Structure function correlation of high resolution retinal imaging in early age-related macular degeneration and physiological aging

• Applicant: Dr. Lukas Goerdt
• Subject Area: Ophthalmology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531685551

Although age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and has long been a major focus of research in ophthalmology, its pathogenesis is yet to be fully understood. First subtle changes in the central retina usually develop after the age of 50. For the neovascular late disease stage (macular neovascularization, MNV) there is a successful therapy with the application of intravitreal anti-VEGF agents (vascular endothelial growth factor). For the dry late stage (geographic atrophy, GA) there are no therapeutic options so far. Therefore, the goal must be to distinguish physiologically aging eyes from those developing AMD at an early stage in order to provide them with possible preventive measures before one of the late stages develops. Currently, the so-called "center-surround model" of pathogenesis is being discussed. Here it is postulated that a central focus of the cone photoreceptors resilience, mediated by a concentration of Müller cells and xanthophyll macular pigment, is surrounded by a rod photoreceptor vulnerability, mediated by a lack of xanthophyll macular pigment and an increased occurrence of drusen, which limit the exchange of nutrients between retinal pigment epithelium and choriocapillaris. The aim of the present research project is to further validate this "center-surround model". Using data collected in the natural history study ALSTAR-2, modern high-resolution imaging (optical coherence tomography [OCT], fluorescence lifetime ophthalmoscopy [FLIO], macular pigment density measurements [MPOD]) and detailed assessments of retinal function (Rod mediated dark adaptation, RMDA) will be used to investigate to what extent physiologically aging eyes differ from AMD-developing eyes. In addition, questionnaires will be used to investigate whether and to what extent nutritional habits of the study participants affect xanthophyll levels measured in blood serum. The present research project can be divided into four distinct work packages: 1) Analysis of the influence of individual retinal thicknesses in the ETDRS grid region on the FLIO signal. 2) Analysis of the influence of individual retinal layer thicknesses in the area of the ETDRS grid on the MPOD signal. 3) Analysis of a possible correlation between FLIO and MPOD signal and RMDA values in the area of the test loci. 4) Analysis of the influence of study participants' nutritional habits on serum xanthophyll levels and MPOD measurements in the ETDRS grid area. If further validation of the center-surround model including the influence of serum xanthophyll levels on FLIO/MPOD signal and RMDA test values is successful and an association of dietary habits with xanthophyll levels and MPOD measurements is found, new behavioral recommendations for AMD prevention and reduction of progression of early-stage AMD patients will be developed.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professorin Dr. Christine Curcio, Ph.D.