Assessment of visual field progression in glaucoma : Current Opinion in Ophthalmology

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GLAUCOMA: Edited by Donald Budenz

Assessment of visual field progression in glaucoma

Chen, Rebecca I.a; Gedde, Steven J.b

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Current Opinion in Ophthalmology 34(2):p 103-108, March 2023. | DOI: 10.1097/ICU.0000000000000932
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Abstract

INTRODUCTION

Perimetry plays an important role in the diagnosis and management of glaucoma. Visual field changes provide a basis for adjustments in treatment. Imaging of the optic disc, retinal nerve fiber layer, and ganglion cells complements, but does not replace, visual field testing. Notably, a floor effect with optical coherence tomography measurements limits detection of further deterioration in eyes with advanced disease.

A paradigm shift in glaucoma management has occurred over the past decade. Prior focus on whether visual field progression has occurred is increasingly shifting to the rate of progression and the risk of future visual disability. The goal of glaucoma treatment is preventing loss of visual function and preserving quality of life. 

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SELECTING A TEST STRATEGY

Selecting the best visual field test strategy for an individual patient can increase the likelihood of detecting glaucomatous progression.

Test patterns

The 30-2 test pattern includes 76 test points within the central 30° of field, spaced 6° apart, and the 54 most central points constitute the 24-2 test pattern. The 24-2 test pattern has replaced the 30-2 in glaucoma management because of its lower test–retest variability and shorter test duration, without significant loss of diagnostic information [1].

The 10-2 test pattern covers the area within 10° of fixation with test points spaced 2° apart. It may be preferred in glaucoma patients with advanced visual field constriction or scotomas close to fixation at any stage of disease. In early glaucoma, there is mixed evidence regarding whether the 10-2 test pattern may have greater sensitivity to detect visual field defects that are missed with the 24-2 test pattern [2,3▪]. A shortcoming of 10-2 visual fields is the lack of a reference database for progression analysis. However, an event-based algorithm similar to Guided Progression Analysis (GPA) for 24-2 and 30-2 SITA tests was recently developed [4].

Stimulus size

The size III stimulus is most commonly used and is the basis for normative data and the Humphrey GPA package. The larger size V stimulus extends the available range of sensitivities to monitor for progression and is sometimes used for patients with advanced glaucoma or media opacity. Unfortunately, nonstandard stimulus sizes are incompatible with SITA strategies and require a more time-consuming algorithm (Fastpac or Full Threshold). A normative database and GPA are not available with a size V stimulus [5].

Test algorithm

The Swedish Interactive Thresholding Algorithm (SITA) has supplanted the traditional full threshold strategy and includes SITA Standard, SITA Fast, and SITA Faster. Whereas older algorithms repeatedly test points until reaching specific numbers of stimuli crossing, SITA algorithms cease testing once predetermined thresholds of certainty have been achieved [5]. SITA algorithms demonstrate comparable sensitivity and specificity for detecting visual field changes compared with full threshold testing [6].

SITA Fast and Faster gain efficiency over SITA Standard by reducing the certainty threshold required to cease testing. Additionally, SITA Faster only tests each location once and eliminates false-negative catch trials. Despite shorter test duration, SITA Faster has similar reproducibility as SITA Fast and SITA Standard [5].

SITA Fast and Faster algorithms may yield higher threshold sensitivities and corresponding amelioration of mean deviation and pattern standard deviation (PSD) values compared with SITA Standard [7,8▪▪]. When transitioning from SITA Standard to SITA Faster, groups have noted higher mean deviation and preservation of normal-appearing visual field patterns [8▪▪,9▪▪]. SITA Standard tests may be more precise than SITA Fast [5,10▪]. The magnitude of these differences remains of unclear clinical significance but could represent correction of visual field loss overestimation by SITA Standard, masking of field progression, or a fatigue effect [8▪▪].

There are some situations in which a particular SITA algorithm may be preferred. SITA Faster demonstrates higher test–retest variability at low thresholds [11]. SITA Standard starts with a threshold of 25 dB whereas SITA Fast starts with an age-matched threshold, which translates to barely visible stimuli that potentially increases test difficulty and biases towards false positives [5,8▪▪]. Patients who struggle with visual field testing may find SITA Standard to be easier. Fortunately, tests obtained using any SITA strategy can be utilized in the Humphrey perimeter's GPA.

INTERPRETING VISUAL FIELDS

Automated analysis of perimetric data can assist clinicians in evaluating the quality of information collected and the likelihood that visual field changes are abnormal.

Reliability indices

Reliability indices are an important marker of visual field quality. The false-positive rate in catch trials have the greatest effect on visual field reliability, particularly in advanced glaucoma, in which the mean deviation may be falsely increased. Conversely, false-negatives can falsely reduce mean deviation in early glaucoma, though they may also reflect increased variability in an area of visual field damage [12]. Excessive test duration (such as 2–3 min beyond typical) is also associated with poor test reliability [12]. Fixation losses can represent learning effect of test-taking, inattention, or eccentric visual fixation, although one study did not detect any impact on test reliability [12].

Differing thresholds for acceptable reliability indices have been proposed for use in clinical trials and practice. The Ocular Hypertension Treatment Study (OHTS) set a 33% limit for maximum fixation loss, false-positive, and false-negative rates to be considered a reliable field [13]. False-positive is the most influential and fixation loss is the least influential index for visual field reliability, and a mathematical formula has been developed to calculate the acceptable reliability indices to achieve a desired threshold of visual field reliability, which can vary by glaucoma severity [12].

Threshold sensitivities, deviations, and maps

The Humphrey perimeter STATPAC analytical package generates numerical threshold sensitivities (in decibels) at each test point. The total deviation map presents the numerical deviation from age-matched normative data, while the pattern deviation map presents localized loss after correction for generalized depression, such as from concurrent cataract. Their associated probability maps use a grayscale shading system to represent the statistical significance of any visual field defects at each test point.

Global visual field indices

The STATPAC analysis calculates several indices to describe deviation from the norm. The mean deviation is a weighted average of the numerical values of the total deviation map, with zero indicating no deviation from age-matched normative data and large negative values associated with advanced field loss. Its derivative, the visual field index (VFI), corrects for the effects of cataract and preferentially weighs central visual field changes. The VFI summarizes a patient's visual field status as a percentage of normal age-corrected sensitivity, with 100% being normal and 0% representing perimetric blindness. The PSD ignores the effects of generalized depression and summarizes localized visual field loss. These indices are helpful for disease staging and monitoring for progression over time.

REPEAT TESTING

Visual field testing should be repeated soon after glaucoma diagnosis because obtaining two similar and representative baseline tests is foundational to future management decisions. A new or worsening visual field defect should prompt repeat testing. Clinical trials have highlighted the importance of repeat testing to confirm or refute progression. Stricter endpoint criteria with confirmatory visual fields were adopted during the Collaborative Normal Tension Glaucoma Study, which reduced false calls of progression from 57 to 2% [14]. In OHTS, 85.9% of new visual field defects were not confirmed on repeat testing [13].

It can be difficult to differentiate between long-term variability and glaucomatous progression. Variable sensitivity measurements occurring in the same area commonly precede definitive visual field progression. Glaucoma progresses from occult damage without detectable visual field changes, to transient visual field defects, to progressive density of replicable visual field defects [15]. Variability is highest in areas of reduced threshold sensitivity, and in patients with moderate field loss, the 95% confidence intervals can span the entire measurement range of the Humphrey field analyzer [16,17].

At least five threshold visual fields are needed to quantify the rate of progression. Identifying rapidly progressing patients at risk for visual disability is a clinical priority. More frequent testing is associated with earlier detection of visual field change. A study found the time to detect rapid progression (defined as mean deviation change of 2 dB/year) was 1.7 years with triannual testing versus 5 years with annual testing [18]. Compared with triannual testing in the first 2 years, annual testing in the first 2 years was associated with delayed detection of visual field progression, though the positive-predictive and negative-predictive values of individual fields were unaffected [19]. Frontloading visual fields (two visual fields per visit, per 6 months) has been proposed as an approach to overcome challenges associated with obtaining multiple sets of perimetry data; compared with annual testing, frontloading achieved earlier detection and reduced mean deviation change prior to detecting visual field progression [20▪,21▪]. Using SITA Faster, generally both eyes could be tested twice within 20 min; however, reimbursement and repeatability at lower thresholds remain challenges [21▪].

It has been recommended that two to three visual fields per year (including baseline tests) be obtained during the first 2 years following newly diagnosed glaucomatous visual field loss [18,22,23]. The National Health and Medical Research Council and European Glaucoma Society have published formal recommendations for testing frequency [22,23]. More frequent visual field testing should be performed in glaucoma patients with field loss until stability or acceptably slow progression has been established. Nonetheless, the majority of glaucoma patients in one insurance claims database did not receive the recommended frequency of visual field testing, suggesting a discrepancy between recommended and actual clinical practice [24▪].

GUIDED PROGRESSION ANALYSIS

The Humphrey perimeter's GPA offers both event and trend analysis [5]. Subsequent visual fields are compared with baseline visual fields to quantify the amount and rate of change. Baseline tests should define the patient's therapeutic status, such as the initiation or significant modification of therapy [5]. By default, GPA selects the first two reliable visual fields as baseline. The clinician may assign different visual fields as baseline, such as in cases of significant learning effect, poor initial visual field quality, or following a therapeutic intervention. Any visual fields preceding the baseline tests are excluded from GPA analysis. The SITA testing strategies (Standard, Fast, and Faster) may be intermixed in the upgraded GPA program.

Event analysis

The goal of event analysis is to identify any statistically significant visual field worsening compared with baseline. It can be helpful in assessing clinical stability versus progression following a change in therapeutic management. The GPA's Glaucoma Change Probability Map highlights test points on 24-2 and 30-2 visual fields in which pattern deviation values have deteriorated from baseline by more than the expected range of testing variability found in glaucoma patients. Open, half black, and filled-in black triangular symbols indicate test points showing deterioration from baseline that is statistically significant at the P less than 0.05 level on 1, 2, and 3 or more consecutive visual fields, respectively. Test points falling outside the range that can be analyzed for statistically significant change are marked with an ‘X’. The GPA Alert displays progression analysis based on criteria used in the Early Manifest Glaucoma Trial (EMGT) [25]. ‘Possible Progression’ and ‘Likely Progression’ denote statistically significant deterioration of the same three or more test points on two, or three or more, consecutive tests, respectively.

Event analysis based on EMGT criteria is highly sensitive and specific (96 and 90%, respectively) [26]. In one study, EMGT criteria had superior sensitivity and earlier detection of progression compared with criteria from the Advanced Glaucoma Intervention Study (AGIS) and Collaborative Initial Glaucoma Treatment Study (CIGTS) [26].

Quantification of visual field change is particularly helpful in the setting of clinical trials to enable meaningful comparisons, but clinical judgment is necessary to ascertain their clinical significance. Some investigators have customized event analysis algorithms to account for variability change and lower sensitivities, resulting in higher sensitivity for detecting glaucomatous progression, particularly in advanced glaucoma [27▪].

Trend analysis

The aim of trend analysis is to quantify the rate of visual field progression to help clinicians evaluate the risk of future visual impairment. Clinical trials have shown that many treated patients with glaucoma will progress [25,28,29]. The GPA trend analysis estimates the progression rate using linear regression analysis of VFI over time. The use of VFI instead of mean deviation minimizes confounding by cataract and yields more accurate predictions [30].

The GPA trend analysis is automatically calculated when five or more eligible visual fields are available. A projection of the linear regression line into the future for up to 5 years, not exceeding the duration of visual field data collection, is provided by GPA if five or more visual fields over at least 2 years are available and if the width of the 95% confidence interval for VFI slope is less than ±2.5%. The projected VFI slope has been verified to accurately predict future visual field progression and may help identify rapidly progressing patients (VFI decline of greater than 2% annually) [30]. Clinicians should be aware that trend analysis may underestimate the rate of visual field progression in severe glaucoma because of the large number of points with undetectable sensitivity, which precludes identification of further progression at those points [31▪▪]. Additionally, event analysis has earlier detection and greater sensitivity for visual field progression compared with trend analysis, and may therefore prompt assessment for clinically significant visual field change [32].

ARTIFICIAL INTELLIGENCE

Artificial intelligence is an emerging area in visual field analysis. Though not yet commercially available, various machine learning models have been utilized to detect visual field change [33▪▪,34▪–36▪]. Deep archetypal analysis identified a novel pattern of visual field loss predictive of rapid progression in OHTS [33▪▪]. Integration of spatial–ordinal visual field data or clinical information can enhance artificial intelligence prediction or detection of visual field progression [34▪,35▪]. Though still nascent, artificial intelligence-based tools may provide valuable insights in visual field assessment in glaucoma management.

CONCLUSION

Many treated glaucoma patients will experience progression. Selecting the best test strategy and establishing a baseline of visual fields optimizes the likelihood of detecting visual field change. When visual field change is suspected, testing should be repeated to confirm or refute progression. In clinical practice, statistically significant changes on event analysis can prompt examination for clinically significant changes on trend analysis.

Perimetric progression rates vary widely among glaucoma patients. An important minority will progress at rates leading to functional impairment without appropriate treatment. More frequent visual field testing following glaucoma diagnosis helps establish a personal baseline and identify rapid progressors.

Acknowledgements

None.

Financial support and sponsorship

This work was supported by funding from the Heed Fellowship from the Heed Ophthalmic Foundation.

Conflicts of interest

There are no conflicts of interest.

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

▪ of special interest

▪▪ of outstanding interest

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Keywords:

event analysis; glaucoma progression; trend analysis; visual field

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