Jill A. Foster

Botulinum toxin type a for dysthyroid upper eyelid retraction.

Purpose:To evaluate the safety and efficacy of botulinum toxin type A for treatment of eyelid retraction resulting from thyroid eye disease (TED) during the inflammatory phase of the condition.Methods:In this prospective, nonrandomized case series, 18 patients with inflammatory eyelid retraction cau

Long-term Botulinum Toxin Treatment of Benign Essential Blepharospasm, Hemifacial Spasm, and Meige Syndrome

PURPOSEnTo report the clinical success and incidence of adverse events of repetitive botulinum toxin treatment of 15 years or greater.nnnDESIGNnRetrospective cohort study.nnnMETHODSnThe study sample consisted of 37 patients from a clinical practice, 11 male and 26 female. Inclusion criteria consisted of patients treated a minimum of 15 consecutive years for facial dystonia. Seven patients had hemifacial spasm, 4 Meige syndrome, and 26 benign essential blepharospasm. Main outcome measures consisted of treatment efficacy and adverse events.nnnRESULTSnMean treatment duration was 19.4 years (SD 2.2) with an average of 62 (SD 22) treatments of 70.2 (SD 20.8) neurotoxin units. Mean duration of treatment efficacy was 127 days (SD 37) with a 5% physician-reported minor adverse event rate and no major adverse events over each patients clinical course. Patients reported no major and 20% incidence of minor adverse events over the treatment course.nnnCONCLUSIONnResults suggest that long-term botulinum toxin treatment produces clinical success in the alleviation of facial dystonia symptoms. Treatment produced a low incidence of major adverse events and minor adverse events. Previous studies may under-report clinical success and over-report adverse events because of study design.

IgG4 Immunostaining and Its Implications in Orbital Inflammatory Disease

Objective IgG4-related disease is an emerging clinical entity which frequently involves tissue within the orbit. In order to appreciate the implications of IgG4 immunostaining, we analyzed gene expression and the prevalence of IgG4- immunostaining among subjects with orbital inflammatory diseases. Methods We organized an international consortium to collect orbital biopsies from 108 subjects including 22 with no known orbital disease, 42 with nonspecific orbital inflammatory disease (NSOI), 26 with thyroid eye disease (TED), 12 with sarcoidosis, and 6 with granulomatosis with polyangiitis (GPA). Lacrimal gland and orbital adipose tissue biopsies were immunostained for IgG4 or IgG secreting plasma cells. RNA transcripts were quantified by Affymetrix arrays. Results None of the healthy controls or subjects with TED had substantial IgG4 staining. Among the 63 others, the prevalence of significant IgG4-immunostaining ranged from 11 to 39% depending on the definition for significant. IgG4 staining was detectable in the majority of tissues from subjects with GPA and less commonly in tissue from subjects with sarcoidosis or NSOI. The detection of IgG4+ cells correlated with inflammation in the lacrimal gland based on histology. IgG4 staining tissue expressed an increase in transcripts associated with inflammation, especially B cell-related genes. Functional annotation analysis confirmed this. Conclusion IgG4+ plasma cells are common in orbital tissue from patients with sarcoidosis, GPA, or NSOI. Even using the low threshold of 10 IgG4+ cells/high powered field, IgG4 staining correlates with increased inflammation in the lacrimal gland based on histology and gene expression.

Preoperative Evaluation of the Brow-Lid Continuum

This article presents a thorough review for evaluation of the upper eyelid and brow preceding rejuvenation surgery. It is emphasized that surgical and nonsurgical rejuvenation is directed toward modifying the anatomic causes of facial aging. Relevant anatomy of the lid and brow area is delineated. The discussion includes surgical notes that highlight cautions or tips related to the anatomic area concerned.

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

IMPORTANCEnSarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy.nnnOBJECTIVEnTo determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis.nnnDESIGN, SETTING, AND PARTICIPANTSnIn a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis.nnnMAIN OUTCOMES AND MEASURESnSignificantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of Pu2009<u2009.05.nnnRESULTSnSignals from 2449 probe sets (transcripts fromu2009approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues.nnnCONCLUSIONS AND RELEVANCEnGene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

Reconstructive options for the medial canthus and eyelids following tumor excision

General principles provide the framework for eyelid and periorbital reconstruction following tumor excision. Eyelid tumors involving the medial canthus region and/or lacrimal system add to the complexity of reconstructive planning. The nature of the tumor, patient and tissue factors, and surgeon preference guide repair design choices. Reconstructive considerations and options following medial canthal tumor resection are described.

Fibrosis, gene expression and orbital inflammatory disease

Background/aims To 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. Methods We 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. Results Within 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. Conclusions A pathologists 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.

The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment.

Background Although thyroid eye disease is a common complication of Graves’ disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. Methods An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. Results Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. Conclusion This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.

Management of Complications of Upper Eyelid Blepharoplasty

Upper eyelid blepharoplasty is a commonly performed functional and aesthetic surgical procedure. As such, it is important for the eyelid surgeon to be familiar with the identification and treatment of the spectrum of potential postoperative complications inherent to the procedure. These complications range from annoying suture granulomas to vision-threatening orbital compartment syndrome. Some of these problems may be avoided with appropriate preoperative planning and experienced intraoperative decision making. Other complications are unpredictable, not preventable, and require management in a timely fashion. This chapter introduces the spectrum of postoperative complications related to upper eyelid blepharoplasty and reviews considerations for their prevention and management.