Visual Field Testing Background

Many eye care practitioners would agree that glaucoma is difficult to confidently diagnose in a single visit. Open angle glaucoma usually presents as a symptomless condition and manifests itself gradually. The doctor must combine several tests including history, visual fields, intraocular pressure, gonioscopy, optic nerve head analysis and nerve fiber layer analysis to make the correct diagnosis. Sometimes a patient is followed for years before a decision to treat is made. Conversely, a patient may present for the first time with extensive vision loss that should have been prevented long ago. Along with glaucoma, many other ocular diseases can lead to visual field loss. The main goal of the practitioner is to preserve as much of the patient's visual field for the rest of his or her life. As such, one of the key tests to this goal is visual field testing, or perimetry.

Early visual field tests conducted over a century ago were based mainly on kinetic stimulus presentation ­ that is, a response to a moving peripheral stimulus was made while the patient looked straight ahead at a stationary fixation point. The classic Tangent Screen and Goldmann Bowl Perimeter are good examples and are still used today in certain practice situations.

Goldmann Bowl Perimeter Shown on Left; Illustration of Goldmann Testing Shown on Right

Other variations on the kinetic perimeters include the arc and auto tangent screen perimeters.

As computerized, automated visual field testing became more popular, various companies such as Zeiss-Humphrey, Dicon, Synemed, Medmont, Oculus, Kowa Optimed, and InterZeag utilized static "white-on-white" stimulus presentations (e.g., a white light of various intensities is flash-presented in numerous areas on a uniform white background). This has resulted in highly quantifiable, sensitive visual field results.

Newer test algorithms have resulted in testing strategies such as:

SWAP (Short Wavelength Automated Perimetry) or "blue-on-yellow" perimetry (Humphrey) ­ This method presents blue static stimuli on a uniform yellow background, intended to test a smaller population of retinal neurons that selectively respond to those color wavelengths. The test is thought to potentially reveal visual field loss 5-6 years ahead of traditional white-on-white automated perimetry, but it requires a significantly longer testing time.

FASTPAC, SITA (Swedish Interactive Testing Algorithm) Standard, SITA Fast (Humphrey) ­ These tests use "intelligent" analysis of the patient's responses and age-normed statistical data to significantly shorten the testing time. There may be some limitations in terms of analysis of field loss progression, as well as limitations on the number of missed point re-tests, but statistical correlation with traditional threshold testing is good.

Kinetic Fixation Perimetry (Dicon) ­ A feature unique to these perimeters is that the patient is constantly looking at a moving fixation target during testing, which has been found to make the visual field testing more comfortable for the patient.

Multiple Stimulus Presentation (Dicon) ­ One to four stimuli are presented at a time, requiring the patient to respond one to four times, respectively. Meant to speed the visual field testing, it is not used regularly for most patients.

Examples of some contemporary automated visual field analyzers. From left to right: Dicon Autoperimeter, Oculus Easyfield, Zeiss-Humphrey Field Analyzer II

Frequency Doubling Theory

The human retina has approximately 1.2-to-1.5 million neurons (also called retinal ganglion cell axons or nerve fibers) that bundle together to comprise the optic nerve. The irreversible loss of these retinal nerve fibers occurs in glaucoma and other ocular conditions, associated with the classic gradual increase in optic nerve "cup" size over time. Some studies have suggested that up to 40 percent of these retinal nerve fibers could die before any notable visual field loss is found, so the patient may be unaware of any visual problem. It may take an average of 4-6 years of gradual nerve fiber loss before varied amounts and patterns of glaucomatous visual field loss become apparent.

Retinal nerve fibers can be simply classified into two main types that transmit signals from the retinal receptor cells by way of the optic nerve to the lateral geniculate body and ultimately to the visual cortex. These are the Magno-cellular (or M) cells, and the Parvo-cellular (or P) cells.

The M-cell pathway is responsible for low-contrast, high temporal frequency (or motion) stimulus detection. For example, a black car rapidly passing by a driver's side window at night may stimulate the driver's M-cell neurons. The P-cell pathway is responsible for high-contrast, low temporal frequency (or static) stimulus detection. An example would be a patient attempting to read the smallest letters possible on a standard projected Snellen eye chart.

The larger diameter M cell neurons constitute approximately 10% of the total number of retinal nerve fibers. It has been found that a particular M-cell neuron sub-set comprising a third to a half of the M-cell neurons (called "non-linear" M-cells) are usually the first to die in glaucoma, and this unique pathological characteristic established the basis for frequency doubling testing.

When a low spatial frequency sinusoidal grating with alternating wide light and dark bars undergoes high temporal-frequency counterphase flicker, (i.e., the black bands reverse to become white and the white bands reverse to become become black in rapid sequence) the grating appears to have twice as many light/dark bars (i.e., its spatial frequency appears doubled) as shown in the example below. This phenomenon is called the frequency doubling illusion:

High frequency (e.g., 20-30 Hz) alternation between light and dark bars (e.g., 1 cycle per degree) shown on the left two images creates the doubling illusion (2 cycles per degree grating) shown on the right image. (One cycle = light + dark bar.)

It is the vulnerable "non-linear" M-cell neurons that are thought to transmit signals related to this illusion. Since these M-cell neurons tend to be among the first to die, selective testing by presenting alternate grating stimuli was developed to attempt to identify earlier retinal neuron loss than by traditional automated perimetry. This resulted in development of the Frequency Doubling Technology (or FDT) Perimeter by Humphrey/Welch-Allyn/Zeiss.

Frequency Doubling Perimeter

Frequency Doubling Testing

The Frequency Doubling Technology (FDT) Perimeter is a portable device that specifically tests for visual field loss due to non-linear M-cell neuron death, typically from glaucoma. Since this instrument targets a specific sub-set of nerve fibers that transmits larger, low-contrast, motion-based stimuli rather than detailed, high-contrast static stimuli, FDT perimetry will tolerate up to 6 diopters of blur and is not affected by external room illumination or variations in the pupil size, so long as the pupil diameter is greater than 2 mm.

The device is relatively easy to use with a series of menu screens that allow selection of the test to be conducted (e.g,, screening versus threshold), the age of the patient, report printing, etc. Instructions to the patient are also quite simple: look at a black dot in the center of the screen and press a button any time a grating pattern is seen. During the test, a 5-degree square pattern is presented at a total of 17 different locations within the central 20 degree by 20 degree visual field.

Test options include a a screening field (Screening C-20) in which 5-degree gratings with three contrast levels are show at 17 locations in the central 20 degree field. Results are reported based on how much contrast is required for the patient to detect the grating.

FDT screening mode perimetry is considered abnormal when the following are present:
Any defect in the central five locations
Two mild or moderate defects in the outer 12 squares
One severe defect in the outer 12 squares
Screening test time greater than 90 seconds per eye

There are also two full threshold test options: Full Threshold N-20 and Full Threshold N-30. Using these options, the FDT uses more contrast levels to search for the patient's threshold at each of the locations tested. Again, each grating is 5 degrees square, but in the N-30 test the horizontal area tested is extended to include an extra portion of the nasal visual field, resulting in a total 30 degree horizontal field.

The sample printout below shows actual threshold levels in dB for each location tested and an age-referenced deviation chart on which symbols are used to indicate how likely it is that a normal patient would have that threshold level. These probabilities are shown as p values with smaller values indicating that smaller percentages of the normal population would have the corresponding threshold.

Example of FDT Printout

The FDT perimeter uses central static fixation with classic Heijl-Krakau (blind spot) fixation checks. Defects are noted as varied gray scale depths called probability symbols. The darker the depth of gray, the less probable (based on age-related norms) that the defect is a normal occurrence. As seen in the printouts above, probability varies from 5% (somewhat unlikely that the defect is normal) to <0.5% (very unlikely that the defect is normal).

Reliability indices (fixation errors, false positive errors, and false negative errors) are provided, as well as Mean Deviation (average deviation from a normal visual field based on age-related norm) and Pattern Standard Deviation Indices (a measure of how locations differ from each other in the overall field) for the threshold tests, similar to the indices provided with traditional automated threshold perimetry statistical analyses.

With high sensitivity and specificity for detecting visual field loss, the FDT perimeter shows great promise for relatively early and quick detection of glaucoma.

Case Examples

Case 1
A 57-year-old Caucasian male presented with a prior diagnosis of early glaucoma. Dicon Threshold Grid 76/30 Visual Field Testing showed diffuse, mild, arcuate areas of reduced sensitivity OD, and nonsignificant changes OS. Frequency Doubling Technology N-20 Threshold Visual Field Testing showed much greater visual field loss, with inferior arcuate pattern loss in each eye, right eye greater than left eye. The patient was subsequently placed on more aggressive treatment by adding a topical prostaglandin to his regimen.

Dicon Threshold Grid 76/30 Visual Field OD

Dicon Threshold Grid 76/30 Visual Field OS

FDT Threshold Visual Field

Case 2
A 30-year-old Hispanic male presented for a routine vision exam with no complaints. Frequency Doubling Technology C-20 Screening Visual Field Testing showed loss of his left visual field along a vertical line and a single point loss above the blind spot on his right eye. A Humphrey II 120-Point Neurological Screening Visual Field Test showed a bitemporal hemianopsia with central involvement of the left eye and mainly central sparing on the right eye. Immediate referral revealed a large pituitary adenoma on magnetic resonance imaging (MRI) and prompt surgery resulted in tumor removal with a successful outcome.

Humphrey Visual Field OD

Humphrey Visual Field OS

FDT C-20 Screening Visual Field

Case 3
A 62-year-old African-American male with history of stroke and a blind left eye due to long-term ischemic optic neuropathy. Frequency Doubling Technology C-20 Screening Visual Field Testing revealed an inferior arcuate-like visual field loss in the right eye which corresponded well with Humphrey II 120-point Neurological Screening Visual Field Test results. Fields could not be assessed for the left eye with either test. Dilated fundus examination revealed retinal vascular sheathing and a shunt vessel superiorly on the right optic nerve head, suggesting a prior superior branch retinal vein occlusion. These findings, along with an elevated blood pressure, prompted referral to a cardiologist, who noted hypertension and hypercholesteremia and modified the patient's treatment regimen accordingly.

Humphrey Visual Field

FDT C-20 Screening Visual Field

Frequency Doubling Versus Traditional Automated Perimetry

Although newer objective instruments allow a detailed, quantifiable means of determining retinal nerve fiber thickness, optic nerve cupping, ocular pressure, and retinal blood flow, there are still many variances in what is considered "normal" with these tests. In addition, a "normal" retina does not necessarily mean normal visual functioning. As such, the ultimate criteria for glaucoma is still functional retinal sensitivity loss. This functional sensitivity loss can only be determined by subjective measurement through visual field testing. Unfortunately, even automated perimetry can be a burden for both patient and the tester because threshold visual field testing can take what feels to the examiner and patient like an exceedingly long time.

FDT perimetry provides a much more rapid means of testing, reducing patient fatigue. However, even with this faster testing speed, FDT perimetry has been found to correspond closely to traditional white-on-white Humphrey 30-2 threshold visual fields with regard to detection of glaucomatous field defects.

Percent correlation to Humphrey 30-2 threshold visual fields has been found to be approximately:

82% sensitive and 95% specific for mild defects
96% sensitive for moderate defects
100% sensitive for severe defects

Some studies have shown that the Frequency Doubling Technology may not be more sensitive than conventional perimetry in certain situations, such as early peripheral glaucomatous visual field loss outside of 30 degrees and neurological defects that spare the central visual field. However, there does appear to be a strong correlation with conventional threshold perimetry for central glaucomatous field changes, and may be superior in identifying moderate to advanced glaucomatous visual field loss.

FDT Perimetry Benefits and Drawbacks

The FDT is easy to use for both operator and patient with very simple menus. However it tests only the central 30 degrees of vision.

Screening tests with the FDT take approximately 1 minute and threshold tests take only 3 to 8 minutes/eye. However, the FDT can miss neurological defects that obey the vertical midline and spare the central field.

The FDT will work well with refractive error blur of up to +/-6 diopters and room lighting is not significant a factor in testing. However, small (i.e., 5 degree or less) scotomas might be missed due to large stimulus targets.

The FDT is small in size and weight (15 pounds).

Summary
At this time, Frequency Doubling Technology perimetry may serve as a good screening tool. However, at the time of this article even the manufacturer does not advocate sequential threshold tests to monitor glaucoma on this device. As such Frequency Doubling perimetry should be used as an adjunct test for those practitioners who are managing glaucoma patients, and as a routine test for lower-risk patients.

In conclusion, Frequency Doubling Technology provides a unique, rapid means of evaluating visual field loss, particularly with the glaucoma population. Further hardware and software upgrades are likely to refine this form of visual field testing in the future. The simplicity and effectiveness of Frequency Doubling Technology will likely make it a powerful tool in the management of glaucoma patients for many years to come.

References

Frequency Doubling Technology Visual Field Analyzer User's Manual ­ Zeiss-Humphrey-Welch Allyn. 2001

Humphrey II Visual Field Analyzer User's Manual ­ Zeiss-Humphrey, 2000

Arango S, Trigo Y, Sponsel WE. Assessment of Glaucomatous Visual Field Loss by Frequency Doubling Perimetry Against Humphrey 30-2 Reference Standards. 1997 ARVO Abstracts/Invest Ophthalmol Vis Sci 38: S567

Cello KE, Johnson CA, Nelson-Quigg JM, Samuels SJ. Visual Field Indices for Frequency Doubling Perimetry. 1997 ARVO Abstracts/Invest Ophthalmol Vis Sci 38: S571

Chauhan BC, Johnson CA. Test-Retest Variability Characteristics of Frequency Doubling Perimetry and Conventional Perimetry in Patients with Glaucoma and Normal Controls. 1998 ARVO Abstracts/Invest Ophthalmol Vis Sci 39: S655

Johnson CA, Samuels SJ. Screening for glaucomatous visual filed loss with the frequency-doubling perimetry. Invest Ophthalmol Vis Sci 1997; 38: 413-425

Maddess T, Goldberg I, Dobinson J, Wine S, Jame AC. Clinical Trials of the Frequency Doubled Illusion as an Indicator of Glaucoma. 1995 ARVO Abstracts/Invest Ophthalmol Vis Sci 36: S335

Maddess T, Goldberg I, Dobinson J, Wine S, James AC. A psychophysical test based on the frequency-doubled illusion as an indicator of glaucoma. Joint european Research Meetings in Ophthalmology and Vision (JERMOV), Montpellier, 1996: 68- 69

Neahring RK, Wall M, Withrow K. Sensitivity and Specificity of Frequency Doubling Perimetry in Neuro-Ophthalmologic Disorders. 1997 ARVO Abstracts/Invest Ophthalmol Vis Sci 38: S390

Noriko Yamada, et al. Screening for glaucoma with frequency-doubling technology and Damato campimetry. Arch Ophthalmol. 1999;117:1479-1484

Quigley HA. Identification of glaucoma-related visual field abnormality with the screening protocol of frequency doubling technology. Am J of Ophthalmol Jun-98: 819-829

Schwartze G, Erb C, Rust A, Sistani F. A comparison of visual fields by frequency doubling perimetry and white on white perimetry in glaucoma patients. Department of Ophthalmology, Medizinische Hochschule Hannover Carl-Neuberg-Str. 1, D-30625 Hannover, Germany

Sponsel WE, Arango S, Trigo Y, Mensah J. Clinical classification of glaucomatous visual field loss by frequency doubling perimetry. Am J of Ophthal Jun-98: 830-836

Van Coevorden RE, Wang L, Mills RP, Stanford DC The Efficacy of Frequency Doubling Technology and Dicon Suprathreshold Screening in Detecting Visual Field Loss. 1998 ARVO Abstracts/Invest Ophthalmol Vis Sci 39:S26

Questions or concerns about courses should be directed to the individual authors and/or the Continuing Education Department at the College of Optometry at kundart@pacificu.edu.