SITA-STANDARD AND SHORT-WAVELENGTH AUTOMATED PERIMETRY IN THE EARLY DIAGNOSIS OF GLAUCOMA

G. MILANO1 and C. KLERSY2

1University Eye Clinic and 2Biometry & Clinical Epidemiology, Research Department, I.R.C.C.S., Policlinico San Matteo, Pavia, Italy

Abstract

Purpose: To compare the Swedish Interactive Threshold Algorithm (SITA-standard) and short-wavelength automated perimetry (SWAP) for detecting early glaucomatous functional abnormalities in a population at risk for glaucoma. Methods: At the Glaucoma Center of the University Eye Clinic, Pavia, the authors studied 50 patients (99 eyes) with intraocular pressure (IOP) normalized (IOP < 21 mmHg) by topical therapy. The patients were periodically submitted to automated perimetry with 24-2 pattern and SITAstandard and SWAP strategies of the Humphrey Field Analyzer 750. Each visual field was classified as normal or pathological on the basis of clinical criteria taken from the 1998 guidelines of the European Glaucoma Society. The agreement between the two algorithms in visual field testing was evaluated by kappa statistics and then McNemar’s test. Results: Of the 99 eyes studied, 37 showed a pathological SITA test and 23 a pathological SWAP test. In 21 cases, the visual field was abnormal with SITA only, and in seven cases with SWAP only. In 16 cases, early defects were identified by both SITA and SWAP. The agreement between the two strategies was statistically poor (κ = 0.35). The average test duration was 11.57 ± 3.02 minutes for SWAP and 5.16 ± 1.02 minutes for SITA-standard, the difference between the two kinds of test being statistically significant (p < 0.001). Conclusions: Automated perimetry seems to be able to document early glaucomatous abnormalities in many cases. Compared to SWAP, SITA takes less time, is less tiring for the patient, and achieves the same, if not better, quality and accuracy.

Introduction

Automated perimetry can be considered the ‘gold standard’ in the diagnosis of glaucomatous optic neuropathy. Nevertheless, it has been demonstrated that early perimetric defects are detected when a substantial and irreversible loss of ganglion cells and nerve fibers has already taken place.1-4 A clinical test capable of detecting glaucomatous defects at a very early stage would permit the prompt initiation of therapy, in order to avoid progression of the disease. In addition to the traditional full threshold strategies with white-on-white stimulation, Humphrey automated perimetry offers the possibility of visual evaluation using recently proposed threshold strategies, such as short-wavelength automated perimetry (SWAP), considered to be sensitive in the early

Address for correspondence: Giovanni Milano, MD, Clinica Oculistica dell’Università, IRCCS Policlinico San Matteo, Piazza C. Golgi 2, I-27100 Pavia, Italy

Perimetry Update 2002/2003, pp. 227–232

Proceedings of the XVth International Perimetric Society Meeting, Stratford-upon-Avon, England, June 26–29, 2002

edited by David B. Henson and Michael Wall

© 2004 Kugler Publications, The Hague, The Netherlands

228 G. Milano and C. Klersy

diagnosis of glaucoma,5-15 and the Swedish Interactive Threshold Algorithm (SITAstandard).

SITA is a new algorithm for threshold evaluation that takes about half the time normally required for the corresponding examination performed with the traditional full threshold algorithm. It is not selective for one type of retinal cell only because it uses white stimuli (size III Goldmann) projected onto a white background (luminance 31.5 asb).

With SWAP, a blue stimulus (wavelength of 440 nm) is projected onto a yellow background (luminance 100 cd/m2) to isolate the response of retinal cells sensitive to short wavelengths.10-12 These cells include the larger P (parvocellular) cells, a small group of retinal ganglion cells.21 Glaucomatous optic neuropathy is characterized by irreversible loss of ganglion cells and nerve fibers. It was thought that, in the early stage of such damage, M (magnocellular) and the larger P ganglion cells can be involved.22,23 SWAP, which can detect the functional consequence of the loss of a cell type that can be involved early in glaucomatous neuropathy, may be a sensitive clinical test. It can also be considered effective in early diagnosis because it can point out the loss of a few elements from the small number of blue-sensitive cells, a not ‘redundant’ retinal system.

It was thought that early glaucomatous damage is not always exclusively selective for larger ganglion cells, but that other cell types are involved.24,25 In this case, an achromatic and sensitive perimetric test would also be able to detect the glaucomatous defect at an early stage.

The aim of this study was to verify the early detection of perimetric defects in a population at risk for glaucoma, submitted to visual field examinations with SITAstandard and SWAP.

Methods

We studied 50 patients (99 eyes) selected from among subjects examined at the Glaucoma Service of the University Eye Clinic in Pavia. There were 21 males and 29 females with an average age of 60.32 ± 15.42 years. Each patient had had an IOP > 22 mmHg before treatment, and this pressure had then normalized (average IOP, 15.23

± 3.28 mmHg) in response to topical therapy with the following drugs:

In 95 cases, IOP was well controlled by monotherapy and in only four patients was a drug association prescribed. The optic discs, analyzed with the help of the Heidelberg Retina Tomograph II, did not show any relevant changes during the course of the follow-up.

Each patient was periodically submitted to automated perimetry with the SITAstandard and SWAP strategies and the 24-2 pattern of a Humphrey 750 Visual Field Analyzer. The most recent visual field tests were utilized in this study, and were

classified on the basis of clinical criteria taken from the guidelines of the European Glaucoma Society.26

The visual field was considered pathological if one of the following situations occurred in two successive tests:

•glaucoma hemifield test (GHT) outside normal limits;

•pattern standard deviation (PSD) in SITA or corrected pattern standard deviation (CPSD) in full-threshold with p < 5%; or

•a cluster of three or more points not adjacent to the blind spot, with p < 5% and

one of these with p < 1% in a pattern deviation plot.

The defects were stable and were classified as early glaucomatous damage according to Hodapp and Parrish.27

The agreement between the two algorithms (SITA and SWAP) in identifying pathological fields was assessed by calculating the kappa statistic. This statistic is scaled between 0 and 1. Substantial agreement is retained for values > 0.6 and almost perfect agreement for values > 0.8. The agreement was computed overall (on the reasonable hypothesis that the amount of agreement would not suffer from lack of independence between eyes, but would solely depend on the respective recognition algorithms), and by eye.

Secondarily, McNemar’s test was applied to verify whether the number of discordant pairs between the two algorithms was significantly different from the expected.

The sensitivity and specificity of SWAP with respect to SITA were also computed, together with their 95% confidence intervals (95% CI). Duration of the examinations was compared by Wilcoxon’s matched paired test. Stata software (College Station, TX) was used for all the calculations.

Results

Of the 50 patients included in the study, bilateral eye disease was identified in ten and six patients, respectively, by the SITA and SWAP algorithms, while 17 and 11 patients, respectively, had involvement of a single eye. The SITA test took less time to administer (5.16 ± 1.02 minutes) than SWAP (11.57 ± 3.02 minutes; p < 0.001).

The algorithms yielded concordant results for 71.7% of the eyes, with 55 eyes being considered normal and 16 eyes pathological with both algorithms, corresponding to a low value of the kappa statistic of 0.34. In fact, 21% of eyes that were identified as being diseased by SITA, were not so identified by SWAP. Conversely, only 7% of eyes identified as being diseased by SWAP were not so identified by SITA. The number of discordant SITA-SWAP pairs was significantly higher than expected (McNemar p = 0.014). The sensitivity of SWAP in diagnosing a pathological eye (with respect to SITA) was computed to be 43% (95% CI; 33.5-53.0%) and the specificity 88.7% (95% CI). Comparable results were obtained when considering each eye separately, although these statistical tests had less power; in particular, the power of the separate McNemar tests was < 60% in detecting the observed differences in proportions of pathological fields with both methods of 12% and 16% for the left and right eyes, respectively (Table 1).

*NN/PP: normal with SITA and SWAP respectively/pathological with SITA and SWAP, respectively; **PN/NP: normal with SITA and pathological with SWAP/pathological with SITA and normal with SWAP

Discussion

The diagnosis of early glaucomatous optic neuropathy is of primary importance when initiating the correct therapy, which could arrest the irreversible loss of ganglion cells and nerve fibers.

Functional analysis usually exploits different strategies of automated perimetry, which make it possible to stimulate the different types of retinal cells that are thought to be involved in early glaucomatous neuropathy.

This study included patients whose IOP, the main risk factor for glaucoma risk, was well controlled by topical therapy, and whose morphological and functional defects were stable.

Forty-four of 99 eyes had at least one pathological perimetric test, but SITA identified defects more frequently than SWAP (37 versus 23 eyes, respectively). In 16 eyes, both perimetric tests were pathological; in 21 eyes, only the SITA test was pathological; and in seven eyes, only the SWAP test was pathological with a normal SITA test.

The statistical analysis elicits a rather poor agreement between the two algorithms in glaucomatous visual field evaluation (kappa statistics below 0.40 for both the overall and the per-eye analysis). The number of discordant pairs is not low. The ability of SWAP to identify early perimetric defects was less than that of SITA, as shown by both McNemar’s test and the calculation of sensitivity. Overall results are presented together with per-eye analysis, since, while the presence of any intrinsic characteristic is usually correlated within patients, a within-patient correlation should not be expected when the ability of detection of two different algorithms is analyzed.

In our study group at least, SITA identified a higher number of defective visual fields than SWAP. These results seem to be in contrast with those of previous articles in which SWAP was compared to achromatic automated perimetry performed with a full-threshold algorithm.5-15 The range of normal threshold values with SITA is narrower, and can uncover milder defects than the full-threshold algorithm. This could also occur when SITA is compared to SWAP, which uses a full-threshold algorithm.

SWAP selectively stimulates the blue-light-sensitive retinal system, which ends up on larger P-ganglion cells probably damaged in glaucoma, whether or not the early loss is selective for larger ganglion cells or involves all ganglion cells types.

If glaucomatous optic neuropathy is not always the selective loss of larger ganglion

cells and fibers, but in some cases could involve other cell types,24,25 then the achromatic test would also be appropriate for eliciting early signs of dysfunction, as shown by SITA results in this study.

SITA is fast (5.16 ±1.02 minutes in the study population), interactive because it is able to adjust test pacing to the patient’s reaction time, and probably more precise in threshold determination and more accurate in statistical definition of abnormality than the traditional threshold test.

Test duration (11.57 ± 3.02 minutes in the study group) and the difficulties in perceiving blue stimulus make SWAP particularly tiring. Moreover, the influence of cataract and miosis, and a greater threshold fluctuation that produces a larger range of normality than the achromatic test, can make it difficult to pick up the slight threshold elevations that occur in early glaucomatous damage.

Taking into account that the white-on-white SITA test seemed to be more effective than SWAP in detecting early damage in the study population, we might suppose that there is a diffuse ganglion cell loss. At present, the true pattern of early glaucomatous optic neuropathy and its relationship to psychophysical tests are still not completely known.

In conclusion, SITA-standard is fast, accurate in light sensitivity evaluation, fits all patients, and can be considered an appropriate clinical test for the early diagnosis of glaucomatous neuropathy.

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