Apr 2016

with
Prof Charles McGhee
& A/Prof Dipika Patel
Series Editors
The ABCs of OCT in glaucoma
Background
BY HANNAH KERSTEN*
AND PROFESSOR HELEN DANESH-MEYER
Glaucoma is a multifactorial optic neuropathy characterised by
slowly progressive degeneration of the retinal ganglion cells and
their axons. Unfortunately, there is not yet one single test that can
discriminate glaucomatous eyes from normal eyes; the diagnosis
of glaucoma is made based on a specific pattern of structural and
functional changes. In the past, the retinal nerve fibre layer (RNFL)
was only able to be assessed subjectively by slit-lamp examination
and retinal photography, providing qualitative data. Optical
coherence tomography (OCT) was first described by Huang and
colleagues in 1991 1 . OCT, as used to acquire high resolution, crosssectional
images of the ocular structures, utilises low-coherence
near infrared light (800-1400 nm) generated by a super-luminescent
diode, which passes through the pupil to the posterior structures
of the eye 1 . It is analogous to B-scan ultrasound except that it uses
light instead of sound. Over the past 10 to 15 years, OCT has become
an invaluable tool and is in widespread use in both optometry
and ophthalmology. OCT is used in the diagnosis and longitudinal
analysis of a multitude of ophthalmic disorders that affect the optic
nerve and macula, including glaucoma. Newer spectral-domain OCT
has increased resolution (approximately 3 – 5 µm) and faster scan
acquisition time than older time-domain OCT technology. Common
spectral-domain OCT models include the Zeiss Cirrus and the
Heidelberg Spectralis.
Peripapillary Retinal Nerve Fibre Layer Measurements
Measurement of the peripapillary RNFL thickness using OCT
is now a routine component of the comprehensive glaucoma
assessment. In healthy eyes, the RNFL is generally thickest in
the in the inferior quadrant, followed by the superior, nasal and
temporal quadrants (the “ISNT” rule). There is, however, a large
degree of RNFL variability in “normal” eyes, and there is some
overlap in the structural characteristics of normal eyes and eyes
with early optic nerve damage due to glaucoma 2 . Many patients
will have anomalous structural features that may confound
the interpretation of OCT measurements, and the eye may be
incorrectly classified as “abnormal”. In patients with perimetric
glaucoma, the location of the RNFL thinning should correlate
with the visual field defect. In those with pre-perimetric disease,
it is important to compare the peripapillary RNFL thickness in the
individual quadrants with the appearance of the optic nerve head
on clinical examination.
The ability to detect and measure structural change is essential
in the diagnosis and management of glaucoma. Progression
analysis software, included with some OCT models, is able to
track the progression of RNFL thinning over time (figures 1 and 2).
It is necessary to review the RNFL overview at each visit, as well
as the progression scans, as these overview scans will give more
comprehensive information regarding RNFL thickness in each eye
(as well as the differences between the two eyes). It is important
to discriminate true disease-related changes from measurement
variability and normal age-related change. When a scan is accurate
and well-centred, the 95% tolerance for average RNFL thickness
is approximately 4 µm 2 . Spectral-domain OCT is more sensitive at
detecting glaucoma progression than time-domain OCT 3 .
Fig 1. Guided progression analysis on Zeiss Cirrus OCT. This shows progression of left RNFL
thinning. The first two exams are used as baseline measurements, with subsequent scans
compared to baseline. The signal strength is good in all scans however the first baseline shows
an area nasal to the optic disc with an incomplete scan, hence the reason for the lower average
RNFL thickness in Baseline 1 compared with Baseline 2. Over time, there has been a significant
reduction in RNFL thickness in both the superior and inferior quadrants.
Fig 2. Guided progression analysis on Zeiss Cirrus OCT. This shows stable RNFL thickness over
six consecutive OCT scans. There is marked RNFL thinning, particularly in the superior and
inferior quadrants. The fluctuation in average RNFL thickness between exams is within the 95%
confidence limits for scan repeatability. Signal strength is adequate in all scans.
Macular OCT Scans in Glaucoma
Although the use of OCT in glaucoma has been primarily focused on
the assessment of peripapillary RNFL thickness, in recent years the
macular region has emerged as an area of interest; glaucomatous
macular damage can occur early in the disease process. Although the
macular region represents less than 2% of the retinal area, it contains
30% of the retinal ganglion cells 4 . One of the main advantages of
12 NEW ZEALAND OPTICS April 2016
macular assessment in glaucoma is that a significant portion of
retinal thickness at the macula is composed of the RNFL, ganglion
cell layer and the inner plexiform layer. Spectral-domain retinal
layer segmentation algorithms have allowed for the quantification
of individual layers in the macular region, and the measurement
of ganglion cell complex thickness (the combined thickness of the
RNFL, ganglion cell layer and the inner plexiform layer, although
macular analysis in some OCT models includes only the ganglion
cell and inner plexiform layers) 3 . The GCC thins as the glaucomatous
damage progresses, with lower thickness values associated with
poorer mean deviation scores on visual field testing 2,5 . Ganglion cell
complex thickness in glaucoma can correlate well with RNFL thinning
and visual field loss (figure 3). Repeatability of ganglion cell complex
measurements may be reduced in more advanced glaucoma 6 .
Fig 3. Structure-function correlation. The top left image shows a glaucomatous right optic nerve
with vertical elongation of the optic cup and thinning of the superior and inferior neuroretinal
rim. The rim thinning is most pronounced inferiorly. This correlates with functional changes on
visual field testing, with almost complete loss of the superior visual field, and greatly reduced
sensitivity in the inferior visual field. The lower images show diffuse thinning of the ganglion
cell complex (measured with the Zeiss Cirrus OCT), with more extensive thinning in the inferior
region. This correlates with the optic nerve and visual field appearance.
Consider Other Ocular and Systemic Pathology
Glaucoma is not the only condition that can cause thinning of the
retinal layers. A vast number of ocular and systemic disorders can
lead to peripapillary RNFL and macular thickness changes on OCT
and it is always important to consider these conditions as part of
the examination process. A comprehensive history and complete
eye examination is essential. The patterns of RNFL loss can vary
greatly between conditions. For example, patients with optic neuritis
are more likely to have temporal RNFL thinning (figure 4) and the
degree of RNFL loss may be out of proportion to visual field results.
Multiple sclerosis is associated with thinning of the RNFL and macula
(including the ganglion cell complex), even in patients with no history
of optic neuritis 7 . Patients with compressive optic neuropathies
can present with thinning of the RNFL. These patients are likely to
have reduced RNFL thickness in the nasal and temporal quadrants
compared with glaucoma patients 8 . A tilted disc, particularly in
myopic patients, can cause a localised RNFL defect in the superior or
inferior quadrants, similar to glaucomatous RNFL loss 9 . Longitudinal
follow-up is necessary to determine whether the RNFL thinning is
glaucomatous or due to the tilting of the optic nerve head 10 .
Fig 4. RNFL thinning in a patient with a history of optic neuritis. This patient had a single episode
of right optic neuritis (confirmed by MRI examination). Note the dramatic reduction in RNFL
thickness, particularly in the temporal quadrant (less likely to be affected in glaucoma). The
average RNFL thickness was 55 µm. The visual field was normal.
Factors Affecting OCT Measurements
A number of factors influence the quality and accuracy of retinal
measurements acquired with OCT:
••
Image resolution is affected by eye movement. The degradation
of the image is a function of the frequency and size of saccadic
eye movements, compared with the image acquisition time and
the transverse resolution of the OCT 11 . Newer OCT technology
attempts to counter this with the use of eye-tracking systems
incorporated into the software 12 .
••
Scans should be well-centred: macular scans should be centred
at the fovea and accurate measurement of the peripapillary
RNFL requires the reference to be centred precisely at the optic
nerve head 13 .
••
The signal strength of the scan needs to be adequate.
Recommended minimum signal strength varies by manufacturer.
Even scans with adequate signal strength may show software
segmentation failure, where the automatic segmentation of
the retinal layers is incorrect. If possible, these scans should be
re-taken.
••
Scans can be acquired effectively over a range of pupil sizes,
however if the pupil size is less than 3 mm this can affect
thickness measurements and scan quality 14 .
••
Opacities of the lens generally give rise to lower thickness
values (affecting results by up to 12%), with more advanced lens
opacities leading to a greater decrease in thickness 14 . Image
repeatability significantly improves following cataract extraction
••
OCT measurements are affected by axial length and,
subsequently, refractive error 15 , and measurements are most
accurate within the range of +5 to -5 dioptres 14,16 . Longer, more
myopic eyes tend to have thinner RNFL thickness values 15 .
••
RNFL values for people of different ethnicities vary modestly,
although it has been found that all ethnicities examined had
95% confidence limits that overlapped 15 .
••
RNFL thickness decreases with age - by approximately 2 µm per
decade, with loss of about 5000 axons per year 15 .
Anterior Segment OCT in Glaucoma
It is worth briefly mentioning the role of OCT in the examination of
the anterior segment of glaucoma patients. Anterior segment OCT
imaging, using a 1310 nm light source, permits the visualisation
of the angle structures and provides quantitative data that can be
useful in the identification of the mechanism of IOP elevation and
the diagnosis of angle closure glaucoma (figure 5) 17,18 . OCT of the AC
angle is a tool that is a useful addition to gonioscopy, but it should
not replace gonioscopic examination. It can be used to measure
the actual size of the angle, and is also particularly helpful for
visualising structural changes to the angle following YAG peripheral
iridotomy. Anterior segment OCT can also be used to as a noninvasive
measure of central corneal thickness, a useful measure in
initial glaucoma assessment.
Fig 5. Anterior segment OCT scan showing narrow anterior chamber angles
Conclusion
There have been significant developments in glaucoma imaging
over the last decade, and these imaging modalities, particularly
OCT scans of the peripapillary RNFL and macula, are now used
routinely in glaucoma diagnosis and on-going management. There
are continuous advances in spectral-domain OCT technology, with
increased resolution, reduced scan acquisition time, progression
analysis software updates, en face imaging and eye movement
tracking allowing for more accurate and reproducible scans, and
more in-depth analysis of the ocular structures. Although OCT
examination is an important component of the modern glaucoma
assessment, it is not a diagnostic tool 3 ; it is a useful test in the
armamentarium of the ophthalmologist and optometrist, and it
should be used in conjunction with other measures of optic nerve
structure and function. ▀
References
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2. Grewal DS, Tanna AP. Diagnosis of glaucoma and detection of glaucoma progression using spectral
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3. Bussel, II, Wollstein G, Schuman JS. OCT for glaucoma diagnosis, screening and detection of glaucoma
progression. British Journal of Ophthalmology 2014;98 Suppl 2:ii15-19.
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5. Hood DC, Raza AS, de Moraes CG, Liebmann JM, Ritch R. Glaucomatous damage of the macula. Prog
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1516-1523
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13. Cheung CYL, Yiu CKF, Weinreb RN, et al. Effects of scan circle displacement in optical coherence
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14. Savini G, Zanini M, Barboni P. Influence of pupil size and cataract on retinal nerve fiber layer
thickness measurements by Stratus OCT. Journal of Glaucoma 2006;15:336-340.
15. Budenz DL, Anderson DR, Varma R, et al. Determinants of normal retinal nerve fiber layer thickness
measured by Stratus OCT.[Erratum appears in Ophthalmology. 2008 Mar;115(3):472]. Ophthalmology
2007;114:1046-1052.
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17. Sharma R, Sharma A, Arora T, et al. Application of anterior segment optical coherence tomography in
glaucoma. Survey of Ophthalmology 2014;59:311-327.
18. Smith SD, Singh K, Lin SC, et al. Evaluation of the anterior chamber angle in glaucoma: a report by
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* Hannah Kersten is a therapeutically qualified optometrist with
glaucoma prescriber accreditation. She has recently completed
her doctoral studies in the Department of Ophthalmology
at the University of Auckland, under the supervision of
Professor Helen Danesh-Meyer, and Dr Richard Roxburgh of the
Department of Neurology. The topic of her thesis was optical
coherence tomography in neurodegenerative disease. Hannah
is currently working as a post-doctoral research fellow in the
Department of Ophthalmology and she is also involved in
glaucoma co-management with Professor Danesh-Meyer at Eye
Institute in Auckland.