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A wide variety of tumors can arise in the retina, having their origin either in retinal cells (retinocytes and glial cells), the retinal vasculature (vascular endothelium) or the retinal pigment epithelium. This article summarizes the clinical features of the retinal tumors that are encountered primarily in adults. With the advent of molecular genetic testing, the majority of these tumors can be associated with a genetic disorder, which further helps the early detection of associated pathologies in other organs. The best-known example is probably the von Hippel–Lindau syndrome, which is caused by a mutation of the VHL gene. The ophthalmologist is often the first physician to recognize and establish the diagnosis, since retinal capillary hemangioblastomas are commonly the first sign of this syndrome. Retinal astrocytomas are often associated with the tuberous sclerosis complex, combined hamartomas can be associated with neurofibromatosis type 1 or 2 and retinal pigment epithelium hamartomas can be associat...

Purpose: To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer. Methods: Twenty-two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies. Results: In eight of 22 (36%; 95% confidence interval [CI] 17–59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65–97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies. Conclusions: Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.

Background: The aim of this study was to evaluate patients with solitary juxtapapillary capillary retinal angioma for the presence of von Hippel—Lindau disease (VHL). Methods: A retrospective case series of 11 patients, each presenting with a solitary juxtapapillary capillary retinal angioma, was examined. Patients were evaluated for type of angioma, presence of other VHL lesions, and mutations of the VHL gene. Results: Juxtapapillary angioma was exophytic in 7 patients and endophytic in 4 patients. VHL could be diagnosed in 7 patients (64%). Four patients were affected by VHL-related lesions as distinct from ocular angioma. A mutation of the VHL gene could be detected in 6 patients; in 1 of these patients, this mutation of the VHL gene was the only evidence of VHL.There was no difference in the age at manifestation or the type of juxtapapillary angioma in VHL patients compared with non-VHL patients. Interpretation: A solitary juxtapapillary angioma may indicate the presence ofVHL in a majority of patients, irrespective of the growth pattern of the tumour. Molecular genetic diagnostics is the most effective method of detecting VHL. Because of the high risk of the presence of other VHL lesions,thorough screening for VHL is mandatory for patients presenting with a solitary juxtapapillary angioma.

Objective To characterize the clinical course of retinal angiomatosis (RA) in von Hippel–Lindau (VHL) disease. Design Retrospective observational case series from a tertiary referral center. Participants Fifty-seven consecutive VHL disease patients with RA with a mean follow-up of 7.3 years. Methods A retrospective chart review was performed to characterize the clinical course and functional outcome of RA to substantiate ophthalmic screening recommendations for VHL disease patients. Main Outcome Measures Age and visual acuity (VA) at diagnosis, angioma number, size, fundus position and growth behavior, functional outcome, and risk factors for adverse visual outcome (VA ≤20/1000) were evaluated. Results The onset of RA was observed to occur between the ages of 5.5 and 62.5 years. Ocular disease was unilateral in 58% of patients at diagnosis; prevalence of bilateral RA as calculated by Kaplan–Meier analysis was 100% at age 56.4 years. Twenty-seven eyes showed an adverse visual outcome, occurring at a mean age of 23.2 years. Risk factors included large angiomas at presentation, first manifestation at a younger age, and symptomatic RA. In most eyes, development of new angiomas was slow and only small angiomas were detected on annual follow-up. Eyes harboring multiple angiomas or RA complicated by retinal detachment were at risk of developing large angiomas after short follow-up intervals. Formation of new angiomas was largely independent of patient age. Conclusions Retinal angiomatosis in VHL disease bears a high risk of severe vision loss at a young age. In uncomplicated RA, annual ocular screening for presymptomatic angiomas is sufficient. Because RA can occur at any age, lifelong ocular screening is recommended in VHL disease gene carriers starting at preschool age.

Primary pars plana vitrectomy (PPPV) has gained widespread popularity in the treatment of rhegmatogenous retinal detachments (RRD). However, the surgical procedure is still flawed by a significant rate of anatomical and functional failures. The study was conducted to analyse the risk factors for a dissatisfying postoperative outcome.We carried out a retrospective study of 512 cases of PPPV with a minimum follow-up of 3 months from one institution over a 9-year period. Preoperatively, 24.8% of patients (127 out of 512) were pseudophakic, 16.4% (84 out of 512) highly myopic, 19.9% (102 out of 512) had preoperative proliferative vitreoretinopathy (PVR) and 14.6% (75 out of 512) had vitreous haemorrhage.The follow-up period ranged from 3 to 108 months (median 14.8). Retinal reattachment was achieved with one operation in 70.7% (362 out of 512) and after one or more operations in 97.5% of cases (499 out of 512). The major reasons for redetachments were new retinal breaks, followed by a combination of new breaks and PVR, and PVR without apparent breaks. Postoperative visual acuities ofor =0.1 andor =0.4 were achieved in 82.8% (424 out of 512) and 48.2% (247 out of 512) respectively. Out of 376 phakic patients at study entry, 66.4% (250 out of 376) underwent cataract surgery either in combination with PPPV or during the postoperative course. Factors that were significantly associated with either anatomical or functional failure included duration of symptoms, low preoperative visual acuity, myopia, amblyopia, hypotony, macular detachment, preoperative PVR, extent of detachment, involvement of inferior quadrants, no detectable breaks, large breaks, breaks posterior to the equator, surgeon, level of surgical training, endocryotherapy, and combined scleral buckling surgery.Primary pars plana vitrectomy is still flawed by a relatively high primary redetachment rate following the initial procedure. The advantages of the technique are a high final reattachment rate and relatively good functional results in a subset of patients with more complicated types of RRD. The risk factors for postoperative failures following PPPV for RRD match to a large extent those following scleral buckling surgery (SBS). Future improvements of the technique will have to focus on modifiable risk factors, such as details of the surgical procedures, surgical training and case selection, to distinguish it from SBS.

Von Hippel-Lindau disease (VHL) and neurofibromatosis type 1 (NF 1) are hereditary multitumor syndromes that show associated ocular manifestations. Capillary retinal angioma, a benign vascular tumor, is the classical ocular lesion in VHL. It often appears as the first manifestation of the disease and may thus lead to the diagnosis of VHL. Since small angiomas can be treated easily by laser photocoagulation, a regular ocular screening of VHL patients is recommended. Ocular manifestations of NF 1 are more diverse as compared to VHL. Lisch nodules of the iris are an important diagnostic criteria of NF 1 since they can be found in almost every affected patient. Optic glioma can occur both intraorbitally and intracranially. The intraorbital form causes progressive protrusion of the globe and eventually blindness. Extension of the tumor beyond the chiasm worsens the prognosis quoad vitam. The hallmark of NF 1, namely cutaneous neurofibroma can cause visual impairment when affecting the skin of the eyelids. The rare intraorbital pexiform neurofibroma is associated with abnormal development of the orbital bones and infantile glaucoma. It may result in orbital mass effects and therefore may need surgical excision.

In June 1998, proton-beam therapy of ocular tumors started at the Hahn-Meitner Institute Berlin, Germany. The purpose of the present study is to evaluate treatment outcome for uveal melanomas. 245 consecutive patients with primary melanoma of the uvea were treated from June 1998 to April 2003 with a 68-MeV proton beam. In 96.2% of all patients, a uniform fractionation scheme was applied: single dose 15 CGE (cobalt gray equivalent), total dose 60 CGE on 4 consecutive days. Follow-up is available in 229 patients. At the time of median follow-up (18.4 months), local control is 96.4% and 95.5% at 3 years. Eye retention rate is 92.6% at 20 months (median follow-up) and 87.5% at 3 years. Proton-beam irradiation of uveal melanomas at the Hahn-Meitner Institute after the first 5 years of its initiation reveals local tumor control and eye retention rates in the range of other centers with larger experience. Delivering high treatment quality in hadron therapy from the beginning has been achieved.

Hintergrund Grose uveale Melanome, die sich in der Nahe der Papille und/ oder der Fovea befinden, haben wegen der zu erwartenden Spatkomplikationen eine ungunstige Prognose bezuglich des Visus- und Bulbuserhaltes. Die Endoresektion dieser Tumoren ist eine neue Behandlungsmodalitat, die moglicherweise Vorteile in der Therapie dieser komplizierten Falle bieten wird.

To determine the clinical incidence and characteristics of symptomatic choroidal metastasis (CM) in breast cancer.Forty-six consecutive patients with CM from breast cancer were retrospectively reviewed in respect of ocular findings, medical history and systemic disease. Clinical incidence of CM was determined and compared with the incidence predicted from prevalence data obtained in ocular screening studies.Choroidal metastasis occurred with a median interval of 42.4 months after diagnosis of breast cancer and was predominantly unilateral (63% patients) and solitary (57% affected eyes). A total of 32% of patients had no history of metastatic tumour disease, but systemic screening with CT and scintigraphy revealed metastatic disease in 100% of patients. A median number of three other organs were affected by metastasis. Median survival from diagnosis of CM was 13.1 months. The mean number of local patients diagnosed with CM was 2.9 per year, which was one order of magnitude less than predicted from clinical screening studies.Choroidal metastasis occurs in advanced metastatic breast cancer, indicating a grave vital prognosis. In a minority of patients (32%) it is the first sign of metastatic disease. The clinical incidence of CM is far smaller than predicted from prevalence data obtained from ocular screening studies.

The aim of this study was to evaluate patients with solitary juxtapapillary capillary retinal angioma for the presence of von Hippel-Lindau disease (VHL).A retrospective case series of 11 patients, each presenting with a solitary juxtapapillary capillary retinal angioma, was examined. Patients were evaluated for type of angioma, presence of other VHL lesions, and mutations of the VHL gene.Juxtapapillary angioma was exophytic in 7 patients and endophytic in 4 patients. VHL could be diagnosed in 7 patients (64%). Four patients were affected by VHL-related lesions as distinct from ocular angioma. A mutation of the VHL gene could be detected in 6 patients; in 1 of these patients, this mutation of the VHL gene was the only evidence of VHL. There was no difference in the age at manifestation or the type of juxtapapillary angioma in VHL patients compared with non-VHL patients.A solitary juxtapapillary angioma may indicate the presence of VHL in a majority of patients, irrespective of the growth pattern of the tumour. Molecular genetic diagnostics is the most effective method of detecting VHL. Because of the high risk of the presence of other VHL lesions, thorough screening for VHL is mandatory for patients presenting with a solitary juxtapapillary angioma.

To determine the effectiveness and risk profile of combined ruthenium- (Ru)-106-brachytherapy and transpupillary thermotherapy (TTT) of the tumour apex for the treatment of large choroidal melanoma.A consecutive series of 31 large choroidal melanoma treated by Ru-106-brachytherapy and adjuvant TTT was studied. TTT was performed 1 day prior to plaque removal and up to 3 times (mean: 1.8) during follow-up. Evaluation comprised tumour regression, treatment-related adverse events, necessity of additional treatment and visual results.Mean follow-up was 21.6+/-7.8 (10.8-38.3) months. Mean tumour thickness was 6.8+/-1.0 (5.0-8.9) mm prior to treatment. Mean residual tumour thickness at the end of follow-up was 2.5+/-1.0 mm. Relevant adverse treatment effects were exudative maculopathy or macula oedema (22.6%), vitreous haemorrhage (16.1%), optic neuropathy (16.1%) and retinal detachment (9.7%). One tumour recurrence occurred during follow-up, and was treated by enucleation.The combination of Ru-106-brachytherapy with TTT allows for the treatment of large posterior choroidal melanoma. The rate of treatment-related adverse events appears to be acceptable.

Purpose To describe the treatment of juxtapapillary capillary angioma by pars plana vitrectomy (PPV) and tumor excision. Design Interventional case report. Methods A 6-year-old girl with symptomatic juxtapapillary capillary retinal angioma with associated epiretinal membrane (ERM) underwent PPV and extraction of the tumor and ERM. A clinical and molecular genetic workup for the presence of von Hippel–Lindau disease (VHL) was performed. Results A favorable functional result without tumor recurrence was achieved. Capillary retinal angioma was confirmed by histology of the surgical specimen, and familial VHL was revealed. Conclusions PPV and extraction of the tumor is applicable in juxtapapillary capillary retinal angioma with associated ERM. A workup for the presence of VHL is pertinent in patients presenting with this tumor entity.

To characterize the clinical course of retinal angiomatosis (RA) in von Hippel-Lindau (VHL) disease.Retrospective observational case series from a tertiary referral center.Fifty-seven consecutive VHL disease patients with RA with a mean follow-up of 7.3 years.A retrospective chart review was performed to characterize the clinical course and functional outcome of RA to substantiate ophthalmic screening recommendations for VHL disease patients.Age and visual acuity (VA) at diagnosis, angioma number, size, fundus position and growth behavior, functional outcome, and risk factors for adverse visual outcome (VAor =20/1000) were evaluated.The onset of RA was observed to occur between the ages of 5.5 and 62.5 years. Ocular disease was unilateral in 58% of patients at diagnosis; prevalence of bilateral RA as calculated by Kaplan-Meier analysis was 100% at age 56.4 years. Twenty-seven eyes showed an adverse visual outcome, occurring at a mean age of 23.2 years. Risk factors included large angiomas at presentation, first manifestation at a younger age, and symptomatic RA. In most eyes, development of new angiomas was slow and only small angiomas were detected on annual follow-up. Eyes harboring multiple angiomas or RA complicated by retinal detachment were at risk of developing large angiomas after short follow-up intervals. Formation of new angiomas was largely independent of patient age.Retinal angiomatosis in VHL disease bears a high risk of severe vision loss at a young age. In uncomplicated RA, annual ocular screening for presymptomatic angiomas is sufficient. Because RA can occur at any age, lifelong ocular screening is recommended in VHL disease gene carriers starting at preschool age.

Background and purpose There is no evidence in the literature about the incidence of synchronous brain metastases in patients with choroidal metastases. This is of major importance, because the radiation fields of choroidal metastases and, later on, brain metastases, if treated consecutively, are partly overlapping, thus potentially increasing the rate of late side effects such as brain necrosis. The goal of this study was to determine the frequency of synchronous brain metastases. Patients and methods 50 patients with choroidal metastases were enrolled into a study of the "Arbeitsgemeinschaft Radiologische Onkologie" of the German Cancer Society (ARO 95-08) with standardized 40 Gy radiotherapy, 2 Gy single dose. All patients were staged before treatment with a computed tomography of the brain (CCT). No patient showed clinical signs of brain metastases. Results 13 out of 50 patients (26%) had brain metastases in the CCT leading to radiotherapy of the brain and choroidal metastases in one volume. Conclusion A CCT is indicated at the diagnosis of choroidal metastases for screening of synchronous brain metastases. The incidence is about 25%, and the diagnosis of brain metastases results in a different target volume: the whole brain including the posterior parts of the eyes compared to the posterior parts of the eyes alone. Therefore, the risk of late side effects could be reduced compared with an additional later radiotherapy of the whole brain with partly overlapping fields.

The vascularisation features of intraocular tumours may be characterised by indocyanine green angiography (ICG-A) and fluorescein angiography (FA). Proton beam irradiation is an established method of treating malignant melanoma of the choroid. The aim of this study was to describe the vascularisation features of small choroidal melanomas and to examine the influence of proton beam irradiation on these tumours.We examined 39 choroidal melanomas by ICG-A and FA from 1998 to 2001 in a prospective study. The tumours had a mean prominence of 3.65 mm (1.2-7.5 mm) and a common feature of all was their parapapillary or paramacular localisation. Angiography was always performed immediately before proton beam radiotherapy and at intervals of 3 months, half a year and 1 year thereafter. Two hundred and forty angiographies were analysed in total.Intra-tumoral vessels could be visualised in 89% of all tumours by ICG angiography but in only 33% by FA. Neither ICG-A nor FA detected changes 3 months after irradiation; however, ICG-A disclosed strong leakage from vessels in the tumour area after 6 months. These changes increased markedly after 12 months and were also visible by FA. A disadvantage of FA, however, was the faster escape of dye from the vessels, which caused rapid leakage in the tumour area and meant that details could no longer be demonstrated.ICG-A and FA detect marked vascular changes within the tumours examined.

Background: To evaluate the significance of angioma number (single or multiple) for the presence of von Hippel-Lindau (VHL) disease in patients presenting with capillary retinal angioma. Methods: Forty-one nonrelated patients presenting with capillary retinal angioma were evaluated. An ophthalmic workup, screening for other organ lesions, and molecular genetic screening for a mutation of the VHL gene was performed. The diagnosis of VHL was made on the basis of the personal and family history, the presence of other VHL-associated organ lesions, or the presence of a mutation of the VHL gene. Results: Thirteen patients (32%) presented with a single angioma and 28 patients (68%) presented with multiple angiomas. In 81% of all patients, VHL could be diagnosed. Diagnosis of VHL could be readily made by the personal or family history in 51% of all patients. In another 27% of all patients, VHL disease was evidenced by screening for other VHL-associated lesions. In two patients (3%) VHL could be diagnosed by molecular genetics only. All patients with multiple retinal angiomas had VHL disease and, in 38% of patients with a single angioma, VHL was present. Reasons for a missing family history in patients with VHL disease were the presence of a de novo mutation (15% of VHL patients) or clinical anticipation of VHL disease (18% of VHL patients). Conclusion: The presence of multiple retinal angiomas strongly suggests VHL disease, which, however, can be obscured by presence of a de novo mutation or by clinical anticipation of VHL disease in affected families. A single retinal angioma may be sporadic as well as the presenting sign of VHL. Diagnosis and screening for this multitumor syndrome is substantially supported by molecular genetics.

A short-circuit current experiment on epithelial ion transport is described that is suitable for student classes in human and animal physiology. Segments of late distal colon from either pig or cow are obtained from the slaughterhouse depending on the animals' daily schedule. Initial tissue preparation already in the slaughterhouse, cold storage, and proper choice of bath solutions are essential prerequisites for success. Students monitor spontaneous transepithelial voltage and short-circuit current (Isc) by use of manually operated voltage clamp units. Two main transport mechanisms are studied, electrogenic Na+ absorption and Cl- secretion. Electrogenic Na+ absorption is studied by measuring the Isc drop after amiloride. Then Cl- secretion is stimulated by theophylline and subsequently inhibited by furosemide. In some experiments K+ secretion can be detected by the blocking effect of mucosal Ba2+. Response of tissues from pig and cow is qualitatively similar but quantitatively different. The equipment is sturdy and inexpensive, can be provided by most departmental workshops, and has been tested for 3 yr in regular lab courses. Observations made during these experiments are closely related to clinical states, such as secretory diarrhea, cystic fibrosis, and hyperaldosteronism, as well as to the mechanisms of clinically used diuretics.