Title: New therapeutic strategies in retinal vascular diseases: A lipid target phosphatidylserine and Annexin A5 a future theranostic pairing in ophthalmology
Abstract:
Despite progress in the management of patients with retinal vascular and degenerative diseases, there is still an unmet clinical need for safe and effective therapeutic options with novel mechanisms of action. Recent mechanistic insights into the pathogenesis of retinal diseases with a prominent vascular component, such as Retinal Vein Occlusion (RVO), Diabetic Retinopathy (DR) and wet age-related macular degeneration (AMD), may open up new treatment paradigms that reach beyond the inhibition of Vascular Endothelial Growth Factor (VEGF).
Phosphatidylserine (PS) is a novel lipid target that is linked to the pathophysiology of several human diseases, including retinal diseases. PS acts upstream of VEGF and complement signaling pathways. Annexin A5 is a protein that targets PS and inhibits PS signalling. This key note will explore the current understanding of the potential roles of PS as a target and Annexin A5 as a therapeutic. RVO and DR share disease pathways, with long-term need and mostly short-lasting treatments available to patients today. Currently available treatments target macular oedema and retinal neovascularisation, but no treatment so far has been able to target the actual cause of the disease, that is, the vascular occlusion or the loss of retinal vascular perfusion that leads to retinal ischaemia.
The clinical development status of Annexin A5 as a therapeutic in retinal vein occlusion and diabetic retinopathy and the potential utility of PS-Annexin A5 as a theranostic pairing in retinal vascular conditions in particular will be presented. Cases such as below will be presented: The patient diagnosed with DR had moderate retinal swelling, minimal visual impairment and multiple functional and anatomical changes in the retina common in DR. Thirty days after a course of ANXV treatment, improvements in relevant clinical parameters regarding both function and anatomical structure of retina were noted. There was a significant improvement of retinal perfusion/retinal capillary density on OCT Angiography (OCTA). The retinal response to light and electrical conduction of sensory input were improved as determined by microperimetry and electroretinogram, respectively. The macular swelling (intraretinal fluid) was decreased, and vascular anatomy was improved (less microaneurysms and less haemorrhages). It is considered very unlikely that these improvements are spontaneous. Visual acuity measured by the visual chart and the assessment of the degree of diabetic retinopathy remained stable at Day 30.
