Public defence, Neuroscience and Biomedical Engineering, MSc Ossi Kaikkonen

Title of the thesis: Retinal thermometry with electroretinography: adaptive dosimetry for non-damaging retinal laser therapy

Thesis defender: Ossi Kaikkonen 
Opponent: Professor Pekka Hänninen, University of Turku
Custos: Professor Ari Koskelainen, Aalto University School of Science

The heat shock response is a general cellular defense mechanism in which cells respond to stress by enhancing their natural protective mechanisms. When properly dosed, laser treatment induces a heat shock response in the retinal pigment epithelium, improving the cells' ability to repair misfolded proteins and remove accumulated cellular waste. Impaired waste processing in the retinal pigment epithelium is one of the factors contributing to the development of age-related macular degeneration, making controlled heating of the pigment epithelium a promising approach to slowing disease progression before significant vision loss occurs. 

The main challenge of the treatment is achieving the correct temperature: excessive heating can cause permanent visual impairment, while insufficient heating does not adequately activate the protective mechanisms. The temperature increase in the retinal pigment epithelium depends on individual characteristics of the eye, such as the melanin content of the pigment epithelium and the optical transmission of the ocular media. Consequently, reliably achieving the optimal thermal dose requires patient-specific adjustment of the laser power. 

This doctoral research developed a method for determining retinal temperature during laser treatment. The method was integrated into a laser treatment device that enables individual adjustment of laser power for each treatment area. The accuracy of the method and the biological effects of the treatment were investigated in a series of experiments on anesthetized pigs, in which laser treatments were applied to different areas of the retina and their effects were analyzed using tissue samples. The target temperature was varied to determine the temperature range in which cellular defense mechanisms could be activated without causing tissue damage. Treatments targeting a temperature of approximately 44 °C successfully activated the heat shock response and autophagy, a process involved in the degradation of cellular waste, without detectable tissue damage. 

The research demonstrated that temperature determination based on the electrical responses of the retina enables personalized dosing of retinal laser therapy. The method allowed reliable treatment dosing despite nearly fourfold variation in retinal heating at the same laser power between the investigated treatment areas. The research establishes a technical and biological foundation for the further development of a novel laser treatment method. In the future, the method could enable safer and more effective laser treatments for retinal diseases such as age-related macular degeneration, although its applicability to patient care still needs to be demonstrated in clinical studies.

Keywords: electroretinography; focal electroretinography; retinal thermometry; thermal dosimetry; non-damaging retinal laser therapy; heat shock response; autophagy; retinal pigment epithelium.

Thesis available for public display 7 days prior to the defence at Aalto University's public display page.