Leonardo da Vinci, universal genius of the Renaissance, called the eye a window to the soul. While not wanting to contradict da Vinci, the ophthalmologist and clinical pharmacologist Gerhard Garhöfer would like to emphasize the importance of the eye for research and medicine, and describes it as “a window to microcirculation in the finest blood vessels”. Easily observable in the eye, these finely ramified vessels supplying the retina manage gas exchange and metabolism in tissues all over the body, from the kidneys to the toes. The condition they are in can indicate not only diseases of the eye, but also various other medical conditions. One such disease is the widespread type 2 diabetes, a form of this severe metabolic disorder that is strongly linked to age and lifestyle. With funding from the Austrian Science Fund FWF, Garhöfer's research group has succeeded in proving what was previously only a suspected connection between reduced oxygen transport in the retina and the retinal damage known as diabetic retinopathy, which ultimately leads to irreversible visual impairment.
Damaged and overstrained microvessels
Diabetic retinopathy is the most common cause of blindness in industrialized countries today. This widespread eye complication occurs in about half of patients with type 2 diabetes who have had the disease for a long time and/or whose sugar levels are poorly managed. The high blood sugar level causes damage to the blood vessels and prevents them from doing their job. Although new blood vessels are formed in response to the lack of oxygen in the retina, these are not functional and increasingly impair vision. As type 2 diabetes is strongly on the rise, doctors also expect to see an increasing number of cases with this secondary disease. In its atlas, the International Diabetes Federation estimates that in 2019, 9.3 percent of the population worldwide, or 463 million people, suffered from diabetes – mainly in cities and countries with higher average incomes. By 2030, that number is expected to rise to 10.2 percent (578 million). It often takes time for the diagnosis to be made: one in two diabetes patients are not aware of having the disease.
Contact-free measurement techniques
Garhöfer’s clinical study involved 70 type 2 diabetics with an average age of 65 without or with different degrees of advanced retinal damage. They were compared with a control group of 20 individuals without diabetes. Since one cannot directly measure oxygen extraction from the blood into the tissue, blood flow and oxygen saturation in the retina of the patients were measured with a contact-free technique. In a precursor project, a mathematical model had already been developed to convert the data from the measurements (using Doppler optical coherence tomography and oximetry) into values for oxygen extraction into the tissue.
Contact-free measurement of oxygen saturation at the retinal vessels. In the center, the optic disc through which the vessels enter the retina: blue means low saturation, read means high saturation.
Medical University of Vienna / Garhöfer
The investigations provide clear proof of what was previously only an assumption: “Our results show that with increasing severity of the disease, less and less oxygen finds its way from the blood into the tissue. On the other hand, we found that even in type 2 diabetics who did not yet show any visible changes in the retina, less oxygen was already supplied to the retina. This means that the gas exchange was already compromised before the damage was clinically diagnosable.”
Pathophysiology as the basis of treatment
Gerhard Garhöfer works at the University Clinic for Clinical Pharmacology at the Medical University of Vienna, which researches and develops active substances, treatment methods and drugs. Given the “window function” of the eye, his research group on “ocular pharmacology” is of interest to many disciplines. “In order to administer the right treatment, we need to understand the development and progression of a disease. Our research has helped to improve our understanding of the pathophysiology of the eye in diabetes,” Garhöfer explains. The study results confirm that oxygen delivery to the retina is reduced in patients with diabetes. The measured parameters could help to identify high-risk patients and to instruct them better in terms of therapy and compliance. Gerhard Garhöfer also plans to apply this technique to other diseases, such as neurodegenerative eye diseases.
Gerhard Garhöfer is an ophthalmologist at the Medical University of Vienna. He is in charge of the ophthalmology-pharmacology group with a focus on drug development for the eye, the eye as a route of administration, and the physiology and pharmacology of the eye. An Associate Professor of Clinical Pharmacology, Garhöfer has served as Vice President of the European Association for Vision and Eye Research (EVER) and is currently a member of the Executive Board of the European Glaucoma Society (EGS).
Hommer N., Kallab M., Schlatter A. et al.: Retinal oxygen metabolism in patients with type II diabetes and different stages of diabetic retinopathy, in: Diabetes 2022
Hommer N., Kallab M., Schlatter A. et al.: Neuro-vascular coupling and heart rate variability in patients with type II diabetes at different stages of diabetic retinopathy, in: Frontiers in Medicine (Lausanne) 2022