Management of thyroid eye disease in the United Kingdom: A multi-centre thyroid eye disease audit.

This article aims to provide baseline data and highlight any major deficiencies in the current level of care provided for adult patients with thyroid eye disease (TED). We undertook a prospective, nonrandomized cross-sectional multicenter observational study. During a 3-month period June-August 2014, consecutive adult patients with TED who presented to nominated specialist eye clinics in the United Kingdom, completed a standardized questionnaire. Main outcome measures were: demographics, time from diagnosis to referral to tertiary centre, time from referral to review in specialist eye clinic, management of thyroid dysfunction, radioiodine and provision of steroid prophylaxis, smoking, and TED classification. 91 patients (mean age 47.88 years) were included. Female-to-male ratio was 6:1. Mean time since first symptoms of TED = 27.92 (73.71) months; from first visit to any doctor with symptoms to diagnosis = 9.37 (26.03) months; from hyperthyroidism diagnosis to euthyroidism 12.45 (16.81) months. First, 13% had received radioiodine. All those with active TED received prophylactic steroids. Seven patients who received radioiodine and did not have TED at the time went on to develop it. Then, 60% patients were current or ex-smokers. 63% current smokers had been offered smoking cessation advice. 65% patients had active TED; 4% had sight-threatening TED. A large proportion of patients (54%) were unaware of their thyroid status. Not enough patients are being provided with smoking cessation advice and information on the impact of smoking on TED and control of thyroid function.

Different bone loading patterns due to fixation of three-unit and five-unit implant prostheses.

BACKGROUND: It has been considered that implant prostheses ought to display passive fit. The objective of this finite element analysis (FEA) was to simulate the bone loading resulting from the fixation of implant-supported three and five-unit fixed partial dentures (FPDs). METHODS: Based on a patient case, six different FPD-groups were fabricated using either two or three implants for support. Strain gauges on the pontics of the prostheses were used for in vivo measurements. Based on the values obtained, bone loading models were simulated using three-dimensional finite element analysis and the results obtained were represented as von Mises equivalent stress. RESULTS: The mean strain (epsilon) values ranged from 15 micro epsilon to 170 micro epsilon for the three-unit FPDs and from 32 micro epsilon to 302 micro epsilon for the five-unit FPDs. FEA revealed von Mises stresses up to 30 MPa in the cortical area, while in trabecular bone values up to 5 MPa were observed. Static implant loading of similar magnitude can be provoked through 200 N axial load. CONCLUSIONS: Although the in vivo measured strain levels (epsilon) were of higher magnitude for the five-unit prostheses, FEA revealed bone loading of comparable magnitude for both three- and five-unit FPDs. Multi-unit prostheses may demonstrate greater inaccuracies compared with single implant restorations, but due to the absence of moment loading the multi-implant configuration appears to compensate for the higher strain development.

A questionnaire survey on the management of Graves' orbitopathy in Europe.

OBJECTIVE: To determine management patterns among clinicians who treat patients with Graves' orbitopathy (GO) in Europe. DESIGN AND METHODS: Questionnaire survey including a case scenario of members of professional organisations representing endocrinologists, ophthalmologists and nuclear medicine physicians. RESULTS: A multidisciplinary approach to manage GO was valued by 96.3% of responders, although 31.5% did not participate or refer to a multidisciplinary team and 21.5% of patients with GO treated by responders were not managed in a multidisciplinary setting. Access to surgery for sight-threatening GO was available only within weeks or months according to 59.5% of responders. Reluctance to refer urgently to an ophthalmologist was noted by 32.7% of responders despite the presence of suspected optic neuropathy. The use of steroids was not influenced by the age of the patient, but fewer responders chose to use steroids in a diabetic patient (72.1 vs 90.5%, P<0.001). Development of cushingoid features resulted in a reduction in steroid use (90.5 vs 36.5%, P<0.001) and increase in the use of orbital irradiation (from 23.8% to 40.4%, P<0.05) and surgical decompression (from 20.9 to 52.9%, P<0.001). More ophthalmologists chose surgical decompression for patients with threatened vision due to optic neuropathy, who were intolerant to steroids than other specialists (70.3 vs 41.8%, P<0.01). CONCLUSION: Deficiencies in the management of patients with GO in Europe were identified by this survey. Further training of clinicians, easier access of patients to specialist multidisciplinary centres and the publication of practice guidelines may help improve the management of this condition in Europe.

The use of a dental implant as an abutment in three unit implant-tooth supported fixed partial denture: a case report and 32 month follow-up.

The combined use of dental implants and teeth as abutments in fixed partial dentures may offer advantages to both patients and practitioners in certain clinical situations. An implant-tooth retained prosthesis may reduce surgical intervention and cost to the patient. It may also mean that anatomical restrictions to the provision of an implant-retained fixed prosthesis may be overcome. In this case report, the steps in provision of a three unit implant-to-tooth fixed partial denture are described and the treatment planning and prognosis of a restoration of this type are discussed.

Expression of the angiogenic factor thymidine phosphorylase/platelet-derived endothelial cell growth factor in primary bladder cancers.

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in bladder cancer angiogenesis. To examine its role more clearly, we have quantified and localized its expression using Western analysis and immunohistochemistry in a series of 105 bladder cancers. We have also assessed the relationship between TP expression and other tumor parameters including quantitative angiogenesis, p53 status, ploidy, and survival. By Western analysis, TP expression was 5-fold higher in tumors than in normal bladder samples (P < 0.02). Expression was 15-fold higher in invasive tumors than in normal bladder (P < 0.001) and 8-fold higher than in superficial tumors (P < 0.005). Immunohistochemistry of the tumors showed TP was present in the neoplastic epithelium in 27% of the tumors, in the inflammatory cells in 72% of the tumors, in stromal cells in 30% of the tumors, and in tumor-associated endothelium in 11% of the tumors. Expression by Western blotting and immunohistochemistry was significantly up-regulated in tumors compared with normal bladder (P < 0.05). Tumor cell TP expression correlated with tumor grade (P < 0.02), but there was no correlation between tumor cell TP expression and tumor stage (P = 0.46), ploidy (P = 0.52), p53 expression (P = 0.9), tumor vascularity (P = 0.8), relapse-free survival (P = 0.57), or overall survival (P = 0.94). TP protein is expressed in bladder cancers, and expression is associated with an aggressive phenotype. Because TP can activate a number of cytotoxic agents, it provides a potential therapeutic target in bladder cancer.

A 10-year review of orbital biopsy: the Newcastle Eye Centre Study.

PURPOSE: To review the histopathological diagnoses, visual outcome, and complication rate of orbital biopsy in a UK tertiary referral centre. METHODS: This was a retrospective, clinical-pathological, interventional, consecutive case series. All orbital biopsies performed between July 2004 and June 2014 in Newcastle Eye Centre (Newcastle upon Tyne, UK) were included in this study. All relevant data collected from the local electronic database and medical records were analysed. RESULTS: A total of 166 orbital biopsies were identified during the study period: 86 patients (53.1%) were female and the mean age was 53.7 ± 19.7 years. Of all the cases, orbital biopsies were performed unilaterally in 158 (97.5%) patients and bilaterally in 4 (2.5%) patients. The mean follow-up period was 2.2 ± 2.3 years. The two most common histopathological diagnoses were non-specific inflammatory disease (62, 38.3%) and lymphoproliferative disease (40, 24.7%). None of the patients experienced ≥ 2-Snellen line visual loss. There were 7 (4.2%) postoperative complications noted: 1 (0.6%) orbital haemorrhage with no loss of vision, 4 (2.4%) diplopia, 1 (0.6%) short-term symblepharon, and 1 (0.6%) conjunctival granuloma. Postoperative diplopia was associated with lateral orbitotomy (P = 0.044) and excisional biopsy (P = 0.015). CONCLUSIONS: Orbital biopsy serves as a safe diagnostic tool in managing orbital diseases. Patient should be made aware of the risk of postoperative diplopia. Our data provides useful guidance to clinicians when counselling patients for orbital biopsy.

The procarcinogen hypothesis for bladder cancer: activities of individual drug metabolizing enzymes as risk factors.

Bladder cancer provides the most definitive example for an association between environmental agents and cancer. However, in the absence of industrial occupational exposure, the primary carcinogen is rarely identified, and the mechanisms involved in cancer formation are poorly understood. The environmental procarcinogen hypothesis of tumour pathogenesis proposes that many carcinogens require metabolic activation by drug metabolizing enzymes to form the proximate carcinogen. A balance of exposure to the carcinogen, the activity of the enzymes involved in either formation of proximate carcinogen, or production of non-toxic metabolites, will determine tumour risk. We have used mephenytoin, debrisoquine and dapsone as selective probes for the phenotypic measures of activity of CYP2C19, CYP2D6, and CYP3A4, respectively. Within subject reproducibility of phenotypic measures, and the lack of cross-inhibition when the three drugs are given in a concurrent cocktail, have been confirmed. We have applied the cocktail drug approach in two, non-overlapping series of cases with bladder cancer and matched controls. In both series, patients with aggressive bladder cancer (GIII histopathology) had a history of excess alcohol intake, an under-representation of poor metabolizers of debrisoquine, a significant mean reduction in dapsone recovery ratio, but no difference in mephenytoin phenotype. Collectively, these observations involving multiple routes of drug metabolism support the procarcinogen environmental hypothesis for bladder cancer and suggest that measurement of activity of selected individual drug metabolizing enzymes involved in the pathogenesis of this tumour can be used to identify subjects at high risk of developing bladder cancer.

Inflammation of the retinal pigment epithelium: a unique presentation of ocular schistosomiasis.

We report the first case of inflammation of the retinal pigment epithelium (RPE) caused by Schistosoma mansoni and discuss its possible pathogenesis. This is of particular interest because the lesions resembled those found in acute multifocal placoid pigment epitheliopathy (AMPPE).

The use of porous polyethylene (Medpor) lower eyelid spacers in lid heightening and stabilisation.

BACKGROUND/AIMS: The management of lower eyelid retraction can be challenging, and established techniques to correct it are not always successful. Previous reports have suggested a role for the ultrathin high density porous polyethylene lower eyelid spacer (Medpor LES) in such patients. The authors report the experience of three surgeons implanting Medpor LES over 1 year, and ascertain whether such implants are a safe and effective alternative to autogenous spacers. METHODS: A prospective, interventional, non-comparative case series of consecutive patients. Surgical indications for Medpor LES were noted. Preoperative and postoperative lower marginal reflex distance (L-MRD), vertical palpebral aperture (PA), lagophthalmos, and scleral show inferior to the limbus (LSS) were recorded, together with major and minor complications. RESULTS: 32 patients (35 eyelids) had a Medpor LES inserted, 22/32 under local anaesthetic, and nine with adjunctive procedures. Mean follow up was 22 months (range 15-28 months). The Medpor LES was effective in reducing the palpebral aperture (p<0.001) and lagophthalmos (p = 0.04) and raising the lower eyelid height by reducing both L-MRD (p = 0.006) and LSS (p<0.001). However there were major complications in 7/32 patients and minor complications in 8/32, most requiring further surgery. Final outcome was good in 24/35 eyelids and satisfactory in 5/35. CONCLUSIONS: Despite a good or satisfactory final outcome in the majority of patients, the value of this technique is limited by complications, and should be reserved for those unsuitable for safer techniques.

The Wisconsin Age-related Macular Degeneration grading system: performance in an independent centre.

INTRODUCTION: Age-related Macular Degeneration (AMD) is the commonest cause of blindness in developed nations. Despite this, the epidemiology of AMD is poorly understood. A need for the documentation of AMD prevalence and incidence at a population level has stimulated the development of a comprehensive, observer-based, photographic grading method for AMD in Wisconsin. AIM: To independently assess the performance of the Wisconsin method by self-taught graders outside its centre of inception. METHOD: The inter-observer variability and confidence limits for detection of change were assessed for two self-taught graders (ophthalmologists). Self teaching was achieved exclusively from documentation and photographs provided by the system developers in Wisconsin. 295 retinal photographs of elderly people were independently assessed for 13 features by each of the two graders. RESULTS: Weighted and unweighted kappa statistics, % exact and one step apart agreement, and confidence limits for detection of change were calculated for the graded features on a "by eye' basis, and where appropriate, on a "by retinal subfield' basis. Levels of agreement for weighted kappa were moderate to substantial for most features. 95% and 90% confidence limits for significant change beyond measurement error were determined in terms of scale increments. CONCLUSION: We conclude that the Wisconsin AMD grading system can be independently learnt from documentation and photographs alone, and that an acceptable level of performance is attainable by self-taught graders.

Development of embryonic cells containing serotonin, catecholamines, and FMRFamide-related peptides in Aplysia californica.

This study demonstrates the presence of a relatively extensive but previously unrecognized nervous system in embryonic stages of the opisthobranch mollusc Aplysia californica. During the trochophore stage, two pairs of cells were observed to be reactive to antibodies raised against the neuropeptides FMRFamide and EFLRIamide. These cells were located in the posterior region of the embryo, and their anterior projections terminated under the apical tuft. As the embryos developed into veliger stages, serotonin-like immunoreactive (LIR) cells appeared in the apical organ and were later observed to innervate the velum. Also, aldehyde-induced fluorescence indicative of catecholamines was present in cells in the foot, oral, and possibly apical regions during late embryonic veliger stages. Just before the embryo hatches as a free-swimming veliger, additional FMRFamide-LIR and catecholamine-containing cells appeared in regions that correspond to the ganglia of what will become the adult central nervous system (CNS). Neurons and connectives that will contribute to the adult CNS appear to develop along the pathways that are pioneered by the earliest posterior FMRFamide-LIR cells. These observations are consistent with the hypothesis that, besides their presumed roles in the control of embryonic behaviors, some elements may also guide the development of the CNS. Embryonic nervous systems that develop prior to and outside of the adult CNS have also been reported in pulmonate and prosobranch species of molluscs. Therefore, the demonstration of early developing neurons and their transmitter phenotypes in A. californica presents new opportunities for a better understanding of the ontogeny and phylogeny of both behavioral and neuronal function in this important model species.

Examination and diagnosis of common craniomandibular disorders.

The disorders of the craniomandibular complex are often a combination of disorders of the temporomandibular joint itself as well as the orofacial and neck muscular. A definitive diagnosis and subsequent treatment plan can only be reached by gaining sufficient information to allow a decision as to which components of the craniomandibular complex, and to what extent, are contributing to the patients problem. A systematic approach to an examination procedure commencing with a simple screening evaluation is discussed, which, when followed, will allow a differential diagnosis.

Orbital decompression for Graves' orbitopathy in England.

AIMS: The purpose of this study was to obtain data on orbital decompression procedures performed in England, classed by hospital and locality, to evaluate regional variation in care. METHODS: Data on orbital decompression taking place in England over a 2-year period between 2007 and 2009 were derived from CHKS Ltd and analysed by the hospital and primary care trust. RESULTS AND CONCLUSIONS: In all, 44% of these operations took place in hospitals with an annual workload of 10 or fewer procedures. Analysis of the same data by primary care trust suggests an almost 30-fold variance in the rates of decompression performed per unit population. Expertise available to patients with Graves' orbitopathy and rates of referral for specialist care in England appears to vary significantly by geographic location. These data, along with other outcome measures, will provide a baseline by which progress can be judged.

Periocular basal cell carcinoma: 5-year outcome following Slow Mohs surgery with formalin-fixed paraffin-embedded sections and delayed closure.

AIM: The aim of the study was to determine the 5-year outcome of periocular basal cell carcinoma (BCC) managed by Mohs surgery using formalin-fixed, paraffin-embedded sections (Slow Mohs). METHODS: This was a prospective, non-comparative, interventional case series of all patients with periocular BCC treated by Slow Mohs in Newcastle upon Tyne, UK, between 1985 and 1999. Data collected included demographic information, indication for Slow Mohs, tumour site, histology, recurrence rate after 5 years and cosmetic outcome. RESULTS: Of 287 BCCs in 278 patients, 5-year follow-up data were available for 173 (60.2%). Recurrence following Slow Mohs occurred in one patient: 0.34% of total and 0.58% of those with 5-year follow-up. The main indication for Slow Mohs was most frequently due to the tumour site. Cosmetic outcome was deemed excellent in 56%, good in 18%, adequate in 8%, unknown in 14% and revision advised in only 4%. CONCLUSION: The low 5-year recurrence rate (0.58%) reported in this prospective series confirms the importance of margin-controlled removal of recurrent, poorly defined or critically sited BCCs, and illustrates that Slow Mohs is equivalent to standard Mohs. While delayed closure does not appear to compromise cosmetic outcome, this technique offers a histologically superior and cheaper alternative to frozen-section Mohs surgery.

Outcome of orbital decompression for disfiguring proptosis in patients with Graves' orbitopathy using various surgical procedures.

AIM: To compare the outcome of various surgical approaches of orbital decompression in patients with Graves' orbitopathy (GO) receiving surgery for disfiguring proptosis. METHOD: Data forms and questionnaires from consecutive, euthyroid patients with inactive GO who had undergone orbital decompression for disfiguring proptosis in 11 European centres were analysed. RESULTS: Eighteen different (combinations of) approaches were used, the swinging eyelid approach being the most popular followed by the coronal and transconjunctival approaches. The average proptosis reduction for all decompressions was 5.0 (SD 2.1) mm. After three-wall decompression the proptosis reduction was significantly greater than after two-wall decompression. Additional fat removal resulted in greater proptosis reduction. Complications were rare, the most frequent being worsening of motility, occurring more frequently after coronal decompression. The average change in quality of life (QOL) in the appearance arm of the GO-QOL questionnaire was 20.5 (SD 24.8) points. CONCLUSIONS: In Europe, a wide range of surgical approaches is used to reduce disfiguring proptosis in patients with GO. The extent of proptosis reduction depends on the number of walls removed and whether or not fat is removed. Serious complications are infrequent. Worsening of ocular motility is still a major complication, but was rare in this series after the swinging eyelid approach.

Orbital lymphatics: do they exist?

INTRODUCTION: Although the lymphatic system was first described almost 400 years ago, it is only in very recent years that researchers have been able to identify lymphatic channels with reasonable accuracy. Through advances in molecular biology and the development of endothelial cell markers the long held view that the human orbit is devoid of lymphatics has now been challenged. DISCUSSION: This review discusses the current evidence on this topic, which confirms the presence of orbital lymphatics in lachrymal gland and optic nerve sheath.

Controversies in the clinical evaluation of active thyroid-associated orbitopathy: use of a detailed protocol with comparative photographs for objective assessment.

Despite many learned publications over recent decades, the assessment of active thyroid-associated orbitopathy (TAO) remains difficult and controversial. There are no biochemical, immunological or imaging investigations which can identify active disease reliably, and clinical assessment is still of paramount importance. We therefore review the strengths and weaknesses of all methods of clinical assessment. A new atlas for clinical assessment of soft tissue signs has been developed, and its reproducibility assessed. It details a suggested protocol that could help standardize descriptions of TAO and allow more objective assessment of its activity and severity. This is relevant to general endocrinologists, who have a crucial role in the identification of patients who require ophthalmological assessment. Certain aspects are more relevant to ophthalmologists and endocrinologists who have a special clinical and research interest in TAO. Unless a reproducible system of assessment is devised and widely adopted, it will remain difficult to interpret research meaningfully, particularly if results appear to contradict.