Thesis Abstract - Hautamäki Asta
Genetic and Structural Variations Associated with the Activity of Exudative Age-Related Macular Degeneration Lesion
Age-related macular degeneration (AMD) is the leading cause of visual impairment in developed countries. Geographic atrophy and exudative AMD, the advanced forms of AMD account for the majority of visual impairment. No evidence-based medical treatment exists for geographic atrophy, but the choroidal neovascularization (CNV) forming exudative AMD lesion can be targeted with therapy. Vascular endothelial growth factor (VEGF) has a crucial role in ocular neovessel formation. VEGF-inhibitors form the mainstay of present-day treatment of exudative AMD. Although response to anti-VEGF agents is usually good, marked individual variations exist in treatment outcomes. The reasons behind the variations are largely unknown.
The IL-8 (rs4073) promoter polymorphism has been associated with regulation of the production of IL-8, a potent mediator of inflammation and neovascularization. It was the only genetic factor in the analyses that had an association with the initial anatomic treatment response. It also had a marked cumulative effect on the long-term anatomic response together with the risk variants of VEGF and CFH genes. CNV lesion characteristics affected both functional and anatomic outcomes of initial treatment, but were less important in predicting long-term response. In the long term follow-up also the genetic variant of ARMS2 was associated with functional outcome. Flare reflected poorly the lesion activity and did not predict treatment response. However, the fellow eyes that developed exudative AMD later had higher flare values at the beginning of follow-up compared with the eyes that remained free of exudative AMD features. An association was also found between the variant of IL-8 and age of onset of exudative AMD. These findings support the hypothesis that IL-8 has a role in the process leading to CNV growth in exudative AMD and in the regulation of activity of exudative AMD lesion during anti-VEGF treatment.
Dissertationes Scholae Doctoralis ad Sanitatem investigandam Universitatis Helsinkiensis - URN:ISSN:2342-317X