To Identify New Factors That Play a Role in Early Onset Drusen Maculopathy

The goal of the project is to study early-onset drusen maculopathy by looking at patients and family members, genetic factors, and markers in blood samples in order to identify new factors that are involved in this disease.

1. We will collect EODM patients and families and characterize them by detailed ophthalmic imaging and questionnaires. Blood samples will be collected for aims 2 and 3.
2. We will measure components of the complement system and lipids/lipoproteins associated with AMD in EODM patients. In addition, we aim to use a proteomics platform to test numerous biomarkers.
3. We will perform whole genome sequencing in EODM families to identify rare genetic variants in pathways associated with AMD. We will phenotypically characterize all carriers of rare variants and study genotype-phenotype correlation.

With the focus on early onset drusen maculopathy (EODM), we will study the grey area that lies between the monogenetic inherited retinal degenerations and the multifactorial pathogenesis of AMD. This overlapping field, where strong genetic factors seem to be involved, still holds many mysteries, and further unraveling the missing heritability can change the way we think about the future treatment of dry AMD. As of today, there have been no reports of whole genome sequencing in EODM cases, we will therefore be exploring a new field.

More knowledge about EODM allows us to better inform the general public about the disease and when to consult an ophthalmologist. I will be able to give EODM patients more detailed information about their disease and involved risk factors, including the risks for family members. I will also be able to offer them genetic testing in the outpatient clinic.

Identification of (new) genetic factors can aid in the design of future clinical trials and the selection of the right patients for these trials. The results from this study will therefore bring us closer to a treatment.