Uveal melanoma, as opposed to cutaneous melanoma, is a tumor which is predominantly located in the center of the eye. Given its potential aggressive nature with fatal consequences, it is important... Show moreUveal melanoma, as opposed to cutaneous melanoma, is a tumor which is predominantly located in the center of the eye. Given its potential aggressive nature with fatal consequences, it is important to start treatment in a timely manner. Currently, treatment consists of decreasing the size of the tumor by means of radiation therapy or surgery, but by mapping the genetic makeup of uveal melanoma, personalized treatment potentially becomes possible. In this thesis we tried to solve a piece of this genetic puzzle by focusing on genetic and cellular differences within and between different uveal melanoma. By means of an innovative new technique, digital PCR, we aimed to visualize this so-called heterogeneity. We demonstrate that we can accurately assess which genetic aberrations are present in uveal melanoma. Moreover, we show in what percentage of cells these aberrations are present. Additionally, we illustrate which cell types play an important role in uveal melanoma development. This way, we characterized a substantial amount of different uveal melanoma based on their heterogeneity profile. Lastly, we display whether and how uveal melanomas with a specific heterogeneity profile are susceptible to treatment. Show less
The research described in this thesis implemented Magnetic Resonance Imaging (MRI) as a diagnostic imaging technique in uveal melanoma, by developing a dedicated eye MRI protocol and extensively... Show moreThe research described in this thesis implemented Magnetic Resonance Imaging (MRI) as a diagnostic imaging technique in uveal melanoma, by developing a dedicated eye MRI protocol and extensively evaluating the MR imaging characteristics of uveal melanoma. This improved the diagnosis and treatment of uveal melanoma, sometimes enabling an eye-preserving therapy instead of enucleation.Furthermore, the imaging characteristics of orbital inflammation were reviewed and a systematic approach for the radiological evaluation of these patients was proposed. It allows one to recognize an orbital solid enhancing lesion as inflammatory, and not to mistake it for infection or tumor, and it will help recognizing its underlying inflammatory disease. This enables the treating physician to establish an adequate treatment and at times a biopsy can be avoided. Finally, a dedicated eyelid MRI protocol was developed and it was assessed whether the different eyelid layers are possibly to identify on MRI (as well as on Computer Tomography), in order to improve the evaluation of the local extension of an eyelid tumor, important for the surgical planning and outcome. Show less
Purpose: Individuals with gray, blue, or green eyes have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might be related not... Show morePurpose: Individuals with gray, blue, or green eyes have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might be related not only to predisposition to UM but also to its behavior; therefore, we compared the clinical, histopathologic, and genetic characteristics of UM between eyes with different colors. Design: We determined iris color in a large cohort of patients enucleated for UM. Clinical and histopathologic tumor characteristics, chromosome status, and survival were compared among 3 groups on the basis of iris color. Participants: A total of 412 patients with choroidal/ciliary body UM, who had undergone primary enucleation at the Leiden University Medical Center, Leiden, The Netherlands, between 1993 and 2019, were divided into 3 groups based on iris color: gray/blue, green/hazel, and brown. The validation cohort included 934 patients with choroidal/ciliary body UM treated at Wills Eye Hospital (WEH). Methods: Comparison of clinical, histopathologic, and genetic characteristics of UM in patients with different iris colors. Main Outcome Measures: Melanoma-related survival in UM patients, divided over 3 iris color groups, in relation to the tumor's chromosome 3 and 8q status. Results: Moderate and heavy tumor pigmentations were especially seen in eyes with a brown iris (P < 0.001). Survival did not differ between patients with different iris colors (P = 0.27); however, in patients with a light iris, copy number changes in chromosome 3 and 8q had a greater influence on survival than in patients with a dark iris. Likewise, chromosome 3 and chromosome 8q status affected survival more among patients with lightly pigmented tumors than in patients with heavily pigmented tumors. The WEH cohort similarly showed a greater influence of chromosome aberrations in light-eyed individuals. Conclusions: Although iris color by itself did not relate to UM-related survival, chromosome 3 and 8q aberrations had a larger influence on survival in patients with a light iris than those with a brown iris. This suggests a synergistic effect of iris pigmentation and chromosome status in the regulation of oncogenic behavior of UM. Iris color should be taken into consideration when calculating a patient's risk for developing metastases. (C) 2021 by the American Academy of Ophthalmology. Show less
The subject of this Thesis is the role of the immune system in age-related eye diseases, such as glaucoma. Glaucoma is a disease that afflicts nearly 70 million people worldwide. Little is known... Show moreThe subject of this Thesis is the role of the immune system in age-related eye diseases, such as glaucoma. Glaucoma is a disease that afflicts nearly 70 million people worldwide. Little is known about the origins of the disease, which damages the retina and optic nerve and can lead to blindness. One of the biggest risk factors for glaucoma is elevated eye pressure. Our study found that glaucoma may in fact be an autoimmune disorder. We found that the body’s own T cells are responsible for the progressive retinal degeneration seen in glaucoma. Furthermore these T cells appear to be primed to attack retinal neurons as the result of previous interactions with bacteria that normally live in our body. This opens a new approach to prevent and treat glaucoma. Currently most treatments focus on lowering eye pressure. However, in many patients, the disease worsens even after intraocular pressure returns to normal. We showed that when we blocked these autoreactive T cells in the eye, not only does it diminish the loss of retinal ganglion cells and axons, but it also preserves retinal function. Show less
