OCT from the Past to the Future

Abstract

OCT is a high-resolution, non-invasive imaging technique that relies on time-of-flight information. Different patterns such as time domain and spectral domain were implemented until the introduction of the longer wavelength new generation, swept-source OCT. Anterior segment OCT has different implications as AC angle assessment, tear meniscus measurement, corneal pathologies, etc. In posterior segment, macular lesions are easier to image (vitreoretinal interface, intraretinal changes, subretinal and choroidal pathologies). OCT-ON is an important tool in investigating glaucoma and optic neuropathies. Recent advances made OCT indispensable tool in everyday practice. Functional extension providing information on retinal and choroidal circulations without the need for dye injection is the OCT angiography. ONH-OCTA and AS-OCTA imaging vasculature are useful for various clinical applications, ranging from diagnosis to treatment with many challenges. Major advances occurred in the intraoperative OCT, from portable probe to the microscope-integrated system and handheld type. Developing technologies are coming as doppler OCT, in-vivo retinal images and polarization-sensitive OCT.

1. Introduction

Optical coherence tomography (OCT) is a high-resolution, cross-sectional imaging technique. It is fast, safe and non-invasive modality. Over the past 25 years, OCT has advanced to become the most commonly used investigative tool in ophthalmology. The 3D imaging allows qualitative and quantitative structural analysis of different locations in the retina and optic nerve head. It helps not only to improve the diagnosis but also to understand the pathogenesis of various diseases and to evaluate the effect of the implemented therapies.

2. Evolution of OCT technology

Originally, OCT technology was used to localize faults in fiber optic networks in the telecommunications industry [1]. A back light was reflected from a disruption in a fibreoptic cable, and the time-of-flight information was extracted by low-coherence interferometry to enable distance mapping [2]. OCT was introduced in ophthalmology in 1991 as an application of low-coherence interferometry used in axial length measurement [3]. Other developments that added much to the industry of OCT were semi-conductor, super-luminescent diode SLD (low cost and low maintenance light source), optical heterodyne detection (improving safe detection and interpretation of faint signals) and high-speed line camera technology (incorporating fast repetitive A-scans to give the 2D images “B-scan”). Then, James Fujimoto and his coworkers were the first to represent brightness by employment of the color codes [2].

The first commercially available OCT device was by Zeiss in 1996 after the scanning patterns with reproducible measurements were implemented. In 2000, the second OCT generation was fairly acceptable in ophthalmology practice due to slow speed (100 axial scans/second) and low resolution [2]. Then, the speed was increased in 2002 to 400 axial scans in the third-generation devices for scanning of the anterior segment, retinal layers and optic nerve, and these A-scans became incorporated into a commercial system with an axial resolution of ∼10 μm² [4]. In 2006, the faster Fourier domain approach using 27,000 A-scans/second was introduced (RTVue, OptoVue, USA).

The adaptive optics AO to correct the ocular monochromatic aberrations was first reported in OCT by Miller et al. in 2003 improving the transverse resolution [5]. However, this AO had a narrow depth of focus that prevented simultaneous visualization of layers at different depths and restricted field of view.

The polarization sensitive was used in OCT in 2001 to measure birefringence of the RNFL of the monkeys [6], and then later on, it was used for birefringence measurement of the retina and anterior segment.

3. OCT: basic principles and preclinical application

OCT is a type of “optical ultrasound” as it relies on time-of-flight information, similar to the ultrasound. It is like an in-vivo optical biopsy analyzing the signals from different locations at different depths [7]. The OCT resolution fills the gap between the ultrasound and conofocal microscopy resolutions.

Light interference is the core principle in OCT imaging based on the optical fiber-based Michelson setup. When the light emits from a low-coherence source, it will split by a coupler into two parts traveling to both arms, namely sample and reference arms. To control different beam parameters (as shape, depth of focus and intensity distribution), the light emitted from the fiber end of either arm is shaped by various optical components (mirrors, lenses, etc.). The backscattered light from both arms will pass through the coupler to be recorded by the detector (Figure 1). The difference in the light backscattered from the sample arm will exit when it encounters an interface between structures of different refractive indices. The corresponding interference pattern is formed between the light propagating in the reference arm traveled a certain optical distance and the light that traveled the same optical distance along the sample arm (including the portion of the distance traveled inside the sample). The depth information of light backscattered from the locations of various structures within the sample can be measured in this way. The detector records the OCT signal during a complete travel of the reference mirror “Depth or A-scan” which is recorded at each beam position. While the B-scan is formed by a consecutive set of A-scans [8].

Figure 1.

Optical fiber-based Michelson setup demonstrating the basic concept of light interference in OCT imaging (figure taken from Popescu et al. [8]).

The 3D imaging allows not only analysis from different locations but also incorporation of A-scans to form the OCT fundus (en face) image [4]. This is called full-field OCT (FF-OCT) with an axial resolution of ~1 μm², similar to that of the conventional microscopy [8]. Also, the built-in tracking system allows better sensitivity and higher reproducibility.

In OCT imaging, the axial and transverse resolutions are independent. The axial resolution (depth resolution and coherence gate) is the coherence length of the source which is inversely proportional to its bandwidth. Therefore, broadband optical sources are required to achieve high axial resolution. While the transverse resolution is determined by the minimum spot size of the focused probing beam (inversely proportional to the numerical aperture NA of the focusing lens). This transverse resolution affects the depth of field (a low NA with a greater beam diameter will offer a large depth of field, as in most OCT imaging). The transverse resolutions used by the commercially available OCT systems are between 20 and 25 μm² [8]. The lateral resolution is considered to be equal to the illumination spot size on the retina (14 μm for Spectralis OCT) [9].

4. First clinical applications and the early diagnostic efficacy

The time-domain (TD)-OCT imaging was firstly developed in 1990s. It included 3.4 mm scan around the optic nerve head and six radial scans (6 mm) at the macula for assessment of glaucoma, optic neuropathies and retinal diseases [4]. Then, the introduction of the 3D approaches allowed the imaging of ganglion cell complex GCC, RNFL thickness map, comparison to a normal population and comparison of different scans over time for detection of any subtle structural changes reflecting the disease progression. Also, the progression in OCT development allowed better thickness measurements, analysis of the vitreoretinal interface and detection of biomarkers as predictors of the surgical outcome and visual prognosis.

Anterior segment AS-OCT is a non-contact imaging device that provides the detailed structure of the anterior part of the eye including the cornea and anterior chamber angle. It is beneficial in presurgical and postsurgical assessment of corneal and lenticular refractive surgeries. Unlike ultrasound biomicroscopy UBM, it does not allow visualization of the ciliary body.

5. Time domain vs. Fourier domain

5.1 Advantages and disadvantage

TD-OCT uses low coherence interferometry with the light being split to be sent to both a scanning reference mirror and the sample. The interference occurs when the reflected beams recombine. The intensity information can be extracted from the interference profile. Different depths in the tissue sample can be scanned by changing the location of the reference mirror [4]. The TD-OCT approach encodes the location reflections and relates them to the position of the moving reference mirror, and the time-encoded signals are recorded sequentially. It is limited by the slow-scan acquisition time and 2D imaging with an axial resolution of ∼10 μm² [2] (Figure 2).

Figure 2.

Principles of different approaches of OCT, time domain versus Fourier domain (figure is taken from Wolfgang et al. [10]).

The A-scans in the other approach are obtained using a Fourier transform of the detected frequencies. It uses a single axial scan by evaluating spectrum of interference between stationary reference mirror and reflected light. The light echoes come at the same time from all axial depths with simultaneous capture of all the spectral components, hence the advantages of improving 3D scan resolution with an axial resolution of ∼2-5 μm² and reducing the acquisition time up to 27,000–100,000 A-scans/second9. The Fourier domain includes both the spectral domain (SD) and the swept-source (SS)-OCT. In the SD-OCT approach, a broad-bandwidth light source, charge-coupled device (CCD) camera and a spectrometer are used to acquire frequency information, while the SS-OCT is sweeping a narrow band through broad range with a photodetector [2] (Figure 3). The limits of pixels of CCD camera and the dispersed interference pattern immediately before detection are drawbacks of SD over SS-OCT, while the SS-OCT has the advantages of point detection, less movement artifacts, better signal-to-noise ratio with better visualization of different retinal and choroidal pathologies [4, 8] (Figure 3).

Figure 3.

Normal OCT-macula as captured by A: Time-domain OCT, B: Spectral domain OCT and C: Swept source OCT [11].

5.2 The swept-source technology

It is a unique combination of high speed, deep tissue penetration and high-resolution OCT technology. It allows simultaneous visualization of the vitreous, retina and choroid. Visualization of choroidal structure may play a role in understating the pathogenesis of retinal diseases. Presenting the optic nerve and macula on the same scan is possible with its wide scans. Longer wavelengths are beneficial in eyes with hazy fundus view due to media opacity as in cataractous eyes [12].

The advantage in SS-OCT performance is due to the laser source performance (a wavelength-swept laser). The advances in development of several types of wavelength-swept lasers improve the speed and depth of imaging and eliminating the mechanical movement (active mode-locking (AML) laser) [13].

6. Developing technologies

Longer wavelengths OCT systems for better visualization of the choroid and retina are emerging. Major advances occur in the intraoperative iOCT; from a handheld portable probe used in infants and bed-ridden patients (it was used firstly in patient undergoing vitrectomy for better visualization of the macular disease [4]) to the microscope-integrated system (firstly demonstrated in the anterior segment surgeries) guiding the image during ophthalmic surgeries.

OCT-slit lamp incorporation also is advancing for close monitoring of chorioretinal diseases. The visible-light (Vis) OCT technology develops to capture retinal fine details. FF-OCT provides 2D enface high resolution images at different depth. The wide-field (WF) and ultrawide-field (UWF) increases the field of imaging to 40–55 degrees in WF up to 200 degrees in UWF allowing visualization of the periphery.

The AO-OCT improves the quality of images by using wavefront component and advanced software to compensate the ocular aberrations. At-home OCT is a self-imaging technique for better monitoring of the disease when compared to the in-office imaging.

Polarization-sensitive OCT analyses the tissue polarization and depolarization quantitively of the retinal pigment epithelial layers. Doppler OCT and, In-vivo retinal images developing technologies are coming [14].

7. OCTA introduction and the future of FFA

Over the past years, OCT was used to assess the structural anatomy (3D) of the posterior segment, while fluorescein angiography (FA) was used to assess the retinal vasculature (2D). Then, optical coherence tomography angiography (OCTA) develops since 2014 to represent the functional extension of structural OCT that allows non-invasive visualization and qualification of the retinal and choroidal microcirculations, without the need for dye injections. Also, OCTA shows developmental progression in earlier diagnosis of glaucoma and neuro-ophthalmology diseases. OCTA decreases the use of the invasive FA especially after the diagnosis [15].

The main principle of OCTA is the detection of signal change over time emitted from intravascular blood cells motions. The scan consists of multiple individual A-scans using the laser light reflected from the surface of moving red blood cells, which integrated into a B-scan providing cross-sectional information (Figure 4). There are two methods used for motion detection: amplitude decorrelation (differences in amplitude between two different B-scan) or phase variance (the variation of phase of the emitted light wave when it intercepts moving objects). The same tissue area is repeatedly imaged, analyzing the differences between scans to differentiate between areas of high flow and that of slow/no flow [16]. The signals are amplified with different motion correction technologies aiming to improve the image quality.

Figure 4.

Basic principle of optical coherence tomography angiography; when the B-scans are sequentially taken from the same retinal location, any changes in signal amplitude or phase will represent the blood flow, and mathematical assessment of signal changes will represent the amount of the blood flow [15].

OCTA machines are characterized by autosegmentation which referred to splitted slabs from a known anatomical layer of the retinal vasculature. In Optovue OCTA software, the four slabs represent the following: superficial capillary plexus SCP, deep capillary plexus DCP, outer retina and choriocapillaris as shown in Figure 5. While the SCP is seen on FA, the DCP is poorly seen on FA and hence the advantage of OCTA in diagnosis of certain pathological conditions as retinal angiomatous proliferation, paracentral acute middle maculopathy and parafoveal telangectasia. The outer retinal slab is useful in identification of type 2 (subretinal) neovascular membranes, while the choriocapillaris slab helps to detect early type 1 (sub-RPE) choroidal neovascular membrane (CNV) [15].

Figure 5.

Optovue OCTA four slabs; a: Inner retinal slab extends from 3 μm below the internal limiting membrane (ILM) to 15 μm below the inner plexiform layer (IPL) representing the superficial retinal vascular plexus. B: Middle retinal slab representing the deep capillary plexus; extends from 15 μm below the IPL to 70 μm below the IPL. C: Outer retinal slab showing no vessels in normal individuals, extends from 70 μm below the IPL to 30 μm below the retinal pigment epithelium (RPE). D: The last slab represents the choriocapillaris extending from 30 μm below the RPE to 60 μm below the RPE.

Variable interscan time analysis (VISTA) allows visualization of different ranges of blood flow speeds using a color-encoded images in which high flow is represented in red color and blue represents areas of relatively low flow.

OCTA provides images of blood cell movements (perfusion) and not anatomical structure of the vessels. Areas of ischemia are represented as dark zones. There are different chorioretinal pathologies that can be diagnosed using OCTA; abnormal flow in areas with no flow (like presence of CNV in the outer retina), abnormal areas of non-perfusion in the SCP (normally there is a foveal avascular zone in the center) with an extension of the non-perfused area as in diabetic retinopathy.

There are many challenges in OCTA that are tried to be corrected by various technologies as shown in Table 1 (as longer data acquisition times needed for repeated B-scans, corrected by SSADA, motion artifacts corrected by dual track technology). We should note that OCTA does not give us full details about retinal periphery, and also, it gives no information about blood retinal barrier (no dye to leak), an important sign in many retinal diseases. Some limitations and artifacts are also important to consider in the OCT-A images interpretation.

OCTA device	Used technology	Advantages
1. ZEISS Angioplex™ OCT angiographic imaging on the CIRRUS™ HD-OCT platform	FastTrac™ software	Scanning rate up to 68,000; A-scans per second.
2. Optovue AngioVue® (Optovue, Inc., Freemont, CA)	Split-spectrum amplitude-decorrelation angiography algorithm (SSADA)	Minimizes motion; Noise, allows quantitative; Analysis of flow area and flow density maps.
3. Topcon®	OCTA RatioAnalysis paired with SD-OCT	Reduces motion artifacts, Preserves axial resolution; Improves detection sensitivity of low blood flow
4. Heidelberg engineering®	Active eye-tracking system (TruTrack™)	Simultaneously acquisition of fundus and OCT images for better signal-to-noise ratio.

Table 1.

Main commercially available devices of OCT-A [16].

8. Conclusion

This introduction chapter gives a brief review about the history of development of OCT. OCT is a non-invasive revolutionary imaging modality with vast growing technology. Starting from the past, the progression in wavelengths, sensitivity, reproducibility and decrease scan acquisition time are evolving. Recent advances in technology make OCT indispensable tool in everyday practice and accepted as the standard of care. OCTA is giving new information that FA and ICGA cannot provide. iOCT and handheld models are considered the next big step in OCT development.

Conflict of interest

The authors declare no conflict of interest.