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Show Optical Coherence Tomography Technologies: Which Machine Do You Want to Own? Fiona E. Costello, MD, FRCP Abstract: Optical coherence tomography (OCT) has evolved over the past decade to become one of the most important ancillary tests in ophthalmic practice. This noninvasive ocular imaging technique provides high-resolution, cross-sectional images of the retinal nerve fiber layer (RNFL), macular region, ganglion cell layer, and optic nerve head. With OCT, we can learn much about axonal-neuronal integ-rity in the anterior aspect of the afferent visual pathway and gain insights about mechanisms of brain injury in various central nervous system disorders. Journal of Neuro-Ophthalmology 2014;34(Suppl):S3-S9 doi: 10.1097/WNO.0000000000000161 © 2014 by North American Neuro-Ophthalmology Society Spectral of "Fourier" domain optical coherence tomog-raphy (OCT) has been commercially available since 2006, and since this time OCT has become a cornerstone in clinical ophthalmic practice. Previous generations of time-domain OCT (TD-OCT) featured an axial resolu-tion of approximately 8-10 mm of tissue (1). In the modern era, spectral domain OCT (SD-OCT) provides scan rates of 20,000-52,000 A-scans per second to achieve a resolution of 5-7 mm (1). This is approximately 50-fold faster than the previous generations of TD-OCT (2). OPTICAL COHERENCE TOMOGRAPHY: WHAT IS OUT THERE? Currently, there are several different SD-OCT machines (Table 1). The decision regarding which machine to buy should take into account a variety of factors including: the main purpose of the machine (research vs clinical), the setting (neuro-ophthalmic vs general ophthalmic practice), cost, space, and the ability to build on existing platforms with future software developments. The cautious consumer should also consider hardware, image quality, and software issues. Hardware When choosing an SD-OCT machine, there are several hardware specifications to keep in mind, including the light source, speed of the image sensor, and the instrument's non-OCT imaging capabilities (6). The quality of axial resolution is determined by the light source in the OCT machine, such that broader bandwidth sources produce better results. Recent progress in the field of broadband superluminescent diodes has made high resolution imaging (5-7 mm) with SD-OCT more affordable. As advanced superluminescent diodes and laser technologies become cheaper, commercial ultrahigh resolution (approximating 2-3 mm) machines will emerge as options to consider (6). In addition to axial resolution, image acquisition speed is another important hardware specification. Some SD-OCT machines enable 3D retinal reconstructions. The fast scanning speeds that facilitate this feature should translate into more efficient patient flow, improved patient comfort, reduced opportunity for disruptive eye movements, and increased opportunities for the machine to control noise (6). That said, enhanced speed may affect image quality, partic-ularly in patients with anterior segment abnormalities. When evaluating the performance of a given OCT machine, it is important to think above and beyond the demonstration images and review the quality of the more rapidly acquired 3D-OCT images, which will better reflect data collected in a clinical setting (6). Several commercially available OCT instruments allow for "upgrade" options, such as the line-scanning laser oph-thalmoscope, fluorescein angiography, indocynanine green, autofluorescence, and microperimetry. These "combo" packages present potential advantages and disadvantages. The upgraded features may allow comparisons between OCT and non-OCT images that may assist diagnostic or management decision making. Yet, combining too many critical functions into a single machine can become Departments of Clinical Neurosciences and Surgery, University of Calgary, Calgary, Alberta, Canada. The author reports no conflicts of interest. Address correspondence to Fiona Costello, MD, FRCP; E-mail: fiona. costello@albertahealthservices.ca Costello: J Neuro-Ophthalmol 2014; 34(Suppl): S3-S9 S3 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. problematic if the device breaks down or if patients requir-ing only OCT scans are delayed by patients receiving time-consuming angiography and/or microperimetry studies (6). Other important hardware factors to consider include the ergonomics of the device and the service and support of the manufacturer. Image Quality SD-OCT machines have a "sweet spot" of maximum sen-sitivity, and by extension, image quality that resides either on the vitreous or the choroid side of the retina (6). For this reason, before capture, the operator using the machine may need to select which tissue to image with higher sensitivity (inner retina or choroid) and then keep the patient's eye in a position that maximizes this signal. Some SD‐OCT machines may be more susceptible than previ-ous TD-OCT devices to disruptions caused by media opacities and corneal disease. In these situations, increased "noise" may obscure subtle features including subretinal fluid and make it difficult to distinguish pathological findings from normal tissue structures. It is important to look for devices that consistently produce a brighter signal in the outer retinal layers as compared with the vitreous. Because grayscale images may hide the "speckles" that signify vitreous opacities and mask noise problems, pseudocolor images should be used to assess the quality of the vitreous signal and to expose potential problems that can be masked with grayscale images (6). Software The large data sets acquired by SD‐OCT instruments allow for several capabilities. Dense 3D-OCT scans produce maps that can be aligned with non‐OCT imaging modalities, such as color fundus imaging. Any well‐designed SD‐OCT instrument should include point‐to‐point registration capa-bilities that allow users to identify areas either in the OCT or non‐OCT image and see the corresponding point of interest (6). With proper software, the same point in the fundus can be compared between visits improving the reproducibility of longitudinal clinical measurements (6). For an SD-OCT device to perform effective intervisit alignment or produce good 3D reconstructions, it must account for eye movements that occur during image acquisition. Effective eye-tracking software can help correct this problem. Therefore, when evaluating SD-OCT machines, it is wise to evaluate 3D reconstruc-tions and intervisit comparisons to demonstrate registra-tion problems. This requires ergonomic software that can be easily operated by the clinic staff. Furthermore, it would be optimal for SD-OCT machines to have the capacity to integrate robust network support software, so that large files can be transferred efficiently and rapidly across local networks directly to patient-care areas (6). TABLE 1. Currently available spectral-domain optical coherence tomography machines (3-5, 9-12) Machine Manufacturer Product Description Features CIRRUS HD‐OCT 5000 and 500 Carl Zeiss Meditec The Cirrus HD‐OCT 5000 is described as "the clinical powerhouse" for an advanced care practice, whereas the 500 model is an "essential" technology for a comprehensive ophthalmic practice Cirrus compares retinal measurements from prior visits to recent visits to generate a thickness map, aided by a retinal tracking system (FastTrac). This feature helps to reduce eye motion artifacts, provide precise macular thickness measurements, and enable advanced RPE analysis. Glaucoma applications include RNFL, ONH, ganglion layer, and angle analyses. Specialized software (Guided Progression Analysis) makes it possible to determine change for RNFL and ONH parameters. State-of-the-art technology ensures that the ETDRS and ganglion cell + inner plexiform layer measurements are centered on the fovea (FoveaFinder). The RNFL, macular thickness, and optic disc measurements have been validated, showing excellent repeatability and accurate segmentation. The ONH algorithm is designed to measure the neuroretinal rim while accounting for tilted discs, disruptions to the retinal pigment epithelium, and other pathology. There is an automatic means of centering the 3.4-mm diameter peripapillary RNFL calculation (AutoCenter), which is not operator dependent. The Cirrus HD-OCT technology allows expanded capabilities to share data between instruments and review stations S4 Costello: J Neuro-Ophthalmol 2014; 34(Suppl): S3-S9 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. (Continued ) Machine Manufacturer Product Description Features SPECTRALIS HRA + OCT Heidelberg Engineering The platform includes multiple models at various price points. The so‐called "workhorse" is the SPECTRALIS OCT, an economical, easy-to-use version with one‐touch preset scan patterns. Additional models built on this base platform allow clinicians to tailor a system to the evolving needs of their practice. Using an upgradeable platform approach, SPECTRALIS has enhanced the role of SD‐OCT by integrating it with cSLO. Different SPECTRALIS models include: OCT, OCTPlus with Multicolor, HRA, FA + OCT, HRA + OCT, OCTPlus with BluePeak, OCT with BluePeak The advantages of cSLO over traditional fundus photography include: improved image quality, small depth of focus, suppression of scattered light, increased patient comfort (less bright light exposure), 3D-imaging capability, video capability, and effective imaging of patients who fail to dilate well. The specialized (TruTrack) eye tracking system reduces eye motion artifact and ensures point-to-point correlations between OCT and fundus images without postprocessing the data. This technology (TruTrack) also minimizes operator variability in follow-up scans (AutoRescan) adding precision to measuring changes in RNFL values over time. The Heidelberg Noise Reduction option provides enhanced image detail. The noninvasive blue laser autofluorescence (BluePeak) imaging takes advantage of the natural fluorescent properties of lipofuscin to capture FAF images, providing structural and metabolic information about the retina. Deeper retinal structures are imaged with the EDI feature, which provides detailed views of choroid and lamina cribrosa. The SPECTRALIS Anterior Segment Module offers image acquisition of the cornea, sclera, and the anterior chamber angle, providing a detailed view of the anterior segment. IR imaging provides a variant of fundus photography that uses infrared light rather than white light for illumination. This provides several advantages including: reduced light exposure and decreased patient sensitivity, improved penetration through unclear media, and enhanced visualization of epiretinal membranes and cystoid macular edema compared with fundus photography and red‐free imaging. Foveal-to-Disc Alignment technology (FoDi) tracks and aligns circle scans to improve the accuracy of RNFL scans, by overcoming effects of head tilt and eye rotation. The Region Finder software allows the instrument to quantify and track dark areas on BluePeak images. SPECTRALIS MultiColor imaging delivers high contrast, detailed images even in difficult patients including those with cataracts or nystagmus. SPECTRALIS confocal scanning laser ophthalmoscope (cSLO) with Blue Reflectance imaging uses blue light to illuminate the retina. This wavelength accentuates the visibility of blood vessels and enhances the contrast of certain structures on the surface of the retina, making them easier to see relative to white light illuminated images. The SPECTRALIS cSLO technology enhances FA by increasing the signal-to-noise ratio and blocking out-of-focus and scattered light. SPECTRALIS FA can be combined with ICGA to view retinal and choroidal blood flow. The Widefield imaging feature allows a broader view of the retina beyond the macula. The Noncontact Ultrawidefield Angiography module offers the widest view of the retina with a 1-shot view, making it possible to detect peripheral changes of interest. This feature can be combined with fluorescein and indocyanine green techniques, either individually or together. The machines use the Heidelberg Eye Explorer (HEYEX) software platform and database to store patient information and images. Image acquisition and analysis is controlled by HEYEX plug-in software modules that are specific to each device. Network connections between devices allow access to the common HEYEX database Costello: J Neuro-Ophthalmol 2014; 34(Suppl): S3-S9 S5 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. (Continued ) Machine Manufacturer Product Description Features iVue SD‐OCT Optovue, Inc The iVue is described as the most compact SD‐OCT system This machine is designed to be very easy and fast and includes a convenient footswitch control and touch screen on the scanner head. Anterior Segment imaging provides visualization and measurement of the angle and the cornea. Corneal thickness is offered as a full 6 · 6-mm pachymetry map with minimum thickness marker, in addition to a user-defined corneal point thickness. Additional features includes: ganglion layer thickness imaging with ganglion cell compex upgrade, and 3D "En Face" analysis upgrade. The iVue SD-OCT is available with a 21.5 inch screen or with the optional laptop configuration for maximum portability. Color-coded retinal thickness mapping enables segmenting of the inner, outer, and full retina with overlayed ETDRS thickness values 3D OCT 2000 Topcon Medical Systems This is the first SD-OCT to incorporate a high resolution fundus camera and a color touch screen display in a compact, space saving design It is possible to obtain dynamic viewing of data, with 3D, 2D, and fundus images simultaneously (FastMap software). Moreover, users can determine the location of the OCT image within the fundus image (Pin‐Point Registration). Serial examinations may be viewed and compared. The EyeRoute Image Management System provides access to images OCT/SLO combination imaging system Optos, Inc The OCT SLO system combines SD-OCT imaging with a cSLO in 1 instrument The cSLO provides high resolution images and retinal tracking before, during, and after the OCT scan. The SLO "Lock and Track" function ensures that follow-up scans are obtained from the same location in an operator-independent fashion. The SLO confocal fundus image and the OCT image are generated through the same optics and are pixel-to-pixel correspondent, ensuring precise OCT registration. Furthermore, 3D topographies can be aligned to the SLO image to compensate for rotation and shift. The "AutoCompare" features allows automatic comparison of multiple topographic maps taken over time including retinal thickness. With Optos' "Viewer Software," any clinician can view the system database from a remote computer or laptop, including OCT scans, 3D topography scans, RNFL scans, and optic nerve views SD‐OCT Copernicus Optopol/Canon, Inc SOCT Copernicus HR is a SD-OCT with UHR (3 mm) Ultrahigh scanning speed (52,000 A-scans per second) shortens data collecting and improves the comfort of examination for both patient and operator. The SOCT Copernicus HR Glaucoma Module allows for the detection and management of glaucoma. The tool tracks progression with time. Software features include retina and RNFL volume maps, optic nerve head analysis, 3D visualization, and traction visualization. The DDLS provides a novel way to analyze the optic nerve. Instead of a cup/disc (c/d) ratio, a rim/disc (r/d) ratio and the nerve size is measured. This method is reported to be superior than any other reporting measure because it eliminates the effects of disc size and provides more weightage to the neuroretinal rim damage. The anterior segment module allows cornea and anterior imaging with a resolution of 3 mm. The new advanced 3D module allows visualization of 3D reconstructions. SD-OCT images can be stored in the central area and be accessible from different locations DDLS, Disc Damage Likelihood Scale; ETDRS, Early Treatment Diabetic Retinopathy Study; FA, fluorescein angiography; FAF, fundus autofluorescence; ICGA, indocyanine green angiography; ONH, optic nerve head; cSLO, confocal scanning laser ophthalmoscopy; RNFL, retinal nerve fiber layer; RPE, retinal pigment epithelial analysis. S6 Costello: J Neuro-Ophthalmol 2014; 34(Suppl): S3-S9 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. CONSIDERING THE BELLS AND WHISTLES Retinal Sector Analysis Retinal axons of some retinal sectors are more vulnerable than others in certain disease states. Quantitative analysis of retinal sectors allows for sensitive detection of axonal loss in all regions (7). Retinal Nerve Fiber Layer Thickness and effectivity Maps Using individual circular RNFL scans at the optic nerve to accurately localize focal and peripheral loss of retinal axons is challenging. One possible approach is the development of RNFL thickness maps. An integrative approach combining polarizing sensitive OCT data with RNFL thickness maps may help predict the topography of RNFL loss in neuro-ophthalmic diseases (7). Retinal Layer Segmentation Algorithms With the introduction of SD-OCT, RNFL image quality allows for segmentation and quantification of individual layers. New segmentation algorithms for quantitative analyses of individual retinal layers may facilitate better tracking of progression in neuro-ophthalmic diseases (7). Fluorescence Labeling As an example, fluorescence labeling of a protein that binds to a key component initiating apoptosis enables real-time in vivo monitoring of retinal ganglion cell apoptosis. Detection of this phenomenon provides a promising surrogate outcome for neuroprotective treatment strategies in glaucoma, dementia, and poten-tially multiple sclerosis (7). Optical Coherence Microscopy and Action Potentials With optical coherence microscopy, the structural assessment of action potentials has become a reality. Functional imaging of the human retina in vivo may allow us to investigate whether axonal dysfunction precedes retinal ganglion cell layer or RNFL loss in different disease states (7). Choroidal Imaging Most commercially available SD-OCT systems can be used to evaluate choroidal thickness (1). The method used for choroidal thickness analysis involves manual measurements taken perpendicularly from the outer edge of the retinal pigment epithelial analysis to the inner sclera (choroid- sclera junction) using the software within the system (1). Color Imaging Multicolor imaging delivers high contrast, detailed images, even in patients with cataracts or nystagmus. The image clarity and detail is highly improved and can increase sensitivity in the detection of pathology in the posterior pole. FUTURE DIRECTIONS: EMERGING APPLICATIONS OF OPTICAL COHERENCE TOMOGRAPHY Ultra-High Resolution Optical Coherence Tomography Ultra-high resolution OCT uses an ultrabroadband with light sources to provide axial resolutions approximating 2- 3 mm, which reveals retinal morphology in high detail. However, because this technology requires fematosecond lasers and expensive light sources, it has not been widely used as a commercially available OCT system for clinical settings (8). Mobile Spectral Domain Optical Coherence Tomography The commercialization of mobile SD-OCT systems may expand the application spectrum to allow analysis of subjects manifesting significant motion, including adult and pediatric patients groups. The first commercialized mobile SD-OCT scanner (Bioptigen Inc, Research Triangle Park, NC) provides a light hand-held imaging probe that can be maneuvered independently. This technique may be used in the imaging of small animal eyes in the research setting. Other applications for this technique include evaluating foveal architecture in pediatric ocular albinism, and the extent of retinal pathology accrued from shaken-baby syndrome (8). Spectral Domain Optical Coherence Tomography for Intraoperative Use in Vitroretinal Surgery Vitreoretinal surgeons have long relied on the optical stereo microscope to visualize the surgical field. Even with recent design improvements, there are limitations to intraoperative visualization and accurate localization with this approach (8). Current imaging modalities do not provide real-time cross-sectional images of the change in location of a surgical instru-ment relative to tissue or of tissue deformation during surgery. This feedback may be important in judging whether to con-tinue a specific maneuver. A SD-OCT surgical microscope could potentially provide a base for significant advances in ocular surgery and other branches of microsurgical interven-tion. Moreover, this imaging modality may also be useful for subretinal drug-delivery applications (8). Functional/Targeted Spectral Domain Optical Coherence Tomography Imaging Unlike many other medical imaging modalities with functional adjuncts, such as CT and magnetic resonance Costello: J Neuro-Ophthalmol 2014; 34(Suppl): S3-S9 S7 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. imaging (MRI), ophthalmic use of SD-OCT has been restricted to structural imaging (8). Two new functional SD-OCT imaging modalities are emerging with a wide spectrum of potential diagnostic applications: • Doppler SD-OCT for blood-flow imaging: Doppler OCT technology was first developed using TD-OCT systems and was later used for retinal flow analysis (8). However, the slow data acquisition cou-pled with patient head motion restricted the reliabil-ity of the data. In SD-OCT systems, Doppler flow velocities are acquired much more quickly, and recent extensions to Doppler SD-OCT are enabling complete 3D mapping of the retinal vasculature for the first time, with potential applications in moni-toring diabetic retinopathy and other blinding dis-eases with a vascular component (8). In multiple sclerosis, perivasculitis is believed to lead to extra-vascular hyaline deposits in a process referred to as "vascular sheathing." These changes may lead to increased rigidity of retinal vasculature and, by extension, rapid pulse propagation from the poste-rior (choriodal) to the anterior (retinal vasculature) circulation (7). This hypothesis could potentially be investigated by combination of SD-OCT with Doppler velocity measures. This technique is non-invasive and allows for accurate topographic locali-zation of retinal blood vessels (7). • Polarization-Sensitive OCT: Polarization-sensitive SD-OCT (PS SD-OCT) yields depth-resolved infor-mation about any light polarization changing proper-ties of the sample related to tissue birefringence (7,8). The birefringence of the RNFL is related to the struc-ture of neurofilaments and microtubules. Studies have shown that the birefringence of the RNFL is not constant, but varies by a factor of 3 around the optic-nerve head, with higher values reported in the superior and inferior quadrants and lower values in the nasal and temporal quadrants. This property distinguishes the RNFL from other retinal struc-tures, which are either polarization preserving (e.g., photoreceptor layer) or polarization scrambling/depolarizing (e.g., retinal pigmented epithelium) (8). Because changes to the axonal cytoskeleton such as neurofilament compactness, phosphorylation, and stoichiometry can precede axonal loss, there might be an opportunity to detect early stages of axonal pathology in diseases like multiple sclerosis with PS-OCT (7). Longer Wavelength and Swept Source Technology For adequate analysis of choroidal thickness and volume in healthy and diseased states, the clarity of the choroid-sclera interface is important. This can be achieved by increasing the depth of tissue penetration using a longer wavelength of incident light centered near 1050 nm, so that attenuation from scattering can be reduced (1). The acquisition of scans is much faster in swept source OCT (SS-OCT), when com-pared with the SD-OCT systems. The SS-OCT systems have axial scan rates of up to 100,000-236,000 A-scans per second, which is 5-10 times that of the SD-OCT sys-tems (1). Data can be acquired much faster, and volumetric assessment of the choroid is also feasible (1). As longer-wavelength OCT systems including SS-OCT become avail-able, the visualization of choroid-sclera interface is expected to improve (1). Volumetric analysis of the choroid and that of the various pathological features such as choroidal neovascularization and subretinal/intraretinal fluid, may be possible (1). Such volumetric analysis is expected to help with monitoring the progression of diseases such as diabetic retinopathy, as well as assessment of the response to treatments. Enface Imaging Enface imaging allows the clinician to visualize 3D data in a fundus projection. Using this technique, particular retinal and/or choroidal layers at a given depth are projected onto an enface view. Although cross-sectional images (B-scans) have helped in delineating pathological features in retinal diseases, the microstructural changes and morphology of the retinal and choroidal vasculature are difficult to evaluate using B-scans (1). This is expected to improve because enface imaging provides more detail about the subtle pathological features in the retina and choroid in diseased states (1). In addition, the involvement of the specific vascular layers of the choroid in different diseases, such as diabetic retinopathy, and in-herited retinal dystrophies is expected to be unveiled in additional details using this technique (1). REFERENCES 1. Adhi M, Duker JS. Optical coherence tomography: current and future applications. Curr Opin Ophthalmol. 2013;24: 213-221. 2. Galetta KM, Calabresi PA, Frohman EM, Balcer LJ. Optical coherence tomography (OCT): imaging the visual pathway as a model for neurodegeneration. Neurotherapeutics. 2011;8:117-132. 3. 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