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

The precision of the image obtained depends on the scan

1number of deep retinal zones. The signal obtained also partly depends on the degree of absorption of light by the various retinal and subretinal structures.

The time necessary for this scanning and for acquisition of these sections is the essential determinant of the quality of the signal, hence the name of Time-Domain given to conventional OCT or TD-OCT.

Spectral-Domain OCT

of artifacts related to patient movements (eye and respiratory movements) during the examination. This rapid scanning considerably increases the number and density of scans of the retina.

The use of image processing systems based on real-time averaging reduces the signal-to-noise ratio (SNR) and increases image definition and image quality.

Comparison

Further progress is underway with the development of Spectral-Domain OCT (SD-OCT), which allows much more rapid image acquisition.

A method based on the famous Fourier transform mathematical equation (1807) eliminates the need for a moving mirror in the path of the reference beam.

In Spectral-Domain OCT, the interferences between the sample beam and the reference beam are obtained in the entire spectrum, and all frequencies are analyzed simultaneously by a spectrometer (Figure 3).

In SD-OCT, the interference signal is a function of the wavelength, and all echoes of light from the various layers of the retina can be measured simultaneously (Figure 4).

SD-OCT image acquisition is therefore much more rapid than with the conventional system (TD-OCT) and provides excellent resolution. This property enables SD-OCT systems to capture a large number of high-resolution images.

SD-OCT imaging is 50 times faster than standard TD-OCT and 100 times faster than the first ultrahigh-resolution (UHR)-OCT. As the examination can be performed simultaneously in various planes, real high-speed 3D reconstructions can be obtained with hundreds of images per second.

Rapid scanning allows a large number of B-scans to be obtained in a very short time, with a marked reduction

Comparison of images obtained with successive TimeDomain OCT systems (OCT 1; OCT 3, or Stratus) and those now obtained with Spectral-Domain systems demonstrates clearer images with higher resolution.

These SD-OCT systems have been more recently improved with the addition of various complementary functions (fundus photography, angiography, microperimetry, etc.) (Figure 6).

Various image fusion systems can be used to follow the natural history or response to treatment, sometimes even automatically by means of eye-tracking systems.

This book will discuss the applications and advantages of these systems for the diagnosis and treatment of the various forms of AMD.

The contribution of OCT is now widely recognized and applications of OCT are developing very rapidly in various fields (Figure 6).

The imaging of AMD has been considerably improved, not only for diagnosis but also for staging.

This imaging is also essential to guide the indications for current treatments and to assess the response to treatment.

OCT facilitates correlations with clinical data, angiographies, and functional investigations.

The higher resolution and more rapid scanning of SD-

1OCT provides advances in imaging (Figure 5).

The high resolution of SD-OCT images allows a better discrimination of retinal and subretinal layers.

SD-OCT imaging allows a reduction of movement artifacts, which cause distortion of the surface and the retina-RPE junction.

This more rapid image acquisition allows the creation of 3D images and more precise quantitative measurements (total volume) of macular changes (fluids, drusen, CNV, edema), allowing follow-up after treatment.

The essential improvement that has yet to be made concerns very fine interpretation of the images obtained, associated with functional investigations and statistical analysis of data derived from large series of clinical cases.

The various technological parameters have been considerably improved over recent years, allowing substantial progress in the performances of OCT imaging.

Technological Parameters

Parameters that significantly influence the research and clinical value of these imaging modalities are:

▬Axial resolution (or depth), which allows visualization of the morphological architecture of each retinal layer by means of the ultrahigh-resolution technique

allow optical biopsy while providing physiological and metabolic information about the tissues.

All these image improvements obtained by these new techniques will probably have an important role in clinical applications (Drexler 20086).

Ultrahigh-Resolution OCT

The axial resolution of OCT imaging is essentially determined by the bandwidth for the low coherence light source used for this imaging.

lar aberrations, but which, with the development of adaptive optics, could reach a sufficient level to distinguish cells themselves.

▬The data acquisition time determines the number of transverse pixels of the OCT image (and the number of OCT images or the dimension of 3D data that can be acquired) has been improved by spectral domain techniques and progress in CCD cameras

▬The sensitivity of detection determines the ease with which good quality OCT images can be acquired (particularly in the case of ocular opacities). However, rapid acquisition limits this improvement of sensitivity.

axial resolution of the image of the order of 2 μm to 3 μm compared to the standard resolution of 10 μm.

This almost cellular resolution allows visualization of each retinal layer similar to the level of resolution obtained by histopathology (Drexler 20037).

Correlation Studies

Correlation studies have been conducted between UHROCT retinal sections in pigs and monkeys with histological sections from the same animals.

(ie, it is highly dependent on the tissue studied and the imaging wavelength).

Studies are underway to visualize the choroid with different wavelengths.

▬Image contrast to improve visualization of morphological structures as an additional diagnostic parameter.

▬Functional extensions of OCT are currently under development to obtain functional retinal imaging including Doppler studies of blood flow, birefringence, spectroscopic properties, or retinal activity in response to light stimuli.

This technological progress may enable OCT to visualize tissue morphology at the cellular level, which would

histological intraretinal layers with the corresponding features on UHR-OCT.

Clinical studies have demonstrated alterations of the photoreceptor layer in various macular diseases, and one study has even demonstrated a direct correlation with functional disorders in patients with Stargardt’s disease (Ergun 20058 ).

These studies appear to confirm the potential of UHR-

OCT:

▬To improve early diagnosis,

▬Guide interpretation of images from the OCT systems already used in clinical practice,

▬Guide treatment, and

▬Contribute to a better knowledge of the pathogenesis of AMD.

Chapter 1 · Principles of OCT Examination Techniques Main OCT Systems

3D OCT

In clinical practice, the acquisition of 3D volume information constitutes a major progress, as it provides structural information.

This information can then be used to generate anteroposterior images, fundus images, and measurements of retinal thickness by mapping and volume images of retinal structures, analogous to those of MRI images.

It is now possible to visualize not only the total thickness of the retina and/or nerve fiber layers, but also the thickness of other retinal layers, thereby providing previously unknown information.

Similarly, the total volume of intraretinal fluid can be demonstrated, quantified, and monitored, allowing objective assessment of the course of the disease.

The essential parameter to obtain 3D imaging (3D-OCT) is more rapid acquisition

A remarkable improvement of OCT image acquisition has been obtained by spectral domain detection based on Fast Fourier Transform, with a significant gain in sensitivity and speed, as all A-scan signals are measured simultaneously rather than successively (de Boer 20039).

This much faster acquisition speed not only decreases eye movement artifacts on B-scans and therefore preserves the natural contours of the posterior segment, but it also allows better delineation of intraretinal layers as a result of improved axial resolution and an increased transverse pixel number (A-scan).

A series of closely spaced horizontal B-scans can be obtained to cover a volume of retina. Pilot clinical studies have been conducted with 3D UHR-OCT using the SDOCT system (Schmidt-Erfurth 2005 11 ).

Another important aspect of 3D-OCT is that it can generate a virtual image of the fundus, similar to that of fundus photography. This image of the posterior pole demonstrates the entire retinal vascular network, similar to that visualized by angiography, without the use of a contrast agent, but based on detection of the shadow projected by vessels onto the fundus image.

These 3D images allow subtraction of various parts of the retina to reveal information concerning deeper structures of the volume, which would be promising for the study of photoreceptor changes.

Segmentation

Another advantage of UHR-OCT would be objective and quantitative morphometric measurements and clearer differentiation of retinal layers at early stages of disease.

Imaging of the Choroid

Although OCT imaging generally uses a wavelength of 800 nm, this wavelength has the disadvantage of limited penetration beyond the RPE due to absorption and backscatter accentuated by melanin or opacities of the media. These absorption properties are much lower at longer wavelengths.

Imaging at a wavelength of 1050 nm would allow better penetration and better visualization of choroidal structures, facilitating earlier and more precise diagnosis (Povaz 200712).

Imaging of the choroid requires numerous technical improvements (high speed, light source, spectrometers, and adapted CCD cameras), allowing better visualization of the choriocapillaris and some choroidal vessels.

Adaptive Optics

Adaptive optics (AO) appears to be a promising approach to correct ocular optical aberrations in order to improve transverse resolution.

Over recent decades, AO is no longer confined to astronomy but is now applied in ocular optics with the use of deformable mirrors.

The combination of AO and SD-OCT can allow an axial resolution of 3 μm and a transverse resolution of 3 μm with decreased diffraction, raising hopes for resolution at the cellular level.

Numerous studies combining several technical improvements have allowed visualization of the interface, inner and outer segments, and the cone mosaic (Fernandez 2005 13 , Zawadzki 200514, Zhang 200615). The preliminary results show that the combination of AO and 3D UHROCT could achieve cellular resolution despite its marked technical complexity.

Many diseases, especially AMD, already benefit from this intense research designed to visualize the outer layers, more clearly understand and predict the various stages of the disease and its complications, and to adapt treatments accordingly.

As a result of multiple technological advances and interpretation of changes of architecture and cellular organization, morphological imaging will be completed by functional data.

Progress in OCT is a remarkable example of the advancement that can be achieved by collaboration between research scientists and clinicians for the benefit of our patients.

References

1.Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA. Optical coherence tomography. Science 1991;254:1178-1181.

2.Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, Puliafito CA, Fujimoto JG. Optical coherence tomography of the human retina. Arch Ophthalmol 1995;113:325-332.

3.Puliafito CA, Hee MR, Lin CP, Reichel E, Schuman JS, Duker JS, Izatt JA, Swanson EA, Fujimoto JG. Imaging of macular

10. Monson, B.K., Greenberg, P.B., Greenberg, E., Fujimoto, J.G., Srinivasan, V.J., Duker, J.S., High-speed, ultra-high-resolution

optical coherence tomography of acute macular neuroretin-

opathy. Br. J.Ophthalmol. 2007;91:119–120.

11. Schmidt-Erfurth, U., Leitgeb, R.A., Michels, S., Povazay, B.,

Sacu, S., Hermann, B., Ahlers, C., Sattmann, H., Scholda, C.,

Fercher, F., Drexler, W., Three-dimensional ultrahigh-resolution

optical coherence tomography of macular diseases. Invest. Oph-

thalmol. Vis. Sci. 2005;46:3393–3402.

12. Považay, B., Hermann, B., Unterhuber, A.H.S., Zeiler, F., Morgan, J.E., Falkner-Radler, C., Glittenberg, C., Binder, S., Drexler, W., Three-dimensional optical coherence tomography at 1050nm vs. 800nm in retinal pathologies: enhanced performance and choroidal penetration in cataract patients. Journal of Biomedical Optics2007, in press

13. Fernandez, E.J., Drexler, W., Influence of ocular chromatic aberration and pupil size on transverse resolution in ophthalmic adaptive optics optical coherence tomography. Optics Express

2005;13:8184–8197.

14. Zawadzki, R.J., Jones, S.M., Olivier, S.S., Zhao, M.T., Bower, B.A., Izatt, J.A., Choi, S., Laut, S., Werner, J.S., Adaptive-optics

optical coherence tomography for high-resolution and high-

speed 3D retinal in vivo imaging. Optics Express 2005;13:8532–

8546.

15. Zhang, Y., Cense, B., Rha, J., Jonnal, R.S., Gao, W., Zawadzki, R.J., Werner, J.S., Jones, S., Olivier, S., Miller, D.T., High-speed volumetric imaging of cone photoreceptors with adaptive optics spectral-domain optical coherence tomography. Optics Express 2006;14:4380–4394.

High-resolution optical imaging of objects hidden in scattering media such as the human eye is a challenging and important problem with many industrial and medical applications.

To achieve this goal and create virtually blur-free images, several imaging systems have been developed that separate photons travelling through the scattering medium in a straight line from scattered photons (Farsiu

20071 ).

Optical Coherence Tomography (OCT) first described in 1991 (Huang 19912), used this type of system and was rapidly adopted for medical applications, especially for ophthalmic imaging.

Principle

OCT imaging systems are based on the principle of low coherence interferometry (Dunsby 20033, Fercher

20034).

In this modality, a broadband light beam (or a very short wavelength coherent pulse) is split into two identical copies (Figure 1).

One copy travels through a predetermined distance in the free space (reference beam).

The other is directed into the eye and reflected back by the fundus (sample beam).

Interferometer

These two reflected beams are then incident on an interferometer, which generates a signal if the distances travelled by both the reference and sample beams are approximately equal.

This is the fundamental property of OCT systems, in which, although light is reflected back from all layers of the eye, only the photons from a preselected layer contribute to the interferometric signal.

To create axial images, the conventional time-domain OCT systems (TD-OCT) use a moving mirror in the reference beam path.

As the mirror is mechanically moved back and forth, the reference path is shortened or lengthened, creating interference images from shallower (towards vitreous cavity) or deeper (towards choroid) layers, respectively (Huang

19912, Wojtkowski 20056).

Awidely used clinical Time-Domain (TD) OCT system (marketed as the Stratus* OCT, Carl Zeiss Meditec, Dublin, CA) acquires 512 axial scans (A-scans) of 8 to 10 micron axial resolution in 1.28 seconds (Srinivasan 20065).

Amore recent technology called ultrahigh-resolution OCT (UHR-OCT) employs femto-second lasers as the light source.

This source provides images with axial resolutions of 2 μm to 3 μm, demonstrating retinal morphology in much greater detail (Pieroni 20067).

However, these systems are often slower than the TDOCT systems (approximately 150 to 250 axial scans per second). The use of femto-second lasers in a commercial OCT system is complex and expensive.

Time-Domain OCT

Optical coherence tomography imaging has improved the visualization of vitreal, retinal, and subretinal structures.

These new data have allowed considerable progress in our understanding of pathological processes (Huang 19912

Hee 19958, Puliafito 19959, Toth 199710, Toth 199711, Gallemore 200012, Ting 200213).

Time-Domain OCT (TD-OCT) has been used for evaluation and monitoring of retinal diseases.

It has also been used for evaluation of the optic nerve and nerve fiber layer, particularly in glaucoma, and for imaging of the cornea and anterior chamber (Radhakrishnan 2001 14, Nolan 200715 Hess 200516).

However, the relatively unsatisfactory signal-to-noise ratio (SNR), and the slow image acquisition have limited the applications of these systems.

Involuntary patient eye movement during the image acquisition period also reduces image quality.

2This remains a drawback even despite the use of algorithms that automatically align adjacent axial scans or eye-tracking protocols (Srinivasan 20065).

Spectral-Domain OCT

Fortunately, spectral-domain OCT (SD-OCT) is now able to acquire images much more rapidly than the classic TD-OCT systems.

This progress has been achieved by the development and utilization of a new imaging technique based on (Fast) Fourier Transformation (Paris, 1807), providing higher resolution and better SNR (de Boer 200317).

With the SD-OCT system, the interference signal is a function of optical wavelength, simultaneously measuring all echoes of light from different layers

This property eliminates the need for a mechanically “moving” mirror.

This enables the state-of-the-art SD-OCT imaging systems to capture tens of high-resolution and high SNR frames, with an axial resolution of less than 5 microns in less than one second.

SD-OCT imaging is 50 times faster than standard TDOCT and 100 times faster than previous UHR-OCT imaging systems (Srinivasan 20065).

Future SD-OCT systems will go even further, acquiring 3D scans at a speed of hundreds of high-resolution frames per second.

The use of compact, relatively inexpensive, robust, and low maintenance super-luminescent diodes (SLD) as the light source has significantly reduced the manufacturing cost and maintenance of SD-OCT systems and has

made them much easier to use ( Chen 200518, Costa

200619).

Speed

When examining a human eye with a scanning technique, speed is important because patients blink, breathe, pulsate, and move their eyes.

This limits acquisition of images within the time constraints of the device and may require adjustments for eye movements.

The rapid scanning of SD-OCT allows the number and density of axial scans on the retina to be dramatically increased ( Chen 200518, Costa 200619, Leitgeb 200520).

Comparison

Comparison of a conventional TD-OCT scan and an SDOCT scan (Figures 2A, 2B, and 2C) shows a clearer image with higher resolution.

In the time required to capture the TD-OCT image, tens of SD-OCT scans can be recorded, registered, and averaged creating an image with much better SNR.

In this chapter, we will successively study the applications of SD-OCT

▬For the diagnosis and treatment of AMD

▬By describing the advantages of this imaging system,

▬The specific features of various clinical forms of AMD, and

▬The possibility of combining SD-OCT imaging with other imaging modalities

The development of automatic image processing systems for SD-OCT and future research for the detection and prognosis of AMD will then be discussed.