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 annu-
ally. For future reference, they should have their disc features recorded by instru-
mental 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 dis-
ease. Both procedures entail different lev-
els of responsibility and require different
approaches for testing. In this paper, I
discuss the processes involved in screen-
ing and detection. When detecting glau-
coma, it must be remembered that, as sev-
eral 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, glaucoma-
tous optic neuropathy (CON) becomes
more prevalent with age.’-JThus, increas-
ing age (older than 60 years) is a signifi-
cant risk factor for glaucoma (Table 1 ) .
Figure 1 shows the prevalence of glau-
coma 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 two-
line trend has been plotted to the epide-
miological data, assuming that the preva-
lence of glaucoma is constant at younger
ages (up to 49 years) and increases sig-
nificantly beyond 60 years of age, imply-
ing that older patients warrant frequent
screening at two-year intervals to ensure
early detection.
Screening involves assessing ‘risk fac-
tors’ 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

Clinical and Experimental Optometry 83.3 May-June 2000

145
Detecting the nerve head changes of glaucoma Vzngrys
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.
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 surround-
ing 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 Panda-
Jonass for particularly good reviews on this
topic). In this paper, primary open angle
Clinical and Experimental Optometry 83.3 May-June 2000
General
Positive family history for glaucoma
Systemic hypertension, diabetes
Race (Afro-Americans, Australian Aborigines, Japanese for NTG)
Increasing age (> 60 years)
Myopia (> -2 D)
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
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 sensitivity, so I have added these to the list
optic disc or in the surrounding tissues. of signs (Table 2 ) .
This logic is consistent with the position For its earliest diagnosis, GON requires
adopted by many professional associa- the concurrent appearance of multiple
tions, for example, the American Acad- signs of optic nerve or nerve fibre dam-
emy of Ophthalmology. However, it is my age or a documented progression in one
opinion that functional losses should of these signs. Table 2 lists the signs that
either precede or occur concurrently with indicate GON and Table 3 gives the func-
such change. The reason that they are not tional losses that can be produced by
found most likely reflects a lack of test glaucoma. From Table 3, it is apparent
146
 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 diag-
nosis or be involved in its management.
In doing so, they should adopt a strategy
that yields high sensitivity and specificity
Figure 2. Scaled schematic appearance of the optic nerve head for three sizes of scleral-disc
(greater than 0.90) by considering risk
openings:left panel, the scleral disc diameter is 33 per cent larger than normal opening CDR
factors. These have been listed in Table 1
= 0.71; central panel, the scleral disc has a normal opening CDR = 0.40; right panel, the scleral
under the headings General and Ocular.
disc diameter is 33 per cent smaller than normal CDR = 0.17 (cup hidden by blood vessels).
The presence of a single ocular risk fac-
The arrow in the central panel shows the scleral ring, which defines the insertion of the disc,
tor identifies glaucoma suspects, whereas
whereas the small arrow heads show the edges of the neuro-retinal rim that starts on the
the presence of multiple ocular risk
inside margin of the scleral ring and which may be distinct (left edge) or diffuse (right edge).
factors (two or more) warrants further
The central retinal artery has a normal insertion, the NRR shows the ISNT configuration (see
evaluation or referral due to the high like-
text) and circular lamina pores are visible in the left panel. The aperture in the lower part of
lihood for glaucoma. In this paper, I will
the right panel represents the light from an ophthalmoscope.
not consider any of the risk factors other
than those involving the optic nerve or its
adjacent region.

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 dough-
nuts 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.',3,6,7However, 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 in-
terpreted only after evaluation of the size
of the disc (Figure 2). The following dis-
cussion 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 pre-
dictor 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.
CLINICIAN-DEPENDENTFACTORS
AFFECTING CDR MEASURES
These involve recording and assaying
factors such as reliability, precision and
accuracy.
Accuracy describes how close a determi-
nation is to the true value. The difference
between your average judgement and the
true value is sometimes called bias. Non-
expert clinicians have been shown to
make poorer judgements of CDR com-
pared 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

Clinical and Experimental Optometry 83.3 Mdy-JUnt? 2000

147
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. Identifica-
tion of this feature is challenging and it is
best to use coloration or shading as your
guide. In younger eyes, the NRR is orange-
pink (least pink in the macula bundle) so
estimating the edge in these eyes is rela-
tively 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 glau-
coma 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 red-
free filter can help by emphasising this
change in shading.
These judgments are easier to appreci-
ate and, in some cases, can be made only
through a dilated pupil with an indirect
lens (78 D or 90 D). Similarly, the abnor-
mally steepened slope of early glaucoma
(temporal shelving) can be appreciated
only with indirect biomicroscopy by using
a horizontal slit (about 1/8 disc diam-
e 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 inter-
observer 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).
Clinical and Experimental Optometry 83.3 May-June 2000
Clinicians vary in their capacity for con-
sistency in their measures, from being
rather poor to highly precise and reliable.
Experience appears to have a major influ-
ence on precision and reliability, with
expert clinicians giving more precise and
reliable outcomes.’
To promote accuracy, precision and re-
liability, 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 Figure 3. The right eye of a 78-year-oldocular
purpose. hypertensive (24 mmHg, R and L) patient
who had been followed for the past 10 years.
DISC DEPENDENT FACTORS AFFECTING The disc shows a sloped NRR typical of age
CDR MEASURES (small arrows), two notches in the NRR
The CDR can be influenced by many fac- (arrow heads), vessel bayonetting at the
tors (Figures 2 and 3), and the size of the superior notch (upperyellow arrow),a zone
scleral opening and age are just two of of peripapillary scleral atrophy (largearrows
them. The effect that age has on the at 3 o’clock) and a diffuse RNFL loss. The
appearance of the normal NRR has been visual field showed an absolute inferior
discussed in the previous section. The fol- arcuate defect consistent with the superior
lowing details the size effect, which is a notch and a variable relative superior arcuate
more common cause for large (greater loss. The fellow eye was suspicious for early
than 0.5) or small (less than 0.5) CDRs damage.
than is glaucoma.
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 related to the square of the radius (area =
refractions ranging from +5 D to -8 D) and m y ) ,we have a 77 per cent increase in disc
has about 1.4 million nerve fibres ar- area due to the 33 per cent larger scleral
ranged in this a p e r t ~ r eThis
. ~ average disc opening, resulting in a CDR of 0.71. Note
results in a CDR of 0.44 as shown in the that in this case (CDR = 0.71) this is still a
middle panel of Figure 2. What effect normal disc with a normal complement
would increasing the scleral opening by of nerve fibres but these nerves are now
33 per cent (7 degrees x10 degrees) have located in a larger scleral opening. In con-
on the resultant CDR? The schematic trast, a halving of nerve fibres in a normal
appearance of such discs is shown to scale sized disc results in about the same sized
in Figures 2 and 4. CDR as for the large opening (0.40 to
The schematics shown in Figures 2 and 4 0.63: 158 per cent increase). A similar loss
presume that the nerve fibres retain the in a small disc yields large CDR changes
same size and number in each eye, that (Figure 4: 0.17 to 0.42: 247 per cent in-
the area of the disc will determine the crease) and a vertical cupping (loss of the
resultant CDR and that pathological cup- ISNT sign, to be discussed later). In fact,
ping is more extensive vertically (see in the small disc, the number of optic
below). In Figure 2, left panel, as area is nerve fibres has to decrease to o n e
148

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 dis-
cussion have been based on mathemati-
cal principles, they are supported by clini-
cal 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 re-
cently 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
Clinical and Experimental Optometry 83.3 May-June 2000
Detecting the nerve head changes of glaucoma Vingrys
For the CDR assay to be considered sen-
sibly 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 di-
rect ophthalmoscope (the 5 degree aper-
ture 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 horizon-
tal 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,
149
Figure 2 , left panel). Similarly, a small
disc occurs when the disc subtends 75 per
cent or less of the light aperture. Clini-
cians should record whether the disc is
large, normal or small and make CDR
measures in patients with normal-sized
openings. Adopting a grid (amblyo-
scope) 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 moni-
tored, 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, giv-
ing the appearance of large CDRs. Typi-
cally, 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.'" Colo-
boma may be unilateral (Figure 5) and
may have associated visual field losses,
which manifest as generalised depressions
with or without arcuate defects. The pres-
ence of arcuate loss challenges the diag-
nostic process because these large CDRs
are more likely to get GON especially as a
congenital glaucoma. However, the level
of generalised or macula sensitivity reduc-
tion 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, peripap-
illary 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.
greater prevalence of glaucoma.'," Due to
this higher risk, patients with greater than
two dioptres of myopia should be investi-
gated 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 glau-
coma 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 dam-
age in high myopia tends to occur at a
lower IOP than might be considered ab-
normal (16 to 25 mmHg) and has a shal-
low cupping making CDR an unreliable
indc=x.45It is characterised by a substan-
tial ring of peripapillary atrophy, called a
halo (Figure 6). Studies have shown that
the vascular status in the region of the halo
Clinical and Experimental Optometry 83.3 May-June 2000
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.
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.
is compromised,22implying that ischaemic
insult might be the mechanism of myopic
glaucoma. It is thought that the ischae-
mia results from vascular changes subse-
quent to scleral stretching associated with
the axial elongation.'
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 glau-
coma. 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
150
6b. The fellow eye had an absolute inferior
arcuate loss
many glaucomatous eyes have small CDRs
(approximately 15 per cent) .',I'
Harper and Reevesg report that visual
field screening is the best single predic-
tor of glaucoma, although it yields a lim-
ited diagnostic capacity in isolation (sen-
sitivity = 0.85, specificity = 0.91). These
authors showed that reasonable diagnos-
tic 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 test-
ing 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 posi-
tive 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 Table 4. The diagnostic capacity of several
sized disc shows a loss of the ISNT configuration (CDR = 0.65). Centre panel: abnormal clinical signs for GON when taken in isolation
insertion of the central retinal artery (CDR = 0.50) and an abnormally thinned NRR opposite or together (modified after Okoshi and
the artery insertion should be evaluatedby comparing artery widths as indicated by the arrow colleaguesM)
(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.

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 pur-
poses. 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 nianage-
ment of GON and that these should yield
high capacity for early detection.” In some
cases, such as with large or small open-
ings, high myopia o r coloboma, CDR
measures a n d screening cannot be
applied.
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 pro-
duce 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 rela-
tive crowding at the vertical poles and,
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 sus-
pected in people when the NRR becomes
of similar size in the temporal and verti-
cal regions-for example I = S = T as
shown in Figures 4 and 7-and is defi-
nitely suspicious when the temporal mar-
gin (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 sym-
metry in the same eye or between eyes. In
particular, early GON will produce an asym-
metry 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

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 sen-
sitivity of 0.45 at a specificity of 0.93. Al-
though this might sound like a poor diag-
nostic 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 glau-
coma4 (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-
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.
Figure 8. The appearance of several optic nerves with large vertical CDRs (greater than 0.5)
Clinical and Experimental Optometry 83.3 May7June 2000
bution and number) is not present.
Although the ISNT sign is useful, de-
termining the edge of the NRR in elderly
people (older than 70 years) is a clinical
challenge that can frustrate the apprecia-
tion 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 arteri-
ole in this region, shelving may be appre-
ciated by the kinking of this vessel (Fig-
ure 8c), although this is not a reliable
indicator. In small to normal discs, shelv-
ing is best appreciated with a thin hori-
zontal 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 chal-
lenging to make, as we have shown else-
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).
152
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 shelv-
ing. 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 thick-
ness of the rim plateau to detect NRR loss
and thinning in large discs. NRR thick-
ness can be estimated using the diameter
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 circum-
linear 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.

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 com-
parison 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
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).
Clinical and Experimental Optometry 83.3 May-June 2000
Detecting the nerve head changes of glaucoma Vzngrys
be on the temporal side, near the hori-
zontal. 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).4,19Notches 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
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.
153
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 pal-
lor of the NRR (Figure 10).
Cup configuration (doughnut hole)
Early glaucoma produces a vertical cup-
ping compared with the normal horizon-
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).
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)
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 par-
ticularly 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 (Fig-
ure 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 gradu-
ally 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
(:linical and Experimental Optometry 89.3 May+ne
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.
Figure 12. The left eye of a 56-year-old male with a family history of glaucoma
orbital mass, ischaemic anterior optic neu-
ropathy (AION) or carotid insufficiency.
In some eyes with deep cups the configu-
ration 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 ver-
tically oriented and slit-like as the glauco-
matous damage progressed. This was con-
firmed 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 struc-
tures following axonal death or that i t may
represent a fusion of the pores due to shear-
ing 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 investiga-
tion. However, vertical slits are most likely
due to glaucoma and can be used as signs
of this disease (Figure 1 1 ) .
2000
154
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)
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 cor-
related to the degree of glaucomatous
neuropathy (Figure 7, centre panel). They
argue that this might be due to mechani-
cal 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 arter-
ies 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
KINKING AND BARING
As the blood vessels within the papilla lie
near the top of the nerve fibre layer, un-
dermining or erosion of the NRR will re-
sult in changes either to the configuration
of these vessels or to their orientation.
Such changes are visible with ophthalmos-
copy 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 re-
gion of the blood vessel (using a 90 D
lens), otherwise they might arise from
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 (Fig-
ures 8c and 12). This makes those blood
vessels that track along the inner margin
of the NRR (circumlinear vessels) par-
ticularly 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
photographs for early detection (com-
pare Figures 12a and 12b). Figure 12
demonstrates the importance of photo-
graphic 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 peripapil-
lary 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 (prob-
ably due to hypertensive and/or arterio-
sclerotic effects), means that this sign has

Clinical and Experimental Optometry 83.3 May-June 2000

155
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 hall-
mark 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.g5How-
ever, as most persist for only six to eight 15a. Upper left. A colour photograph of a 15h. Upper right. Early localised RNFL losses
weeks, this means that many disc haemor- normal RNFL configuration showing the with three wedge defects (arrows). These
rhages are likely to go undetected. This typical bright-dark-brightlight reflex moving demonstrate how a local disruption to the
transient characteristic yields a relatively vertically from superior to inferior in the BDB pattern facilitates detection. (Courtesy
low prevalence in clinical practice (seven temporal region A Litwak)
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 pro-
gression.

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 cres-
cent is present (Figures 3, 6 and 8d), it
lies adjacent to the disc, whereas the
pigmented crescent can be removed from 15c. Lower left. The worn corduroy effect 15d. The panel on the lower right is a red-
the disc or it can be adjacent to the disc found in an early wedge defect. This effecl free colour photograph showing a small CDR
iffound in isolation (Figure 13). Pigmen- usually becomes evident o n higher (0.3) in a small scleral opening. There is
tary crescents can appear as local thin magnification (compare Figures 15b to 15c). marked loss of RNFL in the macula bundle
strips (Figure 6) or as thick regional dis- (Courtesy A Litwak) (yellow arrows) that makes this area darker
ruptions (Figure 8d, 7 to 9 o'clock, Fig- than the nasal region, with the blood vessels
ure 13, 9 to 11 o'clock). Histologically, prominent in relief. There is also a mild worn
the scleral crescent (zone beta) corre- corduroy effect in the inferior bundle (white
sponds to a loss of retinal pigment epi- arrows). This patient has a pronounced
thelium and photoreceptorsggand ap- glaucomatous field loss.
pears to be associated with a region of
deficient blood flow.'l The significance
Figure 15. The appearance of the RNFL in normal and glaucomatous eyes
of the scleral crescent is that it occurs fre-
quently in some forms of GON and rarely
in normal eyes." However, it must be
differentiated from the temporal cres-
cent of myopia, the scleral crescent of
tilted discs (often inferonasal) and the

Clinical and Experimental Optometry 83.3 May-June 2000

156

peripapillary crescent of highly myopic
eyes (greater than 8 D, usually a thin cres-
cent). 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 in-
frequently 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 creep-
ing angle closure glaucoma."' In the
myopic form of glaucoma, the usual tem-
poral crescent gives way to a total circum-
ferential scleral halo delimited by a
pigmentary edge (Figure 6), which is as-
sociated with a high risk for GON. Myopic
GON is a challenge to detect as it gives a
shallow cupping at normal, or near nor-
mal, IOP (16 to 25 mmHg) with general-
ised 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 non-
glaucomatous 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, myo-
pia 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 red-
free filter can be used to enhance the vis-
ibility 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
Clinical and Experimental Optometry 83.3 May-June 2000
Detecting the nerve head changes of glaucoma Vzngrys
pattern that can be appreciated with a
14 D or 20 D lens and indirect ophthalm-
oscopy, 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 re-
flections 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 re-
stricted field of view makes subtle differ-
ences harder to detect using a brightness
comparison.
Diffuse loss of RNFL is difficult to de-
tect, 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 be-
come 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 appear-
ance 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 gen-
eral direction of the nerve fibres. In nor-
mal eyes these vessels are less distinct, as
the nerve fibres partly bury them. In sus-
pect cases, comparisons of the BDB pat-
terns between poles or eyes may be use-
ful, as GON typically affects one pole o r
eye more than the other. Increasing age,
light skin pigmentation and high myo-
pia 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.
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; Fig-
ures 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 us-
ing the global appraisal method described
above, although early loss needs high
magnification (90 D, 78 D ) for apprecia-
tion. In these early cases, the wedge will
appear slightly dimmed and have a tex-
tured component that looks like worn
corduroy, with slit-like troughs and valleys
running throughout, indicating a non-
uniform 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 abnor-
malities (notches). Typically, they can pre-
cede 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 evalu-
ation for signs of GON.
Screening
When screening, practitioners need to
determine the level of ocular risk by pre-
forming 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 abnor-
malities 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 myo-
pia (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

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)
Anterior chamber depth assay RNFL loss (diffuse or local), notching
IOP measurement Slit-like lamina pores (especially vertical)
CDR evaluation Kinking or baring of the blood vessels andlor non-central artery insertion
Visual field screening Splinter disc haemorrhage, focal arterial narrowing

Table 5. Visual field screening should be Table 6. Optic disc characteristicswhich may indicate glaucoma. The first
performed if patients fail any of the other four items (bold) may be the earliest evidence which may occur prior to the
three tests. detection of field defects.

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 gonio-
scopic evaluation.
The IOP measure should record a fail-
ure 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 consid-
ered 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 asymmet-
ric (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 undertak-
ing 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. Ini-
tial failures must be retested (once or
twice at two- to four-week intervals) to
establish that learning effects are not
present and that the defects are reproduc-
ible. 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 con-
ducted 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 per-
formed on the patient to yield a high sen-
sitivity (0.94) at a moderate specificity
(0.69). Subsequent field testing will im-
prove the specificity to clinically accept-
able levels.YHowever, it was noted previ-
ously 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 un-
dertake 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 compari-
son. Optic disc photographs (or docu-
mentation with other instrumental meth-
ods) at two-yearly intervals in low risk
cases (one sign only), and at five-yearly
intervals for suspects (hypertensives,
high myopes, large or small srleral open-
ings) should facilitate the early detection
of GON.
At these reviews, a disc is judged as hav-
ing 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 indi-
cation 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, photogra-
phy (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 phe-
nylephrine is good for this purpose.''
However, a larger pupil might be needed
for photography. Abnormal disc observa-
tions should be confirmed with functional
testing, although the existence of func-
tional 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 mir-
ror the level of risk and should range from
six to 24 months.

Clinical and Experimental Optometry 83.3 May-June 2000

158

DIAGNOSTIC CAPABILITY
The diagnostic capability of the signs de-
scribed in the previous discussion has not
been rigorously tested by prospective tri-
als, and there exists a need for such re-
search. However, in the absence of these
trials, aspects of the sign's diagnostic ca-
pacity 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 dur-
ing an unrelated health check.44The pho-
tographs were evaluated for signs of a
large CDR, NRR notching, vessel bayonet-
ting, splinter haemorrhages and RNFL
defects. These were found in 309 eyes (3.5
per cent) of the original group who sub-
sequently 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. Neverthe-
less, the sensitivity and specificity of these
signs were determined for cases that were
positively identified as having a glaucoma-
tous field defect.
The outcomes of this comparison have
been summarised in Table 4. This shows,
as might have been expected, that any sin-
gle sign is a poor predictor of glaucoma-
tous field loss, often due to the low occur-
rence 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 sensi-
tivity for glaucoma. Improved diagnostic
reliability can be achieved if multiple signs
(at least two) are present, preferably in-
cluding RNFL or ISNT defects. It is im-
portant 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
Clinical and Experimental Optometry 83.3 May-June 2000
Detecting the nerve head changes of glaucoma Vingrys
cumulative evidence provided by several
different signs, as none is a perfect pre-
dictor 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 glau-
coma 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. Find-
ing three or more signs in the same eye
(not necessarily at the same visit) indicates
the presence of CON and requires medi-
cal intervention, regardless of the status
of the visual field.
Once the diagnosis of CON is made,
patients must have their discs photo-
graphed, anterior chambers evaluated,
IOPs measured and be subject to thresh-
old visual field testing. A sensible recall
schedule and monitoring program should
be developed and implemented. Having
patients return in the month of their birth-
day 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 diag-
nose the presence of glaucoma. As the
disease is a lifelong condition, and the
medications are not benign, the instiga-
tion of medical therapy should not be
undertaken lightly. Thus, reaching the
correct diagnosis is important. By adopt-
ing 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
159
elderly undiagnosed (50 per cent) glau-
coma 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.
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