[Family screening in patients with retinal angiomatosis]. / Familienuntersuchungen bei Patienten mit Angiomatosis retinae.

BACKGROUND: The aim of this study was to characterise the results of a screening for von Hippel-Lindau disease (VHL), angiomatosis retinae (AR) and further VHL lesions in at-risk relatives of ophthalmological VHL index patients. METHODS: A retrospective analysis of 20 VHL index patients identified by the presence of angiomatosis retinae and a mutation of the VHL gene was carried out. A molecular genetic test for a VHL mutation and funduscopy was offered to all available at-risk relative. In the case of a positive test result, repeated screening for AR and further VHL lesions were suggested. RESULTS: Fifty-one out of 86 first- and second-degree relatives were screened, and 73 % showed a VHL mutation. At first presentation, asymptomatic AR was present in 55 %, at the end of the study in 72 % of gene carriers. In contrast to the index patients, angiomas were small and could be treated without functional loss. During the study 4 eyes of index patients developed blindness, whereas in the affected relatives no such event occurred. Affected relatives developed further VHL lesions to the same number and extent as the index patients. CONCLUSIONS: This study demonstrates the necessity of a screening of at-risk relatives of patients with AR and VHL. Molecular genetic screening allows an early identification of affected relatives. Early and regular screening enables the detection of small retinal angiomas and their treatment without functional loss.

[Treatment modalities for conjunctival melanoma]. / Therapeutische Optionen in der Behandlung des malignen Melanoms der Bindehaut.

BACKGROUND: Because of high local recurrence rates after excision of conjunctival melanoma adjuvant local chemotherapy employing mitomycin C (MMC) or irradiation is recommended. Brachytherapy is possible with ruthenium-106-plaques ((106)Ru) or with the strontium-90-plaques ((90)Sr). PATIENTS AND METHODS: Fifty-six patients received an excision and adjuvant radiotherapy of conjunctival melanoma between 1992 and 2007. The mean follow-up was 42 months (12 - 151 months). Mean age was 62 (28- 86) years. As an adjuvant radiotherapy 15 patients received X-ray irradiation, 12 patients received (106)Ru-brachytherapy, 4 patients received proton beam therapy and 16 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. Four patients received proton beam irradiation and in 13 patients an exenteratio was performed. RESULTS: Twelve patients (21 %) developed tumour recurrences in or adjacent to the irradiated area. Thirteen patients (22 %) showed a recurrence distant from the primary site. Ten patients (18 %) developed systemic metastasis during follow-up. Seven patients (46 %) had no recurrence during the follow-up. Three patients (20 %) had a recurrence in the treated or adjacent areas. Eight patients (53 %) developed new tumours in non-treated areas. CONCLUSIONS: Adjuvant radiotherapy allows an acceptable local tumour control rate after excision of conjunctival melanoma. No obvious differences regarding tumour control or systemic metastasis could be seen between the different modes of radiotherapy used.

[Recurrence rate following adjuvant strontium-90 brachytherapy after excision of conjunctival melanoma]. / Rezidivhäufigkeit nach Exzision von Bindehautmelanomen und adjuvanter Strontium-90-Kontaktbestrahlung.

BACKGROUND: Because of the high local recurrence rates after excision of conjunctival melanomas, adjuvant local chemotherapy or irradiation is recommended. Strontium-90 brachytherapy is one radiotherapeutic option due to its low penetration depth. METHODS: 15 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. The treatment was fractionated into 9 irradiation sessions with 6 Gy each. The mean follow-up was 35 months (12-60 months). RESULTS: Seven patients (46%) had no recurrence during the follow-up. Three patients (20%) had a recurrence in the treated or adjacent area. Eight patients (53%) developed new tumours in non-treated areas. CONCLUSIONS: Strontium-90 brachytherapy is a useful adjuvant in the treatment of conjunctival melanomas. Regular ophthalmoscopic controls are necessary because of the high rate of new tumours in non-irradiated areas, especially in cases with primary acquired melanosis.

[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.

[Juxtapapillary capillary retinal angioma with epiretinal membrane of the macula in familial Von-Hippel-Lindau-Syndrome]. / Juxtapapilläres kapilläres retinales Angiom mit epiretinaler Membran der Makula bei familiärem Von-Hippel-Lindau-Syndrom.

A case of juxtapapillary capillary retinal angioma associated with a vascularized epiretinal membrane of the macula in a 6-year-old girl is presented. Von-Hippel-Lindau-Syndrome was revealed by molecular genetic methods, and further family members were identified as gene carriers. The retinal angioma embedded in an epiretinal membrane was removed completely with the membrane by pars plana vitrectomy with a good functional result. Histopathology confirmed the diagnosis of capillary angioma.

[Endoresection following proton beam irradiation of large uveal melanomas]. / Endoresektion von grossen uvealen Melanomen nach Protonenbestrahlung.

PURPOSE: Large uveal melanomas located close to the optic nerve and/ or to the fovea have an unfavourable prognosis with regard to visual preservation and eye retention, due to the high incidence of radiation and tumour necrosis induced complications. Endoresection of the tumour after proton beam irradiation, is an alternative approach, aiming to reduce the incidence of ocular morbidity caused by tumour necrosis after sole radiotherapy. PATIENTS AND METHODS: 32 patients with large uveal melanomas (mean tumour thickness: 9.1 mm, mean tumour volume: 0.77 cc), received a primary proton beam irradiation (60 CGE) and underwent subsequent endoresection via a 3-port pars plana vitrectomy. The median pretreatment visual acuity was 0.2. The mean follow-up was 13.9 months. RESULTS: The postoperative visual acuity after 12 months was 0.12 (median, mean visual acuity loss 0.08). The probability of developing radiation retinopathy or papillopathy within the first year after treatment was 35% and 28% respectively and the probability of enucleation was 9% within the first postoperative year. No tumour recurrences were observed and 2 patients developed liver metastases. CONCLUSIONS: Endoresection following irradiation of large uveal melanomas located close to the optic nerve and/ or the fovea seems to be a useful and safe alternative to the traditional irradiation or enucleation. The incidence of complications following our approach seems to be lower when compared to radiation alone, where tumour necrosis is a substantial problem.

[Clinical characteristics of choroidal metastasis]. / Klinische Charakteristika der Aderhautmetastasierung.

BACKGROUND: Choroidal metastasis (CM) is the most common malignant intraocular tumor. The aim of this study was the characterization of the ophthalmoscopic aspect, the underlying tumor disease and differential diagnosis of this entity. STUDY DESIGN: Retrospective observational case series. PATIENTS AND METHODS: A total of 71 consecutive patients with CM were evaluated. Special attention was given to ocular symptoms, the ophthalmoscopic and sonographic aspects and the characteristics of the underlying tumor disease. All patients had undergone screening (CCT, CT of thorax and abdomen; bone scintigraphy) for the primary tumor and further organ metastases. RESULTS: Of the patients 95% had symptomatic CM, in 5% of the patients CM was detected by chance, 60% had a single CM, 40% showed multiple (2-14) lesions and 18% ( n=13) had no history of tumor disease. In 12 of these patients lung cancer could be diagnosed. In 53% of the patients the primary tumor was breast cancer, in 26% lung cancer, in 3% kidney cancer, bowel cancer, choroidal or cutaneous melanoma and in single patients cervical, ovarian, thymus or prostate cancer. In one patient who died from disseminated metastases, no definite primary tumor could be detected. Of the patients 96% had further metastases, CM occurred with a mean interval after diagnosis of the primary of 9 months in lung cancer and 68 months in breast cancer. CM was the first clinical sign of tumor disease in 58% of patients with lung cancer and the first clinical sign of metastatic disease in 28% of patients with breast cancer. CONCLUSIONS: Choroidal metastasis occurs almost exclusively in metastatic disease. In breast cancer it typically occurs years after diagnosis of the primary tumor and may be the first sign of metastatic disease. In lung cancer choroidal metastasis may be the first sign of the tumor disease.

[Indocyanine green angiography in choroid metastases]. / Indocyaningrün-Angiographie bei Aderhautmetastasen.

BACKGROUND: Up to now the diagnosis of choroidal tumors was mainly based on ophthalmoscopy and ultrasound examination. Indocyanine green angiography allows the identification of vascular patterns in these tumors, which could be helpful in the differential diagnosis. The aim of the study was to characterize the staining patterns of choroidal metastases. METHODS: In the years 1996-2000 we performed ICG-A of 15 choroidal metastasis using the scanning laser ophthalmoscope from Rodenstock. The mean tumor height was 3.7 mm (2.0-9.0). These angiographies were compared to the angiographies of 38 choroidal malignant melanomas with a mean height of 3.6 mm (1.4-6-6). RESULTS: All metastases showed a blockage of the background staining and a patchy staining of the tumor surface. Intratumoral vessels could be detected in 13% of all cases of metastases. The choroidal melanomas examined showed a blockage of the background staining in all cases and tumor vessels in 89%. CONCLUSION: The angiographic picture of the metastatic lesions was characteristic. Intratumoral vessels could not be detected using ICG-A. Most of the metastases showed a patchy staining of the tumor surface.

[Vitrectomy in advanced Coats disease]. / Vitrektomie bei fortgeschrittenem Morbus Coats.

BACKGROUND: Coats disease is a retinal vasculopathy of unknown cause. Untreated cases usually lead to an exudative retinal detachment and rubeosis iridis with secondary glaucoma. Photocoagulation and/or cryotherapy are generally the first interventions in treating the disease. Pars plana vitrectomy may be indicated in cases of vitreous hemorrhage or retinal detachment. METHODS: We performed pars plana vitrectomy in 9 eyes with Coats disease between 1992 and 1999. A retinal detachment was present in 3 cases, and three showed a vitreous hemorrhage. In two cases surgery was indicated because of paramacular localization of the pathological vessels with associated exudations. RESULTS: The two cases with paramacular involvement showed improvement in visual acuity of eight lines. In the remaining cases visual acuity remained within two lines compared to the initial visual acuity. All eyes except one could be saved. CONCLUSION: Pars plana vitrectomy is a useful option in treating advanced Coats disease, especially in cases associated with vitreous hemorrhage or retinal traction.

[Intraocular metastases of metastatic breast carcinoma in the woman. Incidence, risk factors and therapy]. / Intraokulare Metastasen bei metastasiertem Mammakarzinom der Frau. Inzidenz, Risikofaktoren und Therapie.

BACKGROUND: The breast cancer metastasis is the most common intraocular tumor in females. Aim of this study was to determine incidence and risk factors for intraocular metastasis and to evaluate the benefit of an early treatment. PATIENTS AND METHODS: 151 patients suffering from metastatic breast cancer were screened for the presence of intraocular metastasis. The medical history and the tumor status at the time of screening were evaluated and risk factors for intraocular metastasis were determined. In case of choroidal metastasis external beam radiotherapy was performed. RESULTS: Intraocular metastasis was found in 7 out of 151 patients screened (4.6%). In one patient metastasis was located in the iris, in 6 patients in the choroid. Intraocular metastasis was only found in patients with more than one other organ system involved into disease (p = 0.002). In this subgroup of patients (n = 65) prevalence of intraocular metastasis was 10.8%. Other risk factors for intraocular metastasis were presence of lung metastasis or brain metastasis. In 5 out 6 patients with choroidal metastasis external beam radiotherapy was performed, resulting in durable regression of metastasis and stabilization or improvement of visual acuity. CONCLUSION: The prevalence of intraocular metastasis in metastatic breast cancer was determined to be 4.6%. It is most commonly located in the choroid and develops in the course of advanced metastatic disease. Since early external beam radiotherapy of choroidal metastasis prevents functional loss, patients at risk should be given an ophthalmological screening for intraocular metastasis.

Radiotherapy of Choroidal Metastases in Patients with Disseminated Cancer.

BACKGROUND: Choroidal metastasis is the most common ocular tumor, in most cases related to breast and lung cancer. Radiotherapy (RT) mostly is the therapy of choice. However, there is a lack of data about the results of uniformly, prospective treated patients. PATIENTS AND METHODS: Between November 1994 and September 1997, 37 patients with 49 metastatic eyes were enrolled into the study. 25 patients (68%) had unilateral and 12 patients (32%) had bilateral metastases. 21 patients had breast cancer as primary tumor, 12 patients lung cancer, and 4 patients other tumors. 3 patients were excluded from analysis, 34 patients with 46 involved eyes were available for analysis. 29 of those patients had symptomatic metastases, 5 patients had asymptomatic choroidal metastases. RT was performed with bi- or unilateral asymmetric fields, total dose was 40 Gy with a single dose of 2 Gy, 5 fractions per week. 12 patients (35%) had a chemotherapy following RT due to diagnosis of general tumor progression. Endpoints of the study were visual acuity (VA), local tumor control, survival, and side effects. RESULTS: The median follow up was 6 months, 22 out of 34 patients died of metastatic disease. In 17 of symptomatic eyes (53%) an increase of VA and in 11 of symptomatic eyes (34%) a 'no change' was achieved. The local tumor control rate after 18 months was 83%. One patient with asymptomatic metastasis (1/14 eyes) developed symptoms until death. The median survival time was 15 months. Altogether, in 2 patients late side effects (6%) were observed (1 patients with bilateral retinopathy, 1 patient with optic nerve atrophy). CONCLUSIONS: RT with 40 Gy is highly effective in the treatment of symptomatic and asymptomatic choroidal metastases, VA was stable or improved in almost 90% of treated eyes. The rate of side effects is low. Copyright 2000 S. Karger GmbH, Freiburg

Retinal angiomatosis and von Hippel-Lindau disease.

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.

Choroidal metastasis in men with metastatic breast cancer.

PURPOSE: To report two cases of choroidal metastasis in metastatic breast cancer in men. METHOD: Case reports of a 50-year-old man with an 8-year history of breast cancer who was initially examined with a solitary amelanotic choroidal tumor and a 62-year-old man with an 8-month history of breast cancer who was initially examined with numerous unilateral amelanotic choroidal tumors. RESULTS: Ophthalmoscopic and echographic characteristics of the choroidal tumors were typical for breast cancer metastasis. Systemic screening disclosed advanced metastatic disease in both patients. Choroidal metastasis could be effectively treated by external beam irradiation. CONCLUSIONS: Although breast cancer is a rare condition in men, it should be considered as a possible primary cancer in cases of choroidal metastasis.

[Retinal capillary angioma. Clinical and molecular genetic studies]. / Kapilläres retinales Angiom. Klinische und molekulargenetische Untersuchungen.

UNLABELLED: Capillary retinal angiomas are rare vascular tumors that frequently occur in von Hippel-Lindau syndrome (vHL) but may also be sporadic. In all patients presenting with this tumor a thorough search for other vHL-associated lesions must be performed. After identification of the vHL gene on the short arm of chromosome 3 (3p25-26), the diagnosis is supported by molecular genetic analysis. PATIENTS: In 20 patients with retinal angioma a clinical search for other manifestations of vHL was performed. In 5 patients only one angioma was present. In all patients molecular genetic tests for a mutation of the vHL gene were performed by SSCP and direct sequencing. RESULTS: In 16 (80%) patients vHl was present, and in 15 it could be diagnosed by clinical findings or a positive family history. Organ lesions in vHL patients were CNS hemangioblastoma in 10 (63%), pancreatic cysts in 7 (43%) and renal cysts in 7 (43%) patients. In two patients (13%) renal carcinoma could be detected; in one patient a pheochromocytoma was present. A mutation could be detected in all 15 patients with clinically confirmed vHL. In three patients a new mutation of vHL disease was diagnosed genetically. In one of these patients a single retinal angioma was the only sign of vHL. CONCLUSION: In patients presenting with capillary retinal angioma a careful search for other vHL lesions has to be performed. A mutation of the vHL gene can be detected in the majority of patients; thus, molecular genetic testing is a powerful tool for diagnosis and detection of asymptomatic gene-carriers.

Radiotherapy of unilateral choroidal metastasis: unilateral irradiation or bilateral irradiation for sterilization of suspected contralateral disease?

Radiotherapy is the highly effective standard in the treatment of choroidal metastasis. Visual acuity can be stabilized or increased in about 70-80% of eyes treated, thus prevailing the quality of life in these worse prognostic patients. In about 30-40% bilateral macroscopic disease is found at diagnosis. The best treatment for unilateral metastasis remains controversial: unilateral or bilateral irradiation for sterilization of suspected contralateral metastasis or unilateral irradiation without irradiation of the contralateral choroidea. In the analysis of a prospective study (ARO 95-08) 35 out of 50 patients with choroidal metastasis had unilateral disease and received unilateral irradiation with a lateral field using 6 MeV-photons (40 Gy in 20 fractions) without sparing the contralateral choroidea. Therefore the posterior contralateral choroidea received 50-70% of the total dose (20-28 Gy) for suspected micrometastasis. None of these patients developed contralateral choroidal metastasis during the median follow up time of 11.5 months. A unilateral field with 40 Gy for unilateral choroidal metastasis without sparing the contralateral choroidea seems to be effective in destroying contralateral micrometastasis with a lower risk of late side effects compared with bilateral fields.

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.

Frequency of asymptomatic choroidal metastasis in patients with disseminated breast cancer: results of a prospective screening programme.

AIM: To determine the frequency of visually asymptomatic choroidal metastasis in patients with disseminated breast cancer and its dependence on the incidence of metastasis by number and site of other organ metastases. METHODS: From January 1995 until April 1997 120 patients irradiated for disseminated breast cancer underwent ophthalmological screening for choroidal metastasis. No patient was symptomatic for ocular disease. 68 out of 120 patients were found to have metastases in one organ and 52 patients had metastases in more than one organ. 80% of the patients had bone metastases, 25% lung metastases, 22% liver metastases, 15% brain metastases, and 22% had metastases in other organs. RESULTS: Six patients (5%) were found to have asymptomatic choroidal metastases. Five patients had unilateral and one patient bilateral metastases. 52 patients with more than one involved organ had a significantly higher risk for asymptomatic choroidal metastasis (6/52, 11%) than 68 patients with metastases in only one organ (0/68) (p = 0.006). In univariate analysis a significantly higher risk was seen for patients with lung metastases (14% choroidal metastases versus 2% in patients without lung metastases, p = 0.03) and for patients with brain metastases (17% choroidal metastases versus 3% in those without brain metastases, p = 0.04). CONCLUSION: In disseminated breast cancer the incidence of asymptomatic choroidal metastases was 5% and increased to 11% when more than one organ was involved in metastatic spread. Risk factors for choroidal metastases were dissemination of disease in more than one organ and the presence of lung and brain metastases.