Translational Medicine

This Special Issue of EYE highlights the accelerated pace of translational research in the field of retinal vascular diseases and age-related macular degeneration. Each review demonstrates significant strides in our understanding of these conditions and yet frustratingly also highlights gaps in our knowledge. Whilst the discovery of the first anti-vascular endothelial growth factor (VEGF) therapy initiated a paradigm shift in the management of most of these conditions, these reviews highlight that we have just scratched the tip of the iceberg of molecular mechanisms responsible for these devastating conditions. For example, while durability remains a major issue with anti-VEGF therapy and we welcome novel agents that could reduce treatment burden, another ‘me-too’ anti-VEGF agent is not going to improve the current benchmark of visual outcome set by current anti-VEGF trials for these indications. A clear dissociation between improvement in diabetic retinopathy severity grades with anti-VEGF therapy and the progression of retinal capillary non-perfusion in diabetic retinopathy is an example that demonstrates the need to target other molecular mechanisms and disease pathways.

Similarly, fibrosis and atrophy are key sequelae of several retinal diseases, and these remain untreatable and need to be prevented. Failed trials provoke the need for novel end-points and yet regulatory authorities need to be convinced that these end-points are beneficial to patients. Although better phenotyping with technological advancements in retinal imaging may facilitate better predictive models on outcome date, we should not forget that inflammation is a key driver of retinal and choroidal diseases and failed clinical trials. Identifying and exploiting the ideal inflammatory pathway(s) will likely yield clinically meaningful advances in therapeutics soon. Moreover, research into the crosstalk between metabolic pathways and inflammation is also gathering momentum.

Regardless of the challenges faced with novel therapies, the reviews in this issue shows that the interface between basic and translational science is well-established in this field and we look forward to more discoveries and break-through therapies for these conditions.

Special issue cover