In the last decades, laser photocoagulation has been established as a modality for the treatment of diabetic retinopathy, age-related maculopathy, neovascular complications after vascular occlusion and a variety of other eye diseases and proved to be one of the most successful implementation of laser techniques for the treatment of the human retina. However, if not monitored, the thermal diffusion during treatment can seriously harm or irreversibly destroy nervous layers as well as complete large nerve trajectories. Since a considerable number of retinal diseases is thought to be directly associated to pathological changes in or degradation of the retinal pigment epithelium (RPE) monolayer, a specific procedure for retinal diseases only treating the RPE layer and leaving neural layers as well as choroid and photoreceptors unaffected must be employed.
The goal of this project ist to develop a reliable and repeatable dosimetry control for the sub-threshold Selective Retina Therapy treatment approach using non-invasive imaging modalities such as optical coherence tomography (OCT).
Selective Retina Therapy (SRT)
As an extension to conventional photocoagulation, the SRT approach has proved to be an efficient and minimally invasive modality to treat retinal pathologies linked to the RPE layer. The main advantage of the SRT over conventional therapies is the selectivity, i.e. the introduced lesions occur only at the desired layer sparing the neural layers of the retina.
Since melanosomes are the main absorbers of the laser energy in the RPE layser, their concentration in the RPE plays a crucial role in the determination of the appropriate pulse energy and number. The concentration of these melansomes can differ both inter- and intra-patiently by a factor of up to 2, hence it becomes immediately clear that for a reliable and successful therapy, a feasible dosimetry control is needed.
Currently, optoacoustic methods are used as an indicator for therapy success but suffer from the drawback that only the burst of the RPE cells can be detected. The physical collapse of the cell, and hence its optoacoustic signal, represent an isolated event in time. In consequence, if the optoacoustic signal passes undetected for whatever reason, an overradiation can occur.
The SRT approach is currently being evaluated in a clinical study conducted at the Eye Clinic at the Inselspital in Bern. The study is executed in close collaboration with the Medical Laser center in Lübeck, Germany (MLL), which provides the sub-threshold laser system employed in this project.
Optical Coherence Tomography (OCT)
OCT represents an imaging modality based on interferometry methods and has proved to be a valuable and powerful approach to the challenge of noninvasive, high resolution medical imaging. With OCT imaging, maps of the optical properties of the sample layers are recorded and a 3D tomogram of the area under investigation is provided. Changes in reflectivity or the distortion of sample layers can thus be detected, making OCT a promising modality for a SRT dosimetry control. OCT is completely non-invasive and operating in the near-infrared range. With OCT it is expected that during SRT treatment, the progress of bubble formation and cell destruction can be monitored in real-time. Moreover, OCT imaging also enables a repeated and time-independent measurement of the introduced RPE lesions. As a consequence, OCT imaging will not only provide the modality for dosimetry control but also for the evaluation of therapy success and progress over an arbitrary timeline after the treatment.
Fot the monitoring of the retinal layers during therapy, a custom made OCT system has been specified, designed and realized, providing the necessary axial resolution of 1.8 um in air. The experimental system is optically coupled into the SRT treatment system and will be capable of simultaneous measurtement during application of the laser pulses to the retina.
Experimental Results
First results have already been achieved under simplified conditions using enucleated porcine eyes with removed anterior segment. The porcine retina was treated with the SRT laser and the samples subsequently imaged with a preceding model of the OCT system. The volume scans were segmented offline to better illustrate the effects of the laser irradiation. Lesion patterns can clearly be seen in the volume scans, proving OCT to be a promising modality.
Future Steps
In the future course of the project, the OCT imaging will be tested and evaluated on whole porcine eyes and in-vivo during therapy of patients at the Augenklinik of the Inselspital in Bern. Based on the acquired results, an automatic detection of therapy success shall be developed and intergrated into the treatment system, thus increasing the reliability and repeatability and supporting the proliferation of the SRT therapy approach.
