in immune responses and is related to the pathogenesis of various inflammatory disorders. In this study, we investigated the role of PLC-γ and the therapeutic effect of the PLC-specific inhibitor U73122 using orbital fibroblasts from patients with Graves’ orbitopathy (GO). Methods The expression of phospholipase C gamma 1 (PLCG1) and phospholipase C gamma 2 (PLCG2) was evaluated using polymerase chain reaction in GO and normal orbital tissues/fibroblasts. The primary cultures of orbital fibroblasts were treated with non-toxic concentrations of U73122 with or without interleukin (IL)-1β to determine its therapeutic efficacy. The proinflammatory cytokine levels and activation of downstream signaling molecules were determined using Western blotting. Results PLCG1 and PLCG2 mRNA expression was significantly higher in GO orbital tissues than in controls (P<0.05). PLCG1 and PLCG2 mRNA expression was significantly increased (P<0.05) in IL-1β, tumor necrosis factor-α, and a cluster of differentiation 40 ligand-stimulated GO fibroblasts. U73122 significantly inhibited the IL-1β-induced expression of proinflammatory molecules, including IL-6, IL-8, monocyte chemoattractant protein-1, cyclooxygenase-2, and intercellular adhesion molecule-1 (ICAM-1), and phosphorylated protein kinase B (p-Akt) and p38 (p-p38) kinase in GO fibroblasts, whereas it inhibited IL-6, IL-8, and ICAM-1, and p-Akt and c-Jun N-terminal kinase (p-JNK) in normal fibroblasts (P<0.05). Conclusion PLC-γ-inhibiting U73122 suppressed the production of proinflammatory cytokines and the phosphorylation of Akt and p38 kinase in GO fibroblasts. This study indicates the implications of PLC-γ in GO pathogenesis and its potential as a therapeutic target for GO

Resolution of self-injurious behavior in a nonverbal and developmentally delayed patient after surgical treatment of a blind painful eye

Changes in behavioral patterns can be the only indication of the presence of pain in nonverbal patients. Phthisis bulbi results in shrinking, disorganization, and sometimes severe inflammation of the ocular globe and can occur after eye injury or multiple eye surgeries. Chronic tearing, frequent eye rubbing, and self-injurious behavior focused around the eye and periocular region may indicate ocular discomfort in nonverbal patients. In eyes that become painful and refractory to medical treatment, ocular evisceration or enucleation can provide immediate pain relief. An ocular prosthesis provides excellent cosmetic results to restore normal facial appearance after surgery. Keywords: Blind painful eye, Phthisis bulbi, Enucleation, Evisceration, Self-injurious behavior, Nonverba

Principles of Periocular Reconstruction following Excision of Cutaneous Malignancy

Reconstruction of periocular defects following excision of cutaneous malignancy can present difficulties for oculofacial and reconstructive surgeons. The intricate anatomy of the eyelids and face requires precise restoration in order to avoid postoperative functional anesthetic concerns. Various reconstructive procedures based on common principles, location and size of the defect, can be applied to achieve restoration with the best possible functional and aesthetic outcomes

Introduction to Brow Lifting

The brow and upper face undergo various changes with age resulting in brow ptosis and various other changes in the forehead and periocular region. This chapter reviews the differences in brow configuration between the male and female brow, the youthful and aged brow, and the modern conception of brow aesthetics. Various brow lifting and brow rejuvenation procedures are introduced along with the relevant anatomy of the brow, forehead, and scalp. The chapter reviews the clinical history and physical exam findings relevant to the brow and forehead evaluation so that readers can masterfully evaluate and choose an appropriate procedure for individual patients

Customised 3D Printing: An Innovative Training Tool for the Next Generation of Orbital Surgeons

Additive manufacturing or 3D printing is the process by which three dimensional data fields are translated into real-life physical representations. 3D printers create physical printouts using heated plastics in a layered fashion resulting in a three-dimensional object. We present a technique for creating customised, inexpensive 3D orbit models for use in orbital surgical training using 3D printing technology. These models allow trainee surgeons to perform 'wet-lab' orbital decompressions and simulate upcoming surgeries on orbital models that replicate a patient's bony anatomy. We believe this represents an innovative training tool for the next generation of orbital surgeons

Secondary Orbital Reconstruction in Patients with Prior Orbital Fracture Repair

To evaluate clinical characteristics, preoperative imaging findings, pre- and post-operative outcomes, and satisfaction of patients requiring secondary reconstruction after inadequate primary orbital fracture repair. Retrospective review of 13 patients requiring secondary orbital reconstruction following unsatisfactory primary repair. Primary outcomes were postoperative changes in enophthalmos, hypo- or hyper-globus, superior sulcus deformity, and restrictive strabismus. Secondary outcomes included patient satisfaction. Of 13 patients, 9 patients had primary orbital implants, and 4 patients did not. Of the 9 with implants, 6 had inferior displacement posteriorly, 2 had superior displacement posteriorly, and 1 had good position but had entrapped orbital tissues beneath it. Findings from primary surgery included enophthalmos (12/13), hypoglobus (10/13), hyperglobus (1/13), superior sulcus deformity (9/13), restricted supraduction (12/13), and restricted infraduction (7/13). Mean preoperative enophthalmos and hypoglobus were 4.4 ± 2.6 mm and 2.9 ± 1.4 mm, respectively. Secondary reconstruction resulted in mean reduction of enophthalmos by 3.4 ± 1.4 mm (p < 0.001), of hypoglobus by 2.9 ± 1.5 mm (p < 0.001), and of hyperglobus by 1 mm (n = 1). All 9 patients had resolution of their superior sulcus deformity. Of 12 cases with restricted ocular motility, all had improvements in postoperative motility following secondary surgery. Mean improvement in supraduction and infraduction was 1.8 ± 1.0 points (p < 0.001) and 1.4 ± 1.3 points (p = 0.025), respectively. Twelve patients reported being very satisfied or satisfied with secondary surgery; 1 patient was neutral. This study demonstrates that secondary orbital reconstruction can achieve excellent functional and cosmetic results with high patient satisfaction and minimal complications. Secondary reconstruction of previously repaired orbital fractures should be considered when clinically indicated