Estefania Cobos

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.

Background: Inherited retinal dystrophies (IRDs) are a genetically heterogeneous group of conditions, with approximately 40% of cases remaining unresolved after initial genetic testing. This study aimed to assess the impact of a personalised genomic approach integrating whole-exome sequencing (WES) reanalysis, whole-genome sequencing (WGS), customised gene panels and functional assays to improve diagnostic yield in unresolved cases. Subjects/Methods: We retrospectively reviewed a cohort of 597 individuals with IRDs, including 525 probands and 72 affected relatives. Among the 221 genetically unresolved cases, a subset of 101 was selected for stepwise re-evaluation. This included WES reanalysis with updated virtual panels, WGS in selected cases and targeted sequencing of complex regions. Variant interpretation was refined using updated classification criteria, segregation analysis and functional assays such as mRNA and minigene/midigene studies. Results: An initial diagnostic yield of 59.6% (313/525) was achieved through first-tier genetic testing. Re-evaluation of the 101 prioritised cases resulted in 42 new diagnoses in probands and resolution of 7 more familial cases, yielding 49 additional diagnoses among previously unresolved patients (48.5%). This increased the overall diagnostic rate for probands to 67.6% (355/525). Functional assays confirmed pathogenicity of variants in ABCA4 , ATF6 , REEP6, and TULP1 , while WGS enabled the detection of structural and deep intronic variants, further enhancing diagnostic accuracy. Conclusions: A patient-centred, stepwise genomic approach significantly improved the molecular diagnosis of IRDs. This strategy supports the clinical utility of periodic WES reanalysis and targeted use of customised panels, WGS and functional assays. The proposed workflow is scalable and applicable to routine clinical practice, contributing to precision medicine in IRDs.

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.

Background/Objectives: Biallelic pathogenic variants in the CEP290 gene are typically associated with severe, early-onset inherited retinal dystrophies (IRDs) in both syndromic and non-syndromic forms. This study explores the phenotypic variability of non-syndromic IRDs associated with CEP290 variants, focusing on two siblings with biallelic variants, one of whom exhibits a remarkably mild phenotype, thereby expanding the clinical spectrum. Methods: Whole-exome sequencing (WES) and mRNA analysis were performed to identify and characterize CEP290 variants in the siblings. Comprehensive ophthalmologic evaluations assessed retinal function and disease progression. Results: Two CEP290 variants, a frameshift (c.955del, p.(Ser319LeufsTer16)) and a missense (c.5777G>C, p.(Arg1926Pro)), were identified in trans in both siblings. Despite sharing the same genetic variants, the sister exhibited significantly preserved retinal function, while the brother presented with a more severe, progressive retinal dystrophy. Conclusions: This study broadens the phenotypic spectrum of non-syndromic CEP290-related IRDs, demonstrating variability in disease severity ranging from mild to severe. These findings highlight the importance of personalized monitoring and tailored management strategies based on individual clinical presentations of CEP290-related IRDs.

Background/Objectives: Biallelic pathogenic variants in the CEP290 gene are typically associated with severe, early-onset inherited retinal dystrophies (IRDs) in both syndromic and non-syndromic forms. This study highlights the phenotypic variability of CEP290-related non-syndromic IRDs, focusing on two siblings with biallelic CEP290 variants. One sibling presents with a milder phenotype, expanding the known spectrum of CEP290-related IRDs and emphasizing the importance of personalized clinical monitoring; Methods: Whole-exome sequencing (WES) was used to identify CEP290 pathogenic variants in the siblings. Comprehensive ophthalmologic evaluations were performed to assess the severity and progression of retinal degeneration; Results: Both siblings were found to carry compound heterozygous pathogenic variants in CEP290, inherited in trans. Clinical evaluations revealed significantly preserved retinal function in the sister, whereas the brother exhibited a more aggressive and progressive retinal dystrophy; Conclusions: This study expands the phenotypic spectrum of non-syndromic CEP290-related IRDs, demonstrating that biallelic CEP290 variants can result in a wide range of severity, from mild to severe. These findings highlight the need for personalized monitoring and tailored management strategies in CEP290-related IRDs.

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.