Purpose: To compare retinal vessel oxygenation in eyes with an untreated choroidal nevus or choroidal melanoma. Methods: The affected and fellow eye of patients with an untreated choroidal nevus (n... Show morePurpose: To compare retinal vessel oxygenation in eyes with an untreated choroidal nevus or choroidal melanoma. Methods: The affected and fellow eye of patients with an untreated choroidal nevus (n = 42) or choroidal melanoma (n = 45) were investigated using noninvasive retinal oximetry (Oxymap T1). Oxygen saturation of arterioles (ArtSat) and venules (VenSat) was determined, together with the arteriovenous difference (AV-difference). Results: In choroidal nevus patients, retinal oximetry did not differ between the affected and fellow eye: the mean ArtSat was 94.5% and 94.2% (P = 0.56), the VenSat was 60.5% and 61.3% (P = 0.35), and the AV-difference was 34.0% and 32.9% (P = 0.18), respectively. In choroidal melanoma patients, alterations were detected: the mean ArtSat was 94.8% and 93.2% (P = 0.006), the VenSat was 58.0% and 60.0% (P = 0.014), and the AV-difference was 36.8% and 33.2% (P < 0.001), respectively. The largest increase in AV-difference was observed between the retinal halves without the lesion in melanoma eyes compared with the corresponding half in the fellow eye (37.5% vs. 32.1%, P < 0.001). Conclusion: Although retinal oximetry was not significantly altered in eyes with a choroidal nevus, eyes with choroidal melanoma showed an increased ArtSat and decreased VenSat, leading to an increased AV-difference. These changes may be caused by inflammation and a higher metabolism, with larger oxygen consumption, leading to altered blood flow and intraocular oxygen relocation. Show less
Filali, M. el; Ly, L.V.; Luyten, G.P.M.; Versluis, M.; Grossniklaus, H.E.; Velden, P.A. van der; Jager, M.J. 2012
PURPOSE Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A), was originally developed as an anti-tumor treatment. In ocular oncology, it is being used to... Show morePURPOSE Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A), was originally developed as an anti-tumor treatment. In ocular oncology, it is being used to treat macular edema due to radiation retinopathy, but it may also be useful for the treatment of primary uveal melanoma (UM) or its metastases. We determined the effect of bevacizumab on the growth of B16F10 cells inside the eye and on B16F10 and UM cells cultured in vitro. METHODS B16F10 melanoma cells were placed into the anterior chamber of the eye of C57Bl/6 mice and tumor growth was monitored after injection of different doses of bevacizumab or mock injection. In addition, the effect of bevacizumab on in vitro growth of B16F10 and human UM cells and on the expression of VEGF-A, GLUT-1, and HIF-1α was evaluated. RESULTS Following intraocular injection of bevacizumab into murine B16 tumor-containing eyes, an acceleration of tumor growth was observed, with the occurrence of anterior chamber hemorrhages. Bevacizumab did not affect proliferation of B16F10 cells in vitro, while it inhibited UM cell proliferation. Expression analysis demonstrated that addition of bevacizumab under hypoxic conditions induced VEGF-A, GLUT-1 and HIF-1α in B16F10 cells as well as in UM cell lines and two of four primary UM tumor cultures. CONCLUSIONS In contrast with expectations, intraocular injection of bevacizumab stimulated B16F10 melanoma growth in murine eyes. In vitro exposure of B16 and human UM cells to bevacizumab led to paradoxical VEGF-A upregulation. The use of VEGF inhibitors for treatment of macular edema (due to radiation retinopathy) after irradiation of UM should be considered carefully, because of the possible adverse effects on residual UM cells. Show less
Uveal melanoma (UM) is a disease with many faces: ophthalmologists treat the primary tumor, but the patient faces the problem of developing metastases, which are often deadly after a short period.... Show moreUveal melanoma (UM) is a disease with many faces: ophthalmologists treat the primary tumor, but the patient faces the problem of developing metastases, which are often deadly after a short period. Recent insight, indicates the need for knowledge-based treatment of UM. The __pseudohypoxic__ and tumor promoting effects of bevacizumab as described in this thesis is especially relevant. Bevacizumab is frequently used off-label to treat macular edema in UM patients suffering of radiation retinopathy, without the knowledge of possible effect on still viable UM cells. We further observed that specific peptides, such as UMAP1, which can successfully be internalized by targeted UM cells, have demonstrated potential for UM-targeted treatment. These peptides have to be investigated in vivo, to ascertain whether they are a viable clinical tool. Labeling the peptides with radionuclides, and demonstrating specificity for UM cells are some of the challenges which have to be overcome. Another aspect in the patient-specific treatment of UM is the in vitro analysis of primary UM samples to predict treatment responses. In case of Dasatinib, we describe treatment responses associated with monosomy 3 and __kinase__ activity in different primary UM samples. Show less
Jager, M.J.; Ly, L.V.; Filali, M. el; Madigan, M.C. 2011
