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159 result(s) for "Harris, Gerald J"
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Does delayed repair of eyelid lacerations compromise outcome?
Lacerations requiring repair in the operating room typically include those affecting children, those involving the canalicular system or deeper tissue planes, and complex lacerations requiring extensive reconstruction and/or exploration. Variables affecting the interval between injury and repair include delayed presentation, availability of the operating room and staff, and concomitant injuries or comorbidities that may supersede ophthalmologic concerns or preclude safe administration of anesthesia. [...]the retrospective nature of this study and dependence on proper coding in the emergency room setting may have not have captured all lacerations evaluated and repaired by the ophthalmology service in the study interval.
Teprotumumab for Thyroid-Associated Ophthalmopathy
In patients with thyroid-associated ophthalmopathy, responses to treatment are rare and usually minor. Teprotumumab, an antibody to the insulin-like growth factor I receptor, led to significant responses in 69% of patients and to decreased proptosis. Medical therapies for moderate-to-severe thyroid-associated ophthalmopathy (Graves’ orbitopathy) that have proved to be effective and safe in adequately powered, prospective, placebo-controlled trials are lacking. This unmet need is due to the incompletely understood pathogenesis of the disease. 1 Current treatments are inconsistently beneficial and often associated with side effects, and their modification of the ultimate disease outcome is uncertain. 1 – 3 Previous clinical trials, which were rarely placebo-controlled, suggest that high-dose glucocorticoids, alone 3 – 5 or with radiotherapy, 6 , 7 can reduce inflammation-related signs and symptoms in patients with active ophthalmopathy. However, glucocorticoids and orbital radiotherapy minimally affect proptosis and can cause dose-limiting adverse . . .
Cavernous Hemangioma of the Orbital Apex: Pathogenetic Considerations in Surgical Management
To consider the pathogenesis and growth of cavernous hemangioma, particularly within the crowded orbital apex, in decisions regarding surgical indications, timing, and technique. A perspective based on analysis of the microanatomic relationships and growth potential of apical cavernous hemangiomas, with representative case studies illustrating management recommendations. Analysis of microscopic findings in typical and vision-loss cases; review of tumor growth patterns as reported in observational and interventional studies; consideration of surgical approaches and reported functional outcomes. An ongoing, local hemodynamic imbalance may drive the proliferation of a cavernous hemangioma. Extension into neighboring tissue induces a fibrous capsule, which is continually reconstituted as the lesion expands, and which may incorporate visually critical structures in the confines of the apex. The extent of this microanatomic intimacy is not detectable preoperatively. The tumor's remaining growth potential at the time of diagnosis or following incomplete resection is not predictable. Patients without significant vision deficits should be observed for progression. Those with significant deficits or signs of progression should be offered timely surgery, with recognition of the risks. The surgical approach should be individualized based on macroanatomic relationships. The decision to intervene should not be a commitment to complete resection at any cost; intraoperative recognition of \"inoperable\" attachments may dictate modifications in order to preserve vision.
Enrichment of IGF-1R and PPARγ signalling pathways in orbital inflammatory diseases: steps toward understanding pathogenesis
BackgroundOrbital inflammatory disease (OID) encompasses a wide range of pathology including thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis and non-specific orbital inflammation (NSOI), accounting for up to 6% of orbital diseases. Understanding the underlying pathophysiology of OID can improve diagnosis and help target therapy.AimsTo test the hypothesis that shared signalling pathways are activated in different forms of OID.MethodsIn this secondary analysis, pathway analysis was performed on the previously reported differentially expressed genes from orbital adipose tissue using patients with OID and healthy controls who were characterised by microarray. For the original publications, tissue specimens were collected from oculoplastic surgeons at 10 international centres representing four countries (USA, Canada, Australia and Saudi Arabia). Diagnoses were independently confirmed by two masked ocular pathologists (DJW, HEG). Gene expression profiling analysis was performed at the Oregon Health & Science University. Eighty-three participants were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 25 with NSOI and 20 healthy controls.ResultsAmong the 83 subjects (mean (SD) age, 52.8 (18.3) years; 70% (n=58) female), those with OID demonstrated perturbation of the downstream gene expressions of the IGF-1R (MAPK/RAS/RAF/MEK/ERK and PI3K/Akt/mTOR pathways), peroxisome proliferator-activated receptor-γ (PPARγ), adipocytokine and AMPK signalling pathways compared with healthy controls. Specifically, GPA samples differed from controls in gene expression within the insulin-like growth factor-1 receptor (IGF-1R, PI3K-Akt (p=0.001), RAS (p=0.005)), PPARγ (p=0.002), adipocytokine (p=0.004) or AMPK (p=<0.001) pathways. TAO, sarcoidosis and NSOI samples were also found to have statistically significant differential gene expression in these pathways.ConclusionsAlthough OID includes a heterogenous group of pathologies, TAO, GPA, sarcoidosis and NSOI share enrichment of common gene signalling pathways, namely IGF-1R, PPARγ, adipocytokine and AMPK. Pathway analyses of gene expression suggest that other forms of orbital inflammation in addition to TAO may benefit from blockade of IGF-1R signalling pathways.
Orbital Inflammation in Pregnant Women
Objective To analyze overlaps between pregnancy and orbital inflammation (OI). Design Retrospective observational case series. Methods Eight new cases from 1997 to 2015 and 2 previously published cases were identified for inclusion in this investigation to provide the fullest clinical picture. Medical records, imaging studies, and the results of biopsies were reviewed. Results Three categories of association were discovered: (1) OI arising for the first time during pregnancy (5 cases); (2) OI arising within 3 months of delivery (2 cases); and (3) previously diagnosed OI reactivated or exacerbated by pregnancy (3 cases). One patient had a preexistent systemic autoimmune disease and another's was later diagnosed. One patient had attacks during sequential pregnancies. Findings included eyelid swelling and erythema, conjunctival chemosis, pain on eye movement, minimal diplopia, the usual absence of proptosis, and general preservation of visual acuity. Imaging studies disclosed extraocular muscle swelling (8 cases), most frequently of a single lateral rectus muscle. There were 2 cases of dacryoadenitis; 1 of these and an additional case displayed inflammation of the retrobulbar fat. Corticosteroids effected resolution of most symptoms. Singleton births were normal with the exceptions of an intrauterine fetal demise owing to acrania and a molar pregnancy. Conclusion OI usually affects a single rectus muscle (typically the lateral) and, less often, the lacrimal gland and is often mild when it arises during or after pregnancy. Independent systemic autoimmune disease is an uncommon feature. Corticosteroids were efficacious except in 1 case with severe orbital scarring. No definitive causal relationships between pregnancy and OI could be established based on the clinical data.
Fibrosis, gene expression and orbital inflammatory disease
Background/aimsTo clarify the pathogenesis of fibrosis in inflammatory orbital diseases, we analysed the gene expression in orbital biopsies and compared our results with those reported for idiopathic pulmonary fibrosis.MethodsWe collected 140 biopsies from 138 patients (58 lacrimal glands; 82 orbital fat). Diagnoses included healthy controls (n=27), non-specific orbital inflammation (NSOI) (n=61), thyroid eye disease (TED) (n=29), sarcoidosis (n=14) and granulomatosis with polyangiitis (GPA) (n=7). Fibrosis was scored on a 0–3 scale by two experts, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray.ResultsWithin orbital fat, fibrosis was greatest among subjects with GPA (2.75±0.46) and significantly increased in tissue from subjects with GPA, NSOI or sarcoidosis (p<0.01), but not for TED, compared with healthy controls (1.13±0.69). For lacrimal gland, the average score among controls (1.36±0.48) did not differ statistically from any of the four disease groups. Seventy-three probe sets identified transcripts correlating with fibrosis in orbital fat (false discovery rate <0.05) after accounting for batch effects, disease type, age and sex. Transcripts with increased expression included fibronectin, lumican, thrombospondin and collagen types I and VIII, each of which has been reported upregulated in pulmonary fibrosis.ConclusionsA pathologist's recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts that are considered essential in fibrosis. Many transcripts implicated in orbital fibrosis have been previously implicated in pulmonary fibrosis. TED differs from other causes of orbital fat inflammation because fibrosis is not a major component. Marked fibrosis is less common in the lacrimal gland compared with orbital adipose tissue.
Langerhans Cell Histiocytosis of the Orbit: A Need for Interdisciplinary Dialogue
Purpose To explore specialty-related perceptions and treatment strategies in Langerhans cell histiocytosis (LCH) of the orbit. Design A perspective. Methods We reviewed the reported ophthalmic experience with unifocal LCH of the orbit, analyzed current oncologic clinical trial protocols, and provided a brief Results Ophthalmic literature indicates that unifocal LCH of the orbit is usually responsive to local intervention. Current international oncologic protocols identify orbital LCH as a \"central nervous system-risk\" lesion (at risk for delayed-onset diabetes insipidus) and mandate a 6-month course of chemotherapy. Analysis suggests that the latter strategy is based on cases of orbital involvement in multifocal and multisystem disease. The pathologic Langerhans cell continues to define and unite the LCH variants, but cytokine activation of that cell may be an earlier pathogenetic determinant. Despite a common cellular mediator, LCH may be a heterogeneous process, with severity related to varied \"upstream\" trigger events. Conclusion Treatment perspectives in LCH are influenced by dissimilar patient encounters and varied interpretations of the basic disease process. Pending documentation of linkage between unifocal orbital LCH and diabetes insipidus, we recommend local intervention, with systemic treatment reserved for incomplete response or local reactivation or the appearance of lesions elsewhere. LCH underscores the need for close interaction between specialists with intersecting clinical interests.
Superior Oblique Myectomy and Trochlear Resection for Superior Oblique Myokymia
To describe our experience with myectomy of the superior oblique muscle combined with resection of the trochlea for recurrent or primary superior oblique myokymia (SOM). Retrospective, interventional case series. We performed superior oblique myectomy combined with resection of the trochlea in 3 patients with SOM in whom medical management had failed. In 2 patients, the symptoms of myokymia were recurrent after previous superior oblique tenectomy, and in 1 patient, our procedure was the first surgery. All 3 patients have experienced complete symptomatic relief from SOM with follow-up ranging from 1 to 22 years. Iatrogenic superior oblique palsy has been managed in each patient. Dysesthesia in the infratrochlear and supratrochlear regions was judged by each patient to be much less bothersome than the symptoms of SOM. We recommend myectomy of the superior oblique muscle combined with resection of the trochlea if symptoms of SOM recur after a prior superior oblique tenectomy. Based on this small series with long follow-up, the procedure also may be considered as the primary operation for SOM that fails medical management.
Teprotumumab for the Treatment of Active Thyroid Eye Disease
In a good example of translational research, investigators who had initially demonstrated a role for insulin-like growth factor I in the pathogenesis of thyroid eye disease showed that an antibody to the receptor (teprotumumab) produced a meaningful improvement in 83% of patients.
BCL10 Expression in Ocular Adnexal Lymphomas
Purpose To study BCL10 expression in ocular adnexal lymphoma in the US population and its association with clinical outcomes. Design Institutional, retrospective study. Methods Immunohistochemistry was performed with antibody against BCL10 on two tissue microarray blocks that were constructed with paraffin-embedded tissues from the same cohort of 48 patients with ocular adnexal lymphomas. The main outcomes that were measured include extraorbital involvement, recurrence rate, and time to recurrence. The median length of the follow-up period was 40 months. Results Aberrant BCL10 expression (nuclear [moderate intensity] and cytoplasmic [weak to moderate intensity] staining) was observed in 10 of 33 cases (30.3%) of mucosa-associated lymphoid tissue (MALT) lymphoma, in 4 of 10 cases (40%) of follicular lymphoma (grade 1, 9 cases; grade 2, 1 case), in 0 of 2 cases of diffused large B-cell lymphoma, in 0 of 1 case of chronic lymphocytic leukemia/small lymphocytic lymphoma and in 1 of 1 case (100%) of mantle cell lymphoma. There were no differences in clinical parameters at examination (ie, average age, gender, site of occurrence, laterality, extraorbital involvement at diagnosis), recurrence rate, and time to recurrence for patients (MALT lymphoma or follicular lymphoma) with or without aberrant nuclear BCL10 expression. Conclusion Aberrant BCL10 expression can occur in other types of ocular adnexal lymphomas besides MALT lymphoma. Ocular adnexal MALT lymphoma may have slightly lower frequency of aberrant BCL10 expression than gastric/pulmonary MALT lymphomas that have been reported in the literature. Furthermore, aberrant BCL10 nuclear expression in ocular adnexal lymphoma does not seem to correlate with clinical outcome. Further studies that include a larger number of cases and longer follow-up period are needed to confirm our observation.