Andrea Langmann

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Women Underrepresented on Editorial Boards of 60 Major Medical Journals

BACKGROUND Although there has been a continuous increase in the number of women working in the field of medicine, women rarely reach the highest academic positions as full professors or editorial board members. OBJECTIVE We aimed to determine the proportion of women on the editorial boards of top-ranked medical journals in different medical specialties. METHODS We analyzed the gender of editorial board members of 60 top-ranked journals of 12 Thomson Reuters Web of Knowledge Journal Citation Reports categories. A total of 4175 editors were included in our analysis. RESULTS Only 15.9% (10 of 63) editors-in-chief were female. In the 5 categories, critical care, anesthesiology, orthopedics, ophthalmology and radiology, nuclear medicine and medical imaging, currently not 1 woman holds the position of editor-in-chief. Less than one fifth (17.5%, 719 of 4112) of all editorial board members were women. There were significant differences among the evaluated categories, with the highest percentage of women in the category of medicine, general and internal and the lowest in the category critical care, followed by orthopedics. In every category, the proportion of women as editorial board members was substantially lower than that of men. CONCLUSIONS Women are underrepresented on the editorial boards of major medical journals, although there is a great variability among the journals and categories analyzed. If more women are nominated to serve on editorial boards, they will be a visible sign of continuing progress and serve as important role models for young women contemplating a career in academic medicine.

Predictive diagnosis of the cancer prone Li–Fraumeni syndrome by accident: new challenges through whole genome array testing

Background: Li–Fraumeni syndrome greatly increases the risk of developing several types of cancer and is usually caused by TP53 germline mutations. Predictive testing of at-risk family members is only offered after a complex genetic counselling process. Recently the clinical implementation of array comparative genomic hybridisation (CGH) has revolutionised the diagnosis of patients with syndromic or non-syndromic mental retardation and has evolved to a routinely performed high resolution whole genome scan. Methods and results: When using array CGH to identify the cause for mental retardation in a 7-year-old child we found a submicroscopic de novo deletion of chromosome 17p13.1, which includes several genes likely to be causative for her phenotype, and also of TP53. Conclusion: Thus, array CGH resulted in an unintended predictive diagnosis of an increased tumour susceptibility as observed in Li–Fraumeni syndrome.

The clinical and molecular genetic features of idiopathic infantile periodic alternating nystagmus

Periodic alternating nystagmus consists of involuntary oscillations of the eyes with cyclical changes of nystagmus direction. It can occur during infancy (e.g. idiopathic infantile periodic alternating nystagmus) or later in life. Acquired forms are often associated with cerebellar dysfunction arising due to instability of the optokinetic-vestibular systems. Idiopathic infantile periodic alternating nystagmus can be familial or occur in isolation; however, very little is known about the clinical characteristics, genetic aetiology and neural substrates involved. Five loci (NYS1-5) have been identified for idiopathic infantile nystagmus; three are autosomal (NYS2, NYS3 and NYS4) and two are X-chromosomal (NYS1 and NYS5). We previously identified the FRMD7 gene on chromosome Xq26 (NYS1 locus); mutations of FRMD7 are causative of idiopathic infantile nystagmus influencing neuronal outgrowth and development. It is unclear whether the periodic alternating nystagmus phenotype is linked to NYS1, NYS5 (Xp11.4-p11.3) or a separate locus. From a cohort of 31 X-linked families and 14 singletons (70 patients) with idiopathic infantile nystagmus we identified 10 families and one singleton (21 patients) with periodic alternating nystagmus of which we describe clinical phenotype, genetic aetiology and neural substrates involved. Periodic alternating nystagmus was not detected clinically but only on eye movement recordings. The cycle duration varied from 90 to 280 s. Optokinetic reflex was not detectable horizontally. Mutations of the FRMD7 gene were found in all 10 families and the singleton (including three novel mutations). Periodic alternating nystagmus was predominantly associated with missense mutations within the FERM domain. There was significant sibship clustering of the phenotype although in some families not all affected members had periodic alternating nystagmus. In situ hybridization studies during mid-late human embryonic stages in normal tissue showed restricted FRMD7 expression in neuronal tissue with strong hybridization signals within the afferent arms of the vestibulo-ocular reflex consisting of the otic vesicle, cranial nerve VIII and vestibular ganglia. Similarly within the afferent arm of the optokinetic reflex we showed expression in the developing neural retina and ventricular zone of the optic stalk. Strong FRMD7 expression was seen in rhombomeres 1 to 4, which give rise to the cerebellum and the common integrator site for both these reflexes (vestibular nuclei). Based on the expression and phenotypic data, we hypothesize that periodic alternating nystagmus arises from instability of the optokinetic-vestibular systems. This study shows for the first time that mutations in FRMD7 can cause idiopathic infantile periodic alternating nystagmus and may affect neuronal circuits that have been implicated in acquired forms.

Repeated mobility testing for later artificial visual function evaluation

The study investigates the utility of a newly designed mobility test for repeated testing of visual function in patients with severe visual impairment and future application in evaluating functional progress in patients with artificial vision. Ten subjects divided into three groups based on visual acuity (VA) ranging from light perception to 20/200 and reduced visual field (VF) were included in the study. The mobility test consisted of using a set of four different but structurally similar and relatively short mazes having a constant number of obstacles of various sizes. The subjects, divided into three groups by acuity, passed through each course several times. In general, the patients with better VA had a larger extent of VF. Average speed and number of contacts were recorded as measures of performance. The average passing times of the groups through the courses were significantly different (p = 0.03), which was influenced by VA and VF. There was no significant difference in average number of contacts between the groups (p = 0.15). The mobility test proved to be appropriate for gaining statistically relevant results in repeated individual testing of patients with severe vision impairment. Results show promise for use this mobility test as a tool for assessing visual function of patients undergoing implantation of a visual prosthesis for artificial vision.

The Relation between Reading Skills and Eye Movement Patterns in Adolescent Readers : Evidence from a Regular Orthography

Over the past decades, the relation between reading skills and eye movement behavior has been well documented in English-speaking cohorts. As English and German differ substantially with regard to orthographic complexity (i.e. grapheme-phoneme correspondence), we aimed to delineate specific characteristics of how reading speed and reading comprehension interact with eye movements in typically developing German-speaking (Austrian) adolescents. Eye movements of 22 participants (14 females; mean age = 13;6 years;months) were tracked while they were performing three tasks, namely silently reading words, texts, and pseudowords. Their reading skills were determined by means of a standardized German reading speed and reading comprehension assessment (Lesegeschwindigkeits- und -verständnistest für Klassen 6−12). We found that (a) reading skills were associated with various eye movement parameters in each of the three reading tasks; (b) better reading skills were associated with an increased efficiency of eye movements, but were primarily linked to spatial reading parameters, such as the number of fixations per word, the total number of saccades and saccadic amplitudes; (c) reading speed was a more reliable predictor for eye movement parameters than reading comprehension; (d) eye movements were highly correlated across reading tasks, which indicates consistent reading performances. Contrary to findings in English-speaking cohorts, the reading skills neither consistently correlated with temporal eye movement parameters nor with the number or percentage of regressions made while performing any of the three reading tasks. These results indicate that, although reading skills are associated with eye movement patterns irrespective of language, the temporal and spatial characteristics of this association may vary with orthographic consistency.

Vorschlag einer Vereinheitlichung der Retinoblastomtherapie in Österreich

ZusammenfassungHintergrundVor dem Hintergrund neuer Erkenntnisse auf dem Gebiet der Retinoblastomtherapie (primäre Chemoreduktion, Verbannung der perkutanen Strahlentherapie wegen der Induktion von Sekundärmalignomen) wurde vom Department für Hämatologie/Onkologie der Universitäts-Kinderklinik in Graz zusammen mit der Universitäts-Augenklinik ein Protokoll für eine österreichweit einheitliche Retinoblastomtherapie erarbeitet.Patienten und MethodenZwischen 2003 und 2008 sollen alle uni- und bilateralen Retinoblastome, die neu in Österreich auftreten, entsprechend diesem Protokoll erfasst und einer Therapie zugeführt werden. Beim Auftreten eines Sekundärglaukoms (Buphthalmus), bei Medientrübungen, Infiltration des Sehnerven und extraokulares Tumorwachstum ist nach wie vor die Enukleation Therapie der Wahl. Geeignete uni- und bilaterale Retinoblastome werden mit einer primären Chemoreduktion behandelt (2 Zyklen zu je 3 Blöcken bestehend aus Vincristin, Cyclophosphamid, Carboplatin und Etoposid in wechselnder Zusammensetzung). Zum Zeitpunkt der maximalen Tumorregression wird die Entscheidimg bezüglich einer Lokaltherapie getroffen: 1. kleine v. a. peripher lokalisierte Tumoren werden mit einer 3-fach Kryotherapie behandelt, 2. mittelgroße Tumoren (6–8 mm Prominenz) mit einer Ruthenium-106-Brachytherapie, 3. zentral lokalisierte Tumoren mit transpupillarer Thermotherapie, 4. Tumoren prominenter als 8 mm können alternativ zur Enukleation mit kombinierten Therapiekonzepten wie der Brachychemoradiotherapie behandelt werden.ErgebnisseDie Ergebnisse werden im Protokoll dokumentiert, im Sinn einer Qualitätskontrolle anlässlich der Jahrestagung der onkologisch tätigen Pädiater Österreichs sowie der Jahrestagung der Österreichischen Ophthalmologischen esellschaft bzw. des alljährlichen Symposiums über Strabologie und Neuroophthalmologie vorgestellt und kommentiert.SchlussfolgerungZiel dieses Protokolls ist eine österreichweite Erfassung und Vereinheitlichung der Retinoblastomtherapie mit dem Ziel einer engen Kooperation aller onkologisch tätigen Zentren Österreichs. Teile dieses Vortrages wurden anlässlich der 44. Jahrestagung der Österreichischen Ophthalmologischen Gesellschaft in Salzburg präsentiert.SummaryBackgroundIn view of the background of new findings in retinoblastoma therapy (primary chemoreduction, banishing the percutaneous radiotherapy thus avoiding the induction of secondary malignomas) the Department of Paediatric Oncology/Haematology together with the Department of Ophthalmology, Medical University Graz, developed a protocol for an uniform retinoblastoma treatment in Austria.Patients and methodsBetween 2003 and 2008 unilateral and bilateral retinoblastomas, which arise in Austria, will be treated according to this protocol. Limiting factors for a globe preserving treatment are the occurrence of secundary glaucoma (buphthalmus, neovascular glaucoma), opaque media or an infiltration of the optic nerve. Selected unilateral and bilateral retinoblastomas will undergo a primary chemoreduction (3 cycles consisting of Vincristin, Cyclophosphamide, Carboplatin and Etoposid in different composition repeated once). Local tumor therapy is applied when maximum tumor regression has been achieved. 1. small, peripherally located tumors will be treated with cryotherapy, 2. medium sized tumors (6–8 mm prominence) with Ruthenium 106 brachytherapy, 3. centrally located tumors with transpupillary therapy (TTT). Tumors higher than 8 mm will be treated with combined therapy concepts like brachychemoradiotherapy as an alternative to enucleation.ResultsThe results are documented in the protocol, as a tool of quality control and presented during the annual meeting of the Austrian Ophthalmologic Society and the Symposium on Strabism and Paediatric Ophthalmology.ConclusionA goal of this protocol is a collection of data of Austrian retinoblastoma patients and the standardisation of retinoblastoma therapy in Austria facilitating the communication within all centers in Austria involved in the care for ocular tumors in children.

European Foundation for Quality Management (EFQM) an der Schielambulanz der Universitäts-Augenklinik Graz

ZusammenfassungHintergrundNachdem die Universitätsaugenklinik sich das Ziel gesetzt hat, die Qualität der FachärztInnenausbildung durch das EFQM Modell und einen vereinheitlichten Lernzielkatalog anhand von internationalen Richtlinien (ICO, EBO) zu sichern, ist es nun ein zentrales Anliegen, zusätzliche vertiefende Curricula zu implementieren. In dieser Arbeit wird eine vertiefende Ausbildung beziehungsweise ein weiteres Curriculum für AssistentInnen in Facharztausbildung im Teilbereich der Strabologie vorgestellt.Material und MethodenBasierend auf dem Wunsch, verschiedene Curricula zur vertiefenden Ausbildung von AssistenzärztInnen zu etablieren, wurde mit der RADAR Logik nach dem EFQM Qualitätssicherungsmodell ein strukturiertes Curriculum nach internationalen Kriterien und Feedbacksystem eingeführt. Eine Selbstbewertung – ein „Quickscan“ und eine „SOLLstanderhebung“ – wurde durchgeführt und mittels Arbeitsgruppen ein Konzept erstellt.ErgebnisseDie Selbstbewertung ergab, dass teilweise eine strukturierte Ausbildung nach internationalen Kriterien mit Zielen und einem Feedbacksystem fehlt. Es wurde ein Konzept mit definiertem Ausbildungsziel festgelegt, eine Einführungsphase, eine Umsetzungsphase, eine Evaluierungsphase und ein laufendes Feedbacksystem implementiert. Das Curriculum liegt vor und ist freigegeben, es besteht aus einem klar strukturierten Ablauf der 6-monatigen Ausbildung. Der Lernzielkatalog ist auf internationalem Niveau und es gibt klare Verantwortlichkeiten Lehrender. Im Sinne des EFQM Modells wird ein Feedbacksystem während und am Ende der Ausbildung festgelegt.ZusammenfassungDas EFQM Modell mit der RADAR Logik ist ein geeignetes System um erfolgreich vertiefende Ausbildungen für AssistenzärztInnen zu etablieren und mit einem strategischen Feedbacksystem auf ständige Erfordernisse in der Umstrukturierung der Curricula reagieren zu können.SummaryBackgroundThe Department of Ophthalmology of the Medical University of Graz has set the common goal to improve the quality of ophthalmic resident training with the EFQM-model and unified learning targets based on international guidelines (ICO, EBO). Now there is a central request to implement additional in-depth curricula in Ophthalmology. Aim of this paper is to present a detailed 6 months curriculum in ophthalmic resident training in Strabology within the training period for a general ophthalmologist.Materials and MethodsBased on the desire to establish different curricula for in-depth training of residents in Ophthalmology, a structured curriculum in accordance with international criteria and a feedback system—with the RADAR logic based on the EFQM quality model—was introduced. A self-assessment—a “quick scan” and “should stand survey”—was performed and, based on that, a concept was created by three working groups.ResultsThe self-assessment showed that there is partially a lack of a structured training according to international criteria with goals and a feedback system. A concept with a defined training aim was set, an initial phase, an implementation phase, an evaluation phase and an ongoing feedback system were established. The curriculum is approved and it consists of a clearly structured process of a six-month training. The learning targets are accorded with international education levels and there are clear responsibilities of certain educators. For the purposes of the EFQM model a feedback system was implemented during and at the end of the 6-month training set.ConclusionThe EFQM model and the RADAR-logic is a suitable system to establish successfully in-depth training for residents in Ophthalmology. With its strategic feedback system it is responding to the needs of constant restructuring procedures of the curricula.

Das Grazer Modell der Facharztausbildung, Teil 1: Die Struktur

ZusammenfassungHintergrundZiel dieser Arbeit ist der Vorschlag einer strukturierten Facharztausbildung, die sowohl an einer Augenabteilung als auch einer Universitätsklinik praktiziert werden kann. Das International Council of Ophthalmology (ICO) hat anlässlich des letzten Kongresses in Sydney 2002 Richtlinien für eine Facharztausbildung bzw. Ausbildung zum Spezialisten erlassen, die in dieses Curriculum einflössen. Die einzelnen Länder in verschiedenen Kontinenten sind nun aufgerufen, diese Richtlinien umzusetzen.Material und MethodeBasis für ein Curriculum ist ein detaillierter, schriftlich festgelegter Lernzielkatalog. Während das ICO Mindestrichtlinien vorgibt und jedem Land die praktische Umsetzung freistellt, wird nun in unserem Curriculum jedes Lernziel detailliert festgelegt. Die Lernziele werden in zu erlernendes Wissen (im ICO alsKnowledge beschrieben) und in Fertigkeiten (skills) unterteilt. Die Fertigkeiten können weiter indiagnostische undtherapeutische Fertigkeiten gegliedert werden.Grundvoraussetzung für das Erlernen vonpraktischem Wissen undFertigkeiten ist die Möglichkeit einerRotation auf einer Augenabteilung wie auch Universitätsklinik. Neben der Bettenstation zum Erlernen der basalen Fähigkeiten zu Beginn der Ausbildung ist ein Schwerpunkt dieses Curriculums die Tätigkeit in der Ambulanz. Ein zweiter Schwerpunkt ist dieBegleitung des jungen Assistenten durch einen älteren Assistenten, übergeordnet und letztverantwortlich findet sich der Facharzt, Stationsführer, Oberarzt oder Leiter einer Abteilung oder Klinik.Großer Wert wird auf daspraktische,begleitende Lernen von Anfang an gelegt. Nach einer kurzen Phase des Erlernens der einfachen Untersuchungstechniken wie subjektive Sehprobe für Ferne und Nähe, Spaltlampenuntersuchung, Tonometrie und direkte wie indirekte Fundusuntersuchung werden die Krankheitsbilder am Patienten erlernt. Der junge Assistent versucht, die Untersuchung alleine durchzuführen, erst danach tritt je nach Ausbildungstand der ältere Assistent — die ältere Assistentin, oder die Fachärztin, der Facharzt — in Aktion. Das erlernte Wissen wird im Sinn einerEvidenz basierten Medizin (EbM) mittels Lehrbuch kontrolliert, ergänzt und sinnvollerweise nochmals mit dem Facharzt (Oberarzt) diskutiert. Entscheidend scheint neben der Momentaufnahme (Erstuntersuchung oder Kontrolluntersuchung) derKrankheitsverlauf des Patienten.DiskussionZiel dieses Curriculums ist, dem Assistenten vom ersten Tag seiner Facharztausbildung einenschriftlichen Leitfaden für seine Ausbildung zur Verfügung zu stellen. Die Verantwortung der Ausbildung liegt nicht nur beim Ordinarius oder Primär, sondern auch beim erfahrenen Assistenten — der erfahrenen Assistentin — oder der Fachärztin (dem Facharzt). Entscheidend ist ein begleitendes, kontrolliertes Lernen über die gesamte Zeit der Ausbildung, an dessen Ende die Facharztprüfung steht. Dieses Curriculum soll die Basis für eine Facharztausbildung darstellen, ergänzt durch die Module der ÖOG, Lehrbücher oder auch Leitartikeln von Zeitschriften (z. B. Der Ophthalmologe).SummaryBackgroundAim of this paper is a suggestion for a residency in ophthalmology at a university eye clinic in Austria. The International Council of Ophthalmology (ICO) has introduced curriculum guidelines during the last annual meeting in Sydney 2002. Part of these guidelines were included into our curriculum. The ICO guidelines are not all inclusive, but were introduced to be adapted in each country to meet the local requirements.MethodOur curriculum should serve as a guideline for resident and specialist education at the University Eye Clinic in Graz. In order to achieve maximum efficacy the resident should rotate during his (her) education into subspecialities in regular intervals. First of all basic diagnostic skills like slit slamp exam, tonometry, direct and indirect ophthalmoscopy should be learned at the ward. Practise in the outpatient clinic is important to see the emergency cases residents have to deal with during their first duties. The main focus of our curriculum is the supervision of the resident by an elder resident, fellow or assistent professor. After having learned the basic diagnostic skills the young resident tries to complete his (her) exam at his (her) own responsibility, his diagnostic and therapeutic suggestions are supervised by the tutor.In difficult cases or in doubt the knowledge is double-che-ckedcked by means of a book (Kanski) or Pubmed to fulfil the requirements of Evidence based medicine (EbM).DiscussionOur curriculum provides the resident with a written framework for his residency from the very beginning of his training. He is supervised by an elder resident, by a fellow or an assistant professor. This curriculum is complemented by an annual continuing education during the annual meeting of the Austrian Ophthalmological Society.