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© 2011 Wichtig Editore - ISSN 1120-6721
Eur J Ophthalmol (2011 ; :00) 000-00000
1
DOI:
INTRODUCTION
Central visual field testing with 24-2 and 30-2 programs
is commonly used to diagnose and monitor patients with
glaucoma as well as other diseases affecting visual function
(such as pseudotumor cerebri or visual pathway injuries). It
has been accepted as a standard procedure for endpoint
determination in various clinical trials (1-4). However, a re-
cent report demonstrated that central testing strategy is
not ideal for detecting or monitoring disturbances in the
visual field originating more peripherally, such as defects
caused by drug toxicity (5). Visual field loss has been ob-
served as a result of treatment with different medications
such as antiepileptic drugs (topiramate and vigabatrin) (6-
10), synthetic antimicrobial agents against Gram-positive
Peripheral visual field thresholds using Humphrey
Field Analyzer program 60-4 in normal eyes
Tamara L. Berezina, Albert S. Khouri, Anton M. Kolomeyer, Patrick S. Clancy, Robert D. Fechtner
Institute of Ophthalmology and Visual Science, UMDNJ–New Jersey Medical School, Newark, NJ - USA
Pu r P o s e . Various methods have been used for testing peripheral visual field disturbances such as de-
fects caused by drug toxicity. Static threshold perimetry with Humphrey Field Analyzer (HFA) is widely
available. The aim of this study was to better define the normal thresholds for peripheral visual field
(PVF) sensitivity and to refine analysis strategies.
Me t h o d s . Automated PVF testing was performed with HFA 60-4 program in 33 normal subjects. Test
locations were organized into inner, middle, and outer eccentricity rings and divided into 4 zones: na-
sal, temporal, superior, and inferior. The threshold visual sensitivity (TVS) in decibels was established
for each point.
re s u l t s . The majority of points with the lowest TVS and highest between-subject variability were
located within the nasal area of the outer ring. Points with the highest TVS and least variability were
detected in the inner ring and in the temporal area of the middle and outer rings. Mean zone TVS de-
creased and variability increased with increasing eccentricity.
Co n C l u s i o n s . The areas that demonstrate the highest between-subject consistency and thus might
best reveal peripheral visual abnormalities with HFA 60-4 are the inner ring, inferior and temporal zone
of the middle ring, and temporal zone of the outer ring. These observations may be useful for develo-
ping strategies to detect peripheral field loss at an early stage when central vision is not yet affected.
Ke y Wo r d s . Eccentricity, Humphrey Field Analyzer, Peripheral visual field, Program 60-4
Accepted: November 28, 2010
ORIGINAL ARTICLE
bacteria (linezolid) (11), corticosteroids (12-15), antineopla-
stic agents (docetaxel, paclitaxel) (16), and antiarrhythmic
drugs (amiodarone), among others (17). The assessment
of more peripheral visual field regions becomes particularly
important during treatment monitoring and ocular safety
trials of new treatments when the aim of testing is the de-
tection of subtle visual field disturbances that often start
outside the central 30 degrees. The Humphrey Field Analy-
zer (HFA, Carl Zeiss-Meditec, Dublin, CA, USA) is widely
available and offers screening and threshold peripheral
test programs. Utilizing wider visual field testing programs
(up to 60 degrees) might have the advantage of early de-
tection of peripheral field defects that would appear later
on conventional central visual field testing.
Limitations of peripheral visual field examination include a
EJO-D-10-00468.indd 1 24-01-2011 14:52:29
© 2011 Wichtig Editore - ISSN 1120-6721
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HFA program 60-4 in normal eyes
Exclusion criteria
Glaucoma•
Ocular hypertension•
Current use of eyedrops to lower intraocular pressure•
Known visual field defects•
High myopia (greater than –6 diopters)•
Macular disease (e.g., age-related macular degenera-•
tion, diabetic maculopathy, cystoid macular edema)
Diabetic retinopathy worse than mild nonproliferative •
disease
Retinal disorder that could affect visual field (e.g., prior •
retinal detachment, retinitis pigmentosa)
Cataract causing visual acuity less than 20/40.•
Testing
Testing was performed in 33 subjects of both sexes. All
participants underwent slit-lamp and retinal examination.
Automated visual field testing was performed using the
HFA. The program utilized for testing in the study was the
Humphrey 60-4, 3-zone static perimetry test, full-threshold
strategy with size III white stimulus, and background il-
lumination of 31.5 apostilbs. Duration of the test ranged
from 4.10 to 7.95 minutes (mean 6.24±0.74 minutes) per
eye. As the primary objective of our study was to examine
variability of peripheral visual field sensitivity, we included
both eyes for all subjects. Visual fields were determined to
be unreliable if fixation losses were greater than 30%, or
if false-positive or false-negative rates were greater than
30%. The test was repeated in one subject because the
result of the first test was unreliable.
The total number of locations tested in the Threshold Site
List for HFA 60-4 was 60 (Fig. 1). Each point was labeled
with a nasal/temporal/superior/inferior coordinate system
denoting its location by degrees from fixation on the 60-4
printout (e.g., N30_S6, nasal 30 degrees, superior 6 de-
grees, or T30_I6, temporal 30 degrees, inferior 6 degrees)
with a measured threshold for visual sensitivity in decibels.
Points were organized into inner, middle, and outer ec-
centricity rings (Fig. 2). The corresponding location data
points for left and right eyes were overlaid and combined
for analysis. The inner, middle, and outer rings included 16,
20, and 24 points, respectively.
To better characterize the data by location, we also divided
the inner and middle rings into 4 zones: superior, inferior,
nasal, and temporal. The outer ring was divided into 3 zo-
wide range of test results caused by variable peripheral
retinal sensitivity and anatomic features of the face such
as nose or eyebrows that may obscure the peripheral field.
Interpretation of results depends, in part, on the expected
range of normal values.
Analysis and interpretation of central visual field testing is
supported by multiple validated statistical tools; for exam-
ple, total deviation indicating the degree to which the pa-
tient’s field deviates from age-adjusted normal controls,
pattern deviation adjusting results for any depression in
the overall field, the glaucoma hemifield test, and global
indices. Similar analysis tools are not developed for peri-
pheral visual testing. We have reported pilot data on the
use of HFA peripheral 60-4 threshold test for the asses-
sment of visual fields in cocaine users before and after vi-
gabatrin treatment (18). In that report, we only used the
standard software to report our results. However, expected
normal values and local variability of peripheral visual field
sensitivity have not yet been well-established. At which lo-
cations in the peripheral field might there be useful data on
program 60-4 to allow determination of normal values or to
detect change? Exploring this should help determine whe-
ther this test could be useful in detecting peripheral vision
loss. The aim of the present study is to investigate the nor-
mal expected thresholds and between-subject variability
for peripheral visual field sensitivity as tested by the HFA
60-4 threshold test as well as to refine analysis strategies.
MATERIALS AND METHODS
Automated peripheral visual field assessment was perfor-
med using HFA 60-4 program (HFA model 750i, softwa-
re version 4.2). The study protocol was approved by the
institutional review board at UMDNJ–New Jersey Medical
School, Newark, NJ, USA. All recruited subjects provided
signed informed consent.
Participant inclusion and exclusion criteria for the study
were as follows.
Inclusion criteria
Age from 18 to 80 years•
Absence of history of ophthalmic diseases•
Normal biomicroscopic evaluation performed by •
ophthalmologist, and intraocular pressure <21 mmHg
by Goldmann tonometry.
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© 2011 Wichtig Editore - ISSN 1120-6721 3
Berezina et al
Visual sensitivity in different zones of inner, middle, and ou-
ter rings was compared using analysis of variance followed
by Tukey test. The level of statistical significance was set at
p<0.05. Analysis was performed using SPSS 9.0 for Win-
dows (SPSS, Chicago, IL, USA).
RESULTS
The age of enrolled subjects ranged from 18 to 55 years
(mean 35.3+12.8 years). A total of 66 eyes from 33 parti-
cipants were included in the analysis. Mean threshold and
standard deviation values in dB for each spatial location
were calculated as presented in Figure 3. The mean total
threshold sensitivity for the right eye (the sum of sensitivi-
ties in all location points) did not significantly differ from the
mean total threshold sensitivity for the left eye (1290±105
dB vs 1299±104 dB, p>0.05). The majority of points with
the lowest visual sensitivity were located within the nasal
area of the outer ring (N30_S42, N54_S30, N54_S18, N54_
S6, N54_I6, N54_I18, N42_I30, N42_I42, N30_I42) (Fig. 3).
Most of those points demonstrated high data variability
with a standard deviation that was either equal to or hi-
gher than the mean (Tab. I). Data in the majority of points in
the nasal area were not normally distributed. Hierarchical
nes: inferior, nasal, and temporal (the outer ring lacked a
superior zone because points in that location are not te-
sted by the program due to the anatomy of the brow). We
calculated mean and total sensitivity for each zone and
ring. The total sensitivity for each zone was calculated by
averaging total individual sensitivities within a zone. The
total sensitivity for each ring was calculated by averaging
all individual point sensitivities within a ring.
Data were expressed as mean ± standard deviation in de-
cibels. To explore the distribution of data, they were tested
for normality by the one-sample Kolmogorov-Smirnov test.
To identify coordinates of similar variability, hierarchical
cluster analysis was applied. Clustering was based on the
value of standard deviation. The threshold visual sensitivity
data collected from individual healthy volunteers were ag-
gregated and analyzed in 5 distinct ways:
1. Mean threshold visual sensitivities were calculated for
each point by spatial location.
2. Points with highest and lowest sensitivity were identi-
fied.
3. Summation of threshold values for each zone was com-
puted (total zone sensitivity).
4. Summation of threshold values for each of the 3 rings
(total ring sensitivity) was computed.
5. Variability in results was analyzed.
Fig. 1 - Printout of Humphrey Field Analyzer 60-4. The total number
of points is 60.
Fig. 2 - Explanation of eccentricit y rings. Each rectangle represents
one point of spatial location. Points of locations that belong to an
inner, middle, and outer ring are shown in green, tan, and purple,
respectively. Zones are identified using letters: I = inferior, N = nasal,
S = superior, T = temporal. ∆ = shows temporal side.
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HFA program 60-4 in normal eyes
cluster analysis confirmed that there were 2 homogeneous
clusters (groups) of points with higher or lower data varia-
bility. The cluster with a high data variability united points
located in the nasal area of the outer ring.
The majority of points with the highest threshold visual
sensitivity were located in the inner ring as well as the tem-
poral area in the middle and outer rings.
The total threshold sensitivities for the inner, middle, and
outer rings were 426.48±27.79 dB, 464.33±38.70 dB, and
404.32±55.80 dB, respectively. Note that rings had diffe-
rent numbers of test points. The means of the sensitivi-
ties for the rings were 26.59±1.87 dB, 23.18±3.69 dB, and
16.89±8.49 dB.
The standard deviation increased with increasing eccentri-
city (from inner to outer ring), reflecting greater data varia-
bility with greater eccentricity.
The level of mean threshold sensitivity in each zone de-
creased from the center to the periphery (Tab. II). The lo-
west threshold sensitivity was detected in the nasal zone
of the outer ring. Data in this zone were not normally di-
stributed and showed high variability (Fig. 4). Zones that
also demonstrated high data variability were the superior
zone of the middle ring and the inferior zone of the outer
ring. The total threshold sensitivity for each zone is presen-
ted in Table III. Note that zones had different numbers of
test points. Comparisons of totals were appropriate only
among zones with equal number of spatial location test
Fig. 3 - Visual sensitivity mean threshold values in dB for each spa-
tial location. Upper line of each rectangle shows mean ± standard
deviation. Lower line of each rectangle shows a range of ±2 standard
deviations from the mean. ∆ = shows temporal side.
TABLE I -
POINTS OF LOCATION ARRANGED BY THE VAL-
UE OF STANDARD DEVIATION
Point Location Mean SD
T42 _ I18 T, M 27. 4 7 1.70
T42 _ S 6 T, M 27. 3 2 1.76
T30_I30 T, M 27.7 3 1.79
T54_S6 T, O 25.67 1. 90
T42 _ I 6 T, M 28.09 1.92
T30_I6 T, I 29.44 1.99
T54_I6 T, O 26.26 2.00
T30_S30 T, M 25.73 2.00
T18_I30 I, I 28.27 2.02
T18_I42 I, M 25.76 2.08
T42 _ S1 8 T, M 26.35 2.09
T42 _ I 30 T, O 26.33 2.11
T6_I42 I, M 25.82 2.11
T30_I42 T, O 25.53 2.1 3
N6_I30 I, I 26.91 2.26
T30_S6 T, I 29.52 2.31
T54_ I18 T, O 25.79 2.31
T30_ S18 T, I 2 8 .11 2.32
T6_I30 I, I 2 8.17 2.32
N42_I42 N, O -1.4 2 2.35
T18_S 30 S, I 25.91 2.43
T30_ I18 T, I 28.95 2.45
T42_I42 T, O 23.61 2.58
T42 _ S 30 T, O 24.18 2.75
N6_I42 N, M 23.26 2.77
N18_I30 I, I 2 6 .17 2.77
T54_ S18 T, O 24.68 2.80
N18_I42 I, M 22.30 2.94
N30_I18 N, I 25.98 3.02
N42_S6 N, M 22.67 3.25
N30_S6 N, I 25.95 3.55
N30_I6 N, I 26.03 3.58
T6_S30 S, I 23.97 3.66
N6_S30 S, I 24.2 9 3.70
N42_I6 N, M 22 .74 3.82
T6_I54 I, O 21. 68 3.86
T54_S30 T, O 21.3 6 4.10
N18_ S30 S, I 23.98 4.1 9
T18_I54 I, O 21.67 4.23
N30_S30 N, M 23.45 4.26
N42 _S18 N, M 21. 38 4.34
N6_I54 I, O 18.3 0 4.48
N30_S18 N, I 24.8 3 4.72
N54_S30 N, O 1.18 5.26
N30_I30 N, M 23.68 5.31
N42 _I18 N, M 21. 33 5 .41
T30_S42 T, O 19.62 5.99
T6_S42 S, M 16.48 6.04
T18_S 42 S, M 19.4 5 6.46
N18_I54 I, O 15. 20 6.56
N6_S42 S, M 17. 48 6. 74
N54_ I18 N, O 3.29 7.12
N42_S30 N, O 1 7. 8 6 7.16
N18_ S42 S, M 15.8 3 7. 3 9
N54_S6 N, O 11. 79 8.05
N54_I6 N, O 11. 3 9 8.29
N54_ S18 N, O 8.52 8.45
N30_S42 N, O 12.73 8.69
N42_I30 N, O 7.18 9.55
N30_I42 N, O 11. 92 10.8 5
Each point of location is defined by 2 letters. The first letter indicates the zone
(nasal [N], temporal [T], superior [S], or inferior [I]), and the second letter indi-
cates the ring (inner [I], middle [M], or outer [O]). The 60-4 program assigns a
threshold of –2 if there is no response at a test location.
EJO-D-10-00468.indd 4 24-01-2011 14:52:34
© 2011 Wichtig Editore - ISSN 1120-6721 5
Berezina et al
A B
Fig. 4 - Peripheral visual field in healthy subjects with different values of threshold sensitivity in the nasal zone of the outer ring. (aA) Threshold
sensitivity is equal to zero in 6 points of the nasal zone of the outer ring. (bB) Threshold sensitivity in the majority of points of the nasal zone of
the outer ring ranges from 14 dB to 23 dB, and is equal to zero in only one point (N42_I42).
TABLE II - MEAN ZONE VISUAL SENSITIVITY IN DB
Inner ring Middle ring Outer ring
Superior zone 24.55±3.61 17.37±6.78* —
Inferior zone 27. 3 1± 2 . 4 4 24.2±2.92* 19.22±5.57 *†
Temporal zone 28.92±2.29 27.56±1.74* 23.8±4.41*†
Nasal zone 25.6 5±3.75 22.53±3.97* 8.63±8.97
*p<0.01 vs inner ring.
†p<0.01 vs middle ring.
TABLE III - TOTAL ZONE VISUAL SENSITIVITY IN DB
Inner ring Middle ring Outer ring
Superior zone 98 . 20±10. 96
(4 points)
69.47±22.58*
(4 points)
—
Inferior zone 10 9 . 2 3 ±7. 0 1
(4 points)
96.82±7.57*
(4 points)
76.88±14.62*†
(4 points)
Temporal zone 115 .68 ± 6 . 57
(4 points)
16 2 . 2 3± 7. 6 5
(6 points)
243.02±17.09
(10 points)
Nasal zone 102.59±10.0 3
(4 points)
13 5 . 0 5 ±17. 4 9
(6 points)
85.50±44.17
(10 points)
*p<0.01 vs inner ring.
†p<0.01 vs middle ring.
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HFA program 60-4 in normal eyes
tivity were located within the nasal zone of the outer ring.
These points also exhibited high variability. Whether this
observation was related to retinal sensitivity or to anatomic
limitation by obstruction by the nose is difficult to deter-
mine. Other physiologic features such as brows may have
prevented the stimulus from reaching the eye. For further
analysis, we have grouped points in each ring into several
zones. The inner and the middle ring have 4 zones: su-
perior, inferior, temporal, and nasal. The outer ring has 3
zones: temporal, inferior, and nasal. The most consistent
results were received in all zones of the inner ring, inferior
and temporal zone of the middle ring, and in the temporal
zone of the outer ring. The nasal zone of the outer ring was
highly variable and might not be useful for the assessment
of the peripheral visual field. The inferior zone of the outer
ring as well as the superior zone of the middle ring might
also have a limited clinical value.
To some extent, a component of high interindividual varia-
bility might in part be explained by the fact that we most-
ly tested inexperienced individuals (28 from 33 subjects).
Heijl et al (21) observed that the normal range of visual sen-
sitivities becomes very wide when inexperienced subjects
are tested. On the other hand, Bengtsson et al (22) em-
phasized that the performance of tested volunteers with
significant experience in automated perimetry can be “su-
pernormal.” That is why the authors reasonably point out
that the selection of volunteers from a broad population
might give more objective results. One of our interests is to
study peripheral visual field as a safety measure for clinical
trials. Therefore, we believe an inexperienced group would
best represent the likely populations.
Heijl et al (21) have reported decreasing sensitivity with
increasing eccentricity for 30-2 program of the HFA (21).
We have shown that the level of visual field threshold
sensitivity is decreasing from 30° to 60° eccentricity. It is
also known that variability increased with eccentricity in
the central visual field. We have found that this effect is
maintained in the region tested by program 60-4. Periphe-
ral visual field testing with Humphrey program 60-4 shows
patterns of sensitivity and variability that might be useful in
designing studies or following clinical disease. Our obser-
vations suggest that the areas that might be most useful to
reveal visual abnormalities are all zones of the inner ring,
inferior and temporal zone of the middle ring, and temporal
zone of the outer ring. Our study has certain limitations. It
has a relatively small sample size. However, it is not the
objective of the study to establish the normative database
points. This comparison demonstrated that similar to the
mean threshold sensitivity, the total sensitivity was decrea-
sing from the center to the periphery.
DISCUSSION
The variability of the threshold sensitivity in the central 30°
has been studied and described by other investigators (19,
20). The variability of the threshold sensitivity of the peri-
pheral 30° to 60° area has not been described. While the
central field is widely used to monitor glaucoma and other
diseases, some conditions might be better detected in the
30° to 60° field. HFA 60-4 program is widely available and
is used for testing peripheral visual field but there is little
available information about expected thresholds and varia-
bility. We have previously reported use of the HFA 60-4 pro-
gram for the monitoring of peripheral visual field of cocaine
or methamphetamine users during short-term vigabatrin
treatment (18). However, the commercially available sof-
tware for the interpretation of results of HFA 60-4 testing is
not suited for clinical trials. Moreover, normal values have
not been well-described for this program.
We performed HFA 60-4 threshold test on normal subjects
to determine which location points may be most useful
for testing abnormalities. One of the particularly challen-
ging aspects of this analysis was the notable variability in
visual sensitivity in relation to test point spatial location.
We analyzed our data by dividing spatial locations into ec-
centricity rings (inner, middle, and outer ring representing
peripheral visual field locations ranging between 30° and
60°) and zones (superior, inferior, nasal, and temporal). This
approach can be adopted for interpretation of peripheral
visual fields and comparisons to normative data in various
clinical settings.
It is important to note that eccentricity rings consisted of
an unequal number of points. The least points (16) were
in the inner ring and the most (24) were in the outer ring.
Subjects with no history of ophthalmic diseases and nor-
mal eye examination demonstrated a low threshold value
of visual sensitivity at certain areas. That implies that de-
tecting visual field loss in a disease state in such areas
may be beyond the dynamic range of this test at specific
coordinates. This can be related to the inherent low mean
visual field sensitivity as well as the high interindividual va-
riability of measured retinal sensitivity in those spatial loca-
tions. The majority of points with the lowest visual sensi-
EJO-D-10-00468.indd 6 24-01-2011 14:52:35
© 2011 Wichtig Editore - ISSN 1120-6721 7
Berezina et al
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for program 60-4. Our results reveal zones that are most li-
kely to be useful for the evaluation of peripheral visual field
abnormalities. We tested a relatively young (18–55 years)
population. Our observation should be confirmed in an ol-
der age group.
These results can be useful for guiding the development of
strategies for the detection of visual loss at an early stage of
a disease or a condition when central vision is not yet alte-
red. Additional studies are needed to validate this concept.
ACKNOWLEDGEMENTS
Statistical consultation was provided by Tatiana Koudinova,
PhD, GfK Healthcare (East Hanover, NJ, USA).
Supported in part by Research to Prevent Blindness, New York, NY,
The Glaucoma Research and Education Foundation, Inc., NJ, and an
unrestricted gift from Joseph and Marguerite DiSepio.
Presented in part at the ARVO 2010 annual meeting, Fort Lauderdale,
FL, May 2–6, 2010.
The authors report no proprietary interest.
Address for correspondence:
Tamara L. Berezina, MD, PhD
Institute of Ophthalmology and Visual Science
UMDNJ–New Jersey Medical School
90 Bergen Street, Suite 6100
Newark, NJ 07103
USA
berezitl@umdnj.edu
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