Real-Time Temperature-Controlled Retinal Laser Irradiation in Rabbits.

Purpose: Subdamaging thermal retinal laser therapy has the potential to induce regenerative stimuli in retinal diseases, but validated dosimetry is missing. Real-time optoacoustic temperature determination and control could close this gap. This study investigates a first in vivo application. Methods: Two iterations of a control module that were optically coupled in between a continuous-wave commercial laser source and a commercial slit lamp were evaluated on chinchilla rabbits. The module allows extraction of the temperature rise in real time and can control the power of the therapy laser such that a predefined temperature rise at the retina is quickly achieved and held constant. Irradiations with aim temperatures from 45°C to 69°C were performed on a diameter of 200 µm and a heating time of 100 ms. Results: We analyzed 424 temperature-guided irradiations in nine eyes of five rabbits. The mean difference between the measured and aim temperature was -0.04°C ± 0.98°C. The following ED50 values for visibility thresholds could be determined: 58.6°C for funduscopic visibility, 57.7°C for fluorescein angiography, and 57.0°C for OCT. In all measurements, the correlation of tissue effect was higher to the temperature than to the average heating laser power used. Conclusions: The system was able to reliably perform temperature-guided irradiations, which allowed for better tissue effect control than simple power control. This approach could enhance the accuracy, safety, and reproducibility of thermal stimulating laser therapy. Translational Relevance: This study is a bridge between preclinical ex vivo experiments and a pilot clinical study.

LPV modeling of nonlinear systems: A multi-path feedback linearization approach.

This article introduces a systematic approach to synthesize linear parameter-varying (LPV) representations of nonlinear (NL) systems which are described by input affine state-space (SS) representations. The conversion approach results in LPV-SS representations in the observable canonical form. Based on the relative degree concept, first the SS description of a given NL representation is transformed to a normal form. In the SISO case, all nonlinearities of the original system are embedded into one NL function, which is factorized, based on a proposed algorithm, to construct an LPV representation of the original NL system. The overall procedure yields an LPV model in which the scheduling variable depends on the inputs and outputs of the system and their derivatives, achieving a practically applicable transformation of the model in case of low order derivatives. In addition, if the states of the NL model can be measured or estimated, then a modified procedure is proposed to provide LPV models scheduled by these states. Examples are included to demonstrate both approaches.