Clinical Applications of Optical Coherence Tomography in Macular Diseases

Optical coherence tomography (OCT) is a new type of medical diagnostic imaging modality that performs high-resolution, micron-scale, cross-sectional tomography imaging of ocular structures in vitro and in vivo.1 Researchers at Harvard, the Massachusetts Institute of Technology, and Tufts University developed this technology. The first commercial device for use in posterior segment structures became available in 1995 (Humphrey Instruments, Dublin, CA). The OCT image has an axial resolution of 10 µm, and this resolution is significantly higher than those achieved by the scanning laser ophthalmoscope, B-scan ultrasound, and ultrasound biomicroscopy (UBM), which have image resolutions of 300, 150, and 20 µm, respectively.2

Basic Principles

Optical coherence tomography imaging is analogous to B-scan ultrasound imaging, except that it uses infrared light reflections instead of ultrasound of ocular tissues. Optical coherence tomography is based on an optical measurement technique known as low coherence interferometry, which can be used to measure distances to objects (ocular structures) with high precision by measuring the light reflected from them. The low coherence light used is produced by a superluminescent diode that is directly coupled into an optical fiber of Michelson’s interferometer. Two hundred microwatts (µW) of infrared light at 820 nm are emitted on the retina, which are consistent with the American National Standards Institute (ANSI) for intrabeam viewing.3 The interferometer divides the light source into a measurement light path, and a reference light path. The light beam is launched into the eye, and backscattered or backreflected light gives information about the distance and thickness of the different retinal microstructures.

The coherence length of the light source determines the axial resolution of the OCT, and systems used in experimental research can achieve resolutions of 14 µm in air and 10 µm in the retina.4 A high-power objective lens (+78 diopters) is used so that the retina is imaged onto an image plane

inside the instrument. Optical coherence tomography generates cross-sectional images of the internal structures by measuring the echo time delay and intensity of backscattered or back-reflected light, this measurement is analogous to A-scan ultrasound, except that light is used rather than sound. Optical coherence tomography bidimensional B-scan images are constructed by performing rapid, successive axial measurements at different transverse points, similar to B-scan ultrasound imaging. The OCT instrument has an axial scan repetition rate of approximately 400 (128 to 768) axial scans per 2.5 seconds (1 second in the commercial unit). Each A-scan consists of 1.024 pixels in the axial direction so that the current OCT integrates from 131,072 to 786,432 pixels to build a crosssectional image.

Optical coherence tomography is well tolerated because it is a noninvasive procedure, and images can be acquired rapidly without eye contact and low light intensity. The position of each scan is registered by the computer to allow future OCT examinations to be performed on the same exact location. The final OCT image is displayed using a false color map that corresponds to detected backscattered light levels from the incident light. The high reflectivity signals are represented by white and red colors, while the low reflectivity signals are represented by black and blue colors. The scattering from cataracts, vitreous hemorrhage, and corneal edema produces a reduction in image intensity; however, it does not degrade image quality except in cases of severe opacity.

Ophthalmology Applications

Optical coherence tomography is especially convenient in ophthalmology, due to the optic eye properties and easy accessibility of the retina for the exam. The OCT system hardware consists of the patient module and the computer unit (Fig. 11.1). The patient module sends the OCT scan to the retinal area of interest, and the video monitor receives and analyzes the OCT image. Optical coherence tomography has characterized a wide variety of retinal disease, and the OCT

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FIG. 11.1. Optical coherent tomographer (OCT 3000).

images correspond with the retinal morphology of these illnesses view by light microscopy.5,6 Optical coherence tomography provides a powerful adjunct to conventional fundus and fluorescein angiography (FA) that can function not only as a sensitive disease diagnostic test, but also to track disease progression and monitor treatment.

Interpretation

Optical coherence tomography is a new method of high-res- olution, cross-sectional visualization of tissue that requires appropriate knowledge of the normal anatomy of the eye fundus. Optical coherence tomography enables carrying out an “optic biopsy” because it delineates the layers of the retina (Fig. 11.2). Foveal thickness has been calculated to be 147 ± 17 µm in normal eyes with OCT.7 A highly scattering layer (70 µm in thickness), which is visible as red, delineates the posterior boundary of the retina in the tomogram and corresponds to the retinal pigment epithelium (RPE) and choriocapillaris complex.8 The nerve fiber layer appears as a highly backscattering red layer at the vitreoretinal interface. The RPE and nerve fiber layer define the posterior and anterior boundaries of the sensory retina, respectively; these boundaries are important in quantifying neurosensorial retinal thickness on OCT.9 Retinal areas of relative low reflection correspond to the location of the nuclear layers, and the photoreceptor inner and outer segments. The vitreoretinal interface can be seen in OCT images as a high-contrast boundary between the vitreous and retina. The normal vitreous gel is optically transparent and therefore not visible in OCT imaging. The choroid and RPE together match to a wide band of retinal high reflection that decreases at greater choroidal depth and sclera.

Optical coherence tomography images demonstrate reproducible patterns of retinal morphology that correspond to the

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FIG. 11.2. Optical coherence tomography (OCT) of a normal eye. It has been found that OCT enables carrying out an “optic biopsy” because it delineates the layers of the retina. (A) Pathologic anatomy of the fovea. ILM/NFL, internal limiting membrane/nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer of Henle; ONL, outer nuclear layer; OS PR, photoreceptor’s outer segments; RPE/Choriocapillaris, retinal pigment epithelium and choriocapillaris complex.

(B) Optical coherence tomography of normal macula with different layers of the retina labeled. (C) Optical coherence tomography showing the optic nerve head.

location of retinal layers seen on light microscopic.10 Layers of relative high reflectivity corresponded to horizontally aligned retinal components such as the nerve fiber layer and plexiform layers as well as to RPE and choroid. In contrast, the nuclear layers, and the photoreceptors inner and outer segments demonstrate relative low reflectivity. In the fovea, there is convergence of relative low reflection layers with only a single outer band of relative low reflection present in the center of the fovea (Fig. 11.2A,B).

Vitreomacular Traction and Epiretinal

Membranes

Optical coherence tomography can reveal macular traction in the vitreomacular traction syndrome (VMTS) associated with incomplete posterior vitreous detachment (PVD) (Fig. 11.3). Posterior vitreous detachment is visible on the OCT image as a linear reflectivity suspended above the retinal surface. The OCT tomogram can demonstrate increased retinal thickness associated with VMTS. Careful comparative analysis of OCT

11. Optical Coherence Tomography in Macular Diseases

images between visits can determine the need for or timing of surgical intervention in VMTS.11

Epiretinal membranes are visible as a highly reflective layer on the inner retinal surface (Fig. 11.4) on OCT. Optical coherence tomography provides a means to evaluate the crosssectional characteristics of an epiretinal membrane, enabling a quantitative measurement of retinal thickness, membrane thickness, and the separation between the membrane and inner retina. The OCT tomogram can help to distinguish between membranes globally adherent to the retina, and epiretinal membranes separated from the inner retina.12 Quantitative

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measurements of membrane thickness and reflectivity can be used to establish the degree of membrane opacity.6 In addition, OCT can reveal retinal distortion caused by epiretinal membrane contraction. Optical coherence tomography information such as membrane location and membrane thickness may be prognostic indicators of operative success after epiretinal membrane surgery. Preoperatively, OCT can help direct the operative approach, and postoperative imaging can be used to document surgical response. Optical coherence tomography measurements of macular thickness have been correlated with visual acuity in patients with epiretinal membranes.12

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Macular Hole

Optical coherence tomography is effective in staging macular holes, and quantitative information may be directly extracted from the OCT tomograms, including status of the vitreoretinal interface, the diameter of the hole, and the extent of surrounding subretinal fluid accumulation.4,13 Stage 1 holes may be distinguished by a reduced or absent foveal pit and the presence of an optically clear space beneath the fovea, suggesting a foveolar detachment. Evidence of traction by the posterior hyaloid on the fovea may be present. Stage 2 holes show a partial break in a surface of the retina with a small full-thickness loss of retinal tissue (Fig. 11.5) < 400 µm in size. Stage 3 holes have a full-thickness retinal dehiscence > 400 µm in size with a complete break in the outer retinal tissue, and variable amounts of surrounding macular edema that increase retinal thickness and decrease reflectivity in the outer retinal layers (Fig. 11.6). Stage 4 holes can be characterized by the complete loss of tissue >400 µm in size, and a complete detachment of the posterior vitreous. Stage 1 and 2 macular holes are very difficult to differentiate ophthalmoscopically, and

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high-resolution OCT images can help to classify them. Stage 2 often progresses to stage 3 with some visual loss; therefore, appropriate staging with OCT can help to determine when surgery is indicated.14

Vitreoretinal traction is very important in the pathogenesis of macular holes, and it can be identified by OCT.15 Furthermore, OCT may be a useful method of assessing the risk of hole formation in the fellow eye of patients with a unilateral macular hole. Duker et al.16 found vitreoretinal interface abnormalities with OCT in 21% in the fellow eye. Posterior vitreous detachment as small as 150-µm elevation over the inner retinal surface can be detected by OCT.6 In addition, macular hole size and postoperative resolution can be evaluated by OCT. Optical coherence tomography imaging has the ability to differentiate a full-thickness macular hole from a macular pseudohole, partial-thickness hole, or a macular cyst. Lamellar holes show an increased foveal pit contour with an intact outer neurosensory retina. Macular pseudoholes show a steepened foveal pit contour with intact outer neurosensory retina. Macular cysts and retinal detachments show a localized intraretinal and subretinal accumulation of optically clear serous fluid, respectively.

11. Optical Coherence Tomography in Macular Diseases

Retinoschisis and Retinal Detachment

Differentiating the diagnoses retinoschisis and retinal detachment is usually done on the basis of clinical examination, but for those patients in whom the diagnosis cannot be made clinically, OCT appears to be a useful tool. Optical coherence tomography images of retinoschisis show a splitting of the neurosensory retina consistent with classic histopathology findings, and OCT images of patients with retinal detachment show separation of full-thickness neurosensory retina from the underlying RPE.

The principal limitation of OCT in retinoschisis and retinal detachment is the difficulty in obtaining images anterior to the equator. However, most lesions posterior to the equator and lesions with a component posterior to the equator can be effectively imaged with OCT.17

Macular Edema

Optical coherent tomography is a retinal imaging technique that has applications in the diagnosis and management of macular edema produced by diabetic retinopathy, retinal vein occlusion, uveitis, epiretinal membrane, and cataract surgery.6

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In addition, OCT is able to quantify the development and resolution of macular edema after treatment (Fig. 11.7).7

Optical coherent tomography images of macular edema depict the presence of low intraretinal reflectivity, which corresponds to intraretinal fluid accumulation and is consistent with an increased macular thickness (Fig. 11.7B). Cystoid macular edema has cystic spaces that are visible as rounded low scattering areas, which typically occur in the neurosensorial retina (low reflective intraretinal areas). Retinal thickness is measured easily between the nerve fiber layer, and the highly backscattering red layer that represents the RPE/choriocapillaris complex. Hee et al.18 designed an OCT protocol for monitoring macular thickness in patients with diabetic macular edema. For each eye, six consecutive OCT scans are obtained in a radial spoke pattern centered on the fovea. Therefore, retinal thickness measurements are performed at a total of 600 points on the macular area. Macular thickness is then represented as a false color topographic map and as numeric averages over nine regions covering the macula (the OCT retinal thickness map) (Fig. 11.7D,E).

The advantages of OCT include high reproducibility and accuracy. Optical coherent tomography may be more sensitive in evaluating small changes on retinal thickness than slit-lamp examination.7 Although FA shows vascular leakage

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in macular edema, it does not provide a quantitative assessment. Therefore, patients may present with loss of vision with an increment in retinal thickness in the absence of vascular leak detectable by FA. Optical coherent tomography measurements of macular thickness tend to correlate with visual acuity in patients with diabetic macular edema, although that is not always the case depending on the chronicity of macular edema. Similar characteristics have been found in patients with epiretinal membrane (Fig. 11.4).7,12

Central Serous Chorioretinopathy

Central serous chorioretinopathy (CSCR) is characterized by serous detachments of the neurosensory retina in the macular region (Fig. 11.8A). The fovea is frequently involved, and small associated RPE detachments are commonly seen. The OCT in a neurosensory detachment appears as a shallow elevation of the retina, with an optically clear space between the retina and the high reflection of RPE/choriocapillaris, and the height

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of the cavity can be exactly measured (Fig. 11.8B).6 Examination with OCT is more sensitive to identify small elevations of the neurosensory retina than slit-lamp biomicroscopy.19 The detached RPE may be distinguished by a focal elevation of the higher reflective layer over a clear cavity (Fig. 11.8B). The detached RPE causes attenuation of the reflected light, resulting in extensive shadowing of the underlying choroidal signal. A neurosensory detachment may be connected with an RPE detachment by the discontinuity on the RPE. Longitudinal examinations with OCT can detect exact changes in height measurements of subretinal fluid, and detect CSCR resolution. Montero and Ruiz-Moreno20 recently described bulges protruded from the RPE under a neurosensory detachment in acute and chronic CSCR, which probably meant activity of the disease. Optical coherent tomography in CSCR can provide additional information and may help distinguish it from subretinal neovascularization (SRNV) and other macular diseases. Finally, OCT has been shown to be superior to biomicroscopy and FA in identifying CSCR.21

FIG. 11.8. (A) Fluorescein angiography (FA) in central serous chorioretinopathy (CSCR) shows a pinpoint area of dye leakage in the retinal pigment epithelium (RPE) and a large serous detachment under the neurosensory retina. (B) Optical coherence tomography scan through the macula demonstrates the RPE (focal leakage point on FA) and neurosensory detachment.

Choroidal Neovascularization

and Age-Related Macular Degeneration

Optical coherent topography has been used to characterize drusen, geography atrophy, choroidal and subretinal neovascularization, neurosensory detachment and RPE detachment associated with age-related macular degeneration (AMD).6,22 Soft drusen are observed as focal elevations in the external, highly reflective band (RPE/choriocapillaris complex) consistent with the accumulation of amorphous material within or beneath Bruch’s membrane. Geographic atrophy is highly distinctive on OCT because the overlying retina is thinned and the hypopigmented RPE causes increased penetration of the optical probe beam into the deeper choroid, significantly enhancing the reflections from this layer. Hyperpigmented RPE areas (hypertrophy or hyperplasia) on OCT show as high reflectivity from the RPE with shadowing of the reflections from the choroid. Intraretinal edema appears as an area of low intraretinal reflectivity, which corresponds to intraretinal fluid accumulation and is consistent with an increased retinal thickness. An RPE detachment demonstrates an elevation of the reflective band corresponding to the RPE/choriocapillaris complex and shadowing of the reflections returning from the deeper choroid. In contrast, neurosensory retinal detachments appear as elevations of the sensory retina above an optically clear space.

Subretinal neovascularization is characterized by increased optical reflectivity of the RPE or disruption of the highly reflective band layer RPE/choriocapillaris. Angiographically well-defined subretinal neovascularization is visualized as a localized disruption and fusiform thickening of the RPE/choriocapillaris reflection with defined boundaries (Fig. 11.9A,B). In contrast, occult subretinal neovascularization tends to show an irregular elevation of the RPE with a

deeper area of mild backscattering corresponding to fibrous proliferation. Laser treatment of subretinal neovascularization leads to atrophic scarring, which appear on OCT as highly reflective at the chorioretinal interface. Argon laser retinal lesions evaluated in vivo by OCT demonstrated relative high reflection in the middle of the lesion and relative low reflection around the lesion.23

Optical coherence tomography has been used to confirm subretinal neovascularization resolution after photodynamic therapy (PDT) with verteporfin (Visudyne) (Fig. 11.9C,D).24,25 Optical coherence tomography is effective in AMD because it can detect subretinal neovascularization darkened by a thin layer of fluid or hemorrhage, delineate SRNV boundaries, and quantify changes in response to therapy.

Retinal Vascular Occlusion Disease

Retinal vascular diseases are common etiologies for central visual loss. Optical coherence tomography shows increased retinal thickness with cystic spaces of low reflectivity in patients with branch retinal artery occlusion and central retinal artery occlusion. In addition, the inner retinal layers tend to be more highly reflective in OCT, probably due to ischemia of

these layers. Therefore, this high reflection causes shadowing of the optical signal of the RPE/choriocapillaris complex. The increased thickness of the inner retina typically seen in acute artery occlusions corresponds to the intracellular edema (Fig. 11.10). Optical coherence tomography complements the information obtained from FA in retinal vascular diseases.26

Occlusion of the retinal venous system is the second most common retinal vascular disease after diabetic retinopathy.27 Optical coherence tomography findings include cystic macular edema (CME), serous retinal detachment, epiretinal membranes, pseudoholes, lamellar holes, and subhyaloid or preretinal hemorrhages in branch retinal vein occlusion (Fig. 11.11) and central retinal vein occlusion (Fig. 11.12). A significant proportion of patients with occlusion of the retinal venous system have OCT evidence of CME and serous retinal detachment. Optical coherence tomography shows hyporeflective intraretinal cavities in a cross-sectional scan radiating from the center of the macula in CME (Fig. 11.11B,C). Macular edema is associated with serous retinal detachment in retinal venous system occlusion.27 Optical coherence tomography plays a pivotal role in quantitatively monitoring changes in retinal thickness after treatment such as intravitreal triamcinolone injection or radial optic neurotomy.28,29

Parafoveal Telangiectasis

Retinal telangiectasis refers to a developmental retinal vascular disorder characterized by an ectasia of capillaries of the retina, in which irregular capillary dilation and incompetence occur in the retinal periphery of the macula. Gass30 described a classification of three subgroups.

Optical coherence tomography depicts clearly the involvement of the intraretinal and subretinal spaces in this condition (Fig. 11.13). Parafoveal telangiectasis may show low reflective intraretinal areas of macular edema and highly reflective lipid exudates on OCT. Plaques of RPE hyperplasia appear as intraretinal hyperreflective spots associated with shadowing of the reflections from the tissue below. In addition, OCT may show subretinal neovascularization associated with juxtafoveal telangiectasis.26

Other Retinal Diseases and Response to Therapy

Optical coherence tomography is useful to visualize other retinal diseases such as RPE detachments with or without AMD (Fig. 11.14), subhyaloidal hemorrhages (Fig. 11.15), proliferative diabetic retinopathy with new vessels on disc (NVD) (Fig. 11.16), and cytomegalovirus retinitis with flat retinal detachment in a patient with the acquired immunodeficiency syndrome (Fig. 11.17). Optical coherence tomography enables the differentiation between types I and type II choroidal neovascularization (CNV) (Fig. 11.18). In addition, OCT enables demonstrating subretinal serous fluid accumulation and deposits in choroidal melanoma (Fig. 11.19), the natural course of drusen (Fig. 11.20), diabetic macular edema (Fig. 11.21),

and CSCR (Fig. 11.22); these conditions can be followed with OCT as well as the response to therapeutic interventions. Optical coherence tomography provides information in a reproducible way, such as monitoring the course of macular hole in degenerative myopia successfully closed with vitrectomy surgery (Fig. 11.23). Retinoschisis sometimes is very difficult to differentiate ophthalmoscopically in degenerative myopia, and high-resolution OCT images can help to demonstrate its features (Fig. 11.24).

Acknowledgments. The authors have no proprietary or financial interest in any products or techniques mentioned in this chapter. This work is supported in part by the Fundacion ArevaloCoutinho para la Investigacion en Oftalmologia (FACO), Caracas, Venezuela.

FIG. 11.24. Myopic degeneration with retinoschisis. (A) Color fundus photograph distinctly shows a myopic crescent as a white, sharply defined area where inner surface of the sclera is seen. Retinoschisis inferior to the optic disc was not differentiated ophthalmoscopically.

(B) A horizontal OCT scan obtained inferior to the optic disc demonstrates a splitting of the neurosensory retina (arrow) and separation of full-thickness neurosensory retina from the underlying retinal pigment epithelium (arrowhead).

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