No abstract

Purpose: In patients with uveal melanoma, tumor cell dissemination and subsequent formation of metastases are confined mainly to the hematogenous route. Here, we sought to isolate circulating melanoma cells in peripheral blood of patients with primary uveal melanoma and clinically localized disease. Experimental Design: Blood samples from 52 patients with clinically localized uveal melanoma and from 20 control individuals were prospectively collected before therapy of the primary tumor. Tumor cells expressing the melanoma-associated chondroitin sulfate proteoglycan were enriched by immunomagnetic cell sorting and visualized by immunocytologic staining. Results were compared with clinical data at presentation. Uveal melanoma is the most common primary intraocular malignant tumor in adults and 98% of these patients present with clinically localized disease (1, 2). Despite successful local tumor control, one half of the patients with primary uveal melanoma will die from metastatic disease (3). The 10-year survival rates in patients with nonmetastatic tumors range from 81% (T 1 N 0 M 0 ) to 15% (T 4 N 0 M 0 ; ref. 4). Metastasis-related deaths occur as long as 35 years after diagnosis, indicating that disseminated tumor cells may stay quiescent for decades and change their biological behavior even after this time (5). As therapeutic options in metastatic disease are poor, with a mean survival of 12 to 14 months (6, 7), there is an urgent need for early identification of patients at increased risk for metastases. This will allow evaluation of adjuvant therapeutic strategies in high-risk patients.Established prognostic factors for clinically localized ocular disease include largest basal tumor diameter (LBD), ciliary body involvement, and extraocular growth (8 -17). A number of staging classifications use combinations of the abovementioned criteria (for review, see ref. 4). However, neither of these factors alone or in combination is adequate for predicting the occurrence of metastatic disease in an individual patient. Other prognostic factors such as histologic subtype (11 -14, 16, 18) as well as genomic changes (19 -21) of the primary tumor also correlate with clinical outcome. Yet, these factors are increasingly difficult to determine as patients are currently often treated with radiotherapy. Although a diagnostic biopsy may be done before treatment, in most cases tumor tissue is not available for analysis.Metastatic spread in uveal melanoma is confined to the hematogenous route as long as the conjunctiva is not infiltrated trans-sclerally (22 blood is an obligate (although not sufficient) event in the metastatic cascade. Detection of circulating tumor cells might therefore represent a unique tool to identify patients at increased risk for metastatic disease. A recent systematic metaanalysis (23) of the prognostic value of tumor cell detection in peripheral blood in melanoma patients identified and evaluated two major approaches, PCR-based detection of melanomaassociated mRNA (n = 52 studies) and our rece...

ABSTRACT.Purpose: We aimed to evaluate the longterm effects of intraocular bevacizumab (Avastin Ò ) injections as adjuvant treatment in patients with neovascular glaucoma. Methods: Twenty eyes of 18 consecutive patients with secondary neovascular glaucoma caused by proliferative diabetic retinopathy (n = 7), ischaemic central retinal vein occlusion (n = 7), ischaemic ophthalmopathy (n = 2) and retinal ischaemia resulting from persistent detachment (n = 2) were treated with intraocular bevacizumab injections (1.25 mg ⁄ 0.05 ml) in addition to other treatments. The main outcome measure was the change in degree of iris rubeosis. Secondary outcomes included intraocular pressure (IOP), best corrected visual acuity (BCVA) and numbers of additional interventions or antiglaucoma medications administered after injection. Results: Mean (± standard deviation) follow-up was 67.7 ± 13.8 weeks (range 50-93 weeks). At the last follow-up, complete regression of rubeosis was detectable in five (20%) eyes, incomplete regression in seven (35%), stabilization in six (30%), and an increase in two (10%) eyes. Mean IOP was 26.0 ± 8.9 mmHg at baseline and significantly decreased to 14.75 ± 5.3 mmHg at the last follow-up visit (p = 0.000005). Mean baseline BCVA (logMAR [logarithm of the minimum angle of resolution] 1.43 ± 0.89) was stabilized during the follow-up period (logMAR 1.5 ± 0.98). Patients received an average of 2.75 injections. Additional treatments were laser photocoagulation in 13 (65%) eyes, cyclodestructive procedure in 14 (70%), cryopexy in six (30%), drainage procedures in two (10%), and vitrectomy in five (25%) eyes. Conclusions: Bevacizumab may be beneficial as adjuvant treatment in neovascular glaucoma because of its anti-angiogenic properties and its ability to prevent establishment or progression of angular obstruction. The causative disease inducing the angiogenic process requires treatment in all cases. Antiglaucoma treatment is needed in cases of persistent elevated IOP.