Contrast enhanced AOOCT for imaging the human retina in vivo

The human retina is organized in several layers that perform the complex task of converting the incoming light into electrical signals and preprocessing the information before it is sent to the brain. Diseases of the eye degrade its functionality which can lead, untreated, to vision loss and finally blindness. Different techniques have been developed over the past centuries to investigate the retina in vivo. Direct funduscopy and the following fundus photography are still regarded as "gold" standard in the diagnostics of retinal diseases. However, no depth information can be obtained with this technique. More recently, two powerful imaging techniques, namely scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) evolved into valuable, modern clinical examination tools. Remarkable in this context is the unprecedented depth resolution of OCT that allows the visualization of all different retinal layers and therefore for an improved diagnosis compared to all other techniques. However, commercially available OCT systems are not capable to provide i) cellular resolution ii) additional image contrast and iii) functional imaging capabilities. Ad i): Imperfections of the imaging optics of the eye limit the achievable transverse resolution and limit therefore the cellular imaging capabilities. With the use of adaptive optics (AO) the influence of these imperfections can be corrected in order to achieve a resolution close to the diffraction limit of the eye. Ad ii) Several contrast techniques have been introduced for OCT to achieve additional image contrast; Doppler OCT which detects and measures the velocity of moving particles, polarization sensitive OCT (PS-OCT) which uses the polarization properties of the light to gather additional information (e.g. birefringence, depolarization) on the sample and phase contrast OCT which uses the phase information of the OCT signal to generate additional image contrast. Ad iii) initial experiments investigated the capabilities of SLO and OCT to measure retinal function. Promising results have been obtained with SLO and AO-SLO although with poor depth resolution. Up to now retinal function has not been investigated with OCT on a cellular level. The aim of this project is to develop a new instrument that combines AO with a simultaneous SLO/OCT imaging device. In a pilot study we have shown the benefit of this combination compared to other AO-OCT systems. Furthermore, different additional image contrast techniques (Doppler OCT, PS- OCT, phase contrast OCT) shall be implemented into this new system. Additionally we intend to implement an autofluorescence imaging capability into the instrument to provide molecular contrast. The newly developed system shall be capable to provide in vivo images of the human retina with cellular resolution and shall be tested on volunteers and on patients with different retinal diseases. In the final phase of the project retinal functionality (changes of the retina to a light stimulus) shall be investigated. Data acquired with the new system may provide new insights into the status and progression of various retinal diseases. The measurement of retinal functionality yields additional information and might, in combination with the structural measurements, provide a more accurate diagnosis of the disease. On the long term it might be possible with the new system to monitor the progression of the disease as well as the success of a treatment more accurately than ever before which might enable an optimization of treatment.

Vision is one of the most complexes of human senses. Diseases may degrade the functionality of the vision process. This may lead, untreated to severe vision loss and finally blindness. An essential part of the eye is the retina which converts the incoming light into electrical signals. These signals are pre-processed within retina before the information is then finally sent to the visual cortex of the brain. For a better diagnosis and an optimization of current therapies, not invasive imaging technologies are needed that gather in vivo as many details of the retina as possible. Within the framework of this project instruments have been developed that are capable to image even smallest structures (such as light sensitive cells as cones and rods) within the retina in vivo. In order to achieve the necessary resolution the so called adaptive optics technique was used. This technology is already successfully applied in astronomy in order to obtain even sharper images. In order to improve the depth resolution of the images, adaptive optics was combined with optical coherence tomography. Optical coherence tomography is a meanwhile well-established method in ophthalmology which generates cross sectional images of the retina with a depth resolution of a few micrometers. Through the combination of both techniques, images of the retina with to date unprecedented sharpness and level of detail could be recorded. The method is non-invasive and was used to record images in volunteers and patients. In addition it is now possible to in observe processes on the retina on a cellular level with this technique. One example of these processes is the renewal of parts of the light sensitive cells. This renewal is essential in order to prevent photo damage of the cells. Although this process is known from experiments in various animal models, an application of the used techniques in the human eye is not possible because the data can only be collected ex-vivo. Within the framework of this project this renewal process could be observed for the first time in vivo in humans. This represents an essential step towards a better understanding of these processes which are quite likely perturbed in the aging eye, thereby promoting the formation of retinal diseases such as age related macula degeneration.