8MARCH 2014

What is the earliest test forglaucoma?

Use of the ganglion cell complex as a
new diagnostic indicator

Dr Adrian S Bruce
BScOptom PhD FAAO FACO
Australian College of Optometry
and The University of Melbourne

Iris Huang
BOptom PGDipAdvClinOptom­PGCertOcTher
Australian College of Optometry

haemorrhage, or bayoneting and baringof blood vessels.
Retinal nerve fibre layer

In some glaucoma patients, a diffused
loss of RNFL can be seen as a wedge
of diminished light reflection. This isbest appreciated with a red-free (greenor blue) filter. However, early glaucoma
RNFL loss often appears as subtle
attenuation of the light reflection andcan be difficult to detect.
Visual field

GLAUCOMA IS AN OPTIC neuropathy
characterised by the loss of retinal
ganglion cells and the retinal nerve
fibre layer.1 There is a diversity offactors that may lead to glaucoma but
key issues in common are the effecton the retinal ganglion cells andpotentially devastating visual loss.2
What is the earliest test for glaucoma?
The answer depends on the typeof glaucoma. If the pressure isconsistently high, that measurement
alone will alert the clinician thatfurther work-ups, monitoring andpossible treatment are required.
However, in many patients the pressure
is not that high but the discs areasymmetrical or suspicious, or there
are other risk factors. What should webe assessing?
As retinal ganglion cell (RGC) loss
cannot be visualised in a standard
clinical examination, the standard
procedure for glaucoma assessment
often relies on detection of secondarychanges in the optic nerve head (ONH),
careful examination of the retinal nerve
fibre layer (RNFL) and visual field test.
Optic nerve headClassic glaucomatous signs at the ONH
include thinning or notching of theneuroretinal rim (NRR), asymmetry ofNRR, excavation and enlarged cup todisc ratio over a period of time, Drance

Glaucomatous visual field defects
include an early paracentral scotoma,
which may slowly merge and form anarcuate defect that continues to theblind spot. A nasal step may be present
and one hemifield more depressed thanthe other. The visual field defect should
correspond to the NRR change and/orRNFL loss.
As clinical examination is subjectiveand clinician dependent, earlyglaucoma signs can be overlookedfrom time to time. Early treatment
opportunities may be missed if relying
primarily on a visual field defect. Thisis because a substantial reductionin RGC population can occur before
clinically significant visual field defectcan be detected. Since the introductionof optical coherence tomography(OCT), the technology has assisted
clinicians in the detection of RNFL
loss associated with glaucoma. Dueto advances in OCT technology, we
can now acquire a 6 x 6 mm cube ofdata in the peripapillary region in lessthan 1.5 seconds. Using OCT ONH
scan to analyse peripapillary RNFL is
now a widely employed parameter for
diagnosing glaucoma.
More recently, the measurement of theperimacular ganglion cell layer has
emerged as a new diagnostic parameterin glaucoma with spectral domain
OCT. Various OCT machines now use
this technique to capture the thicknessof the innermost three retinal layers

around the macula. These three layers,
known as the macular ganglion cellcomplex (GCC), are the retinal nerve
fibre layer, ganglion cell layer and inner
plexiform layer.3 The GCC contain theaxons, cell bodies and dendrites of
the ganglion cells, respectively, whichhave been shown to be preferentiallyaffected by glaucoma.4 This newparameter may assist early glaucoma
detection, especially in cases where
the ganglion cell loss is predominately
macular rather than peripheral.

CASE REPORTS
Examples of using GCC measurement
in assisting glaucoma diagnosis

Case 1 (Figure 1) shows a large
glaucomatous cupping with a slit ofinferior RNFL defect (as shown in
the red free photo). The Nidek OCT
macular scan highlighted the inferiorarcuate loss, enabling us to quantify thetotal GCC loss and compare superior
and inferior hemifields. Note that
there is no visual field defect in thiscase, once again echoing the previous
studies that structural loss can precede
detectable functional loss by up to fiveyears.5
Case 2 (Figure 2) shows an exemplary
structure-function relationship with aclassic glaucomatous inferior arcuate
field loss, which corresponds to thesuperior temporal rim notch. RNFL
loss is not readily detectable in the
red-free photo; however, the Nidek
OCT macular GCC scan shows a clearsuperior arcuate loss.
Since the new macular GCC scan
has gained popularity in glaucoma
management, many studies havebeen performed in the past few years
to investigate its diagnostic ability.
Studies comparing the diagnostic
performance of the GCC parameterto peripapillary RNFL have found a9MARCH 2014

Figure 1. Nidek OCT scan of the macular ganglion cell complex(GCC) shows right inferior shallow arcuate loss in a 57-year-old female with early glaucoma. The right inferior GCC is 15 µm thinner thanthe left inferior GCC (not shown). The red-free fundus image showsinferior nerve fibre loss (arrow) but the visual field is normal.

Figure 2. Nidek OCT scan of the macular ganglion cell complex(GCC) shows right superior arcuate loss in a 64-year-old male withglaucoma. The right superior GCC is 19 µm thinner than the left
superior GCC (not shown). The red-free fundus image shows superior
temporal rim notch (arrow) and the visual field shows a corresponding inferior arcuate loss.

GCC scan to be comparable with theONH scan in detecting early, moderate
and advance glaucoma.4 The studies
also found that GCC measurementsand ONH scan had similar structurefunction relationships with visual fieldsensitivity.

advantage in glaucoma diagnosis
as RGC loss occurs early in thepathogenesis of the disease. Besides,
ONH scanning may be complicated byother non-glaucomatous conditions,such as extensive peripapillary atrophy
in high myopia.

Limitations of GCC parameter werealso discussed in many of these papers.
Common issues that are also sharedwith peripapillary RNFL scan includes
signal quality and image artifact. Any
coexisting macular pathology suchas ARMD may affect GCC thicknessmeasurement. In addition, most GCC
scans cover a 7 x 7 mm grid on themacula; patients who present with
RNFL defect outside of this area may
escape detection.

In summary, macular GCC scan is able
to illustrate areas of glaucomatous
ganglion cell loss with the advantage
of correlation with visual field defects
point by point, as shown in Case 2above. Clinicians should carefullyinterpret the individual patient’s
clinical signs and consider including
macular GCC thickness as part of theglaucoma assessment procedure.

This is less of an issue now as imaging
technology has advanced. Nidek OCT
RS 3000 software V2.0.0 or higher
allows 3-D scanning over a 9 x 9mm square in only 1.6 seconds. Thisfunction provides clinicians with theopportunity to measure GCC thickness
across a wider area. Furthermore,
GCC measurement has a theoretical

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A-Z. Oxford: Elsevier 2008, 336 pp.
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Nakano N, Takayama K, Kimura Y et al.
Wide 3-dimensional macular ganglion
cell complex imaging with spectraldomain optical coherence tomography
in glaucoma. Invest Ophthalmol Vis Sci
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relationship and diagnostic valueof macular ganglion cell complex
measurement using fourier-domain OCTin glaucoma. Invest Ophthalmol Vis Sci
2010; 51: 4646–4651.
5. Quigley HA, Katz J, Derick RJ et al.
An evaluation of optic disc and nerve
fibre layer examinations in monitoring
progression of early glaucoma damage.
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