1 Ophthalmic Optical Coherence Tomography Scanner Optical coherence tomography (OCT) scanner is hailed as among the most critical innovations in ophthalmic practice. The scanner performs non-invasive imaging in ancillary tests of the eye and can provide valuable information concerning the retina, the optic nerve head, and the retinal nerve fiber layer (RNFL) (Adhi & Duker, 2013). Earlier scanning systems like the Stratus OCT employed the time-domain detection technique (Fujimoto et al., 2000). The technology has since evolved to produce spectral-domain OCT (SD-OCT). SD-OCT utilizes an interferometer containing a high-speed spectrometer to measure the interference spectrum, simultaneously detecting light echoes (Adhi & Duker, 2013). For most of its existence, OCT has been used to inform clinical decision-makers and to monitor several posterior segment diseases based on the optic nerve, macular, and RNFL imaging (Adhi & Duker, 2013). Choroid was largely excluded from the technology's application spectrum until novel innovations in SD-OCT software and hardware emerged that allowed for precise choroidal thickness evaluations. This technological update also allows the appreciation of choroidal morphological changes in OCT. As such, OCT technology has opened newer platforms of choroidal imaging as a promising field of research. Targeted areas by OCT, such as the macula, optic nerve, and RNFL, are monitored for their morphology, and analysis is carried out to quantify transformations in disparate disease states. For instance, the SD-OCT systems generate automated retinal thickness measurements that are useful for keeping tabs on disease progression (Gabriele et al., 2011). Such diseases include diabetes-induced macular edema, retinal vein occlusion, and wet age-related macular degeneration (AMD). Detection of fluid within the retina and the fluid-induced thickness modifications inform clinical decisions concerning treatment. OCT has enabled straightforward
2 diagnosis of macular holes and has clarified the distinction between the macular hole and pseudoocular and lamellar holes (Adhi & Duker, 2013). The technology aids in assessing the vitreoretinal interface, which is vital in monitoring and treating vitreomacular diseases such as vitreomacular traction and epiretinal membranes (Adhi & Duker, 2013). Moreover, OCT determines the macular hole configuration and size. Additionally, OCT is instrumental in the quantitative evaluation of treatment responses of glaucoma patients through monitoring optic disc morphology and measuring RNFL thickness. Compared to other medical imaging techniques, such as ultrasound and magnetic resonance imaging (MRI), OCT displays a much higher resolution as it merges an axial resolution with a lateral resolution. The lateral resolution is similar to confocal scanning laser ophthalmoscopy, and the axial resolution is comparable to confocal microscopy (Aumann et al., 2019). The axial resolution is determined by the light source rather than the focusing optics, which is explained by the interferometric measurement technique used in the technology. As such, the technology overcomes the deficiencies of optical focusing brought about by the limited pupil size of the eye (Aumann et al., 2019). Mainly, OCT operates with light in the near-infrared, and together with the extended focus, it maintains a penetration depth of hundreds of microns, covering the entire retina. OCT imaging can be analogized to ultrasound imaging B mode imaging. The major difference is the OCT utilization of light rather than sound (Chopra et al., 2020). Apart from the difference in resolution and imaging depths, these technologies also differ in their mechanisms to achieve contrast. In ultrasound, different tissues display different acoustic impedance of ultrasound scattering, producing differences in the intensity of backscattered or reflected sound
3 waves. OCT imaging is sensitive to distinctions in refraction indices of optical scattering between disparate tissues.
Principles of Operation OCT produces high-resolution cross-sectional images by measuring the delay of echo time and magnitude of backscattered light. The fundamental principle of operation underlying OCT is light interference (Popescu et al., 2011). Every OCT system has at its core a light interference configuration. Several types of interference setups have been used, albeit the optical fiber-based Michelson setup will constitute the focus of this review. An OCT system has a lowcoherence light source and a coupler that splits the light into two paths and motions it along an interferometer's disparate arms (a reference and sample arm).
4 The fiber end of each arm has a variety of optical components that shape the departing light to control certain beam properties like depth of focus, intensity distribution, and form. A reference mirror causes back-reflection in the reference arm, where the light is reflected along the same path into the interference system (Popescu et al., 2011). In the sample arm, a similar procedure takes place, except the sample backscatters the beam. An inhomogeneous sample contains different structures with different refraction indices (Popescu et al., 2011). The backreflected and backscattered light merge at the coupler and produce an interference pattern that the detector records. The reference mirror determines the measurement of the depth of intensity of backscattered light through its position. For a specific position in the reference arm, light travels over an optical distance. Light that has traveled a comparable optical distance along the sample arm is the only kind of light that causes it to produce the corresponding interference paradigm (Popescu et al., 2011). As the reference mirror is moved along the direction of light propagation for various mirror positions, the returning reference forms interference patterns with light backscattered from matching depths within the sample (Popescu et al., 2011). This technique enables the measurement of the depth dependence of the intensity of light backscattered from the sample surface. A depth scan, also known as an A-scan, is the OCT signal captured by the detector across the reference mirror's entire trip. The sample beam must be moved across the sample surface to create an OCT image, with an A-scan taken at each place. As a result, a Bscan, also known as an OCT image, is created by a series of sequential A-scans (Popescu et al., 2011). With a 5 m gap between each scan, the image (B-scan) consists of 600 depth scans (Ascans). The sample often determines the maximum depth an OCT instrument may investigate. The highest depth of the finger picture was around 1.5 mm (Popescu et al., 2011). The image
5 also possesses the spatial resolution required to discern the sweat glands emerging to the skin surface after passing through the epidermis. The multi-layered structure of the skin at the fingertip can be seen. Typically, a low-coherence semiconductor super-luminescent diode serves as the light source in an OCT system (SLD). Since the axial resolution, sometimes referred to as the depth resolution or the coherence gate, is the source's inherent coherence length, which is inversely proportionate to its spectral bandwidth, the properties of the SLD are a crucial design parameter (Popescu et al., 2011). High axial resolution requires the use of broadband optical sources. Using white-light sources like halogen lamps or sources with a very wide spectral band, such as femtosecond pulsed lasers, allows for the achievement of axial resolutions in the micron and submicron range. There are two main OCT technologies used in point-scanning/point-detection technology: time-domain OCT (TD-OCT) and Fourier-domain OCT (FD-OCT). Moreover, there are two methods for performing Fourier-domain OCT imaging: spectral-domain OCT (SD-OCT) and swept-source OCT (SS-OCT) (Popescu et al., 2011). Another technique, full-field OCT, allows for the direct capture of 2D OCT pictures (FF-OCT). The foundation of TD-OCT is a detection method that makes use of a scanning reference delay and a low-coherent light source. The majority of the fundamental ideas and criteria that characterize this OCT imaging technique were covered in the section on fundamental ideas. An optical splitter divides the light source, typically a low-coherence SLD or pulsed laser, into two pathways (Popescu et al., 2011). The reference light travels a defined path length and experiences a quantifiable variable time delay thanks to back reflection from a reference mirror that is moving in a controlled translation motion. When the light from the second path is focused
6 onto the sample, the internal structure causes backscattering, which creates interference patterns with the reference light that traveled an equivalent optical distance, revealing the depth of the sample as well as the locations of different internal structures (Popescu et al., 2011). In contrast to TD-OCT measurements, where light echoes are detected sequentially by the step-movement of a reference mirror, FD-OCT measurements detect light echoes as modulations in the source spectrum at all axial depths. Performance Verification Techniques The axial resolution z is given as:
where and are the SLD's central wavelength and bandwidth when its spectral distribution is Gaussian. The focused probing beam's minimum spot size, which is inversely related to the focusing lens's numerical aperture (NA), determines the transverse resolution:
In this equation, f is the focal length of the objective lens, which is the lens or lens system at the end of the sample arm, and d is the size of the probing beam's projected spot on the objective lens. The trade-off between transverse resolution and depth of field is a significant point that has to be made (Popescu et al., 2011). A high numerical aperture has a strong focusing ability that translates into outstanding transverse resolution, or a narrow- focused beam diameter with a shallow depth of field. A high NA delivers a narrower field of view but a larger diameter of the beam at the focus point. The majority of OCT imaging is carried out with a low NA lens to
7 guarantee a depth of field of the order of millimeters, significantly longer than the source's coherence length. Transverse resolutions of 20–25 m are the norm for commercial OCT systems.
Technical Specifications OCT Scan Axial Resolution
5 micrometers
Horizontal resolution
15 micrometers
Scan depth
2 mm
Optical source
850 nm
Scan speed
35 KHz
Maximum Scan Range
12 MM * 12 MM
Fundus Tracking Scan Scan Frequency
30 Hz
Field of View
36 * 30
Optical Source
750 nm
Scan Mode Line Scan 4096
A-scan with adjustable length, angle, and position
5 line scan Area Scan
512*128 A-scan
Area Scan
320*320 A-scan
Area Scan
240*240 A-scan
PV-OCT fundus blood vessel scan
8 Large volume scan PV OCT
Large-volume scan imaging of fundus vessels
Ring scan
0.5*4.5mm 300*300 scan
Database and Analysis Software Macular thickness tracking analysis software Age-related RNFL and normative database of macular parameters Automated macular fovea centering. Remote reading analysis software 3D imaging and angiography analysis software Refractive Compensation Range +10D—10D Pupil Diameter Requirements 2.0 mm OCTscan.com (2023) Factors Affecting Performance The scan quality of OCT is a crucial tenet to consider since it affects OCT's ability to detect and monitor glaucoma progression, among other ophthalmic illnesses. Different factors have been identified that affect the technology's scan quality. These factors can be categorized as either patient-dependent, device-dependent, or operator dependent. Patient-dependent factors Any obstruction in the sample path that reduces the signal-to-noise ratio will make it more difficult for the OCT automated algorithm to identify the edges of the retinal nerve fiber
9 layer (RNFL) or other critical characteristics of the optic nerve head, such as the margins of the optic disc and cup, which will result in inaccurate measurements (Taibibi et al., 2015). A small pupil, for instance, can reduce the amount and quality of signal the gadget can detect. Current studies support the hypothesis that pupil size shouldn't affect OCT results by showing that RNFL thickness before and after dilatation does not differ significantly. Yet, when the pupil size is small, pharmacological dilation may be necessary in a few cases (Taibibi et al., 2015). Scanners can be used on eyes with pupils larger than two millimeters. Due to the high frequency of these diseases in adult and aging populations, coexisting conditions such as glaucoma, dry eye, and cataract are common. Patients who use topical ocular hypotensive medications frequently have dry eyes and ocular surface disease. In OCT investigations, dry eye and cataracts have been found to reduce the RNFL thickness measurements and the scan quality index (Taibibi et al., 2015). This effect should always be taken into account during cross-sectional or longitudinal assessment of the RNFL due to the likelihood of false positives in detecting glaucoma or the progression of the disease. Cirrus HD-OCT macular and optic disc scans have revealed floaters and other vitreous opacities. By interfering with the light beam path, these opacities may reduce scan quality. However, their location within the scan area is more directly correlated with the impact on OCT measurements (Taibibi et al., 2015). A traditional vertical shadow of signal attenuation or interruption can be seen in the appropriate area of the circular tomogram when a floater is placed on the scan circle. The existence of the floater, especially when it is positioned superotemporally or inferotemporally, may mimic beginning glaucomatous damage or falsely suggest thinning of a preexisting RNFL defect, hence caution is advised when interpreting the results. Floaters near the optic disc area may be undetected because of the presence of significant retinal vessels and other
10 graphic elements seen on the en-face image, even though this artifact is typically easily visible on the printout. It is necessary to evaluate the tomograms that cross the optic disc (Taibibi et al., 2015). By requesting the subject to make quick back-and-forth eye movements just before scan acquisition, floaters can be successfully removed from the scan circle and the area around the optic disc. Several vitreopathies, besides the floaters, could be the cause of variations in RNFL thickness. In eyes with epiretinal membrane (ERM), studies have found increased temporal and average RNFL thickness, which is probably due to the tractional stresses the ERM exerts on the retina (Taibibi et al., 2015). Thus, care must be taken when interpreting RNFL thickness measurements in eyes with ERM. Eye movements during scan acquisition, such as horizontal saccades, can cause motion artifacts. They normally show up on the en-face image as horizontal variations in the blood vessel's course, but if they are confined to the optic disc region or to regions without retinal vessels, they could go unnoticed (Taibibi et al., 2015). Motion artifacts in OCT scans are less likely now thanks to faster SD-OCT scanning and shorter acquisition times. For devices without an eye tracking system or motion correction algorithms, eye motions still pose a potential issue. To prevent motion artifacts, the patient must maintain a constant fixation. Hence, it may be beneficial to provide a thorough description of the scanning processes and prompt information of the impending image acquisition (Taibibi et al., 2015). Motion artifacts identification may be facilitated by on-screen image enlargement. The route of the retinal arteries and the form of the optic disc should both be closely scrutinized for this reason. Rescans should be tried, especially when motion artifacts cross the scan circle or the area of the optic disc. In scans with a motion
11 artifact going through the optic disc, careful interpretation of the results is required, including clock hours RNFL thickness. As a traditional method of measuring the objectivity of scan quality, the "intensity" of the light signal backscattered by the ocular structures—calculated as the signal to noise ratio—has been used. Commercially accessible SD-OCT equipment have the convenience of displaying numerical scan quality scores on printouts (Taibibi et al., 2015). Cirrus HD-OCT scan quality index, or signal strength, for instance, runs from 0 to 10. As advised by the manufacturer, only scans with a signal strength of 6 or higher should be taken into account. Thus, one of the operator's objectives should be to maximize signal strength. However, as mentioned above, a number of patient-related variables, such as dry eye and media opacities, impair OCT scan quality and reduce the signal strength (Taibibi et al., 2015). Operator-dependent variables may also be at play, such as faulty OCT lens cleaning or inadequate image centration. Many independent investigations have demonstrated a correlation between higher RNFL thickness measurements and scans with higher signal strength. This association also shows that RNFL thickness decreases with signal strength reduction, which may be misinterpreted as glaucomatous damage on a cross-sectional evaluation or as glaucomatous progression over time when many OCT scans are compared (Taibibi et al., 2015). Hence, while analyzing RNFL thickness measurements, signal strength values should always be taken into account. Because the Cirrus HD-OCT capture time is less than 2 seconds, this test is appropriate for normal clinical use. Blinks, however, could still happen throughout this period (Taibibi et al., 2015). Without an eye monitoring device, the acquisition process goes on without interruption even when there are blinks. As a result, there is a temporary loss of data that is inversely correlated with the blink time. Blinks' effects on OCT measurements depend on where they are
12 relative to the scan region. Blink artifacts are typically avoided by allowing the subject to blink naturally up to the point at which the camera has been properly aligned, then promptly alerting them that the scan acquisition is about to begin (Taibibi et al., 2015). Artificial tears or other lubricants may be recommended in certain circumstances. Patients are frequently told not to blink while the camera is aligned and the scan is being acquired, but this can lead to tearing film evaporation and breakdown, especially in patients who already have ocular surface diseases (Taibibi et al., 2015). Consequently, it is advised that the live funduscopic "en-face" image and the OCT tomograms be carefully observed. Device-dependent factors Image quality may be lowered, and RNFL thickness measurements may be negatively impacted by opacities of the OCT lens, such as those caused by fingerprints or unintentional contact with the patient's periocular region or face (for example, the nose). Throughout multiple tests, OCT lens opacities often keep their similar size and location on the facial image (Lee et al., 2017). Incorrect axial alignment occurs when the ocular structures are only partially included in the acquisition frame, leading to image truncation. The innermost features in Cirrus HD-OCT scans (such as the peripapillary inner retinal layers) and the outermost features (such as the optic disc cup) are particularly prone to this type of artifact due to their proximity to the front and posterior margins of the acquisition window. Operator-dependent factors Through automated delineation of the optic disc and cup boundaries, OCT gives several optic disc metrics (such as optic disc area, rim area, average and vertical cup-to-disc ratios, and cup volume). The optic disc area must be accurately delineated to compute the optic disc center and set the scan circle uniformly around it.
13 The capacity of Cirrus HD-OCT to separate the RNFL from the other retinal layers is necessary for estimating the thickness of the RNFL. Inaccurate RNFL segmentation may be caused by many causes, including OCT signal attenuation with decreased RNFL reflectance brought on by ocular media opacities (Taibibi et al., 2015). Blinks or floaters may cause the OCT signal to be partially interrupted, resulting in a localized inability to recognize the RNFL boundaries and lower RNFL thickness measurements. Additionally, the shortening of the inner retinal layers may reveal algorithmic failure or glaring segmentation faults in the RNFL. Finally, erroneous RNFL segmentation may be facilitated by motion artifacts that cross the scan circle. The circular tomogram must be carefully examined after scan acquisition to rule out RNFL segmentation artifacts. It is recommended to magnify the circular tomogram on the screen (Taibibi et al., 2015). Additionally, the grayscale view could reveal minute retinal features and segmentation flaws that the conventional false-color imaging option might overlook.
Potential Hazards, Limitations, and Methods of Mitigation Since OCT uses light waves for operation, it can encounter interference from media opacities. As such, OCT is limited in dense cataracts, vitreous hemorrhage, or corneal capacities. Patient cooperation is needed with OCT, just like most diagnostic tests. Rapid movement by the patient can lower the image quality. However, newer machines have shorter acquisition times, mitigating motion-related acquisition. No adverse effects or risks have been identified with OCT scans, except eye dryness or fatigue. Vessel Density Parameter Vessel density is a critical parameter in the diagnosis of primary open-angle glaucoma. Glaucomatous optic neuropathy is linked with vascular dysfunction, thus, providing an imaging
14 target for early monitoring and diagnosis of glaucoma (Khayrallah et al., 2021). OCT-A has been identified as the technology of choice for imaging due to its non-invasiveness combined with the rapidity and detail of the quantitative information it offers on the choroid and retinal micro vascularization of the eye. Through the stages of glaucoma severity, analysis of the point clouds of the structure-vascularization and vascularization function interactions has revealed a varied behavior. One study found that the correlation between peripapillary vessel densities (ppVD) and mean deviation (M.D.) is more linear in early glaucoma than with RNFL when the M.D. level was less than 6 dB. Song et al. [27] present a similar conclusion, demonstrating that the link between the ppVD and M.D. is more linear in the early stages of glaucoma and stronger with M.D. than with RNFL thickness. They use a nonlinear statistical broken-stick model. This shows that ppVD may be able to monitor visual function in eyes with early-onset glaucoma, especially for those unable to perform a good quality visual field. Conclusively, both ppVD and pfVD enable better monitoring of the visual function than RNFL or GCC thickness, even in advanced glaucoma.
15 References Adhi, M., & Duker, J. S. (2013). Optical coherence tomography- current and future applications. Current Opinion in Ophthalmology, 24(3), 213–221. https://doi.org/10.1097%2FICU.0b013e32835f8bf8 Aumann, S., Donner, S., Fischer, J., & Muller, F. (2019). Optical coherence tomography (OCT): Principle and technical realization. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK554044/ Chopra, R., Wagner, S. K., & Keane, P.A. (2020). Optical coherence tomography in the 2020soutside the eye clinic. Eye, pp. 35, 236–243. https://www.nature.com/articles/s41433020-01263-6 Cleveland Clinic. (2023). Optical coherence tomography. Cleveland Clinic. https://my.clevelandclinic.org/health/diagnostics/17293-optical-coherencetomography#:~:text=There%20aren't%20any%20risks,heavy%20bleeding%20in %20your%20vitreous. Fujimoto, J. G., Pitris, C., Boppart, S. A., & Brezinski, M. E. (2000). Optical coherence tomography: An emerging technology for biomedical imaging and optical biopsy. Neoplasia, 2(1-2), 9-25. https://doi.org/10.1038%2Fsj.neo.7900071 Gabriele, M. L., Wollstein, G., Ishikawa, H., Kagemann, L., Xu, J., Folio, L. S., & Schuman, J. S. (2011). Optical coherence tomography: History, current status, and laboratory work. Investigative Ophthalmology and Visual Science. https://doi.org/10.1167/iovs.10-6312 Khayrallah, O., Mahjoub, A., Abdesslam, N. B., Mahjoub, A., Ghorbel, M., Mahjoub, H., Knani, L., & Krifa, F. (2021). Optical coherence tomography angiography vessel density
16 parameters in primary open-angle glaucoma. Annals of Medicine and Surgery, 69. https://doi.org/10.1016/j.amsu.2021.102671 Lee, R., Tham, Y., Cheung, C. Y., Sidartha, E., Siantar, R. G., Lim, S., Wong, T. Y., & Cheng, C. (2017). Factors affecting signal strength in spectral-domain optical coherence tomography. Acta Ophthalmologica, 96(1). https://doi.org/10.1111/aos.13443 OCTscan.com. (2023). Technical specifications. https://www.octscan.com/technicalspecifications Popescu, D.P., Choo-Smith, L., Flueraru, C., Mao, Y., Chang, S., Disano, J., Sherif, S., & Sowa, M.G. (2011). Optical coherence tomography: Fundamental principles, instrumental designs, and biomedical applications. Biophysics Revision, 3(3). https://doi.org/10.1007%2Fs12551-011-0054-7 Song, M.K., Shin, J.W., Jo, Y., Won, H.J., & Kook, M.S. (2020). Relationship between peripapillary vessel density and visual field in glaucoma: a broken-stick model. British Journal of Ophthalmology. https://doi.org/10.1136/bjophtalmol-2020-315973 Spirn, M. J. (2015). Optical coherence tomography. American Academy of Ophthalmology. https://eyewiki.aao.org/Optical_Coherence_Tomography#:~:text=can%20be %20visualized.-,Limitations,patient%20cooperation%20is%20a%20necessity. Taibibi, G., Vizzeri, G., & Nelson, S.C. (2015). Factors affecting cirrus-HD OCT optic disc scan quality: A review with case examples. Journal of Ophthalmology. http://dx.doi.org/10.1155/2015/746150
