Hemodynamic parameters in blood vessels in choroidal melanoma xenografts and rat choroid.

Choroidal melanoma is a solid tumor arising from choroidal melanocytes. Although the occurrence of this tumor is relatively rare compared with other types of cancer, it is the most common adult primary intraocular malignancy, accounting for 70% of all primary intraocular eye cancers.1 Its dangerous metastatic potential makes it of special concern to ophthalmologists. The median survival after a diagnosis of metastasis is only 4 to 7 months.2,3 Despite significant research effort, there is still a need for improved treatment of choroidal melanoma. The two most commonly used treatments for medium-sized tumors are enucleation or radiation therapy. Although radiation therapy spares the eye, vision may be adversely affected. In one report, only 36% of all patients maintained visual acuity better than 6/12 three years after radiation therapy.4 Because of this risk of treatment-related vision loss, there has been a recent trend to optimize radiation therapy5 and to investigate more local, conservative, eye-sparing therapies.6 The ultimate goals of any treatment of choroidal melanoma should be eradication of the primary tumor, prevention of metastatic spread, and maintenance of the patient’s vision. To improve existing therapies and to develop new, vision-sparing treatments for choroidal melanoma, it is necessary to gather detailed information about the blood supply and microcirculation in this tumor. Not only is blood flow essential for tumor growth and metastasis, it is also a major factor in a tumor’s response to many therapies. Delivery of chemotherapeutic drugs is dependent on the distribution of blood flow within the tumor and the permeability of the vasculature.7 The efficacy of some therapies is affected by the microenvironment within the tumor, which is shaped by the blood flow, among other factors. For example, several different forms of cancer therapy are dependent on tumor oxygen levels, including radiation therapy8 and photodynamic therapy.9 In addition, some chemotherapeutic drugs (hypoxic cytotoxins) are sensitive to the oxygen level and are much more effective under hypoxic conditions.10 Therefore, information about the blood flow characteristics of a specific tumor is imperative before rationally designing new therapies or optimizing existing treatments. Over the past decade, there has been an increased effort to study blood flow and vascular architecture in choroidal melanoma. Beginning in the early 1990s, attempts were made to measure global blood flow in choroidal melanomas in patients by means of color Doppler imaging.11,12 More recently, the technique was used to measure blood velocity and vascular resistance in the major ocular arteries in patients with choroidal melanoma before and after radiotherapy.13 The most interesting findings have been in the area of vascular architecture. In 1993, Folberg et al.14 identified nine different vascular patterns in histologic sections of choroidal melanoma and determined that the presence of loops and networks was correlated with poor prognosis. Subsequent work suggested that these network patterns were composed of extracellular matrix–lined channels generated by the tumor cells themselves in a process called vasculogenic mimicry.15 This link between vascular pattern and prognosis has stimulated an interest in imaging the microvasculature of choroidal melanoma in patients. In 1995, indocyanine green videoangiography was used to evaluate vascular patterns in choroidal tumors.16 More recently, confocal indocyanine green angiography has been used to visualize the microcirculation and to identify vascular patterns in experimental and clinical choroidal melanoma.17,18 Although this information about the architecture of the blood vessels and overall blood flow in the tumor is extremely important, there is still little or no knowledge about the factors that help determine the microvascular flow properties in choroidal melanoma. In general, tumors are characterized by chaotic vascular networks and very heterogeneous, unstable blood flow.19,20 One of the causes of this abnormal blood flow is high viscous resistance within the tumor vasculature.20 The viscous resistance is a function of hemodynamic parameters in the microvessels (e.g., the microvascular hematocrit [HCTm]).21 In a review in 1988, Jain20 stressed the need to measure the microvascular hematocrit and other rheologic parameters within individual tumor microvessels to better understand the factors that determine the tumor’s overall blood flow. In the current study, we determined the hemodynamic parameters in blood vessels in a human choroidal melanoma xenograft model and compared them with those found in normal choroidal blood vessels. We hypothesized that there are differences in the blood flow properties between choroidal melanoma microvessels and normal choroidal microvessels. Specifically, we hypothesized that HCTm would be higher in the microvessels of choroidal melanoma than in vessels in the normal choroid.