To obtain an overview of all methods to assess glaucomatous visual field progression, a systematic literature search was performed in April 2009 «Ernest PJ, Schouten JS, Beckers HJ ym. The evidenc...»1 (PubMed, EMBASE and all databases and registers of the Cochrane Library). A total of 2450 articles were identified. Based on predefined exclusion criteria, studies reporting on patients with glaucoma who were followed for a minimum of 1 year with the use of standard visual field examinations were included so that progression could be assessed. 412 articles were included. From this search, 21 articles that used the Humphrey Visual Field Analyzer (HFA) and studied mean follow-up IOP as a prognostic factor for glaucomatous visual field progression were included. The reproducibility of progression methods in patients with glaucoma was evaluated by performing a second systematic search in PubMed in April 2009.
Ten Questions and Answers
1. How many methods can we choose from to assess visual field progression?
A total of 301 different methods were used in 412 articles. Fifteen different perimeters were found to have been used to assess progression in the literature. As the majority of 222 studies (54 %) HFA, increasing to 77 % of the articles published since 2000, the review focused on HFA. HFA methods were further classified into qualitative and quantitative methods. A qualitative method implies that the ophthalmologist decides on the occurrence of progression, whereas a quantitative method uses numeric units for defining progression. Qualitative methods were used 32 times (8 %), and quantitative methods, 355 times (92 %). Quantitative methods that calculate a rate of progression were used 166 times (47 % of quantitative methods). However, most of these studies dichotomized the rate of progression because they aimed to compare different progression methods or estimated treatment effects in a large group of patients. Therefore, even these methods did not really quantify the rate of progression needed for decision making in individual patients.
2. Which method to assess visual field progression can predict the loss of QoL?
The prediction of loss in QoL has not been shown for any method. The ultimate goal of glaucoma management is to prevent the loss of QoL. A method to assess progression should therefore identify patients who will lose vision-related QoL in the future if treatment is not intensified. Although this constitutes the essential goal of monitoring progression, it has not been addressed in empirical research. Empirical research should ideally randomize patients to different monitoring strategies with a subsequent long follow-up period to evaluate differences in QoL. Future studies should address this issue with the inclusion of methods quantifying the rate of progression.
3. What is the gold standard to assess glaucomatous visual field progression?
There is no gold standard to assess visual field progression.
4. Which methods have been compared with a substitute gold standard of visual field progression or stability?
Several methods have been compared with a substitute gold standard to assess visual field progression. There is much variation in several accuracy measures within studies and between studies. There seems to be no superior method, although some have a lower diagnostic odds ratio when compared with other methods within one study.
5. Which methods have been compared with other parameters of disease progression?
One study that used progressive optic disc cupping as a reference standard was found (the Advanced Glaucoma Intervention Study, AGIS).
6. Which methods give a good prediction of future visual field loss?
One way to investigate the sustainability of progression is to use the outcomes after a limited number of follow-up years to predict outcomes after a longer period, both using the same baseline as a reference. Several methods have shown high sustainability (AGIS, CIGTS, EMGT, CNTGS and pointwise linear regression analysis methods). Instead of looking at the sustainability of positive test results, one study used correlations to validate the continuous Visual Field Index (VFI) rate, i.e. whether the VFI rate in the initial 3.3 years could reliably predict the VFI after a mean follow-up time of 8.2 years. A correlation coefficient of 0.78 was found when the predicted VFI was compared with the actual last VFI.
7. Which methods have shown to be related with a presumed prognostic factor of glaucomatous progression?
In total, 20 different methods have been studied in relation with mean intraocular pressure (IOP) in 21 articles. Thirteen methods (65 %) found a positive relationship between mean IOP and glaucomatous visual field progression. Six of these methods (30 %) showed a statistically significant positive difference (p < 0.05) in mean IOP between the progressive and non-progressive groups.
8. Which methods have shown to be reproducible?
No studies about the reproducibility of methods to assess visual field progression have been conducted. 21 articles studying cross-sectional reproducibility of visual field measures wew found derived from the HFA. In general, these studies showed that mean deviation (MD) values have a higher reproducibility than poin twise values.
9. Taking into account the evidence above, which method should we select from the 301 available methods?
The selection from 301 methods was limited to 48 different methods for which data on validity were present. Excluding the different cut-off points, the selection was limited to twelve methods (AGIS, CIGTS, PLR, MD, Glaucoma Change Probability (GCP), EMGT, VFI, Threshold Noiseless Trend (TNT), Werner, clinical scoring system(CSS), CNTGS, and subjective methods).
Methods based on the VFI, MD, GCP or EMGT may be usable, because the required information is available on the printed output of the HFA. Among them, the EMGT method is the only method that has shown to correlate with mean IOP during follow-up. Methods based on MD and EMGT seem to perform well in some studies although they probably overestimated the accuracy of methods. The odds ratio of the EMGT method was relatively low in the other studies.
Qualitative methods could also be useful, although the interpretation of results is dependent on the capacity of the observer. This may cause high interobserver variability. These methods have frequently been used as a substitute for a gold standard. In these cases, however, the assessment was based on the judgement of more than one observer. Qualitative methods have also shown to correlate well with mean IOP, but these findings could be biased because these qualitative assessments were not masked for other clinical information.
The current evidence base is not perfect but seems to be fair for a few methods that have been validated. As numerous methods are available, one should probably stop developing many new methods to assess visualfield progression. The ultimately relevant question, whether using one method to monitor patients is superior to another in preventing loss of QoL, has not been answered. Methods that quantify the rate of visual field progression seem to be the most appropriate for guiding subsequent medical actions in individual patients, because they can be used to estimate individual risk of lifetime visual disability. This should ideally be studied in prospective studies with long follow-up periods.