Chromosome 3 and 8q aberrations in Uveal Melanoma show greater impact on survival in patients with light iris versus dark iris color

Ophthalmology. 2021 Nov 12;S0161-6420(21)00867-8. doi: 10.1016/j.ophtha.2021.11.011. Online ahead of print.


Purpose: Individuals with gray, blue, or green iris have a higher chance of developing uveal melanoma (UM) than those with brown eyes. We wondered whether iris pigmentation might not only be related to predisposition to UM, but also to its behavior and therefore compared clinical, histopathologic, and genetic characteristics of UM between eyes with different iris colors.

Design: We determined iris color in a large cohort of patients who had undergone an enucleation for UM. Clinical and histopathological tumor characteristics, chromosome status, and survival were compared between three groups, based on iris color.

Participants: 412 patients with choroidal/ciliary body UM, who had undergone primary enucleation at the Leiden University Medical Center (LUMC), Leiden, The Netherlands, between 1993 and 2019, divided into three groups, based on iris color (gray/blue, green/hazel, and brown). Validation cohort: 934 choroidal/ciliary body UM patients treated at Wills Eye Hospital (WEH), Philadelphia, United States.

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 three iris color groups, in relation to the tumor's chromosome 3 and 8q status.

Results: Moderate and heavy tumor pigmentation was especially seen in eyes with brown iris (p < 0.001). Survival did not differ between patients with different iris colors (p = 0.28). 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. Similarly, 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: While iris color by itself did not relate to survival of UM patients, chromosome 3 and 8q aberrations had a much larger influence on survival in patients with light iris compared to those with 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 the risk for developing metastases.

Keywords: Eye disease; Iris color; Oncology; Uveal Melanoma; color; inflammation; prognosis.