Daniel Lorenzo

To assess the outcomes of a modified surgical approach for the treatment of uveal melanoma involving endoresection with intentional residual tumor at the margins, combined with adjuvant ruthenium-106 brachytherapy. This technique aims to reduce surgical morbidity, while preserving visual function and maintaining effective local tumor control and survival. We conducted a retrospective observational study including 33 patients with choroidal melanoma treated between January 2017 and August 2024 at a single tertiary ocular oncology center in Spain. Patients underwent pars plana vitrectomy and endoresection leaving residual tumor followed by ruthenium-106 brachytherapy. Clinical, functional, and oncological outcomes were analyzed, including tumor recurrence, metastasis, visual acuity, complications, and cytogenetic findings. Kaplan–Meier analysis was used to estimate survival and recurrence rates. After a mean follow-up of 41.7 months, local tumor recurrence occurred in 2 patients (6.06%) and enucleation was performed in 1 patient (3.03%). Two patients (6.06%) developed metastases, with one disease-specific death, resulting in a 5-year survival rate of 97%. Visual acuity of 20/200 or better was preserved in 60.61% of patients. The most frequent complications were retinal detachment (36.36%) and macular edema (45.45%). Cytogenetic analysis showed a significant association between chromosome 1p loss and both recurrence and metastasis (p = 0.032). No cases of phthisis bulbi or severe hypotony were observed. This modified endoresection technique with intentional tumor residuals and adjuvant ruthenium-106 brachytherapy offers a safe and function-preserving option for selected patients with choroidal melanoma. It achieves good tumor control and visual outcomes, with a low rate of enucleation and metastasis. Further studies are required to validate its long-term efficacy.

In the published publication [...].

Objectives: The aim of this study was to establish the concordance between conventional 20 Mhz ultrasonography and an ultrawide-field (UWF) imaging system (Optos^® California) in the measurement of basal diameters of melanocytic choroidal tumors. Methods: A retrospective study comparing diagnostic tests was conducted in patients with untreated melanocytic choroidal lesions (either nevus or melanoma) who had undergone both UWF imaging and ultrasonography. Only cases with a clear visualization of tumor borders in both imaging modalities were included. Longitudinal and transversal base diameters of the melanocytic tumors were measured by 20 MHz US (one observer) and UWF fundus photography (two observers). Interobserver agreement was assessed for UWF imaging first to validate the technique. Then, UWF imaging measurements were compared with 20 MHz US results. Results: In total, 106 patient images were reviewed, of which 61 were excluded due to unclear visualization of tumor margins. We found excellent concordance (from ICC and defined Bland–Altman plots) for interobserver and inter-technique agreement in estimating basal diameters when using pseudocolor composite and red laser images by comparing them with 20 MHz US results. Conclusions: UWF fundus imaging, when complete visualization of the tumor margins is possible, could be as reliable as ultrasonography in the measurement of the basal diameters of choroidal melanocytic tumors.

Uveal melanoma (UM) is the most common primary malignant intraocular tumor in adults. Distant metastasis is common, affecting around 50% of patients. Prognostic accuracy relies on molecular characterization of tumor tissue. In these patients, however, conventional biopsy can be challenging due to the difficulty of obtaining sufficient tissue for the analysis due to the small tumor size and/or post-brachytherapy shrinkage. An alternative approach is liquid biopsy, a non-invasive technique that allows for real-time monitoring of tumor dynamics. Liquid biopsy plays an increasingly prominent role in precision medicine, providing valuable information on the molecular profile of the tumor and treatment response. Liquid biopsy can facilitate early detection and can be used to monitor progression and recurrence. ctDNA-based tests are particularly promising due to their ease of integration into clinical practice. In this review, we discuss the application of ctDNA in liquid biopsies for UM. More specifically, we explore the emerging technologies in this field and the advantages and disadvantages of using different bodily fluids for liquid biopsy. Finally, we discuss the current barriers to routine clinical use of this technique.

UM is an aggressive intraocular tumor characterized by high plasticity and a propensity to metastasize in the liver. However, the underlying mechanisms governing liver tropism remain poorly understood. Given the emerging significance of exosomes, we sought to investigate the contribution of UM-derived exosomes to specific steps of the metastatic process. Firstly, we isolated exosomes from UM cells sharing a common genetic background and different metastatic properties. A comparison of protein cargo reveals an overrepresentation of proteins related to cytoskeleton remodeling and actin filament-based movement in exosomes derived from the parental cells that may favor the detachment of cells from the primary site. Secondly, we assessed the role of macrophages in reprogramming the HHSCs by exosomes. The activation of HHSCs triggered a pro-inflammatory and pro-fibrotic environment through cytokine production, upregulation of extracellular matrix molecules, and the activation of signaling pathways. Finally, we found that activated HHSCs promote increased adhesion and migration of UM cells. Our findings shed light on the pivotal role of exosomes in pre-metastatic niche construction in the liver.

In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify the predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our centre from 2016 to 2021. Clinical management involved active surveillance followed by brachytherapy if growth was detected. The lesions were classified into two groups according to whether they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to identify the possible predictors of growth. Significant between-group differences were observed in thickness (p = 0.00), greatest basal diameter (p = 0.00), number of risk factors (p = 0.00), symptoms (p = 0.001; relative risk [RR]: 4.3), orange pigment (p = 0.00; RR: 6.02), and ultrasonographic hollowness (Kappa sign); p = 0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm (p = 0.02; RR: 2.46). The time to growth in these lesions was significantly shorter (p = 0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can help differentiate between choroidal nevi and small melanomas, when considered together with clinical risk factors.

Aims: To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). Methods: Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes. Results: A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector. Conclusions: Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features.

In this study, we aimed to identify the features of indeterminate choroidal melanocytic lesions visualized on optical coherence tomography angiography (OCTA) and to identify predictors of growth. We retrospectively evaluated 86 patients with indeterminate lesions treated at our cen-tre from 2016 to 2021. Clinical management involved active surveillance followed by brachy-therapy if growth was detected. The lesions were classified into two groups according to wheth-er they grew (small melanomas) or remained stable (choroidal nevi). Growth was detected in 19 (22.1%) lesions. All patients underwent OCTA at baseline. These images were compared to iden-tify possible predictors of growth. Significant between-group differences were observed in thickness (p=0.00), greatest basal diameter (p=0.00), number of risk factors (p=0.00), symptoms (p=0.001; relative risk [RR]: 4.3), orange pigment (p=0.00; RR: 6.02), and ultrasonographic hol-lowness (Kappa sign); p=0.000; RR: 5.3). The melanomas had significantly more vessels with a diameter ≥ 76.3 µm (p=0.02; RR: 2.46). The time to growth in these lesions was significantly shorter (p=0.05) than in lesions with smaller vessels. These findings show that vessel diameter quantified by OCTA can differentiate between choroidal nevi and small melanomas, especially when considered together with clinical risk factors.

The objective of this study was to determine the correlation between topographic vessel density (VD) and retinal thickness (RT) reductions induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiography (OCTA). This was a prospective, interventional case series. VD and RT measurements were separately taken in four parafoveal subfields at baseline and after six months of treatment. This correlation was statistically assessed using Spearman’s rho correlation coefficient after adjustment for multiple comparisons. The study included a total of 48 eyes in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (±3.5) to 44.6% (±3.2) in the superficial capillary plexus and from 50 (±3.3) to 49% (±3.9) in the deep capillary plexus). Statistically significant reductions in RT were observed in all ETDRS sectors (p < 0.0001). No significant association was found between RT and VD, even when analyzing responders and non-responders separately. After six months of anti-VEGF treatment, no significant correlation was observed between the topographic VD and RT values. These findings suggest that reductions in VD values may not solely result from a reduction in microaneurysms, also being affected by the repositioning of displaced vessels due to edema and a reduction in their caliber. Therefore, VD changes may not be a suitable indirect OCTA biomarker of microaneurysm turnover and treatment response.