Current Applications of Optical Coherence Tomography in Ophthalmology

Optical coherence tomography (OCT) was first reported in 1991 as a non-invasive ocular imaging technology (Huang et al, 1991; Hrynchak & Simpson, 2007). It generates a false-color representation of the tissue structures, based on the intensity of the returned light. Over years, the clinical applications of OCT have improved dramatically in precision and specificity. It has been compared to an in vivo optical biopsy. As the resolution of OCT has been getting more and more refined, the identification, detection, localization and quantification of the tissues has accordingly, become more superior and reliable (Ryan SJ, 2006). There are several nonophthalmic applications of OCT as well, but this chapter shall focus on its clinical applications in ocular diseases alone (Aguirre et al., 2003; Fujimoto, 2003).


Introduction
Optical coherence tomography (OCT) was first reported in 1991 as a non-invasive, cross-sectional ocular imaging technology (Huang et al., 1991) and today is the most promising noncontact, high resolution tomographic and biomicroscopic imaging device in ophthalmology. It is a computerized instrument structured on the principle of low-coherence interferometry (Huang et al., 1991;Hrynchak & Simpson., 2007) generating a pseudo-color representation of the tissue structures, based on the intensity of light returning from the scanned tissue. This noninvasive, noncontact and quick imaging technique has revolutionized modern ophthalmology practice. The current applications of OCT have been improvised and expanded dramatically in precision and specificity in clinical medicine and industrial applications. In medicine, the technique has been compared to an in-vivo optical biopsy. As the resolution of OCT has been improving with time, the localization and quantification of the tissues has accordingly, become more refined, faster and predictable (Ryan SJ, 2006). What was initially and mainly a posterior segment procedure, OCT has now wider applications in anterior segment of the eye as well. The first anterior segment OCT (AS-OCT) was available in 1994. Its current use in cornea and refractive surgery including phakic intraocular lens implantation, laser-assisted in situ keratomileusis (LASIK) enhancement, lamellar keratoplasty and intraoperative OCT has opened promising therapeutic and diagnostic options in both research and clinical applications in ophthalmology. With an improved scan speed and resolution, the new models of spectral-domain (SD)-OCT allow measurements with an even lower variability (Leung et al., 2009). Due to reduced measurement errors, e.g. due to motion artifacts, the precision to track and interpret tissues has increased sharply (Leung et al., 2011). OCT is intended for use as a diagnostic device to aid in the detection and management of ocular diseases, however, it is not intended to be used as the sole aid for the diagnosis. Ultra-high resolution (UHR) OCT is a new imaging system that is being used in several clinical and research purposes. It is an objective technique and has been used for evaluation of tear fluid dynamics, contact lens fitting, imaging of corneal structures, and to describe the characteristics of epithelium, stroma and Descemet's membrane in corneal dystrophies and degenerations (Wang et

The machine
There are different models of OCT machine available in the market. This chapter is based on observations made with Cirrus-high definition (HD) spectral domain (SD) OCT (Carl Zeiss Meditech Inc., Dublin, CA; software version 4.0). The light source of OCT is a broadband superluminescent diode laser with a central wavelength of 840 nm. This light generates back-reflections from different intraretinal depths represented by different wavelengths. The acquisition rate of Cirrus-HD-OCT is 27 000 A-scans /second. The axial and transverse resolutions are 15 and 5 µm, respectively. The vast increase in scan speed makes it possible to acquire three-dimensional data sets. Current OCT models are mainly designed for analysis of optic nerve head (optic disc cube), macula and anterior segment of the eye. The tomograms are stored on the computer and/or archive medium, and can be quantitatively analyzed. A CCD video monitors the external eye and assists with scan alignment, while a line scanning ophthalmoscope provides a clear image of the tissue addressed by the scan.
The main hardware components of the OCT include the scan acquisition optics, the interferometer, the spectrometer, the system computer and video monitor. Before scanning the patient looks into the imaging aperture and sees a green star-shaped target against a black background ( Figure 1). When scanning stars, the background changes to a bright flickering red, and the patient may see thin bright lines of light, which is the scan beam moving across the field of view. Normally, the patient can look inside the imaging aperture for several minutes at a time without discomfort or tiredness. Patient should be instructed to look at the center of the green target, and not at the moving lights of the scan beam. (Figure 1).

Before scanning
During scanning Anterior segment OCT uses light source with longer infrared wavelengths (1310 nm) to improve the penetration through light scattering tissues, such as sclera and limbus. Unlike posterior segment OCT, AS-OCT requires greater depth of field. AS-OCT also requires higher energy levels than retinal OCT systems. Visualization of retroiridial structures is limited in current AS-OCT, especially in presence of ocular surface opacities and heavy iris pigmentation (Goldsmith et al., 2005]. Currently Cirrus HD-OCT versions 4.0 and 5.0 cannot be used for anterior segment structures, however, one of the latest software updates of Stratus OCT (version 6.0) can measure corneal thickness and visualize structures of the anterior chamber angle.
UHR-OCT uses broadband light sources and has an axial resolution below 5 microns in the tissue.
Intraoperative 3D SD-OCT is the current hot spot in ophthalmology. These systems are separate from the operating microscope and surgery has to be halted while performing the scans. An ideal intraoperative OCT system must be integrated into the operating microscope with a head-up display so that real-time imaging of the operative field can be made without disrupting the surgery (Tang et al., 2010). This scan measures the retinal nerve fiber layer (RNFL) thickness in a 6 x 6-mm 2 area consisting of 200 x200 pixels (axial scans). The RNFL thickness is measured at each pixel and a RNFL thickness map is generated. The optic disc (black arrow) and the cup (red arrow) are represented in the center of the scan. A calculation circle of 3.46-mm diameter consisting of 256-A scans is automatically positioned around the optic disc. It is ideal to have signal strength ≥ 6 for the scans. The scan gives an hour-pattern, quadrant-pattern and mean RNFL thickness, which are color coded (white-thickest; green-normal; yellow-borderline, and redabnormally thin). The printout gives all credible measurements about the RNFL thickness, rim area, disc area, cup-disc ratio and RNFL symmetry.
The scans of two eyes can be compared for symmetry. Latest models can detect saccadic eye movements with the line-scanning ophthalmoscope overlaid with OCT en face during the scanning. Images with motion artifact are rescanned. The SD-OCT has given a precise correlation between optic disc neuroanatomy and histomorphometric reconstruction, which in turn helps understand the pathogenesis in glaucoma (

The macular cube (Figure 3)
Generates a cube of data through a 6mm square grid by acquiring a series of 28 horizontal scan lines each composed of 512 A-scans, except for the central vertical and horizontal scans, which are composed of 1024 A-scans each. There are two versions of the macular cube, 512x128 ( Figure 3) and 200x200.

Current applications of OCT in clinical ophthalmology
Optical coherence tomography provides both qualitative and quantitative (thickness and volume) analyses of the tissues examined in-situ. OCT has been exploited in evaluating both anterior and posterior segments of the eye.
The highest impact of OCT has been in aiding the diagnosis and following the response to treatment and in patients suffering from diabetic retinopathy (DR) (Cruz-Villegas et al.

Anterior segment
There are several advantages of AS-OCT over conventional imaging methods like slit illumination, slit-scanning tomography, Scheimpflug imaging and ultrasound biomicroscopy (UBM). The imaging resolution of AS-OCT is higher than these modalities and gives high resolution cross-sectional 3D images of the anterior segment ( Another milestone in OCT technology has been development of intraoperative 3D SD-OCT in the supine position (Dayani et al., 2009). This technique has been used for intraoperative evaluation of the presence of interface fluid between the donor and the recipient corneas in DSAEK.

Ocular surface disorders
OCT can be used for assessment of conjunctival and corneal tissue planes with high axial resolution. (

Ultrahigh Resolution (UHR) OCT
Ultrahigh resolution (UHR) OCT has been more practical and advantageous over confocal microscopy in making a clear distinction between morphologic and histopathologic features between normal and abnormal epithelium in ocular surface squamous neoplasia and pterygia. This is so because OCT is a noncontact method, has rapid image capture, and provides a cross-sectional view of the tissue. One of the recent clinical applications of UHR-OCT is the identification of the opaque bubble layer as a bright white area in mid stroma in femtosecond laser-assisted LASIK flap creation (Nordan et al., 2003). This technique has been of im- OCT is not a substitute for histopathologic specimens; however, it can be a potential noninvasive diagnostic adjuvant in diagnosis and surveillance of anterior segment pathologies of the eye.

Posterior segment
OCT now has a role in varied types of posterior segment pathologies (inflammatory, noninflammatory, degenerative, vascular, traumatic, neoplastic, and metastatic) where the technique clearly defines the levels of various pathologic lesions in the posterior hyaloid, retina, retinal pigment epithelium and choroid, which in turn defines the mode and success of therapy. Such lesions may be superficial (epiretinal and vitreous membranes (Figures 6, 9 and 10), cotton wool spots, retinal hemorrhages, hard exudates ( Figure 11), cysts ( Figure 12), retinal fibrosis, and retinal scars ( Figure 13) or deep (drusen- Figure 14), retinal pigment epithelial hyperplasia and detachment (Figure 15), intraretinal and subretinal neovascular membranes (Figure 16), scarring (figure 13) and pigmented lesions).

Disorders of vitreous and posterior hyaloid
Vitreomacular traction (VMT) and vitreomacular adhesion (VMA) may be difficult to detect clinically. OCT is extremely helpful in such cases by showing hyperreflectivity. The traction by the membrane to the retina induces deformations of the retinal surface ( Figure 17).

Retinal edema
The most common primary cause of retinal thickening is edema. One of the major achievements of OCT has been quantitative assessment of retinal edema in terms of measuring its thickness and volume, evaluate the progression of the pathologic process, and monitor surgical or non-surgical intervention (Kang et al., 2004). Retinal edema may manifest in different categories: Focal or diffuse edema: Common causes include diabetic retinopathy, central retinal venous occlusion, branch retinal venous occlusion, arterial occlusion, hypertensive retinopathy, preeclampsia, eclampsia, uveitis, retinitis pigmentosa and retraction of internal limiting membrane. OCT helps in diagnosis of edema in preclinical stage when there may be no or few visible changes.
Cystoid macular edema (CME): (Figure 18) Common causes of CME include diabetic retinopathy, age-related macular degeneration (ARMD), venous occlusions, pars planitis, Uveitis, pseudophakos, Irvine-Gass syndrome, Birdshot retinopathy and retinitis pigmentosa. OCT usually shows diffuse cystic spaces in the outer nuclear layer of central macula, and increased retinal thickness which is maximally concentric on the fovea .

Retinal pigment epithelial detachment (Figure 20)
Its pathophysiology involves passage of serous fluid from the choriocapillaries to the sub-RPE space or collection of blood under RPE causing its separation and elevation from the Bruch's membrane. OCT scans show a classical dome-shaped detachment of the RPE with intact contour in early stages ( Figure 14).

Retinoschisis
It is the separation or splitting of the neurosensory retina into an inner (vitreous) and outer (choroidal) layer with severing of neurons and complete loss of visual function in the affected area (Figure 21). Typically the split is in the outer plexiform layer. In reticular retinoschisis, which is less common, splitting occurs at the level of nerve fiber layer. Retinoschisis may be degenerative, myopic, juvenile or idiopathic. Presence of vitreoretinal traction is an important cause. OCT reveals wide space with vertical palisades and splitting of the retina into a thinner outer layer and thicker inner layer (Eriksson et al., 2004).

Inflammatory lesions
OCT displays common associations of inflammation like edema, hemorrhage and scarring ( Figure 26).

Trauma and foreign bodies
Though clinical details of retinal foreign bodies may be quite discernible superficially, OCT gives a detailed description of the retinal layers affected and the sequel of impacted deeper foreign bodies ( Figure 27). The sequel of blunt eye injuries may be sub-clinical and OCT helps in determining the cause of unexplained reduced vision in such cases ( Figure 27A).

Neoplastic /metastatic lesions
OCT yields valuable information in such lesions especially when clinical examination may not be decisive due to media opacities ( Figure 29).

Limitations of OCT
As with any new technology, limitations are inherent and so are with UHR-OCT. In anterior segment, leukoplakic or hyperreflective lesions often cast shadows on the underlying tissue. This may hide the diagnosis of underlying pathology.

Future strategies in OCT
Besides having OCT integrated slit lamp, increasing scanning speed and better axial resolution which would allow us to visualize tissues at the cellular level would be and should be the objective of future OCT imaging.