Pre- and Postoperative Quantitative Analysis of Contour Abnormalities in Graves Upper Eyelid Retraction

Purpose: One of the most common problems of the surgical management of Graves upper eyelid retraction is the occurrence of eyelid contour abnormalities. In the present study, the postoperative contour of a large sample of eyelids of patients with Graves orbitopathy was measured. Methods: The postoperative upper eyelid contour of 62 eyes of 43 patients with Graves orbitopathy was subjectively classified by 3 experienced surgeons in 3 categories: poor, fair, and good. The shape of the eyelid contours in each category was then measured with a recently developed custom-made software by measuring multiple midpupil eyelid distances each 15 degrees along the palpebral fissure. The upper eyelid contour of 60 normal subjects was also quantified as a control group. Results: The mean ratio between the sum of the lateral and medial midpupil eyelid distances (lateral/medial ratio) was 1.10 +/- 0.11 standard deviation in controls and 1.15 +/- 0.13 standard deviation in patients. Postoperatively, the mean midpupil eyelid distance at 90 degrees was 4.16 +/- 1.13 mm standard deviation. The distribution lateral/medial ratios of the eyelids judged as having good contours was similar to the distribution of the controls with a modal value centered on the interval between 1.0 and 1.10. The distribution of lateral/medial ratios of the eyelids judged as having poor contour was bimodal, with eyelids with low and high lateral/medial ratios. Low lateral/medial ratios occurred when there was a lateral overcorrection, giving the eyelid a flat or a medial ptosis appearance. High lateral/medial ratios were due to a central or medial overcorrection or a lateral peak maintenance. Conclusions: Postoperative upper eyelid contour abnormalities can be quantified by comparing the sum of multiple midpupil eyelid distances of the lateral and medial sectors of the eyelid. Low and high lateral/medial ratios are anomalous and judged as unpleasant. (Ophthal Plast Reconstr Surg 2012;28:429-433)

Orbital Abscess during Endodontic Treatment: A Case Report

Introduction: Orbital infections may result in permanent morbidity because of the severity of infection. Furthermore, delayed diagnosis or treatment of orbital infections can lead to intracranial complications and even death. The majority of orbital infections develop from paranasal sinus infections, cutaneous infections, and periorbital trauma. Dacryocystitis and odontogenic infection are also accounted as potential etiologies but are scarcely reported in scientific literature. Methods: The patient revealed a history of having endodontic treatment on left maxillary second molar performed 2 weeks previously. Moreover, she exhibited signs of facial pain accompanied by sinusitis symptoms, fever, and nasal obstruction the week after this endodontic procedure. The patient presented proptosis, impairment of ocular motility to the right side, facial tenderness, palpebral erythema, and referred decreased visual acuity. Intraoral exam revealed root fragments of left maxillary first molar and an extensive carious lesion on left maxillary second molar. Computed tomography enabled the observation of frontal sinus, left-sided maxillary, opacity of sphenoidal and ethmoidal sinuses, and apical lesion of left maxillary first and second molars, all suggesting the presence of their apex in the maxillary sinus. In addition, images revealed ocular proptosis and presence of high-density areas suggestive of pus in the medial orbital wall region. Results: The patient was submitted to surgical drainage under general anesthesia approximately 8 hours after the clinical evaluation. Conclusions: Early detection of orbital infection, proper diagnostic tests, and treatment may provide successful outcomes of this rarely occurring disease. (J Endod 2012;38:1541-1543)

Efeitos de detomidina e xilazina intravenosa sobre as variáveis basais e respostas comportamentais em bovinos

Avaliaram-se, durante 60 minutos, 10 bovinos após administração intravenosa de 0,1mg.kg-1 de xilazina ou 10μg.kg-1 de detomidina, quanto às frequências cardíaca e respiratória, movimentos ruminais, pressão arterial média, temperatura retal e respostas comportamentais como ataxia ou decúbito, ptose palpebral, estado de alerta ou sedação e redução da altura da cabeça em relação ao solo, além da presença de salivação, micção e concentração sanguínea de glicose. Observou-se que a xilazina, via intravenosa, em bovinos, ao mesmo tempo que promove sedação mais intensa e prolongada que a detomidina, induz a uma maior quantidade de efeitos indesejáveis, como salivação e decúbito, e redução das frequências cardíaca e respiratória, da pressão arterial média, da motilidade ruminal e da temperatura, sendo estas alterações mais prolongadas. Conclui-se que a detomidina pode ser utilizada com segurança em bovinos na dose de 10μg.kg-1, promovendo sedação e permanência do animal em posição quadrupedal.

Multiple Radial Midpupil Lid Distances: A Simple Method for Lid Contour Analysis

Purpose: To describe a new computerized method for the analysis of lid contour based on the measurement of multiple radial midpupil lid distances. Design: Evaluation of diagnostic technology. Participants and Controls: Monocular palpebral fissure images of 35 patients with Graves' upper eyelid retraction and of 30 normal subjects. Methods: Custom software was used to measure the conventional midpupil upper lid distance (MPLD) and 12 oblique MPLDs on each 15 degrees across the temporal (105 degrees, 120 degrees, 135 degrees, 150 degrees, 165 degrees, and 180 degrees) and nasal (75 degrees, 60 degrees, 45 degrees, 30 degrees, 15 degrees, and 0 degrees) sectors of the lid fissure. Main Outcome Measures: Mean, standard deviation, 5th and 95th percentiles of the oblique MPLDs obtained for patients and controls. Temporal/nasal MPLD ratios of the same angles with respect to the midline. Results: The MPLDs increased from the vertical midline in both nasal and temporal sectors of the fissure. In the control group the differences between the mean central MPLD (90 degrees) and those up to 30 degrees in the nasal (75 degrees and 60 degrees) and temporal sectors (105 degrees and 120 degrees) were not significant. For greater eccentricities, all temporal and nasal mean MPLDs increased significantly. When the MPLDs of the same angles were compared between groups, the mean values of the Graves' patients differed from control at all angles (F = 4192; P<0.0001). The greatest temporal/nasal asymmetry occurred 60 degrees from the vertical midline. Conclusions: The measurement of radial MPLD is a simple and effective way to characterize lid contour abnormalities. In patients with Graves' upper eyelid retraction, the method demonstrated that the maximum amplitude of the lateral lid flare sign occurred at 60 degrees from the vertical midline. Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article. Ophthalmology 2012; 119: 625-628 (C) 2012 by the American Academy of Ophthalmology.

Nevo de células fusiformes de Reed na conjuntiva

Os autores relatam um caso de nevo de Reed, lesão que apresenta aspecto histológico de malignidade, mas tem evolução benigna. Paciente de 48 anos, masculino, cor parda, apresentava pterígio nasal no olho direito, associado a uma lesão pequena e pouco pigmentada localizada na cabeça do mesmo. Realizou-se exérese de ambos, sem intercorrências, sem sinais de recidiva. O exame histopatológico revelou lesão com bordas definidas, restrita ao epitélio, constituída por células fusiformes perpendiculares à superfície, com pigmentação melânica esparsa. O diagnóstico inicial foi nevo de Spitz, mas, posteriormente, chegou-se à conclusão que se tratava do nevo de células fusiformes de Reed. O presente relato é o segundo na literatura mundial e o primeiro no Brasil.

Discovery and Pharmacological Characterization of a Novel Small Molecule Antagonist of Integrin α4β1: Focus on Antiallergic Activity

Allergy is a common hypersensitivity disorder that affects 15% to 20% of the population and its prevalence is increasing worldwide. Its severity correlates with the degree of eosinophil infiltration into the conjunctiva, which is mediated by chemokines that stimulate the production of adhesion molecules like intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell surface. The α4β1 and α4β7 integrins are expressed in eosinophils and contribute to their activation and infiltration in AC through the binding to VCAM-1 or fibronectin, expressed on vascular endothelial cells. Blockade of α4 integrins might be a therapeutical achievement in allergic eye diseases. DS 70, that show an IC50 in the nanomolar range against α4β1 integrin in Jurkat cells and in the eosinophilic cell line EOL-1. This compound was able to prevent cell adhesion to VCAM-1 and FN in vitro. In a scintillation proximity assay DS70 displaced 125I-FN binding to human α4β1 integrin and, in flow cytometry analysis, it antagonized the binding of a primary antibody to α4β1 integrin expressed on the Jurkat cells surface as well. Furthermore, we analysed also its effects on integrin α4β1 signalling. In an vivo model of allergic conjunctivitis, topical DS70 reduced the clinical aspects of EPR (early phase reaction) and LPR (late phase reaction), by reducing clinical score, eosinophil accumulation, mRNA levels of cytochines and chemochines pro-inflammatory and the conjunctival expression of α4 integrin. In conclusion, DS70 seems a novel antiallergic ocular agent that has significant effects on both early and late phases of ocular allergy.

Giulio Cesare Aranzio (Arantius) (1530-89) in the pageant of anatomy and surgery

Giulio Cesare Aranzio in Italian (Julius Caesar Arantius in Latin) has not received full acclaim for his achievements in the field of anatomy and surgery that remain unknown to most physicians. His anatomical books Observationes Anatomicas, and De Humano Foetu Opusculum and surgical books De Tumoribus Secundum Locos Affectos and Hippocratis librum de vulneribus capitis commentarius brevis printed in Latin and additional existing literature on Aranzio from medical history books and journals were analysed extensively. Aranzio became Professor of Anatomy and Surgery at the University of Bologna in 1556. He established anatomy as a distinguished branch of medicine for the first time in medical history. Aranzio combined anatomy with a description of pathological processes. He discovered the 'Nodules of Aranzio' in the semilunar valves of the heart. He gave the first description of the superior levator palpebral and the coracobrachialis muscles. Aranzio wrote on surgical techniques for a wide spectrum of conditions that range from hydrocephalus, nasal polyp, goitre and tumours to phimosis, ascites, haemorrhoids, anal abscess and fistulae, and much more. Aranzio had an extensive knowledge in surgery and anatomy based in part on the ancient Greek and his contemporaries in the 16th century but essentially on his personal experience and practice.

The Validation of a New Visual Anaemia Evaluation Tool HemoHue HH1 in Patients with End-Stage Renal Disease

In chronic haemodialysis patients, anaemia is a frequent finding associated with high therapeutic costs and further expenses resulting from serial laboratory measurements. HemoHue HH1, HemoHue Ltd, is a novel tool consisting of a visual scale for the noninvasive assessment of anaemia by matching the coloration of the conjunctiva with a calibrated hue scale. The aim of the study was to investigate the usefulness of HemoHue in estimating individual haemoglobin concentrations and binary treatment outcomes in haemodialysis patients. A prospective blinded study with 80 hemodialysis patients comparing the visual haemoglobin assessment with the standard laboratory measurement was performed. Each patient's haemoglobin concentration was estimated by seven different medical and nonmedical observers with variable degrees of clinical experience on two different occasions. The estimated population mean was close to the measured one (11.06 ± 1.67 versus 11.32 ± 1.23 g/dL, P < 0.0005). A learning effect could be detected. Relative errors in individual estimates reached, however, up to 50%. Insufficient performance in predicting binary outcomes (ROC AUC: 0.72 to 0.78) and poor interrater reliability (Kappa < 0.6) further characterised this method.

Detection of surfactant proteins A and D in human tear fluid and the human lacrimal system

PURPOSE: To evaluate the expression and presence of surfactant protein (SP) A and SP-D in the lacrimal apparatus, at the ocular surface, and in tears in healthy and pathologic states. METHODS: Expression of mRNA for SP-A and SP-D was analyzed by RT-PCR in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal ducts as well as in a spontaneously immortalized conjunctival epithelial cell line (HCjE; IOBA-NHC) and a SV40-transfected cornea epithelial cell line (HCE). Deposition of SP-A and SP-D was determined by Western blot, dot blot, and immunohistochemistry in healthy tissues, in tears, aqueous humor, and in sections of different corneal abnormalities (keratoconus, herpetic keratitis, and Staphylococcus aureus-based ulceration). Cell lines were stimulated with different cytokines and bacterial components and were analyzed for the production of SP-A and SP-D by immunohistochemistry. RESULTS: The presence of SP-A and SP-D on mRNA and protein levels was evidenced in healthy lacrimal gland, conjunctiva, cornea, and nasolacrimal duct samples. Moreover, both proteins were present in tears but were absent in aqueous humor. Immunohistochemistry revealed the production of both peptides by acinar epithelial cells of the lacrimal gland and epithelial cells of the conjunctiva and nasolacrimal ducts, whereas goblet cells revealed no reactivity. Healthy cornea revealed weak reactivity on epithelial surface cells only. In contrast, SP-A and SP-D revealed strong reactivity in patients with herpetic keratitis and corneal ulceration surrounding lesions and in several immigrated defense cells. Reactivity in corneal epithelium and endothelium was also seen in patients with keratoconus. Cell culture experiments revealed that SP-A and SP-D are produced by both epithelial cell lines without and after stimulation with cytokines and bacterial components. CONCLUSIONS: These results show that SP-A, in addition to SP-D, is a peptide of the tear film. Based on the known direct and indirect antimicrobial effects of collectins, the surfactant-associated proteins A and D seem to be involved in several ocular surface diseases.

Microcirculation in hypertensive patients

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

Chronic bovine besnoitiosis: intra-organ parasite distribution, parasite loads and parasite-associated lesions in subclinical cases.

Bovine besnoitiosis caused by Besnoitia besnoiti is a chronic and debilitating disease. The most characteristic clinical signs of chronic besnoitiosis are visible tissue cysts in the scleral conjunctiva and the vagina, thickened skin and a generally poor body condition. However, many seropositive animals remain subclinically infected, and the role that these animals may play in spreading the disease is not known. The aim of the present study was to assess the intra-organ parasite distribution, the parasite load and the parasite-associated lesions in seropositive but subclinically infected animals. These animals were seropositive at the time of several consecutive samplings, had visible tissue cysts in the past and, at time of slaughter, had detectable specific anti-Besnoitia spp. antibody levels, but they did not show evident clinical signs at culling. Thus, histopathological, immunohistochemical and molecular analyses of several samples from the respiratory tract, reproductive tract, other internal organs and skin from six cows were performed. The tissue cysts were located primarily in the upper respiratory tract, i.e., in the rhinarium and larynx/pharynx (four cows), followed by the distal genital tract (vulva/vagina) and the skin of the neck (three and two cows, respectively, out of the four cows with cysts in the respiratory tract). We were unable to detect any parasites in the two remaining cows. Cysts were associated with a significant non-purulent inflammatory infiltrate consisting predominantly of T lymphocytes and activated monocytes/macrophages in two cows. The parasite burden, estimated by quantitative real-time PCR, was very low. It is noteworthy that the only animal that showed a recent increase in the antibody titre had the highest parasite burden and the most conspicuous inflammatory reaction against the cysts. In conclusion, although these cows no longer displayed any visible signs of besnoitiosis, they remained infected. Therefore, cows without visible signs of disease may still be able to transmit the parasite.

An inter-laboratory comparative study of serological tools employed in the diagnosis of Besnoitia besnoiti infection in bovines

Bovine besnoitiosis is considered an emerging chronic and debilitating disease in Europe. Many infections remain subclinical, and the only sign of disease is the presence of parasitic cysts in the sclera and conjunctiva. Serological tests are useful for detecting asymptomatic cattle/sub-clinical infections for control purposes, as there are no effective drugs or vaccines. For this purpose, diagnostic tools need to be further standardized. Thus, the aim of this study was to compare the serological tests available in Europe in a multi-centred study. A coded panel of 241 well-characterized sera from infected and non-infected bovines was provided by all participants (SALUVET-Madrid, FLI-Wusterhausen, ENV-Toulouse, IPB-Berne). The tests evaluated were as follows: an in-house ELISA, three commercial ELISAs (INGEZIM BES 12.BES.K1 INGENASA, PrioCHECK Besnoitia Ab V2.0, ID Screen Besnoitia indirect IDVET), two IFATs and seven Western blot tests (tachyzoite and bradyzoite extracts under reducing and non-reducing conditions). Two different definitions of a gold standard were used: (i) the result of the majority of tests ('Majority of tests') and (ii) the majority of test results plus pre-test information based on clinical signs ('Majority of tests plus pre-test info'). Relative to the gold standard 'Majority of tests', almost 100% sensitivity (Se) and specificity (Sp) were obtained with SALUVET-Madrid and FLI-Wusterhausen tachyzoite- and bradyzoite-based Western blot tests under non-reducing conditions. On the ELISAs, PrioCHECK Besnoitia Ab V2.0 showed 100% Se and 98.8% Sp, whereas ID Screen Besnoitia indirect IDVET showed 97.2% Se and 100% Sp. The in-house ELISA and INGEZIM BES 12.BES.K1 INGENASA showed 97.3% and 97.2% Se; and 94.6% and 93.0% Sp, respectively. IFAT FLI-Wusterhausen performed better than IFAT SALUVET-Madrid, with 100% Se and 95.4% Sp. Relative to the gold standard 'Majority of test plus pre-test info', Sp significantly decreased; this result was expected because of the existence of seronegative animals with clinical signs. All ELISAs performed very well and could be used in epidemiological studies; however, Western blot tests performed better and could be employed as a posteriori tests for control purposes in the case of uncertain results from valuable samples.

First cases of besnoitiosis in cattle in Switzerland

Bovine besnoitiosis has been diagnosed in neighboring countries but not in Switzerland so far. This disease occurs endemically in France and focal outbreaks have been reported in Germany and Italy. To determine if Besnoitia besnoiti is introduced into Switzerland through the import of breeding cattle from France, a systematic serological survey was performed. A total of 412 breeding cattle (from 114 farms) imported from France into Switzerland between 2005 and 2011, were serologically examined for antibodies against B. besnoiti using a commercial ELISA kit (PrioCHECK© Besnoitia Ab 2.0, Prionics AG, Zurich, Switzerland). Sixty-four (15.5 %) animals reacted positive in ELISA. The serologic diagnosis was confirmed by an indirect immunfluorescence test (IFAT) and a Western blot (WB) in only 2 Limousin cows imported from France on a farm in Eastern Switzerland. Subsequently, this whole herd (n = 16) was examined clinically and serologically and 2 additional Limousin cows imported from Germany also reacted positive in the three serological tests. One of these cows presented B. besnoiti tissue cysts in the scleral conjunctiva and typical skin lesions in the head region. The infection was further confirmed cytologically, histopathologically and by PCR. It can be concluded that the parasite is most likely being introduced into Switzerland through the import of infected animals.

Whole Genome Analysis of Pinkeye Scores in Angus Cattle

Infectious Bovine Keratoconjunctivitis (IBK), known as pinkeye, is a common infectious disease affecting the eyes of cattle. It is characterized by excessive tearing, inflammation of the conjunctiva, and ulceration of the cornea. Although pinkeye is non-fatal, it has a marked economic impact on the cattle industry, due to the decreased performance of infected individuals. Genetic effects on the susceptibility of IBK have been studied and Hereford, Jersey, and Holstein breeds were found to be more susceptible to IBK than Bos Indicus breeds. The objectives of our study were: 1) to estimate genetic parameters of IBK scored in different categories by using genomic threshold model, and 2) to detect markers in linkage disequilibrium with quantitative tract loci (QTL) associated with IBK.

Síndrome MAPE, heavy eye y esclerodermia

Paciente de 60 años de edad y sexo femenino con esclerodermia y miopía alta bilateral que consulta por estrabismo y ptosis palpebral. El estrabismo consiste en esotropía progresiva con hipotropía de ojo derecho (OD) asociado a miopía alta axial con gran tamaño del globo ocular medido por ecometría ultrasónica que conjuntamente con imágenes de Resonancia Magnética Nuclear (RMN) llevan al diagnóstico de Síndrome MAPE (Miopic Acquired Progressive Esotropia). La hipotropía se diagnostica como heavy eye (ojo pesado). El tratamiento del estrabismo mediante cirugía de retroceso de recto medio derecho con técnica de suturas ajustables corrigió la esotropía mientras que la normalización del trayecto del recto lateral descendido no mejoró la hipotropía en esta paciente. Ésta se compensó parcialmente con el plegamiento ajustable del recto superior. Persiste la ptosis palpebral causada por la esclerodermia.