Quantitative Perfusion-Weighted Magnetic Resonance Imaging in Uveal Melanoma.

Purpose: Perfusion-weighted imaging (PWI; magnetic resonance imaging [MRI]) has been shown to provide valuable biological tumor information in uveal melanoma (UM). Clinically used semiquantitative methods do not account for tumor pigmentation and eye movement. We hypothesize that a quantitative PWI method that incorporates these, provides a more accurate description of tumor perfusion than the current clinical method. The aim of this study was to test this in patients with UM before and after radiotherapy. Methods: Perfusion-weighted 3T MRIs were retrospectively analyzed in 47 patients with UM before and after radiotherapy. Tofts pharmacokinetic modeling was performed to determine vascular permeability (Ktrans), extracellular extravascular space (ve), and reflux rate (kep). These were compared with semiquantitative clinical parameters including peak intensity and outflow percentage. Results: The effect of tumor pigmentation on peak intensity and outflow percentage was statistically significant (P < 0.01) and relative peak intensity was significantly different between melanotic and amelanotic tumors (1.5 vs. 1.9, P < 0.01). Before radiotherapy, median tumor Ktrans was 0.63 min-1 (range = 0.06-1.42 min-1), median ve was 0.23 (range = 0.09-0.63), and median kep was 2.3 min-1 (range = 0.6-5.0 min-1). After radiotherapy, 85% showed a decrease in Ktrans and kep (P < 0.01). Changes in tumor pigmentation before and after radiotherapy were small and not significant (median increase in T1 of 33 ms, P = 0.55). Conclusions: Quantitative PWI parameters decreased significantly after radiotherapy and can therefore can serve as an early biomarker for treatment response assessment. However, due to the nonsignificant changes in tumor pigmentation before and after radiotherapy, the current semiquantitative method appears to be sufficiently sensitive for detection of changes in tumor perfusion.

Shear-wave elastographic imaging in choroidal melanomas: clinical and hemodynamic correlations.

PURPOSE: This study evaluated the role of shear wave elastography imaging (SWEΙ) in uveal melanomas and the associations between SWEI and clinical and hemodynamic findings. STUDY DESIGN: Prospective, clinical study METHODS: Twelve patients with uveal melanomas, scheduled to undergo Ru-106 brachytherapy, were prospectively recruited from the Department of Ophthalmology of the University Hospital of Heraklion (September-December 2022). B-mode, hemodynamic and SWEI ultrasonography examinations were performed with the HiScan (OPTIKON 2000) and the LOGIQ E9 (GE Healthcare) sonographic systems, respectively. Differences in SWEI scores (kPa) between tumor (TS) and adjacent non-affected choroid (CS), as well as between TS and orbital fat (FS) were examined. Correlations between SWEI and intra-tumoral hemodynamic parameters, including peak systolic and end diastolic velocities and resistivity index (RI) were also examined. RESULTS: TS was significantly correlated with intra-tumoral RI (Pearson's bivariate correlation coefficient 0.681, p=0.015) and with maximal tumor height (Pearson's bivariate correlation coefficient 0.620, p=0.031). TS was significantly higher than both FS and CS scores (paired-samples t-test, p=0.003 and p=0.006, respectively). CONCLUSIONS: SWEI score is applicable as a quantitative biomechanical marker in the assessment of choroidal melanoma. Choroidal melanomas are stiffer than both adjacent choroid and orbital fat. Moreover, choroidal melanomas with higher RI as well as those with higher apical elevations display higher SWEI scores.

Leiomyoma - Ciliary Body Tumor. A Case Report.

AIM: To demonstrate a rare case of ciliary body leiomyoma in our patient Case report: A 72-year-old female reported to our clinic for a preventive examination, upon which we found a dome-shaped grey-brownish mass on the retinal periphery. After completing gonioscopic and ultrasound examinations, we referred the patient to a specialist facility. Due to a finding of suspicious malignant melanoma, we completed the MRI scan and recommended enucleation of the eyeball. A histopathological examination showed a leiomyoma of the ciliary body. CONCLUSION: The aim of this case report is to demonstrate the difficulty of intraocular leiomyoma diagnosis. Only immunohistochemical examination differentiated the tumor from malignant melanoma and determined the diagnosis of ciliary body leiomyoma. Perhaps because of the extreme rarity of this type of tumor, we often neglect to consider a diagnosis of leiomyoma.

Anterior segment swept-source optical coherence tomography and ultrasound biomicroscopy in iris and ciliary body lesions.

OBJECTIVES: Differentiation of iris and ciliary body lesions as benign or malignant and cystic or solid is important. The aim of this study was to compare anterior segment swept-source optical coherence tomography (AS SS-OCT) and ultrasound biomicroscopy (UBM) findings in iris and ciliary body tumors. RESEARCH DESIGN AND METHODS: Forty-two eyes of 38 cases with iris and ciliary body tumors imaged with UBM and AS SS-OCT between September 2018 and September 2023 were evaluated retrospectively. RESULTS: Of 42 eyes, 14 had melanoma, 14 iris pigment epithelial (IPE) cysts, 7 nevi, 3 Lisch nodules, 2 iris stromal cysts, 1 pars plana cysts, and 1 iris mammillations. An equivalent (100%) visualization of the anterior tumor margin was obtained with both techniques. Compared to AS SS-OCT, UBM was superior for posterior margin visualization in melanocytic tumors and IPE cysts. Bland-Altman plots demonstrated good agreement between UBM and AS SS-OCT for melanocytic tumors < 2.5 mm in base diameter and < 2 mm in thickness. CONCLUSIONS: Although, UBM is the gold standard for ciliary body and iridociliary tumors. AS SS-OCT should be considered as an excellent alternative to UBM, especially in minimally elevated iris lesions.

Multifocal choroidal melanoma: a clinicohistopathological correlation.

A woman in her late 50s presented with on-and-off redness and diminution of vision in her left eye for 6 months. Her best corrected visual acuity was 20/40 in the right eye and hand motion in the left eye. Anterior segment examination revealed a greyish-white lesion extending from 3 to 6 o'clock hours posterior to the iris and protruding into the anterior chamber. Left eye B-scan ultrasonography showed a multifocal choroidal lesion, a smaller one involving the posterior pole, and a larger lesion involving the complete nasal quadrant and anteriorly extending to the ciliary body and iris. Fine-needle aspiration biopsy performed from the anterior lesion showed a possible neoplastic aetiology of melanocytic origin of the cells. Finally, the patient underwent left eye enucleation with a ball implant. Histopathological examination of the enucleated eye confirmed the final diagnosis of multifocal choroidal melanoma involving the adjacent ciliary body and iris.

Tumor Shape-Specific Brachytherapy Implants by 3D-Printing, Precision Radioactivity Painting, and Biomedical Imaging.

In brachytherapy (BT), or internal radiation therapy, cancer is treated by radioactive implants. For instance, episcleral plaques (EPs) for the treatment of uveal melanoma, are designed according to generic population approximations. However, more personalized implants can enhance treatment precision through better adjustment of dose profiles to the contours of cancerous tissues. An original approach integrating biomedical imaging, 3D printing, radioactivity painting, and biomedical imaging, is developed as a workflow for the development of tumor shape-specific BT implants. First, computer-aided design plans of EP are prepared according to guidelines prescribed by the Collaborative Ocular Melanoma Study protocol. Polyetheretherketone (PEEK), a high-performance polymer suitable for permanent implants, is used to 3D-print plaques and the geometrical accuracy of the printed design is evaluated by imaging. The possibility to modulate the dose distribution in a tridimensional manner is demonstrated by painting the inner surfaces of the EPs with radioactive 103Pd, followed by dose profile measurements. The possibility to modulate dose distributions generated by these 3D-printed plaques through radioactivity painting is therefore confirmed. Ex vivo surgical tests on human eyeballs are performed as an assessment of manipulation ease. Overall, this work provides a solution for the fabrication of tumor-specific radioactive implants requiring higher dose precision.

MR-based follow-up after brachytherapy and proton beam therapy in uveal melanoma.

PURPOSE: MRI is increasingly used in the diagnosis and therapy planning of uveal melanoma (UM). In this prospective cohort study, we assessed the radiological characteristics, in terms of anatomical and functional imaging, of UM after ruthenium-106 plaque brachytherapy or proton beam therapy (PBT) and compared them to conventional ultrasound. METHODS: Twenty-six UM patients were evaluated before and 3, 6 and 12 months after brachytherapy (n = 13) or PBT (n = 13). Tumour prominences were compared between ultrasound and MRI. On diffusion-weighted imaging, the apparent diffusion value (ADC), and on perfusion-weighted imaging (PWI), the time-intensity curves (TIC), relative peak intensity and outflow percentages were determined. Values were compared between treatments and with baseline. RESULTS: Pre-treatment prominences were comparable between MRI and ultrasound (mean absolute difference 0.51 mm, p = 0.46), but larger differences were observed post-treatment (e.g. 3 months: 0.9 mm (p = 0.02)). Pre-treatment PWI metrics were comparable between treatment groups. After treatment, brachytherapy patients showed favourable changes on PWI (e.g. 67% outflow reduction at 3 months, p < 0.01). After PBT, significant perfusion changes were observed at a later timepoint (e.g. 38% outflow reduction at 6 months, p = 0.01). No consistent ADC changes were observed after either treatment, e.g. a 0.11 × 10-3mm2/s increase 12 months after treatment (p = 0.15). CONCLUSION: MR-based follow-up is valuable for PBT-treated patients as favourable perfusion changes, including a reduction in outflow, can be detected before a reduction in size is apparent on ultrasound. For brachytherapy, a follow-up MRI is of less value as already 3 months post-treatment a significant size reduction can be measured on ultrasound.

Prognostic Value of the Radiomics-Based Model in the Disease-Free Survival of Pretreatment Uveal Melanoma: An Initial Result.

OBJECTIVE: The aim of this study was to develop a pretreatment magnetic resonance imaging (MRI)-based radiomics model for disease-free survival (DFS) prediction in patients with uveal melanoma (UM). METHODS: We randomly assigned 85 patients with UM into 2 cohorts: training (n = 60) and validation (n = 25). The radiomics model was built from significant features that were selected from the training cohort by applying a least absolute shrinkage and selection operator to pretreatment MRI scans. Least absolute shrinkage and selection operator regression and the Cox proportional hazard model were used to construct a radiomics score (rad-score). Patients were divided into a low- or a high-risk group based on the median of the rad-score. The Kaplan-Meier analysis was used to evaluate the association between the rad-score and DFS. A nomogram incorporating the rad-score and MRI features was plotted to individually estimate DFS. The model's discrimination power was assessed using the concordance index. RESULTS: The radiomics model with 15 optimal radiomics features based on MRI performed well in stratifying patients into the high- or a low-risk group of DFS in both the training and validation cohorts (log-rank test, P = 0.009 and P = 0.02, respectively). Age, basal diameter, and height were selected as significant clinical and MRI features. The nomogram showed good predictive performance with concordance indices of 0.741 (95% confidence interval, 0.637-0.845) and 0.912 (95% confidence interval, 0.847-0.977) in the training and validation cohorts, respectively. Calibration curves demonstrated good agreement. CONCLUSION: The developed clinical-radiomics model may be a powerful predictor of the DFS of patients with UM, thereby providing evidence for preoperative risk stratification.

Stereotactic irradiation on linear accelerator - ultrasound versus MRI in choroidal melanoma volume calculation.

BACKGROUND: Stereotactic irradiation is one of the treatment modalities for intraocular uveal melanoma. The study's purpose was to describe the background of stereotactic one-day session radiosurgery, how the comparison in the difference between the tumor volume measured values from the magnetic resonance imaging (MRI) method and the ultrasound method was related to it, and which method was more precise to be used for tumor regression after irradiation. METHODS: The group of 147 patients with choroidal melanoma was treated by stereotactic irradiation on the linear accelerator with a single dose of 35.0 Gy. During the standard treatment process the uveal melanoma volumes, needed for dose calculation, were obtained using MRI from the individual stereotactic planning scheme and by ultrasound from the ultrasound device. All volumes were statistically compared using the paired t-test, and for the visualization purpose, the Bland-Altman plot was used. RESULTS: In the group of patients, it was 70 (47.6%) males and 77 (52.4%) females. The tumor volume median was from MRI equal to 0.44 cm3 and from ultrasound equal to 0.53 cm3. The difference between the ultrasound and the MRI volume measured values was statistically significant. However, the Bland-Altman plot clearly documents that the two methods are in agreement and can be used interchangeably. In most of the cases, the measured values of the ultrasound-calculated volume achieved slightly higher measured values. CONCLUSIONS: The calculation of the intraocular uveal tumor volume is a crucial part of the stereotactic irradiation treatment. The ultrasound volume measured values were in most of the cases higher than the measured values from the MRI. Although the methods are comparable and can be used interchangeably, we are recommending using the more precise MRI method not only during the treatment but also on later regular medical checks of tumor regression or progression.

MRI and FUNDUS image fusion for improved ocular biometry in Ocular Proton Therapy.

INTRODUCTION: Ocular biometry in Ocular Proton Therapy (OPT) currently relies on a generic geometrical eye model built by referencing surgically implanted markers. An alternative approach based on image fusion of volumetric Magnetic Resonance Imaging (MRI) and panoramic fundus photography was investigated. MATERIALS AND METHODS: Eighteen non-consecutive uveal melanoma (UM) patients, who consented for an MRI and had their tumour base visible on panoramic fundus photography, were included in this comparative analysis. Through generating digitally-reconstructed projections from MRI images using the Lambert azimuthal equal-area projection, 2D-3D image fusion between fundus photography and an eye model delineated on MRI scans was achieved and allowed for a novel definition of the target base (MRI + FCTV). MRI + FCTV was compared with MRI-only delineation (MRIGTV) and the conventional (EyePlan) target definition (EPCTV). RESULTS: The combined use of fundus photography and MRI to define tumour volumes reduced the average discrepancies by almost 65% with respect to the MRI only tumour definitions when comparing with the conventionally planned EPCTV. With the proposed method, shallow sub-retinal tumour infiltration, otherwise invisible on MRI, can be included in the target volume definition. Moreover, a novel definition of the fovea location improves the accuracy and personalisation of the 3D eye model. CONCLUSION: MRI and fundus image fusion overcomes some of the limitations of ophthalmological MRI for tumour volume definition in OPT. This novel eye tumour modelling method might improve treatment planning personalisation, allowing to better anticipate which patients could benefit from prophylactic treatment protocols for radiation induced maculopathy.

Identification of extraocular extension in uveal melanoma by ophthalmological ultrasound.

BACKGROUND AND PURPOSE: Uveal melanoma is the most common primary malignant intraocular tumour in the adult population, with a survival rate of 50% despite advances in treatment and knowledge of this disease. The presence of extraocular extension (EE) worsens the prognosis of these patients, so its proper identification can ensure its management and early intervention. Ophthalmological ultrasound is the technique of choice for the diagnosis and follow-up of these patients, both of the anterior EE using ultrasonic biomicroscopy (UBM), and the posterior EE using A and B ultrasound. The aim of this study is to describe the ultrasound characteristics of the BMU and the A and B ultrasound. MATERIAL AND METHODS: A descriptive and retrospective study is carried out on patients diagnosed with uveal melanoma (UM) and EE from 2003 to 2019. The ultrasound characteristics of the local disease and the follow-up after treatment were recorded completely and at each visit. In the case of anterior EE, photographs of the anterior segment and UBM were taken, while those involving the posterior segment were explored under A and B mode ultrasound. All enucleated eyes were sent for anatomopathological study. RESULTS: Ten patients with an average age of 72.3 years were included. The largest proportion of them were medium-sized tumours, followed by large and small ones. The most frequent morphology of the primary tumour was cupuliform. All the EE presented lower internal reflectivity compared to the primary tumour. No trans-scleral connection bridges were found between the primary tumour and the EE in the ultrasound studies. 50% of patients underwent primary enucleation at the time of diagnosis of intraocular MU due to the presence of the EE, and the remaining 50% presented the EE after initial treatment of the primary tumour with I125 brachytherapy. Sixty percent of the patients presented with posterior EE, and were therefore diagnosed with ultrasound A and B. The most frequent histopathological pattern with 87.5% of patients was the epithelioid pattern. DISCUSSION: Ultrasound scanning in patients with MU is mandatory for diagnosis and follow-up of EE. BMU and A and B ultrasound are the test of choice for anterior and posterior EE, respectively. EE have particular ultrasound characteristics such as low internal reflectivity, regularity of their contour and their location usually adjacent to the base of the primary intraocular tumor.

MR imaging characteristics of uveal melanoma with histopathological validation.

PURPOSE: To evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology. METHODS: MR images from 42 UM were compared with US and fundoscopy, and on 14 enucleated cases with histopathology. RESULTS: A significant relationship between the signal intensity on T1 and pigmentation on histopathology was found (p=0.024). T1 hyperintense UM were always moderately or strongly pigmented on histopathology, while T1-hypointense UM were either pigmented or non-pigmented. Mean apparent diffusion coefficient (ADC) of the UM was 1.16 ± 0.26 × 10-3 mm2/s. Two-thirds of the UM had a wash-out and the remaining a plateau perfusion time-intensity curve (TIC). MRI was limited in evaluating the basal diameter of flat tumors. US tends to show larger tumor prominence (0.5mm larger, p=0.008) and largest basal diameter (1.4mm larger, p<0.001). MRI was good in diagnosing ciliary body involvement, extrascleral extension, and optic nerve invasion, but limited on identifying scleral invasion. An increase of tumor prominence was associated with lower ADC values (p=0.030) and favored a wash-out TIC (p=0.028). An increase of tumor ADC correlated with a plateau TIC (p=0.011). CONCLUSIONS: The anatomical and functional MRI characteristics of UM were comprehensively assessed. Knowing the MRI characteristics of UM is important in order to confirm the diagnosis and to differentiate UM from other intra-ocular lesions and because it has implications for treatment planning. MRI is a good technique to evaluate UM, being only limited in case of flat tumors or on identifying scleral invasion.

A Comparison of 3 T and 7 T MRI for the Clinical Evaluation of Uveal Melanoma.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis and treatment planning of uveal melanoma (UM), the most common primary intraocular tumor. Initially, 7 T MRI was primarily used, but more recently these techniques have been translated to 3 T, as it is more commonly available. PURPOSE: Compare the diagnostic performance of 3 T and 7 T MRI of UM. STUDY TYPE: Prospective. POPULATION: Twenty-seven UM patients (19% female). FIELD STRENGTH/SEQUENCE: 3 T: T1- and T2-weighted three-dimensional (3D) spin echo (SE) and multi-slice (MS) SE, 7 T: T1-weighted 3D gradient echo (GE), T2-weighted 3D SE and MS SE, 3 T and 7 T GE dynamic contrast-enhanced. T1 weighted images: acquired before and after Gadolinium (Gd) administration. ASSESSMENT: For all sequences, scan and diagnostic quality was quantified using a 5-point Likert scale. Signal intensities on T1 and T2 relative to choroid and eye muscle respectively were assessed as well as the tumor prominence. Finally, the perfusion time-intensity curves (TICs) were classified as plateau, progressive, or wash-out. STATISTICAL TESTS: Image quality scores were compared between both field strengths using Wilcoxon signed-rank and McNemar tests. Paired t-tests and Bland-Altman were used for comparing tumor prominences. P < 0.05 was considered statistically significant. RESULTS: Image quality was comparable between 3 T and 7 T, for 3DT1, 3DT2, 3DT1Gd (P = 0.86; P = 0.34; P = 0.78, respectively) and measuring tumor dimensions (P = 0.40). 2DT1 and 2DT2 image quality were rated better on 3 T compared to 7 T. Most UM had the same relative signal intensities at 3 T and 7 T on T1 (17/21) and T2 (13/17), and 16/18 diagnostic TICs received the same classification. Tumor prominence measurements were similar between field strengths (95% confidence interval: -0.37 mm to 0.03 mm, P = 0.097). DATA CONCLUSION: Diagnostic performance of the evaluated 3 T protocol proved to be as capable as 7 T, with the addition of 3 T being superior in assessing tumor growth into nearby anatomical structures compared to 7 T. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Efficacy and tolerability of chemosaturation in patients with hepatic metastases from uveal melanoma.

BACKGROUND: Patients with hepatic metastatic uveal melanoma still have a poor outcome. PURPOSE: To evaluate overall survival (OS), progression-free survival (PFS), and response predictors in these patients treated with chemosaturation by percutaneous hepatic perfusion with melphalan (CS-PHP). MATERIAL AND METHODS: Between June 2015 and March 2020, a total of 29 patients (median age 69.7 years; age range 30-81 years; 60% women; median BMI 25.7 kg/m2; range 18.7-35.3kg/m2; 1-6 procedures per patient) were treated with 53 CS-PHPs. All patients received cross-sectional imaging for initial and follow-up examinations. Baseline tumor load, extrahepatic tumor load, tumor response, PFS, and OS were assessed. Non-parametric statistics were used. RESULTS: After the initial CS-PHP, a partial response was observed in 11 patients (41%), stable disease in 12 patients (44%) and progressive disease in 4 patients (15%); two patients died before the response was evaluated. After initial CS-PHP, median OS was 12.9 ± 7.4 months and median PFS was 7.1 ± 7.4 months. OS after one year was 50%. After the second CS-PHP, median PFS was 7.9 ± 5.7 months. Seven patients had a liver tumor burden >25%, associated with a significantly shorter OS (6.0 ± 2.4 vs. 14.1 ± 12.7 months; P = 0.008). At the time of first CS-PHP, 41% (12/29) of the patients had extrahepatic metastases that did not affect OS (11.1 ± 8.4 months vs. 12.9 ± 13.6 months; P = 0.66). CONCLUSION: CS-PHP is a safe and effective treatment for the hepatic metastatic uveal melanoma, especially for patients with a hepatic tumor burden <25%.

Assessment of sorafenib induced changes in tumor perfusion of uveal melanoma metastases with dynamic contrast-enhanced ultrasound (DCE-US).

PURPOSE: Dynamic contrast-enhanced ultrasound (DCE-US) was used to monitor early response to sorafenib therapy in patients with liver metastases from uveal melanoma. METHODS: In total, 21 patients with liver metastases were recruited within a prospective trial and underwent daily sorafenib therapy. DCE-US of a target lesion was performed before initiation of treatment, on day 15 and 56. Two independent blinded investigators performed software analysis for DCE-US parameters and inter-observer-correlation was calculated. Response to treatment was evaluated on day 56. DCE-US parameters were correlated with clinical response and RECIST1.1 criteria. RESULTS: Inter-observer-correlation (r) of DCE-US parameters [time-to-peak (TTP), mean-transit-time (MTT), peak intensity (PI), regional blood volume (RBV), regional blood flow (RBF)] at baseline, day 15, and day 56 was highly significant (r-range 0.73-0.97, all p < 0.001). Out of 17 evaluable patients, 12 patients survived day 56 (clinical responders, cRE), whereas, five patients died before day 56 and were classified as non-responders (cNR). TTP values significantly increased in the cRE group 15 days after initiation of treatment for investigator 1 (p = 0.034) and at day 56 for both investigators (p = 0.028/0.028). MTT had increased significantly in the cRE group on day 56 (p = 0.037/0.022). In the cNR group changes for TTP and MTT remained insignificant. Thus, increase of the DCE-US parameters TTP and MTT are associated with response to treatment and prognosis. CONCLUSION: An increase of TTP and MTT at frequent intervals could serve as a surrogate marker for early response evaluation to anti-angiogenic treatment of metastatic uveal melanoma.

[Intraocular perivascular epithelioid cell tumor: report of two cases].

Two male patients presented with painless vision loss to blindness in one eye, and the radiography examinations revealed an intraocular mass suspicious for choroidal melanoma. They underwent enucleation. The histopathological and immunohistochemical findings were compatible with the diagnosis of intraocular perivascular epithelioid cell tumor. Because of its rarity, intraocular perivascular epithelioid cell tumor is easy to be confused with other intraocular tumors on histopathological and immunohistochemical examinations. (Chin J Ophthalmol, 2021, 57: 857-860).