Introduction
The Grading of Digital fundus Examination (GRADE) Reading Center was established to fulfill the increasing need of standardized and systematic analysis of digital retinal imaging for prospective clinical trials. This involves studies on the natural history of potentially blinding retinal diseases as well as interventional trials to evaluate the efficacy and safety of new therapeutic strategies.
The origin of GRADE goes back to the FAM (Fundus Autofluorescence in Age-related Macular Degeneration)-Study - a multicenter national history study on patients with geographic atrophy secondary to age-related macular degeneration. This project was initiated in 2000 and funded by the German Research Council (DFG). Along with new emerging imaging technologies and the development of new therapeutic strategies, the GRADE Reading Center was founded in 2006.
GRADE was involved in the design and conduct of the first large-scale randomized interventional Phase II study in geographic atrophy (Fenretinide study, Sirion Therapeutics, Inc.). Since then, GRADE has collaborated within various projects both with national and international partners, including pharmaceutical companies, international networks and other reading centers. In 2012, the organization of GRADE was transformed from a university research unit to a research center of the Steinbeis network.
New emerging imaging technologies such as confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography provide new insights in the human retina in-vivo and give information above and beyond that obtained by conventional imaging methods. They also contribute to our understanding of pathophysiological mechanisms, diagnostics, phenotype-genotype correlation, identification of both prognostic and predictive markers for disease progression, and monitoring of novel therapies.
While retinal imaging represents an important tool for the assessment of efficacy and safety of new therapeutic interventions, there is an additional unmet need for robust, reliable and meaningful tests that allow the direct assessment of functional impairment and that are also accepted by regulatory agencies, health technology assessment bodies, and payers. This also includes a better understanding about the impact of disease-specific morphological changes to measurable retinal sensitivity. In this context, GRADE's activities have been recently also focused on the more detailed structural-functional analysis using mesopic and scotopic fundus-controlled perimetry (also called microperimetry) in combination with high-resolution retinal imaging.
State-of-the-art clinical trials require standardized acquisition, processing and analysis of clinical data. National and international agencies demand internal validation of all applied procedures. Reproducibility and observer variability of new retinal imaging techniques and functional tests as well as their evaluation must be ensured. These challenging tasks are realized by the Steinbeis-Forschungszentrum GRADE Reading Center, located at the Department of Ophthalmology of the University of Bonn.
