Over the past thirteen years, intensive research of an international and interdisciplinary consortium of researchers has led to significant advances in our understanding of the pathogenesis, natural history, prognostic markers and development of novel therapeutic approaches for MacTel. A recently published paper in the New England Journal of Medicine (NEJM) showed that elevated systemic deoxysphingolipid levels and low systemic serine levels are risk factors for MacTel and peripheral neuropathies.
An international natural history and registry study helped characterizing the natural course and determining genetic risk factors of this disease. A clinical phase III intervention study with the Renexus implant, which delivers CNTF into the vitreous, promises a first treatment approach.
As with other chronic and slow progressing diseases, one of the challenges in clinical trials for MacTel is to determine functional endpoints that reflect patients’ everyday impairments as well as disease progression. MacTel patients with advanced morphological changes and severe functional impairment often present with good central visual acuity. This represents a particular problem in clinical trials as the success of therapy cannot be adequately monitored. Thus, the establishment of alternative functional measurements such as reading speed or microperimetry plays an important role for the success of future clinical trials.
Anatomical structural investigations of the macular region are another important pillar of MacTel research. In addition to histological examinations of donor tissue, novel imaging methods such as OCT angiography offer a deeper insight into the pathophysiology of the disease. These studies revealed that the neurodegenerative component in MacTel precedes the observed vascular changes emphasizing the chronic neurodegenerative character of the disease. However, the presence of secondary vascular changes may still have an influence on treatment success. Early detection of the disease as well as early therapeutic intervention is therefore of great importance. Multimodal (autofluorescence, blue light reflectance) and novel imaging techniques (FLIO) improve the possibilities of early detection.