The many faces of glaucomatous optic neuropathy - Wiley Online Library

5 downloads 0 Views 5MB Size Report
Aug 16, 2000 - abnormal backward W-shaped bowing of the lamina cribrosa ..... Harper RA, Reeves BC. Glaucoma screen- .... Carlton VIC 3052. AUSTRALIA.

C L I N I C A L

A N D

E X P E R I M E N T A L

OPTOMETRY

The many faces of glaucomatous optic neuropathy Algis J Vmgys PhD Department of Optometry and Vision Sciences, The University of Melbourne

Accepted for publication: 16 August 2000

Background: Glaucoma manifests mostly in the elderly, who frequently have other ocular changes that frustrate clear visualisation of the optic nerve head or nerve fibre layer. In the past, a large or asymmetric cup/disc ratio has been used to indicate the possibility of glaucoma. In this paper, I will argue that cup/disc ratios alone have poor sensitivity to glaucoma, and a more sophisticated approach is needed to make the earliest diagnosis. Methods: This paper reviews the literature and describes the changes that occur at the optic nerve head and in the peripapillary region as a consequence of glaucomatous optic neuropathy (GON). Results: The concept of ‘risk factors’ is developed to help screen for glaucoma. Glaucoma suspects require a full clinical investigation (visual field, IOP, assessment of anterior chamber, disc features and nerve fibres) and need to be monitored annually. For future reference, they should have their disc features recorded by instrumental methods o r with photography at an early age. As no single sign provides the perfect diagnostic marker for the disease, clinicians need to examine for a group of signs before making the diagnosis. A clinical logic is developed in this paper to enhance the detection of glaucoma. Conclusion:Adoption of a protocol similar to that detailed in this paper will enhance the early and reliable detection of glaucoma. (Clin Exp Optom 2000; 83: 3: 145-160)

Key words: cup/disc ratio, glaucoma, neuroretinal rim, optic disc haemorrhage, retinal nerve fibre layer

Optometrists have an obligation to detect the presence of glaucoma, either by screening or looking for signs of the disease. Both procedures entail different levels of responsibility and require different approaches for testing. In this paper, I discuss the processes involved in screening and detection. When detecting glaucoma, it must be remembered that, as several mechanisms (intraocular pressure, vascular and neurotoxic) are thought to be responsible for the damage, the appear-

ance of the disc a n d its surrounding tissue can vary. Other than congenital cases, glaucomatous optic neuropathy (CON) becomes more prevalent with age.’-JThus, increasing age (older than 60 years) is a significant risk factor for glaucoma (Table 1 ) . Figure 1 shows the prevalence of glaucoma in an Australian p ~ p u l a t i o n This .~ gives some indication of the age at which screening becomes important. The twoline trend has been plotted to the epideClinical and Experimental Optometry 83.3 May-June 2000

145

miological data, assuming that the prevalence of glaucoma is constant at younger ages (up to 49 years) and increases significantly beyond 60 years of age, implying that older patients warrant frequent screening at two-year intervals to ensure early detection. Screening involves assessing ‘risk factors’ and needs to be differentiated from detecting signs of the disease. Risk factors imply that individuals are more likely to develop t h e condition, as they have

Detecting the nerve head changes of glaucoma Vzngrys

General Positive family history for glaucoma Systemic hypertension, diabetes Race (Afro-Americans, Australian Aborigines, Japanese for NTG) Increasing age (> 60 years) Myopia (> -2 D)

40

60

80

100

Average age (years) Figure 1. Prevalence of glaucoma in an Australian population (after Wensor and colleagues') as a function of average age of the group. Atwo-line functionhas been fitted by floating the parameters and minimising the root-mean-squareerror term presuming a fixed prevalence below a certain age (49 years) and an increasing prevalence above this age.

Ocular High IOP (> 21 mmHg if age less than 75,otherwise > 18 mmHg) Large CDR (> 0.5) in a normal-sized eye CDR asymmetry between eyes (> 0.2) in normal-sized eyes Non-central insertion of CRA Compromised anterior chamber: shadow test or material present (pigmenVexfoliative) Screening field loss Table 1. Patient attributes that are known risk factors for glaucoma

Abnormal neuro-retinal rim (NRR) configuration: no ISNT or notches Abnormal cup configuration: cup size for disc size, lamina pore slits Blood vessel changes and compromise: kinking, baring, disc haemorrhage Peripapillary atrophy: halo, large pigment crescent Retinal nerve fibre layer (RNFL) losses: diffuse or local Functional loss typical of glaucoma Table 2. Signs of glaucomatous optic neuropathy

attributes that place them at higher risk. These attributes have been established by epidemiological trials and the presence of any general risk factor (Table 1) should lead to testing of the ocular risk factors. However, risk factors say little about the actual presence of the disease. Signs, if reliable and multiple, are used to make the diagnosis o r establish a differential diagnosis. Their presence means that glaucoma is most likely present, with some signs being more reliable and specific than others. This paper develops a logical screening protocol and reviews the changes that take place at the optic nerve and its surrounding tissue that indicate glaucoma. Scaled schematics and fundus photographs are used to demonstrate each point under discussion, as much has been learned from recent research (see Jonas and Budde" and Jonas, Budde a n d PandaJonass for particularly good reviews on this topic). In this paper, primary open angle

Pattern ERG Flicker perimetry, frequency doubling technology (FDT), short wavelength automated perimetry (SWAP) and others* Afferent pupil defect Automated static (achromatic) perimetry (ASP)

* Theories of selective loss or reduced redundancy explain why these tests are better than ASP. As a consequence, motion thresholds, random dot motion or other test paradigms may be just as useful for this purpose, but have not been included in this list due to their lack of general availability. Table 3. Functional tests known to be affectedby glaucoma listed in order of decreasing sensitivity

glaucoma is defined by the changes at the optic disc or in the surrounding tissues. This logic is consistent with the position adopted by many professional associations, for example, the American Academy of Ophthalmology. However, it is my opinion that functional losses should either precede or occur concurrently with such change. The reason that they are not found most likely reflects a lack of test Clinical and Experimental Optometry 83.3 May-June 2000

146

sensitivity, so I have added these to the list of signs (Table 2 ) . For its earliest diagnosis, GON requires the concurrent appearance of multiple signs of optic nerve or nerve fibre damage or a documented progression in one of these signs. Table 2 lists the signs that indicate GON and Table 3 gives the functional losses that can be produced by glaucoma. From Table 3, it is apparent

Detecting the nerve head changes of glaucoma Vingrys

that automated static (achromatic) perimetry (ASP) is least sensitive for early GON, although it is often the mainstay for decision-making in the diagnosis a n d management of GON. ASP should be used with all suspects and alternate methods adopted only if the disc and fields d o not match.

RISK FACTORS Many practitioners may choose to screen for glaucoma, rather than make the diagnosis or be involved in its management. In doing so, they should adopt a strategy that yields high sensitivity and specificity (greater than 0.90) by considering risk factors. These have been listed in Table 1 under the headings General and Ocular. The presence of a single ocular risk factor identifies glaucoma suspects, whereas the presence of multiple ocular risk factors (two or more) warrants further evaluation or referral due to the high likelihood for glaucoma. In this paper, I will not consider any of the risk factors other than those involving the optic nerve or its adjacent region.

Figure 2. Scaled schematic appearance of the optic nerve head for three sizes of scleral-disc openings:left panel, the scleral disc diameter is 33 per cent larger than normal opening CDR = 0.71; central panel, the scleral disc has a normal opening CDR = 0.40; right panel, the scleral disc diameter is 33 per cent smaller than normal CDR = 0.17 (cup hidden by blood vessels). The arrow in the central panel shows the scleral ring, which defines the insertion of the disc, whereas the small arrow heads show the edges of the neuro-retinal rim that starts on the inside margin of the scleral ring and which may be distinct (left edge) or diffuse (right edge). The central retinal artery has a normal insertion, the NRR shows the ISNT configuration (see text) and circular lamina pores are visible in the left panel. The aperture in the lower part of the right panel represents the light from an ophthalmoscope.

The role of cup/disc ratio (CDR) The optic disc can be thought of as a doughnut. The neuro-retinal rim (NRR), which represents the nerve fibre axons, is the doughnut ring and the cup, or cavity internal to t h e NRR, represents t h e doughnut hole. In doughnut parlance, if you have a large CDR for a fixed size doughnut, you should buy your doughnuts elsewhere. CDR refers specifically to the vertical cup-to-disc ratio, as this is the most sensitive index of GON.5 The presence of a large cup/disc ratio (CDR) is a n ocular risk factor for GON.',3,6,7 However, in isolation it should not be taken as a sign of glaucoma, as GON can be present with small cups (CDR = 0.2-0.5).' As such, the CDR can be interpreted only after evaluation of the size of the disc (Figure 2). The following discussion will develop these concepts. Epidemiological studies show that a large CDR (CDR greater than 0.5) or a large asymmetry in CDR between eyes (greater than 0.2) is more common in

g l a u ~ o m a , ' making ~ ~ ~ ' ~ both risk factors for the disease. However, this finding probably reflects the referral criteria used in these studies (large o r asymmetric CDR), as it is now appreciated that large CDRs have only a modest sensitivity for GON (0.70) and that any cupping in a small disc can indicate GON.4 However, given that fewer than 15 per cent of a clinical population have small discs and glaucoma,' a large CDR (greater than 0.5) is a useful screening tool for the majority of people.','-" Disc asymmetry (greater than 0.2) is also a limited predictor of GON as it is found in 24 per cent of diseased eyes and six per cent of normal eyes (sensitivity = 0.24, specificity = 0.94).1° Many factors contribute to undermine the reliability of CDR readings. These will be considered under two headings: those that are clinician-dependent and those that a r e not, being regulated by t h e anatomy of the disc itself. Clinical and Experimental Optometry 83.3 Mdy-JUnt? 2000

147

CLINICIAN-DEPENDENTFACTORS AFFECTING CDR MEASURES These involve recording and assaying factors such as reliability, precision and accuracy. Accuracy describes how close a determination is to the true value. The difference between your average judgement and the true value is sometimes called bias. Nonexpert clinicians have been shown to make poorer judgements of CDR compared with expert clinicians (sensitivity 0.54 for trained paramedics versus 0.95 for ophthalmologists).' It must be recognised that in older eyes the neuro-retinal rim becomes hard to define and the presence of peripapillary atrophy can confound identification of the scleral edge of the disc margin. To determine CDR, start by finding the scleral rim of the disc (Figure 2, arrow) which is a white ring, about the size of a small artery, and most visible on the nasal and temporal margins. Make sure that you

Detecting the nerve head changes of glaucoma V i n p y

identify the scleral rim and not a zone of sclera visible due to peripapillary atrophy (Figure 3 ) . Next, determine the inner edge of the neuro-retinal rim (NRR), that is, the outer limit of the cup. Identification of this feature is challenging and it is best to use coloration or shading as your guide. In younger eyes, the NRR is orangepink (least pink in the macula bundle) so estimating the edge in these eyes is relatively easy, apart from the fact that they can show a large transition zone (rounded e d g e ) . With age, t h e NRR becomes sloped, its colour becomes yellow-grey from media changes and it loses the ‘flush of youth’. In an elderly eye, expect a slow change in shade (or tone of colour) as you look along the NRR, which indicates such sloping (Figure 3) caused by the natural attrition of nerve fibres (3,000 to 7,000 p e r year) with age. However, slope changes can also be a sign of early glaucoma by way of temporal shelving (see below). In the elderly, the transition from a yellow-grey NRR to yellow-white cup becomes difficult to recognise, but a redfree filter can help by emphasising this change in shading. These judgments are easier to appreciate and, in some cases, can be made only through a dilated pupil with an indirect lens (78 D or 90 D). Similarly, the abnormally steepened slope of early glaucoma (temporal shelving) can be appreciated only with indirect biomicroscopy by using a horizontal slit (about 1/8 disc diame t e r ) . As practitioners become more skilled at slitlamp ophthalmoscopy, these judgements can be made without dilation, although they are more difficult through small pupils. Although, CDR assays can be inaccurate, ophthalmoscopic methods have been shown to yield small bias a n d interobserver errors (three to six per cent) if performed This means that well-trained clinicians should be able to estimate CDRs to within 0.1, which is needed if early losses are to be detected by screening. Precision and reliability indicate how closely you give the same outcome over a short term (precision; standard deviation of readings) or long term (reliability).

Clinicians vary in their capacity for consistency in their measures, from being rather poor to highly precise and reliable. Experience appears to have a major influence on precision and reliability, with expert clinicians giving more precise and reliable outcomes.’ To promote accuracy, precision and reliability, so that the earliest changes may be detected, I suggest that all suspects must be followed with some permanent documentation (hard copy) of their disc. Photographs (colour or black and white) or the scanning laser ophthalmoscope (SLO) or other nerve head or nerve fibre measuring methods are ideal for this purpose. DISC DEPENDENT FACTORS AFFECTING CDR MEASURES

The CDR can be influenced by many factors (Figures 2 and 3), and the size of the scleral opening and age are just two of them. The effect that age has on the appearance of the normal NRR has been discussed in the previous section. The following details the size effect, which is a more common cause for large (greater than 0.5) or small (less than 0.5) CDRs than is glaucoma.

Figure 3. The right eye of a 78-year-oldocular hypertensive (24 mmHg, R and L) patient who had been followed for the past 10 years. The disc shows a sloped NRR typical of age (small arrows), two notches in the NRR (arrow heads), vessel bayonetting at the superior notch (upperyellow arrow),a zone of peripapillary scleral atrophy (largearrows at 3 o’clock) and a diffuse RNFL loss. The visual field showed an absolute inferior arcuate defect consistent with the superior notch and a variable relative superior arcuate loss. The fellow eye was suspicious for early damage.

SIZE OF SCLERAL OPENING

People vary in the size of their scleral openings (Figure 2) just as they d o in the size of any other physical dimension. The average disc has an opening dimension of about five degrees by seven degrees (for refractions ranging from +5 D to -8 D) and has about 1.4 million nerve fibres arranged in this a p e r t ~ r eThis . ~ average disc results in a CDR of 0.44 as shown in the middle panel of Figure 2. What effect would increasing the scleral opening by 33 per cent (7 degrees x10 degrees) have on the resultant CDR? The schematic appearance of such discs is shown to scale in Figures 2 and 4. The schematics shown in Figures 2 and 4 presume that the nerve fibres retain the same size and number in each eye, that the area of the disc will determine the resultant CDR and that pathological cupping is more extensive vertically (see below). In Figure 2, left panel, as area is Clinical and Experimental Optometry 83.3 May-June 2000

148

related to the square of the radius (area = m y ) ,we have a 77 per cent increase in disc area due to the 33 per cent larger scleral opening, resulting in a CDR of 0.71. Note that in this case (CDR = 0.71) this is still a normal disc with a normal complement of nerve fibres but these nerves are now located in a larger scleral opening. In contrast, a halving of nerve fibres in a normal sized disc results in about the same sized CDR as for the large opening (0.40 to 0.63: 158 per cent increase). A similar loss in a small disc yields large CDR changes (Figure 4: 0.17 to 0.42: 247 per cent increase) and a vertical cupping (loss of the ISNT sign, to be discussed later). In fact, in the small disc, the number of optic nerve fibres has to decrease to o n e

Detecting the nerve head changes of glaucoma Vingrys

Figure 4. Schematic scaled appearance of change to the apparent cup size and resultant CDR for the small disc of Figure 2, right panel (redrawnhere in the left panel) as the NRR decreases in nerve fibre count to 50 per cent (centre panel, CDR = 0.42) and 25 per cent (right panel, CDR = 0.65). Note the thinning of the NRR on the nasal margin and that the ISNT sign does not appear in the centre and right panels.

quarter of their normal complement for the CDR to reach a similar magnitude (0.65 versus 0.71) as in a large disc. This demonstrates that small discs can have normal CDRs even with large losses of nerve fibres and they will show marked relative changes in their CDR as early signs of CON. Although the above schematics and discussion have been based on mathematical principles, they are supported by clinical observation. It has been reported that the CDR varies among normal people, being a function of disc size.14-16Large discs were called megalopapilla by Franceschetti and Bock" and more recently have been labelled as macrodiscs by Jonas and B ~ d d eSmall . ~ openings (or microdiscs) will have no cup, so a small CDR (Figure 4) in these eyes can indicate glaucoma.18 Hence, the relationship between disc size and the resultant cup size makes a simple CDR measure a n unreliable sign for GON.'3~'5~'8~19

For the CDR assay to be considered sensibly in patients, a determination of the size of the scleral opening is needed. There are many methods that can be used in making such estimate^"'^^^" but the direct ophthalmoscope method provides a simple yet reliable technique. Such an a p p r o a c h was first suggested by Franceschetti and Bock17 but developed and quantified by Gross and Drance.8The principle of this m e t h o d is shown schematically in Figure 2. The horizontal disc dimension is compared against the extent of the 5 degree aperture of the direct ophthalmoscope (the 5 degree aperture should subtend a diameter of 5 cm at 67 cm). Making this estimate is easier if you place the aperture slightly below the disc (Figure 2 ) and compare the horizontal dimension of the scleral opening and the size of the light spot, concurrently. Any disc that is larger than the aperture by 25 per cent should be expected to have a large CDR (that is, light fills the cup only, Clinical and Experimental Optometry 83.3 May-June 2000

149

Figure 2 , left panel). Similarly, a small disc occurs when the disc subtends 75 per cent or less of the light aperture. Clinicians should record whether the disc is large, normal or small and make CDR measures in patients with normal-sized openings. Adopting a grid (amblyoscope) can improve the accuracy of such measurements. Epidemiological studies show that large CDRs, as found in large scleral openings, are at higher risk for glaucoma, perhaps due to mechanical compromise of their lamina.',g Such patients should be monitored, but so should small cups in small disc openings. Large a n d small discs should not be screened by using a simple CDR ratio. The following discussion will identify conditions other than normal variability, that can produce variations in the size of the scleral opening and that will limit CDR assays. CONGENITAL DISC ANOMALIES Any of the congenital optic nerve head anomalies (tilted disc etcetera) will affect the appearance of the disc limiting the role that CDR measures have in these cases. However, colobomatous changes isolated to the optic nerve head will have the most significant effect on disc size, giving the appearance of large CDRs. Typically, they will show an arterial pattern that radiates like bicycle spokes from a hub (Figure 5 ) , whereas glaucoma will have a more normal arterial insertion.'" Coloboma may be unilateral (Figure 5) and may have associated visual field losses, which manifest as generalised depressions with or without arcuate defects. The presence of arcuate loss challenges the diagnostic process because these large CDRs are more likely to get GON especially as a congenital glaucoma. However, the level of generalised or macula sensitivity reduction is much greater in coloboma than would be found in glaucoma and the arcuate losses are non-progressive. MYOPIC DISCS High myopia (6 D or more) is a risk factor for glaucoma, especially with age, whereas moderate myopia (greater t h a n two dioptres) is known to be associated with a

Detecting the nerve head changes of glaucoma Vzngrys

Figure 5. The appearance of a disc with optic nerve head coloboma. Note the anomalous blood vessel pattern, large CDR, peripapillary crescent and indistinct NRR. The visual field of this eye showed a general depression and the acuity was 6/36. The fellow eye was normal. In juvenile glaucoma, disc blood vessels often show a radiating pattern consistentwith a coloboma. This might imply a common causative agent.

6a. There is peripapillaryhalo (pigment and scleral crescents,arrow) and shallow cupping with temporal shelving (arrow head). The visual field of the right eye showed a biarcuate defect.

greater prevalence of glaucoma.'," Due to this higher risk, patients with greater than two dioptres of myopia should be investigated for glaucoma after 40 years of age and at routine intervals (two-yearly o r more regularly depending on other risk factors) thereafter. Although the glaucoma in moderate myopia is similar to other CON, the neuropathy of highly myopic patients is atypical. These discs are large, elongated (usually vertical) and have a thinned nerve fibre layer. They require indirect viewing (78 D or 90 D lenses) for assessment and baseline visual fields and photographs for the detection of' early changes. The glaucomatous damage in high myopia tends to occur at a lower IOP than might be considered abnormal (16 to 25 mmHg) and has a shallow cupping making CDR an unreliable indc=x.45It is characterised by a substantial ring of peripapillary atrophy, called a halo (Figure 6). Studies have shown that the vascular status in the region of the halo

is compromised,22implying that ischaemic insult might be the mechanism of myopic glaucoma. It is thought that the ischaemia results from vascular changes subsequent to scleral stretching associated with the axial elongation.'

6b. The fellow eye had an absolute inferior arcuate loss

Figure 6. The appearance of the disc in a highly myopic 74year-old male (RE -9.00 DS, LE -10.00/-1.50 x 175) who has been monitored for 10 years as a contact lens wearer. The IOP for this patient was 22 mmHg R and 21 mmHg L.

SUMMARY OF THE ROLE OF CDR MEASURES

It is apparent that the CDR measure can vary between normal people and that it can be affected by factors other than glaucoma. Hence, it provides a limited and unreliable sign of glaucoma, particuhrly in myopic eyes. When screening, the CDR must be considered in conjunction with other factors and especially with an assay of disc size. In the absence of information on disc size a large CDR (greater than 0.6) provides a modest sensitivity (0.70) and specificity (0.88) for g l a u c ~ r n a Even .~ using a conservative CDR criterion for failure (a CDR of greater than 0.4) returns a sensitivity of only 0.88,9 indicating that Clinical and Experimental Optometry 83.3 May-June 2000

150

many glaucomatous eyes have small CDRs (approximately 15 per cent) .',I' Harper and Reevesg report that visual field screening is the best single predictor of glaucoma, although it yields a limited diagnostic capacity in isolation (sensitivity = 0.85, specificity = 0.91). These authors showed that reasonable diagnostic performance can be achieved by the testing of three factors (CDR, IOP, field loss) in a serial manner. A failure at either CDR (greater than 0.4) o r IOP yields suspects, who must then have fidd testing to improve specificity. However, such an approach will have limitations. If we assume test accuracy of 0.95 (sensitivity = specificity), which is better than reported in the literature for such serial logic' and a prevalence of 3.5 per cent for an average group of elderly Australians,' serial screening should yield an approximately 60 per cent false positive rate and a miss rate of approximately eight per cent. Such performance does

Detecting the nerve head changes of glaucoma Vingrys

Signls

Sensltlvlty

Splinter haemorrhage 0.10 Notching 0.20 Large CDR 0.25 ISNT sign 0.45 RNFL defect 0.46 Large CDR t bayonetting 0.29 Large CDR t splinter haemorrhage 0.36 RNFL defect t large CDR 0.51 RNFL defect t splinter haemorrhage 0.67 3 or more of the above signs 0.80-1.O Figure 7. Scaled schematic of the earliest disc changes due to glaucoma. Left panel: a normal sized disc shows a loss of the ISNT configuration (CDR = 0.65). Centre panel: abnormal insertion of the central retinal artery (CDR = 0.50) and an abnormally thinned NRR opposite the artery insertion should be evaluatedby comparing artery widths as indicated by the arrow (yellow).Note that the ISNT sign cannot be applied to such eyes. Right panel: penpapillary atrophy (pigmented zone shown by arrows; scleral zone shown by arrow heads), lamina slits, notch and baring of the superior circumlinear blood vessel (single arrow head) with a kink of the superior arterioles in this region.

Table 4. The diagnostic capacity of several clinical signs for GON when taken in isolation or together (modified after Okoshi and colleaguesM)

not yield a satisfactory clinical outcome in terms of detection although the high false positive rate can be considered as a conservative outcome for screening purposes. It can be improved, if clinicians were also to consider the size of the disc opening and the level of asymmetry in CDR between eyes: small or large discs should not be screened using a CDR in isolation. In the next section, I will describe the signs of glaucomatous optic neuropathy that can be used to diagnose the disease. I recommend that clinicians use these signs for the early detection and nianagement of GON and that these should yield high capacity for early detection.” In some cases, such as with large or small openings, high myopia o r coloboma, CDR measures a n d screening cannot be applied.

with the downward displacement of the fovea, this means that the inferior pole has the greatest number of axons. Jonas and Budde4 suggest that CON should be suspected in people when the NRR becomes of similar size in the temporal and vertical regions-for example I = S = T as shown in Figures 4 and 7-and is definitely suspicious when the temporal margin (macula bundle) becomes thicker than either vertical pole. However, in seven per cent of normal people the ISNT sign does not exist,I6 due to a vertical alignment of the cup (Figure 8) in these cases,4 thus minimising the diagnostic capacity of the ISNT sign. In those normal eyes, where the ISNT sign is missing, the eye will show symmetry in the same eye or between eyes. In particular, early GON will produce an asymmetry between the NRR thickness of the poles of a given eye with one pole being thinner than the temporal margin. A GON prevalence typical of an aged Australian population (3.5 per cent) means that the

INDICATORS FOR GLAUCOMATOUS OPTIC NEUROPATHY As glaucoma can coexist with a small CDR (less than 0.5) and large CDRs may be normal, clinicians need to record disc size (large, small, normal) and make their diagnosis in eyes with small or large discs using the signs of glaucoma rather than the risk factors. The following discussion will review these signs.

Neuro-retinal rim (NRR or doughnut ring) NRR CONFIGURATION-THE ISNT SIGN The NRR in a normal eye is known to produce an ISNT configurationlfi with the inferior margin ( I ) being thickest, followed by the superior (S), then the nasal (N) and the temporal (T) margins (called the ISNT sign; Figure 2 ) . This happens because the NRR produces a relative crowding at the vertical poles and, Clinical and Experimental Optonietry 83.3 May-June 2000

151

Detecting the nerve head changes of glaucoma Vzngrys

ISNT sign can be expected to yield a sensitivity of 0.45 at a specificity of 0.93. Although this might sound like a poor diagnostic capacity, it is quite reasonable compared to other signs (see Table 4). The ISNT sign becomes unreliable with aberrant (congenital) blood vessel insertions. Here, the thickest NRR region is usually in the area of the insertion of the central retinal artery (Figure 7, central panel). As an abnormal insertion of the central retinal artery is a risk factor for glaucoma4 (Table l ) , these patients should be closely monitored using other signs. In addition, the ISNT sign may not be useful in cases of large scleral openings, myopia and coloboma. In these latter cases, the cause of the ISNT configuration (size of the scleral opening and nerve fibre distri-

bution and number) is not present. Although the ISNT sign is useful, determining the edge of the NRR in elderly people (older than 70 years) is a clinical challenge that can frustrate the appreciation of this sign. In these cases, consider the shelving of the temporal NRR (slope of the rim) to help confirm the presence of neuropathy. In patients with an arteriole in this region, shelving may be appreciated by the kinking of this vessel (Figure 8c), although this is not a reliable indicator. In small to normal discs, shelving is best appreciated with a thin horizontal slit over the temporal NRR surface. U n d e r these conditions, look for a deviation in the slit as the NRR forms a depression. These judgments are challenging to make, as we have shown else-

where that stereopsis cannot be used for such purpose^.'^ Dynamic evaluation by scanning up and down the tissue can help expose the saucer-like nature of the shelving. It must be remembered that ageing produces a greater slope in the NRR, so sloping per se is not indicative of disease. Rather, a saucer-like configuration must be elicited (Figure 8d). In cases in which the light is angled correctly, a difference in shade (glow o r shadow) becomes apparent with saucer-like NRR margins. With large scleral openings, the NRR is naturally thinned and the ISNT sign may not exist. Hence, the clinician needs to develop a method of appraisal of the thickness of the rim plateau to detect NRR loss and thinning in large discs. NRR thickness can be estimated using the diameter

8a. A vertical cup in a normal sized scleral opening. This large CDR (0.6) is in an otherwise normal eye (IOP is 18 mmHg, R and L) in this 52-year-old female, who has a family history of glaucoma. The fellow eye had a similar configuration for its cup (CDR 0.6). The NRR does not show the ISNT sign (due to the vertical cup), but there are no other indicators for glaucoma in this eye. This person needs a photograph and monitoring in the future as a low-risk case.

8b. A large CDR (0.7)in a large scleral opening (greater than 33 per cent) in an otherwise normal eye (IOP is 14 mmHg R and L) of this young man (33 years). The fellow eye had a similar configuration for its cup (CDR 0.7). The NRR does not show the ISNT sign typical of large openings, but there are no other indicators for glaucoma. This person needs a photograph and routine monitoring in the future as a low risk case with careful attention to the NRR opposite the arterial insertion and the circumlinear vessel at this margin (6 to 8 o'clock).

8c. Alarge CDR (0.6) with a scleral rimvisible (arrow) in this58year-old female. The scleral opening is of a normal 'size, the ISNT sign is missing (I = S = T) and the superior circumlinear blood vessel is bared (arrow). The IOP was normal (18 mmHg, R and L), as were visual fields. Is this a normal variant as per Figure 8a or is this the earliest sign of CON? The visual fields and optic nerve heads have remained unchanged over the past seven years (since age 51 years) and the patient is being monitored as at medium risk.

Figure 8. The appearance of several optic nerves with large vertical CDRs (greater than 0.5) Clinical and Experimental Optometry 83.3 May7June 2000

152

Detecting the nerve head changes of glaucoma Vzngrys

of the first division of the central retinal artery as a guide. The NRR should never be thinner than one artery width, and an NRR of one to two artery widths should be considered as suspicious (Figure 7, centre panel). This sign should be looked for in the macula bundle for cases with diffuse loss (Figure 4, right panel) and elsewhere for focal losses. However, the thinnest margin of NRR should never be found at the poles. As a person ages and arterio-sclerosis ensues, the arterial comparison of NRR thickness may become less reliable, so the artery/vein (A/V) ratio must be recorded and this index used only when the A/V is close to 2/3 (Figure 3 shows a small A/V ratio). Local thinning of NRR will produce a notch. In normal eyes, these should always

be on the temporal side, near the horizontal. When notches are found removed from the horizontal (Figure 8 d ) , they must be treated as suspicious because they can indicate a pathological cause of focal erosion. The closer a notch is found to the vertical poles, and the greater their number (for example, Figure 9 ) , the greater the level of suspicion. Although the appearance of localised NRR curvature disruptions (notches) are signs of localised neuropathy, they are not found often with open angle glaucoma where diffuse losses tend to occur in the majority of cases (80 per cent).4,19 Notches tend to occur more often in cases of normal tension glaucoma where they can give the appearance of pseudo-pits, but the low prevalence limits their diagnostic role in other forms of

GON (predicted sensitivity of 0.20). Pallor of the NRR is found with advanced glaucoma only in the presence of near total NRR destruction. The nasal margin will usually retain coloration until very late in the disease. The macula region of the NRR in pigment dispersion eyes is paler than normal, but not consistent with the pallor of advanced atrophy. As a consequence, pallor is not a good sign for early glaucoma and its presence suggests the possibility of other neuropathy (ischaemia, mass et cetera) ; clinicians should re-evaluate their diagnosis in the presence of marked pallor of the NRR (Figure 10).

8d. The appearance of the optic nerve of a 59-year-old hyperopic female, who has been monitored for narrow angles over the past 10 years. This eye has lost the ISNT sign, there is baring of a superior blood vessel (arrow head), the scleral rim (arrows) identifies a prominent temporal zone of peripapillary scleral and pigmentary atrophy (arrow) with notches in the adjacent NRR (blue arrow heads). This eye also had a visual field loss (courtesy T Fncke).

Figure 9. The appearance of a large disc with a large CDR (0.75) from a 58-year-old woman with low-tension glaucoma (IOP 13 mmHg, R and L). The arrow heads locate four notches. The notch at the bottom of the disc is very deep and shows lamina pores in its base: this is called a pseudo pit. The patient’s field showed a biarcuate defect with losses near fixation.

Figure 10. A large CDR (0.8) in a young woman, who has a large scleral opening and normal IOPs (12 mmHg, Rand L). Note that the RNFL is visible in the superior and inferior arcuate regions as a bright zone, but is thiined and dark in the macula bundle, which is about as dark as the nasal region (not normal). Also note the marked optic atrophic pallor on the nasal and temporal edges of the NRR. This woman has compression in the region of her chiasm and not glaucoma (courtesy N Mantzioros).

Clinical and Experimental Optometry 83.3 May-June 2000

153

Cup configuration (doughnut hole) Early glaucoma produces a vertical cupping compared with the normal horizon-

Detecting the nerve head changes of glaucoma Vingrys

Figure 11. A large CDR (0.7) in a young woman (43 years) who has a normal scleral opening and high IOPs (24 mmHg, Rand L). Her disc has slit-like pores (inferior yellow arrow) compared to the circular pores (superior arrow head). Note that all pores have a vertical orientation. Her visual field has an absolute superior arcuate scotoma and she had narrow anterior angles. (CourtesyJJ Thimons)

12a. In 1993, he had a large CDR (0.5) in a normal scleral opening, high IOPs (26 mmHg R and 24 mmHg L) and a blood vessel bared (inferior arrow). The inferior rim was thinned (abnormal ISNT sign), but the field was normal. This person was followed as a suspect, with yearly reviews.

12b. In 1995, the ISNT sign was definitely abnormal, the baring had become more pronounced (inferior arrow) and the NRR showed a marked generalised erosion along the temporal margin. The superior margin had thinned and had a splinter haemorrhage (arrow head). The field was still normal at this time, although an arcuate field defect developed about four years later. (Courtesy JJ Thimons)

Figure 12. The left eye of a 56-year-old male with a family history of glaucoma

tal or circular cup (compare Figures 2 and 7). This results in the loss of the ISNT sign. Studies also suggest that the deepest cups occur in glaucomatous conditions that have the highest IOPs (pressure cause) and that the deeper the cup, the smaller the zone of peripapillary atrophy (vascular cause, see below). This is particularly true for juvenile onset glaucoma and also has been found in the focal type of normal tension glaucoma..' In these cases, very deep cupping can result, which gives the appearance of a pseudo-pit (Figure 9) of the optic nerve, with the lamina visible in the bottom of the pit, which is not seen in true pits. In contrast, most glaucomatous cupping produces a shallow erosion of the NRR, resulting in a gradually sloped or saucer-shaped rim rather than a steep-sided edge. Eyes that show gross asymmetry in the level of cupping with patent field loss and normal IOPs should be considered for the presrnce of

orbital mass, ischaemic anterior optic neuropathy (AION) or carotid insufficiency. In some eyes with deep cups the configuration of the lamina pores can be seen to alter. Miller and Quigley2$showed that the normal configuration of lamina pores (small horizontal ovals) became more vertically oriented and slit-like as the glaucomatous damage progressed. This was confirmed more recently by Fontana and colleagues"' with SLO methods. Although the cause for this change is not clear, it has been suggested that it may involve greater visibility of normally invisible pore structures following axonal death or that i t may represent a fusion of the pores due to shearing forces.'" Colobomata and large scleral openings can also produce slits, although they tend to be horizontally oriented. Thus, the appearance of slits should be taken as indicating the need for further investigation. However, vertical slits are most likely due to glaucoma and can be used as signs of this disease (Figure 1 1 ) . (:linical and Experimental Optometry 89.3 May+ne

154

2000

An interesting observation made by Jonas and FernandezZ7is that the distance from the central retinal artery trunk (point of entry) to the disc margin is correlated to the degree of glaucomatous neuropathy (Figure 7, centre panel). They argue that this might be due to mechanical causes and propose that the vascular structure strengthens the lamina i n the region of the vessel. Histological data from autopsy eyes that have glaucoma show an abnormal backward W-shaped bowing of the lamina cribrosa, greatest in regions removed from the central retinal artery,gx which supports this theory. Hence, eyes with a displaced central retinal artery are more liable to GON in the region most distal to the point of blood vessel entry. Eyes with mislocated central retinal arteries should be considered to have a greater risk for GON in their distal rim, and be iilonitored for signs of GON in this region. Photographs will help detect the earliest changes to their NRR.

Detecting the nerve head changes of glaucoma Vingry

Figure 13. A small CDR (0.3) in a woman (54 years) who has a normal scleral opening and normal IOPs (13 mmHg, R and L) and a family history of GON. She shows a thin superior NRR (abnormal ISNT), an adjacent zone of pigmentary disruption and local arteriolar thinning (arrow head, thin; arrow, thick) typical of either hypertension or GON. At the time her blood pressure was normal and her fields were normal. She is being monitored as a medium risk suspect, with annual reviews.

Figure 14. Schematic of retinal nerve fibre layer (RNFL)light patterns. The left panel shows the configuration for a normal eye (macula is shown on the left in all panels). Here, the brightest RNFL bands lie supero-temporal and infero-temporal, with the macula zone (M) being slightly darker and the nasal zone being darkest. The typical appearance of the RNFL should be judged in the regions of the circles, where it should give a bright-dark-bright (BDB) appearance as you move vertically downwards on the macula side. The central panel shows the effect of a generalised RNFL loss, in that the BDB pattern and ISNT sign are lost. The right panel shows a region of local RNFL loss (superior temporal) with a local notch.

Blood vessel changes

S-shaped bends in vessels lying o n the same plane. Overpassing occurs as the NRR erodes underneath the blood vessel, leaving it hanging like a bridge over the resultant cavity. Baring is seen when the NRR erodes at the edge of a blood vessel, leaving the vessel distant from the neural tissue (Figures 8c and 12). This makes those blood vessels that track along the inner margin of the NRR (circumlinear vessels) particularly useful for showing baring in early GON (Figure 12). However, not everyone has such vessels, which limits the general applicability of this sign, and in many normal eyes, blood vessels can appear bared to a small degree (usually up to two arterial widths, using the same artery for width estimates). Baring that is greater than two arterial widths is most likely abnormal. Changes in baring are particularly useful signs of progressive CON erosion, although they require

KINKING AND BARING

As the blood vessels within the papilla lie near the top of the nerve fibre layer, undermining or erosion of the NRR will result in changes either to the configuration of these vessels or to their orientation. Such changes are visible with ophthalmoscopy and can be used as indications of GON. Orientational changes result in the appearance of kinking (bayonetting) (Figure 3 ) , whereas configurational changes will give baring or overpassing (Figure 7, right panel). Kinking in blood vessels occurs after neural erosion produces different planes along the vessel path, resulting in a kink as the vessel moves from one plane to the other (Figure 8c). These are reliable signs of neural loss if a cavity (or notch) in the neural tissue can be visualised in the region of the blood vessel (using a 90 D lens), otherwise they might arise from

Clinical and Experimental Optometry 83.3 May-June 2000

155

photographs for early detection (compare Figures 12a and 12b). Figure 12 demonstrates the importance of photographic documentation for the early detection of GON. LOCAL OR DIFFUSE ARTERIAL CALIBRE CHANGES Diffuse and localised narrowing of the

arteries have been reported with optic neuropathy and glaucoma, implying that these signs are not specific for glaucoma but can indicate any optic ne~ropathy.'~-'' Moreover, focal narrowing can be seen in patients with hypertension so its capacity to discriminate CON is limited. A recent angiographic study has shown that the localised arterial narrowing in peripapillary regions represents true stenosis.J' The lack of specificity for glaucoma and the fact that the degree of focal narrowing increases with age in normal eyes (probably due to hypertensive and/or arteriosclerotic effects), means that this sign has

Detecting the nerve head changes of glaucoma Vingrys

limited use in the diagnosis of glaucoma except to confirm the condition in the presence of other signs (Figure 13). As hypertension is a risk factor (Table 1) the presence of arterial calibre changes should alert the clinician to investigate further. HAEMORRHAGES

Flame and splinter haemorrhages at the border of the disc (Figure 12) are a hallmark of CON and are more common in normal tension c a ~ e s .Studies ~ ~ , ~ ~suggest that they are more likely in the early to middle stages of glaucoma and that they indicate progression of the disease.g5However, as most persist for only six to eight weeks, this means that many disc haemorrhages are likely to go undetected. This transient characteristic yields a relatively low prevalence in clinical practice (seven to 10 per cent)'",'" meaning that they have limited sensitivity for CON (0.1) even though, when present, they have a high specificity for the disease. In particular, they are good indicators of disease progression.

15a. Upper left. A colour photograph of a normal RNFL configuration showing the typical bright-dark-brightlight reflex moving vertically from superior to inferior in the temporal region

15h. Upper right. Early localised RNFL losses with three wedge defects (arrows). These demonstrate how a local disruption to the BDB pattern facilitates detection. (Courtesy A Litwak)

15c. Lower left. The worn corduroy effect found in an early wedge defect. This effecl usually becomes evident o n higher magnification (compare Figures 15b to 15c). (Courtesy A Litwak)

15d. The panel on the lower right is a redfree colour photograph showing a small CDR (0.3) in a small scleral opening. There is marked loss of RNFL in the macula bundle (yellow arrows) that makes this area darker than the nasal region, with the blood vessels prominent in relief. There is also a mild worn corduroy effect in the inferior bundle (white arrows). This patient has a pronounced glaucomatous field loss.

Penpapillary crescents or halos Glaucoma produces two types of change in the peripapillary region (Figure 7 , right p a n e l ) , a pigmented crescent (called zone alpha) and a scleral crescent (called zone beta) .3H When a scleral crescent is present (Figures 3, 6 and 8d), it lies adjacent to the disc, whereas the pigmented crescent can be removed from the disc or it can be adjacent to the disc iffound in isolation (Figure 13). Pigmentary crescents can appear as local thin strips (Figure 6) or as thick regional disruptions (Figure 8d, 7 to 9 o'clock, Figure 13, 9 to 11 o'clock). Histologically, the scleral crescent (zone beta) corresponds to a loss of retinal pigment epithelium and photoreceptorsggand appears to be associated with a region of deficient blood flow.'l The significance of the scleral crescent is that it occurs frequently in some forms of GON and rarely in normal eyes." However, it must be differentiated from the temporal crescent of myopia, the scleral crescent of tilted discs (often inferonasal) and the

Figure 15. The appearance of the RNFL in normal and glaucomatous eyes

Clinical and Experimental Optometry 83.3 May-June 2000

156

Detecting the nerve head changes of glaucoma Vzngrys

peripapillary crescent of highly myopic eyes (greater than 8 D, usually a thin crescent). In contrast, pigmentary crescents are often found in normal eyes (15 to 20 per cent), so their presence has a low specificity for disease.'8 However, very large pigmented crescents (greater than thickness of a normal NRR) that have a mottled appearance or thin pigmented strips adjacent to scleral crescents, are infrequently found in normal eyes. The variable appearance of these crescents in both normal and glaucoma eyes makes crescents an unreliable sign of GON in isolation, but good alerts for the clinician to undertake a more rigorous evaluation. Figure 8d is a good example of crescents (pigmentary and scleral) that can be seen in a glaucomatous eye. Here the crescents were suggestive of GON in a case of creeping angle closure glaucoma."' In the myopic form of glaucoma, the usual temporal crescent gives way to a total circumferential scleral halo delimited by a pigmentary edge (Figure 6), which is associated with a high risk for GON. Myopic GON is a challenge to detect as it gives a shallow cupping at normal, or near normal, IOP (16 to 25 mmHg) with generalised NRR loss in an eye that has a thinned nerve fibre layer. The presence of a field loss helps the diagnosis. Peripapillary crescents a r e less common in nonglaucomatous atrophy, so their presence is highly specific for GON.40

Retinal nerve fibre layer (RNFL) The RNFL can be visualised in most eyes (90 to 95 per cent) although age, myopia and large scleral openings make it less visible. Two patterns of loss of RNFL are evident: a diffuse loss that affects the majority of glaucoma cases (80 per cent) and a localised loss (20 per cent). A redfree filter can be used to enhance the visibility of the RNFL but this is not needed for t h e appreciation of diffuse loss (Figure 14). DIFFUSE LOSSES

The RNFL is thickest at the superior and inferior poles of the disc, making these areas most easily visible (Figure 14 and 15a). This yields a characteristic light

pattern that can be appreciated with a 14 D or 20 D lens and indirect ophthalmoscopy, or on fundus photography, as a bright-dim-bright pattern (BDB) going from the superior pole through t h e macula to the inferior pole (Figure 14, left panel). For this appreciation you do not have to visualise the RNFL, only the reflections from it, and as the human eye can detect small variations in brightness, this presents an easy task. For the purpose of these judgements, compare vertically aligned regions about one disc diameter towards the macula (Figure 14, left panel and Figure 15a). Such judgements can also be made with a 90/78 D lens or with direct ophthalmoscopy, although the lack of simultaneous viewing from the restricted field of view makes subtle differences harder to detect using a brightness comparison. Diffuse loss of RNFL is difficult to detect, but it is appreciated when the BDB pattern becomes aberrant. In fact, in early GON, one of the poles (superior or inferior) will become darker and may become as dark as the macula bundle. In advanced GON, all of these regions may become as dark as the nasal retina, which should always have the darkest appearance in a normal eye (Figure 14, centre panel). Once the change in reflection is detected, a direct ophthalmoscopic view ( o r 90/78 D) of this same region will show that the blood vessels stand out in relief, as they lack the normal nerve fibres running over them. This is particularly evident with medium and small calibre vessels that run perpendicular to the general direction of the nerve fibres. In normal eyes these vessels are less distinct, as the nerve fibres partly bury them. In suspect cases, comparisons of the BDB patterns between poles or eyes may be useful, as GON typically affects one pole o r eye more than the other. Increasing age, light skin pigmentation and high myopia can frustrate the visualisation of the RNFL but, with practice and a red-free filter, it should be visible in 90 to 95 per cent of eyes. In those cases in which it is not visible, clinicians should consider the possibility of a generalised thinning of the RNFL. Clinical and Experimental Optometry 83.3 May-June 2000

157

LOCAL RNFL DEFECTS: SLITS OR WEDGES

A minority of CON (20 per cent) give localised RNFL defects. These appear as wedges that run to and touch the edge of the optic disc (Figure 14, right panel; Figures 15b, 15c, 15d). The isolated spindles or slits are more likely to be Muller cell end feet than RNFL losses. The presence of local RNFL defects is best detected using the global appraisal method described above, although early loss needs high magnification (90 D, 78 D ) for appreciation. In these early cases, the wedge will appear slightly dimmed and have a textured component that looks like worn corduroy, with slit-like troughs and valleys running throughout, indicating a nonuniform loss of RNFL (Figures 15c and 15d). The nasal fibres first affected in glaucoma run deep in the nerve fibre layer and these troughs are not regions of loss, but zones of collapse in the underlying fibres. They are usually found about six to eight weeks after a disc haemorrhage and correlate well with local NRR abnormalities (notches). Typically, they can precede visual field loss by up to five years.41 CLINICAL APPLICATION ~

~

All presenting patients should be screened for the existence of general risk factors (Table 1). The presence of one or more general risk factors requires either the testing of ocular risk factors or evaluation for signs of GON.

Screening When screening, practitioners need to determine the level of ocular risk by preforming the tests indicated by bold type in Table 5 and field screening should be performed in patients who fail any of those tests. Patients with repeatable abnormalities in their fields should be fully evaluated for the signs of glaucoma. It needs to be reiterated that large or small scleral openings and eyes with high myopia (greater than 8 D), coloboma or other congenital optic nerve anomalies cannot be screened reliably. The shadow test will identify narrow anterior chambers and a shadow of greater

Detecting the nerve head changes of glaucoma Vzngtys

Anterior chamber depth assay IOP measurement CDR evaluation Visual field screening Table 5. Visual field screening should be performed if patients fail any of the other three tests.

than 0.33 is cause for failure.'"' These patients will need to have the depth of their anterior chamber determined (Smith test o r variant: see Fricke, Mantzionis and Vingrys40) and a gonioscopic evaluation. The IOP measure should record a failure if a patient's IOP is consistently greater than 21 mmHg. This criterion IOP drops to 18 mmHg for people older than 75 years of age. Patients with a single IOP greater than 29 mmHg must be considered as possible cases of angle closure and must have their angles gonioscopically examined. Patients who consistently show an IOP from 22 to 29, but have normal signs, should be classified as ocular hypertensive and therefore as glaucoma suspects. A large (greater than 0.5) o r asymmetric (greater than 0.2) CDR is also reason for screening failure in a normal sized disc. Clinicians must consider disc size (large, normal, or small) before undertaking screening. Any large or small discs must be evaluated for signs of glaucoma as a CDR measure is an unreliable sign of GON in these eyes. Visual field screening should involve a central visual field pattern of at least 26 optimally placed points"' and the use of a three-zone logic or equivalent.9 A failure is recorded if 15 per cent or more of test points are defective (absolute or relative) or if greater than one-third of these are clustered together in one quadrant. Initial failures must be retested (once or twice at two- to four-week intervals) to

Largelasymmetric CDR for the particular disc size NRR does not show ISNT andlor has temporal shelving Peripapillary scleral crescent or large pigment crescent (r NRR) RNFL loss (diffuse or local), notching Slit-like lamina pores (especially vertical) Kinking or baring of the blood vessels andlor non-central artery insertion Splinter disc haemorrhage, focal arterial narrowing Table 6. Optic disc characteristicswhich may indicate glaucoma. The first four items (bold) may be the earliest evidence which may occur prior to the detection of field defects.

establish that learning effects are not present and that the defects are reproducible. A borderline result is when five to 14 per cent of the points are abnormal and this should be viewed in the light of other findings. Glaucoma screening should be conducted at the first visit over the age of 40 years and continue at five-yearly intervals up to 60, at which time it should become a biennial event. The literature suggests that patients who fail IOP or CDR or have narrow chambers should be treated as glaucoma suspects and be evaluated for signs of the disease (see below). When screening, all these tests must be performed on the patient to yield a high sensitivity (0.94) at a moderate specificity (0.69). Subsequent field testing will improve the specificity to clinically acceptable levels.YHowever, it was noted previously that this approach could be associated with many false positives (about 60 per cent) and some misses (about eight per cent). Clinicians who choose to undertake screening need to be aware of these limitations.

Detecting early glaucoma A failure at screening, or an alternative to screening, requires evaluation of the disc for signs of glaucomatous damage. All glaucoma suspects should have their discs photographed for future comparison. Optic disc photographs (or documentation with other instrumental methods) at two-yearly intervals in low risk cases (one sign only), and at five-yearly Clinical and Experimental Optometry 83.3 May-June 2000

158

intervals for suspects (hypertensives, high myopes, large or small srleral openings) should facilitate the early detection of GON. At these reviews, a disc is judged as having a moderate o r high probability of GON, if it has one or more of the signs given in Table 6. The first four of these signs (in bold type) are taken as giving the earliest evidence of GON, and can be solicited before any perimetric defects." A documented change (photographs) in any of these four signs is a definitive indication of disease. The optic nerve evaluations should be made through dilated pupils at the first examination and non-dilated reviews at every second visit. In addition, photography (or other method) is needed for future management a n d t h e earliest detection of progression. Note that for ophthalmoscopic purposes, the level of dilation does not have to be maximal and a four- to five-millimetre non-mobile pupil will usually suffice. A cocktail of 0.25 per cent tropicamide and one per cent phenylephrine is good for this purpose.'' However, a larger pupil might be needed for photography. Abnormal disc observations should be confirmed with functional testing, although the existence of functional loss is not needed for the diagnosis in cases of multiple signs, due to the high diagnostic capability of such changes. Clinical review periods will need to mirror the level of risk and should range from six to 24 months.

Detecting the nerve head changes of glaucoma Vingrys

DIAGNOSTIC CAPABILITY The diagnostic capability of the signs described in the previous discussion has not been rigorously tested by prospective trials, and there exists a need for such research. However, in the absence of these trials, aspects of the sign's diagnostic capacity can be appreciated from the details already given in this paper, along with a recent study conducted in Japan. In that study, 10,490 people (8,579 over 40 years) had their optic nerves photographed during an unrelated health check.44The photographs were evaluated for signs of a large CDR, NRR notching, vessel bayonetting, splinter haemorrhages and RNFL defects. These were found in 309 eyes (3.5 per cent) of the original group who subsequently undertook a clinical work-up (ophthalmic examination plus Humphrey 24-2 perimetric thresholds) to determine the diagnosis. Twenty-four per cent of these eyes were found to have normal fields. This could imply that field loss might not have developed, or that other causes could give rise to the signs and so lead to potential misdiagnoses. Nevertheless, the sensitivity and specificity of these signs were determined for cases that were positively identified as having a glaucomatous field defect. The outcomes of this comparison have been summarised in Table 4. This shows, as might have been expected, that any single sign is a poor predictor of glaucomatous field loss, often due to the low occurrence in CON (for example, splinter haemorrhages). For any single sign, the presence of RNFL defects or an absence of the ISNT sign gives the greatest sensitivity for glaucoma. Improved diagnostic reliability can be achieved if multiple signs (at least two) are present, preferably including RNFL or ISNT defects. It is important to note that once three signs are present in the same eye, glaucomatous optic neuropathy is most likely present. The lower sensitivity for field loss (0.8 to 1.0) in the presence of three signs could reflect the fact that some signs are known to precede field defects. The outcome of this study implies that clinicians must base their diagnoses on the

cumulative evidence provided by several different signs, as none is a perfect predictor of disease when taken in isolation. Patients with one eye sign (Table 2) in the absence of a RNFL or ISNT defect and a normal field should be treated as glaucoma suspects of low risk and reviewed at one yearly intervals. Those with two signs (in the absence of RNFL defects or ISNT) should be treated as moderate risk cases, as should those with an RNFL defect or an absence of an ISNT sign in one eye. Moderate risk cases need review at six to 12-monthly intervals depending on other factors (age, IOP, other general risk signs). Patients with two signs, including an RNFL defect or loss of ISNT (unilateral), should be considered for treatment. If treatment is delayed because the field is normal, they should be reviewed at no greater than six to 12 monthly intervals depending on age, IOP et cetera. Finding three or more signs in the same eye (not necessarily at the same visit) indicates the presence of CON and requires medical intervention, regardless of the status of the visual field. Once the diagnosis of CON is made, patients must have their discs photographed, anterior chambers evaluated, IOPs measured and be subject to threshold visual field testing. A sensible recall schedule and monitoring program should be developed and implemented. Having patients return in the month of their birthday is a good memory aid for annual visits.

CONCLUSION This paper defines the changes to the optic nerve that occur with glaucoma. It defines a protocol that can be used in screening for the disease, and it discusses the efficiency of methods needed to diagnose the presence of glaucoma. As the disease is a lifelong condition, and the medications are not benign, the instigation of medical therapy should not be undertaken lightly. Thus, reaching the correct diagnosis is important. By adopting the procedures outlined in this paper, practitioners should detect the earliest changes due to CON and perhaps can have an impact on the large group of Clinical and Experimental Optometry 83.3 May-June 2000

159

elderly undiagnosed (50 per cent) glaucoma sufferers in Au~tralia."."~ ACKNOWLEDGEMENTS

D Cockburn, A Anderson and S Pellizer provided advice, encouragement and assistance in preparing this manuscript. T Fricke, JJ Thimons, N Mantzioros and T Litwak kindly provided some of the clinical photographs. REFERENCES 1. Buhrmann RR, Quigley HA, Barron Y, West SK, Oliva MS. Mmbaga BBO. Prevalence of glaucoma in a rural East African population. Invrst Ophlhalmol Vis Sri 2000; 41: 40-48. 2. Hollows FC, Graham PA. Intra-ocular pressure, glaucoma and glaucoma suspects in a defined population. Brit J Ophthalmol1966 50: 570-586. 3. Wensor MD, McCarty CA, Stanislavsky YL, Livingston PM, Taylor HR. The prevalence of glaucoma in the Melbourne Visual Impairment Project. Ophthalmology 1998; 105: 733-739. 4. Jonas JB, Budde WM. Diagnosis a n d pathogenesis of glaucomatous optic neuropathy: morphological aspects. Prog Rdinal EyyeKrsenrrh 1999; 19: 1-40. 5. Jonas J B , Budde WM, Panda-Jonas S. Ophthalmoscopic evaluation of the optic nerve head. Sun: Ophthalmol2000; 43: 293320. 6. Tuulonen A, Airaksinen PJ. Initial glaucomatous optic disc and retinal nerve fiber layer abnormalities and the mode of their progression. AmJOlphthalmol1991; 111: 485490. 7. Tielsch JM, Katz J, Singh K et al. A population-based evaluation of glaucoma screening: the Baltimore eye survey. AmJb$piderniol 1991; 134: 1102-1110. 8. Gross PG, Drance SM. Comparison of simple ophthalmoscopic and planimetric measurements of glaucomatous neuroretinal rim areas. JGlaucoma 1995; 4: 314316. 9. Harper RA, Reeves BC. Glaucoma screening: the importance of combining test data. Optom Vi, Sri 1999; 76: 537-543. 10 Ong LS, Mitchell P, Healey PR, Gumming RG. Asymmetries in optic disc parameters. T h e Blue Mountains Eye Study. Invpst Ophthalmol Vis Sci 1999; 40: 849-857. 11 Jonas JB, Beruga A, Schmitz-Valckenberg P, Papastathopoulos KI, Budde WM. Ranking of optic disc variables for detection of glaucomatous nerve damage. Invest Ophthalmol Vis Sci 2000; 41: 17641773. 12. Jonas JB, Papasthapopoulous KI. Ophthalmoscopic measurement of the optic disc. Ophthalmology 1995; 102: 1102-1106. 13. Montgomery DMI. Measurement of optic

Detecting the nerve head changes of glaucoma Vzngrys

disc and neuroretinal rim areas in normal and glaucomatous eyes. Ophthalmology 1991; 98: 50-59. 14. Bengtsson B. The variation and covariation of cup and disc diameters. Artn f)phthnlmol 1976; 54: 804-818. 15. Caprioli J, Miller JM. Optic disc rim area is related to disk size in normal subjects. Arch Ophthalmol1987; 105: 1683-1685. 16. Jonas JB, Gusek GC, Naumann GOH. Optic disc, cup and neuroretinal rim size configuration and correlations in normal eyes. Inunt Ophthalvkol vis Sci 1988; 29: 1151-1158. 17. Franceschetti A, Bock RH. Megalopapilla: a new congenital anomaly. Am J Ophthalmol 1950; 33: 227-239. 18. Jonas JB, Fernandez MC, Naumann GOH. Glaucomatous optic nerve atrophy in small disks with low cup-to-disk rations. Ophthalmology 1992; 97: 1211-1215. 19. Jonas JB, Gusek GC, Naumann GOH. Optic disc morphonietry in chronic primary open-angle glaucoma: I Morphometric intrapapillary characteristics. Gra+s Arrh Clin Exp Ophthalmol1988; 226: 522-530. 20. Debney S, Vingrys AJ. Case report: The morning glory syndrome. Clin Exp Optom 1990; 73: 31-35. 21. Perkins ES, Phelps CD. Open angle glaucoma, ocular hypertension, low-tension glaucoma and refraction. Arch Ophthalmol 1982; 100: 14641467. 22. O’Brart DP, de Souza-Lima M, Bartsch DU, Freeman W, Weinreb RN. Indocyanine green angiography of the peripapillary region in glaucomatous eyes by confocal scanning laser ophthalmoscopy. AmJf3phlhalmol 1997; 123: 657-666. 23. Fraser S, Bunce C, Wormald R. Risk factors for late presentation in chronic glaucoma. Invest Ophthnlmol V ~ Sci A 1999; 40: 2251-2257. 24. Vingrys AJ, Helfrich KA, Smith G. The role that binocular vision and stereopsis have in evaluating fundus features. Optom Vzs Sci 1994; 71: 508-515. 25. Miller KM, Quiggley HA. The clinical appearance of the lamina cribrosa as a function of the extent of glaucomatous optic nerve damage. Ophthalmology 1988; 95: 135138. 26. Fontana L, Bhandari A, Fitzke FW, Hitchings RA. In vivo morphometry of the lamina of the lamina cribrosa and its relation to visual field loss in glaucoma. Cum Eye Res 1998; 17: 363-369. 27. Jonas JB, Fernandez MC. Shape of the nenro-retinal rim and position of the central retinal vessels in glaucoma. B r J Ophthalmol1994; 78: 99-102. 28. Quigley HA, Addicks EM. Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthnlmol1981; 99: 137-143.

29. Ratkin SJA, Drance SM. Peripapillary focal retinal arteriolar narrowing in open angle glaucoma. J Glauc 1996; 5: 22-28. 30. Rader J. Feuer J, Anderson DR. Peripapillary vasoconstriction in the glaucomas and anterior ischemic optic neuropathy. Am J Ophthalmol1994; 117: 72-80. 31. Frisen L, Claesson M. Narrowing of the retinal arterioles in descending optic atrophy. A qualitative clinical study. Ophthalmology 1984; 91: 1342-1346. 32. Papastathopoulos KI, Jonas JB. Fluorescein angiographic correlation of ophthalmoscopic narrowing of retinal arterioles in glaucoma. BrJ Ophthalmol1998; 82: 48-50. 33. Drance SM, Fairclough M, Butler DM, Kottler MS. T h e importance of disc hemorrhage in the prognosis of chronic open-angle glaucoma. Arrh Ophthalmoll977; 95: 226228. 34. Drance SM, Begg IS. Sector haemorrhage. A probable acute disc change in chronic simple glaucoma. CanJOphthalmol1970;5: 137-141. 35. Jonas JB, Xu I,. Optic disc hemorrhages in glaucoma. Am J Ophthnlmoll994; 118: 1-8. 36. Drance SM. Disc hemorrhages in the glaucomas. Sun:Ophthalmol1989;33: 331-347. 37. Airaksinen PJ, Tuulonen A. Early glaucoma changes in patients with and without an optic disc haemorrhage. Actn Ophthalmol 1984; 62: 197-202. 38. JonasJB, Naumann GOH. The parapapillary chorio-retinal atrophy in normal and glaucoma eyes. Inwst Ophthalmol Vis Sri 1989; 30: 919-926. 39. Jonas JB, Konigsreuther KA, Naumann GOH. Optic disc histomorphometry in normal eyes and eyes with secondary angleclosure glaucoma. 11. Parapapillary region. Grneje’s Arch Clin Exp Oplithalmoll992; 230: 134139. 40. Fricke T, Mantzioros N , Vingrys AJ. Management of patients with narrow angles and acute angle-closure glaucoma. Clin Exp Optom 1998; 81: 255-266. 41. Airaksinen PJ, Mustonen E, Alanku HI. Optic disc haemorrhages precede retinal nerve fibre layer defects in ocular hypertension. Acta Ophthalmoll981; 59: 627-641. 42. Henson DB, Bryson H. Clinical results with the Henson-Hamblin CFS2000. In: PPrimetry Update 87/88. Greve EL, Heijl A, eds. Dordrecht: Junk, 1987: 233-238. 43. KabovJ. Factors affecting the pharmacodynamics of tropicamide. Unpublished LJniversity of Melbourne, Parkville, Victoria, Australia. 44. Okoshi H, Kimura N, Hayashi H, Saito M, Endo N, Suzumura H, Usui M. Frequency of normal-tension glaucoma found at health check-ups. In: Perimetry Update 1998/99. Wall M, Wild J M, eds. The Hague: Kugler Publications, 1999: 443-451. 45. Mitchell P, Smith W, Attebo K, Healey PR.

Cliiiical and Experimerital Optometry 83.3 May-June 2000

160

Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology 1996; 109: 1661-1669. Author’s Address: Associate Professor Algis J Vingrys D e p a r t m e n t of O p t o m e t r y and Vision Sciences

The University of M e l b o u r n e Carlton VIC 3052 AUSTRALIA

Suggest Documents