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of test times achieved with Fastpac (up to 70%) has been judged useful for various clinical purposes.

Swedish interactive threshold algorithm

Many efforts have been made to shorten thresholding strategies for VF assessment without reducing the accuracy of the test. Newer algorithms for measuring VFs have been recently developed.

The Humphrey SS and SITA fast demonstrated, in different studies, excellent sensitivity and specificity for glaucomatous VF loss with remarkable savings in time.

Among a cohort of patients experienced with automated perimetry, changing the order of eye testing using the SS 24-2 did not have a significant effect on the MD or the test reliability. While intereye fatigue may not be clinically significant with the SITA, fixation losses represent a problem with the use of this algorithm.

The SITA algorithm showed reduced betweensubject variability. Nevertheless, SS produced slightly higher mean sensitivity values compared with that of existing algorithms. Furthermore, HFA II SS underestimates patients’ false-positive errors, particularly among normal subjects. High false-positive error frequencies can have adverse effects on MD and PSD, leading clinicians and researchers to an inaccurate determination of the amount and severity of VF loss.

Nevertheless, SS reduced test-taking time from FT by 52% in normal subjects and 47% in glaucoma patients (Wild et al., 1999a, b; Barkana et al., 2006; McGwin et al., 2006).

Hoffmann et al. (2006) investigated the inter-eye correspondence between patterns of VF loss on SAP in patients diagnosed with glaucomatous optic neuropathy. All participants performed two SAP VFs using the 24-2 program and SITA thresholding algorithm of the HFA. They found that more advanced VF defects (e.g., partial arcuate) show higher correspondence rates between the eyes than less advanced defects.

Another fast strategy algorithm, the TOP, has been developed for the Octopus perimeter. The TOP strategy tests each position in the VF once

and extrapolates this information to the surrounding points. High correlation was found between the SITA fast (Humphrey) and TOP (Octopus) strategies for measurements of global indices.

The TOP strategy tended to underestimate focal VF loss compared with SITA fast. The TOP strategy resulted faster than SITA fast, while the two algorithms showed similar sensitivity and specificity (King et al., 2002).

SAP VF assessment: the glaucoma staging system

The classification of VF defects identified with SAP has been used to distinguish between healthy and glaucomatous eyes, to establish homogeneous criteria for grading severity of disease, to allow accurate follow-up of disease.

SAP is still the accepted technique for quantifying functional damage in patients suffering from glaucoma.

Several classification systems exist to identify SAP VF defects and patterns of VF loss. None of the different classification methods have been proposed in the past yet have obtained a widespread use.

The Aulhorn and Karmeyer’s classification relies on manual perimetry, a testing procedure that is obsolete; nevertheless, this five-stage classification is still considered to be a reference point in glaucoma clinic and research.

Nowadays, one of the most commonly used methods to stage glaucomatous VF loss severity is the classification proposed by Hodapp et al. in 1993.

In this method, the VF defect is classified as early, moderate, and severe defect on the basis of the MD value and the number of defective points in the STATPAC-2 PD probability map; the defect proximity to the fixation point is also considered. This classification requires an accurate analysis of every single VF result, and therefore, it is time consuming. Furthermore, it may be inaccurate for a fine categorization of VF defects.

Recently, the Bascom Palmer (Hodapp– Anderson–Parrish) classification was selected for a retrospective glaucoma staging system (GSS) on the basis of Humphrey VFs. This system, modified

by a panel of glaucoma specialists after a review of published GSSs was conducted, underwent additional modifications after pilot testing to cover the full range of disease progression, from pre-glaucoma diagnosis to complete blindness.

This GSS, based on the Humphrey perimetry, consists of six ordered stages. It was validated by reviewing patient charts from 12 US glaucoma centers.

Several studies adopted the AGIS Investigators classification method (1994). The AGIS score is based on the number and depth of adjacent depressed test locations. This score ranges from 0 to 20, and it can be used to classify the defect into five severity categories.

The CIGTS classification method is similar to the AGIS method. Both AGIS and CGITS scoring systems need a discrete training to be applied in

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daily clinical practice, although they are analytical and accurate.

Brusini pointed out that both the AGIS and the Hodapp–Parrish–Anderson methods are accurate with regard to localized defects but fail to take into consideration slight diffuse sensitivity depressions, which may at times be due to an early glaucomatous damage.

Most of these methods have been specifically designed to be used with the 30-2 and 24-2 programs of the early Humphrey perimeters. Moreover, they often miss information regarding the characteristic of the defect (Brusini and Filacorda, 2006).

The GSS (Brusini), introduced in 1996 (Fig. 5), is based on the two main VF global indices: MD or mean defect and CPSD, or CLV, plotted on an X–Y coordinate diagram.

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The GSS was developed on the basis of 500 automated VFs (332 Humphrey 30-2 FT VFs and 168 Octopus G1/G1X VFs, normal strategy, three phases) from 471 patients with primary open-angle glaucoma (POAG) at various stages of severity.

A new intermediate stage between Stage 0 and Stage 1 has been added in the more recent GSS 2 (Brusini and Filacorda, 2006) to include borderline cases. One hundred and twenty-eight automated VF tests performed with the HFA 30-2 FT test were analyzed to define the two lines that separate this new borderline stage from both Stage 0 and Stage 1.

Brusini’s GSS has shown to be useful both in staging the damage severity and in identifying the different components of VF loss (generalized, localized, and mixed) and to monitor defect progression over time.

SAP: interocular asymmetries in OHTS

Binocular VF test point asymmetry can assist in clinical evaluation of eyes at risk of development of POAG. In OHTS, asymmetric VF threshold values proved to be an important predictor of POAG. Eyes from an asymmetric pair that have reduced sensitivity were at 59% greater risk of developing POAG.

The OHTS investigators developed a new index, MP (mean prognosis), to discriminate between eyes that developed POAG from eyes that did not (Levine, 2006).

SAP, VF progression

The aim of computerized perimetry over time is to follow the evolution of a glaucomatous defect. The most commonly noticeable progression in worsening glaucoma is an increase in the depth of VF defects, followed progressively by their widening. In approximately half of the cases, the appearance of a new scotoma in different areas is seen (Mikelberg and Drance, 1984).

In order to correctly assess the evolution of the glaucoma, computerized perimetry must be considered the surest method, as long as important

rules are followed. First of all, it is wise to always use the same threshold strategy examinations with the same parameters during the follow-up.

It is necessary to identify the baseline VF, taking this as a first one, while being careful of all possible forms of artifacts: first the learning effect, which is responsible for an improvement of the second test in comparison to the first; the fatigue effect, which can cause a depression of the threshold during the examination; and the demotivation effect, sometimes the reason for a worsening that cannot be otherwise explained, due to the lack of motivation with which a patient faces the examination (Katz et al., 1997; Anderson et al., 2000).

The LF invariably tends to pollute the data so that a suitable number of tests (at least four or five) must be available in order to issue a correct clinical judgment on the evolution of a perimetric defect.

As regards the frequency with which the perimetry should be carried out, it is necessary to consider the extent of the glaucoma, that is to say the perimetric damage at the outset, the intraocular pressure control over time, the age of the patient, his degree of cooperation, and the current therapy (the lesser the care, the more the VF must be controlled). Basically, a frequency of 6 months will be sufficient in most cases, while subjects at risk (e.g., those with a threatened fixation point) should be tested every 3–4 months. Where a test appears clearly different (improved or worsened) in comparison to previous ones, it is always advisable to repeat the test.

At this stage it is essential to establish if the variations observed during the follow-up are important or not. Due to LFs, a not-always-perfect cooperation, altered examination conditions, and many other disturbing factors, it is often difficult to establish if a change should be taken into account or ignored as being without clinical importance. To express such a judgment, one can rely on experience, use standardized criteria, or use special statistical programs (Spry and Johnson, 2002).

The first method offers the advantage of considering the clinical context and of being flexible, but it is subjective and requires considerable knowledge about perimetry so as not to make quite simple mistakes.

The standardized criteria (Hodapp et al., 1993; AMO, AGIS, and CIGTS) are based on the variations in the number of altered points and the depth of the defect: They provide less subjective data, but are too strict for a routine clinical use (Walsh, 1990).

The statistical programs have the advantage of not being influenced by what are only apparently important variations, but deal mathematically with data that is biological and thus subject to physiological fluctuations. Finally, it should be remembered that statistical importance is not always the same as clinical importance.

The most well-known statistical programs are STATPAC, Humphrey, PeriTrend Octopus, and Peridata. The STATPAC’s Glaucoma Change Probability relies on repeatability of multiple negative pointwise changes to thresholds on either the TD or the PD plot.

The Glaucoma Progression Analysis (GPA) is based on PD, defined as the deviation from agecorrected values adjusted for the general height of the VF and relies on EMGT progression algorithm.

The Progressor and Peridata softwares are based on pointwise linear regression analysis (PLRA).

The STATPAC Humphrey program makes it possible to collect up to 16 examinations in one printout without losing any information called ‘‘Overview’’ (Fig. 6). The advantages of the Overview option is to have a simple view of several and in-sequence exams in the same page, while the main limit is that only a clinical and subjective evaluation is possible.

With ‘‘Change Analysis’’ option, the main indices (MD, PSD, SF, and CPSD) are graphed, and if at least five examinations are available, the significance of the variations of the MD over time is produced, based on linear regression analysis (Heijl et al., 1991). The new version of the program (STATPAC-2) also makes it possible to assess point by point the significance of the variations in different light sensitivity with respect to the baseline VF, obtained from the average of the first two examinations called ‘‘Glaucoma Change Probability’’ (Fig. 7). In the Glaucoma Change Probability option, changes in the VF over time are expressed by symbols: D indicates points where the different

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light sensitivity is improved and 7 points where the different light sensitivity is decreased with respect to baseline exams.

With the new Humphrey GPA software, even examinations carried out with SITA strategy can be analyzed. This program also provides a statistical judgment on the possible or probable progression of a perimetrical defect on the basis of the possibility of repeating a worsening that regards the same area in two or more consecutive tests (Fig. 8).

Minimum of three tests are required: two as baseline and other as follow-up exams. Each follow-up exam is compared to averaged thresholds of two baseline exams. Additional follow-up exams are compared both to baseline and to two most recent follow-ups. The results are expressed using the following symbols:

D indicates progression at 95% significance level. 7 indicates progressing point repeated in two

consecutive exams.

&indicates progressing point repeated in three consecutive exams.

GPA Alert TM signal is based on the presence of symbols: Three7in one exam denotes possible progression, and three & indicates likely progression of the VF defect in time.

The PeriTrend Octopus program uses the analysis of linear regression for estimating variations in the MD and LV indices over time. The different colors of the lines for MD and LV indicate the significant or insignificant changes of these indices over time.

With the Peridata program it is possible to visualize and print a series of VFs in chronological order, choosing between types of display, including a pointwise analysis of linear regression (Weber and Caprioli, 2000).

The Progressor (Fitzke et al., 1996) program uses linear regression for highlighting in different colors any significant variations in sensitivity in each point examined.

The GSS can also be used for graphically following the evolution of a defect over time (Kocak et al., 1997).

Other programs that use more complex systems of analysis seem now to be useful but are still not

used in clinical practice (Nouri-Mahdavi et al., 1997; Lin et al., 2003; Vesti et al., 2003).

No matter what method is used for assessing the evolution of a perimetric defect, it should however be emphasized that the results of the perimetry must be compared to the other clinical information, inasmuch as a variation in the VF could be due to reasons other than glaucoma.

Finally, it should be remembered that, in order to be of such a clinical importance as to change current therapy, a worsening of the perimetric defect must be statistically important, capable of being reproduced in a second test and relative to the current illness.

SAP offers different advantages: It is probably the test most used in glaucoma over the past two

decades; it was implemented with complex statistic techniques that allowed to shorten test time without loss of accuracy. The SITA algorithm decreased test time (and patient’s fatigue) but maintained reproducibility.

Studies on SITA show significant reduction in testing time (50%) without affecting diagnostic accuracy. It is associated with a greater sensitivity and reproducibility and less intertest variability when compared with standard FT testing. Part of