Study Of Adaptive Optics Confocal Scanning System For Retinal Macular Lesion Cell-level Imaging

The retinal macula plays an important role on the visual acuity,color vision and fixation because it’s the area of highest cell density in retina.Once there is a lesion in the macula,the photoreceptor cells will be damaged directly and serious visual impairment will happen,which often lead to irreversible blinding.Though current clinical diagnostic techniques can detect macula degeneration lesions,limited by the resolution of the detection equipment,we just can detect the mid and advanced lesions,which have missed the best time of treatment and intervention,actually.With adaptive optics applied to detect and correct human eye aberrations in real time,high-resolution images of the photoreceptor cells were acquired successfully.At present,adaptive optics high-resolution imaging technology has become a research hot spot in the early diagnosis of retinal diseases.Based on the high-resolution imaging needs of patients with eye diseases,aiming at the practical problems of high-accuracy aberration measurement and large aberration correction of human eye,we developed an adaptive optical confocal scanning system for high-resolution retinal imaging of patients in this research.Firstly,we designed the high-precision Hartmann wavefront sensor according to the statistical characteristics of ocular aberrations in large-scale normal human eyes and patients,based on the first-generation adaptive optics confocal imaging system in the laboratory;Secondly,we combined large stroke and miniaturization Bimorph deformable mirror to develop the second-generation high-resolution in vivo retinal imaging technology system;Through the high-resolution imaging experiments of both normal and diseased eyes in the hospital,we studied the core components of adaptive optics,design and development of optical system,performance testing and calibration,and retinopathy research in depth.(1)We described the structure and function of the macula and the production of macular diseases,which directly affected vision acuity and often lead to irreversible blindness;we also investigated the clinical examination methods of macular disease in detail,and focused on the limitation of existing diagnostic techniques.Based on the realistic demand of early diagnosis of macular degeneration,we introduced the successful application of adaptive optical imaging technology on retinal highresolution imaging in vivo.(2)We introduced the basic structure and optical characteristics of the human eye,focusing on the human eye aberrations;With human eye aberration measurement instrument which is based on the Hartmann wavefront measurement technology,we collected and analyzed the eye aberration data of both normal and patients with large scale.It provided the basis for the design of adaptive optics components for the subsequent high resolution imaging system.(3)We introduced the basic composition and working principle of adaptive optics system and determined the adaptive optics components parameters.According to the statistics of human eye aberration,the performance requirements of Hartmann wavefront sensor were optimized in detail and the parameters of it were determined.Combined with the development of the wavefront correctors in our laboratory,the Bimorph deformable mirror with large stroke and small aperture was selected as the wavefront corrector.By analyzing the correction ability of common ophthalmic diseases’ aberrations,the spatial resolution of the Bimorph deformable mirror was determined.(4)We designed the Hartmann wavefront sensor with a detailed optical structure,then used the reflective structure to model and optimize the optical path of the imaging system by Zemax softwave.Through the analysis of image quality evaluation and low-order aberration correction ability,and tolerance analysis of the optical system,the optical components’ parameters of the imaging system were determined;Finally,we used mechanical modeling software to complete the design of the main mechanical structure of the imaging system,and completed finite element analysis and preliminary discussion about the vibration problems affecting system stability.(5)We completed the high-precision calibration of the Hartmann wavefront sensor by the spherical wave calibration method and confirmed the accuracy of the Hartmann wavefront sensor compared with the interferometer.The surface figure accuracy,stroke,influence function,and dynamic response characteristic of the Bimorph deformable mirror were tested.Based on the completion of prototype structure design with some project partners,the adaptive optics confocal scanning imaging system was set up.(6)We tested and calibrated the field of view,transverse resolution,longitudinal resolution and aberration correction ability of the adaptive optics confocal scanning imaging system.The retinal photoreceptor cells with different eccentricity were analyzed quantitatively in high resolution imaging experiment of the normal human eyes.Finally,we recruited patients with common ophthalmic diseases to complete high-resolution imaging of retinal photoreceptor cells in patients,especially with high myopia,hereditary retinal degeneration,and macular degeneration,and found that morphology,function,number,and density of retinal photoreceptor cells changed in patients with different degrees of retinopathy.