Diabetic Retinopathy

Diabetic Retinopathy (DR)

Fundus diabetic retinopathyWith diabetes today a growing problem worldwide and current treatment options insufficient, ThromboGenics saw an unmet need. We are targeting early stage treatment of diabetic eye diseases like diabetic retinopathy (DR) with or without diabetic macular edema (DME), which have a very direct impact on the patient’s quality of life.

 

 

 

 

 

About Diabetic Retinopathy

Diabetic retinopathy (DR) is a condition occurring in diabetic patients, which causes damage to the retina (light-sensitive layer at the back of the eye) . DR is a progressive disease, caused by prolonged high blood glucose levels. Over time, this causes small blood vessel damage to the retina, leading to progressive loss of vision.

- 35% or 1 out of 3 of all patients diagnosed with diabetes will develop DR.
- 7% of all DR patients develop proliferative diabetic retinopathy (PDR) which eventually leads to blindness.
- 28% of all DR patients develop non-proliferative diabetic retinopathy (NPDR) which also progresses from a moderate to severe stage and causes several problems in the eye of the patient before leading to PDR.

(Source(s): Yau 2012; Int’l Diabetes Federation and the Fred Hollows Foundation 2015; National Eye Institute 2015)

In addition to NPDR and PDR symptoms, all DR patients have an increased risk of developing diabetic macular edema (DME). DME occurs when fluid leaks into the macula (central part of the light-sensitive layer atIn addition to NPDR and PDR symptoms, all DR patients have an increased risk of developing diabetic macular edema (DME). DME occurs when fluid leaks into the macula (central part of the light-sensitive layer at the back of the eye). These leakages cause the macula to thicken and swell, progressively distorting acute vision.

Disease Hallmarks

diabetic retinopathy disease hallmarksPatients with diabetes have raised glucose levels in their blood, causing changes in certain proteins and resulting in neurodegeneration and damaged retinal microvasculature. In an early stage, the patient suffers from leaking blood vessels (permeability), causing inflammation in the back of the eye.

The formation of inflammatory and angiogenic factors further increase the damage and potentiate vascular leakage. This results in hyperpermeability and edema and formation of new blood vessels (neo-angiogenesis). The occurrence of blood vessels along the surface of the retina or in the vitreous eventually leads to permanent damage through the development of scar tissue (fibrosis).

At the same time, as soon as a patient suffers from inflammation, the hyperpermeability deteriorates, causing new inflammation, more edema and more proliferation and scar tissue. The loop amplifies itself and the disease progresses.

(Source: ThromboGenics Corporate Highlights 2015 - “Disease-modifying treatments for diabetic retinopathy”)Disease-modifying treatments

 

Current DR treatment options include laser therapy, vitrectomy and anti-vascular endothelial growth factor (VEGF) injections. These often require intravitreal injections which must be repeated several times a year every year. 

 

Laser photocoagulation: Intravitreal injection: Vitrectomy:
laser photocoagulation intravitreal injection vitrectomy

 (Source: Prof. Reinier Schlingemann “Diabetic retinopathy: the patient’s and the ophthalmologist’s perspective” – Presentation at ThromboGenics’ R&D Investor Meeting – 18 March 2016)

Unfortunately, there are indications that this prolonged use of anti-VEGF therapy might cause other complications like neurodegeneration and development of scar tissue (fibrosis) in the back of the eye, caused by prolonged inflammation. Undesirable side effects include partial loss of peripheral and night vision.

In our research for innovative next-generation treatments, we focus on patients with NPDR and/or PDR, with or without DME. Our main goal is to find novel, disease-modifying treatments that can lower the treatment burden and stop the disease from progressing.

A quadrant of groups of DR patients is used to determine which types could benefit from the novel compounds in the pipeline

(Source(s): Yau 2012; Int’l Diabetes Federation and the Fred Hollows Foundation 2015; National Eye Institute 2015)