Circulating tumor DNA (ctDNA) has gained increasing attention as a non-invasive biomarker with potential utility across multiple stages of melanoma. ctDNA reflects tumor-derived genetic alterations in real time and has shown value in detecting minimal residual disease, identifying early recurrence, estimating tumor burden, and monitoring response to systemic therapies. In early-stage melanoma, postoperative ctDNA positivity is strongly associated with higher recurrence risk and often precedes radiologic detection. In advanced disease, ctDNA correlates with tumor volume and can distinguish responders from non-responders during targeted therapy and immunotherapy, while also identifying emerging resistance mechanisms. Despite these advantages, clinical implementation remains limited by low shedding in early-stage disease, variation among detection platforms, and the absence of standardized clinical thresholds. Recent advances, including fragmentomics, methylation assays, and multi-target sequencing strategies, aim to improve sensitivity, particularly in low-tumor-burden settings. Integration of ctDNA with radiomics, artificial intelligence, and digital pathology represents an additional opportunity to enhance precision in risk stratification and treatment adaptation. This review summarizes current evidence on ctDNA biology, detection methods, and clinical applications in melanoma and outlines ongoing challenges and future directions required for translation into routine practice.

Introduction: Retinal layer thickness measured by optical coherence tomography (OCT) correlates with disability and disease activity in multiple sclerosis (MS), yet there is scarce data on the ability of retinal OCT rates of change to predict subsequent continuous disease stability. Aims: To investigate whether the rate of change in retinal OCT measures during the first year of monitoring can predict maintenance of continuous “No evidence of disease activity” (c-NEDA) status in MS. Methods: We conducted a longitudinal study of people with MS (PwMS) from our observational cohort (AMIR) at the American University of Beirut. Cases included had at least three spectral-domain OCT scans at baseline, 12 months, and at the last visit. Mixed effects regression (controlling for age, sex, disease duration, EDSS, gap time from initiation of current DMT to first OCT scan, type of DMT, and history of optic neuritis per eye) was performed to explore the differences between the annualized changes in retinal layer thicknesses (microns/year) during the first year in the c-NEDA group compared to those with evidence of disease activity (EDA) at any point during follow-up. Results: In total, 222 eyes of 111 RRMS cases (67 females, 60.4%) were included and followed up clinically for a median (min-max) of 5.24 (3–8.64) years. During the study period, 51 (45.9%) cases maintained c-NEDA, and 60 (54.1%) had EDA. In regression models, EDA cases had greater mean retinal thinning rates during the first year of observation compared to c-NEDA cases with an annualized loss (microns/year) in pRNFL of −1.84 versus 0.03 ( p < 0.0001); in macular RNFL −1.86 versus −0.76 ( p < 0.0001); in GCIPL −0.13 versus 0.53 ( p = 0.008); and in retinal thickness −3.81 versus −1.06 ( p < 0.0001). Conclusion: Our data support the potential value of retinal OCT in prospectively identifying PwMS likely to maintain c-NEDA status versus EDA during follow-up, guiding proactive treatment strategies.