Optical Coherence Tomography in Macular Diseases and Glaucoma: Advanced Knowledge Sandeep Saxena, Javier A Montero
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Application of Optical Coherence Tomography in OphthalmologyChapter 1

Soosan Jacob, MS, DNB, FRCS, MNAMS
Dhivya Ashok Kumar, MD
Athiya Agarwal, MD, DO
Amar Agarwal, MS, FRCS, FRCOphth
 
Introduction
Optical coherence tomography (OCT) was developed through a collaborative effort between the New England Eye Center, Tufts University School of Medicine, the Department of Electrical Engineering and Computer Science at MIT, and Lincoln Laboratory, MIT. It is a new, noninvasive, noncontact, transpupillary imaging technology for in vivo evaluation of retinal structures. It has a resolution of 10 to 17 microns. Similar to B-scan, it produces cross-sectional images of the tissue, the difference being that it utilizes the optical backscattering of light unlike the sound waves, which are used in B-scan. It therefore utilizes the optical properties, rather than acoustic properties of the tissues and therefore obtains a much higher resolution up to 5 microns. The anatomic layers of the retina can be differentiated and retinal thickness can be measured. It can also be used for anterior segment imaging to visualize the cornea, iris, lens and angle.1 Retinal imaging is performed using infrared light at approximately 800 nm wavelength whereas for anterior segment OCT, light of 1300 nm wavelength is used.
The image is displayed using a false color map that corresponds to detected backscattered light levels ranging between 4 × 10−10 to 10−6 of the incident light. OCT 2can be applied in a wide variety of fields other than ophthalmology.2,3,4 The ability of OCT to perform a non-excisional optical biopsy in real time giving detailed qualitative and quantitative information is its main advantage. Another advantage of OCT is its axial resolution of about 10 microns, which is 10-20 times more than standard ultrasound B mode imaging.5 Research OCT imaging systems have even higher resolution of up to 3 microns.6 The axial resolution of OCT is determined by the physical properties of the light source whereas transverse resolution is determined by the focused spot size of the optical beam and is generally around 20-25 microns. The absolute minimum spot size is limited by the optical aberrations of that particular eye, unlike in other imaging applications.7 Image resolution also depends on the speed of acquisition, pixels in the image and the basic resolution of the system.
 
Principle of OCT
Sir Isaac Newton first established the technique of low coherence or white light interferometry. OCT performs cross-sectional imaging based on low-coherence interferometry by using a continuous beam of low coherence light. This light is back reflected from different tissue boundaries and the machine measures the echo-time delay and intensity of backscattered or backreflected light from the microstructures inside the tissues. The light is backscattered differently from nonhomogenous tissues depending on their optical properties and refractive indices. Serial axial measurements are taken at different transverse positions. These signal intensities are processed by the computer and displayed as grey-scale or as a false color-coded image. In grey-scale, white corresponds to the strongest back-scattered signal and black to the weakest one. Grey scale is not as informative as the false color-coded image as computer monitors have only 8-bit grey resolution, or 256 grey levels. Also the eye has a limited ability to distinguish between subtle shades of grey.7 Post-processing of the image is possible to obtain measurements or to reconstruct topography maps. Softwares are available for different scan patterns and different image processing protocols.
 
Color Coding in OCT
A rainbow of colors are used for ophthalmic Imaging (Table 1).
Images are displayed as gray scale / false color scale. Maximum intensity signal (50dB) is displayed as white in gray scale and red in false color scale. Weakest intensity signal (95dB) is displayed as black & blue.3
Table 1   Color Coding in OCT
Layers of Retina
Back Scattering
False Color in OCT
1
NFL and Plexiform Layers
High
Red
2
Nuclear Layers
Weak
Blue to Black
3
Ganglion Cell Layer
Weak
Blue to Black
4
Outer Plexiform Layer
High
Red
5
Inner Plexiform Layer
Moderate
Green to Yellow
6
Boundary between Photoreceptor Inner Segments and Outer Segments
Thin High
Red
7
RPE
Strong
Red
8
Choriocapillaries
High
Red
 
Interpretation of OCT: The Normal Retina
The light beam of the OCT can be transmitted, absorbed or scattered depending on tissue properties. Tissues with high absorption or backscattering, such as hemoglobin, melanin etc, can cause shadowing of the underlying tissues.
As seen in Figure 1, there is an increase in backscattering at the vitreoretinal interface. The fovea is seen as a thinner area where the inner layers disappear and the photoreceptor layer thickens. Only the outer nuclear layer (ONL) and photoreceptor layer are seen in the fovea. The nerve fibre layer (NFL) is a highly scattering layer at the inner margin of the retina and is seen as red. It is thickest at the optic disc margins and is absent at the fovea.
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Figure 1: Line scan showing normal retinal architecture.
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All axonal layers, ie., the NFL and the plexiform layers are more back-scattering inner plexiform layer (IPL) – moderately back-scattering, and outer plexiform layer {(OPL) or Henle's fibre layer – highly back-scattering} and hence are seen as red whereas the nuclear layers {ganglion cell layer (GCL), inner nuclear layer (INL) and outer nuclear layer(ONL)} are poorly back-scattering and are seen as blue-black. The GCL increases in thickness in the parafoveal region. The reflection between the inner and outer segments is seen immediately anterior to the retinal pigment epithelium (RPE) as another highly scattering layer. This is due to the difference in the refractive index of the inner segment (IS) and the outer segment (OS) which contains rhodopsin. The IS and OS are thicker in the foveal region which can be seen in the OCT. The external limiting membrane (ELM) may sometimes be seen as a thin backscattering layer behind the ONL. The RPE and choriocapillaris are visualized as the posterior limit of the retina and are highly scattering, seen as red. The RPE, Bruch's membrane and the choriocapillaris cannot be identified separately. The light beam gets relatively attenuated on passing through the retinal layers and the choriocapillaris so that structures posterior to this are not seen well due to shadowing.
 
Interpretation of OCT: Optic Nerve Head (ONH)
The optic disc shows a characteristic contour on OCT (Figure 2). The NFL is thickest near the disc rim which is composed almost entirely of the NFL. The back-scattering decreases as the fibres turn to enter the optic disc, as they are no longer perpendicular to the light beam. The photoreceptor layer, RPE and choriocapillaris terminate at the lamina cribrosa.
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Figure 2: Optic nerve head scan on OCT showing a normal nerve head.
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Scanning Protocols
 
Circumpapillary OCT Scans
Boundary detection software automatically detects the NFL and its thickness is measured (Figure 3). The circumpapillary scan is “unwrapped” and the corresponding quadrants are marked. Normally, the thickest NFL layer is seen in the supero-temporal and infero-temporal quadrants. The retinal vessels may be seen as they emerge from the disc as shadowing of the posterior layers.
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Figure 3: Nerve fibre layer analysis by OCT showing a normal study.
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Radial Scans Through the Optic Nerve Head
A series of scans are taken radially, along different clock hours, all intersecting at the centre of the optic nerve head. The orientation of each is shown on a corresponding fundus photograph. The contour of the disc can be studied in each meridian. This is especially useful in conditions such as glaucoma, optic atrophy, papilledema etc. The computer software measures parameters such as diameter and area of the disc, cup and rim, cup to disc ratio etc. The nerve fibre layer thickness can be measured in each scan and different areas compared. It is thickest along the vertical scan where the superior and inferior arcuate fibres enter the disc and thinnest along the horizontal scan where correspondingly less fibres enter the disc.
 
Macular Raster Scans
These scans are useful for studying macular pathology. Six serial raster scans of the macula at fixed intervals are done and each scan is shown on the corresponding fundus photograph.
 
Macular Radial Scans
This is also useful for studying macular pathology. Six serial radial scans through each clock hour, are taken through the macula, all intersecting at the fovea. This allows the software to construct macular thickness maps.
 
Quantitative Analysis Algorithms
 
Retinal Thickness Measurement
Boundary detection software detects the anterior border of the retina at the vitreoretinal interface and posterior boundary between the IS and OS of the photoreceptors and calculates the retinal thickness. Although this doesn't measure the exact anatomical boundaries of the retina, it has good consistency in repeated measurement and therefore, is useful in follow-up of the patient.
 
Nerve Fibre Layer Thickness Measurement and Analysis
NFL thickness is measured directly from a circumpapillary scan at 3.4 mm diameter using an automated computer algorithm. The NFL and total retinal thickness are estimated at each clock hour and quadrant and also gives overall mean 7thickness. Various algorithms are used to analyze and display these measurements and comparisons with age and race adjusted normative database are given. The advantage of OCT over other optic nerve head analyzers and confocal scanning laser ophthalmoscopes is that a reference plane is not required to determine NFL thickness. Instead, it provides an absolute cross-sectional measurement of retinal substructures from which the NFL thickness is calculated.
 
Optic Nerve Head Analysis
Radial optic nerve head scans through different sectors are analyzed by software to measure diameters as well as areas of the disc, cup and neuroretinal rim and the cup: disc ratio along different meridia. The cup diameter is estimated by a line that is offset parallel and anteriorly by a standard amount to the line that defines the disc diameter.8 The optic disc profile along different sectors can also be visualized.
 
Retinal Topography
Multiple scans can be combined to reconstruct a two-dimensional topographical map of the retina. The information is displayed as a false color-coded image, which can be directly compared with the observer's view of the retina.
 
OCT in Different Situations
OCT is of great use in various ocular conditions.
  1. Measurement of optic nerve head structure.
  2. Topographic retinal thickness mapping:-Quantitatively assessing macular edema, central serous retinopathy, and diabetic maculopathy.
  3. Assessment of the size of macular hole and the presence of vitreo macular traction.
  4. Visualize the continuity of the retinal pigment epithelium and choriocapillary complex (eg) RPE defect, RPE detachment and AMD.
  5. Retinal nerve fibre analysis in evaluation of glaucoma.
 
Retinal Vein Occlusions
OCT is useful in evaluating retinal thickening, edema, presence of macular edema, intraretinal, pre-retinal and subhyaloid hemorrhages and other pathologies associated with retinal vein occlusions. It is also of prime importance in deciding 8on management and monitoring response to treatment. (Figures 4 A-B) show the colour picture and OCT of an infero-temporal branch retinal vein occlusion.
 
Non-proliferative Diabetic Retinopathy
Hard exudates and hemorrhages (Figures 5 A-B) are seen as well as retinal edema etc. OCT is of great importance in diagnosing diabetic macular edema, deciding upon management and evaluating the response to various modalities of management.
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Figures 4 A-B: A) Fundus photograph of a non ischemic inferotemporal BRVO showing flame shaped hemorrhages above the inferotemporal arcade extending to the macula. B) Increased perifoveal thickness is seen on the left side along with retinal edema. Hyporeflective cystic spaces seen in the perifoveal and foveal regions are suggestive of macular edema. Loss of foveal contour is seen.
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Figures 5 A-B: A) Fundus photograph of non-proliferative diabetic retinopathy shows hard exudates arranged in a circinate pattern with thickening of macula correlating with clinically significant macular edema. Few scattered dot and blot hemorrhages are also seen. B) Shows retinal thickening in the macular area with intra-retinal fluid accumulation in cystic spaces, seen well on the right side of the OCT. Hyperreflective areas seen with backshadowing correspond to the hard exudates.
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Figures 6 A-B: A) Fundus photograph of proliferative diabetic retinopathy shows extensive fibrovascular proliferation extending anteriorly from the disc. Old laser marks are seen. B) Shows a hyperreflective band in the preretinal area corresponding to the fibrovascular proliferation. Traction is seen on the retina with secondary retinal thickening and intra-retinal fluid accumulation in cystic space, more on the right side.
 
Proliferative Diabetic Retinopathy
Fibrovascular proliferations are seen as hyper-reflective pre-retinal bands. The presence of vitreo-retinal traction at the interface can also be appreciated as well as any secondary retinal change (Figures 6 A-B).
 
Cystoid Macular Edema
Loss of foveal contour is seen when there is retinal edema, with thickening and fluid accumulation in the form of cystic spaces predominantly in the outer plexiform and inner nuclear layers. Tissue bands, probably representing the stretched Muller cells are seen between the cystic spaces (Figures 7 A-B).
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Figures 7 A-B: A) Fluorescein angiography shows hyper fluorescent areas in the perifoveal region in a petalloid fashion which is very typical of CME. B) Line scan of the macula shows loss of foveal contour. Increased retinal thickness in the macula with multiple large optically clear low reflective cystic spaces with septae are seen in the inner retina.
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Epiretinal Membrane
Epiretinal membranes (ERM) are visible on OCT as a hyperreflective layer on the retinal surface. It may be adherent throughout its extent or may be lying separated from the retina. Any edema or retinal structural distortion caused by the membrane can also be identified.9 ERM with pseudohole can be differentiated from other similar entities. OCT is also helpful in planning for surgery10 (Figures 8 A-B and Figures 9 A-B).
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Figures 8 A-B: A) Color fundus photograph of epiretinal membrane (ERM) showing fibrous proliferation arising from the disc extending over both the arcades with contraction of the membrane seen over the macula. B) Horizontal line scan over the macula shows increased retinal thickness with an ERM covering the entire macular area with loss of foveal contour. Hyper reflecting ERM is seen over the neuro sensory retina with hyporeflective spaces showing a well defined area of separation between the inner retina and the epiretinal membrane indicating that membrane peeling is possible.
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Figures 9 A-B: A) Pre-operative horizontal line scan of the macula of a patient with high reflecting ERM. B) Horizontal line scan of patient 2 days post operatively with absence of high reflective ERM after vitrectomy and membrane peeling.
11
 
Macular Hole
The various stages of macular hole can be identified by OCT. A pseudocyst formation11,12 is the initial stage followed by full thickness dehiscence < 400 microns (Stage 2), further enlargement to more than 400 microns with subretinal and intraretinal edema at the edges (Stage 3), and finally large full thickness defects with posterior vitreous detachment in stage 4 holes (Figures 10 A, B, C).
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Figures 10 A-B-C: A) Color photograph shows a full thickness macular hole with a cuff of SRF encircled by RPE defects. B) Fluorescein angiography shows the ring of hyper fluorescence corresponding to the RPE defects seen in the color photograph. C) Line scan through the macula shows full thickness defect in the fovea with minimal SRF seen as a hyporeflective space at both edges of the hole. At the base of the hole only the RPE is seen, typical of a full thickness hole.
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Figures 11 A, B, C: A) Colour photograph of a fundus with central serous retinopathy (CSR) shows an oval area of serous elevation of the neurosensory retina in the macula. B) Fluorescein angiography shows an ink blot hyperfluorescent leak in the early phase. C) OCT confirms the serous separation of the neurosensory retina in the macula, seen as an optically clear zone between the neurosensory retina and the RPE.
 
Central Serous Retinopathy (CSR)
This is seen on OCT as the retinal layers being elevated above an optically clear fluid filled cystic space (Figures 11 A, B, C). A turbid CSR is seen in Figures 12. Any associated pigment epithelial detachment is seen as localized elevation of the hyperreflective RPE layer with shadowing of the choroidal signal behind it. Longitudinal follow-up of the patient can be done to aid in management (observation versus laser).
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Figure 12: OCT shows a turbid CSR recognized as intermediate reflective signals seen in the subretinal space.
13
 
Age Related Macular Degeneration
Drusen: These are seen as alterations in the RPE-choriocapillaris complex which cause localized distortion of this hyperreflective layer.
Geographic atrophy: This is seen as well defined areas of chorioretinal degeneration, which unmasks the larger tape shaped choroidal vessels (Figures 13 A, B, C).
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Figures 13 A, B, C: A) Color fundus photograph shows a well defined area of geographic atrophy in the macular area. B) Fluorescein angiogram shows well defined area of hyperfluorescence with late staining, but no leakage. C) Line scan through the area of geographic atrophy shows thinning of the overlying retina with increased signal seen from the underlying choroid due to attenuation of the RPE choriocapillaris complex.
14
Subretinal neovascular membrane: The findings vary depending on the type and stage of the SRNVM. They are usually seen as an enlargement or thickening, generally fusiform, of the RPE -choriocapillaris complex. Tenting of this layer is also seen. Hemorrhages and fluid filled spaces may also be seen along with disorganization of the overlying neurosensory retina (Figures 14 A, B, C).
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Figures 14 A, B, C: A) Colour fundus photograph is suggestive of a subretinal neovascular membrane. B) FFA shows a fuzzy area of leak in the FAZ in the early phase, suggestive of an occult SRNVM. C) OCT shows fusiform enlargement of the RPE – choriocapillaris complex with blunting of the foveal contour. A posterior hyaloid detachment is also seen on the left side as an intermediate reflective membrane.
15
 
Choroidal Nevus
OCT is of importance especially in following up high risk patients by monitoring the thickness and size of the nevus as well as associated secondary changes (Figures 15 A, B, C).
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Figures 15 A, B, C: A) Fundus photograph shows hyperpigmented, oval choroidal nevus in the inferonasal region with normal overlying retina. B) Fluorescein angiograpghy shows blocked choroidal fluorescence in the region of choroidal nevus with normal overlying retinal vessels. C) Line scan through the choroidal nevus shows the thickened RPE chorio-capillaris complex with increased hyper reflectivity seen in the same area.
16
 
Optic Atrophy
Retinal nerve fibre layer (NFL) analysis shows thinning of the NFL, the site as well the amount of thinning being determined by the type and extent of the optic atrophy (Figures 16 A, B).
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Figures 16 A-B: A) Color fundus photograph of optic atrophy shows marked disc pallor. B) Marked thinning of the RNFL is seen in all quadrants. Statistical analysis shows almost all parameters to be grossly abnormal.
17
 
Glaucoma
RNFL analysis is extremely useful in early diagnosis of glaucoma before perimetric loss. Loss of the double hump pattern is seen in retinal nerve fibre layer analysis. Thinning of the retinal NFL is seen, first in the supero-temporal and infero-temporal quadrants. Age matched and race matched statistical analysis is also done (Figure 17).
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Figure 17: The RNFL analysis of the right eye is within normal limits whereas the left eye shows marked loss of retinal nerve fibres predominantly in the superior and inferior quadrants and also mild loss in the temporal quadrant. There is loss of the double hump pattern in the plotting of the retinal nerve fibre layer of the left eye.
18
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Figure 18: Optic nerve head analysis shows large cup to disc ratio of around 0.8 with correspondingly decreased neuro-retinal rim area.
Optic nerve head analysis uses boundary detection algorithms to quantify cup, disc and neuro-retinal rim parameters (Figure 18).
 
Myelinated Nerve Fibre Layer
This can be seen as a hyperreflective area with shadowing of the underlying layers. An increase in the thickness of the retinal nerve fibre layer in that quadrant is also seen (Figures 19 A, B).
19
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Figures 19 A, B: A) Large areas of myelinated nerve fibre layer are seen around the disc. B) Hyperreflective signal with shadowing of the posterior layers is seen in the area of myelination.
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