Phenotyping of age-related macular degeneration beyond drusen with innovative image analysis

• Applicant: Dr. Sarah Helena Thiele
• Subject Area: Ophthalmology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459530177

Age-related macular degeneration (AMD) is a complex and chronicalprogressive disease of the central retinal/choroidal complex that can lead tothe loss of central visual acuity and thus to blindness of the patients asadvanced diseases stages develop.As extracellular deposits of metabolic products, drusen represent amorphological correlate of an altered metabolism of cellular components ofthe outer retina. In large epidemiological studies, their increase in size couldwas shown to be associated with an higher risk for progression into visionaffecting late AMD-stages. Nevertheless, it is not yet possible to predict theindividual course of the disease of an individual level in patients with early orintermediate AMD, since robust in vivo biomarkers, which could also serveas "outcome measures" in the context of future clinical intervention studies,are still missing. Although drusen are the pathological feature of AMD, theyare ultimately to be understood as an expression, i.e. as a "surrogate" forprogressive photoreceptor degeneration in AMD.With the establishment of innovative retinal imaging techniques, such asspectral domain optical coherence tomography (SD-OCT), it is now possibleto visualize disease-associated changes in the retina with high resolutionand quasi-histologically in vivo. For example, photoreceptors and theirsubcellular compartments can be visualized in the human eye.The aim of this project is to analyse quantitatively the actual location of thepathogenetic event in AMD, i.e. the outer retina, using innovative digitalimage analysis techniques, and to characterise it morphologically in order toestablish a new AMD phenotyping. Morphological and AMD-associatedchanges of retinal photoreceptors and adjacent structures, such as theretinal pigment epithelium, will be systematically, with systematical sparingof drusen, assessed for the first time and their change over time will beanalyzed with respect to their prognostic value for disease progression.Furthermore, these structural changes will be correlated with retinal function (as tested by fundus-controlled microperimetry) as well as with perfusion of the choriocapillaries (as assessed by OCT-angiography) and with established high-risk features of eyes with intermediate AMD. In order to quantify the structural changes, it isalso planned to examine healthy volunteers, i.e. without retinal disease.

• DFG Programme: Research Grants