[Primary meningioma of the optical nerve sheet in infancy as initial presentation of neurofibromatosis type 2]. / Primäres Meningeom des Nervus opticus im Säuglingsalter als Erstmanifestation einer Neurofibromatose Typ 2.

Intraorbital meningiomas are rare tumors, making up less than 4% of all intraorbital tumors. Intraorbital meningiomas of childhood are curiosities with only few documented cases. We present the case of an 8­month-old male infant, presenting with strabismus and nystagmus. Magnetic resonance imaging showed a long segment thickening of the optical nerve and an intraocular tumor. The tumor was suspicious for retinal dysplasia and enucleation of the eye was performed to exclude malignancy. Histological examination revealed a meningothelial meningioma (WHO grade I), extending along the optical nerve and into the eye accompanied by retinal dysplasia and epiretinal membranes. Meningiomas of childhood, retinal dysplasia, and epiretinal membranes are regularly associated with neurofibromatosis type 2. Subsequent genetic analysis led to the final diagnosis. This case documents a very unusual early beginning of a neurofibromatosis type 2.

[Transretinal Biopsy of Intraocular Lymphoma]. / Transretinale Biopsie beim intraokularen Lymphom.

BACKGROUND: Intraocular lymphoma is in most cases a diagnostic challenge. Gold standard is a diagnostic vitrectomy. Vitreous biopsy and transretinal biopsies are therefore employed. METHODS: A retrospective analysis was undertaken of all cases of cytological or histological proven intraocular lymphoma between 2002 and the beginning of 2015 in our clinic. RESULTS: The diagnosis of intraocular lymphoma could be established in 16 cases by cytological or histological analysis. Six patients had previously been treated with steroids in the assumption of uveitis. Five of 16 patients had a systemic or CNS lymphoma in their history. The diagnosis of intraocular lymphoma could be made on the basis of a vitreous biopsy in only in 3 cases. In 7 cases an additional vitrectomy with transretinal biopsy was needed. In 1 case a transretinal biopsy was performed initially and in 1 case a re-transretinal biopsy was needed to establish the diagnosis. Two patients underwent iris biopsy to diagnose a secondary metastatic intraocular lymphoma. One amaurotic eye was diagnosed with intraocular lymphoma after enucleation. DISCUSSION: Due to the high relevance for the diagnosis intraocular lymphoma, when a vitreous biopsy was non-informative, a transretinal biopsy should always be considered in cases of retinal or subretinal involvement.

[Intraocular Tumors other than Retinoblastoma in Children]. / Intraokulare Raumforderungen im Kindesalter ohne Retinoblastom.

The diagnosis of an intraocular mass in children can be challenging as invasive procedures are not allowed, in particular if a retinoblastoma may be present. In eyes with a unilateral tumour mass and loss of function enucleation with subsequent histopathological processing might be the only option to establish a diagnosis and to exclude a malignant tumour. The present paper deals with intraocular tumours other than retinoblastoma in children, with a special focus on the correlation of modern imaging techniques and histopathological findings.

[Initial clinical experience in the treatment of vitreomacular traction and macular holes with ocriplasmin]. / Erste klinische Erfahrungen bei der Behandlung von vitreomakulären Traktionen mit Ocriplasmin.

BACKGROUND: The introduction and approval of Ocriplasmin as an intravitreally applicable drug in the pharmocological treatment of vitreomacular traction represents a new therapeutic approach possibly avoiding vitreoretinal surgery. With our article we report our first experience wih Ocriplasmin in clinical practice. METHODS: The indication for intravitreal therapy with Ocriplasmin was provided for symptomatic VMT or macular hole with VMT in 20 patients since March 2013. Surgery was planned in cases with remaining symptoms. Before IVI we performed SD-OCT. Best visual acuity (BCVA) was evaluated preoperatively, 7 and 28 days after treatment and finally every month in 14 treated eyes. SD-OCT images were analysed before treatment and later on with every follow-up examination. In addition to functional and morphological changes we analysed all side effects. RESULTS: The mean BCVA at the beginning of treatment was 0.3 and 0.4 before injection. The indications for treatment were as follows: symptomatic VMT in 10 patients and 4 patients suffering from full thickness macular hole stage 2. In 3 patients spontaneous regression of VMT could be observed with increasing of vision from 0.3 to 0.5. In one patient his macular hole was closed and BCVA increased from 0.2 to 0.6 within 7 days. Two patients showed significant enlargement of their macular holes after 7 days and finally underwent surgery. A massive cystoid macular oedema occurred in one patient. No change in the SD-OCT image could be observed 28 days after treatment. The mean visual acuity improved to 0.6 during a follow-up period of 90 days. Photopsia and disturbing vitreous opacities up to 28 days post injection could be regarded as minor side effects. CONCLUSION: Our first clinical experience with intravitreous injection of Ocriplasmin were performed to confirm the presumed therapeutic effect in patients suffering from VMT. Small macular holes could frequently be closed. The possibility of special side effects must be taken in consideration just as the possibility of spanteous improvement before performing IVI with Ocriplasmin. Further prospective studies must be recommended to be right about Ocriplasmin injections.

[Uveal melanoma: current insights into clinical relevance of genetic testing]. / Aktuelles zur klinischen Bedeutung genetischer Veränderungen bei malignen Melanomen der Uvea.

Uveal melanoma is the most common primary intraocular tumour in Caucasians. There are approximately 500 new cases of uveal melanoma in Germany per year and the incidence rate peaks at the age of 70 years. Half of all uveal melanoma patients develop metastatic disease, which can be observed even many years after successful treatment of the primary tumour. In most cases the liver is the location of first manifestation. Based on the chromosome 3 status uveal melanomas can be divided into two major classes that differ in their metastatic potential. Tumours with a high risk to metastasise usually show monosomy 3, whereas tumours showing disomy 3 rarely metastasise. If a patient wishes to know about his individual risk, prognostic testing of the primary tumour tissue can be performed after obtaining tumour material via transscleral or transretinal biopsy, or by enucleation. To date results of prognostic testing do not influence therapeutic strategies. Recently, major key genes involved in uveal melanoma development, GNAQ, GNA11, BAP1, SF3B1 and EIF1AX, have been identified. Mutation profiling, in addition to chromosomal 3 analysis, will further refine the classification or subclassification of uveal melanomas and will hopefully influence diagnostic or therapeutic concepts. Hereditary mutations in tumour suppressor gene BAP1 are associated with an increased risk for different tumour entities. Detection of germ line mutations in this tumour suppressor gene should implicate further general screening examinations of the patient to be able to detect these tumour entities. Moreover relatives of these patients should be offered a screening for BAP1 mutation.

[Diagnosis and treatment of retinoblastoma: current strategies for effective tumour control and preservation of vision]. / Diagnose und behandlung des retinoblastoms: aktuelle konzepte zur sicheren tumorkontrolle bei erhalt des sehvermögens.

There are approximately 40 new cases of retinoblastoma in Germany per year. Children in whom the tumour is detected when still intraocular have an excellent overall survival rate (> 95%). However, the prognosis of metastasised retinoblastoma remains poor. About 40% of retinoblastoma patients have tumours in both eyes. For these children in particular it is important to save the eye and visual function as much as possible. There are several options for conservative treatment of localised retinoblastoma including laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. In recent years, systemic chemotherapy has become the established standard for primary treatment of intraocular retinoblastoma. In case series, intra-arterial, intravitreal and periocular applications of chemotherapy were also shown to be effective in treating intraocular retinoblastoma. Genetic testing is an integral part of the routine diagnostics of all patients. Mutation analysis of tumour material is invaluable for identification of somatic mutations including mutational mosaicism. Genetic testing also identifies children with heritable retinoblastoma, which represent 50% of cases. These children also have a predisposition for the development of tumours outside of the eye (second primary neoplasm). To adequately address these and other late effects in survivors of retinoblastoma, a multidisciplinary approach is needed that optimises therapy and long-term follow-up. Upcoming multicentre clinical trials will evaluate treatment concepts for localised and metastasised retinoblastoma to improve survival rates and quality of life of children with retinoblastoma. This article was translated and modified and was primarily published in Klin Padiatr 2012; 224: 339-347.

[Endophthalmitis as a serious complication of intravitreal drug delivery]. / Endophthalmitis als schwere Komplikation der intravitrealen Medikamentengabe.

BACKGROUND: Endophthalmitis, regarded as a severe complication, can occur after intraocular injection of drugs (IVI). At present only few reports exist on the development of this disease, although recently the number of intraocular injections to treat especially age-related macular degenerations is increasing considerably. METHODS: In this paper we present our results of a retrospective study of 27 patients suffering from endophthalmitis after IVI. Treatment had been performed between January 2008 and March 2012. The indications for IVI were as follows: age-related macular degeneration 19, venous branch occlusion 1, diabethic retinopathies 6, uveitis 1. The following drugs were injected: bevacizumab in 8, Rranibizumab in 19 patients. The following data were assessed: incubation time, best corrected visual acuity that had been determined before treatment and later 3, 6 and 9 months after therapeutic vitrectomy. Additionally we describe the ophthalmoscopic changes and the results of bacteriological studies. RESULTS: Endophthalmitis was diagnosed 5.8 days after IVI on average. The vision of all patients had only been hand movements during the first examination. During the observation time the postoperative visual acuity could be improved only to 1/35 on average. During vitrectomy in 24 out of 27 patients a whitish retinal infiltration could be observed. 18 of 27 patients showed a hypopyon during slit lamp examination. 11 patients developed a retinal detachment and one eye had to be enucleated. CONCLUSIONS: Endophthalmitis must be regarded as a severe complication causing a high risk of retinal detachment with permanent loss of visual acuity. Retinal infiltrations and haemorrhages occur already in the early stages and cause finally a very poor prognosis. The incubation time as a rule amounts to 6 days. The increasing number of IVI and the high risk of damaged retinal structures due to intraocular infections should make postoperative retinal follow-up examinations mandatory, especially during the first 6 days.

Prognostic significance of chromosome 3 alterations determined by microsatellite analysis in uveal melanoma: a long-term follow-up study.

BACKGROUND: In uveal melanoma (UM), the most frequent primary intraocular tumour in adults, loss of one entire chromosome 3 (monosomy 3 (M3)) is observed in ~50% of tumours and is significantly associated with metastatic disease. The strong association of metastatic disease with M3 offers the opportunity for molecular prognostic testing of UM patients. METHODS: To re-evaluate M3 as prognostic marker in our clinical and laboratory setting and to determine the metastatic potential of rare tumours with partial M3, we performed a comprehensive study on 374 UM patients treated by enucleation in our clinic within 10 consecutive years, starting in 1998. Genotyping of all tumours was performed by microsatellite analysis. RESULTS: Median follow-up time was 5.2 years. The disease-specific mortality rates (death by UM metastases) for tumours with disomy 3 (D3) and M3 were 13.2% and 75.1%, respectively. The disease-specific survival was worse when M3 was observed together with chromosome 8 alterations (P=0.020). Death of UM metastases was also observed in 12 patients (9%) with D3 tumours. The metastasising D3 tumours showed a larger basal tumour diameter (P=0.007), and were more frequently of mixed or epitheloid cell type (P<0.0001) than D3 tumours that did not metastasise. Mortality rate of tumours showing partial M3 (8.3%) was as low as that for tumours with D3. CONCLUSION: This shows that large tumours with disomy 3 have an increased risk to develop metastases. On the basis of these results, our clinic offers routine prognostic testing of UM patients by chromosome 3 typing.

Bilateral Bartonella henselae neuroretinitis with stellate maculopathy in a 6-year-old boy.

PURPOSE: Bartonella henselae, the cause of cat-scratch disease in humans, may lead to characteristic vision-threatening ocular findings, which importantly indicate diagnosis. METHODS: This is an observational case report of a 6-year-old boy who presented with bilateral stellate maculopathy and lymphadenopathy. RESULTS: After serologic verification of B. henselae infection, systemic azithromycin therapy initiated the full recovery of visual acuity and bilateral complete resolution of stellate exudates during the following months. CONCLUSION: Stellate maculopathy should always include the differential diagnosis of B. henselae infection. In this rare case of bilateral stellate maculopathy, we observed full recovery of function following systemic macrolide therapy.

Current concepts for diagnosis and treatment of retinoblastoma in Germany: aiming for safe tumor control and vision preservation.

Retinoblastoma affects approximately 40 children in Germany per year. Most children are diagnosed early with localized intraocular disease, and the overall survival rate exceeds 95%. However, the prognosis of metastasized retinoblastoma remains poor. In 40% of the patients, retinoblastoma occurs bilaterally and, especially for these children, the salvage of the eye and visual function is of major importance. The variety of conservative treatment options for localized retinoblastoma includes laser coagulation, thermotherapy, cryotherapy, brachytherapy and chemotherapy. While systemic chemotherapy has nearly completely replaced external beam radiotherapy in the primary treatment of intraocular retinoblastoma, intra-arterial, intravitreal and periocular application of chemotherapy was also shown to be effective in treating intraocular retinoblastoma in case series. Genetic testing is an integral part of the routine diagnostics of all patients. Available tumor material should be analyzed to detect mutational mosaicism, that affects >10% of children with unilateral retinoblastoma. Genetic testing also identifies children with heritable (50% of patients) retinoblastoma. These children have a genetic predisposition for second malignancies. For this reason, late effects are an increasing concern and the care of patients with retinoblastoma requires a multidisciplinary approach to tailor therapy and long-term follow-up. Multicenter clinical trials are being developed to evaluate evidence-based treatment concepts for localized and metastasized retinoblastoma to improve survival rates and quality of life of children with retinoblastoma.

[TTF-1 (8G7G3/1) positive colon adenocarcinoma: diagnostic implications]. / TTF-1- (Klon 8G7G3/1) positives Kolonkarzinom: Diagnostische Implikationen.

Immunohistochemical evaluation of primary and secondary (adeno-) carcinomas of the lung often includes utilisation of two different clones (8G7G3/1 or SPT24) of TTF-1 (thyroid transcription factor 1) antibodies. In a subgroup of adenocarcinomas with a primary site other than the lung a positive reaction of clone SPT24 and also of clone 8G7G3/1 is described. We report on a patient with TTF-1 (clone 8G7G3/1) positive adenocarcinoma of the colon with metastases to the eye and lung and discuss TTF-1 based diagnostic considerations.

[New developments in molecular genetics and treatment of retinoblastoma]. / Neue Entwicklungen zur Genetik und Therapie des Retinoblastoms.

Retinoblastomas are the most frequent primary malignant intraocular tumours worldwide. Conventional and new treatment modalities have significantly improved the chance for survival and preservation of vision. The armamentarium of treatment modalities has been broadened recently by new techniques like intraarterial chemotherapy, which still has to be considered as experimental since long-term follow-up results are not yet available. The excellent prognosis for retinoblastomas in countries with a well developed health system is contrasted by the miserable prognosis for retinoblastomas in developing countries, which must be changed by a joint effort of all centres.

[Retinoblastoma]. / Retinoblastom.

Retinoblastomas represent 6% of all malignant tumors in children under 5 years old, which untreated lead to blindness in the affected eye and death due to metastases. The main symptoms are leukocoria and strabismus, which if possible, always necessitate a clarification within 1 week for exclusion of a retinoblastoma. The most frequent differential diagnoses are Coats' disease and persistent fetal vasculature (PFV) as well as other intraocular tumors, in particular astrocytomas. Systemic chemotherapy, if necessary in combination with laser hyperthermia, local chemotherapy and brachytherapy are the most important methods for eye-preserving treatment. Advanced cases mostly necessitate enucleation.

[Intraocular medulloepithelioma - series of 10 cases and review of the literature]. / Intraokulare Medulloepitheliome - klinische Serie mit 10 Fällen.

Intraocular medulloepithelioma is an extremely rare unilateral intraocular tumor arising from the nonpigmented ciliary epithelium. Medulloepitheliomas may be classified as benign and malignant and as teratoid and nonteratoid tumors. As a rule a long latency period occurs after first symptoms until the final diagnosis of a medulloepithelioma is made. Differential diagnosis includes in particular unilateral retinoblastoma. Intraocular medulloepithelioma may occur as masquerade-syndrome simulating uveitis. We present 10 patients with intraocular medulloepithelioma. In 7 of these patients the eye had to be enucleated. Metastasis did not occur, but epiretinal tumor seeding did occur in one patient. In one of the 3 not enucleated eyes, ruthenium-106 brachytherapy could salvage the tumor containing eye.

[Anaylsis of the surgeon factor in the treatment results of rhegmatogenous retinal detachment in the "scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment study"]. / Einfluss des Operateurs auf die Operationsergebnisse bei rhegmatogener Ablatio retinae im Rahmen der "Scleral Buckling versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment Study".

BACKGROUND: The effect of the surgeon on the outcome of surgical treatment for rhegmatogenous retinal detachment (RRD) has previously been analysed in a few studies only. In the prospective multicentre SPR study, scleral buckling (SBS) and primary vitrectomy (PV) were compared in RRD with medium complexity in a randomised fashion. In this study, we examined the surgeon factor on the outcome of RRD surgery within the SPR study. MATERIAL AND METHODS: An analysis of the surgeon as a factor on the functional outcome (logMAR visual acuity), primary anatomic success (retinal reattachment central to the aequator without any additional retina-affecting surgery including laser, cryo and macular pucker surgery) and final anatomic success (retinal reattachment one year postoperatively) was carried out. RESULTS: Overall, 416 phakic patients (209 SBS, 207 PV) and 265 pseudophakic patients (133 SB, 132 PV) were recruited by 45 surgeons in 25 centres. In the phakic group, the mean functional outcome of individual surgeons was between 0.2 and 0.74 (mean, 0.41, SD 0.41). This difference reached statistical significance (p = 0.0398). In the pseudophakic subgroup, the mean functional outcome was between 0.09 and 0.64 (mean, 0.42, SD 0.49) without reaching a statistical significance (p = 0.0715). Primary success per surgeon varied between 41.67 % and 90.00 % (mean, 63.16 %) in the phakic subgroup and 33.33- 80.95 % (mean, 61.75 %) in the pseudophakic subgroup. Final anatomic success was achieved in 92.86 - 100.00 % (mean, 97.96 %) in the phakic subgroup and 80.00 - 100.00 % (mean, 95.44 %) in the pseudophakic subgroup. There was no statistically significant correlation between surgeon and anatomic outcomes. CONCLUSION: In the phakic subgroup, a statistically significant correlation between surgeon and functional success could be demonstrated for RRD with medium complexity. This correlation was not interrelated to the surgical method. Functional outcome in pseudophakic patients and anatomic outcomes in both subgroups of phakic and pseudophakic patients showed no statistically significant correlation between surgeon and anatomic success.