Abstract
purpose. To compare short-wavelength automated perimetry, frequency-doubling
technology perimetry, and motion-automated perimetry, each of which
assesses different aspects of visual function, in eyes with
glaucomatous optic neuropathy and ocular hypertension.
methods. One hundred thirty-six eyes from 136 subjects were evaluated with all
three tests as well as with standard automated perimetry. Fields were
not used in the classification of study groups to prevent bias, because
the major purpose of the study was to evaluate each field type relative
to the others. Seventy-one of the 136 eyes had glaucomatous optic
neuropathy, 37 had ocular hypertension, and 28 served as age-matched
normal control eyes. Glaucomatous optic neuropathy was defined by
assessment of stereophotographs. Criteria were asymmetrical cupping,
the presence of rim thinning, notching, excavation, or nerve fiber
layer defect. Ocular hypertensive eyes had intraocular pressure of 23
mm Hg or more on at least two occasions and normal-appearing optic disc
stereophotographs. Criteria for abnormality on each visual field test
were selected to approximate a specificity of 90% in the normal eyes.
Thresholds for each of the four tests were compared, to determine the
percentage that were abnormal within each patient group and to assess
the agreement among test results for abnormality, location, and extent
of visual field deficit.
results. Each test identified a subset of the eyes with glaucomatous optic
neuropathy as abnormal: 46% with standard perimetry, 61% with
short-wavelength automated perimetry, 70% with frequency-doubling
perimetry, and 52% with motion-automated perimetry. In the ocular
hypertensive eyes, standard perimetry was abnormal in 5%, short
wavelength in 22%, frequency doubling in 46%, and motion in 30%.
Fifty-four percent (38/71) of eyes with glaucomatous optic neuropathy
were normal on standard fields. However, 90% were identified by at
least one of the specific visual function tests. Combining tests
improved sensitivity with slight reductions in specificity. The
agreement in at least one quadrant, when a defect was present with more
than one test, was very high at 92% to 97%. More extensive deficits
were shown by frequency-doubling perimetry followed by short-wavelength
automated perimetry, then motion-automated perimetry, and last,
standard perimetry. However, there were significant individual
differences in which test of any given pairing was more extensively
affected. Only 30% (11/37) of the ocular hypertensive eyes showed no
deficits at all compared with 71% (20/28) of the control eyes
(P < 0.001).
conclusions. For detection of functional loss standard visual field testing is not
optimum; a combination of two or more tests may improve detection of
functional loss in these eyes; in an individual, the same retinal
location is damaged, regardless of visual function under test;
glaucomatous optic neuropathy identified on stereophotographs may
precede currently measurable function loss in some eyes; conversely,
function loss with specific tests may precede detection of abnormality
by stereophotograph review; and short-wavelength automated perimetry,
frequency-doubling perimetry, and motion-automated perimetry continue
to show promise as early indicators of function loss in
glaucoma.
During the past several years, psychophysical tests of visual
function have been used not only as diagnostic methods for measuring a
glaucoma patient’s current visual performance, but also as tools for
understanding the underlying changes in retinal ganglion cell function
as a result of the disease. We know that glaucoma damages retinal
ganglion cells and that several visual functions are affected early in
the disease process.
1
Some histologic evidence has suggested that damage to larger diameter
retinal ganglion cell axons occurs first in the course of
glaucoma,
2 but these results have been
questioned.
3 Many have used these histologic results to
assume that “larger axons” means magnocellular axons are most at
risk. This interpretation has also been questioned.
4 Larger diameter optic nerve fibers are not exclusively magnocellular
fibers. The size of the fibers is dependent on eccentricity as well as
ganglion cell type, so that some eccentric parvocellular retinal
ganglion cell axons may be larger than more central magnocellular
retinal ganglion cell axons. The axons from the small bistratified
ganglion cells, which process blue–yellow color vision, are also
larger than those from parvocellular cells.
5
We know that testing vision with standard automated perimetry (SAP) is
not selective for a particular ganglion cell type, and that newer tests
that attempt to isolate specific subpopulation of ganglion cells by
evaluating specific visual functions have shown considerable diagnostic
power. For example, short-wavelength automated perimetry (SWAP)
necessitates detection by the short-wavelength cones and is then
processed through the blue–yellow ganglion cells. Recently, it has
been reported that the blue–yellow ganglion cells are separate from
the parvocellular ganglion cells.
6 7 It is now thought
that these cells project their axons to the interlaminar, koniocellular
layers of the lateral geniculate nucleus (LGN) rather than to the
primary parvocellular layers.
8 To our knowledge, no study
has assessed cell loss at the LGN within the interlaminar layers, but
most likely these layers will be included in future studies. Results
with SWAP consistently show visual field defects before their
appearance on standard visual fields, suggesting that it is not only
the magnocellular axons that are affected in the earliest
stages.
9 10 11
Other visual function tests have been developed in an attempt to
evaluate specific retinal ganglion cell populations. We think
frequency-doubling technology perimetry (FDT)
12 13 and
various forms of motion perimetry
14 15 16 17 18 are most likely to
isolate the magnocellular ganglion cells. High-pass resolution
perimetry most likely isolates primarily the parvocellular ganglion
cells.
19 20 However, we want to point out that the degree
of isolation of a particular ganglion cell type with some of these
tests is unknown. The question is, when damage to a ganglion cell
subtype is present, how severe must the field loss be before another
ganglion cell type detects the stimulus? Several studies of SWAP have
shown that in normal eyes there is a 15-dB cushion before another
system (most likely, the middle wavelength sensitive cells and their
connections) can detect the target.
21 Most of this
isolation is maintained even in areas of moderate SWAP visual field
loss.
22 Although motion automated perimetry (MAP) and FDT
were structured to test magnocellular ganglion cells, their designs
were based on what is known about normal visual processing and from
electrophysiological and lesion studies in cat and
monkey.
12 23 24 The amount of isolation is not yet known
for either FDT or MAP. Results should therefore be interpreted with
this in mind.
These psychophysical tests, which are targeted at specific visual
functions, have been shown to be superior to standard visual fields for
early detection of vision loss associated with
glaucoma.
1 9 10 15 17 18 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 Studies comparing results
of each of these tests in the same patient should help address three
alternate theories of ganglion cell damage due to glaucoma:
-
Early damage is selective for the larger optic nerve fibers of the
magnocellular system.
2 -
All optic nerve fibers are damaged. Tests that favor detection of a
stimulus by one visual pathway or processing subsystem reduce the
ability of the visual system to use other pathways to compensate for
the damaged ganglion cell type under test.
1 3 -
Not all eyes with primary open-angle glaucoma or those at risk for the
disease are affected in the same way. Blue–yellow ganglion cell
function may be reduced first in one individual, whereas magnocellular
ganglion cell function may be affected first in
another.
40 41
In this study, we compared the results of SWAP, FDT, and MAP in
the same individuals. Visual field data were not used to classify
patients into study groups to prevent bias, because the main purpose of
this analysis was to evaluate the relationships among the different
types of field tests.
One hundred thirty-six eyes from 136 subjects were evaluated on
all three tests, as well as on SAP. Fields were not used in
classification of study groups. Seventy-one of the 136 eyes had
glaucomatous optic neuropathy (GON), 37 eyes had ocular hypertension
(OHT), and 28 served as age-matched normal control eyes. Mean age ± SD were 62.46 ± 11.86 years (GON), 60.29 ± 11.26 years
(OHT), and 61.80 ± 9.31 years (control).
Each subject underwent a complete ophthalmologic examination that
included review of relevant medical history, best corrected visual
acuity, slit lamp biomicroscopy (including gonioscopy), applanation
tonometry, dilated funduscopy, stereoscopic ophthalmoscopy of the optic
disc with a 78-D lens, and stereoscopic fundus photography.
This study was approved by the Human Subjects Committee of the
University of California, San Diego, and adhered to the Declaration of
Helsinki, with informed written consent obtained from the participants.
Inclusion Criteria.
Simultaneous stereoscopic photographs were obtained for all subjects
and were of adequate quality for the subjects to be included. All
subjects had open angles, best corrected acuity of 20/40 or better,
spherical refraction within ±5.0 D, and cylinder correction within±
3.0 D. All subjects had reliable visual fields results on all four
tests. For SAP, SWAP, and FDT this was defined as 25% or fewer
false-positive results, false-negative results, and fixation losses.
For MAP, which is a forced-choice test, trials with fixation losses
were aborted, and if more than three of these occurred, the test was
judged unreliable and not used. One eye was selected randomly from each
subject, except in participants in which only one eye met study
criteria, and that eye was included. Candidates with a family history
of glaucoma were included.
Exclusion Criteria.
Normal and ocular hypertensive subjects were excluded if they had a
history of intraocular surgery (except for uncomplicated cataract
surgery). We also excluded all subjects with nonglaucomatous secondary
causes of elevated intraocular pressure (IOP; e.g., iridocyclitis,
trauma), other intraocular eye disease, other diseases affecting visual
field (e.g., pituitary lesions, demyelinating diseases, HIV positivity
or AIDS, or diabetes) or problems affecting color vision other than
glaucoma.
Stereoscopic Optic Disc Photographs.
Subjective evaluation of structural damage to the optic nerve was based
on clinical assessment of stereoscopic optic disc photographs. Two
experienced graders, each of whom was certified after grading
standardized photographs satisfactorily, evaluated all photographs.
Each grader was masked to the subject’s identity, study group
classification, results from the other grader, and other test results.
In cases of disagreement, the two graders re-evaluated to reach
consensus. The diagnosis of GON was based on cup-to-disc asymmetry
between two eyes of 0.2 or more, rim-thinning, hemorrhage, notching,
excavation, or nerve fiber layer defect.
Normal Control Eyes.
Ocular Hypertensives.
Glaucomatous Optic Neuropathy.
Standard Achromatic Automated Perimetry.
Short-Wavelength Automated Perimetry.
Frequency-Doubling Technology Perimetry.
Motion Automated Perimetry.
Abnormality for all tests was determined by comparison with the
manufacturer’s internal normative database for SAP and FDT and for our
laboratory’s normative databases for SWAP (n = 214) and MAP
(n = 99). Although this is consistent with the way these
tests will be used in clinical practice, there may be some bias in this
choice. Ideally, there would be a large normative database of the same
eyes for all tests, but because each test has been developed at a
different time and by different manufacturers or laboratories, there is
no such database with a sufficient number of eyes to accurately assess
probability limits. The criteria for an abnormal field on SWAP, FDT,
and MAP were determined for each to approximate the same specificity
for this study’s normal control subjects (n = 28), none of
whom were part of any of the normative databases. This was intended to
equate the test results somewhat for diagnosing abnormality, because
each test uses different stimuli and test locations and assesses
different visual functions. A variety of different criteria were tried,
and those that will be described gave the closest match for
specificity.
Visual field results were evaluated to determine whether the defective
areas for the tests fell within the same quadrant of the visual field
for extent of these defects, based on number of quadrants affected and
for the percentage of abnormal eyes identified in the two patient
groups, OHT and GON.
Standard and SWAP visual fields were classified as abnormal if the
result of the GHT was outside normal limits, the CPSD was triggered at
5% probability or worse, or the MD was triggered at 5% probability or
worse, with no generalized depression. Quadrants were identified as
abnormal by a cluster of three or more points at 5% probability or
worse on the pattern-deviation plot. These criteria produced a
specificity for SWAP of 86%.
A problem with this study is that because of the longitudinal study
design, the 28 normal controls were all enrolled after it was
determined that they had normal SAP fields. To address this as best we
could, we used the criteria for a normal SAP developed for the National
Eye Institute–sponsored Ocular Hypertension Treatment Study
(OHTS).
56 These criteria require a GHT result within the
normal limits or a CPSD within the 95% normal limits. It was
determined for OHTS that these criteria provided a specificity of
approximately 92% for normal eyes (personal communication, Chris
Johnson, August 1999).
FDT fields were abnormal when a cluster of two adjacent points reached
5% or worse probability limits. This yielded a specificity for FDT of
86%. A MAP field was considered abnormal if a cluster of three
adjacent points 2 SD from normal or two adjacent points 3 SD from
normal were found, resulting in a specificity for MAP of 89%.
The relative extent of defect between paired test results (number
of quadrants) is given in
Table 5 . The total number in each case should equal the numbers given in the
previous paragraph for eyes shown to be abnormal on both tests. The
extent of defect showed individual differences and was not always
greatest on the same test in a given pair. However, overall, defects
were greatest on FDT, followed by SWAP, followed by MAP.
In all 71 GON fields, regardless of overlap, the mean number of
quadrants (from 0 to 4) that were abnormal for each test were 0.59 ± 1.10 (SAP), 1.18 ± 1.38 (SWAP), 1.67 ± 1.62 (FDT), and
0.79 ± 1.34 (MAP). In the 37 OHT eyes, abnormal quadrants were
0.02 ± 0.16 (SAP), 0.47 ± 1.10 (SWAP), 1.00 ± 1.27
(FDT), and 0.95 ± 1.61 (MAP). Normal eyes had an average of 0.25
abnormal quadrants or less for SWAP, FDT, and MAP.