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1 From the School of Optometry, University of Waterloo, Ontario, Canada; 2 School of Life and Health Sciences, Aston University, Birmingham, United Kingdom; 3 University Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom; 4 Department of Optometry and Vision Sciences, Cardiff University, Wales, United Kingdom; and 5 Department of Ophthalmology, Faculty of Medicine, University of Toronto, Ontario, Canada.
| Abstract |
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METHODS. The sample comprised 33 glaucoma suspects and 17 patients with early-to-moderate stable POAG who underwent W-W perimetry and SWAP at each of six visits over a mean period of 12.75 months (SD, 2.29). The LF(Ho), LF(He), and error components of the long-term fluctuation were determined between the third and seventh visual field examinations. The intervening visual field examinations and the optic nerve head parameters, derived both by stereo observation and by the Heidelberg Retinal Tomograph, were used to confirm stability over the follow-up period.
RESULTS. The LF(Ho) and LF(He) components were larger in the POAG patients than in the glaucoma suspects for both W-W perimetry and SWAP; the magnitude was independent of the depth of defect and of the short-term fluctuation. All three components of long-term fluctuation were greater for SWAP than for W-W perimetry, both in the glaucoma suspects and in the POAG patients.
CONCLUSIONS. SWAP exhibits greater long-term fluctuation than white-on-white perimetry. The usefulness of SWAP will be limited if the extent of this variability is not overcome in future statistical procedures developed to detect progressive visual field loss.
| Introduction |
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The development of short-wavelength automated perimetry (SWAP) has attracted considerable interest. In the Humphrey Field Analyzer (HFA; Humphrey Systems Inc, Dublin, CA), a 440-nm narrow band blue Goldmann size V stimulus is presented against a 100 cdm-2 broadband (500700 nm) yellow background.1 The blue stimulus is used to preferentially stimulate the short-wavelengthsensitive (SWS) pathway and the high luminance yellow broadband background to simultaneously suppress rod activity and to adapt the medium- and long-wavelengthsensitive pathways. SWAP has been shown to detect the presence of glaucomatous visual field loss and to identify progressive loss before conventional white-on-white (W-W) perimetry.2 3 4 5 6 7 Nevertheless, SWAP exhibits a greater within-examination variability (SF) in normals8 9 10 and in glaucoma10 than W-W perimetry. SWAP also exhibits a greater between-subject variability in normals compared with W-W perimetry; with the between-subject variability increasing with eccentricity.9 11
The variation in the threshold estimate between examinations is known as the long-term fluctuation (LF). The LF is the variance additional to that of the SF and is present between two or more examinations. Classically, the LF is divided into two components: the homogeneous component, LF(Ho), and the heterogeneous component, LF(He).12 13 The LF(Ho) represents the proportion of the total LF that affects all the specified stimulus locations equally. Conversely, the LF(He) represents the proportion of the total LF that varies between the specified locations.
The magnitude of the between-examination variability, evaluated for a single stimulus location, is greater for SWAP than W-W perimetry in normals8 and in glaucoma patients14 and increases with eccentricity.14 However, the magnitude of the LF(Ho) and LF(He) in POAG patients and in patients who are suspect for glaucoma is unknown. The aim of the study was twofold: to determine the magnitude of the homogenous and heterogeneous components of LF in glaucoma suspects and in stable primary open angle glaucoma patients undergoing SWAP, and to compare the magnitude of the SWAP LF components with those elicited by standard W-W perimetry.
| METHODS |
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To be classified as a glaucoma suspect in the given eye, one or more of
the following inclusion criteria was met in addition to a normal W-W
field: POAG in the fellow eye; a presenting IOP of
26 mm Hg and a
vertical cup to disc (CD) ratio
0.6; a presenting IOP of
26
mm Hg and a positive family history for glaucoma; a presenting IOP of
21 mm Hg and a between-eye asymmetry in CD ratio
0.2; a
presenting IOP of
21 mm Hg and a CD ratio of
0.8; a presenting IOP
of
21 mm Hg and the presence of any focal disc abnormality, notching
or disc hemorrhage; or a presenting IOP of
30 mm Hg. A normal visual
field (HFA Program 30-2; Full Threshold algorithm) was defined by Total
and Pattern Deviation probability analysis at the baseline visual
fields. IOP was determined by Goldmann applanation tonometry.
For the POAG patients, a repeatable, glaucomatous W-W visual field defect (HFA Program 30-2; Full Threshold algorithm) at baseline was required to coexist with an abnormal optic disc, also consistent with a diagnosis of glaucoma (including increase in cup size, increase in cup disc ratio, disc asymmetry, changes in the lamina cribrosa, loss of neuroretinal rim, pallor, evidence of peripapillary atrophy, vessel changes, or disc margin hemorrhage),15 and a presenting IOP of >21 mm Hg. In patients where both eyes fulfilled the inclusion criteria, one eye was arbitrarily selected.
The exclusion criteria for both groups comprised a visual acuity in the
designated eye of worse than 6/9; clinically significant cataract
determined by slit-lamp examination with dilated pupils; a history of
congenital color vision defect or optic nerve disorder not attributable
to glaucoma; previous intraocular surgery, ocular trauma or
inflammation; gonioscopic evidence of anterior chamber abnormality or
angle closure; a history of CNS disorder; systemic medication known to
affect the visual field; and ametropia of
6.00 DS and
2.50
DC.
The designated eye of each of the glaucoma suspects and each of the POAG patients was prospectively monitored for six visits over the follow-up period. Optic nerve head stability was assessed using two separate criteria. At each visit, the optic nerve head in the designated eye was evaluated by stereo observation using slit-lamp biomicroscopy and by scanning laser tomography (Heidelberg Retinal Tomograph [HRT]; Heidelberg Engineering, Heidelberg, Germany). The stereo examination at each visit evaluated features of the optic nerve head (as described above) for progressive damage.15 Twelve stereometric parameters were obtained from seven image series at each visit to describe the optic nerve head topography (disc area, mean height of contour, height variation in contour, cup volume, rim volume, volume above and below surface, mean depth inside contour, and mean retinal nerve fiber layer thickness). Stability was defined as no significant change over the time to follow-up in the parameters using repeated measures analysis of variance (P > 0.01). Although there are currently no standard criteria for defining change using the HRT, the approach adopted was intended to ensure a conservative definition of stability. The optic nerve head had to meet both criteria to be classified as stable.
The visual field was determined for W-W perimetry using the Full
Threshold algorithm of the Humphrey Field Analyzer 640, with Program
30-2 (stimulus size III) and for SWAP using the Full Threshold
algorithm with Program 24-2 and the default stimulus parameters of a
blue size V stimulus and the 100 cdm-2 broadband
yellow background. Program 24-2 was used for SWAP to provide an
examination of duration similar to W-W perimetry.11
The
order of the type of perimetry (i.e., W-W or SWAP) was randomly
assigned between patients but remained constant for each patient at
each examination throughout the period of follow-up. Each visual field
was deemed to be reliable in terms of the responses to the catch trials
(
33% fixation losses,
33% false-positive responses, and
33%
false-negative responses), and all visual field examinations were
obtained by a single examiner (SLH).
All patients had experienced W-W perimetry before commencing the study, and the cohort was deliberately biased toward patients with early visual field loss. The first visual field examination was repeated within 2 weeks, and both examinations were designated as the baseline. These fields were excluded from further analysis. The purpose of the baseline examinations was to ensure that each patient was familiar with the measurement procedure and allowed the examiner to subjectively assess a patients reliability. The mean interval between the third and the seventh examinations for the sample as a whole was 11.88 months (SD, 1.32; median, 11.74 months; range, 9.8415.24 months).
The W-W and SWAP visual fields were reviewed by one of the authors
(JMW), experienced in visual field interpretation, who was masked to
the outcome of any other clinical findings. The W-W visual fields were
assessed by inspection of the Overview, Change Analysis and Glaucoma
Change Probability Analysis print-outs of the HFA STATPAC statistical
software. The SWAP visual fields were assessed by evaluation of the
Overview print-out, alone, as the Change Analysis and the Glaucoma
Change Probability Analysis print-outs are not commercially available.
Linear regression analyses were also carried out for the W-W and SWAP
summary visual field indices over time to follow-up for each of the
glaucoma suspects and for each of the POAG patients. The regression
analyses determined whether a significant change (P <
0.05) was evident in the magnitude of the Pattern Standard Deviation
(PSD) and Corrected Pattern Standard Deviation (CPSD) indices over the
time of follow-up. The PSD and CPSD indices were chosen as the most
likely to indicate change consistent with glaucoma.16
A
second linear regression analysis, only applicable to the POAG
patients, determined if there was any significant difference in depth
and area of an existing cluster of abnormal locations over the duration
of follow-up. A cluster was defined as a nasal step or as two or more
adjacent nonedge locations in the Pattern Deviation plot exhibiting
abnormality at P
0.01 significance. The decibel
depth of each pattern deviation cluster was determined from the STATPAC
print-out.
Patients were excluded from the sample if one or more of the following was present: failure to complete the examinations in the follow-up period; change in topical therapy or surgical intervention during the follow-up period; change in optic nerve head topography and/or progressive visual field loss for either or both W-W perimetry and SWAP; or a learning effect lasting beyond the baseline fields for either, or both, W-W perimetry and SWAP. Forty-five individuals were excluded from the original cohort (Table 1) , and the sample comprised 33 glaucoma suspects and 17 POAG patients. There was no statistically significant difference in the duration of follow-up between the two groups of patients (P = 0.732).
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The LF(Ho) and LF(He) components, expressed in decibels, were
calculated between the third and the seventh visual field examinations
(i.e., using data from the 3rd and 7th examinations only) for W-W and
for SWAP. The determination of the LF(Ho) and LF(He) components has
been previously described.13
Briefly, LF(Ho) and LF(He)
were derived from a two-factor ANOVA with replications,18
based on the double determinations of sensitivity at the 10 standard
stimulus locations incorporated in Program 30-2 and in Program 24-2 of
the HFA, using the formula:
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The respective values of LF(Ho) and LF(He) were determined by
partitioning the variance derived from the ANOVA that is attributable
to each component of LF. The mean square estimates (MSE) for
Vk, attributable to LF(Ho), and
LVjk, attributable to LF(He), were
then reduced to their constituent variances to remove the accompanying
error variance Ejkl by the
hypothesis19
:
![]() | (1) |
![]() | (2) |
![]() | (3) |
k or
jk) was
obtained, the variance(s) that exhibited a negative component of LF was
combined with that of the error term, E. The error term was
then recalculated, the new value more accurately reflecting the
magnitude of both the error term and the previously negative LF
component.13
This value was then used in all subsequent
analyses. The decibel unit of differential light sensitivity is a relative measure referenced to the maximum stimulus luminance. Any decibel value obtained using W-W perimetry is not directly comparable with that using SWAP because of the differing maximum stimulus luminance used by each procedure. Therefore, to enable a more direct comparison to be made between the components of LF derived by each perimetric technique, the log unit equivalents of the LF(Ho) and LF(He) were calculated. This was achieved by converting the decibel value to log units (i.e., relative to the maximum stimulus luminance), and this value was then expressed as a reciprocal. Thus, the reciprocal log unit would approach zero (and the apostilb value approach the maximum stimulus luminance) as the decibel value of the long-term fluctuation approached zero.
| Results |
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The group mean SF of the glaucoma suspects at the third examination was 1.27 dB (SD, 0.44) for the W-W procedure and 1.80 dB (SD, 0.58) for SWAP. Similarly, the group mean SF of the stable glaucoma patients was 2.03 dB (SD, 0.69) for W-W and 1.90 dB (SD, 0.49) for SWAP. Linear regression analysis showed the SF at the third examination to have a positive relationship with the error component of the long-term fluctuation in the glaucoma suspects for W-W perimetry (coefficient of determination, R2 = 0.792; regression coefficient, P < 0.001) and for SWAP (R2 = 0.781, P < 0.001). The corresponding data for the POAG patients did not show such a relationship (W-W: R2 = 0.051; P = 0.384; SWAP: R2 = 0.178; P = 0.092). The SF was unrelated to either the LF(Ho) or the LF(He) in either W-W perimetry or SWAP in either the glaucoma suspect or POAG samples (R2 < 0.50; P > 0.05).
Similarly, the magnitude of the MD and that of the CPSD at the third examination were unrelated to either the LF(Ho) or the LF(He) for W-W perimetry or for SWAP. The R2 values associated with the regression coefficients that failed to reach the criteria for significance ranged from a minimum of 0.001 to a maximum of 0.265.
The relationship between the W-W and SWAP LF(Ho), expressed in reciprocal log units is illustrated in Figure 2 (top). The corresponding data for the LF(He) and the error component are shown in Figure 2 (middle) and (bottom), respectivley. The magnitude of the LF(Ho), LF(He), and error components, specified in reciprocal log units, was significantly larger for SWAP than for W-W perimetry (LF(Ho), P = 0.005; LF(He), P = 0.004; E, P < 0.001).
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| Discussion |
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The difference in the magnitude of the LF reported in this study for SWAP and that reported for normal subjects8 arises in part from the mathematical definition of LF. The LF described by Kwon et al.8 was defined as the statistical variance exhibited by the threshold value at a given single stimulus location over a series of examinations. This latter method is of limited value in separating variability from progressive loss in the clinical environment, because it requires several examinations before the value can be determined. The LF used in the present study can be used between any pair of examinations from the outset and provides an index of reliability between examinations,13 in a similar fashion to the use of the short-term fluctuation as an indicator of reliability within an examination.
Alternative statistical techniques for approximating interval estimates have been described,23 24 and these methods may minimize the instances in which a negative estimate of an LF component is obtained. However, the likely effect of the method used in this study is an overestimation of the magnitude of the components of the LF that, in the first instance, exhibit a negative variance. The method described in this study therefore provides a conservative standard for the definition of excessive long-term fluctuation. For the suspects, correction of a negative variance corresponding to the LF(Ho) was made in nine patients for W-W perimetry and in eight patients for SWAP (two of whom were common to both types of perimetry). A correction for a negative variance corresponding to the LF(He) was made in four patients for W-W perimetry and six patients for SWAP (two of whom were common to both types of perimetry). The equivalent figures for the glaucoma patients were four patients each for W-W and SWAP LF(Ho) and three patients each for W-W and SWAP LF(He).
Previous studies have shown that ocular media absorption adversely influences the SWAP visual field more than the white-on-white field.11 25 26 Although the extent of the ocular media absorption can be quantified,26 27 28 the procedures require specialized techniques,26 28 are time consuming and cannot realistically be undertaken in the routine clinical follow-up of glaucoma. No correction was made for lenticular absorption in this study. However, the exclusion of patients with clinically significant cataract will have lessened the magnitude of the reduction in sensitivity due to age-related lenticular changes. Using the commercially available SWAP stimulus parameters with the Full Threshold algorithm, the difference in the Mean Sensitivity, with and without correction, for ocular media absorption is approximately 0.5 dB per decade.11 By extrapolation, the magnitude of the loss in Mean Sensitivity due to uncorrected ocular media absorption is approximately 0.05 dB over the 12.7 months period described in this study.
It has been suggested that the increased magnitude in the between-individual variability of the threshold estimate in SWAP will increase with age due to the increased effects of absorption and loss of neuronal tissue.11 The greater variability of SWAP compared with W-W perimetry will undoubtedly be exacerbated by the presence of glaucoma. The use of SWAP will therefore necessitate more stringent statistical procedures to account for the increased within- and between-examination variability and to separate age-related changes from that due to progressive field loss.
The positive relationship between the SF and the error component of the long-term fluctuation in the glaucoma suspects for both W-W perimetry and SWAP is an expected finding since the error component is analogous to the mean short-term fluctuation across the two examinations.13 The stable glaucoma patients did not exhibit such a relationship, probably as a result of the greater between-individual variability in the SF, particularly for W-W perimetry. Perhaps more surprising is the lack of relationship of the LF(Ho) or the LF(He) with the MD or CPSD for both W-W perimetry and SWAP. The physiological variation in the sensitivity at a single stimulus location between two examinations using W-W perimetry increases as the threshold increases,22 29 and the long-term fluctuation is correlated with the mean visual field loss.30 31 It might be expected, therefore, that the magnitudes of the LF(Ho), LF(He), and error component of the LF would exhibit a concomitant increase with a decrease in the MD and an increase in the CPSD, particularly in the moderate loss range. No such finding was apparent in this study. This may be explained by the limited number of patients in the moderate-to-severe range of MD and CPSD values. Alternatively, it might be a consequence of the global nature of the visual field indices, which are based on the threshold values derived at all stimulus locations, and the "sampled" nature of the LF components, which are based on the 10 locations at which double determinations of threshold are undertaken. However, the use of the 10 doubly determined locations to derive the visual field indices does not elicit a materially different relationship with the components of LF for W-W perimetry.13 It might also be argued that the LF components derived from these 10 locations do not adequately reflect the physiological variation of the visual field as a whole. However, these 10 stimulus locations are the only common stimulus locations in the HFA at which double determinations of sensitivity are undertaken in successive examinations. The SF is determined from the same 10 stimulus locations and is an accepted measure of within-examination variability despite similar limitations.
The magnitudes of the group means of all three components of long-term fluctuation were higher for the stable glaucoma patients than for the glaucoma suspects for both W-W and SWAP. The difference in the group means between these two samples cannot be attributed to a difference in age and occurred irrespective of the group mean SF of the second field being slightly lower in the glaucoma group for SWAP than for W-W perimetry.
The log unit magnitudes of the LF(Ho), LF(He), and error components were greater for SWAP than for W-W perimetry. The increased short-term8 9 10 and long-term fluctuation8 may result from a decreased sampling of the neuronal constituents with SWAP8 or, more likely, from the flatter frequency-of-seeing curves obtained with SWAP.32 The higher values may have been influenced by the longer duration of the learning effect with SWAP33 and/or a carryover fatigue effect between examinations within each visit. Every effort was made to minimize the learning effect in SWAP by ensuring that the patients were experienced in SWAP perimetry and by excluding patients who exhibited systematic improvement in overall sensitivity over time to follow-up.
It is evident that the increased variability within- and between-examinations exhibited by SWAP compared with W-W perimetry limits the current utility of SWAP in the clinical situation. Such variability must be reduced if SWAP is to become a viable technique.
| Acknowledgements |
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| Footnotes |
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Submitted for publication August 9, 2000; revised March 19, 2001; accepted April 13, 2001.
Commercial relationships policy: N (NH, SLH); R (JMW); F (JGF).
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be marked
"advertisement" in accordance with 18 U.S.C.
1734
solely to indicate this fact.
Corresponding author: Natalie Hutchings, School of Optometry, University of Waterloo, Waterloo, Ontario N2L 3G1, Canada. nhutchin{at}sciborg.uwaterloo.ca
| References |
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