SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN SMALL CHOROIDAL MELANOMAS AND CHOROIDAL NEVI.

PURPOSE: To evaluate the use of swept-source optical coherence tomography angiography to detect distinct vascular features in small choroidal melanomas and choroidal nevi. METHODS: Patients with a choroidal nevus or a treatment-naïve choroidal melanoma were imaged with color fundus photography, ultrasound, and swept-source optical coherence tomography angiography (12 × 12 mm). High-risk features including overlying fluid, orange pigment, shaggy photoreceptors, acoustic hollowness, depth >2 mm, and basal diameter >5 mm were assessed. Optical coherence tomography angiography vascular markers included: choroidal vessel visualization, choroidal vessel depth, and choriocapillaris flow signal, assessed qualitatively by comparison with surrounding, unaffected choriocapillaris. RESULTS: Twenty-nine lesions were included in this study, seven flat choroidal nevi, 17 elevated choroidal nevi, and 5 choroidal melanomas. Distinct vascular patterns were noted between flat nevi, elevated nevi, and small choroidal melanomas. Choroidal melanomas displayed two types of vasculature: "nevus-like" vasculature with straight parallel vessels and complex vasculature with vascular loops and crosslinking. Visualized choroidal vessels were significantly deeper in melanomas (110 µm) than elevated (84 µm) or flat nevi (70 µm). In a size-matched subanalysis of 5 elevated choroidal nevi and 5 choroidal melanomas, choroidal melanomas had increased mean choroidal vessel depth (P = 0.015), deepest choroidal vessel visualized (P = 0.034), and presence of a deep choroidal vessel >155 µm (P = 0.048). CONCLUSION: Swept-source optical coherence tomography angiography may detect distinct vascular features in choroidal nevi and small choroidal melanomas.

Is optical coherence tomography angiography helpful in the differential diagnosis of choroidal nevus versus melanoma?

PURPOSE: To describe the imaging features of choroidal nevus and melanoma using optical coherence tomography angiography, and evaluate the ability of this technique to establish the differential diagnosis based on the display of the tumor's intrinsic vasculature. METHODS: Comparative analysis of optical coherence tomography angiography findings in consecutive patients diagnosed with choroidal nevus or choroidal melanoma following a complete ophthalmic evaluation, including best-corrected visual acuity and several imaging studies: color fundus photography, B-scan ultrasound, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography was used to investigate qualitative differences in the tumor vasculature. RESULTS: Thirty-six eyes (18 cases of choroidal nevus and 18 cases of choroidal melanoma) from 36 consecutive patients were included in the study. Only cases located posterior to equator were included to enable performance of all tests. On optical coherence tomography angiography, choroidal nevus showed well-delimited margins (78%), hyperreflective choroid capillary vasculature (83%), fewer avascular areas (17%), and neovascular membrane in one case (6%). Choroidal melanoma showed imprecise margins (72%), hyporeflective choroidal capillary vasculature (72%), multiple avascular areas (78%), and choroidal vascular changes (e.g. thick vascular networks or vascular loops; 45%). CONCLUSION: Optical coherence tomography angiography can provide useful information for assessing and differentiating between choroidal nevi and small melanomas. Significant differences between these conditions were found for the pattern of reflectivity, and presence/absence of avascular zones and vascular anomalies, which could be helpful for supporting the diagnosis.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN CHOROIDAL MELANOMA: An Analysis of 22 Consecutive Cases.

PURPOSE: To describe the imaging features of choroidal melanoma using swept-source optical coherence tomography angiography (SS-OCT-A) and to evaluate its ability to display tumor intrinsic vasculature. METHODS: Consecutive patients diagnosed with choroidal melanoma underwent a complete ophthalmic evaluation, including best-corrected visual acuity, color fundus photography, B-scan ultrasound, fluorescein angiography, indocyanine green angiography, and SS-OCT-A (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). RESULTS: Twenty-two eyes of 22 consecutive patients were included in the study; 11 cases (50%) were treatment naive. Three lesions (14%) were located at the macula, 14 (63%) between the macula and equator, and 5 (23%) between the equator and the ora serrata. The mean tumor base and thickness were, respectively, 10.3 mm (range 5-15 mm) and 4.3 mm (range 1.5-8.9 mm). Seventeen lesions (77%) were dome shaped, whereas 5 (23%) had a mushroom configuration. Thirteen lesions (59%) were pigmented, 5 (23%) partially pigmented, and 4 (18%) amelanotic. An exudative retinal detachment was documented in 13 eyes (59%). Fluorescein angiography and indocyanine green angiography were performed in 20 patients and disclosed intrinsic microvasculature of the tumor, respectively, in 4 (20%) and 20 (100%) cases. Swept-source optical coherence tomography angiography was performed in 22 eyes and detected microvasculature of choroidal melanoma in all cases. Specifically, intrinsic vasculature could be recognized in 14 eyes (64%) using the automated choroid segmentation, 16 eyes (73%) using the automated whole eye segmentation, and in 22 eyes (100%) with fine manual adjustments of segmentation lines. CONCLUSION: Swept-source optical coherence tomography angiography represents a valid imaging technique to evaluate patients affected by choroidal melanomas. In our series, SS-OCT-A disclosed the intrinsic microvasculature of the tumor in all cases despite their size, location, and history of previous treatments.

Evaluation of Vascular Changes with Optical Coherence Tomography Angiography after Plaque Radiotherapy of Choroidal Melanoma.

AIM: The purpose of this paper was to evaluate whether optical coherence tomography angiography (OCT-A) can be used to quantify the vascular changes in radiation maculopathy, and changes in the tumor vasculature in eyes treated with plaque radiotherapy for choroidal melanoma. METHODS: In this prospective study, we evaluated 39 Caucasian patients with choroidal melanoma (39 eyes) treated with ruthenium-106 plaque radiotherapy. The patients underwent complete ophthalmic examination, bulbar echography, and OCT-A before and 1 year after treatment. RESULTS: At baseline, the mean best-corrected visual acuity (BCVA) in the affected eyes was 0.35 ± 0.40 logMAR, and the mean tumor thickness was 2.68 ± 0.25 mm at A-scan echography. After treatment, the mean BCVA increased to 0.41 logMAR, the mean tumor thickness decreased to 1.66 ± 0.23 mm, and the tumor basal diameter was significantly reduced (U = 108, p = 0.001). Moreover, the capillary vessel density was significantly lower in all Early Treatment of Diabetic Retinopathy Study sectors, and both the vessel and flow areas were significantly reduced (p = 0.030 and p = 0.001, respectively). CONCLUSIONS: OCT-A is a noninvasive, reliable method with which to quantify the vessel changes in radiation maculopathy and, given the association between vascularization and malignancy, this procedure may be an aid in treatment decision-making and in monitoring the efficacy of treatment.

Quantitative Evaluation of Vascular Microcirculation Using Contrast-Enhanced Ultrasound Imaging In Rabbit Models of Choroidal Melanoma.

Purpose: We investigated the application of contrast-enhanced ultrasound (CEUS) to quantify vascular perfusion in two animal models of choroidal melanoma. Methods: B16F10 and choroidal melanoma cell line (OCM1) melanoma xenografts were implanted into the cyclodialysis cleft of rabbits' right eyes. Fundus photography, indocyanine green angiography (ICGA), B-mode ultrasound, and CEUS were used to examine the tumors. Standard vascular parameters of CEUS imaging were evaluated, including the area under the receiver operating characteristic curve (AUC), peak intensity (IMAX), mean transit time (mTT), rise time, and time to peak. Kruskal-Wallis tests followed by Nemenyi tests and Bonferroni corrections were used to analyze the findings. Results: OCM1 and B16F10 animal models of choroidal melanoma were established. Tumor size was larger in the animals receiving B16F10 xenografts compared with the OCM1. Choroidal melanoma received a more abundant blood supply and had higher blood flow velocities than normal eye tissue. The animals receiving B16F10 xenografts had larger blood volume but smaller blood flow velocity compared with the OCM1 models. Vascular mimicry was present in seven of eight OCM1 tumors (87.5%). Growth and blood circulation patterns differed between OCM1 and B16F10 melanomas. Conclusions: CEUS could be used to noninvasively dynamically, and safely detect the microcirculation patterns, quantify blood circulation volume, and velocity in ocular melanoma in animal models. The blood circulation patterns of two models were different in both qualitatively and quantitative analysis under CEUS and ICGA.

INFRARED IMAGING OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMAS.

PURPOSE: To describe the features of choroidal tumors on infrared (IR) imaging and to determine the diagnostic sensitivity and specificity of intratumoral choroidal vascular loops on IR imaging for circumscribed choroidal hemangioma (CCH). METHODS: Infrared and indocyanine green images of CCH, choroidal metastases, and choroidal melanomas were reviewed. The main outcome measure was the presence of intratumoral choroidal vascular loops and tufts on IR images. The secondary outcome measure was the presence of peritumoral vascular expansion on indocyanine green images. RESULTS: Intratumoral CCH vessels appear as dark beaded spaces on IR imaging; 95.5% of CCH had vascular loops compared with the controls of 65% in choroidal melanomas and 64% in choroidal metastases. The sensitivity of intratumoral vessels on IR for CCH was 95.4%. Subanalysis of six patients with CCH showed the presence of peritumoral vascular expansion on indocyanine green images. CONCLUSION: Infrared imaging delineates intratumoral vessels in choroidal tumors appearing as dark beaded loops and tufts. Vascular loops on IR imaging showed a high diagnostic sensitivity for CCH. The absence of these loops on IR can help rule out the diagnosis of CCH. Peritumoral vascular expansion on indocyanine green is an additional diagnostic tool that is helpful in the diagnosis of CCH.

[Choroidal neovascularisation in a patient with choroidal osteoma visualized by OCT angiography]. / OCT-angiographische Darstellung einer choroidalen Neovaskularisation infolge eines Aderhautosteoms.

We present the case of a 38-year-old Asian patient who reported vision loss of her left eye since 4 weeks. The funduscopy showed a choroidal tumor in the papillomacular bundle, which could be identified as a choroidal osteoma with secondary choroidal neovascularization (CNV). OCT angiography (OCT-A) detected abnormal flow in the choriocapillaris; the osteoma showed no flow in the OCT angiogram of the choroid level. Therefore, OCT-A can be a helpful adjuvant for diagnosis of CNV secondary to choroidal osteoma.

A pilot study to compartmentalize small melanocytic choroidal tumors and choroidal vessels with speckle-noise free 1050 nm swept source optical coherence tomography (OCT choroidal "tumoropsy").

PURPOSE: The purpose was to illustrate small melanocytic choroidal tumors with speckle-noise free swept-source optical coherence tomography (SSOCT). METHODS: Twenty-five small melanocytic choroidal tumors in 24 eyes underwent 1050 nm OCT. All tumors were measured manually with the built-in caliper tool and compared to data derived from a semiautomated algorithm that removed speckle noise but preserved the structure of the tumors from the SSOCT data. RESULTS: The average manual measurements for the horizontal, vertical, and axial diameters were 1535.28 µm (range, 547-2807 µm), 1713.8 µm (range, 574-3921 µm), and 227.28 µm (range, 115-489 µm), respectively. The measured average volumes of the tumors were 835,248,212 µm(3) (range, 48,818,700 to 4,567,401,810 µm(3)) and 228,588,535 µm(3) (range, 22,879,641 to 787,668,886 µm(3)) for caliper measurements, respectively, for the extracted volumes. The average volume variation between the two methods was 66.16 % (range, 46.5 % to 82.75 %). The average ratio between the caliper and extracted volumes was 3.402 (range, 1.346-8.198, SD 1.681), 2.367 (range, 1.346-3.258, SD 0.618), 2.321 (range, 1.346-3.258, SD 0.611), 2.402 (range, 1.518-3.258, SD 0.591), and 1.749 (range, 1.518-1.733, SD 0.239) for all tumors, all tumors with the exclusion of extreme parameters, tumor <3 mm, tumor <2 mm, and tumor <1 mm, respectively. The average ratio (tumor index) between the tumor volume and the choroidal vessel volume was 12.539 (range, 0.489-73.701). CONCLUSION: Speckle-noise free swept-source OCT may be an illustrative OCT imaging technology. OCT may be useful for describing and monitoring small melanocytic choroidal tumors and the choroidal vessels.

A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

PURPOSE: To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). METHODS: Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. RESULTS: In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 µm(3) (range of 0.209764406 mm(3) /209764405.9 µm(3)to 1.78105544 mm(3) /1781055440 µm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). CONCLUSION: Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

PURPOSE: To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. METHODS: Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. RESULTS: Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). CONCLUSIONS: Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis.

Enhanced depth imaging optical coherence tomography of circumscribed choroidal hemangioma in 10 consecutive cases.

PURPOSE: The purpose was to evaluate the features of circumscribed choroidal hemangioma using spectral-domain enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Ten patients with newly diagnosed circumscribed choroidal hemangioma. METHODS: Spectral-domain EDI-OCT was performed with a Heidelberg Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). MAIN OUTCOME MEASURES: Tumor thickness and EDI-OCT features. RESULTS: The mean tumor diameter for all eyes was 5.4 mm and mean tumor thickness was 1187 µm by EDI-OCT compared to 2400 µm by ultrasonography. EDI-OCT imaged all tumors as smooth with a gently sloping anterior contour, gradual choroidal expansion, expansion of medium and large size choroidal vessels without compression of choriocapillaris, and intact Bruch's membrane (n = 10, 100%). The height of the medium and large choroidal vessels within the tumor compared to normal medium and large vessels was comparatively increased by a mean of 265% (medium vessels) and 576% (large vessels). Outer retinal abnormalities included subretinal fluid (n = 7, 70%), lipofuscin deposition (n = 1, 10%), irregularity and thinning of retinal pigment epithelium and absence or irregularity of the ellipsoid layer (n = 4, 40%), absent external limiting membrane (n = 2, 20%), and disruption of the outer nuclear layer and outer plexiform layer (n = 3, 30%). The inner retinal abnormalities included irregularity of inner nuclear layer and structural loss or edema of inner plexiform layer (n = 3, 30%). The ganglion cell layer and nerve fiber layer were intact (n = 10, 100%). CONCLUSION: EDI-OCT of circumscribed choroidal hemangiomas depicts a smooth, gently sloping choroidal mass with expansion of medium and large size choroidal vessels without compression of the choriocapillaris. Structural abnormalities of outer and inner retinal layers were noted.

Transscleral delivery of Nd: YLF laser at 1,047 nm causes vascular occlusion in experimental pigmented choroidal melanoma.

PURPOSE: The aims of this study were to determine the scleral attenuation of focused neodymium: yttrium-lanthanum-fluoride laser at 1,047 nm applied transsclerally and whether transscleral delivery can close the vascular supply at the base of experimental choroidal melanoma in rabbits. METHODS: Fifty-two New Zealand albino rabbits were included. Scleral laser attenuation was measured across fresh sclera. B16F10 melanomas were established in the subchoroidal space of 49 rabbits. Twenty-one animals were killed immediately after transscleral treatment, 14 were followed for 2 weeks to 4 weeks, and 14 were followed without treatment. Ophthalmoscopy, fundus photographs, and fluorescein angiography were performed before treatment, immediately after, and weekly during the follow-up. Eyes were examined by light microscopy. RESULTS: Sclera attenuated laser energy by 31% ± 7%. Immediately after treatment, angiography showed diffuse hypofluorescence in 71% (15 of 21 rabbits). Light microscopy showed vascular occlusion extending at least two thirds of the tumor thickness from the base. Seven of the 14 tumors followed for 15 days ± 8 days were eradicated. There was no correlation between tumor height and eradication. CONCLUSION: Rabbit sclera attenuated 31% ± 7% of laser energy. A single transscleral treatment causes tumor vascular closure at the base and may serve as an adjuvant therapy to ensure destruction of deep and intrascleral tumor cells.

In vivo high-frequency contrast-enhanced ultrasonography of choroidal melanoma in rabbits: imaging features and histopathologic correlations.

PURPOSE: To evaluate the use of in vivo imaging of rabbit model of choroidal melanoma using high-frequency contrast-enhanced ultrasound (HF-CE-US) with two-dimensional (2D) or three-dimensional (3D) modes and to correlate the sonographic findings with histopathologic characteristics. METHODS: Five New Zealand white rabbits, which were immunosuppressed with daily cyclosporin A (CsA), were inoculated into their right eyes with aliquots of 1.5×10(6)/50 µl of 92.1 human uveal melanoma cells cultured in RPMI. At week 4, the tumour-bearing eyes were imaged using high-frequency ultrasound (HF-US) with microbubble contrast agent to determine the 2D tumour size and relative blood volume and by 3D mode to determine tumour volume. Histologic tumour burden was quantified in enucleated eyes by ImageJ software, and mean vascular density (MVD) was determined by counting vascular channels in periodic acid Schiff (PAS) without haematoxylin sections. RESULTS: Using HF-CE-US, melanomas were visualised as relatively hyperechoic regions in the images. The correlation coefficients of sonographic size and volume compared with histologic area were 0.72 and 0.70, respectively. The sonographic tumour relative blood volume correlated with the histologic tumour vascularity (r(2)=0.92, p=0.04). CONCLUSIONS: There is a positive correlation between in vivo sonographic tumour volume/size and histologic tumour size in our rabbit choroidal melanoma model. HF-CE-US corresponds to MVD and blood volume.

Metástasis coroideas: clarinada hacia la nada: presentación de casos icónicos / Choroid metastasis: clarion call toward nothing: presentation of two iconic cases

La metástasis intraoculares de tumores sólidos o hematológicos, son un problema clínico para el oftalmólogo práctico y el oncólogo. La localización más frecuente es la coroides, constituyendo el tumor intraocular más frecuente. Suelen diagnósticarsé en pacientes en estadios tumorales muy avanzados, por lo que en el pasado la mayoría de las series publicadas eran descripciones de necropsias. Su diagnóstico generalmente puede hacerse mediante cuidadoso examen. Se estima que la frecuencia general en pacientes que fallecen por cáncer es de aproximadamente 12%, pero puede elevarse en 37% en aquellos con carcinoma mamario, muy superior a la de los tumores primarios, fundamentalmente los melanomas. No obstante, sin compresión ha aumentado en años recientes ofreciendose nuevas formas de tratamiento siendo todavía la radioterapia la que permite a los pacientes mantener una visión.

Intraocular metastases of solid and hematological tumors are clinical problem for the practicing ophthalmologist and oncologist. Its diagnosis can usually be made through careful examination. The most common intraocular tumor. They are often diagnosed in patients in very advanced tumor stages, which is why in the past most of the published series were descriptions of necropsies. The overall frequency of ocular metastases in patients dying of cancer is approximately 12%, but it can be as high as 37% in patients with breast cancer, highly superior to primary tumors, mainly melanomas. Hawever, our understanding of them has increased in recent years, offering new forms of treatment. Radiation therapy is still the cornerstone of treatment, allowing nost patients to maintain usefull vision. Clinical cases with photographic support of an iconic patient are presented to illustrate the problem.

A case of choroidal metastasis of lung cancer successfully treated with erlotinib.

We present a case of choroidal metastasis of lung cancer in which choroidal metastasis, the first manifestation of recurrence, was successfully treated with erlotinib. A 49-year-old woman with a 2. 0 cm nodule in the right lung was diagnosed with adenocarcinoma, and a right upper lobectomy was performed. After 2 months, she presented with blurred vision of the right eye. Her right visual acuity had decreased to 0. 1, and there was a visual field defect temporal to the macula. Fundus examination of the right eye revealed an elevated mass with exudative retinal detachment temporal to the disc. Fluorescein angiography revealed hypofluorescence during the prearterial and arteriovenous phases, and fluorescein leakage surrounded by a circular hypofluorescence area during the venous phase. Spectral-domain optical coherence tomography showed exudative retinal detachment. The cancer cells had a mutation of the epidermal growth factor receptor gene in exon 19. She was treated with erlotinib at 100 mg per day, and after 4 days, her right visual acuity had improved to 1. 2.

[Overexpression of the receptor tyrosine kinase EphA2 in choroidal melanoma: correlation with vesculogenic mimicry and prognosis].

OBJECTIVE: To study the correlation of EphA2 protein expression with vesculogenic mimicry (VM), clinicopathological characteristics and prognosis in choroidal melanoma (CM). METHODS: It was a retrospective case series study. Between January 1992 and December 2005, 56 cases of human CM with clinicopathologic data from the Second Hospital of Tianjin Medical University were studied. HE stainings were performed to observe the microcirculation patterns in tumor tissue specimens. VM was found in 26 of the 56 cases using CD31/periodic acid-Schiff (PAS) double staining and transelectron microscopy. All cases were divided into two groups: VM-positive and VM-negative. Immunohistochemical staining was performed on paraffin sections of the 56 cases of CM specimens to investigate the expression of EphA2. According to tumor cells positive rate and staining intensity of the results of evaluation, the specimens were divided into low expression and high expression groups.χ(2)-test and t-test were used to analyzed the enumeration data and measurement data, respectively. Survival analysis was used to further elucidate its correlation with clinicopathological characteristics, VM and prognosis. Cox proportional hazard model was used to analyzed the influence factors of prognosis. RESULTS: VM channels were found in 26 of the 56 CM cases and VM-negative 30 cases. VM-positivity was related to cell type, tumor size and recurrence and metastasis, and the differences were statistically significant (χ(2) = 4.612, 5.346, 5.213; P = 0.036, 0.021, 0.027). The results showed that EphA2 was up-regulated in the VM-positive group compared with the group of VM-negative group. The positive rates of EphA2 expression in the VM-positive group and VM-negative group were 92.3% (25/26) and 70.0% (21/30), respectively, with a significant difference between the two groups (t = 2.247, P = 0.009). The EphA2 protein was expressed in epithelioid (10/12), mixed (11/15) and spindle (41.40%) cell types, with a significant difference among these histological types (χ(2) = 6.513, P = 0.010). The expression rate of EphA2 protein were significantly higher in large (54.55%, 18/33) than small (45.45%, 15/33) tumors, and the expression of EphA2 in metastatic and recurrence patients (10/11) were significantly higher compared with controls (31.11%, 14/45) (χ(2) = 4.556, 8.211;P = 0.016, 0.005). Kaplan-Meier survival analysis showed the presence of VM resulted in a poor prognosis (t = 9.263, P = 0.000). The Cox proportional hazards model indicated that the EphA2 overexpression and the presence of VM were independent predictors of a poor prognosis (χ(2) = 12.041, P = 0.001). Moreover, there was a significant positive correlation between them (r = 0.412, P < 0.05). CONCLUSION: The results of this study demonstrate that EphA2 may play a critical role in the formation process of VM in CM, implicating EphA2 as a valuable marker for the prediction of recurrence, metastasis and prognosis in CM patients.

Inhibition of tumor growth and vasculogenic mimicry by curcumin through down-regulation of the EphA2/PI3K/MMP pathway in a murine choroidal melanoma model.

This study aims to investigate the underlying mechanism by which curcumin inhibits tumor growth and reduces vasculogenic mimicry (VM) in a murine choroidal melanoma model. Sixty mice were given subretinal injection with B16F10 cells and divided into a treatment and a control group. Curcumin was administered to the treatment group once a day at a dose of 100 mg/kg for 18 days starting at d3 (the day of inoculation is designated as d0); an equivalent volume of poloxamer-F68 was administered to the control group. Immunohistochemical and histochemical double staining were ued to detect the different blood supply patterns. The amounts of epithelial cell kinase (EphA2), phosphatidylinositol-3-kinase (PI3K), and matrixmetalloproteinase-2 and -9 (MMP-2, MMP-9) proteins expressed in the tumor tissue were analyzed using immunohistochemical staining; mRNA levels were measured using real-time PCR analysis. Results indicate that the tumor volume is reduced (P=0.000) and that the numbers of VM (P=0.000), mosaic vessels (P=0.031), and endothelium-dependent vessels (P=0.000) are significantly decreased by curcumin (P=0.001). The expression levels of EphA2, PI3K, MMP-2, and -9 are also lower in the treatment group than in the control group (P=0.001); similarly, mRNA levels in the treatment group are lower than those in the control group (P=0.000). In conclusion, curcumin has the ability to inhibit the growth of engrafted melanoma VM channels through the regulation of vasculogenic factors that could be related to the down-regulation of the EphA2/PI3K/MMPs signaling pathway. Thus, curcumin has the potential of being a clinical inhibitor of VM of choroidal melanoma.

Microcirculation patterns in indocyanine green angiography and the results of plaque therapy in choroidal melanoma.

PURPOSE: To determine the effect of radioactive plaque therapy on blood vessel behaviour in choroidal melanomas using indocyanine green (ICG) angiography. MATERIAL AND METHODS: Fifty-five patients with choroidal melanoma were studied. Ruthenium-106 plaques were used in 30 eyes, in 11 the "sandwich method" (Ruthenium-106 plaque with transpupillary thermotherapy), was applied and 14 tumours were treated with Iodine-125. In all cases ICG angiography was performed prior to treatment and 12 months after, and at different time afterwards. Baseline tumour microcirculation patterns (MCPs) were studied prior to treatment and post-treatment blood vessels changes were evaluated. Total follow-up period ranged from 14-22 months (mean: 16 months). RESULTS: Pre-treatment ICG angiography revealed complex MCPs, combining parallel with cross-linking, arcs with branching, loops and networks patterns in 23 (41.8%) and non-complex MCPs, including straight, parallel without cross-linking and arcs without branching patterns in 32 (58.2%) melanomas. Twelve months after treatment, 38 tumours (69.1%) showed a significant changes in their MCPs. The mean ultrasonographic regression rate in tumours with complex MCPs was 57.4% as opposed to 36.2% in the group with non-complex MCPs (p = 0.01). No statistically significant correlation in the height regression rate was found among the various methods of therapy, however a significant difference between the type of therapy and MCPs changes was observed (p < 0.001). Melanomas treated with Ruthenium-106 and TTT demonstrated slight or no MCPs changes, while tumours treated with Ruthenium-106 and Iodine-125 plaques alone showed a significant MCPs changes (p < 0.001). The statistical analysis showed the correlation between the type of baseline MCPs and the degree of their changes after treatment (p < 0.001). Tumours with networks, loops, arcs with branching and parallel with crossing showed an increased regression as compared to other MCPs. Twelve patients whose tumours contained complex MCPs developed metastatic disease. CONCLUSIONS: This study suggests that the response of choroidal melanoma to irradiation is related to MCPs as identified by ICG angiography; the presence of complex MCPs is associated with a high regression rate after plaque therapy and a high risk of development of systemic metastatic disease.

Nucleolar size in choroidal and ciliary body melanomas and corresponding hepatic metastases.

PURPOSE: This study aimed to investigate the relationship between hepatic metastasis and the mean diameter of the 10 largest nucleoli (MLN) in uveal melanoma. METHODS: A cross-sectional histopathological analysis of 37 metastases (13 surgical or needle biopsies, 24 autopsies) and corresponding primary choroidal and ciliary body melanomas was conducted, using statistical tests appropriate for paired data. The largest nucleoli were measured from digital photographs of silver-stained sections along a 5-mm-wide linear field. Confounders considered were presence of epithelioid cells and microvascular density (MVD), counted as the number of discrete elements labelled by monoclonal antibody QBEND/10 to the CD34 epitope. RESULTS: Hepatic metastases had more frequent epithelioid cells (p = 0.0047) and a higher MVD (median difference, 7.5 counts/0.313 mm(2) more; p = 0.044) than their corresponding primary tumours. Hepatic metastases, especially in autopsy specimens rather than surgical biopsies, tended to have a smaller MLN (median 3.6 mum) than the corresponding primary tumour (median difference, 0.55 mum; p = 0.066). The MLN in hepatic metastases was not associated with presence of epithelioid cells and MVD. Overall survival after diagnosis of metastasis was comparable whether hepatic metastases had a large or small MLN (p = 0.95), whereas a high MVD tended to be associated with shorter survival (p = 0.096) among the 13 patients with known survival. CONCLUSIONS: The results suggest that MLN is not a useful marker for assessing prognosis after diagnosis of hepatic metastasis from uveal melanoma.