Ординатура / Офтальмология / Английские материалы / Glaucoma Identification and Co-management_Edgar, Rudnicka_2007

these fields are from patients who were very experienced in automated perimetry.

5.9 OTHER VARIANTS OF AUTOMATED

PERIMETRY

The following are alternative perimetric testing methods that have been investigated for use in glaucoma, and they are discussed in Chapter 6.

References

■Short-wavelength automated perimetry (SWAP) —also known as blue-on-yellow perimetry, or short wavelength sensitive perimetry

■Frequency doubling perimetry

■High pass resolution perimetry

■Flicker perimetry

■Motion perimetry

■Pattern discrimination perimetry.

Many of the above are still under investigation and are not used routinely in clinical practice.

1.Greve EL. Single and multiple stimulus static perimetry in glaucoma; the two phases of the visual field examination. Doc Ophthalmol 1973; 36:1–355.

2.Heijl A, Krakau CET. An automatic perimeter, design and pilot study. Acta Ophthalmol 1975; 53:293–310.

3.Wood JM, Wild JM, Hussey M, et al. Serial examination of the ‘normal’ visual field using Octopus projection perimetry: evidence of a learning effect. Acta Ophthalmol 1987; 65:326–333.

4.Heijl A, Lindgren G, Olsson J. The effect of perimetric experience in ‘normal’ subjects. Arch Ophthalmol 1989; 107:81–86.

5.Wild JM, Dengler-Harles M, Searle AET, et al. The influence of the learning effect on automated perimetry in patients with suspected glaucoma. Acta Ophthalmol 1989; 67:537–545.

6.Guttridge NM, Allen PM, Rudnicka AR, et al. Influence of learning on the peripheral field as assessed by automated perimetry. In: Mills RP, Heijl A, eds. Perimetry Update 1990/1991. Amstelveen: Kugler and Ghedini; 1991:567–575.

7.Heijl, A. Time changes of contrast thresholds during automated perimetry. Acta Ophthalmol 1977; 55:696–708.

8.Holmin C, Krakau CET. Variability of glaucomatous visual field defects in computerised perimetry. Graefes Arch Clin Exp Ophthalmol 1979; 210:235–250.

9.Heijl A, Drance SM. Changes in differential light threshold in patients with glaucoma during prolonged perimetry. Br J Ophthalmol 1983; 67:512–516.

10.Johnson CA, Adams CW, Lewis RA. Fatigue effects in automated perimetry. Appl Opt 1988; 27:1030–1037.

11.Langerhorst C, van den Berg TJTP, Veldman E, et al. Population study of global and local fatigue with prolonged threshold testing in automated perimetry. Doc Ophthalmol Proc Ser 1987; 49:657–662.

12.Rudnicka AR, Crabb DP, Edgar DF, et al. Pointwise analysis of serial visual fields in ‘normal’ subjects. In: Heijl A, Mills RP, eds. Perimetry Update 1992/1993. Amsterdam: Kugler Publications; 1993:41–48.

13.Jaffe GJ, Alvarado JA, Juster RP. Age related changes of the ‘normal’ visual field. Arch Ophthalmol 1986; 104:1021–1025.

14.Nelson-Quigg JM, Twelker JD, Johnson CA. Response properties of ‘normal’ observers and patients during automated perimetry. Arch Ophthalmol 1989; 107:1612–1615.

15.Flammer J, Drance SM, Zulauf M. Differential light threshold. Shortand long-term fluctuations in patients with glaucoma, ‘normal’ controls and

patients with suspected glaucoma. Arch Ophthalmol 1984; 102:704–706.

16.Flammer J, Drance SM, Fankhauser F, et al. Differential light threshold in automatic threshold perimetry: factors influencing the short-term fluctuation. Arch Ophthalmol 1984; 102:876–879.

17.Henson DB. Visual Fields. Oxford: Butterworth Heinemann; 2000.

18.Henson DB, Anderson RS. Threshold-related suprathreshold visual field testing: which is the best technique of establishing the threshold? In: Mills RP, Heijl A, eds. Perimetry Update 1990/1991.

Amstelveen: Kugler and Ghedini; 1991:367– 372.

19.Henson DB, Artes P. New developments in suprathreshold perimetry. Ophthalmic and Physiol Opt 2002; 22:463–468.

20.Bengtsson B, Olsson J, Rootzen H. A new generation of algorithms for computerized perimetry, SITA. Acta Ophthalmol 1997; 75:368–375.

21.Wild J. SITA—a new outlook for visual field examination in primary shared care. Optician 1997; March 14: 213.

22.Bengtsson B, Heijl A. Evaluation of a new threshold visual field threshold strategy, SITA, in ‘subjects’. Acta Ophthalmol 1998; 76:165–169.

23.Bengtsson B, Heijl A. Evaluation of a new perimetric threshold strategy, SITA, in patients with manifest and suspect glaucoma. Acta Ophthalmol 1998; 76:268–272.

24.Bengtsson B, Heijl A. SITA FAST, a new rapid perimetric threshold test. Description of methods and evaluation in patients with manifest and suspect glaucoma. Acta Ophthalmol 1998; 76:431–437.

25.Bengtsson B, Heijl A. Comparing significance and magnitude of glaucomatous visual field defects using the SITA and Full threshold strategies. Acta Ophthalmol Scand 1999; 77:143–146.

26.Wild J, Pacey IE, Hancock SA. Between-algorithm, between-individual differences in ‘normal’ perimetric sensitivity: full threshold, FASTPAC, and SITA. Invest Ophthalmol Vis Sci 1999; 40:1152–1161.

27.Sekhar GC, Naduvilath TJ, Lakkai M, et al. Sensitivity of Swedish interactive threshold algorithm compared with standard full threshold algorithm in Humphrey visual field. Ophthalmology 2000; 107:1303–1308.

28.Henson DB, Darling MN. Detecting progressive visual field loss. Ophthalmic Physiol Opt 1995; 15:387–390.

29.Henson DB, Spry PG, Spencer IC, et al. Variability in glaucomatous visual fields: implications for shared care schemes. Ophthalmic Physiol Opt 1998; 18:120–125.

CHAPTER CONTENTS

6.1Introduction 77

6.2The Parvo and Magno pathways 78

6.3The nature of glaucomatous damage 79

6.4Visual function in glaucoma 79

6.4.1Visual function in the foveal and para-foveal regions 80

6.4.2Spatial contrast sensitivity 80

6.4.3Temporal contrast sensitivity 81

6.4.4Colour vision 81

6.4.5Visual function in the more peripheral visual field 81

6.4.6Objective tests of visual function 86

6.5Summary 87

References 88

6.1 INTRODUCTION

The function of the retina is to sample the retinal image and convert this information into a form that may be conveyed to the visual areas of the brain. This process is mediated by a rich network of retinal neurones that ultimately outputs a complex transformation of the retinal image to approximately one million nerve fibres that funnel through the optic nerve head. The term ‘glaucoma’ is used to describe a group of pathological conditions that cause progressive damage to these nerve fibres. It is not surprising that damage to this complex conduit of visual information can have subtle and variable effects on visual function.

The effects of glaucoma on differential light sensitivity across the visual field are well documented and still form the basis of the clinical diagnosis.1 In the early stages of the disease, the areas of reduced sensitivity (scotomas) are small and relative but, as the disease progresses, the scotomas deepen, expand and coalesce until, in extreme cases, there is a complete loss of visual function over the entire visual field.

The subtle loss in sensitivity during the early stages of glaucoma usually goes unnoticed and in the absence of any other symptoms, patients are normally unaware of their condition until the field defects are quite advanced, by which stage significant and irreversible damage has occurred. For this reason, a great deal of research has gone into the early detection of the disease. Until relatively recently, much of this research focused on the

detection of ever-more subtle changes in sensitivity across the visual field. This work led to the development of a variety of sophisticated instruments and psychophysical algorithms, which have greatly improved the sensitivity and specificity of visual field screening.

However, over the past 20 years there has been a growing body of evidence to suggest that significant nerve fibre damage can occur before changes are detected by even the most sensitive visual field tests.2 It has also become apparent that some aspects of visual function may be reduced before the appearance of visual field defects and that visual function outside scotomas (including central vision) can show specific functional deficits when probed with appropriate stimuli.3

These findings have stimulated the drive to develop alternative screening tests so that the disease process can be detected and treated at an earlier stage. The rationale behind many of the newer tests has been the finding by Quigley et al4 that larger nerve fibres are more susceptible to damage in the early stages of glaucoma. Such fibres are functionally, as well as anatomically, distinct from the smaller fibres; the two types of fibre being responsible for conveying information about different spatio-temporal components of the retinal image. The working hypothesis has been that selective damage to the large fibres may lead to a specific visual deficit while other aspects of visual function remain unaffected.

6.2 THE PARVO AND MAGNO

PATHWAYS

To understand the nature of these changes, it is necessary to consider the functional organisation of the retina and the visual pathway.

The primate retina contains at least 20 different types of ganglion cell.5 In vitro preparations of the primate retina show three types of ganglion cell projecting to the lateral geniculate nucleus (LGN): the parasol, midget and small bi-stratified cells. The morphology, physiology and projections of these cells have been studied extensively.6,7 The axon diameter is related to cell size, which in turn increases with eccentricity for all types of ganglion cell. At any given eccentricity the parasol cells tend

Fig. 6.1 Schematic representation of the Parvo and Magno pathways.

to be larger than the midget cells. The parasol cells also tend to have larger dendritic fields than the midget cells.

The majority of parasol cells project to the magnocellular layers (1 and 2) of the LGN whereas most midget cells project to the parvocellular layers (3–6).8 There is some evidence that the small bi-stratified cells project to the koniocellular layers of the LGN9 (Fig. 6.1). The segregation of the fibres continues from the LGN to the primary visual cortex and to some extent beyond this in the dorsal and ventral streams. This concept of two anatomically and functionally distinct pathways conveying information from the retina to the brain is now well established.10 The two pathways tend to be referred to as the P and M systems according to whether they project via the Parvocellular or the Magnocellular layers of the LGN.

There are considerable differences between the physiological properties of the two pathways.11–13 Electrophysiological studies in primates have shown that the P system conveys information about colour and is characterised by good spatial resolution (acuity) but poor temporal resolution (i.e. it is unable to respond to rapid changes). In contrast, the M system has good temporal sensitivity and contrast sensitivity, but is achromatic and has poor spatial resolution. The functional specialisation of the two pathways is supported by behavioural studies of monkeys with ablated sections of the LGN. Recent research suggests that blueyellow colour vision is mediated by the small bistratified ganglion cells and red-green colour vision by the P ganglion cells.9

The M and P systems derive their different spatio-temporal properties by virtue of differences in their preganglionic connectivity and, to some extent, differences between the characteristics of the ganglion cells subserving the two systems. Approximately 90% of ganglion cells project to the parvocellular layers of the LGN. Although P ganglion cells are found throughout the retina, their density decreases with eccentricity. The receptive field size of both P and M ganglion cells varies with eccentricity but in general the M cell receptive fields are larger than those of the P cells. The axons from the M ganglion cells are generally larger than those of the P cells and therefore selective damage of the large fibres may produce a deficit in M function before there is any change in the properties of the P system.

6.3 THE NATURE OF GLAUCOMATOUS

DAMAGE

There is strong clinical and histological evidence that nerve fibres at the superior and inferior poles of the optic nerve head tend to be more susceptible to glaucomatous damage.4,14–16 This results in the characteristic arcuate field defects (see section 5.5) in ‘early’ glaucoma.

In addition, a number of studies have found that, at a given location within the optic nerve head, the large nerve fibres are lost at a faster rate than the smaller nerve fibres. For example, Quigley et al4 induced chronic glaucoma in 10 monkeys and compared the optic nerves of the glaucomatous eyes and the normal fellow eyes. They reported that there was a preferential loss of large diameter axons regardless of the location within the optic nerve. Similar results have been found when comparing post-mortem human eyes with glaucoma and age-matched post-enucleated normal eyes.

It is not clear why large fibres appear to be particularly susceptible in glaucoma. It has been suggested that it is due to the fact that they are found mainly in the superior and inferior poles of the optic nerve head, areas that are known to be weaker and susceptible to damage in glaucoma. An alternative suggestion is that in eyes with elevated intraocular pressure (IOP), the absorption of nutrients from the axon membrane is decreased

due to reduced tissue perfusion.17,18 This would tend to affect the large fibres more because of their larger surface-to-volume ratio.

The evidence for preferential large fibre loss is persuasive but not conclusive.19 It is also important to note that axon diameter increases with retinal eccentricity for both P and M cells and the axons of some peripheral P cells may in fact be larger than some more central M cells. It is also wrong to assume the P cells are immune to early damage.

However, it is reasonable to conclude that neural loss in glaucoma is partially selective for the M pathway and therefore some deficits in the aspects of visual function mediated by this pathway may be expected in the early stages of glaucoma.

6.4 VISUAL FUNCTION IN GLAUCOMA

The most widely used test for assessing visual function in glaucoma is static perimetry. The task for the patient is to detect small white stimuli superimposed on a uniform white background at discrete points within the visual field. Ideally, the differential luminance threshold at each point is determined giving a map of relative sensitivity across the visual field which can then be searched for patterns of reduced sensitivity that are considered typical of glaucoma. Modern instruments employ a variety of algorithms in a bid to minimise the number of presentations required to determine a reliable estimate of the threshold at each point.

The clinical diagnosis of glaucoma is currently based on the presence of field loss, assessment of the optic disc and consideration of risk factors such as elevated IOP, family history, race, etc. However, there is now good evidence that between 20% and 40% of ganglion cells may be lost before field defects are detected by conventional visual field analysis.2,16 This is presumably partly attributable to the fact that the small white stimuli used in perimetry are likely to stimulate both P and M cells and are unlikely to detect early deficits in the M system.

In view of this, numerous studies have sought to develop stimuli and tests that will detect glaucomatous damage at an earlier stage.3 Some have specifically targeted the P system, some have