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1From the Department of Optometry and Visual Science, City University, London, United Kingdom; and the 2Glaucoma Research Unit, Moorfields Eye Hospital, London, United Kingdom.
| Abstract |
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METHODS. Data from patients attending a glaucoma clinic were collected longitudinally. The time from baseline until failure to meet the criteria of the drivers license test was modeled with Cox regression. Visual field status at baseline and visual field deterioration rate at 2 years from baseline for various monocular and binocular VF indices were investigated as predictor variables. The model that provided the best fit to the data was validated using bootstrap resampling.
RESULTS. Of the patients, 20% (60/299; 95% confidence interval, 16%–25%) failed to meet the visual field criteria to prevent drivers license loss during an average follow-up of 7 years. The median age of patients was 64 years. The binocular IVF measurements gave a better fit to the observed data than the monocular measurements. Initial average visual field sensitivity and rate of visual field loss of sensitivity were significant predictors of failure to meet drivers license test criteria.
CONCLUSIONS. The IVF provides a method by which binocular visual fields can be incorporated into patient management and allows, for example, a prediction of future drivers license loss. The rate of binocular IVF sensitivity loss at 2 years of follow-up may help identify patients who could benefit from intensified intervention.
One third of people with POAG have POAG with normal intraocular pressure (IOP), or normal-tension glaucoma.5 These patients show evidence of damage to the optic nerve and visual field (VF) loss, but their IOP remains in the normal range. Most evidence suggests that POAG with normal IOP is on a continuum of glaucoma, rather than a separate entity.6 7 At Moorfields Eye Hospital (London, UK), patients with POAG with normal IOP are monitored closely over time, undergoing regular perimetry to monitor VF loss, providing a rich resource of longitudinal VF data.
The loss of vision resulting from glaucomatous damage has significant impact on the quality of life of older people. The Blue Mountains Eye study found a strong relationship between increased visual impairment and low self-rated health.8 In people with glaucoma who are 55 years of age and older, VF damage (as measured by AGIS scores9 ) is associated with reduced health-related quality of life.10 In a large population-based study, people with visual impairment reported difficulties in performing most vision-dependent daily activities, including difficulty with driving.11
A significant proportion of people with POAG lose vision and become ineligible to drive as a result.12 The loss of ones drivers license is a particularly significant life event, resulting in loss of mobility, social independence, and self-esteem. When patients were asked to rate factors in the management and treatment of their glaucoma, one of the most important factors was the ability to continue to drive.13 Elderly people who stopped driving have been shown to be at greater risk of worsening depressive symptoms.14 Thus, the loss of a drivers license considerably affects quality of life, and has more widespread effects on family, caregivers, and voluntary and statutory organizations. Furthermore, for the individual, it represents a milestone to blindness. It can therefore be thought of as a meaningful and relevant patient outcome, and intervention to prevent or delay its occurrence is crucial.
The Driver and Vehicle Licensing Agency (DVLA) is the statutory body in the United Kingdom that maintains registers of drivers. The DVLA also sets out the legal requirements for fitness to drive in terms of visual acuity and VF loss with recommendations from the UK Royal College of Ophthalmologists. Drivers with bilateral glaucomatous VF loss are required to notify the DVLA and may be tested to assess whether they are fit to drive according to medical guidelines. These guidelines specify the acceptable degree of VF loss as follows: "A field of vision of at least 120° on the horizontal.... In addition, there should be no significant defect in the binocular field which encroaches within 20° of fixation... ".15 A significant defect is further clarified as consisting of particular patterns of central VF loss as measured using the binocular Esterman visual field test (EVFT).16 Binocular VF testing is not routinely used in the clinical testing and management of glaucoma, but is of more value than monocular testing in the assessment of functional ability in activities of daily living and to describe visual disability.16 The EVFT is recognized by the International Perimetric Society and recommended by the American Medical Association for assessment of visual disability. It is included as an automated binocular test on the Humphrey visual field analyser (HVFA) II (Carl Zeiss Meditec, Dublin, CA) and other automated perimeters. During the test, a size III white stimulus is presented at 10 dB over a 120-test-point Esterman grid covering a >130° field. Each location is tested once. A location that fails is tested again, and if it fails twice, that location is recorded as a defect. The EVFT provides a quick and easy way of determining central binocular VF defects. However, it has been shown to have limitations, in that it shows poor breadth of measurement over the range of VF loss,17 the testing pattern may miss central defects,18 and it necessarily lacks accuracy since it is not based on threshold data.18
An alternative to the EVFT has been proposed using the integrated visual field (IVF).19 The IVF estimates the central binocular field of view by merging monocular measurements, so that the sensitivity at a given location in the IVF is simply defined as the maximum of the corresponding left and right monocular VF sensitivities at that location. The IVF is illustrated in Figure 1 , showing the gray-scale grid of a single patient. The monocular fields are shown on the top row, and the binocular IVF on the bottom row. The left eye (top left) has significant defects in the upper nasal region, and the right eye (top right) has a large defect in the lower nasal region. Points that have a sensitivity of 10 dB or less (Esterman defects) within 20° of eccentricity (represented by the circle) are shown on the bottom right. When the monocular fields are combined using the IVF, only one point (corresponding to the blind spot in the left eye) is flagged as having a defect, despite significant losses in the monocular fields. The IVF can be calculated directly from monocular sensitivities, and so there is no need for extra testing. The IVF has been shown to agree closely with the EVFT in classifying patients with glaucomatous central defects18 20 and in classifying patients with respect to fitness to drive in glaucoma.21 More recently, the IVF has been shown to be more closely related to glaucomatous patients perceived difficulty with visual tasks than a measure from the EVFT.22
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Time-to-Event Analysis
Patients were initially excluded if they had had fewer than seven VF tests on either eye. Individual sensitivity values at all visits for all points in the 24-2 VF were extracted from the database. The first two tests in each patients series were excluded to obviate learning effects.23 Therefore, baseline data were defined at the third visit (giving a minimum series of five VFs). Tests were not excluded by unreliability indices.
At each visit, each patients drivers license status was determined by using the IVF alternative to the EVFT. The DVLA VF standard for driving defines an unacceptable degree of VF loss in the central 20° field based on the 24 points tested in the EVFT.15 We adjusted this definition to account for the additional eight points tested with the IVF. Thus, our surrogate measure of DVLA failure at a particular time point was defined as (1) a cluster of six or fewer contiguous points <10 dB lying wholly or partly in the central 20° field, or (2) both a single cluster of four contiguous points <10 dB up to and including 20° from fixation and additional separate point(s) <10 dB within the central 20° area.21
The proportion of patients who failed to meet the DVLA test criteria at 10 years of follow-up was estimated by the Kaplan-Meier method for time-to-event analysis.
Modeling
The purpose was to establish, at 2 years of follow-up, what measures of the VF best predict eventual failure to meet the DVLA criteria. Therefore, for this part of the analysis, those patients who failed to meet the criteria within 2 years were excluded. The rate of VF progression was estimated at the 2-year time point for each patient. This change over time was determined by performing a linear regression of average sensitivities values over time and defining the slope of the regression line as the rate of change in sensitivity over time.
The baseline and the 2-year rate of change indices were calculated for the following: (1) left eye, (2) right eye, (3) worse eye (the eye with the lowest baseline sensitivity value, or the eye with the fastest deterioration over time—i.e., the largest negative slope), (4) better eye (the eye with the highest baseline sensitivity value, or the eye with the slowest deterioration over time), (5) IVF, and (6) IVF over the central 20° field.
Cox proportional hazards modeling was used to determine the dependence on VF indices (baseline and 2-year rate of change) of failure to meet DVLA test criteria. Most of the patients in our dataset remained relatively stable with respect to VF loss, so that they did not fail to meet the DVLA criteria at the end of follow-up. These patients are said to have censored observations. The Cox model is a semiparametric regression technique that takes into account this censoring in the data. The details of this approach are described in detail elsewhere.24 25
We controlled for treatment by including independent variables for treatment in our basic model, regardless of their statistical significance. We then added variables for the various VF baseline and 2-year rate-of-change indices and compared the goodness of fit of models to determine which VF indices best predicted DVLA test failure. These predictions were expressed as risk ratios. We also investigated the effect of age by including an age variable in the models.
Model Validation
It is well established that if variable selection is performed on the same dataset as the estimation of the regression relationship between dependent and independent variables, then the regression estimates will be overly optimistic.26 It is also well known that in developing a best-fitting regression model, the variables selected may vary across different samples.27 We investigated the stability of our Cox model using bootstrap validation.28 We took 100 bootstrap samples with replacement from our data, and fitted the same Cox model that best fit our original dataset to each bootstrap sample. The bootstrap estimates of the regression coefficients and their standard errors are then simply given by the means and standard deviations of the bootstrap estimates. We also fitted all the VF baseline and 2-year change variables to each of the 100 bootstrap samples, to determine which variables gave the best goodness of fit.29
Analyses were performed in the statistical programming language R (ver. 2.0.1, The R Foundation for Statistical Computing, Vienna, Austria) and in commercial software (SPSS, ver. 14.0; SPSS Inc., Chicago, IL). The study adhered to the tenets of the Declaration of Helsinki, and both the study and analysis were approved by a local research ethics committee independent of Moorfields Eye Hospital.
| Results |
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| Discussion |
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The main purpose of this study was to identify which monocular and binocular measures of VF loss best predict which patients in a normal-tension glaucoma clinic are likely to meet the DVLA criteria for VF loss, and thus potentially lose their drivers licenses. IVF sensitivity indices provided a better fit to our dataset than monocular measurements, and the IVF over the central 20° field in particular provided a good fit to the observed data. In terms of predicting which patients will lose their drivers licenses in the future, it is important to know both the mean IVF value in the central 20° field at baseline (how severe the binocular defect is at the start of follow-up) and the rate of change in the IVF field at 2 years (how well a patient does over time). This combination appears to be better than simply monitoring the worse eye or the most rapidly declining eye in isolation. It has also been shown that both baseline binocular VF loss and VF loss at 2 years after baseline are significantly associated with driving cessation in older adults.36 Patients who come into a clinic with poor IVF and/or patients who rapidly lose IVF sensitivity over time can be flagged for possible intensified intervention or closer monitoring, to prevent their failing the DVLA VF criteria. It is important to bear in mind that we are predicting a surrogate measure of DVLA failure and as such, we are not able to confirm whether patients did in fact lose their drivers licenses.
In our best-fitting model shown in Table 3 , the variable for glaucoma surgery is statistically significant, so that patients who underwent glaucoma surgery were approximately three times as likely to fail the DVLA test during follow-up than were patients who did not undergo surgery. This finding is almost certainly due to selection bias (i.e., patients with demonstrable disease progression or high risk of further progression are identified early and tend to be referred for surgery).
The value of a model may be further improved by applying it to an independent sample of patients and assessing its performance in predicting failure the VF criteria to prevent loss of drivers license. In the absence of an independent dataset, we used bootstrap techniques to validate our findings. The large-sample approximations for the Cox regression coefficients were broadly confirmed by applying the same model to the bootstrap samples. The superiority of the central 20° IVF baseline sensitivity and 2-year change values as predictors of DVLA failure was supported in 93% of the bootstrap samples (Table 5) .
Our modeling necessitated excluding patients who failed the surrogate DVLA criteria within a short period from the start of follow-up (2 years), because one of our model variables was the rate of change at 2 years. These patients showed rapid rates of loss of VF sensitivity. The patients remaining in our sample had vision that was deteriorating less rapidly. This may explain why the rate of loss parameter is only just equivalent to the initial loss at presentation as a risk factor for failure to meet the surrogate DVLA criteria (Tables 3 4) . In practice the former is probably more important, but the clinical conundrum is estimating rapid rate of loss reliably over a shorter period than say 2 years with a clinically realistic number of fields. Statistical estimation of the rate of loss must be done on a sufficient number of points in time. Perhaps frequency of testing could be increased when monitoring patients with newly diagnosed glaucoma,37 but this issue is beyond the discussion of the results from this study. It should also be noted that the patients in our dataset are likely to be highly motivated, having attended the clinic over a long period, and have received excellent care and so are likely to have more stable glaucoma.
Historically, there has been a great deal of uncertainty about how best to treat POAG with normal IOP (or normal tension glaucoma), since there was little evidence to show that lowering IOP prevents continued VF loss. It has since been shown that IOP-lowering treatments can slow VF loss or progression of optic disc damage38 ; however, the research literature remains mixed: a Cochrane review concluded that there is "not enough evidence about the effects of surgery or medications on vision loss from normal tension glaucoma."39 Given the weak research evidence for effectiveness of treatment in these patients, and the risks of side effects of treatment, many patients with POAG and low IOP are left untreated and instead are monitored frequently for signs of VF damage. We believe that the methods outlined in this study could greatly assist the clinician with the latter.
The IVF has a simple appeal in terms of functional VF status, since it is a measure of binocular sensitivity and thus represents a patients functional field of view. Furthermore, IVF sensitivity is easily calculated directly from output of monocular sensitivities: It is the highest of the left and right monocular sensitivity values. The IVF has been shown to provide accurate predictions of binocular VF sensitivity in patients with glaucoma, so it can be considered a suitable measure when evaluating patients disability in terms of activities of daily living and quality of life. Of course, the IVF cannot provide an estimate of field loss beyond the central areas tested with either 24-2 or 30-2 HVFA, but evidence that peripheral constriction occurs in isolation from central defects in glaucoma is vague.40 Our retrospective examination of a large group of patients with bilateral glaucoma indicated that peripheral constriction rarely occurred (Viswanathan AC et al. IOVS 1998;39:ARVO Abstract 2270).
The relationship between VF loss and driving accidents has not yet been established with any certainty, due in part to the poor methodology of studies investigating this relationship, although the better the methodology, the stronger the link between VF defects and crashes.41 It has been shown that involvement in crashes for older drivers is significantly predicted by binocular VF loss, but not by monocular field loss.42 Other factors contributing to the inconclusive association between VF loss and driving accidents include the tendency for drivers to compensate for poor vision and change their behavior43 and findings that the determinants of accidents are multifactorial, including cognitive and perceptual skills as well as visual function.44 However, standards for VF loss, along with visual acuity, remain the criteria by which the vision component for legal fitness to drive in the United Kingdom is assessed.
In summary, losing ones drivers license is a significant and adverse milestone on the way to functional blindness in progressive glaucoma; 20% of patients in our dataset failed the DVLA VF criteria at some point during follow-up. The development of the IVF should make it possible for clinicians (and others) to start integrating binocular considerations into the diagnosis and management of patients in a user-friendly and clinically valid way. The status of the binocular IVF at presentation and the rate of binocular IVF sensitivity loss may help identify patients who could benefit from intervention or intensified treatment, thus avoiding this milestone to blindness. Furthermore, the rate of IVF loss may provide a way of helping identify those who do not need treatment.
| Footnotes |
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Supported by an unrestricted educational grant from Pfizer Inc. (VMFO and DPC) and the Moorfields Eye Hospital Special Trustees (VMFO and DPC).
Submitted for publication July 12, 2007; revised December 5 and 13, 2007; accepted March 28, 2008.
Disclosure: V.M.F. Owen, None; D.P. Crabb, None; E.T. White, None; A.C. Viswanathan, None; D.F. Garway-Heath, Carl Zeiss Meditec (F, C, R) and Heidelberg Engineering (F, R); R.A. Hitchings, None
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: David P. Crabb, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB, UK; d.crabb{at}city.ac.uk.
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