A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future.

Special Issue A Review of Adaptive Optics Optical Coherence Tomography: Technical Advances, Scientific Applications, and the Future Ravi S. Jonnal, 1 Omer P. Kocaoglu, 2 Robert J. Zawadzki, 1 Zhuolin Liu, 2 Donald T. Miller, 2 and John S. Werner 1 1 Vision Science and Advanced Retinal Imaging Laboratory, University of California-Davis, Sacramento, California, United States School of Optometry, Indiana University, Bloomington, Indiana, United States Correspondence: Ravi S. Jonnal, 4860 Y Street, Suite 2400, Sacra- mento, CA 95817, USA; rsjonnal@ucdavis.edu. Submitted: January 8, 2016 Accepted: May 29, 2016 Citation: Jonnal RS, Kocaoglu OP, Zawadzki RJ, Liu Z, Miller DT, Werner JS. A review of adaptive optics optical coherence tomography: technical ad- vances, scientific applications, and the future. Invest Ophthalmol Vis Sci. 2016;57:OCT51–OCT68. DOI:10.1167/iovs.16-19103 P URPOSE . Optical coherence tomography (OCT) has enabled ‘‘virtual biopsy’’ of the living human retina, revolutionizing both basic retina research and clinical practice over the past 25 years. For most of those years, in parallel, adaptive optics (AO) has been used to improve the transverse resolution of ophthalmoscopes to foster in vivo study of the retina at the microscopic level. Here, we review work done over the last 15 years to combine the microscopic transverse resolution of AO with the microscopic axial resolution of OCT, building AO-OCT systems with the highest three-dimensional resolution of any existing retinal imaging modality. M ETHODS . We surveyed the literature to identify the most influential antecedent work, important milestones in the development of AO-OCT technology, its applications that have yielded new knowledge, research areas into which it may productively expand, and nascent applications that have the potential to grow. R ESULTS . Initial efforts focused on demonstrating three-dimensional resolution. Since then, many improvements have been made in resolution and speed, as well as other enhancements of acquisition and postprocessing techniques. Progress on these fronts has produced numerous discoveries about the anatomy, function, and optical properties of the retina. C ONCLUSIONS . Adaptive optics OCT continues to evolve technically and to contribute to our basic and clinical knowledge of the retina. Due to its capacity to reveal cellular and microscopic detail invisible to clinical OCT systems, it is an ideal companion to those instruments and has the demonstrable potential to produce images that can guide the interpretation of clinical findings. Keywords: adaptive optics, optical coherence tomography, retinal imaging T he 25 years since the advent of optical coherence tomography (OCT) 1 have brought countless improvements in its axial resolution, speed, and sensitivity. The main effort to improve OCT’s transverse (or lateral) resolution has been to combine it with adaptive optics (AO), a union that has been investigated in just a few labs. Nevertheless, AO-OCT now plays important roles in the production of knowledge about the retina and its diseases. Chief among these is its potential to resolve ambiguities present in clinical and research-grade conventional (non-AO) OCT systems. Because AO-OCT reveals the microstructure that makes up clinically observable features, it is indispensable as a scientific companion to conventional OCT. Understanding the differences between the OCT image and the AO-OCT image requires that we describe some of the technical details of AO-OCT imaging and image processing, and how these are motivated by the fundamental biological and physical properties of the living human retina. the retina’s laminar structure. Because retinal diseases often impact this laminar structure, OCT has been used extensively to detect and assess disease and monitor therapeutic efficacy, to such an extent that it has become a standard of ophthalmic care. Each retinal layer contains structural and functional subunits such as cells, organelles, and capillaries, most of which are too small to be resolved by conventional OCT systems such as the commercial systems employed in the clinic (Fig. 1). While cellular imaging is presently of limited interest to clinicians, it is of great interest to basic science researchers, who stand to learn much about these structures and their functions by imaging them in situ. Moreover, an understanding of the gross structural changes observed in clinical OCT images of disease and recovery depends crucially on knowing their microscopic constituents. Cellular imaging of the retina will continue to expand our understanding of retinal disease, and is therefore of great translational significance. The Spatial Scale of Retinal Features Optical Factors Affecting Transverse Resolution The human retina consists of approximately a dozen layers of mostly transparent tissue, together less than half a millimeter thick. The axial resolution afforded by OCT lends itself to imaging The point-spread function (PSF) is a measure of the quality of an imaging system, describing how light originating from a point in tissue manifests in the image of that tissue. The PSF has both iovs.arvojournals.org j ISSN: 1552-5783 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/Journals/IOVS/935468/ on 11/08/2016 OCT51