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Purpose: The purpose of this study was to compare the histopathologic inflammation and fibrosis of orbital adipose tissue in orbital inflammatory disease (OID) specimens., Methods: In this retrospective cohort study, inflammation, and fibrosis in orbital adipose tissue from patients with thyroid-associated orbitopathy (TAO), granulomatosis with polyangiitis (GPA), sarcoidosis, nonspecific orbital inflammation (NSOI), and healthy controls were scored by 2 masked ocular pathologists. Both categories were scored on a scale of 0 to 3 with scoring criteria based on the percentage of specimens containing inflammation or fibrosis, respectively. Tissue specimens were collected from oculoplastic surgeons at 8 international centers representing 4 countries. Seventy-four specimens were included: 25 with TAO, 6 with orbital GPA, 7 with orbital sarcoidosis, 24 with NSOI, and 12 healthy controls., Results: The mean inflammation and fibrosis scores for healthy controls were 0.0 and 1.1, respectively. Orbital inflammatory disease groups' inflammation (I) and fibrosis (F) scores, formatted [I, F] with respective p -values when compared to controls, were: TAO [0.2, 1.4] ( p = 1, 1), GPA [1.9, 2.6] ( p = 0.003, 0.009), sarcoidosis [2.4, 1.9] ( p = 0.001, 0.023), and NSOI [1.3, 1.8] ( p ≤ 0.001, 0.018). Sarcoidosis had the highest mean inflammation score. The pairwise analysis demonstrated that sarcoidosis had a significantly higher mean inflammation score than NSOI ( p = 0.036) and TAO ( p < 0.0001), but no difference when compared to GPA. GPA had the highest mean fibrosis score, with pairwise analysis demonstrating a significantly higher mean fibrosis score than TAO ( p = 0.048)., Conclusions: Mean inflammation and fibrosis scores in TAO orbital adipose tissue samples did not differ from healthy controls. In contrast, the more "intense" inflammatory diseases such as GPA, sarcoidosis, and NSOI did demonstrate higher histopathologic inflammation and fibrosis. This has implications in prognosis, therapeutic selection, and response monitoring in orbital inflammatory disease., Competing Interests: J.T.R. has in the past consulted for Genentech/Roche and was a co-investigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. J.T.R., R.A.D., and D.O.K. are consultants, while G.J.H. and B.S.K. have in the past consulted for Horizon Pharmaceuticals, which manufactures teprotumumab. Other authors have no conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: To describe the utilization of acellular cadaveric dermal matrix (ACDM) in patients undergoing orbital wall reconstruction after orbital preservation surgery for sinonasal malignancy., Methods: Retrospective case series of seven patients with sinonasal malignancy who had orbital reconstruction with ACDM implants from January 2012 to August 2020. Orbital preservation was performed in all patients with tumor extension up to and including periorbital. The main outcome measures were implant exposure, orbital infection, diplopia in primary gaze, enophthalmos, and eyelid malposition., Results: Patients ranged 37-78 years old (median: 66 years) and included 4 females and 3 males. The median follow-up time was 9 months (range 6-43 months) from the date of surgery. Squamous cell carcinoma comprised the majority of tumors with all patients needing medial wall reconstruction. Three patients received postoperative radiation therapy. No patients had any implant exposure, orbital infection, enophthalmos, or eyelid malposition., Conclusions: ACDM grafts can be used safely in orbital wall reconstruction in patients with sinonasal malignancies.

Background: Orbital 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., Aims: To test the hypothesis that shared signalling pathways are activated in different forms of OID., Methods: In 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., Results: Among 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., Conclusions: Although 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., Competing Interests: Competing interests: JTR has in the past consulted for Genentech/Roche and was a coinvestigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. JTR, RAD, BSK, DOK, and GJH are consultants to Horizon Pharmaceuticals which manufactures teprotumumab. JTR receives research support from Horizon Pharmaceuticals., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Thyroid eye disease (TED) is a vision-threatening and debilitating condition that until very recently had no Food and Drug Administration (FDA)-approved medical therapies. Teprotumumab has recently been approved to treat TED. We aim to provide guidance for its use, based on the input of the US investigators who participated in Phase 2 and Phase 3 clinical trials., Methods: An expert panel was convened on October 11th and November 16th of 2019. All panel members had extensive experience as investigators in the Phase 2 and/or Phase 3 clinical trials of teprotumumab. Consensus among those investigators was reached to determine patient characteristics most appropriate for teprotumumab treatment. Safety guidelines were also reviewed and agreed on., Results: The authors recommend that teprotumumab be considered first-line therapy for patients with clinically significant ophthalmopathy, including those with disease duration exceeding 9 months. The clinical activity score (CAS) may be useful for longitudinal monitoring but should not be used to determine treatment eligibility. Criteria will likely be expanded after more experience with the drug. Using teprotumumab for patients with TED with substantial signs, symptoms, or morbidity without a CAS score of >4 (e.g., progressive proptosis, diplopia, and early compressive optic neuropathy) or more, could be considered. Diabetes mellitus and inflammatory bowel disease comorbidities should not be exclusionary, but stringent monitoring in these patients is recommended. Drug dosing, administration interval, and duration should adhere to the study protocol: 8 infusions, separated by 3 weeks. Patients with more severe disease may benefit from additional doses. Corticosteroids can be used before or during teprotumumab therapy. Clinical and laboratory monitoring should be consistent with good clinical practice for patients receiving teprotumumab., Conclusions: Confirming the efficacy of teprotumumab usage outside the narrow parameters of the completed clinical trials will require rigorous scientific validation. As a step in that direction, we believe its on-label usage is appropriately applied to all patients with TED with substantial symptoms or morbidity, as judged by their physician., Competing Interests: R. S. Douglas reports receiving consulting fees from Horizon Therapeutics. R. A. Dailey receiving consulting fees from Horizon Therapeutics. G. J. Harris receiving advisory board fees from Horizon Therapeutics. J. S. Schiffman and R. A. Tang receiving grant support and consulting fees from Immunovant Sciences. S. T. Wester receiving advisory board fees from Horizon Therapeutics. T. J. Smith receiving consulting fees from Immunovant and Horizon Therapeutics, holding patents 6936426 and 7998681 on detection of antibody-mediated inflammatory autoimmune disorders, holding patent 8153121 on diagnosis and therapy of antibody-mediated inflammatory autoimmune disorders, and holding patent 8178304 on diagnostic methods related to Graves disease and other autoimmune disorders. The remaining authors report no conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the North American Neuro-Opthalmology Society.)

Non-specific orbital inflammation (NSOI) is a noninfectious inflammatory condition of the orbit. Although it is generally considered the most common diagnosis derived from an orbital biopsy, it is a diagnosis of exclusion, meaning that the diagnosis requires exclusion of a systemic process or another identifiable etiology of orbital inflammation. The clinical diagnosis of NSOI is ill-defined, but it is typically characterized by acute orbital signs and symptoms, including pain, proptosis, periorbital edema, chemosis, diplopia, and less commonly visual disturbance. NSOI poses a diagnostic and therapeutic challenge: The clinical presentations and histological findings are heterogeneous, and there are no specific diagnostic criteria or treatment guidelines. The etiology and pathogenesis of NSOI are poorly understood. Here we recapitulate our current clinical understanding of NSOI, with an emphasis on the most recent findings on clinical characteristics, imaging findings, and treatment outcomes. Furthermore, gene expression profiling of NSOI and its implications are presented and discussed., (Copyright © 2020. Published by Elsevier Ltd.)

Radiologic orbital imaging provides important information in the diagnosis and management of orbital inflammation. However, the diagnostic value of orbital imaging is not well elucidated. This study aimed to investigate the diagnostic accuracy of orbital imaging to diagnose orbital inflammatory diseases and its ability to detect active inflammation. We collected 75 scans of 52 patients (49 computed tomography (CT) scans; 26 magnetic resonance (MR) imaging scans). Clinical diagnoses included thyroid eye disease (TED) (41 scans, 31 patients), non-specific orbital inflammation (NSOI) (22 scans, 14 patients), sarcoidosis (4 scans, 3 patients), IgG4-related ophthalmic disease (IgG4-ROD) (5 scans, 3 patients), and granulomatosis with polyangiitis (GPA) (3 scans, 1 patient). Two experienced neuroradiologists interpreted the scans, offered a most likely diagnosis, and assessed the activity of inflammation, blinded to clinical findings. The accuracy rate of radiological diagnosis compared to each clinical diagnosis was evaluated. Sensitivity and specificity in detecting active inflammation were analyzed for TED and NSOI. The accuracy rate of radiologic diagnosis was 80.0% for IgG4-ROD, 77.3% for NSOI, and 73.2% for TED. Orbital imaging could not diagnose sarcoidosis. Orbital CT had a sensitivity of 50.0% and a specificity of 75.0% to predict active TED using clinical assessment as the gold standard. The sensitivity/specificity of orbital MR was 83.3/16.7% for the detection of active NSOI. In conclusion, orbital imaging is accurate for the diagnosis of IgG4, NSOI, and TED. Further studies with a large number of cases are needed to confirm this finding, especially with regard to uncommon diseases. Orbital CT showed moderate sensitivity and good specificity for identifying active TED.

Innate immune response to a lipopolysaccharide (LPS) challenge varies among sheep breeds. How different breeds respond to bacterial infections impacts management practices of sheep producers. Hence, clinical response, acute-phase response, and gene expression of pro- and anti-inflammatory markers in peripheral white blood cells (WBCs) were examined after an LPS challenge in Dorset and Suffolk ewes. Ewes received either PBS or 2.5 µg/kg LPS (i.v.) 4 to 5 d after onset of synchronized estrus. Blood was collected via jugular venipuncture intermittently for 24 h to determine WBC counts. Rectal temperatures and observations of behavioral/physical appearances were recorded hourly. After LPS, WBCs decreased the first hour (P = 0.0001) and rectal temperatures (P < 0.0001) increased through 4 h; both returned toward normal 6 h after challenge. Suffolk ewes exhibited greater changes in temperature (P = 0.03) and behavioral/physical responses (P < 0.0001) than Dorset ewes and had an enhanced acute-phase response demonstrated by increased concentrations of plasma haptoglobin (P = 0.04), as well as cortisol concentrations (P = 0.03). Real-time PCR was completed on buffy coat homogenates for expression of pro-inflammatory [CXCL8, IL-6, interferon gamma (IFNG), complement component 3 (C3), toll-like receptor 4 (TLR4), prostaglandin synthase 2 (PTGS2)] and anti-inflammatory [IL-10, superoxide dismutase 2 (SOD2), forkhead box P3 (FOXP3), peroxisome proliferator-activated receptor gamma (PPARG), mannose receptor C type 1 (MRC1), transforming growth factor β (TGFβ)] genes. After LPS treatment, gene expressions increased for CXCL8 (P = 0.0003), TLR4 (P = 0.004), SOD2 (P < 0.0001), and C3 (P = 0.003), while PPARG (P = 0.006) and MRC1 (P = 0.003) decreased. Overall, Dorset ewes had greater expression of TLR4 (P = 0.003), IL-10 (P = 0.045), PPARG (P = 0.002), FOXP3 (P = 0.001), and SOD2 (P = 0.0002), whereas Suffolk ewes had greater expression of IL-6 (P = 0.0007), IFNG (P = 0.02), PTGS2 (P = 0.0002), and C3 (P = 0.008). Suffolk ewes also displayed greater expression of IL-6 (P = 0.002) and C3 (P = 0.0004) in response to LPS. In conclusion, differences in gene expression may explain the enhanced inflammatory response in Suffolk ewes and may predispose Suffolk ewes to be more responsive to bacterial infection than Dorset ewes.

Purpose: To describe success rates and long-term outcomes of conjunctivodacryocystorhinostomy (CDCR) with larger collar (4.5 or 5.0 mm) frosted Jones tubes (FJTs)., Methods: A retrospective chart review of all patients who received a larger collar (4.5 or 5.0 mm) FJT following CDCR by an author (RAD) was performed between January 1, 2010 and July 1, 2016. Patient demographics, etiology of tearing, follow-up time from placement of larger collar FJT, original tube collar diameter, number and sizes of collar adjustments, tearing status, and complications were recorded. Exclusion criteria included follow up less than 6 months after placement of a larger collar FJT. The study was IRB approved, HIPAA compliant, and adherent to the Declaration of Helsinki., Results: Twenty-five patients (29 eyes) met the inclusion criteria. Average follow-up time was 30 months. Twenty-eight out of 29 eyes had complete resolution of tearing after placement of larger collar FJT and no tubes were lost. Fourteen out of 29 eyes required adjustment in collar size after a larger collar was placed. Two out of 13 eyes that had a 5.0 mm collar placed required exchanged due to collar prominence., Conclusion: With the use of larger collar FJTs, the long-term success of CDCR in tearing patients remains highly effective. This study demonstrates larger collar FJTs are well tolerated and help reduce the chance of tube loss.

Importance: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies., Objective: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups., Design, Setting, and Participants: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017., Main Outcomes and Measures: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis., Results: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores., Conclusions and Relevance: Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.

Purpose: To describe success rates and long-term outcomes of conjunctivodacryocystorhinostomy (CDCR) with frosted Jones tubes (FJT) for epiphora with proximal outflow obstruction., Methods: A retrospective chart review of all patients undergoing external and endoscopic CDCR with FJTs by one author (RAD) was performed between January 1, 2006 and November 1, 2014 at the Casey Eye Institute. Patient demographics, etiology of tearing, concurrent endonasal and eyelid procedures, and FJT size were recorded. After CDCR, follow-up time, tube size changes, tube position, and tearing status were noted. Exclusion criteria included follow up less than 6 months and/or prior CDCR. The study was IRB approved, HIPAA compliant, and adherent to the declaration of Helsinki., Results: Forty-two eyes of 31 patients met the inclusion criteria, with the majority having epiphora from canalicular obstruction (31%) or flaccid canaliculi (31%). Average follow up was 1,088 days. Forty of 42 eyes, or 30 of 31 patients, had complete resolution of tearing after surgery. Twenty of 42 eyes required tube size changes, usually an increase in collar size (45%) and/or decrease in tube length (55%). Six of 42 FJTs were lost, one migrating outward, with an average time to loss between 61 and 1,122 days (mean 817 days). After collars larger than 4 mm became available, only one tube was lost. All epiphora resolved after repeat CDCR. The most common complication was intermittent irritation (17%) near the FJT that resolved after antibiotic-steroid drops and/or tube replacement/cleaning., Conclusion: CDCR with FJTs is highly effective in correcting epiphora, and well tolerated by the majority.

Purpose: To investigate the presence and microbiology of bacterial biofilms on Jones tubes (JTs) by direct visualization with scanning electron microscopy and polymerase chain reaction (PCR) of representative JTs, and to correlate these findings with inflammation and/or infection related to the JT., Methods: In this study, prospective case series were performed. JTs were recovered from consecutive patients presenting to clinic for routine cleaning or recurrent irritation/infection. Four tubes were processed for scanning electron microscopy alone to visualize evidence of biofilms. Two tubes underwent PCR alone for bacterial quantification. One tube was divided in half and sent for scanning electron microscopy and PCR. Symptoms related to the JTs were recorded at the time of recovery., Results: Seven tubes were obtained. Five underwent SEM, and 3 out of 5 showed evidence of biofilms (60%). Two of the 3 biofilms demonstrated cocci and the third revealed rods. Three tubes underwent PCR. The predominant bacteria identified were Pseudomonadales (39%), Pseudomonas (16%), and Staphylococcus (14%). Three of the 7 patients (43%) reported irritation and discharge at presentation. Two symptomatic patients, whose tubes were imaged only, revealed biofilms. The third symptomatic patient's tube underwent PCR only, showing predominantly Staphylococcus (56%) and Haemophilus (36%) species. Two of the 4 asymptomatic patients also showed biofilms. All symptomatic patients improved rapidly after tube exchange and steroid antibiotic drops., Conclusions: Bacterial biofilms were variably present on JTs, and did not always correlate with patients' symptoms. Nevertheless, routine JT cleaning is recommended to treat and possibly prevent inflammation caused by biofilms.

Background: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy., Methods: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed., Results: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes., Conclusions: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

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 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., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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.

Importance: Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy., Objective: To 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., Design, Setting, and Participants: In 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., Main Outcomes and Measures: Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05., Results: Signals from 2449 probe sets (transcripts from approximately 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., Conclusions and Relevance: Gene 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., Competing Interests: Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Rosenbaum has consulted for Genentech and was a coinvestigator on a study funded by Genentech to evaluate the use of rituximab for orbital inflammatory diseases. No other disclosures were reported.

Purpose: To describe clinical outcomes of patients receiving porcine dermal matrix implants for lower eyelid retraction repair., Methods: A retrospective review of all patients who underwent lower eyelid retraction repair with porcine dermal matrix implantation between June 2007 and July 2013 at a tertiary care center was conducted. Patient demographics, procedure(s) performed, preoperative and postoperative marginal reflex distance, inferior scleral show, and complications were reviewed. Patients with a prior history of lower eyelid surgery were excluded. The study is Health Insurance Portability and Accountability Act compliant, institutional review board approved, and adherent to the Declaration of Helsinki., Results: One hundred patients (160 eyelids) received porcine dermal collagen implants. Fifty-six patients had thyroid eye disease, 23 had midface descent, 10 had seventh nerve palsies, and 11 had other etiologies of retraction. The average preoperative marginal reflex distance was 7.64 mm in the OD and 7.17 mm in the OS, compared with 6.40 mm in the OD and 6.22 mm in the OS postoperatively. The average preoperative inferior scleral show was 2.04 in the OD and 1.70 in the OS compared with 0.81 mm in the OD and 0.65 mm in the OS postoperatively. Follow up ranged from 1.46 to 66.04 months, with an average of 14.06 months and median of 8.84 months. Nineteen eyelids had implant-related complications: 7 with cyst formation, 7 with exposure/rejection, 2 with long-term pain, 2 with transient inflammation, and 3 with irregular implant contour., Conclusions: Porcine dermal matrix implants provide reliable support, integration, and function in lower eyelid retraction repair without significant resorption or complications in the majority of patients.

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.

Ability to select service sires that minimize partial or complete losses of pregnancy could have major economic impacts in sheep production systems. This study tested the null hypothesis that survival of potential progeny did not vary with breed type of service sire or among individual rams. Data included 980 ewes on 10 farms; each ewe was pregnant to 1 of 67 rams of 12 breeds. Number of conceptuses was estimated once during pregnancy by ultrasonography, either transrectal (embryos) or transabdominal (fetuses), and was compared with number of lambs born to estimate losses. Data were examined first for number of lambs born and second for documented losses. Individual service sires affected number born (P < 0.001), which varied from 0.70 to 2.45 lambs per pregnant ewe. The main effects of breed type on lambs born were not significant, but breed types of both service sires (P < 0.0002) and ewes (P < 0.001) interacted with diagnosed number of conceptuses. Lambs born varied with ewe age (P < 0.0001) and among farms (P < 0.0001), and statistically, farms interacted with number of diagnosed conceptuses (P < 0.0001); season had no effect. In documented losses, there were both main effects of individual service sire and a service sire × number of diagnosed embryos interaction (P < 0.005). Thus, ewes bred to some rams were more apt to lose single pregnancies, whereas ewes bred to other rams were more apt to lose 1 or more embryos or fetuses from multiple pregnancies. Breed type of service sire affected (P < 0.05) prenatal death. Complete losses of single conceptuses tended to be greater in ewes bred to black-faced or hair-type rams (service sire breed type × number of diagnosed conceptuses; P < 0.09). Breed type of ewes also varied in incidence of complete losses (P < 0.05); hair-type ewes (46%) lost more (P < 0.02) documented conceptuses from examination to birth than black-faced (27%), white-faced (20%), or dairy-type (25%) ewes. Greater losses of singles than of multiples occurred in black-faced (37% vs. 18%) and hair-type (64% vs. 27%) ewes than in other breeds (ewe breed type × number of conceptuses; P < 0.03) per ewe. Surprisingly, purebred conceptuses were lost less often (24%) than crossbreds (36.4%; P < 0.002). Selection of rams based on records of prenatal losses in ewes they serviced may be a method to decrease embryonic and fetal wastage. However, further study to determine repeatability of differences among service sires from year to year will be required.

Lateral canthal dystopia can lead to lower eyelid malposition, abnormal lateral eyelid fissure appearance, and lagophthalmos. In most cases, the lateral canthus can be repaired with a standard lateral canthopexy or canthoplasty. In a fraction of cases, especially when recurrent, the surgical repair may require additional lateral canthal reinforcement.

Objective: To determine whether injection every 4 months with onabotulinumtoxinA provides longer-lasting reduction or elimination of glabellar rhytides., Methods: Toxin-naive women (N=45) aged 30 to 50 with moderate to severe glabellar lines at maximum contraction completed the study. Five sites were treated with 4 U of onabotulinumtoxinA. Participants were assessed at day 30; those with glabellar severity of none to mild remained in the study. Participants received identical treatments at months 4, 8, 12, 16, and 20, and were assessed without treatment at 24, 25, and 26 months., Results: Baseline physician- and participant-rated treatment responders at maximum contraction were 84% and 80%, respectively, at month 20; and 56% and 58%, respectively, at month 26. Mean changes from physician- and participant-assessed Facial Wrinkle Scale at maximum contraction from baseline to all postbaseline measurements were significant (p≤.001). The percentage of participants reporting neutral (0) to couldn't be more satisfied (+4) with their appearance ranged from 91% to 100% during months 1 to 24. At month 26, 87% of participants reported satisfaction, with appearance scores between 0 and +4. No adverse events were reported., Conclusions: OnabotulinumtoxinA delivered for 20 months significantly reduces or progressively eliminates glabellar rhytides for up to 6 months after the last treatment., (© 2011 by the American Society for Dermatologic Surgery, Inc.)

Generally, unilateral ovariectomy before a critical period in the latter part of the estrous cycle induces a transitory increase in plasma FSH, which causes subordinate follicles to develop and maintain ovulation rates characteristic of the species. A limiting period for subordinate follicles to assume dominance and from which ovulation occurs has not been shown for cattle. Growth and/or regression of subordinate follicles were characterized following removal of the dominant follicle at different days of the luteal phase of the estrous cycle in cattle in this study. In the mid-luteal phase (Day 13 or 15), the ovary with the dominant follicle of the second wave was ablated via unilateral ovariectomy; the corpus luteum also was removed. In the late luteal phase (Day 17 or 19), the dominant follicle was ablated with an ultrasonically guided 20 gauge needle. When the dominant follicle was removed on Day 13, the largest subordinate follicle of the second wave of follicular development became dominant and ovulation occurred from this follicle in 4 of 4 animals. However, when the dominant follicle was removed on Day 15, 17 or 19, a new wave of follicular development was induced in 14 of 15 animals. Moreover, the recovered subordinate follicle of the second wave of follicular development had similar growth characteristics to naturally occurring dominant follicles. In conclusion, the subordinate follicle in the second follicular wave in cattle retained the ability to become dominant, but this ability was lost by Day 15 of the estrous cycle. However, cattle then were able to maintain ovulation by developing a new wave of follicular growth., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field., (Copyright © 2011 American Academy of Dermatology, Inc. and American Society of Plastic Surgeons. Published by Mosby, Inc. All rights reserved.)

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report summarizes the deliberations and key points made by the panel and presenters to the panel, and includes a summary of the panel's near-term and longer term recommendations for next steps to help guide future efforts to address the safety, efficacy, and effectiveness of facial soft-tissue fillers. This report represents the panel's assessment of the medical knowledge available on facial soft-tissue fillers at the time of the conference., (Copyright © 2011 American Academy of Dermatology, Inc. and American Society of Plastic Surgeons. Published by Mosby, Inc. All rights reserved.)

Summary: : The American Society of Plastic Surgeons and the American Academy of Dermatology, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Society of Plastic Surgeons and the American Academy of Dermatology established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field.

Purpose: To evaluate the effectiveness of a supraciliary approach for upper eyelid margin excisional biopsies., Methods: A retrospective, comparative case series. A 2-year review of medical records of patients who underwent the procedure was performed. Data collected included the dates and type of procedure(s), review of operative and pathology reports, dates of follow up, findings of clinical examination, review of photographs, and postoperative complications. The main outcome measure was to assess both the functional and aesthetic outcomes of the procedure., Results: Six patients with a minimum of 3-month follow-up were included in the study. In each case, eyelid contour and function was preserved, and scarring was nearly unnoticeable. No postoperative complications occurred., Conclusions: The study demonstrates the effectiveness of this surgical approach and as an alternative to more common techniques.

Bacterial infection shortly after mating interferes with establishment of pregnancy. Injection of peptidoglycan-polysaccharide (PG-PS), a component of gram-positive bacteria, into sheep on day 5 after mating reduces pregnancy rate. Experiments were designed to evaluate the acute-phase response (APR) in ewes to injection of PG-PS on day 5 after mating (day 0). Catheters were inserted into the jugular and posterior vena cava on day 4. On day 5, ewes were challenged with saline or 30 microg/kg body weight (BW) PG-PS (Exp 1) or 60 microg/kg BW PG-PS (Exp 2). Blood samples were collected every 15 min for 6 h (Exp 1) and every 15 min for 2 h, hourly for 12 h, and at 24, 36, and 48 h (Exp 2). Body temperature and clinical signs of infection were monitored in Exp 2. Plasma was assayed for concentrations of a pro-inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha); 2 APR proteins, serum amyloid A (SAA) and haptoglobin (Hp); and progesterone (P(4)). Ewes injected with 60 microg/kg BW PG-PS exhibited fever, vaginal discharge, loss of appetite, and lethargy. After challenge with either 30 microg/kg or 60 microg/kg BW PG-PS, TNF-alpha increased in the posterior vena cava. Concentrations of SAA and Hp in the jugular increased after challenge with 60 microg/kg BW PG-PS. Only half (5/10) of the ewes treated with 60 microg/kg BW PG-PS had ultrasonically visible embryos, and none of them had functional corpora lutea (CL) (<1 ng/mL of P(4)) on day 21. On the other hand, 8/9 (88.9%) control ewes had visible embryos and all had functional CL on day 21. Using logistic regression, pregnancy on day 21 was predicted to depend on concentrations of TNF-alpha and Hp on day 5 and concentration of P(4) on day 14. In summary, injection of PG-PS on day 5 after mating resulted in fever; increased concentrations of TNF-alpha, Hp, and SAA on the day of and the day after the PG-PS challenge; and decreased concentrations of P(4) on days 14 and 21. These factors were related to failure to establish pregnancy., (Copyright 2010 Elsevier Inc. All rights reserved.)

The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared with men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular, estrogen. The purpose of this study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mo), middle-aged (14 mo), and old (24 mo) intact, ovariectomized (OVX), and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 +/- 4 vs. old: 34 +/- 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females, and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen replacement improved flow-induced dilation by approximately 160%. The contribution of nitric oxide (NO) to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with N(G)-nitro-l-arginine methyl ester (l-NAME), declined with age. l-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, l-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flow-induced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen, and estrogen supplementation can improve flow-induced dilation, even at an advanced age.

Purpose: To evaluate the use of a chitosan-based hemostatic dressing (CBHD) (ChitoFlex, HemCon Medical Technologies Inc., Portland, OR, U.S.A.) as an effective adjunct for hemostasis in dacryocystorhinostomy surgery and compare its effectiveness to collagen absorbable hemostat (CAH) (Insat, Johnson & Johnson Gateway, New Brunswick, NJ, U.S.A.)., Methods: Retrospective, comparative case series. Thirty-five external or endoscopic dacryocystorhinostomy (DCR) and conjuctival dacryocystorhinostomy (CDCR) procedures were performed on 26 patients using the CBHD from May through October 2007. Thirty-five external or endoscopic DCR or CDCR procedures were performed on 27 patients using CAH from February through May 2007. Collection of patient data in the group treated with CBHD included the types of cases performed, surgical outcome, complications, adverse reactions, and telephone follow-up survey of symptomatic results. Collection of patient data in the group treated with CAH primarily focused on the types of cases performed and postoperative bleeding. The main outcome measures were postoperative bleeding and need for anterior nasal packing., Results: Postoperative bleeding occurred in 2 cases in the group treated with CBHD and in 12 cases in the CAH group., Conclusions: The study demonstrates the effectiveness and safety of CBHD as a hemostatic agent in DCR and CDCR and as a promising alternative to CAH.

Reduced capability of the uterus to support pregnancy in the absence of its interaction with secretions from male accessory glands has been demonstrated in rodents and to some extent in pigs. However, in cattle, the role of postmating inflammatory response on pregnancy success has not been studied. The current study examined the influence of uterine presensitization with seminal antigens at breeding on pregnancy outcome in cows. Lactating beef (n=1090) and dairy (n=800) cows received 0.5 mL seminal plasma (SP), 40 ng recombinant human transforming growth factor-beta1 (rhTGF-beta1), or 0.5 mL bovine serum albumin (BSA), or were left untreated before or at insemination. Semen was deposited into the anterior cervix using a second insemination gun. Pregnancy was diagnosed at 35 to 40 d postinsemination by transrectal ultrasonography or from records of calves born the subsequent calving season. Pregnancy rates in beef cows did not differ among treatments but differed among trials (69.8%, 52.5% vs. 40.3%; P<0.05). In trials where average pregnancy rates were below 50%, treatments with TGF-beta1 but not SP tended (P<0.07) to increase pregnancy rates in beef cows. In dairy cows, SP and TGF-beta1 improved pregnancy outcome by 10 percentage points, but these increments did not achieve statistical significance. In conclusion, this study did not find any conclusive evidence for the effect of TGF-beta1 or seminal plasma on pregnancy outcome in lactating dairy or beef cows but realized marginal improvements when pregnancy rates were below 50% (compromised fertility).

The effect of shifting calf-weaning age on profiles of energy status (BW, BCS, and rib and rump fat) and reproductive performance of beef cows was evaluated in a 3-yr study. Pregnant and lactating crossbred beef cows (n = 408), mainly of Angus and Hereford breeding, were stratified by age and by sex and BW of their calves and assigned randomly into 2 treatments: weaning at approximately 180 d (early weaning) and normal weaning 45 d later (control). Cows were managed together on native range pastures and supplemented with harvested forage during the winter months. Cow BW, BCS, rib fat, and rump fat were measured periodically from early weaning through the next breeding. Reproductive performance was evaluated by calving intervals (CI), days from initiation of breeding to calving (BCI), retention in the herd, and adjusted 205-d weaning BW of the subsequent calf. Early weaned cows had greater (P < 0.001) BW at normal weaning than control cows, but the overall pattern of cow BW did not differ (P > 0.05) among treatments. Peak and nadir BCS occurred at precalving and postcalving periods, respectively and were greater (P < 0.001) at each period in early weaned than in control cows and in cows > or =5-yr-old than in younger cows. Patterns for rib fat and rump fat were nearly identical to those of BCS except for the 3-way interaction (P < 0.001) of treatment, age, and period on rump fat. Mean CI (372.4 +/- 2.1 d) and BCI (299.7 +/- 1.9 d) were not affected (P = 0.42) by treatment but varied (P < 0.001) with age of the cow. Age of cow accounted for 16% of total variation in CI and 12% of total variation in gestation length (P < 0.001). The intervals were longer (P < 0.001) in primiparous cows than in older cows. Early weaning decreased risk of culling in cows and thereby increased (P < 0.05) overall persistence by 11% over control cows. Earlier weaning of cows in the previous year increased (P < 0.001) weaning weight of the subsequent calf by 8.6 kg per cow per yr. Shifting weaning time increased storage of consumed energy as evidenced by increased rump fat, for use later during high-energy demand, ultimately improving overall productivity of the cow-calf system.

Purpose: To report the results of conjunctivodacryocystorhinostomy with primary placement of a frosted Jones Pyrex tube in the treatment of epiphora from upper lacrimal dysfunction., Methods: A retrospective chart review was performed for patients who had undergone conjunctivodacryocystorhinostomy with primary placement of a frosted Jones Pyrex tube performed by a single surgeon (R.A.D.). All patients with at least 6 months of follow-up were included in the study. Efficacy was judged by patient report of resolution of tearing and charts were reviewed for complications., Results: Five conjunctivodacryocystorhinostomy procedures were performed with primary placement of a frosted Jones Pyrex tube. Four of the surgeries were performed for a diagnosis of flaccid canaliculi and one for a congenital upper lacrimal obstruction that had been unsuccessfully treated with previous surgery at another institution. Three of the surgeries were performed with an endoscopic approach and 2 were performed with an external approach. Follow-up ranged from 29 to 34 weeks (mean, 31.2 weeks). All patients reported complete resolution of tearing and no complications were noted, including no evidence of tube migration or extrusion., Conclusions: Primary placement of frosted Jones Pyrex tubes in patients undergoing conjunctivodacryocystorhinostomy seems to retain the efficacy of a standard Jones Pyrex tube while reducing the likelihood of tube extrusion, which is the main complication of this surgery.

Granulosal cells form highly specialized membrane connections with the oocyte and each other, allowing the passage of regulatory molecules and metabolites between cells. Gene expression changes in granulosal cells may adversely affect oocyte competence resulting in early embryonic loss. The present study was conducted to analyze global gene expression profiles in granulosal cells from persistent ovarian follicles in cows. Cows were assigned randomly to two groups: growing follicles on day 8 and persistent follicles on day 15 of the estrous cycle (estrus=day 0). Cows in the persistent follicle group received progesterone from CIDR-B devices on days 4 through 13. Granulosal cells were collected from both growing and persistent follicles and used in a direct comparison microarray experiment using a bovine long oligo array representing approximately 8400 known genes. Analysis of the microarray data revealed up-regulation of 272 genes (M-value>or=0.9) and down-regulation of 203 genes (M-value

Purpose: Müller muscle-conjunctiva resection could be seen as a relative contraindication in patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery. The concern centers around the theoretical risk of bleb-related complications or corneal damage from the palpebral conjunctival sutures. Our study aimed to determine whether any bleb- or cornea-related complications arose in patients who underwent Müller muscle-conjunctiva resection for ptosis correction., Methods: A retrospective chart review was performed on 2 practices of oculofacial plastic surgeons from 2000 to 2006, including patients who had ptosis correction by Müller muscle-conjunctiva resection. Patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery were identified. Each case was reviewed to determine whether any bleb- or cornea-related complications occurred. The postoperative improvement of ptosis measured by interpalpebral distance or margin reflex distance-1 also was noted., Results: Forty-three patients and 55 eyes with a history of a glaucoma filtering procedure (13 patients/15 eyes), corneal disease (1 patient/1 eye), or corneal surgery (29 patients/39 eyes) who underwent Müller muscle-conjunctiva resection were identified. The average follow-up time was 212.4 days. No bleb-related complications occurred. One patient with a history of Reis-Bücklers dystrophy experienced a corneal abrasion. Fifty-two of 55 patients had objective improvement of their ptosis., Conclusions: Müller muscle-conjunctiva resection can provide an effective means for ptosis repair in patients with a prior history of a glaucoma filtering procedure, corneal disease, or corneal surgery. One temporary postoperative corneal complication occurred in our series.

Embryonic and fetal mortality reduce lambing rates and litter sizes, thus contributing to economic losses in the sheep industry. In the current study, the timing of late embryonic and fetal loss in ewes and the factors with which these losses were associated were examined. Ewes lambing and lambs born were compared with pregnancy diagnosis and counts of embryos by ultrasonography near d 25, 45, 65, or 85 of gestation. Approximately 19.9% of the ewes experienced late embryonic loss, fetal loss, or both; and 21.2% of the embryos or fetuses were lost from d 25 to term. Potential offspring were lost throughout gestation; 3.7% of embryos from d 25 to 45, 4.3% of fetuses from d 45 to 65, 3.3% from d 65 to 85, and 11.5% from d 85 to parturition; thus, approximately 3 to 4% of the potential offspring were lost for each 20-d period of pregnancy beyond d 25. A greater proportion of ewes lost one (36.7%) rather than all (20.5% single; 3.8% multiple) embryos or fetuses. The patterns of loss were similar in ewes mated during the anestrous season and the transitional period and did not vary with service period within breeding season or method of synchronization of estrus. Late embryonic or fetal losses were not related to the temperature-humidity index. Maternal serum collected near d 25, 45, 65, or 85 of gestation was assayed for concentrations of progesterone, estradiol-17beta , and vascular endothelial growth factor (VEGF). The proportions of embryos or fetuses lost were associated with breed type (P < 0.05), as were concentrations of progesterone (P < 0.01), estradiol (P < 0.05), and VEGF (P < 0.01). The relationships of loss or retention of pregnancy to hormonal variables at the 4 stages studied were limited. Complete and partial losses increased rapidly as maternal progesterone at d 25 decreased below 2 ng/mL (P < 0.05). Survival of fetuses within a litter from d 25 to 65 was greater for ewes with medium concentrations of VEGF near d 25 and from d 65 to parturition was greater for ewes with high concentrations of VEGF near d 45 (P < 0.05). In summary, late embryonic or fetal losses occurred from d 25 throughout gestation and varied with breed type and with concentrations of progesterone in maternal serum on d 25.

A high incidence of early embryonic loss is associated with prolonged dominance of follicles. The objective of the present experiment was to determine if persistence of a follicle resulted in alterations in mRNA expression of important genes in the oocyte. Cows were assigned to four groups: growing follicles on day 6 (G0h) or day 8 (G48h) and persistent follicles on day 13 (P0h) or day 15 (P48h) of the estrous cycle (estrus = day 0). All cows were super-stimulated on day 1-4. Cows in G48h, P0h, and P48h groups received 25 mg prostaglandin (PG) F2alpha on day 6. Cows in P0h and P48h groups received progesterone from CIDR-B devices on day 5 through 13. Ovaries of cows in G0h, G48h, P0h, and P48h groups were removed on day 6, 8, 13, and 15, respectively. Oocytes were aspirated immediately after colpotomy and denuded of cumulus cells. Quantitative real-time PCR was used to measure the mRNA abundances of 10 selected genes important for early embryogenesis in oocytes obtained from growing and persistent follicles. Relative abundances of MSY2, PARN, and YY1 mRNA (P < 0.05) were significantly lower in oocytes from persistent than from growing follicles. Oocytes from persistent follicles, however, had greater abundances of PAP and eIF-4E transcripts (P < 0.05). The data indicate that persistence of a follicle leads to altered abundances of mRNA for genes important for regulation of transcription and protein translation in the oocyte, which could compromise development of early embryos in cows that ovulate a persistent follicle., ((c) 2006 Wiley-Liss, Inc.)

Initiation of long-term treatment with rbST (Posilac, Monsanto, St. Louis, MO) coincident with first insemination increased pregnancy rates in dairy cattle, but neither the efficacy of using only the initial injection, nor its effects on retention of pregnancy are known. Lactating dairy cows, dairy heifers, and lactating beef cows were assigned at random to treatment (rbST) or control. Dairy cows, dairy heifers, and beef cows received 500 mg rbST (n = 48, 35, 137 inseminations, respectively) at artificial insemination or were left untreated (n = 62, 33, 130 inseminations, respectively). Pregnancy was diagnosed by ultrasonography at 28-36 days. Treatment with rbST at insemination improved conception rates in dairy cows (60.4% versus 40.3%; P < 0.05), but not in dairy heifers or beef cows. Conception rates did not differ in dairy cows at < or =100 days in milk (DIM), but were improved in cows treated with rbST after 100 DIM (64.3% versus 25.8%; P < 0.05). Retention of pregnancy to approximately 60 days and sizes of CL, diameter of follicles > or =5 mm, and crown-rump lengths of embryos were not affected by treatment. The second objective was to examine the effects of rbST at insemination on birth weight and post-natal calf growth in beef cows. However, birth and weaning weights of beef calves were not affected by treatment. In conclusion, a single treatment with rbST at insemination increased conception rates in dairy cows, specifically in those >100 DIM.

Purpose: To describe the use of a new, frosted Jones Pyrex tube in the treatment of obstructed canaliculi of the upper lacrimal system. The frosted Jones tube retains the advantages of the traditional smooth Pyrex tube yet appears to improve the positional stability in the surgically created fistula., Methods: Ten patients of a single surgeon who had previously undergone external conjunctivodacryocystorhinostomy and placement of a Jones Pyrex tube, with subsequent Pyrex tube extrusion, were included in the study. All had previous success with Pyrex tubes, with follow-up ranging from 1 month to 14 years. In each case, when the patient presented with an extruded tube, it was replaced with a frosted Jones tube (Weiss Scientific Glass Blowing Company, Portland, OR, U.S.A.)., Results: In this preliminary study, none of the 10 patients fitted with a frosted Jones Pyrex tube had a recurrence of extrusion. All patients reported proper functioning of the tubes, with no complaints of epiphora or discomfort., Conclusions: Compared with a standard Jones Pyrex tube, a frosted tube functions equally well and reduces the possibility of extrusion, which is the main complication of traditional conjunctivodacryocystorhinostomy. We have exchanged smooth tubes for frosted tubes in patients who have had extrusion of the original tube, and we are currently investigating primary placement of the frosted Jones Pyrex tube.

The apocrine hidrocystoma is a benign adenomatous cystic proliferation derived from apocrine glands, which frequently occurs in periocular tissues. These cystadenomas may occur bilaterally, in multiple disfiguring confluent groups on both the upper and lower lids. Although these lesions have been treated successfully with meticulous surgical extirpation and electrosurgery, this report describes the successful treatment of two patients, each with multiple large (>7 mm) periocular apocrine hidrocystomas by either chemical ablation of the cystic epithelium with trichloroacetic acid (TCA) or surgical excision. Examination of the cysts at 1, 3, and 6 months after TCA treatment revealed well-healed lesions without cyst recurrence. Most of the TCA-treated cysts resolved completely, without leaving any trace to clinical examination. Treatment of cysts with TCA was technically simpler and much less time-consuming than surgical excision. The treatment of large apocrine hidrocystomas with TCA is an effective and expeditious method of treating these disfiguring and recalcitrant lesions.

Purpose: To compare characteristics and outcomes of strabismus surgery in patients who have undergone orbital decompression for thyroid eye disease with those who have not., Subjects and Methods: A chart review of all patients with thyroid eye disease requiring strabismus surgery in one physician's practice., Results: There were 36 patients in the decompression group (DG) and 14 patients in the no-decompression group (NDG). There was a significantly greater amount of preoperative esotropia in the DG ( P = 0.02). There was an increased incidence of A-pattern in the DG ( P = 0.09). There was a slightly higher number of operated muscles in the DG ( P = 0.005). A good or excellent outcome was achieved in 93% of the NDG and in 94% of the DG ( P = 0.83)., Discussion: Previous studies suggest that patients requiring orbital decompression have a more complex thyroid eye disease and a lower success rate after strabismus surgery. Our findings suggest that this is not necessarily the case, and the difference in surgical success rates between the studies may in part be due to orbital decompression technique or indication., Conclusion: In this series, using a fixed suture technique, outcomes of strabismus surgery in patients with thyroid eye disease who underwent orbital decompression are similar to those who did not.

Purpose: To present the clinical outcome in 55 consecutive patients by using a customized, single-incision, 3-wall orbital decompression., Methods: A retrospective chart review was performed of 97 customized, single-incision, 3-wall decompressions in 55 consecutive patients within one surgeon's practice. A standardized surgical technique featuring lateral small-incision, 3-wall decompression with specific "strut" preservation was used in all patients. Success of the procedure was assessed on the basis of the amount of proptosis reduction achieved, as measured by the difference in Hertel exophthalmometry measurements, and by improvement in or preservation of preoperative visual acuity and color vision in the setting of compressive optic neuropathy. Subjective diplopia was recorded before and after surgery, as was the presence of extraocular muscle restriction., Results: A total of 97 orbital decompressions in 55 consecutive patients were reviewed. The majority of surgeries were performed for disfiguring proptosis with some degree of exposure-related symptoms (81%), with other indications including compressive optic neuropathy (17%), and pain (2%). The average amount of proptosis reduction achieved at 3 months was 5 mm (range, 1 to 11 mm). Visual acuity in patients with compressive optic neuropathy improved an average of 2 lines on the standard Snellen chart testing (range, 1 to 5). Color vision improved an average of 5 Ishihara plates (range, 0 to 13). Seventy-one percent of patients had subjective diplopia before surgery; 21% of these patients reported improvement or complete resolution of diplopia after surgery. Of the 29% of patients without preoperative subjective diplopia, all but one (1.8 of total patients) remained symptom free., Conclusions: We find that a customized, single-incision, 3-wall orbital decompression provides adequate decompression and proptosis reduction while minimizing postoperative strabismus and providing an aesthetically desirable result.

Problem: Spontaneous mastitis or induced infections mimicking mastitis reduce pregnancy rates in ruminants. The effect of immunization with either a mastitis-related pathogen component, peptidoglycan-polysaccharide (PG-PS), or killed Streptococcus pyogenes on pregnancy outcome was investigated., Method of Study: Ewe lambs were immunized with PG-PS (n = 50) or killed bacteria (n = 50) or were not immunized (control, n = 100). Titers of PG-PS immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA). Ewes were bred by rams at synchronized estrus. All immunized ewes and half of the ewes not immunized were challenged with PG-PS on day 5 after breeding. Pregnancy maintenance was evaluated., Results: Although the proportion of ewes pregnant at day 42 after breeding did not differ among treatments, the probability of pregnancy decreased with total dose of PG-PS (P < 0.05)., Conclusions: Immunization of ewe lambs with PG-PS or killed S. pyogenes did not improve pregnancy maintenance. Furthermore, the toxic streptococcal component decreased pregnancy rate in immunized sheep in a dose-dependent manner.

Potential factors affecting retention of pregnancy during weeks 5-9 of gestation were studied in dairy cows and heifers (N = 211) on two farms. Cows were examined by ultrasonography for presence of a viable embryo, and sizes of the corpus luteum (CL) and of follicles > or = 5mm were recorded. Blood samples were taken at each examination and assayed for progesterone and estradiol. Overall pregnancy loss was 11.4%. Cows with two CL did not have greater concentrations of progesterone than cows with one CL and they retained fewer pregnancies (P < 0.01; 73% versus 91%). Pregnancy retention was associated positively with concentrations of progesterone and estradiol during week 5 (P < 0.05). Embryos that were lost apparently died before CL regression. Retention of pregnancy declined in cows with high body condition and as age of the cow increased. Pregnancy retention was lower in cows bred to one of four frequently-used service sires (P < 0.05). Days postpartum, milk production, parity, service number, inseminator, synchronization of estrus, diameter of follicles and size of CL did not affect pregnancy retention. In conclusion, retention of pregnancy during placentation varied with concentrations of progesterone and estradiol, age of cow, body condition and service sire.

Purpose: To present an alternative technique for rejuvenating the upper face of patients with high hairlines., Methods: A chart review was performed to ascertain the longevity and aesthetic quality of endoscopically assisted pretrichial brow lifts. The charts of a single surgeon were reviewed (2000 to 2003). The technique was noted to be consistent, and in the majority of cases, additive to other concurrent procedures. Morbidity was defined as asymmetry, poor longevity, and patient dissatisfaction. All patients were included who had the procedure performed. No exclusions were recognized for race, age, gender, medical history, or any other patient demographic., Results: Results for the clinical outcome were graded as excellent, good, fair, or poor. Subjective and objective assessments were made by using history, examination, and photos. A rating of excellent incorporates symmetry, longevity, smoothness of the brow skin, and patient satisfaction both with the recovery process and with the results., Conclusions: In properly selected cosmetic patients, the endoscopic pretrichial brow lift is an effective method for rejuvenating the upper face. A more youthful appearance is achieved with the procedure, and it is easily combined with eyelid rejuvenation. We believe that this technique is the procedure of choice for addressing brow ptosis in patients with high hairlines.

Purpose: To introduce an alternative surgical technique for gold weight implantation for the treatment of lagophthalmos. We suggest that unwrapped intraorbital gold weight implantation provides adequate function, better cosmetic appearance, and lower morbidity than conventional implantation with wrapped or unwrapped pretarsal gold weights., Methods: The charts of a single surgeon were reviewed (1994 to 2003). All patients who underwent intraorbital gold weight implantation were included in the study. The technique was noted to be consistent with intraorbital fixation of a custom 2.2-gm gold weight (MedDev Corporation, Sunnyvale, California). Implants were not wrapped. Efficacy was defined as elimination of exposure keratopathy with preservation of the visual axis. Morbidity was defined as extrusion of the weight, shift of positioning requiring intervention, inflammation/infection of the eyelid, or poor cosmetic appearance., Results: Of 59 patient charts reviewed, 2 patients had morbidity as defined by our study: One had shifting of the gold weight, necessitating repositioning of the weight; the other had extrusion of the gold weight, requiring its removal. The remaining patients had no complaints or cosmetic concerns. Follow-up examinations found no incidence of exposure keratopathy., Conclusions: We found intraorbital gold weight implantation, without the use of a wrap, to be simple and effective, with adequate function, an acceptably low postoperative morbidity rate, and an excellent cosmetic outcome.