Imaging in the 21st century

Ophthal. Physiol. Opt. Vol. 18, No. 2, pp. 210±223, 1998 # 1998 The College of Optometrists. Published by Elsevier Science Ltd All rights reserved. Printed in Great Britain 0275-5408/98 $19.00 + 0.00

PII: S0275-5408(97)00105-1

Imaging in the 21st century W. N. Charman Optometry and Vision Sciences, UMIST, PO Box 88, Manchester M60 1QD, UK Summary Methods which are likely to become increasingly common in the next century for producing images of the eye and related structures are briefly reviewed. Although techniques based on reflected visible light will continue to be of importance, improved versions of methods based on other physical principles will come into increasingly widespread use. Digital image recording will probably play a dominant role and it is concluded that a key feature that will be common to almost all the methods will be their capacity to provide quantitative data on the state of the eye. # 1998 The College of Optometrists. Published by Elsevier Science Ltd

Introduction

developments see, e.g. Degenhardt, 1951; Rucker, 1971; Albert, 1996; Schett, 1996). Although the ®rst fundus photograph, of a rabbit, was taken by Stein in 1885, using Leibreich's stand ophthalmoscope, to be followed soon afterwards by the ®rst photograph of the human retina (Jackman and Webster, 1886), the problems of coping with eye movements when using the slow photographic emulsions of the time meant the 19th century was essentially one in which images of the fundus were recorded by drawing, based on visual observations. Such books as Haab's Atlas of Ophthalmoscopy (Haab, 1895), later translated into English by the well-known Manchester optometrist W. B. Barker and published by the British Optical Association (Haab, 1927) helped to educate generations of ophthalmologists, doctors and optometrists into the characteristic appearances of the normal and abnormal fundus. Authors like Haab also recorded the external appearance of the diseased eye and its adnexa with exquisite coloured lithographs and black and white engravings (e.g. Haab, 1899). In contrast it would in many ways be fair to describe the 20th century as the century of the photographically-recorded ocular image. While the design of direct and indirect ophthalmoscopes using purely visual observation showed steady progress, Gullstrand's development of a way to record re¯exfree fundus images with his indirect ophthalmoscope (Gullstrand, 1911) led directly to the Zeiss-Nordenson fundus camera (Hartinger, 1930). This used a carbon

Until the 19th century, examination of the living eye was e€ectively con®ned to an external inspection. The development of the ophthalmoscope by the great Hermann von Helmholtz in 1850 marked the opening of a new era (von Helmholtz, 1851). For the ®rst time it was possible to observe the optic disc, the complexities of the retinal vasculature and all the other features of the normal and diseased fundus. It is of interest that not all contemporary ophthalmologists approved of Helmholtz's novel device. His biographer, Koenigsberger (1906) remarks `One distinguished surgical colleague told Helmholtz he should never use the instrumentÐit would be too dangerous to admit light into a diseased eye; another was of the opinion that the mirror itself might be of service to oculists with defective eyesightÐhe himself had good eyes and wanted none of it.' Such views continued to be held by many ophthalmologists in the years immediately following the introduction of the ophthalmoscope, but gradually the enthusiasm of such eminent ®gures as Von Graefe, Donders and Bowman spread more widely. Rotatable discs containing lenses were added to the direct instrument as early as 1852 and the same year saw the ®rst indirect ophthalmoscope, designed by Ruete. The `electric' ophthalmoscope, incorporating a battery-powered light bulb, appeared in 1885 (for reviews of these Received: 5 November 1997

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Imaging in the 21st century: W. N. Charman arc source and for the ®rst time allowed retinal photographs to be taken on a routine basis. Subsequent developments in optical design, use of infra-red for setting up, electronic ¯ashes and fast colour ®lms have led to simple recording of wide-angle fundus views, without the need for mydriatics: ¯uorescein angiography has further widened the scope of retinal photography by revealing details of retinal circulation (e.g. Rosen, 1969). The other major 20th century optical method of imaging the ocular structures is, of course, the slitlamp biomicroscope. Although microscopes had been used earlier, it was Gullstrand who in 1911 introduced the concept of the slit beam, using the newly-available arti®cial light sources. Progressive incremental improvements in design have produced the versatile instruments available today which have the potential to examine both the anterior eye and the retina and to record permanent photographic images of the details seen (e.g. Brandreth, 1978; Tate and Sa®r, 1988). Application of the ideas put forward by Scheimp¯ug in 1906 (see, e.g. Brown, 1969; Hockwin et al., 1990) in which a tilted ®lm plane is used to overcome the problem of the limited depth-of-focus of the slit-lamp microscope has allowed extensive photo-documentation of lens shape changes during accommodation and the development of cataract (see, e.g. Henson, 1991 for review). What, then, are likely to be the changes in imaging technology that occur in normal clinical consultingroom practice during the 21st century? Clearly much will necessarily depend on the model of primary eye care that emerges in coming decades. The more sophisticated the role of the optometrist, the greater the need for more complex instrumentation. For the present purposes it will be assumed, possibly erroneously, that only modest changes in basic current practice patterns are likely to occur, but that the practitioners will ®nd it desirable to further improve the equipment that they have in their practices. Crystal balls are notoriously cloudy, but it is already possible to see trends developing that appear almost certain to strengthen in the future. Many of these depend directly on the steadily increasing speed and power of computer technology, allied to its decreasing price: in contrast the cost of optical and mechanical components is likely to remain static.

Extending present technology: improvements in image recording and analysis As the 20th century nears its close, it is already evident that future years will see a much greater use of digital image recording (image capture) for slit-lamps and fundus cameras in place of photographic records,

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using charge-coupled device (CCD) or similar cameras allied to computer storage. The ®rst commercial systems of this type are already available (Morgan et al., 1997). Electronic cameras have the obvious advantages of e€ectively instant readout and higher sensitivity than ®lm. At present ®lm has greater resolution, but rapid strides continue to be made in extending the number of picture elements recorded by CCDs so that even this advantage of ®lm is likely to disappear. Greatly increased computer memory capacity will make it easy to store the large amount of data in these detailed images. Although it will be possible to call up these digital records on screen or to print them out for straightforward visual examination, their chief virtue will be that they will provide quantitative information on the local re¯ectance of each small area of retina which can then be directly manipulated in various ways. Thus, such features as the brightness and contrast of the image might be adjusted to enhance the visibility of features of interest, using methods that are now well developed (e.g. Peli, 1989; Goldbaum et al., 1990; Low, 1991). It is of interest that the image processing techniques which are beginning to be used on diagnostic imaging also seem capable of allowing the partially sighted to use their residual vision more e€ectively (e.g. Peli, 1992; Roelofs, 1997). Alternatively, it will be possible to explore the local spectral re¯ectance characteristics of, for example, the retina in order to reveal speci®c features more clearly (e.g. Cullen, 1971; Hoyt et al., 1972; Delori et al., 1977; Miller and George, 1978; Ducrey et al., 1979; Norden, 1979; Abadi and Dickinson, 1983; Kilbride et al., 1989; Abadi and Cox, 1992; Delori, 1994). More signi®cantly, through the application of increasingly sophisticated image processing algorithms, it will be possible to quantify in a straightforward way such important fundus attributes as disc topography, areas of exudates in diabetic retinopathy, the opacities associated with cataract, or other features (e.g. Gilchrist, 1987; Rehkopf and Warnicki, 1990; Cox and Wood, 1991a,b). This in turn means that it will be easy to grade the severity of any condition and to have quantitative estimates of the changes that have occurred in the eye between successive visits. The images would, of course, be stored to allow retrieval of past records at any time for comparison purposes. Clearly such technology has great potential in such areas as diabetic screening. Perhaps, however, the most exciting prospect is the possibility of using expert computer systems to examine the images and supply a preliminary diagnosis. If an experienced observer can examine an image and place its characteristics in one of a variety of disease categories so, in principle, can a computer. Thus we

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can envisage a situation where an image is acquired, possibly by an ophthalmic assistant, and then analysed by computer to be delivered to the optometrist's chairside monitor with not only the patient record, but also a preliminary evaluation of whether the fundus appears normal or not and, if not, what the condition is likely to be and an indication of what diagnostic tests might be desirable to further re®ne the diagnosis. The input to the expert system might well include additional data on ®elds, pressures or other parameters, again gathered by optometric assistants. Where appropriate, input by voice, rather than keyboard will help to speed the whole process. Interesting questions arise concerning the possible cost of such expert systems. It might be that these will only be within the reach of larger concerns and that the individual practitioner may ®nd it dicult to keep up with advances in technology. Alternatively, the maintenance of such systems might give a new role for the professional bodies. Certainly it is likely that, with rising consumer concern and litigation on matters of alleged professional negligence, courts will expect that properly documented images of patients' ocular characteristics at the time of any examination will be available for scrutiny.

Improvements in retinal imaging: scanning devices Although optically-conventional cameras, in which the whole image ®eld is recorded simultaneously, seem assured of a continuing future, the last two decades have seen steady development of devices based on scanning, the image being built up sequentially with time. With their cost reducing with larger scale production, these instruments seem likely to play an important role in at least some larger practices. Several di€erent designs are now available: Figure 1(a) illustrates one version (Webb et al., 1987). A low-power beam of laser light is shone into the eye via two scanning mirrors: because the beam is of small diameter, no pupil dilation is required and the depthof-focus is large. Rotation of the two mirrors makes the spot of light on the retina trace out a raster analogous to that formed when generating a TV picture. The successive, small regions of the retina each re¯ect the incident light, so that at any instant the re¯ected ¯ux is proportional to the local re¯ectance. In the confocal instrument illustrated, this re¯ected ¯ux passes back out through the full eye pupil and the scanning mirrors, to be refocussed onto the confocal aperture. The light passing through this aperture, to be recorded by the light detector, is thus directly proportional to the local retinal re¯ectance. A raster picture of the fundus can therefore be built up by using the detector sig-

nal to modulate the beam of a synchronously-scanned television monitor. It is obvious that the ®eld covered by the instrument can be varied by altering the scan angles of the mirrors and, with the use of high-sensitivity light detectors, light ¯uxes on the retina can be kept low. Observation at a variety of wavelengths, including the infra-red, is possible by changing the laser and detector and small changes from the confocal arrangement can enhance the visibility of particular retinal structures (e.g. Webb, 1990; Woon et al., 1992). Studies of photopigment distribution are possible (Tornow et al., 1997) and, uniquely, use of the infra-red may allow observation of the fundi of patients with dense nuclear cataracts (Manivannan et al., 1994). However, perhaps the most interesting feature of the SLO is that, by appropriately modulating the incident laser beam, letters or other patterns can be projected onto the retina (Figure 1(b)). Evidently, if the laser is switched o€ at a particular part of its scan, that area of the retina will not be illuminated and a corresponding dark patch will be seen by the patient as well as appearing dark in the monitor image. A computer is used to provide the appropriate sequence of modulating signals and the projected Amsler grids, acuity targets or reading material can be used to assess a variety of aspects of visual function, while simultaneously allowing the ®xation of the patient to be followed on the monitor screen (Timberlake et al., 1982; Mainster et al., 1982). It is, of course, straightforward to record the video images for later analysis if required. One of the most promising areas is the investigation of reading in those with nonspeci®c reading diculties or partial sight, since the recorded images directly show the patients' changes in ®xation (Timberlake et al., 1986, 1987; Culham et al., 1992). A variant of the SLO is the laser topographic scanner (Bille et al., 1990). Here a highly confocal arrangement is used to obtain a very small depth of focus. The 3-D-topography of the optic disc is then explored, using the small depth-of-focus to `slice' the disc image into a series of sequential layers so that a variety of quantitative measurements of disc cupping and other parameters can be made (e.g. Dreher et al., 1991; Fitzke and Masters, 1993; Plesch et al., 1990; Hald et al., 1997). Further quantitative information on the retina can be obtained by adding polarising components to the SLO, when measurements of the thickness of the nerve-®bre layer become possible (e.g. Weinreb et al., 1990; Hollo et al., 1997; Marra€a et al., 1997).

Imaging small scale structures While it seems reasonable to suppose that more re®ned versions of common existing instruments will

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Figure 1. (a) Schematic diagram of a confocal scanning laser ophthalmoscope (SLO) (reprinted with permission from Henson, 1991). (b) Example of SLO image showing a letter stimulus obtained by modulating the scanning beam (reprinted with permission from Mainster et al., 1982 courtesy of `Ophthalmology').

continue in use, as described above, it can be expected that there will be an increasing clinical demand for instruments with improved resolution. The advantages of being able to resolve single retinal receptors in both the normal and pathological eye are obvious. Similarly, given the possible involvement of optometrists in monitoring and treating anterior segment problems, it would prove immensely valuable to be able to visualise cell or other changes over the full thickness of the cornea, from the epithelium to the endothelium, that might occur as a result of pathology, contact lens wear or refractive surgery. Instrumentation now under development holds promise of providing such resolution for the 21st century optometrist.

Adaptive optics At the present time, the quality of retinal images is constrained not only by the quality of the fundus camera or other device used to record the image, but also by the optics of the patient's eye, since these form part of the overall imaging system. The aberrations of the patient's eye have, then, in the past limited our ability to resolve small fundus features, although it has, very recently, been demonstrated that individual retinal receptors may just be resolved in at least some eyes having low levels of aberration (Marcos et al., 1996; Miller et al., 1996; Roorda et al., 1997). Unfortunately, while from the point of view of di€rac-

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Ophthal. Physiol. Opt. 1998 18: No 2 Figure 2(a) shows the principle of the method. For an emmetropic eye, light from any point on the retina ought to emerge from the eye as a parallel beam of rays, corresponding to a series of plane wavefronts. Ocular aberration, however, causes the rays to be nonparallel and the wavefronts to be distorted, that is there is a phase variation across the wavefront. If these e€ects can be measured for the eye of each patient, e.g. by a Hartmann-Shack wavefront sensor (Dreher et al., 1989; Bille et al., 1990; Liang et al., 1994), then the ocular wavefronts can be `¯attened' by an appropriate adaptive system which provides equal and opposite aberrations. Two of these are currently available: a liquid crystal device, in which the local phase of the wavefront is adjusted to give a ¯at emergent wavefront (Bille et al., 1990; Artal et al., 1996), and one based on a mosaic of small mirrors, where adjustment of the height of each mirror achieves the same phase correction (Liang et al., 1997). Early results with such technology already show the promise of such methods in improving the ocular point-spread and modulation transfer functions with large pupils (Figure 2(b)). Further improvements need to be made, but there is every prospect of success and it is evident that the ability to see individual receptors in the living eye could greatly enhance our understanding of both the normal and abnormal retina. Confocal microscopy

Figure 2. (a) Basic arrangement for improving fundus image quality using adaptive optics. The wavefront errors are detected by the Hartmann-Shack lens array and CCD and appropriate signals to compensate for these aberrations are sent to the deformable mirror. (b) Examples of the improvement in ocular MTF as a result of use of adaptive optics. Note that corrected performance approaches the diffraction limit quite closely. (Reprinted with permission from Liang et al., 1997).

tion the best fundus images ought to be obtained with the largest eye pupils, ocular aberrations are largest under these conditions. Hence, with these pupils, normal overall resolution is well below the limit set by diffraction. The last few years have seen an exciting new approach to overcome this problem. This involves the use of adaptive optics, in which the large-pupil aberrations of the patient's eye are actively compensated for in the observing system to yield retinal images of greatly improved clarity, so that in future it should be possible to visualise individual retinal receptors in the living eye.

Imaging thick, living biological structures with conventional high numerical aperture microscopes of adequate resolution has always been dicult. The limited depth-of-focus of the microscope objective restricts clear imagery to a shallow depth-zone of the specimen and yet out-of-focus light scattered or re¯ected from above and below the in-focus region often reduces the contrast so much as to make the detail of interest undetectable. A well-known example of this occurs in the examination of the corneal endothelium, where the ingenious optics of the specular microscope are required to prevent the endothelial image being swamped by light re¯ected from the tear layer (e.g. Maurice, 1968; Sherrard and Buckley, 1983; Hodson and Sherrard, 1988). The confocal microscope works by collecting light only from the region of the object which is in clear focus. Although several versions exist, involving both slit and point sources (e.g. Wilson and Sheppard, 1984; Masters, 1990, Chap. 10 and 11; Webb, 1991; Cavanagh et al., 1993; Koester et al., 1993; Massig et al., 1994; Masters and Thaer, 1994; Auran et al., 1995), Figure 3(a) shows one arrangement (known as a tandem scanning confocal microscope) in which a point of light is scanned across the area of interest.

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Figure 3. (a) Schematic diagram of a tandem confocal microscope (reprinted with permission from Cavanagh et al., 1993 courtesy of `Ophthalmology'). (b) Example of confocal image of the living cornea showing stromal keratocytes and nerves (reprinted with permission from Jester et al., 1990).

This is based on the same Nipkow disc technology which was used by Logie-Baird in his early television equipment. The succession of small holes on the upper area of the rotating disc sweep out a raster, which is imaged onto the specimen. The upper and lower holes of the disc are conjugate to one another so that this same raster, modulated by the re¯ecting characteristics

of the specimen, is recorded by the viewing camera. Since the holes are very small, only light from details which are precisely focused can pass through the lower pinholes. Thus this confocal arrangement means that the problem of unwanted light from the out-of-focus layers of the specimen is eliminated. Instruments of this type are capable of producing beautiful high-mag-

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ni®cation images of the epithelium, endothelium, nerves, keratocytes and other features of the normal and abnormal cornea (Figure 3(b)), and further improvements in their performance and ease of use for observing details of both the cornea and lens can be expected.

Biometry Ultrasound The early work of Mundt and Hughes (1956) showed the potential value of ultrasonography in the examination of the eye and the method is a now a well-established technique that is in routine use, mainly in hospital eye departments (see for reviews, e.g. Coleman and Abramson, 1981; Shammas, 1984; Storey, 1988; Charman, 1991; Calderon, 1991; Messner, 1991; Fledelius and Jensen, 1992; FrazierByrne and Green, 1992; Atta, 1996). A-scan (amplitude-modulation) ultrasonography is probably chie¯y employed as part of the methodology for establishing the power of intraocular lens required following cataract extraction: it has also found considerable use in biometric studies of the development of the refraction of the eye (e.g. Sorsby et al., 1963). B-scan (brightness modulation), in which a cross-sectional image of the eye is produced, is of particular value in the diagnosis of such conditions as retinal detachment, vitreous haemorrhage or tumours. B-scan can give information on the contents of the globe and orbit when conditions such as corneal scarring, cataract or haemorrhage make the eye optically opaque. Doppler methods (Baker, 1970; Marmion, 1986) can be used to detect blood ¯ow (Lieb et al., 1991; Ho et al., 1992; Mawn et al., 1997) and the motion of ¯uids within the eye and extraocular muscles (Canning and Restori, 1989). More recently, improvements in equipment design are allowing much higher quality high-frequency (50± 100 MHz) ultrasound images of the anterior segment to be produced (Pavlin et al., 1991; Silverman et al., 1995) (Figure 4). In general, it seems probable that future use of ultrasound will continue to be concentrated in hospitals rather in general optometric practice. Optical coherence tomography (OCT) OCT is an optical imaging modality that has undergone rapid development over the last few years and is now beginning to produce a substantial amount of new clinical information (e.g. Fercher et al., 1997). It can be simply ®tted into a standard slit-lamp microscope and therefore holds real promise of becoming a standard piece of equipment.

Figure 4. A high-resolution ultrasound image of the anterior chamber angle of a normal eye. C: cornea; S: sclera; AC: anterior chamber; CP: ciliary processes; PC: posterior chamber; L: lens. The large white arrow points to the iris insertion. The small white arrow indicates the termination of Descemet's membrane at the Schwalbe line. Black arrowÐ scleral spur; arrowheadÐiris pigment epithelium. 50 MHz transducer. (Reprinted from Sokol et al., 1996, with permission courtesy of `Ophthalmology').

In many ways OCT is reminiscent of ultrasonographic methods, but it depends on rather di€erent physical principles. The light used comes from a superluminescent diode. Such sources produce quite short wavetrains of light (i.e. their spectral bandwidth is relatively large, about 25 nm). Thus each wavetrain emitted can be visualised as being a short `pulse' of light about 20 mm long. The amplitude of the wavetrain is divided so that part is sent into the eye, to be re¯ected by, for example, the di€erent layers of the retina. Thus this re¯ected eye beam contains a series of similar re¯ected pulses or wavetrains, spaced apart at distances corresponding to twice those of the re¯ecting layers. The other part of the wavetrain is sent down a reference path (Figure 5(a)) where it is re¯ected by a mirror and is then recombined with the eye beam. If the two optical paths are equal in length, the two matching wavetrains will interfere constructively, otherwise they will overlap with di€erent wavetrains to give a much lower resultant intensity. Hence by steadily moving the reference mirror to increase the reference path, constructive interference is given each time the reference wave overlaps with one of the re¯ected waves. A plot of the received signal against time (which e€ectively represents the position of the reference mirror) is, then, with suitable calibration a plot of the positions of the re¯ecting layers. In practice if the beam that is incident on the retina is scanned along a straight-line path the results can be displayed rather

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Figure 5. (a) Arrangement of equipment for optical coherence tomography. (b) Examples of the fundus appearance and the associated retinal section obtained by OCT. In the originals, the intensities are colour-coded (reprinted with permission from Puliafito et al., 1995).

like an ultra-sound B scan, with the brightness or colour of each point on the display indicating the received light signal, to give direct visualisation of a cross-section of the retina (Figure 5(b)). Alternatively a circular scan path around the optic nerve head has been used to indicate possible nerve ®bre defects. Depth resol-

ution is currently about 10 mm and the images take about 2.5 sec to acquire. Work carried out to date using OCT indicates the great potential of the method in studying a variety of vitreoretinal disorders (e.g. Hee et al., 1995a,b, 1996; Schuman et al., 1995; Pulia®to et al., 1995; Krivoy et

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al., 1996; Wilkins et al., 1996). The method may also be useful in the examination of the anterior eye (Izatt et al., 1994).

Other simpler imaging modalities Although it seems unlikely that they will play more than a specialist role, several other imaging techniques exist which can provide important and unique information. One of these is infra-red thermography (Morgan et al., 1993) in which the infra-red radiation passively emitted by the eye is used to generate the image. The method has already been shown to have value in, e.g., the examination of dry eye (Morgan et al., 1995) and recording the ocular temperature changes which occur in laser refractive surgery (Betney et al., 1997). The technology of infra-red detectors is advancing rapidly and it is probable that the price of thermal cameras will reduce and their sensitivity and resolution increase in the next century. A variety of ¯uorescence methods applicable to both the fundus and the anterior eye seem capable of considerable development (e.g. Masters, 1990, Chaps 14, 15, 17, 19, 30), while laser Doppler methods allow mapping retinal blood ¯ow (e.g. Petrig and Riva, 1988).

Beyond the consulting room A number of very sophisticated imaging techniques have been developed in the last few decades which seem certain to become even more important in the future (see for reviews, e.g. Gonzalez et al., 1986; Marg, 1988; Masters, 1990; Thimons, 1991; Charman, 1991). All again depend upon using computing power to extract a 3-D image of ocular and related structures from signals which arrive dispersed in time. While both capital and running costs of this imaging technology will almost certainly continue to con®ne it to hospital use, optometrists and others will undoubtedly need to appreciate its strengths and limitations in order to interpret correctly the images that appear in the literature.

which both the X-ray source and detectors move systematically between di€erent viewpoints have only been available more recently (e.g. Houns®eld, 1973; Ambrose, 1973; Hillal et al., 1981; Steward, 1987). CT scans are particularly useful for imaging bone, intracranial haemorrhaging, the contents of the orbit and calcium-containing tumours, such as retinoblastoma (Burden and Bryant, 1997) with resolution of the order of a millimetre.

Magnetic resonance imaging (MRI) This uses a magnetic ®eld and radio-frequency waves to map the concentration of particular nuclei (usually hydrogen associated with water molecules) in the body (Jay, 1989; Charman, 1991; Gadian, 1995). Details are beyond the scope of this review, but the signi®cant feature is that soft tissue is imaged better than in CT, while bone is seen better in CT (e.g. Tower and Oshinskie, 1989; Albert et al., 1994). Steady advances are being made in the resolution of MRI images, which depending on the exact methodolgy used can now reveal substantial amounts of detail, with resolutions of about 0.5 mm being reached (e.g. Cheng et al., 1992; Mashima et al., 1996). Figure 6 shows an example of the image quality that can currently be achieved (Cheng et al., 1992). Interesting work is being carried out in relating the infarcts revealed by this method to visual ®eld defects found by classical plotting techniques (e.g. Horton and Hoyt, 1990; McFadzean et al., 1994)

Computed tomography (CT) scans Conventional X-rays, with each image obtained from a ®xed viewpoint, have been available throughout the 20th century (e.g. Trokel, 1981). In X-ray images, the more dense the structure (e.g. bone) the whiter it appears on ®lm, while less dense structure (e.g. air) appears darker: contrast can, however, be manipulated by the use of radio-opaque dyes. CT scans, in which any desired 2-D section or `slice' can be obtained from 3-D images built up by complex computer processing from a series of recordings in

Figure 6. Examples of in vivo MR images of hyperopic (A) and emmetropic (B) eyes. The upper views are axial sections, the lower views coronal. (Reprinted with permission from Cheng et al., 1992)

Imaging in the 21st century: W. N. Charman A more recent development is functional MRI (fMRI), in which changes in local brain blood ¯ow caused by various stimuli are recorded, it being necessary to subtract the image for the `steady state' brain from that of the `stimulated' brain to demonstrate the regions where enhanced blood ¯ow occurs. Early work (Belliveau et al., 1991) involved the investigation of activity in the visual cortex in response to visual stimuli. The method has since been extended and improved to map brain activity occurring as a result of a variety of tasks (see, e.g. Turner and Jezzard, 1994; Cohen and Bookheimer, 1994) and promises to become increasingly useful in the future.

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Conclusions It is evident from the above that, as the 20th century draws to its close, the foundations have been laid for the employment of a wide variety of relatively novel methods of imaging the eye and related structures, almost all of which are capable of yielding quantitative data rather than merely delivering an image. While some may remain con®ned to the research laboratory and large hospital, others hold real promise in assisting the optometrist in practice in delivering more e€ective eye care.

References Positron emission tomography (PET) Like functional MRI, PET is of value in making it possible to reveal regions of enhanced blood ¯ow and metabolism in the active brain that occur in response to speci®c visual, auditory or other stimuli (e.g. Raichle, 1986, 1987, 1990). Thus, for example, it is possible to show which parts of the brain are involved in processing pattern or colour information (Fox et al., 1986; Lueck et al., 1989; Roland and Gulyas, 1994), albeit with poor temporal resolution. The method depends on the introduction of a substance containing short-lived radioactive atoms into the body. If this substance is made use of in the relevant physiological processes occurring in the excited areas of the brain, the sites of the positron-decays of the nuclides can be mapped via the associated gamma-ray pair formed when the positron annihilates with an electron, using an appropriate detector array surrounding the head, so that a 3-D image can be built up. Resolution is of the order of 2 mm, this being limited by the fact that the positrons travel a distance of this order before they annihilate. PET is an expensive technique, since a cyclotron is necessary to generate the short-lived radionuclides used, as well as the actual imaging equipment. The closely-related, but rather cheaper, technique of single-photon-emission computed tomography (SPECT) also holds promise of greatly enriching our understanding of the roles of di€erent regions of the brain in relation to vision (e.g. Jaszczak and Coleman, 1985; Coleman et al., 1986; Hung et al., 1990). These more recent methods for studying brain function are likely to be complemented by improvements in electroencephalography and magnetoencephalography, both of which can provide much higher levels of temporal resolution that fMRI and PET (e.g. Gevins et al., 1995), albeit with poorer spatial resolution. One of the challenges of the 21st century will be to properly interpret the information given by the application of all of these remarkable methods (Sergent, 1994).

Abadi, R. V. and Cox, M. J. (1992). The distribution of macular pigment in human albinos. Invest. Ophthalmol. Vis. Sci. 33, 494±497. Abadi, R. V. and Dickinson, C. (1983). Monochromatic fundus photography of human albinos. Arch. Ophthalmol. 101, 1706±1711. Albert, D. M. (1996) The ophthalmoscope and retinovitreous surgery. In: The History of Ophthalmology, (eds D. M. Albert and D. D. Edwards), Blackwell Science, Cambridge, Mass., Chap. 10, pp. 177±202. Albert, D. M., Jakobiec, F. A. and Robinson, N. L. (1994) (eds) Principles and Practice of Ophthalmology: Vol. 5 Clinical Practice, Section XVI, Diagnostic imaging, Saunders, Philadelphia, pp. 3505±3599. Ambrose, J. (1973). Computerized transverse axial scanning (tomography), part 2: clinical applications. Br. J. Radiol. 46, 1023±1047. Artal, P., Vargas, F. and Iglesias, I. (1996) Wavefront correction in the human eye with liquid crystals. OSA Annual Meeting, 20±24 October 1996, Rochester, p. 82. Atta, H. R. (1996) Ophthalmic Ultrasound: A Practical Guide. Churchill Livingstone, London. Auran, J. D., Koester, C. J., Kleiman, N. J., Rapaport, R. A., Bomann, J. S., Wirotsko, B. M., Florakis, G. J. and Kniarek, J. P. (1995). Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea. Ophthalmology 102, 33±41. Baker, D. W. (1970). Pulsed doppler blood-¯ow sensing. IEEE Trans. Sonics Ultrason. 17, 170±185. Belliveau, J. W., Kennedy, D. N., McKinstry, R. C., Buchbinder, B. R., Weiskopf, R. M. and Cohen, M. S.et al. (1991). Functional mapping of the human visual cortex by magnetic resonance imaging. Science 254, 716±719. Betney, S., Morgan, P. B., Doyle, S. J. and Efron, N. (1997). Corneal temperature changes during photorefractive keratectomy. Cornea 16, 158±161. Bille, J. F., Dreher, A. and Zinser, G. (1990) Scanning laser tomography of the living human eye. In: Non-Invasive Diagnostic Techniques in Ophthalmology (ed. B. Masters), Springer, New York, Chap. 28, pp. 528±547. Brandreth, R. H. (1978) Clinical Slit Lamp Biomicroscopy. Blaco Printers, California. Brown, N. (1969). Slit-image photography. Trans. Ophthalmol. Soc. U.K. 89, 397±408. Burden, G. and Bryant, S. A. (1997) Laboratory and Radiologic Tests for Primary Eye Care. ButterworthHeinemann, Oxford.

220

Ophthal. Physiol. Opt. 1998 18: No 2

Calderon, R. M. (1991) Ultrasonography. In: Problems in Optometry Vol. 3 (4), Posterior Pole Disorders (eds C. J. Patorgis and R. London), Lippincott, Philadelphia, pp. 634±652. Canning, C. R. and Restori, M. (1989). Doppler ultrasound mapping of extra-ocular muscles: a preliminary report. Eye 3, 409±414. Cavanagh, H. D., Petroll, W. M., Alizadell, H., Yu-Guang, H., McCulley, J. P. and Jester, J. V. (1993). Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology 100, 1444±1454. Charman, W. N. (1991) Non-optical techniques for visualizing the eye. Vision and Visual Dysfunction: Vol. 1, Visual Optics and Instrumentation, Macmillan, London, Chap. 16, pp. 359±370. Cheng, H.-M., Singh, O. S., Woods, B. T. and Brady, T. J. (1992). Shape of the myopic eye as seen with highresolution magnetic resonance imaging. Optom. Vis. Sci. 69, 698±701. Cohen, M. S. and Bookheimer, S. Y. (1994). Localization of brain function using magnetic resonance imaging. Trends Neurosci. 17, 268±277. Coleman, D. J. and Abramson, D. H. (1981) Ocular ultrasonography. In: Clinical Ophthalmology, Vol. 2 (ed. T. D. Duane), Harper and Row, Philadelphia, Chap. 26. Coleman, R. E., Blinder, R. A. and Jaszczak, R. J. (1986). Single photon emission tomography (SPECT). Part II, clinical applications. Invest. Radiol. 21, 1±11. Cox, M. J. and Wood, I. C. J. (1991a). Microcomputer analysis of the optic nerve head. Ophthal. Physiol. Opt. 11, 27±35. Cox, M. J. and Wood, I. C. J. (1991b) Computerised fundus imaging and image processing. In: Problems in Optometry Vol. 3 (1), Modern Diagnostic Technology (eds P. L. Abplanalp and R. London), Lippincott, Philadelphia, pp. 20±35. Culham, L. E., Fitzke, F. W., Timberlake, G. T. and Marshall, J. (1992). Use of scrolled text in a scanning laser ophthalmoscope to assess reading performance at di€erent retinal locations. Ophthal. Physiol. Opt. 12, 281±286. Cullen, A. P. (1971). Fundus examination with restricted spectrum light. Am. J. Optom. Arch. Am. Acad. Optom. 48, 803±810. Degenhardt, A. H. (1951) The story of the ophthalmoscope. Optician, 17±22. Delori, F. C. (1994). Spectrophotometer for noninvasive measurement of intrinsic ¯uorescence and re¯ectance of the ocular fundus. Appl. Opt. 33, 7439±7452. Delori, F. C., Gragoudas, E. S., Francisco, R. and Pruett, R. C. (1977). Monochromatic ophthalmoscopy and fundus photography. Arch. Ophthalmol. 95, 861±868. Dreher, A. W., Bille, J. F. and Weinreb, R. N. (1989). Active optical depth resolution improvement of the laser tomographic scanner. Appl. Opt. 28, 804±808. Dreher, A. W., Tso, P. C. and Weinreb, R. N. (1991). Reproducibility of topographic measurements with the normal and glaucomatous nerve head with the laser tomographic scanner. Am. J. Ophthalmol. 111, 1320±1324. Ducrey, N. M., Delori, F. C. and Gragoudas, E. S. (1979). Monochromatic ophthalmoscopy and fundus photography: the pathological fundus. Arch. Ophthalmol. 97, 288±293. Fercher, A. F., Drexler, W. and Hitzenberger, C. K. (1997). Optical ocular tomography. Neuro-ophthalmology 18, 39± 49.

Fitzke, F. W. and Masters, B. R. (1993) Three-dimensional visualisation of confocal sections of in vivo human fundus and optic nerve. Current Eye Res. 1015±1018. Fledelius, H. C. and Jensen, P. K. (1992) (eds) Ophthalmic ultrasound. Acta Ophthalmol. 70 (Suppl.), 204,. Fox, P. T., Mintun, M. A., Raichle, M. E., Meizen, F. M., Allman, J. M. and Van Essen, D. C. (1986). Mapping the human visual cortex with positron emission tomography. Nature 323, 806±809. Frazier-Byrne, S. and Green, R. L. (1992) Ultrasound of the Eye and Orbit. Mosby Year Book, St Louis. Gadian, D. G. (1995) NMR and its Application to Living Systems. Oxford Science, Oxford. Gevins, A., Leong, H., Smith, M. E., Le, J. and Du, R. (1995). Mapping cognitive brain function with modern high-resolution electroencephalography. Trends Neurosci. 18, 429±436. Gilchrist, J. (1987). Computer processing of ocular photographsÐa review. Ophthal. Physiol. Opt. 7, 379±386. Goldbaum, M. H., Chatterjee, S., Chaudhuri, S. and Katz, N. (1990) Digital image processing for ophthalmology. In: Noninvasive Diagnostic Techniques in Ophthalmology (ed. B. Masters), Springer, Berlin, Chap. 29, pp. 548±568. Gonzalez, C. F., Becker, M. H. and Flanagan, J. C. (1986) Diagnostic Imaging in Radiology. Springer, Berlin. Gullstrand, A. (1911) EinfuÂÂhrung in die Methoden der Dioptrik des Auges des Menschen. Leipzig. Haab, O. (1895) Atlas und Grundriss der Ophthalmoscopie und ophthalmoscopischen Diagnostik, Lehmann, Munich. Haab, O. (1927) An Atlas of Ophthalmoscopy, Translated into English by W. B. Barker, British Optical Association, London. Haab, O. (1899) Ausseren Erkrankungen des Auges. Lehmann, Munich. Hald, W. V., Flanagan, J. G., Etchells, E. E., Williams-Lyn, D. E. and Trope, G. E. (1997). Laser scanning tomography of the optic nerve head in ocular hypertension and glaucoma. Br. J. Ophthalmol. 81, 871±876. Hartinger, H. (1930) Zeiss-Nordenson's ¯are-free retinal camera. Br. J. Physiol. Opt., Ser. 1 4, 140±147. Hee, M. R., Izatt, J. A., Swanson, E. A., Huang, D., Schuman, J. S., Lin, C. P., Pulia®to, C. A. and Fujimoto, J. G. (1995a). Optical coherence tomography of the human retina. Arch. Ophthalmol. 113, 325±332. Hee, M. R., Pulia®to, C. A. and Wong, C.et al. (1995b). Quantitative assessment of macular edema with optical coherence tomography. Arch. Ophthalmol. 113, 1019±1029. Hee, M. R., Baumal, C. R., Pulia®to, C., Duker, J. S., Reichel, E., Wilkins, J. R., Coker, J. G., Schuman, J. S., Swanson, E. A. and Fujimoto, J. G. (1996). Optical coherence tomography of age-related macular degeneration and choroidal neovascularization. Ophthalmology 103, 1260±1270. von Helmholtz, H. (1851) Beschreibung eines Augen-spiegels zur Untersuchung des Netzhaut im lebenden Auge, Forstner, Berlin. Translated by R. W. Hollenhorst (1951) Description of an ophthalmoscope for examining the retina in the living eye. Arch. Ophthalmol. 46, 565±568, reprinted in J. E. Lebensohn and C. W. Rucker (1969), An Anthology of Ophthalmic Classics, Williams and Wilkins, Baltimore, pp. 53±61. Henson, D. B. (1991) Optical methods for the measurement of ocular parameters. In: Vision and Visual Dysfunction: Vol. 1. Visual Optics and Instrumentation (ed. W. N. Charman), Macmillan, London, Chap. 17, pp. 371±398.

Imaging in the 21st century: W. N. Charman Hillal, S. K., Kreps, S. M. and Trokel, S. L. (1981) Computerized tomography. In Clinical Ophthalmology. Vol. 2: Neuro-ophthalmology, Harper and Row, Philadelphia, Chap. 23. Ho, A. C., Lieb, W. E. and Flaharty, P. M. (1992). Color Doppler imaging of the ocular ischemic syndrome. Ophthalmology 99, 1453±1462. Hockwin, O., Sasaki, K. and Lerman, S. (1990) Evaluating cataract development with the Scheimp¯ug camera. In: Non-Invasive Diagnostic Techniques in Ophthalmology (ed. B. Masters), Springer, New York, Chap. 16, pp. 281±318. Hodson, S. A. and Sherrard, E. S. (1988). The specular microscope: its impact on laboratory and clinical studies of the cornea. Eye 2 (suppl., 81±97. Hollo, G., Suveges, I., Nagymihaly, A. and Vargha, P. (1997). Scanning laser polarimetry of the retinal nerve ®bre layer in primary open angle and capsular glaucoma. Br. J. Ophthalmol. 81, 871±876. Horton, J. C. and Hoyt, W. F. (1990). The representation of the visual ®eld in human striate cortex: a revision of the classic Holmes map. Arch. Ophthalmol. 109, 816±824. Houns®eld, G. N. (1973). Computerized transverse axial scanning (tomography), part 1: description of system. Br. J. Radiol. 46, 1016±1022. Hoyt, W. F., Schlicke, B. and Eckelho€, R. J. (1972). Fundoscopic appearance of a nerve-®bre defect. Br. J. Ophthalmol. 56, 577±583. Hung, G. K., Stahl, T. J. and Powell, A. L. (1990) Neural activity using SPECT. Medical Electronics, 104±107. Izatt, J. A., Hee, M. R. E., Swanson, E. A., Lin, C. P., Huang, D., Schuman, J. S., Pulia®to, C. A. and Fujimoto, J. G. (1994). Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch. Ophthalmol. 112, 1584±1589. Jackman, W. M. and Webster, J. D. (1886). On photographing the retina of the living human eye. Philadelphia Photographer 23, 340±341. Jaszczak, R. J. and Coleman, R. E. (1985). Single photon emission computed tomography (SPECT): principles and instrumentation. Invest. Radiol. 20, 897±910. Jay, W. M. (1989). Advances in magnetic resonance imaging. Am. J. Ophthalmol. 108, 592±596. Jester, J. V., Cavanagh, H. D. and Lemp, M. A. (1990) Confocal microscopic imaging of the living eye with tandem scanning confocal microscopy. In: Non-Invasive Diagnostic Techniques in Ophthalmology (ed. B. Masters), Springer, New York, Chap. 11, pp. 172±188. Kilbride, P. E., Alexander, K. R., Fishman, M. and Fishman, G. A. (1989). Human macular pigment assessed by imaging fundus re¯ectometry. Vision Res. 29, 663±674. Koenigsberger, L. (1906) Hermann von Helmholtz, Translated by F. A. Welby, Oxford University Press, Oxford. Reprinted by Dover, New York, 1965. Koester, C. J., Auran, J. D., Rosskothen, H. D. and Florakis, G. J. (1993). Clinical microscopy of the cornea utilizing optical sectioning and a high-numerical-aperture objective. J. Opt. Soc. Am. A 10, 1670±1679. Krivoy, D., Gentile, R., Liebman, J., Stegman, Z., Walsh, J. B. and Ritch, R. (1996). Imaging congenital optic disk pits and associated maculopathy using optical coherence tomography. Arch. Ophthalmol. 114, 165±170. Liang, J., Grimm, B., Goelz, S. and Bille, J. F. (1994). Objective measurement of the wave aberrations of the human eye with the use of a Hartmann-Shack wavefront sensor. J. Opt. Soc. Am. A 11, 1949±1957.

221

Liang, J., Williams, D. R. and Miller, D. T. (1997) Supernormal vision and high resolution retinal imaging through adaptive optics. J. Opt. Soc. Am. A, 14, 2884± 2892. Lieb, W. E., Flaharty, P. M., Sergott, R. C., Medlock, R. D., Brown, G. C., Bosley, T. and Savino, P. J. (1991). Color Doppler imagery provides accurate assessment of orbital blood ¯ow in occlusive carotid artery disease. Ophthalmology 98, 548±552. Low, A. (1991) Introductory Computer Vision and Image Processing. McGraw Hill, Maidenhead. Lueck, C. J., Zeki, S., Friston, K. J., Deiber, M-P., Cope, P., Cunningham, V. J., Lammertsma, A. A., Kennard, C. and Frackowiak, A. A. (1989) The colour centre in the cerebral cortex of man. Nature 340, 386±389. Mainster, M. A., Timberlake, G. T., Webb, R. H. and Hughes, G. (1982). Scanning laser ophthalmoscopy. Ophthalmology 89, 852±857. Manivannan, A., Kirkpatrick, J. N. P., Sharp, P. F. and Forester, J. V. (1994). Clinical investigation of an infrared digital scanning laser ophthalmoscope. Br. J. Ophthalmol. 78, 84±90. Marcos, S., Navarro, R. and Artal, P. (1996). Coherent imaging of the cone mosaic in the living human eye. J. Opt. Soc. Am. A 13, 897±905. Marg, E. (1988). Imaging visual function of the human brain. Am. J. Optom. Physiol. Opt. 65, 828±851. Marmion, V. J. (1986). Strategies in Doppler ultrasound. Trans. Ophthalmol. Soc. UK 105, 562±567. Marra€a, M., Mansoldo, C., Morbio, R., De Natale, R., Tomazzopli, L. and Bononi, L. (1997). Does nerve ®ber layer thickness correlate with visual ®eld defects in glaucoma? Ophthalmologica (Basel) 211, 338±340. Mashima, Y., Oshitari, K., Imamura, Y., Momoshima, S., Shiga, H. and Oguchi, Y. (1996). High resolution magnetic resonance imaging of the intraorbital optic nerve and subarachnoid space in patients with papilledema and optic atrophy. Arch. Ophthalmol. 114, 1297±1303. Massig, J. H., Preissler, M., Wegener, A. R. and Giada, G. (1994). Real-time confocal laser scan microscope for examination and diagnosis of the eye in vivo. Appl. Opt. 33, 690±694. Masters, B. (1990) (ed.) Non-Invasive Diagnostic Techniques in Ophthalmology. Springer, New York. Masters, B. R. and Thaer, A. A. (1994). Real-time scanning slit confocal microscopy of the in vivo human cornea. Appl. Opt. 33, 695±701. Maurice, D. M. (1968). Cellular membrane activity in the corneal endothelium of the intact eye. Experientia 24, 1094±1095. Mawn, L. A., Hedges, T. R., Rand, W. and Heggerick, P. A. (1997). Orbital color Doppler imaging in carotid occlusive disease. Arch. Ophthalmol. 115, 492±496. McFadzean, R., Brosnahan, D., Hadley, D. and Mutlukan, E. (1994). Br. J. Ophthalmol. 78, 185±190. Messner, L. V. (1991) Ophthalmic echography. In: Problems in Optometry Vol. 3 (1), Modern Diagnostic Technology (eds P. L. Abplanalp and R. London), Lippincott, Philadelphia, pp. 143±159. Miller, D. T., Williams, D. R., Morris, G. M. and Liang, J. (1996). Images of cone photoreceptors in the living human eye. Vision Res. 36, 1067±1079. Miller, N. R. and George, T. W. (1978). Monochromatic (red-free) photography and ophthalmoscopy of the peripapillary retinal nerve ®ber layer. Invest. Ophthalmol. Vis. Sci. 17, 1121±1124.

222

Ophthal. Physiol. Opt. 1998 18: No 2

Morgan, P. B., Meng Poey Soh and Efron, N. (1993) Potential applications of ocular thermography. Optom. Vis. Sci. 70, 568±576. Morgan, P., Morris, T., Newell, Z., Wood, I. and Woods, C. (1997). Invasion of the image snatchers. Optician 213 (5588, 24±26. Morgan, P. B., Tullo, A. B. and Efron, N. (1995). Infrared thermography of the tear ®lm in dry eye. Eye 9, 615±618. Mundt, G. H. and Hughes, W. F. (1956). Ultrasonics in ocular diagnosis. Am. J. Ophthalmol. 41, 488±498. Norden, L. C. (1979). Spectral re¯ectance photography of the ocular fundus. Am. J. Optom. Physiol. Opt. 56, 586± 591. Pavlin, C. J., Sherar, M. D., Harasiewiz, K. and Foster, F. S. (1991). Clinical use of ultrasound biomicroscopy. Ophthalmology 98, 287±295. Peli, E. (1989). Electro-optic fundus imaging. Survey Ophthalmol. 34, 113±121. Peli, E. (1992). Limitations on image enhancement for the visually-impaired. Optom. Vis. Sci. 69, 15±24. Petrig, B. L. and Riva, C. E. (1988). Retinal laser Doppler velocimetry: towards its computer-assisted clinical application. Appl. Opt. 27, 1126±1134. Plesch, A., Klingbeil, U., Rappel, W. and SchroÈdel, C. (1990) Scanning ophthalmic imaging. In: Scanning Laser Ophthalmology and Tomography (eds J. E. Nasemann and R. O. W. Burk), Quintessenz Verlag, MuÈnchen, Chap. 1, pp. 23±33. Pulia®to, C. A., Hee, M. R., Lin, C. P., Reichel, E., Schuman, J. L., Duker, J. S., Izatt, J. A., Swanson, E. A. and Fujimoto, J. G. (1995). Imaging of macular disease with optical coherence tomography. Ophthalmology 102, 217±229. Raichle, M. E. (1986). Neuroimaging. Trends Neurosci. 9, 525±529. Raichle, W. H. (1987) Images of the brain. In: The Oxford Companion to the Mind (ed. R. H. Gregory), Oxford U. P., Oxford, pp. 347±353. Raichle, W. H. (1990) Images of the functioning human brain. In: Images and Understanding (eds H. Barlow, C. Blakemore and M. Weston-Smith), Cambridge U. P., Cambridge, pp. 284±296. Rehkopf, P. G. and Warnicki, J. W. (1990) Ophthalmic image processing. In: Non-Invasive Diagnostic Techniques in Ophthalmology (ed. B. Masters), Springer, New York, Chap. 1, pp. 1±16. Roelofs, T. (1997) Image enhancement for Low Vision. Thesis, Eindhoven University of Technology, Holland. Roland, P. E. and Gulyas, B. (1994). Visual imagery and visual representation. Trends Neurosci. 17, 281±289. Roorda, A., Campbell, M. C. W., Atkinson, M. R. and Munger, R. (1997) Scanning laser ophthalmoscope for real-time photoreceptor imaging in the human eye. OSA Technical Digest Series 1997, Vol.1, Vision Science and its Applications, Santa Fe, pp. 90±93. Rosen, E. S. (1969) Fluorescence Photography of the Eye. Butterworths, London. Rucker, W. F. (1971) A History of the Ophthalmoscope. Whiting, Rochester. Schett, A. (1996) Hirschberg History of Ophthalmology. The Ophthalmoscope: a Contribution to the History of its Development up to the Beginning of the 20th Century. Translated by D. L. Blanchard, Wayenbourgh, Ostend. Schuman, J. S., Hee, M. R., Pulia®to, C. A., Wong, C., Pedut-Kloizman, T., Lin, C. P., Hertzmark, E., Izatt, J. A., Swanson, E. A. and Fujimoto, J. G. (1995). Quanti®cation

of nerve ®ber layer thickness in normal and glaucomatous eyes using optical coherence tomography. Arch. Ophthalmol. 113, 586±596. Sergent, J. (1994). Brain-imaging studies of cognitive functions. TINS 17, 221±226. Shammas, H. J. (1984) Atlas of Ophthalmic Ultrasonography and Biometry. Mosby, St Louis. Sherrard, E. S. and Buckley, R. J. (1983). Visualisation of the corneal endothelium in the clinic. Ophthalmologica 187, 118±128. Silverman, R. H., Rondeau, M. J., Lizzi, F. L. and Coleman, D. J. (1995). Three-dimensional high-frequency ultrasonic parameter imaging of anterior segment pathology. Ophthalmology 102, 837±843. Sokol, J., Stegman, Z., Liebmann, J. M. and Ritch, R. (1996). Ophthalmology 103, 289±293. Sorsby, A., Leary, G. A., Richards, M. J. and Chaston, J. (1963). Ultrasonographic measurements of the components of ocular refraction in life. 2. Clinical procedures: ultrasonographic measurements compared with phakometric measurements in a series of 140 eyes. Vision Res. 3, 499±505. Steward, E. G. (1987) Fourier Optics, 2nd edn. Ellis Horwood, Chichester. Storey, J. (1988) Ultrasonography of the eye. In: Optometry (eds K. Edwards and R. LLewellyn, Butterworths, London, pp. 342±352. Tate, G. W. and Sa®r, A. (1988) The slit lamp: history, principles and practice. In: Clinical Ophthalmology, Vol. 1 (ed. T. D. Duane), Lippincott, Philadelphia. Timberlake, G. T., Mainster, M. A., Webb, R. H., Hughes, G. W. and Trempe, C. L. (1982). Retinal localization of scotoma by scanning laser ophthalmoscopy. Invest. Ophthalmol. Vis. Sci. 22, 91±97. Timberlake, G. T., Mainster, M. A., Peli, E., Augliere, R. A. Essock, E. A. and Arend, L. E. (1986) Reading with a macular scotoma. I. Retinal location of scotoma and ®xation area. Invest. Ophthalmol. Vis. Sci. 27, 1137±1147. Timberlake, G. T., Peli, E., Essock, E. A. and Augliere, R. A. (1987). Reading with a macular scotoma. II. Retinal locus for scanning text. Invest. Ophthalmol. Vis. Sci. 28, 1268±1274. Thimons, J. J. (1991) Diagnostic imaging in optometry. In: Problems in Optometry Vol. 3(1), Modern Diagnostic Technology (eds P. L. Abplanalp and R. London), Lippincott, Philadelphia, pp. 160±170. Tornow, R.-P., Beuel, S. and Zrenner, E. (1997). Modifying a Rodenstock scanning laser ophthalmoscope for imaging densitometry. Appl. Opt. 36, 5621±5629. Tower, H. and Oshinskie, L. J. (1989). An introduction to computed tomography and magnetic resonance imaging of the head and visual pathways. J. Am. Optom. Ass. 60, 619±628. Trokel, S. L. (1981) Radiology of the orbit. In Clinical Ophthalmology. Vol. 2: Neuro-ophthalmology, Chap. 22. Harper and Row, Philadelphia. Turner, R. and Jezzard, P. (1994). How to see the mind. Physics World 7 (8, 29±33. Webb, R. H. (1990) Scanning laser ophthalmoscope. In: Non-Invasive Diagnostic Techniques in Ophthalmology (ed. B. R. Masters), Springer, New York, Chap. 22, pp. 438± 450. Webb, R. H. (1991) Confocal microscopy. Optics and Photonics News 2, July, 8±13.

Imaging in the 21st century: W. N. Charman Webb, R. H., Hughes, G. W. and Delori, F. C. (1987). Confocal scanning laser ophthalmoscope. Appl. Opt. 26, 1492±1498. Weinreb, R. N., Dreher, A. W., Coleman, A., Quigley, H. A., Shaw, B. and Reiter, K. (1990). Histopathalogic validation of Fourier-ellipsometry measurements of retinal nerve ®bre thickness. Arch. Ophthalmol. 108, 557±560. Wilkins, J. R., Pulia®to, C. A., Hee, M. R., Duker, J. S., Reichel, E., Coker, J. G., Schuman, J. S., Swanson, E.

223

A. and Fujimoto, J. G. (1996). Characterization of epiretinal membranes using optical coherence tomography. Ophthalmolgy 103, 2142±2151. Wilson, T. and Sheppard, C. (1984) Theory and Practice of Scanning Optical Microscopy. Academic Press, London. Woon, W. H., Fitzke, F. W., Bird, A. C. and Marshall, J. (1992). Confocal imaging of the fundus using a scanning laser ophthalmoscope. Br. J. Ophthalmol. 76, 470±474.