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 non-contact, 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 al., 2010; Shen et al., 2010; Shousha et al., 2010]
2. 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).
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).
2.1. The optic disc cube (Figure 2)
This scan measures the retinal nerve fiber layer (RNFL) thickness in a 6 x 6-mm2 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 red-abnormally 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 (Alexandre et al., 2012; Strouthidis et al., 2009 ).
2.2. 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.
The 512 x 128 module has greater resolution in each line from left to right but less resolution from top to bottom. The 200x200 module also has 6mm square grid and acquires 200 horizontal scans each composed of 200 A- scans, except for the central vertical and horizontal scans, which are composed of 1000 A-scans each. Detailed description of the basics of OCT and its images are available on line (Wali & Kharousi., 2012) A 3-D option offers an added advantage in defining the lesions (Figure 4).
2.3. Anterior segment OCT
This is a custom-built, high speed ultra high resolution device which uses a 3-module superluminescent diode light source allowing an axial resolution of 2 to 3µm. This enables morphologic visualization of conjunctival and corneal architecture. (Shousa et al., 2011 & 2010). The noninvasive nature and quick acquisition time (seconds) makes AS-OCT an ideal imaging technique in handicapped and elderly patients.
3. 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., 2004), age-related macular degeneration (ARMD) (Mavro frides et al., 2004) and venous occlusions.
Other applications include imaging morphology and lesions of posterior hyaloid like vitreomacular traction (Figure 5), vitreomacular adhesion (Figure 6) (Kang et al., 2004), detection of fluid within and under the retina which may not be visible clinically. The retinal edema can be measured and localized to different retinal layers. Macular holes (Mavrofrides et al., 2005) and pseudoholes can be more accurately graded, defined and differentiated. Other indications include diagnosis and defining of epiretinal membranes (ERMs) (Mori et al., 2004), retinoschisis (Eriksson et al., 2004), retinal detachment, drug toxicities, RNFL thickness and optic disc parameters.
OCT should not be the only criteria for diagnosis of any ocular disease. Valid perspectives of patient’s systemic and ocular disease, clinical examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), biomicroscopy, and above all, the relevant history of the disease process should always be made partner with OCT imaging.
3.1. 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 (Dawczynski et al., 2007; Tan et al., 2011; Goldsmith et al., 2005) Recent models of AS-OCT provide topographic analysis, anterior and posterior elevation maps of the cornea and reliable pachymetric maps (Milla et al., 2011; Nakagawa et al., 2011). It is an ideal research tool to demonstrate ciliary body contraction and lens movement during accommodation (Baikoff et al., 2004).
3.1.1. Cornea and refractive surgery
AS-OCT can be used to determine presurgical parameters in planning different anterior segment procedures. These parameters include anterior chamber depth, crystalline lens rise (distance between anterior pole of crystalline lens and the line joining two iridocorneal angle lines) and anterior chamber angle morphology with reference to the scleral spur (Dawczynski et al., 2007; Tan et al., 2011; Goldsmith et al., 2005). Such parameters can also be used to analyze post-surgical chamber angle dynamics and in intraocular lens (IOL) power calculations (Dinc et al., 2010; Tan et al., 2011) Phakic IOL is becoming a very popular refractive surgery technique for treatment of high refractive errors. AS-OCT simulates the position of the phakic IOL before surgery by evaluation of anterior segment structures (Mamalis N., 2010). Postoperatively AS-OCT can visualize the contact between the collamer refractive lens and the crystalline lens (Lindland et al., 2010). In cataract surgery AS-OCT has been instrumental in analyzing the structure, integrity and configuration of corneal incisions after cataract surgery (Jagow Von & Kohnen., 2009) yielding information about corneal wound architecture, Descemet’s detachment and wound leaks. Studies with AS-OCT have also revealed that corneal epithelial closure after cataract surgery was completed in 1-8 days (Can et al., 2011; Torres et al., 2006), postoperative Descemet’s detachment occurred in 40-82% of patients on day one (Fukuda et al., 2011] and that stromal hydration persisted for up to 7 days.
AS-OCT has proved very useful in early recognition of localized or total graft dislocation in Descemet stripping automated endothelial keratoplasty (DSAEK), especially in eyes with corneal edema and limited anterior chamber visualization (Kymionis et al., 2010). The technique can also aid in diagnosis of eccentric trephination and inverse implantation of the donor (Ide et al., 2008; Kymionis et al., 2007; Suh et al., 2008). AS-OCT has been pivotal in documenting the cause of hyperopic shift in DSAEK eyes, which was induced by a high ratio of central graft thickness to peripheral graft thickness (Yoo et al., 2008). Epithelial in growth in refractive surgery can be confirmed by OCT images (Stahl et al., 2007).
OCT imaging and femtosecond laser-assisted surgeries are the most rapidly advancing technologies in modern day ophthalmology. Thickness is an important parameter in refractive surgery and no technique other than OCT can give accurate, uniform and predictable thickness measurements before, during and after surgery. The pachymetry map of AS-OCT can be used in femtosecond laser-assisted astigmatic keratotomy, LASIK enhancement and intrastromal tunnel preparation for intracorneal ring segments (Hoffart et al., 2009; Nubile et al., 2009). AS-OCT is very helpful in determining the accurate depth of the arcuate incisions, and in the postoperative follow up of patient with femtosecond astigmatic keratotomy and intracorneal ring segments. The images can explain the reasons behind unexpected postsurgical surprises (Yoo & Hurmeric., 2011). Femtosecond-assisted lamellar keratoplasty (FALK) is a highly promising refractive surgical technique that requires OCT data in accurate presurgical planning (Yoo et al., 2008). These procedures include anterior lamellar keratoplasty and deep anterior lamellar keratoplasty. AS-OCT imaging is the first step to measure the depth of anterior stromal scar and this determines the preparation of the donor and the recipient corneas. The morphology of the perfect match (donor and recipient) is confirmed by AS-OCT imaging. AS-OCT helps in careful planning of structure, thickness and shape of LASIK flap (Li et al., 2007; Rosas et al., 2011]. It is the depth of corneal incisions as obtained from AS-OCT that determines the success of new surgical techniques like femtosecond-assisted corneal biopsies, corneal tattooing and collagen crosslinking (Kymionis et al., 2009; Kanellopoulos et al.,2009; Nagy et al., 2009).
New platforms provide integrated OCT systems in the operating microscopes to perform the anterior segment procedures like corneal incisions, continuous curvilinear capsulorrhexis, nucleus softening, lens fragmentation, and focusing the laser in 3D manner in femtosecond-assisted cataract surgery (William et al., 2011; Wang et al., 2009).
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.
3.1.2. Ocular surface disorders
OCT can be used for assessment of conjunctival and corneal tissue planes with high axial resolution. (Christopoulas et al., 2007 ; Shousha et al., 2011]. The technique acts as an adjuvant tool in diagnosing ocular surface squamous neoplasia and pterygia (Jeremy et al.,2012). OCT is in potential use for diagnosis and patient follow-up during the course of medical treatment and continued watch for recurrence of neoplasia without any need for repeated biopsies. Also the technique may be helpful in determining the extent of the tumor to facilitate its complete excision. AS-OCT guided subtenon injections of drugs like triamcinolone has reduced chances of inadvertent perforations and unwanted targets.
3.1.3. Glaucoma (anterior segment)
Recently Fourier-domain OCT has been used to examine the position, patency and the interior entrance site of the anterior chamber aqueous tube shunts. This high resolution OCT shows exact position of the AC entrance relative to Schwalbe’s line and growth of fibrous tissue between the tube and the corneal endothelium. Such findings could not be seen with slit-lamp examination or lower resolution time-domain OCT. The tube position visualized by slitlamp examination differed from OCT finding (Jiang et al., 2012). OCT is also very helpful in correlating the clinical and visual field changes in glaucoma and ocular hypertension patients (Figure 7 & 8).
3.1.4. 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 immense help to refractive surgeons in analyzing the flap integrity, indistinct flap interface or epithelial breakthrough in LASIK surgery (Seider et al., 2008; Ide et al., 2009; Ide et al., 2010). 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.
3.2. Posterior segment
OCT now has a role in varied types of posterior segment pathologies (inflammatory, non-inflammatory, 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).
3.2.1. 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).
3.2.2. 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, pre-eclampsia, 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 ( Mavrofrides et al., 2004 ).
Serous retinal detachment: The cysts of retinal edema over a period of time loose their walls and merge together forming single or multiple pools of fluid within retinal layers or between retinal pigment epithelium (RPE) and the sensory retina (Villate et al., 2004.) (Figure 19)
3.2.3. 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).
3.2.4. Epiretinal membranes (ERM)
Epiretinal membranes are fibroglial proliferations on the vitreo-retinal interface (Figure 10). They may be sequel of chronic intraocular inflammations, venous occlusions, trauma, postsurgical or may be idiopathic. OCT helps in confirming such membranes (Suzuki et al., 2003; Massin et al., 2000).
3.2.5. Secondary retinal lesions
OCT is important to document the presence, degree and extent of subretinal fluid (Villate et al., 2004), assessment of the level of retinal infiltrates and detect macular edema in patients with chronic uveitis where hazy media may prevent clinical examination to find the cause of reduced vision (Antcliff et al., 2002; Markomichelakis et al., 2004).
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).
3.2.7. Macular holes
Lamellar hole: OCT depicts a homogenous increase in foveal and perifoveal retinal thickness, and presence of residual retinal tissue at the base of the hole (Figure 22).
Full thickness macular hole: Majority of macular holes are idiopathic. Other causes include trauma, high myopia, vascular lesions (DR, venous occlusions, and hypertensive retinopathy) and subretinal neovascularization. OCT features in a full thickness macular hole include complete absence of foveal retinal reflectivity with no residual retinal tissue. Thickened retinal margins around the hole with reduced intraretinal reflectivity are clearly seen in such cases (Figure 23).
3.2.8. Diabetic retinopathy
OCT features in DR include retinal edema, cotton wool spots, exudates, hemorrhages and ischemia. (Figures 24, 25)
3.2.9. Drug toxicities
OCT studies have started evaluating the retinal / macular toxic side effects of systemic drugs like hydroxychloroquine (Marmor., 2012), chloroquine (Korah and Kuriakose., 2008), tamoxifen (Hager et al., 2010), ethambutol (Menon et al., 2009 ), vigabatrin (Moseng et al., 2011) and tadalafil. (Coscas et al., 2012) Besides, the technique is being used in many research centers for studying retinal effects of a varied number of compounds in animal models.
3.2.10. Inflammatory lesions
OCT displays common associations of inflammation like edema, hemorrhage and scarring (Figure 26).
3.2.11. 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).
3.2.12. Neoplastic /metastatic lesions
OCT yields valuable information in such lesions especially when clinical examination may not be decisive due to media opacities (Figure 29).
The most exploited use of OCT has been in the field of treatment guidelines and response to therapies in diabetic retinopathy (figure 30), retinal vascular occlusions (figure 31), vascular lesions (figure 32), age related macular degeneration (figure 33), and intraocular inflammations. Physicians, who are used to OCT technology, feel more confident in diagnosing and managing such retinal disorders.
Other therapeutic applications of OCT include accurate assessment of outcome of the effect of pharmacological or surgical interventions like photodynamic therapy (PDT), transpupillary thermotherapy, vitreoretinal surgery, anti-VEGF therapy, intravitreal steroid therapy and therapeutic Intravitreal implants (Rogers et al., 2002).
Recently OCT has confirmed benefit of intravitreal recombinant truncated human plasma serine protease ocriplasmin in treatment of non-symptomatic vitreomacular adhesion including macular hole (Decroos et al., 2012; Stalmans et al., 2010). OCT stays as sheet anchor in confirmation of successful surgical closure of macular holes (Jumper et al., 2000; Sato et al., 2003). In partial or unsuccessful surgeries, OCT evaluates the retinal anatomy to find reason for poor visual outcome.
4. Pediatric ophthalmology
SD-OCT allows detection of subclinical anatomic changes in neonates and infants, although experience on its use in retinopathy of prematurity (ROP) is limited (Chavala et al., 2009; Vinekar et al., 2010; Muni et al., 2010; Maldonado et al., 2010; Lee et al., 2011). Cystoid macular edema (CME) can be detected by SD-OCT in premature infants at risk for ROP but not when using indirect ophthalmoscopy (Maldonado et al., 2011). SD-OCT could be useful in detecting CME in neonates with mild and advanced ROP (Vinekar et al., 2011). Tomographic thickness measurements of cystoid macular edema in ROP predict the risk of requiring laser treatment or developing plus disease or ROP stage 3 (Maldonado et al., 2012). OCT is proving innovative in studying the macular characteristics in amblyopic eyes where the average thickness of foveolar neuroretina has been found to be larger than that of normal eyes (Wang et al., 2012)
5. 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.
6. 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.