Ocular melanoma is a rare disease that originates from melanocytes in the eye. It is the most prevalent primary ocular malignancy in adults, and has a high metastatic rate. Two important questions... Show moreOcular melanoma is a rare disease that originates from melanocytes in the eye. It is the most prevalent primary ocular malignancy in adults, and has a high metastatic rate. Two important questions for good patient care are: 1) How to differentiate between (benign) nevi, and (malignant) melanoma?, and 2) How to treat this tumor best, particularly in cases with metastases?This thesis addresses two types of ocular melanoma: melanoma of the internal parts of the eye (uveal melanoma) and melanoma of the mucous membrane covering the eye (conjunctival melanoma). This thesis combines patient-related projects with projects from the lab.With new imaging techniques we demonstrate that oxygen values differ in eyes with melanoma compared to other eyes including those with a nevus. We use OCT-angiography to depict tumour vessels non-invasively in conjunctival and iris lesions. These two techniques may be used in the future to differentiate lesions, and to monitor patients after treatment.With studies in the lab we show that new drugs (immunotherapy) that are recently used in cutaneous melanoma, can also be used to treat conjunctival melanoma. We show that vascular growth in uveal melanoma is related to other (genetic and immunologic) characteristics, providing new clues for therapy. Show less
Recent developments in oncology have led to a better molecular and cellular understanding of cancer, and the introduction of novel therapies. Conjunctival melanoma (CoM) is a rare but potentially... Show moreRecent developments in oncology have led to a better molecular and cellular understanding of cancer, and the introduction of novel therapies. Conjunctival melanoma (CoM) is a rare but potentially devastating disease. A better understanding of CoM, leading to the development of novel therapies, is urgently needed. CoM is characterized by mutations that have also been identified in cutaneous melanoma, e.g. in BRAF, NRAS and TERT. These mutations are distinct from the mutations found in uveal melanoma (UM), affecting genes such as GNAQ, GNA11, and BAP1. Targeted therapies that are successful in cutaneous melanoma may therefore be useful in CoM. A recent breakthrough in the treatment of patients with metastatic cutaneous melanoma was the development of immunotherapy. While immunotherapy is currently sparsely effective in intraocular tumours such as UM, the similarities between CoM and cutaneous melanoma (including in their immunological tumour micro environment) provide hope for the application of immunotherapy in CoM, and preliminary clinical data are indeed emerging to support this use. This review aims to provide a comprehensive overview of the current knowledge regarding CoM, with a focus on the genetic and immunologic understanding. We elaborate on the distinct position of CoM in contrast to other types of melanoma, and explain how new insights in the pathophysiology of this disease guide the development of new, personalized, treatments. Show less
