Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Settings Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10- μm depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Optical Coherence Tomography of the Human Retina

The diffraction tomography theorem is adapted to one-dimensional length measurement. The resulting spectral interferometry technique is described and the first length measurements using this technique on a model eye and on a human eye in vivo are presented.

Measurement of intraocular distances by backscattering spectral interferometry

State-of-the-art retinal optical coherence tomography

Proposed lexicon for anatomic landmarks in normal posterior segment spectral-domain optical coherence tomography: the IN•OCT consensus.

Optical coherence tomography (OCT) made possible noninvasive visualization of the microscopic anatomy of the retina, a nearly transparent structure. Understanding what is visualized requires proper identification of the layers and substructures within the retina. Comparatively low resolution early OCT devices detected one highly reflective band (or “line”) in the posterior ocular fundus. This band was ascribed to more than one structure depending on the authority.1–6 Introduction of commercial OCT devices occurred in 1996, and initially the retinal thickness was measured from the inner retina to the top of the highly reflective posterior band.4,5 Development of higher-bandwidth illumination in research devices increased attainable resolution to 3 μm to 4 μm and was called “ultrahigh-resolution” OCT. With the newer OCTs, the formerly single highly reflective band was resolved as either three or four separate bands. Various publications attributed diverse anatomical correlates to these bands; the discordance existed not only between different author groups but also between papers from the same group.7–9 The 2007 entry into the commercial market and subsequent widespread adoption of high-resolution spectral-domain OCT created the opportunity for practicing ophthalmologists to have a nearly cellular level of resolution of the retina.10 A practical need for terminology of various layers of the retina arose and an ad hoc nomenclature, based on an amalgamation of previous OCT papers, was adopted by the ophthalmic community.

Commercial spectral-domain OCT instruments conventionally resolve 4 bands in the outer retina outside of the central fovea (Figure 1). The innermost band has been attributed to the external limiting membrane (ELM),8 a linear confluence of junctional complexes between Muller cells and photoreceptors. This band typically is thinner and much fainter than the others. The second of the four bands has been commonly ascribed to the boundary between the inner segments (IS) and outer segments (OS) of the photoreceptors.9,11 The third band is commonly referred to as either the OS tips12 or as Verhoeff membrane.13,14 The outermost highly reflective band has been thought to represent the retinal pigment epithelium (RPE), Bruch membrane, and possibly the choriocapillaris.2,6,8,14,15



Fig. 1

Drawing of the outer hyperreflective bands overlaid on a representative spectral-domain OCT scan of a normal macula. Each of the bands has had different anatomical correlations proposed over time, with varying designations by research group and time period. ...



Close inspection of these four bands raises questions about some of these assignments. For both foveal cones and rods, the length of the OSs is roughly the same as the ISs,16,17 so one would expect the boundary between the IS and OS to lie at the midpoint between the ELM and RPE. However, the second reflective band lies much closer to the ELM than it does to the RPE. Further, the word “boundary” implies a narrow line as a reflection, while the “IS/OS boundary” image typically is nearly as thick as the RPE band. Finally, although the third band is called Verhoeff membrane, what Verhoeff described was an anatomical structure girdling RPE cells,18,19 known now as junctional complexes between RPE cells.20,21 Therefore, a reflective band physically separated from the RPE cannot be Verhoeff membrane.

Over the last century a wealth of information about the anatomical structure of the retina has been published, complete with meticulous measurements. Assembling this information into a database would allow comparisons between known measurements and the structures seen by OCT. We assembled this information and constructed a scale model drawing of the outer retina to enable visual comparisons. Using this model for analysis, we find that the designation of the ELM for the first band is correct and that the fourth band at least contains the RPE, but current assignments of the middle two bands are more problematic.

Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model.

We have combined Fourier-domain optical coherence tomography (FD-OCT) with a closed-loop adaptive optics (AO) system using a Hartmann-Shack wavefront sensor and a bimorph deformable mirror. The adaptive optics system measures and corrects the wavefront aberration of the human eye for improved lateral resolution (~4 μm) of retinal images, while maintaining the high axial resolution (~6 μm) of stand alone OCT. The AO-OCT instrument enables the three-dimensional (3D) visualization of different retinal structures in vivo with high 3D resolution (4×4×6 μm). Using this system, we have demonstrated the ability to image microscopic blood vessels and the cone photoreceptor mosaic.

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Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging

Capable of three-dimensional imaging of the cornea with micrometer-scale resolution, spectral domain-optical coherence tomography (SDOCT) offers potential advantages over Placido ring and Scheimpflug photography based systems for accurate extraction of quantitative keratometric parameters. In this work, an SDOCT scanning protocol and motion correction algorithm were implemented to minimize the effects of patient motion during data acquisition. Procedures are described for correction of image data artifacts resulting from 3D refraction of SDOCT light in the cornea and from non-idealities of the scanning system geometry performed as a pre-requisite for accurate parameter extraction. Zernike polynomial 3D reconstruction and a recursive half searching algorithm (RHSA) were implemented to extract clinical keratometric parameters including anterior and posterior radii of curvature, central cornea optical power, central corneal thickness, and thickness maps of the cornea. Accuracy and repeatability of the extracted parameters obtained using a commercial 859nm SDOCT retinal imaging system with a corneal adapter were assessed using a rigid gas permeable (RGP) contact lens as a phantom target. Extraction of these parameters was performed in vivo in 3 patients and compared to commercial Placido topography and Scheimpflug photography systems. The repeatability of SDOCT central corneal power measured in vivo was 0.18 Diopters, and the difference observed between the systems averaged 0.1 Diopters between SDOCT and Scheimpflug photography, and 0.6 Diopters between SDOCT and Placido topography.

/pdf/3d-refraction-correction-and-extraction-of-clinical-aynjoouay2.pdf

3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea.

We demonstrate high-speed complex conjugate artifact (CCA) resolved imaging of human retina in vivo using spectral domain optical coherence tomography. This technique utilizes sinusoidal reference mirror modulation to implement high-speed integrating buckets acquisition and a quadrature projection reconstruction algorithm in postprocessing. This method is illustrated experimentally using sets of four integrating bucket phase scans, acquired at 52 kHz, for DC suppression of 73 dB and complex conjugate suppression of 35 dB. Densely sampled (3000 A-scans/image, acquired at 4.3 images/s) full-depth in vivo images of optic nerve head show CCA suppression for most image reflections to the noise floor.

High-speed complex conjugate resolved retinal spectral domain optical coherence tomography using sinusoidal phase modulation.

In accordance with this disclosure, methods, systems, and computer readable media for synthetic wavelength-based phase unwrapping in optical coherence tomography are provided. Synthetic wavelength phase unwrapping can be applied to OCT data and can correctly resolve sample motions that are larger than λ o /2. A method for phase unwrapping of an OCT signal can include acquiring raw OCT signal data, interpolating and processing the OCT signal data to obtain a DC spectrum, comparing the raw OCT signal data to the DC spectrum to generate an interference signal, applying Gaussian windows to the interference signal to generate a two separate signals, extracting phase information from the two signals, and comparing the phase information of the two signals to produce unwrapped phase data. A value of 2π can be added to the phase data if the difference between the phase information of the two signals is less than zero.

Methods, systems, and computer readable media for synthetic wavelength-based phase unwrapping in optical coherence tomography and spectral domain phase microscopy

Methods, systems, and computer program products for removing undesired artifacts in Fourier domain optical coherence tomography (FDOCT) systems using integrating buckets are disclosed. According to one aspect, a method includes introducing a variable phase delay between a reference arm and a sample arm of an FDOCT interferometer using sinusoidal phase modulation. Further, the method includes acquiring an interferometric intensity signal using an integrating buckets technique. The method also includes resolving the interferometric intensity signal to remove undesired artifacts.

Methods, systems, and computer program products for removing undesired artifacts in fourier domain optical coherence tomography (FDOCT) systems using integrating buckets

Mingtao Zhao

Papers

Adaptive-optics optical coherence tomography for high-resolution and high-speed 3D retinal in vivo imaging

3D refraction correction and extraction of clinical parameters from spectral domain optical coherence tomography of the cornea.

High-speed complex conjugate resolved retinal spectral domain optical coherence tomography using sinusoidal phase modulation.

Methods, systems, and computer readable media for synthetic wavelength-based phase unwrapping in optical coherence tomography and spectral domain phase microscopy

Methods, systems, and computer program products for removing undesired artifacts in fourier domain optical coherence tomography (FDOCT) systems using integrating buckets