ME20-S as a Potential Biomarker for the Evaluation of Uveal Melanoma.

PURPOSE: We previously identified the presence of the melanocyte-specific secreted (ME20-S) glycoprotein in secretomes of uveal melanoma (UM) cultures. The aim of this study was to test for the presence and levels of ME20-S in the serum of patients with choroidal nevi and UM and correlate these levels with individual clinical data. METHODS: Serum ME20-S levels were determined by ELISA in 111 patients distributed into four categories (53 choroidal nevi, 30 untreated UM, 11 10-year disease-free [DF] UM, 17 hepatic metastatic UM) and 32 age- and sex-matched controls. ME20-S levels were correlated with individual clinical data. RESULTS: The UM and the metastatic groups showed significantly higher levels of serum ME20-S than the other groups (P < 0.001). ME20-S levels in the DF patients did not differ from those in the control group. In addition, log-transformed serum ME20-S levels showed a positive correlation with the thickness of the lesion mass in UM patients (regression coefficient 0.0689, 95% confidence interval 0.0689-0.1123, R2 = 27.1%). CONCLUSIONS: Elevated ME20-S serum levels are associated with tumor size and advanced stages of UM while low levels are characteristic of DF patients. ME20-S might be a promising serum marker for UM and useful for monitoring metastatic disease.

Detection of circulating melanoma cells in choroidal melanocytic lesions.

PURPOSE: To detect and quantify circulating tumour cells (CTCs) in peripheral blood of patients with uveal melanoma primary non-metastatic tumours, and to analyze the possible relationship between CTCs and clinical risk factors. METHODS: Prospective study with two clinical groups: 4 patients diagnosed with choroidal nevus and 8 patients with choroidal melanoma prior to treatment. A single sample of 7.5 mL of peripheral blood was taken and the CTCs were isolated using a CellSearch system that captures positive cells for the CD146 antigen (MUC18). RESULTS: None of the patients with choroidal nevus showed CTCs in peripheral blood. More than one CTC/7.5 mL was detected in 50 % of patients with choroidal melanoma prior to treatment. The higher level of CTC cells in peripheral blood (3/7.5 mL) was detected in the patient with the larger choroidal melanoma which also presented extrascleral extension and epithelioid pathology. CONCLUSION: Performing an analysis with the CellSearch system allows to quantify the choroidal melanoma CTCs in peripheral blood. This finding highlights the potential usefulness of this technique to achieve the correct stratification and monitoring of the treatment.

Detecting ultrasonographic hollowness in small choroidal melanocytic tumors using 10 MHz and 20 MHz ultrasonography: a comparative study.

BACKGROUND: The purpose of this work was to compare the detection of ultrasonographic hollowness (UH), as a risk sign for evolution from small choroidal melanocytic tumors (SCMT) to uveal melanoma (UM), between conventional ultrasonography (standardized 8 MHz ultrasonography and B-mode 10 MHz ultrasonography) and high-resolution 20 MHz ultrasonography. METHODS: Fifty SCMTs from 50 eyes were included in this work. In all cases, ultrasonographic studies were performed using: 8 MHz standardized A-mode, 10 MHz B-mode, and posterior pole 20 MHz B-mode. Comparison between the presence and the absence of UH were carried out between the ultrasonographic images. RESULTS: There were no statistically significant differences between the SCMT dimensions obtained using the 8-10 and 20 MHz techniques. UH was detected in 12 and 20 cases by means of ten and 20 MHz probes respectively. The difference between these proportions was statistically different from zero (McNemar test, p-value = 0.008). Cases without UH by 20 MHz have lower height values than cases with UH. However, these differences were not found by 10 MHz ultrasonography. By receiver operating characteristic (ROC) study, specificity was better by 20 MHz than 10 MHz ultrasonography when the value of tumor height as marker for UH was studied. CONCLUSIONS: UH is easier to detect by 20 MHz than by 10 MHz ultrasonography. This ultrasonographic sign appears to be correlated with the height of the tumor. Thus, we believe UH estimation by 20 MHz ultrasonography could be used as a significant predictive factor for SCMT growth.

Relationship between macular bending and foveoschisis in myopic patients.

PURPOSE: To investigate factors associated with myopic foveoschisis and macular bending and to determine how the presence of macular bending affects the development of myopic foveoschisis. METHODS: In a prospective study of 194 eyes of 105 patients with high myopia, we performed complete ophthalmic examinations, optical coherence tomography (OCT), and A-scan ultrasounds. Patients were divided into three groups according to the OCT results. Group 1 consisted of 25 eyes (17 patients) with myopic foveoschisis; group 2 consisted of 36 eyes (20 patients) with macular bending; and group 3 consisted of 135 eyes (68 patients) without macular bending, foveoschisis, or other diseases. Macular bending was defined as a smooth macular elevation observed upon OCT in patients with pathologic myopia. Age, sex, spherical equivalence, axial length (AXL), and OCT findings were obtained and compared to identify factors that are related to myopic foveoschisis and macular bending. Moreover, using the whole data set, we evaluated and correlated myopic foveoschisis with the presence or absence of macular bending to determine whether this bulge in the macular area influences the development of myopic foveoschisis. RESULTS: In group 1, all eyes presented posterior staphyloma and two factors were independently associated with a higher risk of having myopic foveoschisis: internal limiting membrane detachment (p < 0.001) and retinal arteriolar traction (p < 0.001). In group 2, only retinal arteriolar traction (p < 0.009) was independently associated with macular bending. Furthermore, macular bending was significantly correlated as a protective factor against myopic foveoschisis (adjusted odds ratio, 0.116; 95% confidence interval, 0.019 to 0.701; p < 0.019); the AXL of patients with the same spherical equivalence and macular bending was significantly shorter than that of patients without macular bending (p = 0.005). CONCLUSIONS: Intraocular and extraocular wall factors were associated with myopic traction maculopathy, which plays an important role in its pathogenesis. Moreover, macular bending might be a key factor in preventing myopic foveoschisis by decreasing AXL.

Serum DJ-1/PARK 7 is a potential biomarker of choroidal nevi transformation.

PURPOSE: There is substantial evidence that intraocular melanomas arise from benign nevi in the uveal tract. Previous studies performed by the authors revealed that uveal melanoma cells secrete the oncoprotein DJ-1/PARK7 into the extracellular environment and circulation. The aim of this study was to determine whether circulating DJ-1 serum levels correlate with known clinical risk factors of nevi growth. METHODS: Standardized ultrasonography, optical coherence tomography, and eye fundus examinations were used to evaluate the clinical risk factors of nevi growth. These clinical risk factors (including nevi size, distance of margins to the optic disc, detection of acoustic hollowness, presence of ocular symptoms, orange pigment, subretinal fluid, and absence of drusen) were examined in 53 consecutive patients from January 2009 to February 2011. Serum levels of DJ-1/PARK7 in these patients and in healthy age- and sex-matched controls (n = 32) were analyzed using ELISA. RESULTS: Within the choroidal nevi group, DJ-1 serum levels were higher in those with symptoms (P < 0.033), with a nevus thickness greater than 1.5 mm (P < 0.001), a large basal diameter greater than 8 mm (P < 0.001), and the presence of acoustic hollowness (P < 0.001), compared to those patients without these risk factors. Similar significant differences were found when these at risk nevi subgroups were compared to healthy persons. CONCLUSIONS: Elevated serum levels of DJ-1 are associated with choroidal nevi transformation risk factors. Therefore, DJ-1 appears to be a promising factor for predicting the growth of choroidal nevi and may be a potential biomarker of malignancy.

Prospective clinical trial evaluating the efficacy of photodynamic therapy for symptomatic circumscribed choroidal hemangioma.

PURPOSE: To evaluate photodynamic therapy (PDT) for symptomatic circumscribed choroidal hemangioma (CCH). DESIGN: Prospective, multicenter, nonrandomized clinical trial. PARTICIPANTS: Thirty-one eyes of 31 patients with posterior pole CCH and symptoms caused by exudation into the macular area. INTERVENTION: Photodynamic therapy was applied by Zeiss laser. Intravenous verteporfin at 6 mg/m(2) body surface was administered before treatment, and light emitted at 689 nm for photosensitization. The treatment spot diameter was calculated on early-phase frames of pretreatment indocyanine green angiography. Fifteen minutes after starting the verteporfin infusion, the laser beam was applied to the retina at radiant exposure 50 J/cm(2) and exposure time 83 seconds. One to 4 treatments were applied at 12-week intervals over 1 year. Standardized evaluation was performed before and at 4-week intervals after each treatment, and at 3, 6, 9, and 12 months. All patients were followed for >or=12 months. MAIN OUTCOME MEASURES: The primary outcome measure was the absence of exudative retinal detachment at the 12-month follow-up visit on ophthalmoscopy, fluorescein angiography, and optical coherence tomography. Secondary measures were the visual acuity outcome, with best-corrected visual acuity determined by the Early Treatment for Diabetic Retinopathy Study chart, tumor thickness decrease on B-scan ultrasonography, and adverse events. RESULTS: Among the total, 82.8% of patients required 1, 13.8% 2, and 3.4% 3 PDTs to eliminate exudative retinal detachment. Visual acuity increased from a mean of 20/60 to 20/35 (P<0.001). Sixty-nine percent of patients demonstrated visual recovery (P<0.001). Cystoid macular edema regressed in all cases and exudative macular detachment disappeared in all but 2 cases. The CCH thickness decreased in all cases from a mean of 3.0 to 1.7 mm, with the most intense effect seen after 4 weeks of treatment (P<0.001). Visual fields showed resolution of central scotomas. There were no severe adverse events. CONCLUSIONS: Combining PDT with the standard age-related macular degeneration protocol is an effective treatment for CCH in terms of resolution of exudative subretinal fluid and recovery of VA. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.