Review of Literature 1

Comparative analysis of macular and peripapillary retinal nerve fiber layer thickness in
normal, glaucoma suspect and glaucomatous eyes by optical coherence tomography

study was done by Mita Saha, Sabyasachi Bandyopadhyay, Debabrata Das, Sourav Ghosh
and their team. In this study macular and peripapillary RNFL scans were performed in one
eye of 70 controls, 35 glaucoma suspects and 70 glaucoma patients by TD-OCT. The
discriminating power of each parameter between the groups was determined by area under
the receiver operating characteristic (AROC) curve. The correlation of macular thickness and
RNFL thickness parameters with global field indices were also performed. P-value of less
than 0.05 was considered statistically significant. The differences in all the macular thickness
parameters between the groups were statistically significant (pless than 0.05) except foveal
thickness (FT) and nasal inner (NI) quadrant thickness. The temporal outer (TO) macular
quadrant produced largest AROC curve of 0.90 between controls and glaucoma patients. The
differences in all the RNFL thickness parameters were highly significant between the groups
(pless than 0.001). The AROC curve between control group and glaucoma patients for RNFL
average thickness was 0.99.
Macular retinal and nerve fiber layer thickness in early glaucoma: clinical correlations
study was done by Vassiliki Arvanitaki, Miltiadis K Tsilimbaris, Aristofanis Pallikaris and
their team. In this study examines RT and RNFLT using standard scanning protocols in early
glaucoma. In this prospective, nonrandomized case series, 95 eyes of 95 patients were
evaluated, including 29 nonglaucomatous subjects (control group), 34 glaucoma suspects,
and 32 early manifest glaucoma patients. RT and RNFLT were measured using scanning fast
macular thickness map and Fast RNFLT (3.4) protocols on a 1.70 mm radius around the
macular center (respectively) in all four quadrants. The fast RNFLT (3.4) protocol was
transposed on the macula from the peri-papillary area. Data were statistically analyzed for
differences between groups, and for correlations between parameters. P<0.5 was statistically
significant. Both early manifest glaucoma patients and glaucoma suspects had significantly
lower RT than controls in all quadrants. RNFLT differences in all quadrants were not
statistically significant (P>0.05). RT was significantly inversely correlated with axial length
in early manifest glaucoma patients and glaucoma suspects but not in controls.
Comparative analysis of macular and
peripapillary retinal nerve fiber layer thickness
in normal, glaucoma suspect and glaucomatous
eyes by optical coherence tomography
Mita Saha, Sabyasachi Bandyopadhyay, Debabrata Das, Sourav Ghosh
PMID: 28478464 Nepal J Ophthalmol

DOI: 10.3126/nepjoph.v8i2.16991 Nepal J Ophthalmol 2016 jul
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Nepal J Ophthalmol
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Abstract
Introduction: Peripapillary retinal nerve fiber layer (RNFL) thickness analysis is a
subjective method of analysis of glaucomatous damage. As almost 50% of retinal
ganglion cells are located in the macula, assessment of macular thickness can be an
alternative method for diagnosis of glaucoma.
Objectives: To evaluate the changes in macular and retinal nerve fiber layer
thickness in controls, glaucoma suspects and glaucoma patients using time domain
optical coherence tomography (TD-OCT).
Materials and methods: Macular and peripapillary RNFL scans were performed in

one eye of 70 controls, 35 glaucoma suspects and 70 glaucoma patients by TD-OCT.
The discriminating power of each parameter between the groups was determined by
area under the receiver operating characteristic (AROC) curve. The correlation of
macular thickness and RNFL thickness parameters with global field indices were also
performed. P-value of less than 0.05 was considered statistically significant.
Results: The differences in all the macular thickness parameters between the groups
were statistically significant (pless than 0.05) except foveal thickness (FT) and nasal
inner (NI) quadrant thickness. The temporal outer (TO) macular quadrant produced
largest AROC curve of 0.90 between controls and glaucoma patients. The differences
in all the RNFL thickness parameters were highly significant between the groups
(pless than 0.001). The AROC curve between control group and glaucoma patients
for RNFL average thickness was 0.99.
Conclusion: Macular thickness as detected by TD-OCT had high discriminating

power between controls, glaucoma suspects and glaucoma patients comparable with
peripapillary RNFL thickness parameters.
© NEPjOPH.
2012 Apr-Jun; 19(2): 204–210. Middle East African Journal of Ophthalmology (MEAJO)

doi: 10.4103/0974-9233.95251 midel easte junoral of opthalmology
Macular retinal and nerve fiber

layer thickness in early glaucoma:
clinical correlations
Vassiliki Arvanitaki 1, Miltiadis K Tsilimbaris, Aristofanis Pallikaris, Ioanna
Moschandreas, Evangelos Minos, Ioannis G Pallikaris, Efstathios T Detorakis
Affiliations expand
 PMID: 22623860
 PMCID: PMC3353669
 DOI: 10.4103/0974-9233.95251
Free PMC article

Abstract
Purpose: Previous studies have evaluated macular retinal thickness (RT) and nerve
fiber layer thickness (RNFLT) changes in early glaucoma using elaborate optical
coherence tomography (OCT) scanning protocols.
Materials and methods: This study examines RT and RNFLT using standard scanning
protocols in early glaucoma. In this prospective, nonrandomized case series, 95 eyes
of 95 patients were evaluated, including 29 nonglaucomatous subjects (control
group), 34 glaucoma suspects, and 32 early manifest glaucoma patients. RT and
RNFLT were measured using scanning fast macular thickness map and Fast RNFLT
(3.4) protocols on a 1.70 mm radius around the macular center (respectively) in all
four quadrants. The fast RNFLT (3.4) protocol was transposed on the macula from the
peri-papillary area. Data were statistically analyzed for differences between groups,
and for correlations between parameters. P<0.5 was statistically significant.
Results: Both early manifest glaucoma patients and glaucoma suspects had

significantly lower RT than controls in all quadrants. RNFLT differences in all
quadrants were not statistically significant (P>0.05). RT was significantly inversely
correlated with axial length in early manifest glaucoma patients and glaucoma
suspects but not in controls.
Conclusions: The finding that RT was significantly lower in early manifest glaucoma

patients and glaucoma suspects indicates that the transposition of the OCT fast RNFL
thickness (3.4) protocol from the peri-papillary area to the peri-macular area can be
used for early glaucoma diagnosis. Intraretinal changes in early glaucoma, likely
precede nerve fiber changes.
Keywords: Early Glaucoma; Macula; Optical Coherence Tomography; Retinal

Thickness.
Conflict of interest statement
Conflict of Interest: None declared.

Retinal ganglion cells (RGCs) are the cells that die in glaucoma. RGC axons make up the
retinal nerve fiber layer (rNFL) and exit the eye through the optic nerve. Progression of
glaucomatous optic neuropathy can be seen by increased optic nerve cupping or peripapillary
rNFL losses on SD–OCT. Within ~5mm or 16° of the fovea > 50% of RGC bodies
reside.2 Cell bodies are stacked up to six layers thick.2 Thus, small losses of ganglion cell
bodies (which along with the rNFL constitutes > 30% of the retinal thickness) are detectable
by analyzing total retinal thickness. Total macular thickness is a surrogate measure of tissue
thickness loss due to glaucoma in the absence of other macular pathology (which might affect
other layers of the retina).
REVIEW OF LITERATURE
Taiwan J Ophthalmol. 2016 Jan-Mar; 6(1): 3–7.
Published online 2016 Feb 28. doi: 10.1016/j.tjo.2016.01.003
Macular thickness analysis for glaucoma diagnosis and

management
Divakar Gupta and Sanjay Asrani*
Author information Article notes Copyright and License information Disclaimer
This article has been cited by other articles in PMC.
Abstract
Go to:
1. Introduction
Glaucoma is a progressive, asymptomatic optic neuropathy resulting in characteristic
structural damage and associated visual field loss. In addition to ophthalmoscopy, optic nerve
imaging and perimetry are used to aid in the diagnosis and surveillance of glaucoma.
Automated perimetry, however, lacks the resolution to detect early glaucomatous damage as
greater than 35% of the retinal ganglion cells can be lost before any visual field defects are
detected.1 This observation, that structural changes precede detectable functional deficits, has
led to an increased interest in imaging technology.
To date, imaging modalities have analyzed the structure of the optic nerve head (scanning
laser ophthalmoscopy) and measured retinal nerve fiber layer thickness (scanning laser
polarimetry and optical coherence tomography) to aid in glaucoma diagnosis. In this review,
we explore the role of macular thickness by spectral domain–optical coherence tomography
(SD–OCT) in glaucoma.
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2. Why macular thickness?

Retinal ganglion cells (RGCs) are the cells that die in glaucoma. RGC axons make up the
retinal nerve fiber layer (rNFL) and exit the eye through the optic nerve. Progression of
glaucomatous optic neuropathy can be seen by increased optic nerve cupping or peripapillary
rNFL losses on SD–OCT. Within ~5mm or 16° of the fovea > 50% of RGC bodies
reside.2 Cell bodies are stacked up to six layers thick.2 Thus, small losses of ganglion cell
bodies (which along with the rNFL constitutes > 30% of the retinal thickness) are detectable
by analyzing total retinal thickness. Total macular thickness is a surrogate measure of tissue
thickness loss due to glaucoma in the absence of other macular pathology (which might affect
other layers of the retina).
Changes in total macular thickness loss in glaucoma thus reflect the loss of the rNFL,
ganglion cell bodies, and the inner plexiform layer (IPL)—tissues that are lost in glaucoma.
Total macular thickness (internal limiting membrane to retinal pigment epithelium) is easily
and accurately measured by optical reflective devices such as the OCT due to the high level
of reflectivity from these two boundary regions of the retina. Earliest measurements of the
retinal thickness were performed by the Retinal Thickness Analyzer (Talia Technologies,
Neve Ilan, Israel) and subsequently by time domain OCT (Stratus, Carl Zeiss AG,
Heidenheim, Germany).3,4,5,6 The Stratus OCT measured the central 6 mm × 6 mm perifoveal
area by acquiring data from six radial line scans intersecting at the fovea and created a map of
macular thickness which interpolated the data in between the lines. This strategy of
interpolation of data with sparse measurements in a large retinal region did not prove to be
useful in the diagnosis and management of glaucoma compared with the peripapillary RNFL
measurements.6 Subsequently, SD–OCT permitted the measurements of larger areas of the
retina with higher acquisition speed. This provided the ability of measuring retinal thickness
with greater concentration of data points, and much less interpolation of data, thus providing
a more reliable retinal (macular) thickness map. Different software strategies by different
instrument makers are used for this such as a raster of lines or a grid of lines across the
macular region.
Recently, software advancements have allowed the automated segmentation of the inner
layers of the retina such as rNFL + RGC + IPL, collectively termed as the GCC (Ganglion
cell complex). Such a strategy could be very useful in eyes with coexisting pathologies such
as diabetic macular edema or age related macular degeneration, in which the total macular
thickness is affected but the inner layer thickness changes due to glaucoma can be measured
separately.
Various instruments measure different segmented layers such as RGCs + IPL or rNFL +
RGC + IPL. Instruments such as the Cirrus (Carl Zeiss AG), RTVue (Optovue Inc., Fremont,
CA, USA) and Topcon 3D OCT-2000 (Topcon Medical Systems, Oakland, NJ, USA)
measure approximately the central 4–6 mm of the perifoveal area whereas instruments such
as the Spectralis (Heidelberg Engineering, Heidelberg, Germany) and RS-3000 Nidek (Nidek
Inc., Fremont, CA, USA) measure 9–10 mm of the perifoveal area.
Macular thickness is a highly reproducible measurement on SD–OCT with intravisit and
intervisit coefficients of variation of < 1%.7,8,9 Segmented layers, such as ganglion cell-IPL
(GCIPL), also show good reproducibility.8 High reproducibility thus allows for easier
detection of glaucomatous progression.
2.1. Correlations between rNFL thickness, visual fields, and macular thickness
Macular thickness has been shown to correlate both with optic nerve cupping and
peripapillary rNFL thickness in glaucoma.10,11 Macula thickness losses in glaucomatous eyes
have correlated with estimated RGC count and Humphrey Visual Field (HVF) parameters in
both glaucomatous and normal eyes.4,10,12,13,14 Peripapillary rNFL scans images a ring of tissue
around the optic nerve, whereas, imaging the macula allows for quantification of total macula
thickness. This permits the mapping of macula thickness, and thus RGCs, to the visual field
for comparison.15
The traditional 24-2 or 30-2 visual field has relatively few spots dedicated to the macular
region and visual field deficits in this area require a greater numbers of ganglion cell loss as
compared with the more peripheral retina represented in the visual field.16 Small losses of
macular thickness are thus not detectable on visual field testing, enhancing the potential for
detecting early glaucoma using this modality.2,17
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3. How to use macular thickness
3.1. Glaucoma diagnosis

Pattern recognition of arcuate losses on macular thickness maps permits early detection of
disease. Ganglion cell losses in the perifoveal area are not isolated. They are accompanied by
loss of the ganglion cells along the arcuate track of the rNFL extending to the optic nerve
(Figure 1).18
Open in a separate window

Figure 1
Glaucomatous progression on macular SD–OCT scans. A macular thickness map of the right eye (top)
with arcuate thickness loss (inferior) is shown followed by macular thickness maps and superior–
inferior hemifield asymmetry plots at two separate visits (middle). The bottom figure is a macula
progression (change) map highlighting arcuate retinal thickness losses (red) in the inferior macula
between the two patient visits.
3.2. Glaucoma progression

Continued glaucomatous progression is detected by worsening of existing visual field defects
or by development of new visual field losses. Progression detection on macular thickness
maps is similarly performed by comparison plots between maps at different time points.
Glaucomatous losses are detectable by their arcuate shape in the subtraction maps (Figure 1).
3.3. Asymmetry of macular thickness

Glaucoma is typically a bilateral disease, but frequently asymmetric. A hallmark of glaucoma
is that visual field defects respect the horizontal midline, affecting superior or inferior visual
field differentially. Visual field deficits are also commonly asymmetric between the two eyes
at the time of diagnosis.19 Structurally, asymmetry in optic nerve cup-to-disc ratios is also
considered concerning for glaucoma. These concepts form the basis for the use of SD–OCT
macular thickness maps that compare both intraeye asymmetry (between the superior and
inferior macula) and intereye asymmetry (between the 2 eyes).20,21 As no normative database
is yet available for total macular thickness, using internal patient controls to detect
asymmetry is a powerful tool. This strategy may be limited in patients with end-stage
symmetric disease or with coexisting macular pathology (epiretinal membranes, diabetic
macular edema, and macular degeneration).
3.4. Ganglion cell segments

Use of macular RGC + IPL (GCIPL) thickness for glaucoma diagnosis has shown to yield
results similar to peripapillary rNFL thick-ness.22 Macular layer (GCIPL) asymmetry has also
been shown to be effective in the diagnosis of early glaucoma.23,24,25 Macular losses of the
GCIPL have shown to be correlated with visual field defects.24 Macular GCIPL may also
perform better than rNFL in advanced disease.26 Other strategies using macular thickness
include measuring extramacular ganglion cell complex thickness or using the ratio of
ganglion cell complex to total macular thickness.27,28
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4. Artifacts
Artifacts on SD–OCT are common and many of their causes are shared between scans of the
peripapillary rNFL and macula.29 Artifacts may result from operator/machine errors as well as
coexisting pathologies. Poor signal strength, improper centration, or segmentation errors can
lead to artificial increase or decrease in measured thickness. Epiretinal membrane or vitreous
adherence can artificially increase the thickness of the rNFL or macula by causing improper
identification of the internal limiting membrane. Anterior–posterior vitreous traction, or
retinal microcyst formation in rapidly advancing glaucoma may also confound
measurements.29,30 Inflammatory eye disease (iritis or uveitis) may cause edematous
thickening of the macula and rNFL that could also mask retinal ganglion cell loss.31
There are some artifacts of SD–OCT rNFL scans that are less prominent on macular scans.
For example, nonglaucomatous optic nerve damage or release of vitreous traction may show
up as segmental or diffuse rNFL loss making it difficult to detect glaucomatous damage.
However, on macular scans arcuate-shaped retinal loss, which is more specific for
glaucomatous damage, would allow better detection of glaucomatous damage. In cases of
vitreous traction in the peripapillary region (evolving posterior vitreous detachment), the
macular thickness may still be a reliable test as it may not be influenced by vitreous traction.
Finally, some pathologies affect macular scans greater than rNFL scans. Macular edema,
focal epiretinal membranes, macular degeneration, or atrophy may make macular scans
difficult to interpret or use to monitor for glaucomatous progression. The utility of using only
unaffected layers/segments, rather than total macula thickness, in cases of coexisting retinal
pathologies is not known.
Macular thickness maps may also be helpful in making the diagnosis of nonglaucomatous
optic neuropathies.32 Typical patterns of loss such as those seen in hemianopia or in ischemic
optic neuropathies are easily detectable on the macular thickness map (Figures
(Figures22 and and33).
Figure 2
Nonglaucomatous macular thickness loss from nonarteritic ischemic optic neuropathy. Macular
thickness plots of the right and left eye are shown. In the middle row right–left (OD-OS and OS-OD)
asymmetry plots are shown and in the bottom row superior–inferior hemifield asymmetry plots are
shown. These represent both intereye and intraeye differences. Note the losses (seen in black) in the
superior macula of the left eye and the relative preservation of macular thickness in the inferior left
eye and superior/inferior macula of the right eye. These losses represent altitudinal loss from
nonarteritic ischemic optic neuropathy.
Figure 3
Retrograde loss of macular thickness in a patient with a cerebrovascular accident. A left homonymous
hemianopia is shown by visual field testing. Loss of nasal left eye macular thickness and temporal
right eye macular thickness is seen below on the macular thickness plots (black arrows). Note these
losses respect the vertical (and not horizontal) axis of the fovea. Also the temporal left eye macula and
nasal right eye macula are still preserved (seen as yellow on the macular thickness plots).
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5. Special populations
The use of SD–OCT in children is attractive as they may be unable to perform reliable visual
fields. Macular thickness measurements have been shown to be lower in children with
glaucoma and mirrored the performance of peripapillary rNFL.33
Myopes present several challenges as they may have nonprogressive visual field changes due
to a tilted optic nerve, optic nerve coloboma, or posterior pole staphyloma.34 In addition,
peripapillary atrophy, retinal schisis, and vitreous traction results in unreliable rNFL
measurements. Macular thickness maps in such eyes have been shown to be useful in
glaucoma detection and management.35 Longer axial length is correlated with macular
thinning, specifically thinning of the nuclear layers of the macula.36 Macular scans may help
in these cases because RGCs are thickest in the macula and progressive disease can still be
detected.
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6. Conclusion
Macular thickness measurements are an excellent adjuvant modality in glaucoma diagnosis
complimenting SD–OCT rNFL, perimetry, and optic nerve head examination. They aid in the
ability to confirm changes seen on other modalities, and can overcome some of the
shortcomings of optic nerve assessment and rNFL measurements. The use of macular scans
marks a transition in how structural damage is measured in glaucomariginally the optic nerve
head cup was assessed, then the peripapillary rNFL, and now the macula. There are instances
where macular scans and macular segment analysis may be erroneous due to
operator/machine factors or other coexisting retinal pathology. More studies are needed to
optimize the role of macular SD–OCT in glaucoma care.
Ophthalmology. Author manuscript; available in PMC 2007 Aug 15.
Published in final edited form as:
Ophthalmology. 2003 Jan; 110(1): 177–189.
Optical Coherence Tomography Measurement of Macular

and Nerve Fiber Layer Thickness in Normal and
Glaucomatous Human Eyes
Viviane Guedes, MD,1,2,3 Joel S. Schuman, MD,1 Ellen Hertzmark, MA,1,4 Gadi Wollstein,
MD,1 Anthony Correnti, MD,1 Ronald Mancini, MD,1 David Lederer, MD,1 Serineh Voskanian,
MD,1 Leonardo Velazquez, MD,1 Helena M. Pakter, MD,1,5 Tamar Pedut-Kloizman,
MD,1 James G. Fujimoto, PhD,6 and Cynthia Mattox, MD1
Author information Copyright and License information Disclaimer
The publisher's final edited version of this article is available at Ophthalmology
See other articles in PMC that cite the published article.
Abstract
Glaucoma is a process in which a loss of retinal ganglion cells (RGCs) results in
characteristic optic nerve and visual field abnormalities. Detection of glaucomatous damage
is typically through observation of the optic nerve head and retinal nerve fiber layer (NFL)
and measurement of visual function with perimetry; however, both perimetry and observation
of optic disc changes are subjective examinations that are prone to variability. It is for this
reason that objective methods are under development to aid in the early diagnosis of
glaucoma and to assist in the detection of disease progression.
Defects in the retinal NFL may be an early sign of glaucoma, preceding optic disc and visual
field changes.1–3 The NFL is composed primarily of RGC axons, neuroglia, and astrocytes.
The ganglion cells are arranged in layers of four to six cells in the macula; the ganglion cell
layer is only one cell thick outside the macula. The ganglion cells along with the NFL
constitute 30% to 35% of macular retinal thickness, although the NFL itself is a major
component of total retinal thickness close to the optic nerve head. Loss of macular thickness
in glaucoma can be attributed mainly to RGC and NFL atrophy.4,5 It may be useful, therefore,
to assess macular thickness, because Zeimer et al4,6 hypothesized that macular RGC loss may
result in significant retinal thinning. They proposed quantitative detection of glaucomatous
damage at the posterior pole by retinal thickness mapping. Glovinsky et al,7 Frishman et
al,8 Wygnanski et al,9 and Weber et al10 demonstrated loss of RGCs in the macula in
experimentally glaucomatous monkeys.
Through the use of optical coherence tomography (OCT), an imaging technique that allows
high-resolution (approximately 10 μm) cross-sectional imaging of the eye based on the
principles of low-coherence interferometry, we are able to evaluate and quantify macular and
peripapillary NFL thickness and to analyze the effect of glaucoma in these areas. Because we
have significant experience with our prototype OCT device, but only the commercial OCT
device is available in the community, we analyzed these parameters with both the prototype
and commercial OCT and compared the data obtained with the two devices.
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Materials and Methods

A total of 367 subjects (534 eyes) examined between October 1998 and July 2000 at the New
England Eye Center, Boston, Massachusetts, were enrolled in this cross-sectional study after
informed consent approved by the New England Medical Center Human Investigation
Review Committee.
All subjects underwent a thorough ophthalmologic examination. This consisted of the
following: medical history (including ocular and family histories), visual acuity, refraction,
intraocular pressure (IOP) measurement, Humphrey 24-2 visual field testing, undilated and
dilated slit-lamp examination with stereoscopic biomicroscopy of the optic nerve head
(ONH) and NFL, and indirect ophthalmoscopy. Subjects had OCT testing of both the macula
and peripapillary NFL using the prototype OCT unit on the same day. To compare prototype
OCT results with measurements from the commercial OCT unit, a subset of subjects
underwent commercial NFL (95 eyes) and macular (126 eyes) OCT on the same day as their
prototype OCT scan.
All test eyes had a best-corrected visual acuity of 20/40 or better. Refractive errors were
between +3.00 and −6.75 diopters (D). Eyes were excluded that exhibited signs of retinal
disease, opaque media, or when the fundus was not visible. Subjects were excluded if they
were unwilling or unable to participate in the study.
We divided the eyes according to the following criteria into four diagnostic groups: normal,
glaucoma suspect, early, and advanced glaucoma.
Normal eyes served as the control group. Eyes in this group had no history of glaucoma,
retinal pathology, laser therapy, or intraocular surgery. IOP was 21 mmHg or lower. Optic
nerve heads had a normal appearance. All had normal visual field test results. Normal visual
field test results were defined as those having no cluster of three or more adjacent points
depressed more than 5 dB or of two adjacent points depressed more than 10 dB.
Glaucoma suspect eyes had no history of retinal pathology, laser therapy, or intraocular
surgery. Intraocular pressure was between 22 and 30 mmHg and/or they had asymmetric
cupping (difference in vertical cupping greater than 0.2) or abnormal-appearing ONHs.
Visual field results were normal as defined previously. Glaucoma suspect eyes were divided
into three categories: ocular hypertensive (OHT), increased cupping (vertical cup-to-disc
ratio greater than 0.6), or miscellaneous group (e.g., asymmetric cupping, glaucoma family
history).
Early glaucomatous eyes exhibited a typical arcuate or para-central scotoma and/or nasal step
on their visual field test, with clusters of three or more adjacent points depressed more than 5
dB or two or more adjacent points depressed more than 10 dB. This visual field loss was
present only on one side of the horizontal meridian and/or untreated IOP greater than 35
mmHg despite a full visual field. There was no complete loss of the neuroretinal rim to the
ONH margin in any quadrant, and their ONH cupping and/or NFL defect on stereo
biomicroscopy was in correspondence with their visual field loss.
Advanced glaucomatous eyes possessed all characteristics of the early glaucoma group as
described previously. What distinguished the advanced glaucoma group from the early
glaucoma group was either a complete loss of the neuroretinal rim to the ONH margin or
visual field loss above and below the horizontal meridian as determined by visual field
testing.
To create a normative database we included a set of normal eyes with normal perimetry either
by standard full threshold Humphrey 24-2 automated perimetry, short wavelength automated
perimetry, or Swedish interactive thresholding algorithm. For the other diagnostic groups we
used only 24-2 Swedish interactive thresholding algorithm standard visual field
examinations.
OCT Technology
OCT is an optical technique for high-resolution measurements and cross-sectional imaging of
the human retina.
OCT was performed using prototype and commercial devices. The commercial OCT device
(OCT1, Zeiss-Humphrey, Dublin, CA) ran the A-6 software revision. Detailed descriptions of
the principles of OCT have already been published; a summary follows.11–23
OCT is based on the principles of low coherence interferometry. By directing a low
coherence light beam, which is analogous to a series of short pulses of light, onto a partially
reflective mirror, two beams are created: reference and measurement beam. The measurement
beam is directed onto the subject’s eye, and it is reflected from intraocular microstructures
and tissues according to their distance, thickness, and different reflectivity. The reference
beam is reflected from the reference mirror at a known, variable position. Both beams travel
back to the partially reflective mirror, recombine, and are transmitted to a photosensitive
detector. For the two beams to recombine, their pulses must arrive at nearly the same time.
An interference signal is created when path lengths of the reference and measurement arms
are closely matched to within the coherence length of the light.
OCT measurements are performed using a fiberoptically integrated Michelson interferometer
with a short coherence length superluminescent diode source. Near-infrared illumination (840
nm) is used to minimize subject discomfort. The prototype OCT system was integrated into a
slit-lamp biomicroscope, a 78-diopter condensing lens mounted on the slit lamp in front of
the subject’s eye, and an attached infrared sensitive video camera that provided a view of the
scanning beam on the fundus. The commercial OCT was integrated into a fundus camera.
Axial reflectance profiles (A-scans) were measured versus depth. Tomographic images were
constructed from a series of A-scans. The scan rate used was 100 lateral pixel retinal
tomograms with a depth of 2 to 3 mm. The prototype OCT acquired an image in
approximately 2.5 seconds, whereas the commercial unit captured an image in just less than 1
second. OCT showed good reproducibility,15 and the resolution of the devices used in this
study was approximately 10 μm in the eye.
Optical Technique
Each eye was dilated with 1% tropicamide and 2.5% phenylephrine before recording the
images. Each subject eye underwent three circular scans around the center of the optic disc
using a circle size of 3.4 mm, which have been shown to provide better reproducibility than a
single scan.18,24 Internal fixation was chosen (subject fixated with the eye being studied)
because of better reproducibility than external fixation (subject fixated with the fellow eye).
Retinal and NFL thickness were reported as averages over each quadrant (superior, inferior,
nasal, temporal), as averages for each clock hour, and as averages over the entire cylindrical
section.12,18,24
Figures 1 through through88 show optic nerves, visual fields, and prototype and commercial
peripapillary NFL OCT scans for normal and glaucomatous eyes.
Figure 1
Stereoscopic photograph of a normal optic nerve head.
Figure 8
Commercial optical coherence tomography. Glaucomatous nerve fiber layer scan of eye demonstrated
in Figure 2, showing decreased thickness particularly in the inferior quadrant.
Macular scans consisted of six 100-pixel radial scans centered on the fovea and spaced 30°
from one to another. These scans were used to create a macular thickness map that
represented either approximately the central 20° of vision (6-mm diameter map, prototype
OCT) or approximately 10° of vision (3.45-mm diameter map, commercial OCT). The
macular thickness map was divided into nine sections, and it was displayed as three
concentric circles, including a central circle, an inner ring, and an outer ring, with each ring
divided into four quadrants. The central circle, inner ring, and outer ring in the prototype
macular thickness map had diameters of 1 mm, 3 mm, and 6 mm, respectively. Commercial
thickness maps showed a smaller area than prototype maps. The central disc, inner ring, and
outer ring diameters were 1 mm, 2.22 mm, and 3.45 mm, respectively. Retinal thickness
maps were color coded, with brighter colors for thicker retinal areas and darker colors for
thinner ones. Figures 5, ,6,6, ,9,9, and and10,10, show prototype and commercial macular
OCT scans for normal and glaucomatous eyes.
Figure 5
Prototype optical coherence tomography of eye shown in Figure 1. A, Normal macular

scan. B, Normal macular thickness map. C, Normal nerve fiber layer scan.
Figure 6
Prototype optical coherence tomography (OCT) of eye shown in Figure 2. A, Glaucomatous macular
scan. B, OCT showing glaucomatous nerve fiber layer thickness decreased particularly in the inferior
quadrant. C, Glaucomatous macular thickness map showing decreased macular thickness particularly
in the inferior inner ring and outer ring.
Figure 9
Commercial optical coherence tomography. Normal macular thickness map of eye shown in Figure 1.
Figure 10
Commercial optical coherence tomography. Glaucomatous macular thickness map of eye shown
in Figure 2, showing decreased macular thickness particularly in the inferior inner ring and outer ring.
OCT Analysis
Raw data obtained by OCT were analyzed using standard processing algorithms that
measured total retinal and NFL thickness. In addition, the algorithms corrected for various
artifacts, including eye movement, blood vessel shadows, blinks, and media opacities.
The location of the vitreoretinal interface and the retinal pigment epithelium defined the inner
and outer boundaries, respectively, of the neurosensory retina. These two boundaries were
associated with the sharpest edges in each OCT A-scan because of the high contrast in optical
reflectivity between the relatively nonreflective vitreous and the reflective neurosensory
retina and between the minimally reflective photoreceptor outer segments and the highly
reflective retinal pigment epithelium/choriocapillaris.
The boundaries of the NFL were defined by first determining the thickness of the
neurosensory retina as described previously. The posterior boundary of the NFL was
determined by evaluating each A-scan for a threshold value chosen to be 15 dB greater than
the filtered maximum reflectivity of the adjacent neurosensory retina.
Statistical Analysis
The subject information was entered into a computer database (FileMaker Pro 5, FileMaker,
Inc., Santa Clara, CA) and was analyzed using SAS (SAS Institute, Cary, NC). Because most
subjects in the study had two eyes, we used linear mixed regression models to compute all
means and regression results. Attempts at prediction were done using logistic regression, in
which only one observation per subject was used. The receiver operator characteristic curves
and the areas under them (AROC) were computed empirically using the c statistic produced
by SAS proc logistic.25
To compute correlation coefficients, one randomly chosen eye for each subject was used.
Differences between groups were described as mean difference ± standard error. Dispersion
within groups was shown by the standard deviation. When multiple comparisons were
performed, Bonferroni correction was used.
Go to:
Results
Subject Basic Characteristics

We performed peripapillary NFL and macula scans using the prototype OCT unit on 534 eyes
of 367 subjects. A subset of subjects underwent peripapillary NFL (95 eyes of 61 subjects)
and macular (126 eyes of 81 subjects) scanning with the commercial OCT unit on the same
day as their prototype OCT scan. Demographic data are summarized in Table 1.
Table 1
Demographic Characteristics of Patients Undergoing Optical Coherence Tomography
N Glaucoma Suspect Ea Ad
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
(n Ocul B Misc (n (n
= ar y ellan = =
10 Hype C eous 13 68
9 rtens u (n = 2 Su
Su ion p 10 Su bj
bj (n = pi Subje bj ect
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
A 50 58.3 5 62.8 65 65.

ge .1 (14.9 6. .3 9
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
(S (1 ) 7 (10.6) (1 (1
D) 7. (1 2. 6.3
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
7) 8. 8) )
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
9)
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
% 45 48.2 1 30.0 39 50.

M 5.
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
al .9 8 .7 8
e
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
% 10 15.4 5. 0.0 15 18.

Bl
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
ac .6 9 .5 5
k
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
% 12 11.5 1 33.3 9. 9.2

As 1.
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
ia .5 8 3
n
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
M −0 −0.6 −1 −2.93 −3. −1

ea .3 4 .3 01 2.0
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
n 8 (1.56 6 (1.97) (2. 1

de (1 (1 88 (8.
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
vi .2 ) .6 ) 13
a
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
ti 2) 3) )
o
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
n
(S
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
D)
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
Pa 1. 1.88 1. 2.06 2. 7.8

tt 51 (0.73 6 90 8
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
er (0 ) 8 (0.38) (1. (3.

n .3 (0 73 38
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
st 8) .2 ) )
an
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
da 8)
rd
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
de
vi
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
a
ti
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
o
n
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
(S
or rly va
m Gl nc
al au ed
co Gl
m au
a co
m
a
= ar y ellan = =
9 rtens u (n = 2 Su
Su ion p 10 Su bj
ec 27 n cts) ec s)
ts Subj g ts)
) ects) (n
=
2
1
Su
bj
ec
ts
)
D)
No statistically significant differences between groups except for mean deviation and pattern standard deviation
(P = 0.0001).
*
Numbers of subjects do not add to 367, because some subjects have different diagnoses in the two
eyes.
SD = standard deviation.
OCT
Effects of Age, Gender, and Race among Normal Eyes

There was an effect of age on mean macular thickness. When measurements were performed
with the prototype OCT unit, for which there was a larger population under study, there was a
nonsignificant increase in the central ring macular thickness of +0.26 μm/year (P = 0.06).
Inner ring, outer ring, and mean macular thickness showed decreases of −0.18 μm/year (P =
0.09), −0.03 μm/year (P = 0.72), and −0.03 μm/year (P = 0.73), respectively; these also did
not achieve statistical significance. Men had thicker central rings (by 10.7 ± 4.7 μm, P =
0.03), but there were no other statistically significant differences between the genders. Blacks
and Asians had thinner macular inner rings compared with whites (−18.4 μm, P = 0.003;
−3.9 μm, P = 0.01, respectively), as well as thinner central rings (−18.2 μm, P = 0.02,
−19.5 μm, P = 0.006, respectively) and thinner 0 to 3 μm rings (−13.8 μm, P = 0.009,
−17.2 μm, P = 0.0006, respectively). The effect of age, gender, and race on NFL thickness
was similar to that described previously.20
Effects of Glaucoma on Macular and NFL Thickness

Mean macular thickness (± standard deviation) for prototype and commercial OCT units are
summarized in Tables 2 and and33 by diagnostic group (normal, glaucoma suspect, early
glaucoma, advanced glaucoma). Glaucoma suspects were further subdivided into three
categories (ocular hypertensive, suspicious cupping, miscellaneous) shown in Tables 4 and
and55.
Table 2
Macular and Nerve Fiber Layer Thickness: Relation to Diagnosis (Prototype Optical
Coherence Tomography Device)
N Glaucoma Early Advanced

or Suspect Glaucoma Glaucoma
m
al
(n (n = 83 Eyes, (n = 196 Eyes, (n = 89 Eyes, 68
= 58 Subjects) 132 Subjects) Subjects)
16
6
Ey
es
,
10
9
Su
bj
ec
ts
)
M M P M P M P
ea ea ea ea
n n V n V n V
(S (S a (S a (S a
ta ta l ta l ta l
n n u n u n u
d d e d e d e
ar ar ar ar
d d d d
D D D D
ev ev ev ev
ia ia ia ia
ti ti ti ti
o o o o
n) n) n) n)
C 18 18 0 18 0 19 0
e 3. 4. . 5. . 0. .
n 5 3 7 1 2 9 0
t (2 (2 6 (2 4 (2 6
e 4. 7. 2. 5.
r 3) 4) 5) 5)
ri
n
g
I 24 24 0 24 0 23 0
n 8. 5. . 4. . 2. .
n 2 3 6 3 4 7 0
e (1 (2 1 (1 8 (2 0
r 9. 2. 9. 2. 0
ri 5) 5) 3) 7) 1
n *
O 23 22 0 22 0 21 0
u 0. 7. . 4. . 1. .
t 4 3 3 5 0 5 0
e (1 (1 4 (1 0 (1 0
r 4. 4. 5. 3 9. 0
ri 9) 0) 8) 3) 1
n *
C 22 22 0 22 0 21 0
e 7. 3. . 4. . 8. .
n 4 7 4 1 6 1 0
t (1 (2 1 (1 4 (1 0
e 7. 1. 8. 9. 1
r 5) 4) 2) 1)
+
i
n
n
e
r
M 22 22 0 22 0 21 0
e 9. 4. . 4. . 4. .
a 0 9 2 0 0 5 0
n (1 (1 3 (1 4 (1 0
m 3. 6. 4. 7. 0
a 4) 0) 5) 0) 1
c *
u
l
a
N 13 12 0 11 0 77 0
F 4. 6. . 2. . .9 .
L 6 9 1 4 0 (3 0
s (2 (2 3 (2 0 1. 0
u 3. 1. 8. 0 2) 0
p 3) 3) 0) 1 1
e * *
ri
o
r
N 13 12 0 11 0 76 0
F 8. 7. . 4. . .3 .
L 1 1 0 5 0 (3 0
i (2 (2 2 (2 0 7. 0
n 3. 3. 7. 0 0) 0
f 2) 7) 8) 1 1
e * *
ri
o
r
N 89 82 0 75 0 49 0
F .9 .9 . .9 . .4 .
L (1 (1 1 (2 0 (2 0
t 5. 9. 0 3. 0 3. 0
e 6) 3) 0) 0 9) 0
m 1 1
p * *
o
r
a
l
N 91 86 0 76 0 53 0
F .9 .2 . .1 . .0 .
L (2 (3 3 (3 0 (3 0
n 8. 2. 0 1. 0 6. 0
a 9) 9) 5) 0 0) 0
s 1 1
a * *
l
M 11 10 0 94 0 64 0
e 3. 6. . .7 . .3 .
a 6 0 0 (2 0 (2 0
n (1 (1 6 2. 0 7. 0
N 5. 8. 2) 0 3) 0
F 8) 9) 1 1
L * *

*
Statistically significant after Bonferroni correction.
P value for comparison with normals.

Center ring dimeter, 1 mm; inner ring diameter, 1–3 mm; outer ring diameter, 3–6 mm; center + inner ring
diameter, 3 mm; overall mean macula diameter, 6 mm.
NFL = nerve fiber layer.
Table 3
Macular and Nerve Fiber Layer Thickness: Relation to Diagnosis (Commercial Optical
Coherence Tomography Device)
N Glaucoma Early Advanced

or Suspect Glaucoma Glaucoma
m
al
(n (n = 40 Eyes, (n = 35 Eyes, 22 (n = 18 Eyes, 12

= 26 Subjects) Subjects) Subjects)
33
Ey
es
,
21
Su
bj
ec
ts
)
M M P M P M P
ea ea ea ea
n n V n V n V
(S (S a (S a (S a
ta ta l ta l ta l
n n u n u n u
d d e d e d e
ar ar ar ar
d d d d
D D D D
ev ev ev ev
ia ia ia ia
ti ti ti ti
o o o o
n) n) n) n)
C 20 20 0 19 0 19 0
e 9. 3. . 5. . 1. .
n 0 1 4 2 0 6 0
t (2 (2 1 (1 5 (3 9
e 0. 6. 6. 2.
r 5) 0) 0) 9)
ri
n
g
I 25 24 0 23 0 21 0
n 4. 9. . 8. . 9. .
n 8 4 3 0 0 6 0
e (1 (1 8 (2 2 (4 0
r 6. 9. 0. 2. 0
ri 0) 5) 0) 3) 6
n *
O 25 25 0 23 0 21 0
u 5. 0. . 7. . 2. .
t 2 4 4 9 0 5 0
e (1 (1 2 (2 0 (4 0
r 5. 5. 1. 8 1. 0
ri 9) 5) 4) 4) 1
n *
I 23 23 0 23 0 22 0
n 9. 6. . 4. . 2. .
n 3 3 4 4 0 1 0
e (1 (1 4 (1 6 (2 0
r 4. 7. 5. 0. 0
+ 7) 1) 7) 0) 1
o *
u
t
e
r
M 23 23 0 22 0 20 0
e 6. 0. . 0. . 4. .
a 2 9 3 5 0 0 0
n (1 (1 6 (1 1 (3 0
m 3. 7. 6. 7. 3
a 9) 9) 7) 7)
c
u
l
a
(n (n = 29 Eyes, (n = 33 Eyes, 20 (n = 15 Eyes, 10

= 20 Subjects) Subjects) Subjects)
18
Ey
es
,
11
Su
bj
ec
ts
)
M M P M P M P
ea ea ea ea
n n V n V n V
(S (S a (S a (S a
ta ta l ta l ta l
n n u n u n u
d d e d e d e
ar ar ar ar
d d d d
D D D D
ev ev ev ev
ia ia ia ia
ti ti ti ti
o o o o
n) n) n) n)
N 14 13 0 10 0 48 0
F 2. 0. . 4. . .9 .
L 7 1 0 8 0 (2 0
s (1 (1 8 (1 0 3. 0
u 6. 7. 9. 0 2) 0
p 0) 5) 0) 1 1
e * *
ri
o
r
N 13 12 0 10 0 69 0
F 8. 6. . 3. . .0 .
L 6 4 1 9 0 (2 0
i (1 (2 9 (3 0 1. 0
n 9. 1. 0. 0 0
f 5) 9) 8) 7 6) 1
* *
e
ri
o
r
N 86 77 0 60 0 36 0
F .3 .8 . .2 . .9 .
L (2 (1 1 (1 0 (1 0
t 0. 7. 4 6. 0 6. 0
e 2) 1) 3) 0 8) 0
m 1 1
p * *
o
r
a
l
N 91 80 0 60 0 32 0
F .3 .9 . .2 . .4 .
L (2 (2 2 (1 0 (1 0
n 4. 5. 0 8. 0 2. 0
a 4) 1) 9) 0 9) 0
s 3 1
a * *
M 11 10 0 83 0 47 0
e 4. 4. . .2 . .2 .
a 8 9 0 (1 0 (1 0
n (1 (1 4. 0 4. 0
N 3. 4. 6 2) 0 8) 0
F 1) 4) 1 1
L * *

*
Statistically significant after Bonferroni correction.
P values for comparison with normals.

Center ring diameter, 1 mm; inner ring diameter, 1–2.22 mm; outer ring diameter, 2.22–3.45 mm; inner + outer
rings diameter, 1–3.45 mm; overall mean macular thickness diameter, 3.45 mm.
Table 4
Macular and Nerve Fiber Layer Thickness: Relation to Glaucoma Suspect Group (Prototype
Optical Coherence Tomography Device)
Glaucoma Suspect
Ocular By Cupping Miscellaneous

Hyperten
sion
(n = 39 (n = 29 Eyes, 21 (n = 15 Eyes, 10
Eyes, 27 Subjects) Subjects)
Subjects)
Mean Mean P Mean P

(Standar (Stand Val (Stand Va
d ard ue ard lue
Deviation Deviati Deviati
) on) on)
Cente 192.4 176.3 0.0 176.5 0.1

r ring (29.0) (26.7) 7 (16.0) 8
Inner 252.9 236.9 0.0 242.4 0.2

ring (20.5) (22.9) 2 (18.5) 1
Outer 232.5 222.9 0.0 221.3 0.0

Glaucoma Suspect

Hyperten
sion
(n = 39 (n = 29 Eyes, 21 (n = 15 Eyes, 10
Subjects)
Mean Mean P Mean P

d ard ue ard lue
) on) on)
ring (14.6) (9.6) 2 (16.8) 5
Cente 231.8 215.3 0.0 217.5 0.0

r+ (19.8) (21.9) 2 (16.6) 8
inner
Mean 231.9 218.3 0.0 218.7 0.0

Glaucoma Suspect

Hyperten
sion
(n = 39 (n = 29 Eyes, 21 (n = 15 Eyes, 10
Subjects)
Mean Mean P Mean P

d ard ue ard lue
) on) on)
macul (15.1) (13.4) 1 (14.6) 4

a
NFL 132.2 120.4 0.0 124.2 0.3

super (23.5) (16.9) 6 (19.8) 8
ior
Glaucoma Suspect

Hyperten
sion
(n = 39 (n = 29 Eyes, 21 (n = 15 Eyes, 10
Subjects)
Mean Mean P Mean P

d ard ue ard lue
) on) on)
NFL 125.1 126.6 1.0 133.6 0.2

inferi (25.3) (23.0) 0 (20.2) 4
or
NFL 88.8 72.0 0.0 88.4 0.9

temp (14.7) (21.1) 001 (11.9) 7
oral
Glaucoma Suspect

Hyperten
sion
(n = 39 (n = 29 Eyes, 21 (n = 15 Eyes, 10
Subjects)
Mean Mean P Mean P

d ard ue ard lue
) on) on)
NFL 81.7 92.8 0.4 86.4 0.7

nasal (33.7) (37.0) 4 (22.6) 5
Mean 107.1 103.5 0.3 108.2 0.7

NFL (19.8) (19.5) 0 (14.8) 8

P value for comparison with ocular hypertension.
Differences between cupping and miscellaneous groups are not statistically significant (except for nerve fiber
layer temporal, where P = 0.01).
Center circle diameter, 1 mm; inner ring diameter, 1–3 mm; outer ring diameter, 3–6 mm; center + inner ring
diameter, 3 mm; overall mean macular diameter, 6 mm.
Table 5
Macular and Nerve Fiber Layer Thickness: Relation to Glaucoma Suspect Group
(Commercial Optical Coherence Tomography Device)
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

(Standard (Stand Val (Stand Val
Deviation ard ue ard ue
) Deviati Deviati
on) on)
Cente 205.2 198.1 0.6 206.0 0.9

Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
r ring (25.2) (32.7) 6 (15.2) 2
Inner 251.0 247.7 0.6 249.3 0.7

ring (27.3) (17.7) 8 (14.9) 7
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
Outer 252.6 247.3 0.4 253.3 0.9

ring (20.0) (12.4) 7 (12.5) 5
Inner 242.7 229.9 0.0 231.8 0.1

+ (16.3) (14.7) 1 (17.8) 0
outer
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
Mean 232.8 227.9 0.5 232.9 0.8

macul (21.8) (18.4) 8 (11.8) 9
a
(n = 7 (n = 13 Eyes, 9 (n = 9 Eyes, 6 Subjects)

Eyes, 5 Subjects)
Subjects)
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
Mean Mean P Mean P

) Deviati Deviati
on) on)
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
NFL 137.4 128.7 0.3 125.5 0.2

superi (13.5) (20.1) 7 (14.7) 6
or
NFL 129.9 118.7 0.4 137.5 0.6

Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
inferi (18.9) (24.7) 2 (14.5) 2

or
NFL 87.4 72.2 0.1 80.8 0.5

temp (16.9) (13.1) 5 (20.2) 3
oral
Glaucoma Suspect

Hyperten
sion
(n = 13 (n = 16 Eyes, 10 (n = 11 Eyes, 7
Subjects)
Mean Mean P Mean P

) Deviati Deviati
on) on)
NFL 88.0 80.8 0.7 79.0 0.5

nasal (31.3) (26.5) 4 (17.9) 6
Mean 111.8 100.6 0.2 105.7 0.5

NFL (15.8) (15.8) 5 (8.4) 2

P value for comparison with ocular hypertension.
Differences between cupping and miscellaneous groups are not statistically significant.
Center circle diameter, 1 mm; inner ring diameter, 1–2.22 mm; outer ring diameter, 2.22–3.45 mm; inner +
outer rings diameter, 1–3.45 mm; overall mean macular thickness diameter, 3.45 mm.
Many of the macular parameters showed statistically significant differences in comparing

normal and advanced glaucomatous eyes (Tables 2 and and3).3). Using both the prototype
and commercial OCT units, all NFL parameters were found to be significantly different
between normal and either early or advanced glaucomatous eyes (Tables 2 and and33).
The outer ring and the mean macula were the only prototype macular parameters that differed
between normal subjects and early and advanced glaucoma patients. The commercial macula
measurements of the inner ring, the outer ring, and the mean macula also differed between
the two types of glaucoma and normal subjects (Tables 2 and and3).3). The findings were
similar after adjusting for age, race, and gender using both prototype and commercial devices.
NFL in all sectors and the mean NFL were significantly different between normal subjects
and early and advanced glaucoma patients with both devices (Tables 2 and and3).3). The only
parameter that was found to differ between the normal subjects and the glaucoma suspect
group was the prototype device inferior quadrant NFL measurement.
There was a trend toward a reduction in NFL thickness compared with normal subjects in all
three categories of glaucoma suspects (Tables 4 and and5),5), although this finding did not
achieve statistical significance. Overall, the suspect group had a mean NFL thickness 6.4 μm
(± 3.3, P = 0.06) lower than that of normal subjects. The OHT subgroup had a trend toward
thicker macular measurements than that of the other suspect groups; this finding was
significant for the prototype device in all sectors except the center ring when compared with
that of the cupping subgroup, and the mean macular thickness when compared with that of
the miscellaneous subgroup. For the commercial device only the inner + outer sector was
significantly thicker in the OHT subgroup compared with the cupping subgroup.
AROC
The AROC comparing mean NFL thickness in normal subjects and eyes with advanced
glaucoma using the prototype OCT unit was 0.93. When considering only those individuals
scanned with both the prototype and commercial OCT devices on the same day, the AROC
for both units was 1.00. Comparing mean macular thickness in normal subjects and those
with advanced glaucoma scanned with both the prototype and commercial OCT devices on
the same day, the AROCs were 0.88 and 0.80, respectively (Table 6).
Table 6
Areas Under Receiver Operator Characteristic Curves for Prototype and Commercial Optical
Coherence Tomography Devices > 0.60 Subjects Scanned with Both Devices
Prototype Optical Commercial Optical
Coherence Tomography Coherence Tomography
Normal vs. Advanced Normal vs. Advanced

Glaucoma Glaucoma
Macula
1–3 mm/1– 0.87 0.79

3.45 mm
0–3 mm/0– 0.68 0.80

3.45 mm
3–6 mm 0.81 N/A
0–6 mm 0.88 N/A
NFL
Mean NFL 1.00 1.00
Superior NFL 1.00 1.00


Glaucoma Glaucoma
Inferior NFL 1.00 0.99
Normal vs. Early Glaucoma Normal vs. Early Glaucoma
Macula
1–3 mm/1– 0.69 0.62

3.45 mm
0–3 mm/0– 0.68 0.73

3.45 mm
3–6 mm 0.63 N/A
0–6 mm 0.77 N/A


Glaucoma Glaucoma
NFL
Mean NFL 0.93 0.94
Normal vs. Suspect Normal vs. Suspect
Macula
0–6 mm 0.64 N/A
NFL

Glaucoma Glaucoma
Mean NFL 0.79 0.69
Normal vs. Ocular Normal vs. Ocular

Hypertension Hypertension
Mean NFL 0.69 0.64


Glaucoma Glaucoma
Normal vs. Suspect by Normal vs. Suspect by

Cupping Cupping
Macula
1–3 mm/1– 0.67 0.70

3.45 mm
0–3 mm/0– 0.57 0.61

3.45 mm
3–6 mm 0.70 N/A
0–6 mm 0.67 N/A


Glaucoma Glaucoma
NFL
Mean NFL 0.86 0.68

Prototype and commercial optical coherence tomography center circle diameter, 1 mm; prototype optical
coherence tomography center circle + inner ring diameter, 3 mm; prototype optical coherence tomography inner
ring diameter, 1–3 mm; prototype optical coherence tomography overall mean macular thickness diameter, 6
mm; commercial optical coherence tomography inner + outer ring diameter, 1–3.45 mm; commercial optical
coherence tomography overall mean macular thickness diameter, 0–3.45 mm. N/A = Not available for
commercial optical coherence tomography; NFL = nerve fiber layer.
For the prototype device, measurements without the center ring had higher AROCs than those
with the center ring. For the commercial device, this finding was not duplicated.
Prototype and Commercial OCT Correlations

The correlation between prototype and commercial OCT for overall mean NFL thickness
was r = 0.73. The superior NFL had the best correlation (r = 0.79). The best correlation
between the macular thickness measurements with the two devices was found with the
prototype’s inner ring (diameter, 1–3 mm) and commercial inner + outer ring (diameter, 1–
3.45 mm) with r = 0.93.
Go to:
Discussion
This study was designed with the major objective of evaluating the association between
macular thickness and glaucoma; we found this association to be significant. We also wished
to determine whether macular thickness compared favorably with NFL thickness in its
association with disease and found that NFL thickness was more closely tied to glaucoma
status. Finally, we compared measurements made with our prototype OCT device with those
made with the commercially available device. We found a significant correlation between
measurements made with the two devices.
According to Zeimer et al’s hypothesis,4,6 quantitative detection of glaucomatous damage at
the posterior pole by retinal thickness mapping may provide a unique method for the
detection and monitoring of early glaucomatous tissue loss. The macula is defined
anatomically as that region of the retina where the ganglion cell layer is more than one cell
thick. Because the photoreceptor layer is not believed to decrease in thickness in glaucoma,
this loss of retinal thickness is attributed mainly to the ganglion cell and NFL. The ganglion
cells and NFL contribute 30% to 35% of the retina thickness in the macula, where the
ganglion cells are known to be most concentrated.4,5 According to Zeimer et al’s hypothesis, it
would be logical to expect that glaucoma detection would be most readily accomplished
through macular thickness assessment, because the RGC soma is 15 μm or more in size, and
its axon is only 1 to 2 μm in size.
When first proposed, the concept that macular thickness decreased in glaucoma was viewed
as heretical. It is most unusual to see macular visual field defects early in the disease, but this
is because of the redundancy of the macular visual system. Many studies have shown
generalized loss of RGCs in glaucoma.26–28 Ganglion cells are lost in the macular region, as
well as in the retinal periphery; however, detection by perimetry requires the loss of twice as
many RGCs in the central visual field compared with the more peripheral retina. Each
macular cone is subserved by two to three ganglion cells. The consequently greater number
of ganglion cells in the macular region allows substantial redundancy in the detection of
simple stimuli.7,27,29
We looked at our data in a number of ways, most specifically comparing means between
groups, performing regression analysis, and analyzing AROCs. With regard to AROCs, we
chose this statistical method to facilitate future comparison between studies and because it is
a summary statistic for sensitivity and specificity. The disadvantage of the AROC is that it
does not describe the shape of the curve, only the area underneath it, so the number alone
does not define the relationship between the sensitivity and specificity for the given
comparison; actual visual analysis of the curve provides some of this information (Fig 11).
Figure 11
Receiver operator characteristic (ROC) curve: Overall mean macular thickness comparing normal and
advanced glaucoma (prototype optical coherence tomography); area under the curve (AROC) is 0.87.
This curve is shown as an example of the ROC curves summarized by AROCs in Table 6 but does not
represent the parameter with the best discriminating ability.
Despite the hypothetical advantages to macular thickness assessment in glaucoma in this
study, whereas macular thickness was significantly associated with glaucoma, NFL thickness
showed a still stronger relationship with the disease. This finding may be due to
undersampling of the tissue at risk, because only approximately 50% of the RGC are present
in the macula, yet nearly 100% of the RGC are assessed in a peripapillary OCT NFL scan.
Because glaucoma is a diffuse disease, the ability to measure the damage done by glaucoma
in the entire eye may give peripapillary NFL assessment a distinct advantage over macular
thickness evaluation in detecting glaucoma. Furthermore, the absolute thickness changes are
greater when measuring nearly all of the RGCs, even if just their axons, than when measuring
just the subpopulation in the macula, despite the greater size of the RGC soma than that of its
axon. In addition, the nature of the OCT macular map leaves large areas of the macula
unsampled; another configuration of macular sampling might produce results more related to
glaucoma. The problem in increasing sampling density is balancing the number of scan points
and the length of scan time. As the technology continues to improve, it is possible that
reductions in scan time will allow a higher macular transverse scan density.
Another major advantage of NFL over macular thickness assessment is the confounding of
macular thickness measures by nonglaucomatous macular disease. Entities such as diabetes
and macular degeneration, for example, directly affect macular thickness and could obscure
or exaggerate the abnormalities seen with glaucoma. These are not significant issues in
peripapillary NFL assessment.
This is not to say that macular thickness measurement may not be a useful parameter in the
evaluation of glaucoma. It is significantly associated with the disease, and there may be fewer
technical challenges in its measurement than in the quantitation of peripapillary NFL
thickness. Interestingly, we found that the outer ring macular thickness with our prototype
OCT device provided better correlation than did the inner ring thickness in comparing normal
with glaucomatous. This more peripheral area of the macula showed a stronger association
with the disease than did the more central macula, and yet this area was not presented by the
commercial OCT software (revision A6). This finding points to the importance of the
inclusion of our prototype dataset in this study. Both OCT devices use six 6-mm radial scans
in constructing a macular map; however, whereas the prototype device presents the entire 6-
mm diameter macular map, only the central 3.45 mm is presented using the commercial OCT
software revision A6. Had we not had the prototype data, we would have missed the strength
of the macular thickness–glaucoma association. On the basis of these findings, we
recommend that future software revisions should include at least the central 6 mm of the
macula, data that are already acquired in a macular OCT scan.
Outer ring and mean macular thickness using the prototype OCT device distinguished normal
subjects from both early and advanced glaucoma patients in this study. With the commercial
device, inner ring, outer ring, and mean macula each discriminated between the groups.
Zeimer and coauthors,4 using the Retinal Thickness Analyzer (RTA, Talia Technologies,
Neve-Ilan, Israel), studied 19 eyes of 18 subjects and found losses up to 34% of normal
macular thickness in the posterior poles of patients with glaucoma, presumably because of the
loss of ganglion cells and NFL. Their data were a stimulus for this investigation, because
OCT theoretically offers a significant advantage in macular thickness assessment over the
RTA. Specifically, OCT allows 10 μm resolution (versus approximately 50 μm resolution for
RTA), providing more precise tissue measurement. OCT also uses near-infrared light, as
opposed to visible light used by the RTA; this gives OCT an advantage in patient comfort
during scanning. RTA has the advantage of a tighter scan pattern, producing more scan lines
per unit area than OCT.
This study showed once again that the inferior NFL was the parameter most strongly
associated with glaucoma status. In the prototype OCT data, the inferior NFL was the only
parameter that could show a statistically significant difference between normal subjects and
the glaucoma suspect group. It is well known that optic nerve defects associated with
glaucoma often occur initially at the inferior pole and that visual field defects associated with
glaucoma frequently manifest first in the superior visual field, corresponding to the inferior
pole defects.22
There were other interesting findings in this study. We separated our glaucoma suspects into
three groups: ocular hypertensives, suspicious cupping, and miscellaneous (which included
family history of glaucoma or asymmetric cupping), in reverse hierarchical order. We were
surprised to find that those subjects who were glaucoma suspects by suspicious cupping had a
trend toward the thinnest macular and NFL measurements, although this finding achieved
statistical significance only for the inferior quadrant NFL with the prototype device (P =
0.01; Tables 4 and and5).5). On more thoughtful reflection, however, it is possible that those
individuals who were glaucoma suspects by suspicious cupping might be those most likely to
have glaucoma compared with suspects by OHT, family history, or asymmetric cupping. Our
data bear out the importance and value of careful clinical examination and suggest that those
people with glaucomatous-appearing optic nerves should be the suspects we follow most
closely. Furthermore, these findings confirm the relevance of OCT macular and NFL
measurements in correlating with clinical findings and their potential role in helping to guide
clinical care.
OHTs had a trend toward the thickest macular measurements of any of the suspect groups,
more pronounced with the prototype device where all sectors were found to be significantly
thicker, except the center ring when comparing the OHT and cupping subgroups and only the
mean macula when comparing the OHT and the miscellaneous subgroups (Table 4). In the
commercial device, the OHT was significantly thicker compared with the cupping subgroup
for the inner + outer sector only (Table 5). The reason for these findings is unclear, as is the
reason for the age-related thickness increase of approximately 0.25 μm/year in this parameter.
It is encouraging to find that measurements made with the prototype and commercial OCT
devices were highly correlated and similar. These findings support the ability to extrapolate
from the datasets that have been accumulated using the prototype device to clinical patient
care with the commercial device. The fact that the findings in the larger dataset with the
prototype device were close to the same as those from the smaller commercial OCT dataset
suggest that the two devices function in a similar way, despite different delivery systems (slit-
lamp based for the prototype, fundus camera based for the commercial unit).
Macular thickness measurement may provide a new tool for the detection of glaucoma. Our
study results support Zeimer et al’s hypothesis that macular thickness is reduced in glaucoma.
Conversely, we found that peripapillary NFL thickness was a more sensitive indicator of the
presence or absence of glaucoma than was macular thickness. Nevertheless, macular
thickness assessment clearly may have a role in the assessment and care of glaucoma
patients. Future goals in this direction include the creation of new algorithms to specifically
measure the macular NFL/ganglion cell layer, or ganglion cell layer alone, and the
development of ultrahigh-resolution OCT devices (2–3 μm) to actually image and count
ganglion cells. Further investigation is necessary to improve the early detection of glaucoma
damage. The recognition of the importance and benefits of macular thickness measurements
in glaucoma represents a new approach to the evaluation and management of the disease.
Figure 2
Stereoscopic photograph of a glaucomatous optic nerve head showing moderate cupping and an
inferior notch.
Figure 3
Normal Humphrey 24-2 Swedish interactive thresholding algorithm standard visual field examination
in the normal eye represented in Figure 1.
Figure 4
Humphrey 24-2 Swedish interactive thresholding algorithm standard visual field examination
showing a superior defect in the glaucomatous eye represented in Figure 2.
Figure 7
Commercial optical coherence tomography. Normal nerve fiber layer scan of eye shown in Figure 1.
Optical coherence tomography
measurement of macular and nerve
fiber layer thickness in normal and
glaucomatous human eyes
Viviane Guedes 1, Joel S Schuman, Ellen Hertzmark, Gadi Wollstein, Anthony
Correnti, Ronald Mancini, David Lederer, Serineh Voskanian, Leonardo Velazquez, Helena
M Pakter, Tamar Pedut-Kloizman, James G Fujimoto, Cynthia Mattox
Affiliations expand
 PMID: 12511364
 DOI: 10.1016/s0161-6420(02)01564-6
Free PMC article
Abstract
Purpose: To evaluate the hypothesis that macular thickness correlates with the
diagnosis of glaucoma.
Design: Cross-sectional study.
Participants: We studied 367 subjects (534 eyes), including 166 eyes of 109 normal
subjects, 83 eyes of 58 glaucoma suspects, 196 eyes of 132 early glaucoma patients,
and 89 eyes of 68 advanced glaucoma patients.
Methods: We used optical coherence tomography (OCT) to measure macular and

nerve fiber layer (NFL) thickness and to analyze their correlation with each other and
with glaucoma status. We used both the commercial and prototype OCT units and
evaluated correspondence between measurements performed on the same eyes on
the same days.
Main outcome measure: Macular and NFL thickness as measured by OCT.

Results: All NFL parameters both in prototype and commercial OCT units were
statistically significantly different comparing normal subjects and either early or
advanced glaucoma (P < 0.001). Inner ring, outer ring, and mean macular thickness
both in prototype and commercial OCT devices were found to be significantly
different between normal subjects and advanced glaucomatous eyes (P < 0.001). The
outer ring was the only macular parameter that could significantly differentiate
between normal and early glaucoma with either the prototype or commercial OCT
unit (P = 0.003, P = 0.008, respectively). The area under the receiver operator
characteristic (AROC) curves comparing mean NFL thickness between normal and
advanced glaucomatous eyes was 1.00 for both the prototype and commercial OCT
devices for eyes scanned on both machines on the same day. The AROC comparing
mean macular thickness in normal and advanced glaucomatous eyes scanned on
both machines on the same day was 0.88 for the prototype OCT device and 0.80 for
the commercial OCT.
Conclusions: Both macular and NFL thickness as measured by OCT showed

statistically significant correlations with glaucoma, although NFL thickness showed a
stronger association than macular thickness. There was good correspondence
between findings using both the prototype and commercial OCT units. Macular and
NFL thickness measurements made with OCT may have usefulness in the clinical
assessment of glaucoma.
Figures
Analysis of macular volume in
normal and glaucomatous eyes
using optical coherence tomography
David E Lederer 1, Joel S Schuman, Ellen Hertzmark, James Heltzer, Leonardo J
Velazques, James G Fujimoto, Cynthia Mattox
Affiliations expand
 PMID: 12788124
 DOI: 10.1016/s0002-9394(02)02277-8
Abstract
Purpose: To evaluate macular volume in normal and glaucomatous eyes using
optical coherence tomography (OCT).
Design: Case control study.
Method: The authors assessed 272 eyes of 164 subjects as part of an institutional

study at New England Eye Center in Boston, Massachusetts; 202 eyes were in the
study group and 70 eyes in the control group. Eyes were categorized as normal (70
eyes of 43 subjects), glaucoma suspect (70 eyes of 44 subjects), early glaucoma (70
eyes of 47 subjects), or advanced glaucoma (62 eyes of 43 subjects). Subjects
underwent analysis with the commercially available OCT1 unit. Optical coherence
tomography macular neurosensory retinal thickness maps were used to calculate
macular volume for comparison to Humphrey visual field testing, intraocular pressure
measurement, and stereo biomicroscopy of the optic nerve head and nerve fiber
layer.
Results: Using repeated measures regression, macular volume in normal (2.37 +/-

0.11 mm(3)) glaucoma suspect (2.33 +/- 0.16 mm(3)), and early glaucoma eyes (2.27
+/- 0.13 mm(3)) was significantly greater than in eyes with advanced glaucoma (2.12
+/- 0.23 mm(3), P =.0001, P =.0001, and P =.0008, respectively). Macular volume in
normal eyes was significantly greater than in early glaucoma eyes (P =.01).
Conclusions: Optical coherence tomography retinal macular volume correlates with

known structural defects of glaucoma, providing a potential objective and
quantitative parameter for evaluation. Our data show a significant difference in
macular volume between normal, glaucoma suspect, and early glaucoma eyes,
compared with advanced glaucomatous eyes as well as between normal and early
glaucomatous eyes. This correlates with a trend of decreasing macular volume in
eyes with more advanced disease.
Retinal nerve fiber layer and

macular inner retina measurements
by spectral domain optical
coherence tomograph in Indian eyes
with early glaucoma
H L Rao 1, J G Babu, U K Addepalli, S Senthil, C S Garudadri
Affiliations expand
 PMID: 22079964
 DOI: 10.1038/eye.2011.277
Free PMC article
Abstract
Purpose: To compare the diagnostic abilities of peripapillary retinal nerve fiber layer
(RNFL) and macular inner retina (MIR) measurements by spectral domain optical
coherence tomography (SD-OCT) in Indian eyes early glaucoma.
Methods: In an observational, cross-sectional study, 125 eyes of 64 normal subjects
and 91 eyes of 59 early glaucoma patients underwent RNFL and MIR imaging with
SD-OCT. Glaucomatous eyes had characteristic optic nerve and RNFL abnormalities
and correlating visual field defects and a mean deviation of better than or equal to -6
dB on standard automated perimetry. Areas under the receiver operating
characteristic curves (AUC), sensitivities at a fixed specificity and likelihood ratios
(LRs) were estimated for all RNFL and MIR parameters.
Results: The AUCs for the RNFL parameters ranged from 0.537 for the temporal
quadrant thickness to 0.821 for the inferior quadrant RNFL thickness. AUCs for the
MIR parameters ranged from 0.603 for the superior minus inferior MIR thickness
average to 0.908 for ganglion cell complex focal loss volume (GCC-FLV). AUC for the
best MIR parameter (GCC-FLV) was significantly better (P<0.001) than that of the
best RNFL parameter (inferior quadrant thickness). The sensitivities of these
parameters at high specificity of 95%, however, were comparable (52.7% vs58.2%).
Evaluation of the LRs showed that outside normal limits results of most of the RNFL
and MIR parameters were associated with large effects on the post-test probability of
disease.
Conclusion: MIR parameters with RTVue SD-OCT were as good as the RNFL

parameters to detect early glaucoma.
Figures
Science direct ophthalmology Volume 115, Issue 6, June 2008, Pages 949-956
Original article
Mapping of Macular Substructures with

Optical Coherence Tomography for
Glaucoma Diagnosis
Author links open overlay panelOuTanPhDGisèleLiMDAke Tzu-
HuiLuPhDRohitVarmaMD, MPHDavidHuangMD, PhDAdvanced Imaging for Glaucoma
Study Group⁎
Show more
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https://doi.org/10.1016/j.ophtha.2007.08.011 Get rights and content
Purpose
To use optical coherence tomography (OCT) to identify the specific retinal layers
and macular regions damaged in glaucoma.
Design
Observational cross-sectional study.
Participants
One hundred forty-nine participants in the Advanced Imaging for Glaucoma Study,
divided into 3 groups: normal (N) perimetric glaucoma (PG), and glaucoma
suspect and preperimetric glaucoma (GSPPG) with 44, 73, and 29 persons,
respectively.
Methods
The Zeiss Stratus OCT system (Carl Zeiss Meditec, Inc., Dublin, CA) was used to
map the macula over a 6-mm diameter and to scan the circumpapillary nerve fiber
layer (cpNFL). The macular OCT images were exported for automatic
segmentation using software developed by the authors. The thickness of the
macular nerve fiber layer (mNFL), ganglion cell layer (mGCL), inner plexiform
layer (mIPL), inner nuclear layer (mINL), outer retinal layer (mORL), and total
retinal thickness were measured. Thickness measurements of GSPPG and PG eyes
were compared with those of N eyes. The ability to differentiate between GSPPG
and PG eyes against N eyes was assessed by fractional loss, standardized
deviation, and the area under the receiver operating characteristic curve.
Main Outcome Measures
Area-weighted average thicknesses of retinal sublayers in the macula.

Results
The mNFL, mGCL, mIPL, and mINL were significantly (P<0.001) thinner in both
the GSPPG and PG eyes than in the N eyes. In PG eyes, mNFL, mGCL, and mIPL
thinning was most severe (approximately 20%), mINL thinning was intermediate
(7%), and mORL thinning was minimal (3%). The repeatability (coefficient of
variation and intraclass correlation) of thickness measurements was improved by
combining the mNFL, mGCL, and mIPL measurements as the inner retinal layer
(mIRL). The mIRL was the best macular parameter for glaucoma diagnosis and
had discriminant power comparable with that of the cpNFL. The fractional loss of
mIRL thickness was most severe in the inferior perifoveal region for both the PG
and GSPPG groups.
Conclusions
Glaucoma leads to thinning of the mNFL, mGCL, mIPL, and mINL, even before
detectable visual field changes occur. A combination of the 3 innermost layers
seems to provide optimal glaucoma detection. Increasing the sampling of
peripheral macula with a new OCT scan pattern may improve glaucoma diagnosis
further.

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Comparative analysis of macular and peripapillary retinal nerve fiber layer thickness in

normal, glaucoma suspect and glaucomatous eyes by optical coherence tomography

DOI: 10.3126/nepjoph.v8i2.16991 Nepal J Ophthalmol 2016 jul

Materials and methods: Macular and peripapillary RNFL scans were performed in

Conclusion: Macular thickness as detected by TD-OCT had high discriminating

2012 Apr-Jun; 19(2): 204–210. Middle East African Journal of Ophthalmology (MEAJO)

Macular retinal and nerve fiber

Free PMC article

Results: Both early manifest glaucoma patients and glaucoma suspects had

Conclusions: The finding that RT was significantly lower in early manifest glaucoma

Keywords: Early Glaucoma; Macula; Optical Coherence Tomography; Retinal

Conflict of interest statement

Conflict of Interest: None declared.

Macular thickness analysis for glaucoma diagnosis and

2. Why macular thickness?

3.1. Glaucoma diagnosis

Open in a separate window

3.2. Glaucoma progression

3.3. Asymmetry of macular thickness

3.4. Ganglion cell segments

Optical Coherence Tomography Measurement of Macular

Materials and Methods

Stereoscopic photograph of a normal optic nerve head.

Prototype optical coherence tomography of eye shown in Figure 1. A, Normal macular

Subject Basic Characteristics

A 50 58.3 5 62.8 65 65.

% 45 48.2 1 30.0 39 50.

% 10 15.4 5. 0.0 15 18.

% 12 11.5 1 33.3 9. 9.2

M −0 −0.6 −1 −2.93 −3. −1

n 8 (1.56 6 (1.97) (2. 1

Pa 1. 1.88 1. 2.06 2. 7.8

er (0 ) 8 (0.38) (1. (3.

Effects of Age, Gender, and Race among Normal Eyes

Effects of Glaucoma on Macular and NFL Thickness

N Glaucoma Early Advanced

Open in a separate window

P value for comparison with normals.

N Glaucoma Early Advanced

(n (n = 40 Eyes, (n = 35 Eyes, 22 (n = 18 Eyes, 12

(n (n = 29 Eyes, (n = 33 Eyes, 20 (n = 15 Eyes, 10

Open in a separate window

P values for comparison with normals.

Ocular By Cupping Miscellaneous

Mean Mean P Mean P

Cente 192.4 176.3 0.0 176.5 0.1

Inner 252.9 236.9 0.0 242.4 0.2

Outer 232.5 222.9 0.0 221.3 0.0

Ocular By Cupping Miscellaneous

Mean Mean P Mean P

ring (14.6) (9.6) 2 (16.8) 5

Cente 231.8 215.3 0.0 217.5 0.0

Mean 231.9 218.3 0.0 218.7 0.0

Ocular By Cupping Miscellaneous

Mean Mean P Mean P

macul (15.1) (13.4) 1 (14.6) 4

NFL 132.2 120.4 0.0 124.2 0.3

Ocular By Cupping Miscellaneous

Mean Mean P Mean P

NFL 125.1 126.6 1.0 133.6 0.2

NFL 88.8 72.0 0.0 88.4 0.9

Ocular By Cupping Miscellaneous

Mean Mean P Mean P