Ординатура / Офтальмология / Английские материалы / Optical Coherence Tomography in Age-Related Macular Degeneration_Coscas_2009

Shortly after Optical Coherence Tomography (OCT) was introduced to ophthalmology, Podoleanu et al pioneered an OCT technique, which compiles scans along the Z (depth) axis, while fast scanning in the x-y plane (Podoleanu 19971 ).

In this system, the high-resolution OCT images are combined with the surface imaging capability of a scanning laser ophthalmoscope (SLO), produced simultaneously through splitting of the light beam at its source (OCT/ SLO) (Podoleanu 1998 2 Podoleanu 19993 Podoleanu 20004 Podoleanu 2004 5 van Velthoven 20066) (Figure 1)

This scanning technique produces longitudinal OCT scans, similar to those obtained with other OCT machines, but it is based on a different scanning strategy (Figure 2)

Coronal Scans

In addition, two-dimensional images are generated as coronal scans (ie, parallel to the retinal surface).

However, although these coronal scans are generated in a plane familiar to ophthalmologists, their highly magnified nature make them initially, more difficult to interpret (van Velthoven 2006 6).

Nevertheless, these images allow for three-dimensional visualization of the area under investigation, either mentally or by software rendering.

This coronal scanning can compensate for some of the limitations of conventional OCT, particularly precise localization of the OCT scan and extent of any longitudinal OCT scan and elimination of eye movement artifacts during image acquisition.

Both limitations make it hard to appreciate the extent of any pathological change within the area that is presumably scanned.

Exact Localization of each Scan

One of the advantages of simultaneously acquiring an SLO image and an OCT image is to determine the exact location of each scan.

The designers of the conventional OCT tried to overcome this problem by providing the operator with an infrared fundus video image displaying the scan line.

It is impossible, however, to determine the exact location of the scan, as the images are acquired sequentially and not simultaneously.

The conventional OCT also ignores any lateral eye movement occurring during the 2 seconds required to register the 512 A-scans that form a single line.

Lateral eye movements and saccadic movements occurring during image acquisition, and fixation problems can induce major artifacts As the speed of saccadic movements can exceed 900 degrees per second, if this eye movement occurs during image acquisition, the scan’s second section can be imaging a different retinal area than the first.

Fixation problems are more common with macular pathology, potentially magnifying the degrees of micro-saccadic eye movements as is evident during clinical examination. Axial movement (due to breathing, changes in muscular tension, and pulsatile blood flow in the retina and choroid) can also lead to acquisition shifts.

Within the conventional OCT, post-acquisition processing using a technique called auto-correlation provides some degree of compensation (Schuman 2004 7).

The quality of the OCT/SLO system is due to its ability to display the location and extent of any lesion in the central retinal area. This may provide anatomical clues to understand the underlying pathophysiology (Velthoven 20066)

The high quality fundus image provided by the confocal system is therefore better able to indicate the location of the longitudinal scan line.

Pixel-to-pixel correspondence between the OCT and confocal images ensures that all axial or lateral movements during image acquisition are recorded and visualized on the confocal image as a line shift or blurring.

This system has recently been commercialized by Ophthalmic Technology Inc. (OTI Toronto, Canada). The OCT/SLO is also referred to in the literature as OCTOphthalmoscope, en face OCT, or transversal OCT.

Principle of the OCT/SLO System

A schematic diagram of the OCT/SLO is shown (Figure 1)

(Podoleanu 19998, Podoleanu 20029).

Major differences with conventional OCT concern coronal scanning approach and simultaneous acquisition of

4confocal images

Two mirrors are used in the sample arm to acquire the OCT images in the x-y plane, which resembles the set-up of a confocal scanning laser ophthalmoscope (SLO).

Like conventional OCT, the OCT/SLO system uses a superluminescent diode with a central wavelength of 820 nm and a bandwidth of 20 nm (Podoleanu 19982

Podoleanu 19993 Podoleanu 20004 Podoleanu 20045 van Velthoven 20066 ).

The light beam is split, directing one arm to the patient’s eye (sample arm) and the other arm to a mirror (reference arm).

The returning light beams from the patient’s eye and the reference arm are simultaneously collected through an interferometer to produce the OCT signal.

A fraction of the light returning from the patient’s eye is directed through a pinhole to another detector to produce a confocal signal

The images are produced simultaneously at the same scanning rate, and the images in the confocal and the OCT channels therefore present strict pixel-to-pixel correspondence (Podoleanu 19998, Podoleanu 20029, Rogers 2001 10, Podoleanu 199811)

Depth (Z-axis) Resolution

Depth (Z-axis) resolution is about 10 μm and transverse (x-y plane) resolution is about 15 μm in the OCT channel (Rogers 200110).

The confocal channel provides a depth resolution of about 3 mm (Podoleanu 19998 ).

The focus in the confocal channel is not adjusted when changing the depth value in the OCT channel, and the confocal image therefore has the same appearance in all the pairs collected in the stack.

However, slight variations in the confocal images may be observed as a result of eye movements, and frame-to- frame variations can subsequently be used to correct the stack (Rogers 200012).

C-Scan and B-Scan Acquisition

Longitudinal OCT scans (also called OCT B-scans in conventional OCT) are generated from successive in-depth reflectivity profiles acquired along the Z-axis in the x-z or y-z plane (A-scans) (Schuman 20047 Hee 199513 Huang

199114).

The OCT/SLO produces coronal OCT scans (C-scans) in the x-y plane at a fixed Z-coordinate using en face flyingspot T-scan lines (Figure 2) (Podoleanu 20004).

By changing the Z-coordinate in the OCT channel, OCT C-scans can be acquired at different depths in the retina.

The OCT/SLO can also produce longitudinal B-scans along a fixed axis in the x-y plane by continuously changing the depth (Figure 2)

OCT C-scans are acquired at a rate of 2 frames per second. B-scans are acquired in one second.

The scan depth along the Z-axis is set at 1.125 mm, but can be adjusted to more than 2 mm. The acquisition rate can also be increased but at the cost of decreased image resolution.

In the current system, each scan covers an area of 24° x 24°, roughly equivalent to an area of 8 mm x 8 mm.

Confocal images and coronal OCT images are simultaneously displayed on the computer as a pair, and each part is displayed as an array of 512 x 512 pixels. The images are visualized on a personal computer in gray scale, but can also be displayed in false color.

OCT/SLO Hardware

The commercial version of the OCT/SLO is similar to conventional OCT: the operator faces the patient and the computer screen during acquisition. The patient module comprises an adjustable chin rest.

The device is mounted on a motorized table and consists of the OCT/SLO system with a joystick to move the machine vertically and horizontally, a PC, a flat screen monitor, and a foot pedal to operate the acquisition program.

The acquisition program is preinstalled, and starts up automatically when the system is turned on.

4

The patient’s pupil does not need to be dilated before scanning, although a dilated pupil facilitates scan acquisition, especially in patients with very small pupils.

C-Scan

Images are initially captured as C-scans and, by moving the device back and forth, the operator can sweep through the macula or optic nerve head and analyze the pathology in real-time.

By clicking the foot pedal, the operator can switch to OCT B-scan mode.

The OCT B-scan line can be placed at any given position along the horizontal or vertical axis by dragging the center of the line using the mouse.

Clinical use of OCT/SLO

Compared to the Stratus* OCT, this system appears to require slightly more effort from both the operator and the patient, although the examination procedure is fairly similar.

The operator must understand the combination of coronal OCT images and confocal images to take full advantage of this scanning technique.

The Confocal Image

The confocal image provides the operator with a high quality fundus image, which may reveal areas affected by a change in surface reflectivity. These areas therefore require further attention.

Scanning a patient is only slightly longer than with conventional OCT, as the scanning rate is fairly similar to single scan acquisition rates.

With the OCT/SLO, all captured images are saved, while for the Stratus*, only one image at a time is saved.

A single topographic stack of the OCT/SLO images is acquired in two seconds (similar to the time taken by the Stratus* OCT fast macular thickness protocol, which takes 1.9 seconds).

Although the OCT/SLO software offers various scan modalities, only those suitable for scanning the majority of patients are generally used.

The best option is the “Freeform Acquisition” program, which allows the operator to switch back and forth from OCT C-scanning to OCT B-scanning, as necessary.

Radial lines can also be acquired by dragging the edge of the line to the preferred angle.

During OCT B-scanning, the coronal confocal image is refreshed every 2 seconds, ensuring accurate estimation of the position of the scan line. About 100 successive scans can be saved.

Alternatively, a “Detailed Stack” can be used, which captures 50 consecutive C-scans over an operator-selected fixed distance.

The default distance for this detailed stack is 1.125 mm, with each frame separated by an interval of approximately 20 μm.

Retinal Thickness

The “Retinal Topographic Stack” can be used to evaluate retinal thickness. This program allows acquisition of either macular or optic nerve head topography maps.

It acquires a stack of 100 consecutive C-scans over a fixed distance and an area of 15° x 15° in two seconds.

The operator can choose to examine the macula at a distance of 1.125 mm, retinal thickness at 1.5 mm, or the optic nerve head at 2.0 mm, but for each option the scan depth of the stack can be adjusted from 1 mm to 6 mm.

The scan area can be modified by the operator by dragging the square to the desired position on the fundus.

The current software allows post-acquisition analysis by providing the option to localize areas of interest by either encircling the area or marking a specific point (Figure 3)

Whether the outline is made on the OCT or the confocal image, the corresponding area will be outlined in the fellow image.

On B-scans, a calliper function can be used to measure the distance between two vertical or horizontal lines (Figure 4)

4Retinal Thickness

Retinal thickness can also be measured in the topographic stack and is displayed as a two-dimensional square showing either contour lines indicating various heights.

Retinal thickness can also be measured as a grid giving 16 averaged thickness measurements as areas expressed as X by X mm (Figure 5).

Retinal thickness is defined as the thickness between the vitreoretinal interface and the retinal pigment epithelium

(ie, the second hyper-reflective layer at the outer retina).

The confocal image provides a good quality reference image for aligning consecutive topographic stacks and monitoring changes over time.

The images shown in Figure 6 are part of a stack of OCT C-scans from the right macular area of a healthy subject. Numerous retinal layers become visible at different depths, from the vitreoretinal interface to the choroid

Due to the curvature of the eye, the edge of the scan images the various retinal layers arranged inside out, with the inner and outer retinal layers visible in a manner similar to “onion rings.”

Retinal Vessels

Retinal vessels are easily recognized in the ganglion and inner plexiform layers.

They initially appear white in the more superficial layer (on the OCT C-scan) and then progressively appear darker (shadowing) on OCT C-scans of deeper layers of the retina.

As the foveal pit is the deepest part of the retina, the optically translucent vitreous remains visible as a small central dark circle.

Evaluation of the Normal Fundus

To the uninitiated, individual OCT C-scans can be difficult to interpret. As with all diagnostic imaging techniques, however, it is a matter of pattern recognition and repetition.

OCT/SLO imaging is a dynamic investigation like fluoroscopy.

When acquiring OCT C-scans, abnormal or unusual areas are often seen.

The operator must recognize these areas and capture longitudinal B-scans in these areas of interest.

The operator must be familiar with normal anatomy visualized by OCT C-scans before analyzing pathological changes.

Normal Anatomy

Therefore, the normal anatomy as visualized by the OCT C-scans must first be discussed, before disease-related OCT images are introduced.

The Retinal Layers

The following layers are progressively visualized in the macular region, around the foveal pit:

▬The highly reflective nerve fiber layer (RNFL),

▬The less reflective inner and outer plexiform and nuclear layers,

▬The second highly reflective signal represents the interface of inner/outer segments of the photoreceptors,

▬The following hyper-reflective layer is thought to be the interface with the retinal pigment epithelium (RPE) and choriocapillaris

Taken through the central fovea, the OCT B-scan of the same subject, has a more familiar appearance (Figure 7).

As previously mentioned, the confocal part of the OCT C-scan demonstrates possible movements in the coronal and longitudinal sections.

The most obvious motion artifact is blinking, which is easily recognized (Figure 8).

Rapid (saccadic) eye movements during coronal scanning are seen as an unusual “tear” or “rip” in the confocal image (Figure 9).

Axial movements caused by breathing or change in muscular tension can be seen as distortions in the coronal scan, with complete loss of the circular outline of the globe (Figure 10).

Any lateral movement during scan acquisition causes displacement of these lines, corresponding to displacement

4of the B-scan.

These displacements can be marked on the confocal image to reveal the corresponding movement in the B- scan.

Axial movement in the B-scan can be seen as partial or complete elongations in certain layers of the retina, which can be either subtle or obvious.

Recognition of these motion artifacts on C-scan images allows full use of all captured images to reveal objective information about real changes in the retina.

Example: Cystoid Macular Edema (CME)

For example, the appearance of CME on longitudinal scans is well known (Figure 11A). It can also be easily recognized on C-scans.

Two successive frames in a patient with early CME are shown (Figure 11B and C).

Since the foveal contour has changed from a depression in the macular surface to a fluid-filled mound above the retinal surface, its crest is now seen before any of the retinal layers are visualized in the C-scan.

The area affected by cystoid changes is clearly visualized and even the separate cystoid spaces can be distinguished.

C-scans also allow recognition of more limited macular edema with small cystoid spaces, as in this case of Birdshot retinopathy (van Velthoven 200515 ).

The retinal layers at the border of the C-scan (Figure 12) have an irregular shape, indicative of subtle retinal edema.

At the temporal side of the C-scan, small cystic changes are visible and their presence is confirmed on the usual longitudinal B-scan.

OCT/SLO Tomography

Follow-up

The only objective way to evaluate retinal thickness is to measure it on OCT scans.

Based on a stack of 100 consecutive fast OCT C-scans, the OCT/SLO provides a 3D rendering of an area of interest, such as in the macula (Figure 13).

B-scans are generated from this 3D stack. Although these B-scans show less detailed images than the regular OCT B-scans, the outer borders of the retina and fovea are clearly visible.

They are particularly useful to identify possible misalignment in a stack. A stack is topped with the confocal image and overlaid with a false-color scheme indicating the thickness.

Topographic images (Figure 12) are shown of the patient with CME (Figure 11)

Images were taken at the next visit following treatment

(Figure 14)

The B-scan and the C-scan (Figure 14 top) still show obvious CME, and it is difficult to accurately assess the thickness.

The topographic image (Figure 17, bottom) shows a marked decrease in retinal thickness, clearly visible in the color profile.

Topographic comparison between two different visits is also possible (Figure 15).

These comparisons are generated by first selecting both stacks, and aligning them on a larger confocal image.

This process allows comparison of exactly the same areas.

After both images are satisfactorily aligned, a comparison is given as a subtraction image.

On one side, a 2D image using a different false-color scheme is shown to indicate the loss or gain in thickness, and on the other side, a 3D contour plot showing the change in retinal thickness is generated.