Ординатура / Офтальмология / Английские материалы / Ophthalmology Investigation and Examination Techniques_James, Benjamin_2006

blood vessels after the introduction of contrast medium into an artery remains a definitive way to demonstrate an aneurysm, however (Fig. 14.32a).

Microvascular disease is the commonest cause of a pupil-sparing third-nerve palsy and careful evaluation of the brainstem for signal alteration should be considered.

Fourth-nerve palsy

This is the least common of the ocular motor palsies. The fourth-nerve nucleus is located in the midbrain at the level of the inferior colliculus. This cranial nerve exits the brainstem posteriorly and is susceptible to damage in head trauma. It may also be affected in hydrocephalus by dilatation of the aqueduct or compression of the dorsal midbrain.

Sixth-nerve palsy

The sixth-nerve nuclei lie in the dorsomedial aspect of the pons near the pontine reticular formation. Along the floor of the fourth ventricle, the seventh nerve winds around the sixth nerve to form the facial colliculus. The sixth-nerve nucleus also contains interneurones to form the medial longitudinal fasciculus. The nerve passes ventrally from its nucleus to cross the corticospinal tracts and exit the brainstem. From here it passes through the subarachnoid space, bending sharply forward across the apex of the petrous bone lying beneath the petroclinoid ligament with the canal of Dorelo. It enters the cavernous sinus where it lies lateral to the carotid artery.

The cause of sixth-nerve palsy is very agedependent. In children sixth-nerve palsies may occur after viral infections or as a result of an intracranial

Fig. 14.33 Sagittal T1w magnetic resonance scan showing typical appearance of a brainstem glioma.

Mass

Fig. 14.34 Axial T1w post-contrast magnetic resonance scan showing enhancing mass related to the right cavernous sinus (chondrosarcoma).

or brainstem tumour (Fig. 14.33). In young adults causes include demyelination, trauma and tumour. In patients over the age of 40 it is usually vascular in origin due to microvascular occlusion and imaging is generally not very helpful.

Isolated sixth-nerve palsies are a difficult problem and imaging must include careful evaluation of the skull base and cavernous sinus region (Fig. 14.34).

Internuclear ophthalmoplegia

The medial longitudinal fasciculus (MLF) connects the nuclei of the third, fourth, sixth and eighth cranial nerves. It lies dorsally near the midline throughout the brainstem. A lesion in the MLF causes an internuclear ophthalmoplegia. In a young

person the most likely cause is a demyelinating disorder such as multiple sclerosis. In an elderly patient it is most likely as a result of brainstem infarction. Imaging should include tailored views of the brainstem and midline structures using both sagittal and coronal sequences with T1and T2weighted scans (Fig. 14.35).

Nystagmus

Many forms of nystagmus have excellent localising value and as such it is important to indicate to the radiologist as much detail as possible. For example, downbeat nystagmus is associated with lesions of the craniocervical junction. Gaze-evoked nystagmus is associated with vestibular or cerebellar lesions, and

rebound nystagmus with lesions of the cerebellum. Imaging can thus be tailored appropriately to demonstrate the relevant areas of interest. In all patients with eye movement disorders it is important to evaluate the craniocervical junction and upper cervical cord carefully, and detailed views of the midbrain and midline structures should be obtained. This is best done by means of high-resolution MRI using sagittal T1and T2-weighted sequences through the region of interest (Fig. 14.36).

Summary

Modern imaging techniques can provide precise and detailed information for the referring clinician faced with a patient who has symptoms and signs relating to the orbit and visual pathways. The modalities are complementary and in many cases local experience and preference will dictate what imaging technique is used. Close professional relationships between clinicians and radiologists will allow the best outcomes from imaging. A detailed clinical

■Imaging is one useful diagnostic approach but must be used in conjunction with the clinical picture and history

■It is important to use appropriate modalities of imaging. Discussion with the radiologist as to the most appropriate test can be helpful

■A combination of computed tomography and magnetic resonance imaging may be necessary to define a pathology fully

■Plain radiographs of the orbit are less commonly used now, except in some aspects of trauma and suspected radiopaque foreign bodies

history and examination are vital to the radiologist to ensure that the best technique is used and that the appropriate area of interest is examined.

Further reading

Aviv R, Casselman J. Orbital imaging: part 1. Normal anatomy. Clin Radiol 2005; 60: 854–858.

Aviv R, Miszkiel K. Orbital imaging: part 2. Intraorbital pathology. Clin Radiol. 2005; 60: 288–307.

Forbes G. The orbit. Am Soc Neuroradiol Core Curriculum Course Neuroradiol 1994: 153–161.

Grainger RG, Allison DJ, Dixon AK. Grainger and Allison’s diagnostic radiology, 4th edn. Edinburgh: Churchill Livingstone; 2001.

Hosten N, Bornfeld N. Imaging of the globe and orbit: a guide to differential diagnosis. Stuttgart: Thieme; 1998.

Kahaly GJ. Imaging in thyroid associated orbitopathy. Eur J Endocrinol 2001; 145: 107–118.

Lloyd G. The Orbit. In: DuBoulay GH, ed. A Textbook of Radiological Diagnosis. 5th edn. London: HK Lewis & Co; 1984: 288.

Manfre L, de Maria M, Todaro E et al. MR dacryocystography: comparison with DCG and CT DCG. Am J Neuroradiol 2000; 21: 1145–1150.

Mayer EJ, Fox DL, Herdman G et al. Signal intensity, clinical activity and cross sectional area on MRI scan in thyroid eye disease. Eur J Radiol 2005; 56: 20–24.

Osborn A, Hansberger HR (eds). Diagnostic imaging: head and neck. Salt Lake City: Amirsys; 2004.

Som PM, Curtin HD. Head and neck imaging, 4th edn. Philadelphia: Mosby; 2003.

Introduction

The first measurement of electrical activity in the visual system is attributed to DuBois-Reymond, who in 1849 discovered that excised fish eyes have a potential difference of about 6 mV between the cornea and posterior scleral surface. In the early years of the twentieth century, it was difficult to measure the small and rapid voltage changes in the eye in response to flashes of light, but even with the relatively crude galvanometers available at the time, Einthoven and Jolly, and later, Granit, described the electroretinogram (ERG) in considerable detail in animal eyes (Einthoven, 1908; Granit, 1947).

By the early 1940s, recording equipment had improved to the point where it was possible to measure the human ERG in the clinical setting. In 1934, Adrian and Matthews had recorded electrical responses from surface electrodes placed over the occipital cortex in a human subject. This and other ground-breaking scientific work formed the basis of a new branch of clinical science, allowing the human visual system to be probed in a way that was not previously possible.

Since the 1940s, technological advances such as solid-state electronics, microprocessors and lightemitting diodes (LEDs) have led to huge improvements in equipment for generating and recording electrophysiological responses, and have contributed to a greatly increased understanding of the workings of the visual system in health and disease.

Visual electrophysiology is now firmly established both as a branch of visual science and as a diagnostic support service to clinical ophthalmology.

Standards in visual electrophysiology

Until the 1980s, clinical visual electrophysiology services often relied on equipment that was ‘home-

made’. It was difficult to make valid comparisons of data from different laboratories because of wide variations in recording equipment and the way in which tests were performed. In 1989, the International Society for Clinical Electrophysiology of Vision (ISCEV) published the first internationally agreed standard for electroretinography. Standards for other common electrophysiological tests and for calibration of recording equipment have been published more recently.

It is now possible to buy very sophisticated and comprehensive electrophysiology testing systems ‘off the peg’ from a number of manufacturers, and many of these are designed to comply with ISCEV standards. This has helped to improve the availability of visual electrophysiological tests to ophthalmologists.

It is important to remember, however, that the visual electrophysiologist remains the most important component of the system. No matter how sophisticated the equipment, the process of recording electrophysiological responses requires special training and meticulous attention to detail. Factors such as placement of recording electrodes, ambient lighting levels, pupil size and extraneous electrical interference can have a major influence on responses. Recording equipment must be properly maintained and regularly calibrated. It is still necessary for each laboratory to maintain a database of normal values for each test, which must be updated if the equipment or testing protocols change. The old adage of ‘garbage in, garbage out’ applies as much to visual electrophysiology as to computing.

The relevance of visual electrophysiology to ophthalmology

When modern cars are serviced, the mechanic interrogates the engine management system by plugging

in a diagnostic system connected to a lap-top computer. A variety of faults can be diagnosed and fixed from the data which emerge. There is a common misconception within ophthalmology that visual electrophysiological testing works similarly to a ‘black box’ into which a general request is made and from which a diagnosis emerges without any further intellectual engagement on the part of the requester.

Unfortunately, the human visual system is much more complex than a car engine and the instruments we use to measure its function are still far from perfect. There are some clinical situations where the results of electrophysiological tests provide the sole and definitive proof of a diagnosis, but they are not common. More usually, the tests provide one piece of a diagnostic jigsaw and the results must be interpreted in the context of the clinical history, examination findings and results of other tests.

The common uses of visual electrophysiology in the clinical setting include the following:

•to provide evidence to confirm or exclude a specific diagnosis

•to monitor the progress of a known condition

•to indicate the level in the visual system at which a problem lies, or the cell populations involved in the disease process

•to provide an approximate objective measurement of visual acuity

•to detect early disease or carrier status in relatives of an affected individual

•to provide an indication of the maturity of the visual system in infants

•to provide an indication of visual potential in an injured or diseased eye.

Before requesting any test, a clinician must be able to make an informed judgement as to whether the test is likely to be capable of answering the question being asked. Electrophysiological tests are noninvasive and very safe, but they tend to be timeconsuming to perform and require a reasonable degree of cooperation on the patient’s part. There is no point in requesting these tests if the results are unlikely to shed any light on the clinical question being asked, or if the answer can be obtained more easily by other means. It is important to remember, too, that these tests are sometimes used to diagnose, monitor or exclude potentially blinding conditions. From the patient’s or parent’s perspective, a lot may hang on the results and it is essential that the

clinician is able to counsel the patient and family both accurately and sensitively.

The aim of the remainder of this chapter is to help the clinician to obtain the maximum possible benefit from a clinical visual electrophysiology service.

Obtaining informed consent for visual electrophysiological tests

In view of the fact that visual electrophysiological tests are non-invasive, in the UK it is generally regarded as sufficient to obtain verbal consent for testing from the patient (or parent, where the subject is a child under 16) unless general anaesthesia or sedation is being used, in which case formal written consent must be obtained. The person carrying out the test will be able to explain the procedure, but he or she will not necessarily be medically qualified and may not be able to answer detailed questions about the patient’s clinical condition.

It is good practice, therefore, when a clinician requests electrophysiological tests, to explain to the patient:

•why the tests are being requested

•what the patient is likely to experience during testing

•how long the tests are likely to take

•that the results have to be analysed before a report can be issued.

The clinician who has observed electrophysiological testing at first hand will be well equipped to provide such an explanation.

Most subjects do not find visual electrophysiological testing distressing, and electrophysiologists are highly skilled at engaging the cooperation of even young children or patients with learning difficulties. The placement of skin electrodes can be mildly uncomfortable at first, though topical anaesthesia is normally used with corneal electrodes (Figs 15.1 and 15.2). Full-field electroretinography and electrooculography (EOG) require pupil dilatation and a period of dark adaptation. Patients sometimes find bright flashes of light or the process of light adaptation slightly uncomfortable. Although electrophysiological tests avoid epileptogenic flash frequencies, a history of photogenic epilepsy is normally a contraindication to testing. It is safe to test patients with implanted electronic devices such as cardiac pacemakers or cochlear implants, though they are

Fig. 15.1 Recording a pattern electroretinogram.

Fig. 15.2 Electroretinogram electrodes showing the reference electrode at the outer canthus, a ground electrode on the forehead, and the active corneal electrodes, in this case, DTL-fibre type.

strong sources of electrical interference which can seriously degrade the recordings. The pattern ERG and pattern cortical evoked potential are easily degraded by defocus, and it is important that the patient wears an appropriate refractive correction for these tests.

Interpretation of electrophysiological recordings

In general, the electrical events that occur in the visual system when a visual stimulus enters the eye

Interpretation of Electrophysiological Recordings

follow an orderly sequence. Hyperpolarisation of the photoreceptors associated with phototransduction starts to occur within the first 12 ms following a flash of light and forms the leading edge of the a-wave of the ERG. The events in the middle and inner layers of the retina which generate the pattern ERG (PERG) occur between 35 and 95 ms following pattern onset or reversal. The cortical visually evoked potential (VEP) to a reversing checkerboard stimulus starts at about 75 ms after the onset of the flash.

There is, of course, much more to the ERG than the transmission of the initial impulse from the photoreceptors to the ganglion cells. There is a complex sequence of electrochemical events in the retina and retinal pigment epithelium which continues for several minutes after a single flash, and the ERG is a composite wave with many components. New features of the ERG are still being discovered. The relative contributions of the various ERG components to the composite wave depend on the recording conditions and it is only possible to interpret an ERG recording in the light of detailed information about the stimulus (e.g. flash intensity, colour, repetition rate and level of background illumination) and the subject (e.g. age, degree of dark or light adaptation, pupil diameter, electrode position). It is possible to select out particular components of the ERG by choosing the stimulus characteristics and recording conditions appropriately, and this sometimes allows information to be gleaned about the function of particular cell types in the retina.

At the level of the occipital cortex, the impulse from a flash or pattern of light projected on to the retina has become considerably modulated, having synapsed in the ganglion cell layer and the lateral geniculate nucleus. The relationship between the type of stimulus and the cortical response is therefore much more complex than in the retina.

Full-field (Ganzfeld) electroretinography

The full-field ERG is a recording of the massed response of the cells of the retina in response to a flash of light. An abnormal ERG implies that the causative disease process is affecting the retina diffusely or extensively. A large macular scar which reduces the visual acuity to hand movements will have little effect on the ERG providing that the function of the peripheral retina is normal. Conversely, a disease process that causes extensive photoreceptor death (such as retinitis pigmentosa) but spares the

fovea may almost extinguish the ERG, even though the visual acuity may be 6/5. The ERG is recordable from a healthy retina even in the presence of dense opacities of the ocular media, although the amplitude of the response will be correspondingly reduced.

Ideally, the electrodes used to record the ERG would be placed on the cornea and on the sclera close to the fovea. This is obviously impractical in the clinical situation and instead, one electrode is placed on the cornea and one on the skin at the ipsilateral lateral canthus. Recordings can be made from both eyes simultaneously and a common earth electrode is usually placed in the middle of the

Fig. 15.3 (a, b) Ganzfeld bowl apparatus. (Courtesy of Moorfields Eye Hospital.)

b

forehead. The corneal electrode may be either mounted in a special contact lens, or may consist of a conducting foil or fibre placed at the lid margin in contact with the cornea.

The pupils are maximally dilated and the subject’s head is positioned within a bowl with a white, reflective inner surface and a radius that allows the whole retina to be illuminated as evenly as possible by light reflected from the surface. This is known as a Ganzfeld stimulus. The light source for the ISCEV standard ERG is a xenon discharge tube, but arrays of bright LEDs may also be used (Fig. 15.3).

A normal ERG series is shown in Fig. 15.4.

a

μV 0 –200

–400 1

μV 50 0

–50 1

Fig. 15.4 Normal electroretinogram series. (a) Dark-adapted rod responses to increasing flash intensity and (b) lightadapted cone responses. Note the scaling for cone responses compared with rod responses.

Before recording starts, the subject is dark-adapted for 20 min. Recordings are first made of the response to very dim flashes of white or blue light. The only response at this intensity is likely to be the scotopic threshold response (STR), a negative deflection of a few microvolts in amplitude. The response from many flashes must be averaged in order to detect the response above background noise. Further recordings are then made with flashes of progressively higher intensity. The scotopic b-wave appears, increasing in intensity and decreasing in implicit time as the flash intensity increases. At higher intensities, the a-wave appears and also increases in amplitude with increasing flash intensity. Up to this point, the cones have not made a major contribution to the response. Next, a bright white flash (sometimes known as the ‘standard flash’) is used, which produces a mixed rod and cone response with a large a-wave and b-wave, and wavelets or oscillatory potentials superimposed on the ascending limb of the b-wave. The oscillatory potentials can be recorded separately by repeating the recording with a filter to remove the lower-frequency components of the response. The subject is then light-adapted to suppress rod activity, and a response is recorded to a bright light flickering at 30 Hz. This is a pure cone response. A further recording is made of responses to single flashes of bright light. The cone a-wave and b-wave so generated are of smaller amplitude and are faster than their rod counterparts. There is often a distinct peak (I-wave) on the descending limb of the cone b-wave (Fig. 15.4).

A great deal of research has been conducted into the retinal origins of the components of the scotopic (dark-adapted) and photopic (light-adapted) ERG. Research techniques include the in vitro use of single-cell recordings with microelectrodes and the use of metabolic poisons to block the action of specific cells or receptors. Special test protocols in normal subjects and research on individuals with specific retinal diseases have contributed additional evidence.

The scotopic a-wave is the leading edge of a strong, sustained negative potential. The earliest part of the a-wave originates from the photoreceptors, but the later part (which is normally hidden by the positive deflection of the b-wave) reflects the activity of Müller cells. The scotopic b-wave is probably due to ion fluxes in the middle layers of the retina secondary to the activity of the rod on-bipolar

pathway. There is no rod off-bipolar pathway. The cone a-wave also includes a significant contribution from the horizontal cells and cone off-bipolar cells. The cone b-wave is driven largely by the cone onbipolar cells. The ERG to a 30 Hz flicker contains contributions from both the onand off-bipolar cells but not from the photoreceptors.

A number of retinal conditions produce specific and predictable abnormalities in the standard ERG. Mutations in rhodopsin found in autosomal dominant retinitis pigmentosa cause progressive death of rods with later secondary damage to cones. The scotopic ERG is severely abnormal or unrecordable from an early stage and the photopic ERG is usually better preserved, but deteriorates as the disease progresses. In contrast, the cone dystrophies reduce or extinguish the photopic ERG while leaving the scotopic ERG relatively well preserved. The rare condition of achromatopsia also results in an absent photopic ERG with a preserved scotopic ERG.

Any process that results in the death of photoreceptors will attenuate the ERG if it is extensive enough. Examples include chorioretinitis, myopic chorioretinal atrophy, extensive laser photocoagulation and autoimmune retinopathies such as carcinoma-associated retinopathy.

Processes that disrupt communication between the photoreceptors and bipolar cells characteristically reduce the amplitude of the b-wave of the standard flash dark-adapted ERG, giving the socalled ‘negative ERG’ (Fig. 15.5). Conditions which can give rise to this appearance include X-linked retinoschisis, congenital stationary night blindness and retinal vascular occlusions.

The availability of bright LEDs emitting at a variety of wavelengths has made it possible to design special protocols to select out additional features of the cone pathway. These do not currently form part of the standard ISCEV ERG protocol, but are likely to become part of the standard test in the future as their clinical relevance becomes more firmly established.

For instance, a long flash (e.g. 100 ms) under light-adapted conditions produces an onset response (the cone a-wave and b-wave) at the beginning of the stimulus and an offset response (a positive wave, sometimes referred to as the d-wave) as the light switches off. Both the onset and offset components represent an interaction between the on-bipolar and off-bipolar pathways. The complete form of

XL CSNB

Normal

congenital stationary night blindness prevents transmission between rods and cones and on-bipolar cells. As expected, the long flash photopic ERG shows a deep, sustained a-wave with a small or absent b-wave, followed by a large d-wave (Fig. 15.6).

If dim blue flashes are presented against a brighter orange background, an S cone (blue cone) ERG can be recorded because the rods and L and M (red and green) cones are suppressed by the orange background illumination. The S cone ERG is small and its b-wave implicit time is closer to that of the rods than the L and M cones. Like rods, S cones lack an off-bipolar pathway. There is an uncommon form of night blindness known as enhanced S cone syndrome (ESCS) where all the photoreceptors are cones, of which over 90% are S cones. Apart from night blindness, visual function is usually good, although there can be slow deterioration. Predictably, the scotopic ERG is very small as it contains only a cone contribution. The 30 Hz flicker response is reduced and delayed, and the standard cone ERG is also reduced. However, the S cone ERG is abnormally large.

The causative genes for these and many other inherited retinal diseases have been identified in the last decade, and the ERG has provided valuable information on how mutations modify retinal function.

Pattern electroretinogram

The PERG has become established as a standard part of the electrophysiological repertoire since the early 1990s. Placement of electrodes is the same as

Fig. 15.6 Normal on and off response to a long flash (lower trace) and long flash response in complete congenital stationary night blindness (CSNB: upper trace). (Courtesy of Moorfields Eye Hospital.)

for a full-field ERG, although foil or fibre corneal electrodes are preferred to contact lens electrodes because a clearly focused retinal image is essential. The stimulus is a pattern of high contrast projected on a monitor. The most commonly used stimulus is a checkerboard pattern where each check alternates between black and white twice every second. For many years, there was controversy as to whether the response recorded to this stimulus was simply a result of interaction between ‘mini-ERGs’ produced by areas of illuminated retina, but it is now generally accepted that the PERG is a distinct electrophysiological response which contains information about ganglion cell function, although some uncertainty still surrounds its exact origins.

The PERG is a much weaker response than the ERG, rarely exceeding 8–10 μV in amplitude, so an averaged response to a number of pattern reversals is recorded. It is highly susceptible to defocus, so an accurate spectacle correction must be worn for the test where there is any significant refractive error. Unlike the ERG, the PERG is a macula-dominated response.