[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.

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.

[Capillary hemangioma of the retina in cases of von Hippel-Lindau syndrome. New therapeutic directions]. / Kapilläre Hämangiome der Netzhaut beim Von-Hippel-Lindau-Syndrom. Neue Therapieansätze.

Thermal photocoagulation of small peripheral angiomas is the treatment of choice for capillary hemangiomas in patients with von Hippel-Lindau disease. Larger peripheral angiomas are better treated with beta-ray brachytherapy resulting in improved results in terms of local tumor control and the side effects of treatment. Photodynamic treatment is an alternative option in the management of capillary hemangiomas of the retina. Further improvement of the treatment results of photodynamic therapy may be achieved by combination with intravitreal drugs. External beam radiation using either stereotactic techniques or proton radiation must be considered as experimental. The treatment of juxtapapillary angiomas is still a therapeutic dilemma. Vitreoretinal surgery should be confined to advanced stages with tractional detachment or when no other treatment option is available to salvage the eye.

Ruthenium-106 plaque brachytherapy for symptomatic vasoproliferative tumours of the retina.

AIM: To investigate the safety and efficacy of beta ray brachytherapy in treatment of vasoproliferative tumours of the retina (VTR). METHODS: 35 consecutive patients with symptomatic VTR were treated with a ruthenium-106 ((106)Ru) plaque. Three tumours had been treated previously (two with cryotherapy; one with transpupillary thermotherapy). 32 VTR (91.4%) were located in the lower half of the retina and all of them were found between the mid-periphery and the ora serrata. The mean tumour thickness was 2.8 mm. An exudative retinal detachment was present in 25 eyes (71.4%) and in 15 cases (42.9%) hard exudates were found in the macula. The major symptom was loss of vision (77.1%). RESULTS: Brachytherapy was well tolerated by every patient. The mean applied dose was 416 Gy at the sclera and 108 Gy at the tumour apex. In all but four eyes (88.6%), it was possible to control the VTR activity. The median follow up time was 24 months. Three of the above mentioned four eyes with treatment failure had had secondary glaucoma before therapy. There was no case of radiation induced neuropathy or retinopathy. Cataract surgery was necessary for five patients. The development of epiretinal gliosis was the most common event during follow up (n = 10, 28.6%). The mean visual acuity decreased slightly (0.33 before and 0.29 after brachytherapy). Multivariate analysis showed that the presence of macular pathology before treatment was associated with a 6.1-fold risk of vision of 0.25 or better (p = 0.03). CONCLUSIONS: beta ray brachytherapy with (1106)Ru plaques was able to control the activity of VTR and retain vision. Cases with secondary glaucoma before treatment had a very poor prognosis.

[Development of an epiretinal prosthesis for stimulation of the human retina]. / Entwicklung einer epiretinalen Prothese zur Stimulation der humanen Netzhaut.

Degenerations of the outer retina in retinal diseases such as retinitis pigmentosa lead to blindness due to photoreceptor loss. A therapeutic option for visual rehabilitation is presently not available. Over the last few years, a retinal prosthesis has been developed and its use has been tested in animal experiments as well as in humans. With the epiretinal implant images of the environment are taken by a camera, these data are transmitted to an intraocular encoder, and the retina is electrically stimulated by a retinal stimulator placed epiretinally. The stimulation electrodes are placed as flexible microcontact electrodes by pars plana vitrectomy in an epimacular position. The threshold is determined by stimulations of increasing amplitudes. Initial results of acute epiretinal stimulation using an epiretinal implant in legally blind patients demonstrate that acute epiretinal stimulation of the human retina is feasible and safe.

Thermochemotherapy in hereditary retinoblastoma.

BACKGROUND/AIM: The combination of chemotherapy and transpupillary thermotherapy, thermochemotherapy (TCT) has become an established part of the treatment plan in advanced retinoblastoma. The aim of this study was to identify safe indications, the complications as well as the limitations of this new treatment for retinoblastoma. METHODS: Tumour response and side effects of TCT with an indirect laser ophthalmoscope (spot size about 400 micro m) in 55 tumours of 26 children with bilateral retinoblastoma were analysed. Using the Reese-Ellsworth classification system, nine of 35 eyes were classified as type I, 13 eyes as type II, 10 eyes as type III, and three eyes as type V. The mean age of the children was 0.74 (SD 0.61) years. The mean tumour height was 3.5 (2.3) mm with a mean diameter of 6.1 (4.1) mm. Treatment parameters were 4.3 (1.6) (median 5) thermochemotherapy sessions with a mean energy of 539 (211) mW and a mean duration of 13.5 (5.6) minutes. Chemotherapy courses (vincristine, etoposide, and carboplatin) were repeated every 3 weeks. The mean follow up period was 1.25 (0.6) years. RESULTS: Local recurrence occurred in 21 tumours (38%), with a mean onset of 3.2 (2.9) months after TCT. The risk of tumour recurrence was correlated with tumour height. The recurrence rate was 17% for tumours with a height less than 2 mm, 37% for tumours with a height between 2 and 4 mm, and 63% for larger retinoblastomas. Multivariate analysis identified fish flesh regression after TCT (p = 0.0007) as the most important risk factor for tumour recurrence besides tumour height (p = 0.001) and the necessity of increased laser power during TCT sessions (p = 0.018). Complications during therapy included transient corneal opacification in two eyes (6%), focal iris atrophy (three eyes, 8.5%), peripheral lens opacity (two eyes, 6%), circumscribed transient retinal detachment (one eye, 3%) and diffuse choroidal atrophy (one eye, 3%). CONCLUSION: TCT using an indirect laser ophthalmoscope with a spot size of about 400 micro m was efficient for retinoblastoma with a tumour height less than 4 mm. In larger tumours, the recurrence rate was unacceptably high. Fish flesh regression after TCT correlates with a higher rate of local tumour recurrence. Treatment related complications occurred in less than 9% of the treated eyes.

[Current therapy aspects of intraocular tumors]. / Aktuelle Therapieaspekte intraokularer Tumoren.

The most frequent primary intraocular malignancies are uveal melanoma in adults and retinoblastoma in children. Genetic findings in uveal melanoma now allow a better risk-prediction with regard to metastatic disease. New treatment modalities like endo-resection, trans-scleral resection, proton beam irradiation and trans-pupillary thermotherapy are now being established in clinical routine. Management of retinoblastoma has changed during the last years considerably. In hereditary retinoblastoma external beam radiotherapy (EBR) results in a sixfold increased risk for the development of secondary, non ocular malignant tumors in these patients. New treatment regimens based on systemic chemotherapy were developed to replace EBR. In combination with chemotherapy there has been a continuing trend toward more conservative focal treatment for retinoblastoma. Indications and first results of these new treatment modalities are presented.

Phacoemulsification following treatment of choroidal melanoma.

BACKGROUND: Little is known about the risks, effects and results of phacoemulsification following treatment with different modalities of choroidal melanoma. METHODS: In a retrospective study, records were evaluated of 72 patients who underwent cataract surgery after treatment of choroidal melanoma (35 were treated with iodine-125 plaques, 27 with ruthenium-106 plaques, eight by tumor excision, and two with proton beam irradiation). The data were analyzed with respect to complications, effects on postoperative tumor care and visual outcome. RESULTS: Phacoemulsification was performed at a mean interval of 21.5 months after primary tumor therapy. An intraocular lens (IOL) was implanted in 93% of the cases. The mean postoperative follow-up time was 16.2 months. Preoperative problems were rubeosis iridis (30.5%), secondary glaucoma (34.7%) and posterior synechiae (41.6%). Intraoperatively, defects of the posterior capsule occurred in 12.5%. Visual acuity equal to or better than preoperative vision was found in 95.8% of the patients as the best postoperative measurement and in 72.2% at the last follow-up measurement. A deterioration of more than two lines in visual acuity was observed in 4.2% as the best postoperative vision and in 27.8% at the last documented examination. Phacoemulsification was not the cause of deterioration in any of the cases. After cataract surgery, tumor retreatment was necessary in 19.4%. Treatment of radiation retinopathy was performed for the first time in 13.8%. Metastases developed in six patients (8.3%). CONCLUSION: Phacoemulsification following treatment for choroidal melanoma is both possible and advisable. The majority of patients have enhanced visual acuity. No decrease of vision occurred as a result of cataract extraction. The postoperative care of intraocular tumors and the treatment of radiation retinopathy is improved by timely cataract surgery.

MR of the eye with retrobulbar anesthesia.

MR imaging with retrobulbar anesthesia was performed in eight patients with uveal melanoma. Injection of 2 mL prilocain hydrochloride in 2% epinephrin into the eye muscle cone resulted in improved image quality in seven patients, without side effects. Ocular MR imaging can be indicated to clarify indeterminate sonographic findings in cases of extrascleral growth or to exclude optic nerve invasion in patients with tumors located at the posterior pole of the globe.