The ZEST procedure,
11 a variant of
QUEST,
13 is based on a maximum-likelihood threshold
determination. For each stimulus location, an initial probability
density function (pdf) is defined for all possible thresholds, which
states for each possible threshold (0–20 dB for FDT perimetry) the
probability that any patient will have a threshold at that location.
The first stimulus is presented with a contrast equal to the mean of
this pdf. The subject’s response to that stimulus is used to modify
the pdf for the next presentation.
The top panel in
Figure 2a shows an initial pdf that assumes the most likely threshold for the
patient is 14 dB (probability 0.13), whereas the patient is very
unlikely to have a threshold of 2, 3, 4, 19, or 20 dB
(
P = 0.001). The mean of this pdf is 12 dB, which is
presented to the subject. If the subject responds no, then the pdf is
modified to give more probability to lower decibel levels (
Fig. 2a ,
bottom). The mean of this new pdf determines the next stimulus
presentation at this location (9 dB in this case). If the subject
responds yes, then the pdf is modified to give a pdf as shown in the
bottom panel of
Figure 2b , with more weight on higher decibel levels. A
stimulus of 15 dB, the mean of this new pdf, is presented next.
The rule for generating the new pdf is to multiply the old pdf by a
likelihood function, which represents the likelihood that a subject
will see a stimulus. When the stimulus is at the subject’s true
threshold, the maximum-likelihood function reflects what is called the
psychometric function or frequency-of-seeing curve. The middle panel of
Figure 2a shows one of the 12 likelihood functions used in this study.
It assumes that the chance of seeing a stimulus at threshold is 50%
(dotted lines) and that seeing any stimulus with much lower decibel
levels is a 99% certainty, whereas seeing much higher decibel levels
is only a 1% certainty. A stimulus 1 dB either side of threshold has a
75% and 25% chance of being seen. To derive a new pdf when the
subject responds no, multiply the old pdf by the likelihood function,
which weights lower decibel levels by 99% and higher decibel levels by
1%. When the subject responds yes, the maximum-likelihood function
must be inverted before multiplying, so that high decibel levels are
weighted at 99%, whereas the chance of the subject’s having a
threshold at lower decibel levels is weighted only 1%. This procedure
has been followed in
Figures 2a and 2b 2c 2d 2e 2f 2g enerate the pdf in the
bottom panel from the pdf in the top panel, with the addition of a
normalizing step so that the probabilities in the pdf sum to 1.
Once a new pdf is derived, the new mean is calculated, and a stimulus
contrast equal to that mean is presented. The process is then repeated,
either a fixed number of times, or until the SD of the pdf falls below
a predetermined value. The subject’s threshold is the mean of the
final pdf.
The defining features of a ZEST procedure are the initial pdf, the
likelihood function, and the termination rule. As Vingrys and
Pianta
10 have noted, the initial pdf can be derived from
demographic studies and can be biased by an examiner’s intuition about
the subject’s likely thresholds. The likelihood function should
reflect the variability inherent in the detection task as well as
subjective false error rates. Finally, the termination rule should be
chosen with realistic clinical outcomes in mind. One approach is to
finish the procedure when the SD (ς) of the pdf declines below a
fixed value, which assures a level of confidence about the determined
threshold. For example, if ς is chosen to be 1 dB, then there is a
95% chance that the real threshold lies within a ±2-dB range of the
measured threshold. One disadvantage of this approach is that
unreliable observers may require many presentations. An alternative is
to terminate the procedure after a fixed number of presentations, and
the 95% confidence interval of the final estimate can be determined
from the final pdf.
To determine the effect of the starting pdf on FDT perimetry
thresholds, four classes of pdf were tested in the simulation: uniform
distributions (
pdfu); pdfs equal to the normalized histogram
of sensitivity from the normal eyes in
Table 1 (
pdfn); pdfs
equal to the normalized histogram of sensitivity from the eyes with
glaucomatous visual field loss in
Table 1 (
pdfg); and pdfs
formed by combining the normal and glaucomatous pdfs (
pdfc).
The combined pdfs added the bottom 5% of
pdfg to
pdfn. 10 Before the addition, the bottom 5% of
pdfg was reduced by a weighting factor so that it did not
dominate the normal portion of the pdf. Twelve different weighting
factors were evaluated. The results presented herein are for a
weighting factor of 0.6. Each class of pdf contained a single pdf for
each of the 17 visual field locations. There was little difference in
the form of the 17 pdfs in each class; however, the means of the
peripheral pdfs were generally lower than those for the central five
locations. The resultant
pdfc pdfs were trimodal (
Fig. 2 ,
top panels), unlike the bimodal pdf of Vingrys and
Pianta,
10 which was derived from advanced glaucomatous
deficits.
The following ZEST termination rules were evaluated: stopping after
three or four presentations and stopping when the pdf achieved a SD of
0.5, 1, or 2 dB. A single-likelihood function was used for all ZEST
procedures (
Fig. 2 , middle panels). The ZEST procedures were performed
on discrete functions, one for 0 dB, one for 1 dB, and so on.
Similarly, the likelihood function was defined for whole-number
thresholds in the range 0 to 20 dB. The mean of the pdf at each stage
was rounded to the nearest decibel. This rounded mean was used to
determine the alignment point for the likelihood function. Rounding
introduces a maximal error of 0.5 dB when producing each new pdf. Given
the 90% confidence interval for retest variability for normal
observers for FDT perimetry is approximately 4 dB,
7 this
rounding is unlikely to be clinically significant.