Lisa Tarmann

Ozurdex® reduces the retinal thickness in radiation maculopathy refractory to bevacizumab

pathognomonic for classic WD. He was diagnosed with kidney sarcoidosis before the WD diagnosis and was pharmacologically immunosuppressed. After the patient had his first cataract surgery performed, a severe mostly posterior uveitis was diagnosed. It did not respond to neither topical nor systemic immunosuppressive treatment. Case reports have described uveitis after intraocular operations in patients unknown to have WD, only diagnosed later on by vitreous samples. It is uncertain whether it is the operation in itself or the use of post-operative topical steroids that provokes the development of uveitis in these WD patients (Drancourt et al. 2009). In parallel with the eye problems, the patient developed significant neurological symptoms indicating involvement of the brain. WD is a fascinating disease entity with a wide range of clinical manifestations and has been considered to be an extremely rare disease (Raoult et al. 2000). This makes it difficult for clinicians to identify cases, especially the non-classic cases, with more atypical symptoms and findings. New data indicate that Tropheryma whipplei is ubiquitous in the environment (Maiwald et al. 1998). Clinicians treating patients with diffuse symptoms involving the brain and the eyes should not forget about this very rare disease which can be treated effectively with antibiotics.

Visual acuity after Gamma-Knife radiosurgery of choroidal melanomas

Background/aims To report on conservation of visual acuity after Gamma-Knife radiosurgery of choroidal melanoma. Methods A total of 189 patients with choroidal melanoma were treated with Gamma-Knife stereotactic single-fraction radiosurgery at a single institution between June 1992 and May 2010. The main outcome measure of our retrospective analysis was conservation of pretreatment visual acuity of 20/40 or better, 20/200 or better and counting fingers (CF) or better, over time of follow-up. Patient, tumour and treatment parameters were evaluated as potential risk factors for visual loss. Results Five years after treatment, the actuarial probability of keeping visual acuity better than 20/40, 20/200 and CF was 13%, 14% and 36%, respectively. The majority of patients (84.7%) encountered a deterioration of vision after treatment. The most important risk factors for visual loss were tumour height, longest basal diameter, distance to the optic disk and/or foveola, and retinal detachment before treatment. Treatment dose, and patient characteristics (age, sex, concurrent systemic diseases) were less important. Local tumour control rate was 94.4% after a median follow-up of 39.5 months. Conclusions Visual outcome after single-fraction Gamma-Knife radiotherapy is comparable with linear accelerator (LINAC) based fractionated stereotactic radiotherapy, inferior to proton beam radiotherapy, and depends primarily on tumour size, location and pre-existing retinal detachment.

Local tumour control and eye preservation after gamma-knife radiosurgery of choroidal melanomas

Background/aims To report on local tumour control and eye preservation after gamma knife radiosurgery (GK-RS) to treat choroidal melanomas. Methods A total of 189 patients with choroidal melanoma were treated with GK-RS, with treatment doses between 25 and 80 Grays. The main outcome measures of our retrospective analysis were local tumour control, time to recurrence, eye retention rate and the reason for and time to secondary enucleation. Patient-associated, tumour-associated and treatment-associated parameters were evaluated as potential risk factors. Results Local tumour control was achieved in 94.4% of patients. The estimated tumour control rates were 97.6% at 1 year, 94.2% at 5 years and 92.4% at 10 years after treatment. Recurrence was observed between 3.1 months and 60.7 months post-treatment (median: 13.5 months). Advanced tumour stage (Tumour, Node, Metastasis (TNM) 3–4) was the most important risk factor for recurrence (Fine-Gray model; subhazard ratio, SHR: 3.3; p=0.079). The treatment dose was not related to tumour recurrence. The eye preservation rate was 81.6% at 5 years after treatment, remaining stable thereafter. Twenty-five eyes (14.1%) had to be enucleated at between 17 days and 68.0 months (median: 13.9 months) after GK-RS, and advanced tumour stage (Cox model; p=0.005), treatment dose (p=0.048), pretreatment visual acuity (p=0.016), and retinal detachment (p=0.027) were risk factors for requiring enucleation. Conclusions GK-RS achieved a high tumour control rate, comparable to linear accelerator-based radiotherapy. Advanced TNM stage was a predictive risk factor for tumour recurrence and for secondary enucleation after GK-RS. Lower treatment doses were unrelated to tumour recurrence, although they were associated with an improved eye retention rate.

Ruthenium-106 plaque brachytherapy for uveal melanoma

Background To report on local tumour control, eye preservation and visual outcome after ruthenium-106 brachytherapy for uveal melanoma. Methods Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at one single centre, were included. Primary outcome measures were local tumour control, eye preservation and visual outcome. The influence of patient, tumour and treatment parameters on outcome was analysed by time to event analysis and competing risk regression. Results The median overall follow-up was 37.9 months. Tumour control: recurrent tumour growth was observed in 17 patients. The estimated local tumour recurrence rate at 12, 24 and 48 months after irradiation was 3%, 8.4% and 14.7%, respectively. The only significant risk factors for tumour recurrence were age (p=0.046) and reduced initial visual acuity (VA, p=0.045). No significant difference could be shown for tumour size or tumour category (T1–T2 vs T3–T4), and for any other tumour or treatment parameters (including combined transpupillary thermo-therapy (TTT)). Eye preservation: The likelihood of keeping the eye 12, 24 and 48 months after irradiation was 97.7%, 94.7% and 91.8%, respectively. Most significant risk factors for secondary enucleation were initial VA (p<0.001), tumour height (p=0.002) and tumour category (p=0.015). Vision The chances of keeping VA of 20/200 or better at 1, 2 and 5 years after treatment were 86.4%, 80.8% and 61.7%, respectively. Patients receiving sandwich-TTT showed significantly worse visual outcomes. Conclusions Ruthenium-106 brachytherapy appears to be a useful treatment regarding tumour control, eye preservation and visual function. Adjunct sandwich therapy resulted in worse visual outcome.

Genetic analysis of uveal melanoma by array comparative genomic hybridization before and after radiotherapy

SummaryBackgroundGenetic analysis of choroidal melanoma is frequently used to estimate the risk of metastatic spread of the tumor. Obtaining a biopsy for genetic analysis, however, can be difficult and sometimes unsuccessful. We evaluated the feasibility and accuracy of genetic testing using array comparative genomic hybridization (CGH) after radiotherapy, from tumor samples obtained by endoresection or after secondary enucleation.Material and methodsFifteen choroidal melanoma samples obtained after radiotherapy (Ruthenium-106 plaque brachytherapy or Gamma-Knife radiosurgery) were analyzed by array CGH to detect chromosomal aberrations (monosomy 3 and trisomy 8q), and the results were compared with pre-irradiation findings in five cases.ResultsArray CGH was successfully performed in all 15 cases. Time from radiotherapy to obtaining the sample for cytogenetic testing was between 14 and 879 days. Results of post-radiotherapy genetic analysis did not differ from pre-radiotherapy findings.ConclusionPost-radiation CGH appears to be a promising option for prognostic testing if a first biopsy before radiotherapy failed or was not performed. It could be useful to avoid an additional surgical procedure before radiotherapy if vitrectomy or endoresection is planned after radiotherapy.ZusammenfassungHintergrundDie genetische Untersuchung von Aderhautmelanomen ist eine zunehmend häufiger eingesetzte Methode, um das Risiko der Metastasenentwicklung bei PatientInnen mit Aderhautmelanomen einzuschätzen. Die Gewinnung einer Gewebeprobe zur Durchführung der Untersuchung ist jedoch manchmal schwierig und nicht in allen Fällen erfolgreich. Wir untersuchten die Durchführbarkeit und Genauigkeit der genetischen Untersuchung von Aderhautmelanomen mittels array comparative genomic hybridization (CGH) nach Strahlentherapie, an mittels Endoresektion oder nach Enukleation gewonnenem Tumormaterial.Material und MethodeFünfzehn Gewebeproben von strahlentherapeutisch behandelten Aderhautmelanomen wurden mittels array-CGH auf Veränderungen an den Chromosomen 3 und 8 untersucht (Monosomie 3, Trisomie 8q). Die Ergebnisse wurden mit den in fünf Fällen vorliegenden Resultaten der genetischen Untersuchung vor Bestrahlung verglichen.ResultateDie array CGH konnte in allen 15 Fällen nach Bestrahlung erfolgreich durchgeführt werden. Die Zeitspanne von der Bestrahlung bis zur genetischen Untersuchung lag zwischen 14 und 879 Tagen. Die Resultate der genetischen Untersuchung nach Bestrahlung unterschieden sich nicht von den Ergebnissen der in 5 Fällen vorliegenden Ergebnissen vor der Bestrahlung.SchlußfolgerungDie array CGH von Aderhautmelanomen nach Strahlentherapie erscheint eine vielversprechende Option zur prognostischen Unteruchung in den Fällen zu sein, in denen eine Biopsie vor Bestrahlung nicht durchgeführt wurde oder nicht erfolgreich war. Im Falle einer geplanten Endoresektion nach Bestrahlung, könnte auf einen zusätzlichen Eingiff zu Biopsie vor der Bestrahlung verzichtet werden.

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.

Iris Freckles a Potential Biomarker for Chronic Sun Damage.

Purpose To investigate the role of sunlight exposure in iris freckles formation. Methods We prospectively examined volunteers attending a skin cancer screening program conducted by ophthalmologists and dermatologists. Frequency and topographical variability of iris freckles were noted and associated with behavioral and dermatologic characteristics indicating high sun exposure. Results Six hundred thirty-two participants (n = 360; 57% female) were examined. Mean age of all participants was 38.4 ± 18.4 years (range, 4-84 years). Of all individuals, 76.1% (n = 481) exhibited at least one iris freckle. Most freckles were observed in the inferior temporal quadrant. The presence of iris freckles was associated with higher age (participants with iris freckles: 41.8 ± 16.8 years versus participants without iris freckles: 27.6 ± 19.2 years), a high number of sunburns during lifetime (>10: 31% vs. 19%), sunlight-damaged skin (26% vs. 11%), presence of actinic lentigines (72% vs. 45%), and a high total nevus body count (>10; 78% vs. 67%). Conclusions The association of iris freckles, behavioral factors, and dermatologic findings, as well as the topographical distribution, indicate that sunlight exposure may trigger the formation of iris freckles. The evaluation of iris freckles offers an easily accessible potential biomarker, which might be helpful in indicating sun damage on the skin associated with cutaneous malignancies. Furthermore, the evaluation of iris freckles could also be helpful in understanding the role of sunlight in several ophthalmologic diseases.

Vitreous hyper-reflective dots in pseudophakic cystoid macular edema assessed with optical coherence tomography

Purpose This study compares the presence of vitreous hyper-reflective dots (VHDs) detected with optical coherence tomography (OCT) between eyes with pseudophakic cystoid macular edema (CME) and those with no CME after cataract surgery. In addition, we evaluated the impact of VHDs on the responsiveness of pseudophakic CME to cortisone treatment. Setting Department of Ophthalmology, Medical University of Graz, Austria. Design Retrospective, monocenter case-controlled study. Methods Inclusion criteria for the study group and the control group were CME and no CME within 12 weeks following uneventful phacoemulsification in otherwise healthy eyes, respectively. VHDs (number and size) and the macular thickness were assessed with OCT. Furthermore, the number of peribulbar or intravitreal steroid injections was assessed. Results A total of 284 eyes from 267 patients were analyzed, among which 119 met the inclusion criteria for the study (n = 63) and the control group (n = 56). VHDs were observed in 54 (85.7%) study eyes and 21 (37.5%, p = 0.013) control eyes. The number of VHDs was 3.9±3.4 in the study group and 0.7±1 in the control group (p<0.001). The size of the VHDs was 33.5±9.1 μm and 36.6±17.9 μm in the study and control groups, respectively (p = 0.978). Overall, the number of VHDs correlated with central subfield thickness (r = 0.584, p<0.001), cube volume (r = 0.525, p<0.001), and postoperative best-corrected visual acuity (BCVA) (r = -0.563, p<0.001). The number of VHDs did not correlate with the frequency of peribulbar or intravitreal steroid injections. Conclusion VHDs occurred more often in eyes with CME than in eyes without CME following cataract surgery. In addition, the number of VHDs had an impact on the extent of macular thickening and subsequently postoperative BCVA. No correlation was found between the number of VHDs and the frequency of required peribulbar or intravitreal steroid injections.

Tumor parameters predict the risk of side effects after ruthenium-106 plaque brachytherapy of uveal melanomas

Background To report on radiation-related side effects and complications after ruthenium-106 plaque brachytherapy of uveal melanomas. Methods Medical records of 143 eyes with uveal melanoma, treated by ruthenium-106 brachytherapy between 1997 and 2012 at a single center, were analyzed. We evaluated the occurrence of radiation-related side effects on the anterior and posterior segment of the eye. The influence of patient, tumor and treatment parameters on outcome was analyzed by multivariate time to event analysis considering competing risks. Results The median overall follow-up was 37.9 months. After treatment, the estimated risk at 12, 24 and 48 months for developing anterior segment complications was 25.3%, 37.5% and 50.3% for cataract formation and 5.4%, 6.4% and 8.1% for secondary glaucoma, respectively. The estimated risk for the occurrence of posterior segment complications 12, 24 and 48 months after treatment was 3.1%, 6.7% and 18.3% for radiation retinopathy, 18.3%, 27.1% and 42.6% for radiation maculopathy and 16.5%, 21.0% and 32.8% for radiation neuropathy, respectively. The risk of an increase in retinal detachment after treatment was 14.7%, 14.7% and 17.4% at 12, 24 and 48 months, respectively. The risk of vitreous hemorrhage occurring after treatment was 6.2%, 8.1% and 12.7%, and the risk of tumor vasculopathy was 15.4%, 17.4% and 19.0%. Scleral necrosis was observed in one patient. Conclusion Radiation-related side effects and complications are common among patients treated with ruthenium brachytherapy for uveal melanoma. However, the risk for those largely depends on individual tumor parameters. Before treatment, patients should be informed of their specific risks to develop various side effects. Patient information before treatment should cover not only general information about the treatment and possible complications and side effects but should also give details on the specific risks of the patient in her individual situation. This also includes elucidating the patients individual resources and expectations and her willingness for long-term regular follow-up examinations and secondary adjunct treatments.

Molecular Carcinogenesis of Uveal Melanoma

Melanocytes are derived from the neural crest and enter the eye during embryogenesis. Uveal melanoma of the eye is a rare but deadly disease. About 50% of patients will eventually develop metastatic disease with an inevitable fatal end. Predisposing factors are race, skin and hair color, and familial tumor predisposition syndromes.