Quality of life in the follow-up of uveal melanoma patients after enucleation in comparison to CyberKnife treatment.

PURPOSE: To compare quality of life (QoL) in patients with uveal melanoma after enucleation and stereotactic radiosurgery to that in an age-matched patient collective. METHODS: QoL was assessed in a cross-sectional survey and compared among 32 uveal melanoma patients after enucleation, 48 patients after stereotactic radiosurgery (CyberKnife(®); Accuray(®) Incorporated, Sunnyvale, CA, USA), and an age-matched control group of 35 patients, using the SF-12 Health Survey. Statistical analysis was performed with Fisher's exact test, Student's t test, one-way ANOVA analysis, Wilcoxon rank-sum (Mann-Whitney test), and ordered logistic regression for multivariate analysis. RESULTS: There was no significant difference in QoL between patients treated by stereotactic radiosurgery and the age-matched control group. After enucleation, patients presented significantly lower values in Physical Functioning (PF), Role Physical (RP), and Role Emotional (RE) compared to the radiosurgery and control group. To control for the overall QoL lowering effect of visual loss, the QoL of the patients who underwent enucleation was compared with the QoL of patients suffering severe functional loss after CyberKnife radiosurgery in a subgroup analysis, which showed no statistically significant difference. The number of comorbidities had a significant impact on QoL in multivariate analysis. CONCLUSIONS: Superior performance in PF, RP, and RE suggests that CyberKnife represents a suitable first-line therapy for uveal melanoma. In cases with painful amaurosis or vast tumor recurrence, enucleation can be performed with an acceptable QoL outcome.

Microbial contamination of multi-use ophthalmic solutions in Kenya.

BACKGROUND/AIMS: Contaminated ophthalmic solutions represent a potential cause of avoidable ocular infection. This study aimed to determine the magnitude and pattern of microbial contamination of multi-dose ocular solutions at the Department of Ophthalmology, University of Nairobi, at the Kenyatta National Hospital, Kenya. METHODS: 101 vials were obtained for microbial examination after an average use of 2 weeks. The dropper tip and the residual eye drop were examined for contamination. The specimens were cultured, the number of colonies counted, the organisms identified and susceptibility testing to selected antimicrobial agents was done. RESULTS: Six (6%) of the 101 analysed vials were contaminated: 4/77 vials (5%) from a multi-user setting and 2/24 vials (8%) from a single user setting. Three contaminations (3/38, 8%) occurred in vials from the eye ward, another three (3/59, 5%) in vials from the outpatient clinic. Most bacteria identified belonged to the normal commensal flora of the eye. Isolated contaminants were micrococci (n = 2), Staphylococcus epidermidis, Haemophilus sp, Bacillus sp and a Gram negative rod. The dropper tip was more often contaminated (n = 6) than the residual solution (n = 1), and only one vial showed a contamination of both the drop and the tip. CONCLUSION: Our data show a contamination rate of 6%, which is in the lower range of data published on the contamination of eye drops elsewhere (0.07% to 35.8%).

[International initiatives for the prevention of blindness]. / Internationale Initiativen zur Prävention von Blindheit.

Since 1974, when the International Agency for the Prevention of Blindness (IAPB) was founded, international campaigns for blindness prevention have gained tremendous momentum in collaboration with the WHO's blindness prevention programme. In 1999 WHO and IAPB launched the campaign Vision 2020, The Right to Sight, in which WHO, IAPB, member countries of WHO and nongovernmental organizations (NGOs) that are active in this field are all working together. The major emphasis of the programme is on control of the major disorders leading to blindness and the development of infrastructures, of eye care programmes and of training and continuing education for ophthalmic staff. This campaign is unique in medicine and has the potential for reducing the prevalence of blindness in the world significantly by 2020. Even now, we can assume that 75-80% of cases of blindness can be prevented. The WHO has developed strategies for dealing with individual diseases, such as trachoma, onchocerciasis, childhood blindness and refractive errors. Programmes for glaucoma and diabetic retinopathy will follow. Early successes can already be recognized, especially in the rising numbers of cataract operations.

[International ophthalmology and travel medicine]. / Internationale Ophthalmologie und Reisemedizin.

Medical eye care in developing countries is very different from the situation in industrialized nations. In order to prevent rising numbers of blind people worldwide due to increased life expectancy and population growth, the global initiative Vision 2020 "The Right to Sight" was established in 1999. Coordinated initiatives are important as most causes of blindness are either preventable or curable (e.g. cataract surgery); however, due to a lack of resources eye care in developing countries cannot implement all necessary preventive and therapeutic measures at present. The epidemiology of causes of blindness and the situation of ophthalmic care are discussed. Because of increased mobility of people and goods (e.g. air travel and trucking), imported eye diseases are of increasing importance. The difference between travel medicine, which deals with the medical situation of travelers and international ophthalmology (i.e. diseases in tropical countries) is discussed and illustrated on the basis of several important disease patterns.

Melanoma inhibitory activity: a novel serum marker for uveal melanoma.

The aim of this study was to evaluate the tumour-associated antigen melanoma inhibitory activity (MIA) as a potential novel serological tumour marker in primary and metastatic uveal melanoma in both the laboratory and the clinical setting. In the laboratory setting, immunohistochemical staining with MIA antibody was performed in paraffin-embedded tissues from six amelanotic uveal melanomas and eight metastatic lesions of uveal melanomas. In the clinical setting, serum samples of 139 patients with uveal melanoma were examined; eight of these patients had overt metastatic disease. Sixty-one initially metastatic disease-free patients were followed over time (median follow-up 240 days, 95% confidence interval 60-883 days) and MIA levels were assessed repeatedly. A one-step enzyme-linked immunosorbent assay was used to quantify the MIA serum levels. In the laboratory setting, five of the six primary uveal melanomas and seven of the eight metastatic lesions stained immunohistologically positive for MIA. In the clinical setting, the 131 patients without overt metastatic disease demonstrated a median serum concentration of MIA of 6.6 ng/ml. In the eight patients with overt metastatic disease, the median serum concentration of MIA was 26.28 ng/ml. This difference was highly statistically significant (P < 0.001, analysis of variance). During follow-up, three initially metastatic disease-free patients developed overt metastatic disease, and the MIA level increased from a median of 6.6 ng/ml before to 29.2 ng/ml after clinical detection of metastatic disease. In the 58 other patients, the serum level remained stable during the entire follow-up period. In conclusion, MIA is expressed in primary and metastatic lesions of uveal melanomas, and a statistically significant elevation in MIA serum levels in patients who develop metastatic disease due to uveal melanoma indicates its promising role as a serum marker for monitoring uveal melanoma patients for metastasis.

[Tropical ophthalmology--prevention and therapy"Vision 2020--the right to sight"]. / Tropenophthalmologie--Prävention und Therapie"Vision 2020--das Recht auf Sehen".

Worldwide 45 million people are blind, 180 million people are visually handicapped, 90% of all blind people are living in developing countries and 80% of blindness is preventable. The global economic productivity loss due to blindness was estimated to be 19 billion US$ in the year 2000. The initiative "Vision 2020-the right to sight" aims to increase the cataract surgical rate and to eliminate diseases such as trachoma and onchocerciasis as well as avoidable blindness in children. It is planned that blindness in 100 million people can be avoided by the year 2020.

[Acute hypopyon uveitis with rifabutin therapy of systemic Mycobacterium avium complex (MAC) infection in AIDS]. / Akute Hypopyon-Uveitis unter Rifabutin-Therapie einer systemischen Mycobacterium avium complex (MAC)-Infektion bei AIDS.

BACKGROUND: Hypopyon-uveitis has been identified as a dosage-dependent side effect in patients with acquired immunodeficiency syndrome who are treated for Mycobacterium avium complex (MAC) infection with systemic rifabutin. PATIENTS AND METHODS: We report a 38-year-old female AIDS patient with bilateral hypopyon uveitis under therapy with rifabutin in combination with clarithromycin and indinavir. RESULTS: At the time of presentation of the bilateral hypopyon uveitis the patient was treated with rifabutin (300 mg/day), clarithromycin (1000 mg/day) and ethambutol (1000 mg/day) for an M. avium complex infection. Also, the patient received the protease inhibitor indinavir. The rifabutin dose was reduced to 150 mg/day. Hypopyon and inflammation resolved under therapy with steroids. CONCLUSIONS: The concomitant use of rifabutin, clarithromycin, and protease inhibitors may lead to hypopyon uveitis. Reduction of dosage of rifabutin (150 mg/day) and treatment with topical steroids are required.

[Regression of cytomegalovirus retinitis in AIDS patients without systemic maintenance anti-cytomegalovirus therapy treated with highly active antiretroviral therapy]. / Regression der Zytomegalievirus-Retinitis bei AIDS-Patienten ohne systemische Anti-Zytomegalievirus-Erhaltungstherapie unter hochaktiver antiretroviraler Therapie (HAART).

BACKGROUND: The purpose of this study was to evaluate the course of CMV retinitis after initiation of highly active antiretroviral therapy (HAART) and discontinuation of systemic anti-CMV maintenance therapy. PATIENTS AND METHODS: Case reports are presented for two AIDS patients (2 eyes, ages 34, 43, male) with CMV retinitis. The CD4 count at the time of CMV retinitis was 20/microliter (patient 1) and 35/microliter (patient 2). Under HAART the CD4 count rose up to 202/microliter (patient 1) and 350/microliter (patient 2); the viral load was under detection limit in both patients. At that time systemic maintenance therapy was discontinued in both patients. RESULTS: There was no progression of retinitis during the observation period of 21 months (patient 1) and 24 months (patient 2). CONCLUSIONS: In selected patients with immune recovery under HAART it is possible to discontinue systemic anti-CMV maintenance therapy.

[The Munich/San Diego/Iowa City Collaboration (MuSIC). MuSIC Report I: Design , characteristics of the collective and preliminary results]. / Die Muenchen/San Diego/Iowa City Collaboration (MuSIC). MuSIC-Report-I: Design, Charakterisierung des Kollektives und erste Ergebnisse.

BACKGROUND: We have previously shown that histologically described microcirculation patterns (MCP) can be visualized with indocyanine green (ICG) angiography. We have designed a prospective study to evaluate the prognostic value of these angiographically imaged MCP in small choroidal melanocytic lesions. In this report we describe the design of the study, characterize the patient collective, and present the first results. PATIENTS AND METHODS: In this prospective nonrandomized observational study, unilateral choroidal melanocytic lesions with 1.5-5.5 mm maximum apical height are observed until growth is determined according to defined criteria. Variables are demographic parameters, subjective symptoms, subretinal fluid, location and dimension of tumor, hemorrhage, color, orange pigment, and MCP determined by ICG angiography: normal, straight, parallel without crosslinking, parallel with crosslinking, arcs without branching, arcs with branching, loop, and network. RESULTS: Seventy patients (22 males, 48 females; age: 33-88 years, median: 64 years) have been included up to now: 19 tumors showed growth so far (time to growth: 51-946 days, median: 127 days). The following parameters were statistically significantly correlated with time to tumor growth: flashes (p = 0.082), orange pigment (p = 0.012), subretinal fluid (p < 0.001), maximum basal tumor diameter (p = 0.001), maximum apical tumor height (p < 0.001), parallel with crosslinking (p < 0.001), arcs with branching (p = 0.006), loop (p < 0.001), and network (p < 0.001). Of these, complex MCP (parallel with crosslinking, arcs with branching, loop and/or network) showed the strongest correlation with time to tumor growth in a Cox regression model. Based on our data, the positive predictive value of imaging complex MCP (for growth within 12 months) is 78% and the negative predictive value is 98%. CONCLUSION: Our patient collective demonstrates comparable prognostic parameters for time to growth as described in the literature. In addition, the ICG angiographic detection of complex MCP is more strongly predictive of the time to growth than other clinically determinable factors. Thus, we recommend this examination for patients with small choroidal melanocytic lesions, if the patient is to be counseled regarding the likely biologic behavior of his tumor.

[Correlation between ICG angiography verified networks in uveal melanomas and rate of tumor regression after brachytherapy]. / Zusammenhang von ICG-angiographisch nachgewiesenen "Networks" uvealer Melanome und Tumorrückbildungsgeschwindigkeit nach Brachytherapie.

INTRODUCTION: The post-irradiation regression rate of uveal melanomas is a prognostically significant factor for the development of metastases. Other predictive factors for metastases are histological networks which are imagable with confocal ICG angiography. The purpose of this study was to evaluate a possible connection of networks in the ICGA and tumor regression rates. METHODS: We compared the post-irradiation regression rates (as %) in 20 patients 1 year after brachytherapy with networks identified in pre-treatment indocyanine green angiography (ICGA). The ICG angiography was performed before irradiation, 10 patients were irradiated with Ru-106 and 10 were irradiated with Id-125. RESULTS: The mean preoperative maximum apical height was 5.2 mm [SD: 1.5 mm; Ru106 group: 5.7 mm (SD: 1.0 mm); Id-125 group: 5.0 mm (SD: 1.9 mm)]. In 11 patients (55%) (Ru-106: 5; Id-125: 6) we found networks in the preoperative ICG. The mean regression rate in tumors with networks was 51.3% (SD: 14.7%) and 28.0% (SD: 16.4%) in the group without networks. The difference between both groups was statistically significant (p = 0.003, Mann-Whitney test). No statistically significant difference in the regression rates was found between the two groups of brachytherapy Ru-106 and Id-125 (p = 0.165, Mann-Whitney test). DISCUSSION: Highly proliferative tumors are known to be more sensitive to irradiation. This may be one reason why tumors with a rapid post-irradiation regression are the more aggressive ones with regard to later development of metastases. Histopathological networks are also known to be a strong indication of more aggressive, metastasizing tumors. These networks are also imagable in ICG angiography. Our observation emphasizes a connection between networks in ICG angiography and regression rates of uveal melanomas after brachytherapy.

[Keratography (corneal tattooing) in corneal leukoma]. / Keratographie (Hornhauttätowierung) bei Hornhautleukom.

BACKGROUND: Since antiquity attempts have been made to minimize disfigurement and stigmatization of patients with leukoma. Keratography is a relatively new method for imprinting color pigments into the corneal stroma with an entomological needle. MATERIALS AND METHODS: Keratography was performed in 20 patients at the University Eye Hospital, Munich, between November 1997 and September 1999. Patients had either a leukoma that did not tolerate prothesis or had another cloudy corneal disease. The operation was carried out in our outpatient clinic under local anesthesia. RESULTS: There was a single operation in three patients, two operations in nine, three operations in six, and four operations in two. Postoperatively 33% of patients complained of pain. No postoperative bacterial keratitis or perforation occurred. CONCLUSION: All patients were highly satisfied. The long-term stability of color pigments must still be evaluated.

[Melanoma inhibitory activity (MIA). Evaluation of a new tumor-associated antigen as a serum marker for uveal melanomas]. / Melanoma inhibitory activity (MIA). Evaluierung eines neuen tumorassoziierten Antigens als Serummarker für uveale Melanome.

BACKGROUND: Currently no serological marker for the monitoring of uveal melanoma and its metastases is available. The novel tumor associated antigen Melanoma inhibitory activity (MIA) is expressed in the uveal melanoma and it's metastatic lesions. METHOD: We report about the serum samples of 38 patients with uveal melanomas. 4 of these patients had overt metastatic disease. A nonradioactive one step ELISA was used to quantify the MIA serum levels. RESULTS: In the 34 patients without overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 3.6 +/- 1.0 ng/ml. In the 4 patients with overt metastatic disease the serum concentration of MIA was mean (+/- 1 SD) 27.7 +/- 3.0 ng/ml. The difference was statistically highly significant (student t test: p = 0.0001). CONCLUSION: MIA is expressed in primary and metastatic lesions of uveal melanomas. The elevation of MIA serum levels in patients with metastatic disease from melanomas suggests a promising role as a serum marker for monitoring patients with uveal melanoma.

[Stereotaxic precision irradiation of large uveal melanomas with the gamma knife]. / Die stereotaktische Präzisionsbestrahlung grosser uvealer Melanome mit dem Gamma-Knife.

BACKGROUND: We report our experience with stereotactic radiosurgery using the Gamma-knife in large uveal melanoma unsuitable for brachytherapy (Ru106). PATIENTS AND METHODS: We treated 35 patients (16 male, 19 female; age: median 59 years (95% Confidence interval (CI): 31-84 years; 18 right eyes, 17 left eyes). 7 tumors were located juxtapapillary, 16 tumors were located in the mid-periphery and 12 tumors were located in the ciliary body, The localization and/or the dimension of the tumors did not allow for radiation brachytherapy (Ru106). All patients underwent regular clinical, echographical and neuroradiological follow-up examinations. RESULTS: The follow-up time was median 12 months (95% CI: 4-20 months). A local tumor control defined as either continuous tumor regression or stopping of tumor progression was achieved in 34 (97%) of the 35 treated patients within the observation period. The eye of one patient was enucleated due to tumor regrowth. Maximum apical tumor height according to standardized A-scan before treatment was median 9.1 mm (95% CI: 3.2-13.9 mm) and after treatment median 6.4 mm (95% CI: 2.1 bis 11.9 mm). The difference was statistically highly significant (p < 0.001, one-tailed paired t-test). CONCLUSIONS: Our results in 35 patients indicate that radiosurgery using the Gamma-knife is beneficial in retaining the eyes of patients with large uveal melanomas that are not suitable for brachytherapy (Ru106).

[From conjunctivitis to glaucoma. When is a red eye an alarm signal?]. / Von der Bindehautentzündung bis zum Glaukomanfall. Wann ist das rote Auge ein Alarmsignal?

A red eye is mostly a relatively harmless sign of simple conjunctivitis. Viral conjunctivitis may be extremely contagious. If no improvement is seen after ten days of treatment, referral to an ophthalmologist is indicated. Local corticosteroids and local anesthetics must not be prescribed. The patient should also be referred to an ophthalmologist when the red eye is chronic or recurrent, and when a unilateral red eye is associated with severe pain and vomiting (suspicious for acute glaucoma!), or generally when severe pain or impairment of sight, indicative of corneal infiltration or a hypopyon, presents. The diagnostic use of fluorescein to stain the cornea and any alteration of corneal transparency also belong in the hands of the ophthalmologist.

Radioembolization as locoregional therapy of hepatic metastases in uveal melanoma patients.

PURPOSE: To retrospectively evaluate the overall survival, safety, and efficacy of metastatic uveal melanoma patients after radioembolization as salvage therapy. MATERIALS AND METHODS: Thirteen patients were treated with radioembolization of branches of the hepatic artery with resin-based yttrium-90 ((90)Y)-labelled microspheres. Twelve patients underwent a single application, and 1 patient underwent 4 interventions. Dosages from 644 to 2,450 MBq (mean activity 1,780) were applied. Treatment response was evaluated by way of liver magnetic resonance imaging and computed tomography (CT) as well as whole-body fluorodeoxyglucose positron emission tomography (PET)/CT with evaluation of percentage changes in SUV(max) before and at 2-3 months after therapy. Kaplan-Meier analysis was calculated to determine overall survival. RESULTS: Partial remission (PR) was observed in 8 (62 %), stable disease (SD) in 2 (15 %), and progressive disease (PD) in 3 (23 %) patients under terms of standard criteria and PR in 3 (23 %), SD in 3 (23 %), and PD in 7 (54 %) patients according to PET criteria. Neither RECIST nor PET criteria showed a significant difference in predicting overall survival (P = 0.12 and 0.11, respectively). Median survival time after radioembolization was 7 months. No acute toxicity with in-hospital morbidity was observed. One patient developed hepatomegaly, and 1 patient developed gastric ulceration. Throughout follow-up, progression of extrahepatic metastases was observed. CONCLUSION: Radioembolization may be a promising therapy in uveal melanoma patients with predominant hepatic metastases. At first follow-up, we observed PR or SD in 77 % patients under terms of standard criteria with an acceptable toxicity profile.

CyberKnife radiosurgery for the treatment of orbital metastases.

Purpose of this study is to evaluate radiographic therapy response, clinical outcome and adverse effects of CyberKnife radiosurgery in patients suffering from orbital metastases. Sixteen orbital metastases originating from different solid cancers in fourteen patients were treated by single fraction CyberKnife radiosurgery. Radiographic response and clinical outcome were evaluated. The treated tumor volume ranged from 0.2 to 35 cm3 (median 2.3 cm3, mean 7.0 cm3, SD 6 10.4 cm3, CI 0.9-9.4 cm3). The prescription dose ranged from 16.5-21 Gy (median 18 Gy, mean 18.2 Gy, SD 6 1.2 Gy, CI 17.0-18.4 Gy). A no change situation was observed in nine lesions, partial remission in four as well as complete remission in one metastasis. Tumor growth was stabilized or regressive following CyberKnife therapy in 87% of the cases. Recurrence was observed in two cases (13%). Before therapy, three patients suffered from visual disturbance and five patients reported diplopia. Six patients had no initial symptoms. After therapy, one patient indicated improvement of the present visual deficit and two patients no change. Out of the two patients with persistent diplopia, two reported improvement after therapy and three no change. No progression of symptoms was noted in any of the cases. Fourteen out of sixteen treated lesions were stable or regressive following CyberKnife radiosurgery (87%). As no serious adverse effects were reported in this series, CyberKnife therapy was shown to be of great value for local management of orbital metastases.

[Hepatic metastases in CUP (cancer of unknown primary) and painful amaurosis]. / Hepatische Filiae bei CUP ("cancer of unknown primary") und schmerzhafter Amaurose.

A 63-year-old woman presented with a 9-month history of painful amaurosis of the left eye caused by hemophthalmos. She was already undergoing chemotherapy for histopathologically proven liver metastases caused by an assumed melanoma. The location of the primary tumor was unknown. Whole-body FDG-PET/CT staging identified a lesion with characteristically malignant uptake in the region of the left eye as the primary tumor. After enucleation, a primary uveal melanoma was verified that expressed the serological marker melanoma inhibitory activity (MIA). FDG-PET/CT was able to successfully align hepatic metastases due to CUP with local ophthalmologic diagnostic findings and led to a correct diagnosis.