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Standard automated perimetry, which tests the visual field with a white stimulus against a white background (W-W perimetry) detects a visual field defect when about 40% of the retinal ganglion cells (RGCs) have been lost. It is preferable to detect damage at earlier stages of ganglion cell loss, given the irreversible nature of vision loss in glaucoma.
Different psychophysical strategies have been developed in an attempt to detect glaucomatous field damage at earlier stages. The use of a blue stimulus against a yellow background and a flicker stimulus are two such strategies. They test specific mechanisms within the visual system. Although they may be able to detect earlier loss, they have limitations. The standard W-W perimetry remains the method of choice for following visual fields over time for progressive damage.
Blue on yellow perimetry
Blue-on-Yellow Perimetry (B-Y), also known as Short Wavelength Automated Perimetry (SWAP), can detect early visual field loss before a reduction in differential light sensitivity is seen with standard white-on-white (W-W) perimetry.
Principle
There is an association between glaucoma and short-wavelength (blue) color vision deficits. Sensitivity to blue stimuli is mediated by a subpopulation of retinal ganglion cells with large receptive fields, little overlap in receptive field, and with large axons. These small bistratified ganglion cells connect to the koniocellular pathway in the lateral geniculate ganglion. These cells make up only 5-10% of all retinal ganglion cells. Blue on Yellow perimetry isolates and tests these sparse cells, which are thought to be lost early in glaucoma, thereby detecting glaucomatous retinal ganglion cell death/dysfunction earlier than W-W perimetry, which tests all retinal ganglion cell populations.
Theoretical basis of blue on yellow perimetry
Schematically, the process of seeing can be represented by a system where the rod and cone receptors pass visual signals onto a series of ganglion cells specifically sensitive to differing light stimuli. In glaucoma, certain ganglion cell types may lose their function before others do. Approximately 80% of the ganglion cells are parvocellular P type cells, sensitive to color and contrast; 5% are koniocellular K cells, responsive to blue-yellow opponents; and 15% are magnocellular M (My) cells that react to temporally modulated stimuli. Testing can be optimized to detect the particular function of each population of cells. In SWAP, a yellow background light bleaches or suppresses the red and green cones while blue cones are stimulated by a blue stimulus.
In the 1950s, pioneering work was done by Stiles that provided a means of psychophysically isolating and measuring the sensitivity of individual color vision mechanisms through a two-color increment threshold procedure. The approach involved decreasing the sensitivity of some color vision mechanisms (termed π mechanisms by Stiles) using a chromatic adapting background light, and then measuring the sensitivity of another color vision mechanism by means of a narrow band chromatic stimulus. According to Stiles’ terminology, π0 refers to the sensitivity of the rod system, π1, 2 and 3 are short wavelength (“blue”) sensitive mechanisms, π4 is a middle wavelength (“green”) sensitive mechanism, and π5 is a long wavelength (“red”) sensitive mechanism. Isolation of π1, the principal short wavelength (“blue”) sensitive mechanism, was best achieved with a high luminance (greater than 50 cd/m2) white or broad spectrum yellow background (530 nm short wavelength “cutoff” filter) and a large (greater than 2 degrees in diameter) narrow band (440 nm peak wavelength with a 10-20 nm bandwidth) short wavelength stimulus. The figure shows the spectral sensitivity of three color vision mechanisms (π1, π4, and π5) under normal viewing conditions on the left graph. The vertical blue line indicates the peak of the short wavelength mechanism and the vertical yellow line indicates the peak wavelength of the background. The graph is plotted in a threshold versus wavelength format, in which the background chromaticity and luminance are constant, the stimulus wavelength is varied and the stimulus increment threshold is determined. Note that under these conditions, sensitivity to a short wavelength stimulus is higher for the middle and long wavelength systems than for the short wavelength system. The graph to the right shows the same spectral sensitivity profile in the presence of a bright broadband yellow background. Here one can observe that there is substantially decreased sensitivity for the middle and long wavelength mechanisms, thereby permitting the short wavelength mechanism’s sensitivity to be isolated and measured.
Blue on yellow perimetry has adapted this procedure that isolates and measures the short wavelength sensitive mechanisms for automated perimetric testing. Initially, normal aging effects were found to influence test results, more than in standard automated perimetry. Some of these aging effects were due to due to optical factors (for example, cataracts) and some were due to neural losses. Subsequent investigations found that normal aging effects were essentially equivalent for all visual field procedures if dynamic ranges are taken into account. It has also been reported that there are learning effects that occur for blue on yellow perimetry, as for standard white on white perimetry.
Wild et al reported that during initial examinations care should be taken to ensure that apparent field loss with blue on yellow perimetry in patients exhibiting a normal field by standard W-W perimetry is not the result of inexperience in Blue on yellow perimetry. Apparently, deeper or wider field loss in initial B-Y perimetry examinations compared with that exhibited by standard W-W perimetry in open angle glaucoma may arise from inexperience in B-Y perimetry.
Machine settings
For the background illumination, a broadband yellow filter (OG530 Schott filter – a 530 nm short wavelength cutoff filter) is used at a luminance of 100 cd/m. For the stimulus, a large Goldmann Size V (about 1.7 degrees diameter) light with a narrow band short wavelength interference filter (440 nm peak transmission, with a 15 nm bandwidth) and a 200 millisecond stimulus duration is used. With these specifications, the system reaches perfect isolation of the blue cones resulting in a dynamic range between 18 dB at the fovea and 12 dB at 20° eccentricity. Except for the different background and stimulus color, blue on yellow perimetry is still a basic threshold test in which standard Goldmann stimuli are presented in the conventional way. Blue on yellow perimetry is currently available on several commercially available automated perimeters (along with a normative database and statistical analysis package), include the Octopus perimeters (311) and Humphrey Field Analyzer II (Model 700 and higher).
Studies on blue on yellow perimetry
Various studies have documented the role of Blue on yellow perimetry in the early diagnosis of glaucoma and in the detection of visual field loss earlier than standard automated perimetry with a sensitivity and specificity ranging from 88 percent and 92 percent, respectively.
Johnson et al in their longitudinal study of individuals with ocular hypertension reported an association between the prevalence of localized Blue on yellow perimetry visual field defects and the development of glaucomatous field loss. They concluded that blue on yellow perimetry deficits are an early indicator of glaucomatous damage and are predictive of impending glaucomatous visual field loss for standard W-W perimetry.
Sample et al concluded from their studies that foveal blue and yellow color vision deficits are present in individuals with ocular hypertension and glaucoma and that these deficits appear to be early indicators of glaucomatous damage.
Johnson et al showed that abnormalities detected by Blue on yellow perimetry in patients with early glaucomatous loss are typically larger than corresponding defects detected by SAP. The rate of short wavelength sensitivity loss is also greater in patients who demonstrate progression in their visual field loss as compared with stable visual fields. Progression of defects found with W-W perimetry tends to be observed in areas having a subnormal sensitivity in the Blue on yellow perimetry, years earlier. They concluded that blue on yellow perimetry is thus a sensitive device to monitor patients with early glaucomatous damage and to detect or predict which patients are likely to have progressive loss of visual function as manifested by the standard W-W perimetry.
Johnson et al in a longitudinal and prospective study of individuals with ocular hypertension also observed an association between the prevalence of Blue on yellow perimetry visual field defects and other risk factors predictive of glaucomatous field loss. The combined information derived from Blue on yellow perimetry results and optic disc evaluation may provide the most relevant information in determining whether a suspect is likely to develop glaucomatous field loss.
Mansberger et al concluded that many patients with large C/Ds have normal standard W-W and Blue on yellow perimetry results. Compared with standard W-W, Blue on yellow perimetry results were abnormal in a higher percentage of these patients. If a patient has a large C/D and normal standard W-W results, Blue on yellow perimetry testing may detect functional loss earlier. If glaucoma is defined by both structural and functional loss, patients with large vertical C/Ds, normal standard W-W results, and abnormal Blue on yellow perimetry results may have glaucoma. Longitudinal studies are needed to assess this hypothesis and determine whether these patients subsequently develop abnormal standard W-W results as well. In their study of 86 patients with large C/D ratios, they published that standard W-W and Blue on yellow perimetry results were abnormal in 44 (51%) and 52 (60%) of 86 patients, respectively. In patients with normal standard W-W results, Blue on yellow perimetry results were abnormal in 14 (33%) of 42 patients. In patients with normal Blue on yellow perimetry results, standard W-W results were abnormal in 6 (18%) of 34 patients.
Ferrara et al assessed the ability of short wavelength automated perimetry and frequency-doubling technology (FDT) perimetry to detect glaucomatous damage in preperimetric glaucoma subjects. Their results showed that at least 20% of the patients with preperimetric glaucoma demonstrated functional losses in FDT and SWAP. The more severe the structural damage, the greater the sensitivity for detecting glaucomatous visual field losses.
Recently, several laboratories have examined the relationship between Blue on yellow perimetry deficits and structural deficits produced by glaucoma, thereby enhancing our knowledge of the basis for glaucoma pathophysiology
Advantages of blue on yellow perimetry
Longitudinal investigations performed at several different laboratories have demonstrated that blue on yellow perimetry is able to identify glaucomatous visual field deficits earlier than standard (white-on-white) automated perimetry. Deficits on SWAP are seen in approximately 20-25% of patients at risk of developing glaucoma who have repeatedly normal visual field results for standard automated perimetry.
Blue on yellow perimetry has increased sensitivity for detecting glaucomatous visual field loss with no loss in specificity. Visual field loss patterns correspond to what would be expected with glaucomatous retinal nerve fiber bundle deficits. However, the size of defects on Blue on yellow perimetry are usually larger than those observed for standard automated perimetry and progression of Blue on yellow perimetry deficits is typically greater than for standard automated perimetry.
Perhaps the greatest advantage of Blue on yellow perimetry is that it is able to predict the onset and location of future glaucomatous visual field deficits for standard automated perimetry by 3-5 and possibly 10 years earlier.
Disadvantages
There are a number of disadvantages to blue on yellow perimetry. Test results are more variable than with standard automated perimetry, they are affected by the absorption properties of the crystalline lens, and it is more difficult for some patients to perform. However, these disadvantages do not detract from the clinical value of Blue on yellow perimetry, and methods have been developed to account for some of these disadvantages.
One of the shortcomings associated with the commercial version of Blue on yellow perimetry is the length of time required to perform testing. Typically, Blue on yellow perimetry testing is 2-3 minutes longer than the Full Threshold procedure for standard automated W-W perimetry, creating test times of 15-20 minutes per eye. It also takes the patient two to three minutes for adaptation to the yellow light. This shortcoming has been rectified by utilizing fast threshold strategies.
B-Y perimetry shows large intersubject variability and cluster analysis becomes more important for detecting early changes. Both the intra and inter test variability characteristics have been studied and the current consensus is that Blue on yellow perimetry has higher variability than conventional perimetry, which makes it difficult to determine if there is progression. Various studies have found 25-30% greater short term fluctuations with Blue on yellow perimetry than standard W-W perimetry.
Full threshold vs fast threshold strategies
Blue on yellow perimetry using a fast threshold strategy has been reported to provide sensitivity for detection of glaucomatous visual field loss that is highly similar to the Full Threshold Blue on yellow perimetry approach. Also, the variability of fast threshold Blue on yellow perimetry, both within and between subjects, was found to be equal to or less than that observed for the standard Blue on yellow perimetry procedure.
Additionally, the fast threshold Blue on yellow perimetry procedure has been reported by two independent laboratories to have 4-5 dB of increased sensitivity for each test location, when compared to the standard Blue on yellow perimetry procedure. This has the advantage of increasing the dynamic range of Blue on yellow perimetry, which makes it possible to monitor damaged visual field areas in a better manner, which is a distinct benefit in view of Blue on yellow perimetry.
The fast threshold Blue on yellow perimetry identified at least as much glaucomatous visual field loss as the older full-threshold Blue on yellow perimetry, although test time was considerably reduced. Conventional standard white on white perimetry using fast threshold strategy was not significantly less sensitive than either of the 2 Blue on yellow perimetry programs.
Limitations
- High inter-individual variability and longer learning curve
- Influence of nuclear sclerosis – Occurrence and increase in the grade of nuclear sclerosis may lead to a false appearance or falsely appearing progression of visual field defects on Blue on yellow perimetry
- Patient fatigue and long adaptation time
- The frequency-of-seeing curve (FOSC) for B-Y perimetry is relatively flat causing an increase in the variability of the threshold. The bright yellow background is very intense and the blue stimuli are hard to perceive.
Comparison between blue on yellow perimetry in octopus and humphrey
With 18dB, Octopus has a larger dynamic range for Blue on yellow perimetry than Humphrey with the same size target and background illumination.
References
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