Ординатура / Офтальмология / Английские материалы / Artificial Sight Basic Research, Biomedical Engineering, and Clinical Advances_Humayun, Weiland, Chader_2007

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Question 3: “Are you playing video games in your spare time?” targeted the possible superior hand-eye coordination of such a person. Subjects 2 and 3 responded affirmatively, so the difference under question 1 is equally (un)likely to be related to this activity.

Questions 4 and 5 asked for descriptions of the subjects’ techniques for the counting and checker-placing tasks. Table 4.1 provides the answers as written by 4 subjects; subject 3 chose not to answer these two questions. The answers show that every subject developed his/her own method.

Question 6: When asked what would make a very difficult board, all subjects indicated that the difficulty level rises with the increasing number of white squares, and is attributable to the increasing difficulty of placing the checkers without moving previously placed ones. They also indicated that squares in the corners are hard to detect and that a diagonally adjacent squares increase the difficulty level.

Figure 4.10 shows the board-designs used in the experiments.

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established featuring new visual properties. We cannot expect this new system to behave in a manner fully analogous to the natural system, nor can we assume that a technical device in a biological environment will perform as predicted on technical requirement specification sheets. For this reason it is indispensable to develop a specialized set of tests for evaluating visual functions in patients with an AVD.

In this chapter, we will briefly review standard methods to assess visual functions and their limitations for testing patients with AVDs. Next we will describe the theoretical concept of a new test design based on three main pillars. These pillars will then be discussed in detail and actual implementations for each subtest will be presented.

Testing Visual Functions in Normal Individuals and its Limitations in AVD

Tests used today for assessing natural vision are designed to measure psychophysical thresholds for specific subfunctions like light sensitivity and resolution, or they qualitatively assess functions like stereopsis or certain color vision tests. The most widely used method to describe visual function is visual acuity testing. This test gives a fast first impression about the integrity of the entire system, as it depends on the proper function of optic, sensory, and neuronal systems. Visual acuity is the measurement of the ability to discriminate two stimuli separated in space at high contrast relative to the background. Different charts and characters can be used, and the test result can be expressed with various types of measurements like Snellen notation, logMAR, decimal acuity, or log (decimal acuity) = −logMAR [1, 2]. Some specialized tests for the assessment of very low vision have also been developed (e.g. LoVE [3]).

The visual field can be examined using either static or kinetic perimetry. The first of these presents small light stimuli on a hemisphere with various degrees of eccentricity from the center. By changing light intensity the threshold of perception for each individual spot can be determined. Kinetic perimetry uses a moveable light point that is gradually shifted from the far periphery into the center. The eccentricity is recorded at which the patient can first see this target. This procedure is repeated for several directions, light intensities, and target sizes. Thus rings of equal light sensitivities (“isopters”) are determined. Prerequisite for useful test results are good compliance of the patient and stable fixation of gaze on a central target.

Electrophysiological examinations are capable of detecting fluctuations in locally measured electrical potentials generated by neural activity. Depending on the positioning of electrodes and test procedures, different functional elements can be tested. The electroretinogram (ERG) detects light-evoked potentials generated in the outer retina (a-wave) and inner retina (b-wave) [4]. Inner retina function can be assessed by the pattern ERG [5].

Visually evoked cortical potentials (VEP) can be detected as responses of the visual cortex to a visual stimulus [6]. Area V1 of the brain is responsible

for primary image processing. VEPs recorded over this site can help to detect whether the information of a visual stimulus is perceived and processed in the brain. In animal models, variations on this technique employing multielectrode recordings are widely used to confirm that electrical stimulation by an AVD elicits a response in the visual cortex.

A variety of additional tests exist, e.g. to evaluate contrast or glare, to measure the range of accommodation, to test binocular functions and stereopsis, to test the light reflexes of the pupil, and to measure the ability of the sensory system to adapt to darkness (Table 5.1).

Additional experimental setups exist to assess qualities such as temporal resolution or perception of motion. For severely visually impaired subjects, it is of particular relevance to be able to evaluate their performance in routine activities encountered in daily life, but no widely accepted standard routine exists for this task.

All of the tests mentioned above have certain limitations when applied to the assessment of visual functions in patients with visual prostheses. The way stimulation is performed with electronic devices differs from physiological stimulation, e.g. via neurotransmitters. In the natural system information about color, contrast, fluctuation of brightness over time, motion, and additional characteristics are encoded at the retinal level. This coded information is relayed to the brain and analyzed there [7, 8]. AVDs, however, will encode this information in a different way. Consequently there will be input to the visual cortex that is somewhat different from that experienced earlier in life. In addition to this

Table 5.1. A sample of tests used for assessing visual functions.

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different modulation of information, there are limits to the information that can be provided by AVDs. Most of the AVDs have a limited number of stimulation electrodes. For retinal prostheses they range from about 4 to 1500 electrodes. Even with this limited number of stimulation sites, however, one should be able to generate useful vision, as some studies have demonstrated [9, 10].

For these reasons, a test designed to evaluate visual functions in patients with visual prosthesis must meet special requirements that may differ from those that apply to natural vision.

Designing a Test for Visual Functions with Visual Prostheses

When defining specifications for a new test design, some universally valid or general specifications must be considered first (Table 5.2).

The test has to be reliable and meaningful with a high test–retest reproducibility. Furthermore, the test should be as objective as possible, minimizing investigatoror patient-driven bias. It has to be sensitive enough to detect even small changes in visual performance. Finally, it must be valid, i.e. it should really measure what it claims to measure, which is a basic demand any test has to meet and to prove.

There are additional, more specific requirements due to the nature of the human–machine interface (see Table 5.2). Up to now visual prostheses are not able to restore natural vision. The impression a person gets from an artificial

Table 5.2. Requirement specifications for a new test.

vision system will still be somewhat different from what that person experienced with natural sight. With this in mind, a new test must test functions that are relevant to the patient. In other words, it should not simply measure technical specifications, but rather reflect the patient’s benefit in daily living.

As the development of technical devices for artificial vision is still at the beginning, the first devices under clinical investigation may provide quite basic visual impressions like perception of light or movement of light. For a blind person even the simple ability to gain orientation by being able to localize light sources like windows or doors can mean a substantial improvement in mobility and self-determined life. As the development of these devices proceeds, there is good reason to expect further improvements. Thus, a new test has to cover a wide scope of visual functions, including very basic visual perceptions (see Table 5.2).

With a view to ongoing developments, new tests must be designed to provide a better understanding of the properties of the human–machine interface and functions of the device. They must provide substantial data about the properties of the human–machine interface and the technical data needed to allow the enhancement of the next generation of devices.

A test aimed at characterizing visual abilities provided by AVD should be suitable for generic use. Different prostheses that are under development so far use a variety of coupling methods to connect to the biological system. Devices for epiretinal and subretinal coupling as well as for stimulation of the optic nerve and cortex are being developed [11–15]. All these approaches have special benefits and technical or biological and surgical limitations. A new test should not be tailored to the specific features of one individual prosthesis design, but rather be suitable for generic use. This will facilitate comparability of the functional results of different technical approaches in humans.

Implementation of a New Test Battery

The specifications listed above provide the basis for developing a new test design. However, the demands for a new test may be conflicting to some extent. For example, a test designed for evaluating visual performance may be highly objective and reliable, but may not be suitable for assessing how well a device facilitates everyday activities. Conversely a setup for testing performance in daily activities may show deficiencies in objectivity and validity, because such tests by their very nature are subjective and influenced by habituation to the test.

To approach this problem of conflicting requirements a battery of sequential tests may be advantageous. Individual tests are designed to provide partial information focused on one main topic. The synopsis of this battery of tests will provide sufficient information about the efficacy of an AVD in severely visually impaired patients as well as information needed for further development.

Figure 5.1 illustrates schematically the concept of a set of tests based on three different methodological approaches.

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Figure 5.1. Test battery design consisting of three main pillars to address conflicting requirements. These pillars are 1st: a set of psychophysical tests, 2nd: a set of tests to estimate performance in tasks of daily living, 3rd: a set of questionnaire to address subjective perception.

The first pillar is based on classical psychophysical testing utilizing and extending regular clinical ophthalmologic tests. These tests can be highly standardized, and examiner and patient bias can be minimized. Thus this pillar of the test design mainly contributes to good reliability, validity, and objectiveness of the whole set of tests. However, this kind of tests could turn out to be the least relevant ones in terms of the needs of a patient in coping with everyday life.

The second pillar therefore consists of a setup for testing performance in everyday tasks. This should consist of tests that are as close to real conditions as possible to be relevant, but as “artificial” as needed to be well standardized. As AVDs may provide visual impressions that are different from natural vision, this test is highly important to gain an estimate about the efficacy of such devices in supporting blind patients in leading a more independent life. Testing performance in activities of daily life is not a well-standardized task and there are some methodological obstacles. As there is no direct physical correlation that can be measured, the test has to rely on indirect measuring techniques. The patient himself, or better in cooperation with an experienced, independent mobility trainer, has to give an assessment of performance in this test. As this proceeding is prone to reasonable subjectivity by nature, strategies to control this handicap gain great importance. These strategies include a double-blind or placebo-controlled test design as well as the use of standardized subjective scales rather than free descriptions or even narrations of the patient.

The third pillar of the test battery is meant to get direct information about the impressions and constitution of the patient while carrying an AVD. While testing specifications and performances of visual functions with visual prostheses, it is important to evaluate the subject’s well-being and its implications for test performances. Strong expectation as well as anticlimax or even dysthymic conditions may influence the outcome of the tests and must be controlled. Furthermore information must be recorded about the particular impression using an AVD, about special sensations or discomfort. This information can be provided only by the patient himself and must be addressed in specialized questionnaires. Undoubtedly this pillar is the most subjective one and, when designed to detect short-term fluctuations in psychological conditions, it may not be of high reproducibility, though it is of high reliability.

Test Battery Pillar One: Psychophysical Testing

Since a wide range of visual functions has to be covered, we propose a battery of psychophysical tests with increasing demands on visual performance. At least for the first series of clinical trials presently underway, in most cases, only blind patients can be included, and special consideration must be taken in testing the remaining with very low vision. Even in most blind people some residual visual functions can be noted. If routine methods for assessing visual functions fail, there is a fallback to less standardized methods to categorize remaining functions. Patients are then asked in clinical practice to count fingers held in front of them, or to detect hand movement at a defined distance in front of the patient’s face, and it is noted whether the patient can recognize movement or the direction of movement. Finally a bright light beam is directed into the eye and light perception from different directions is evaluated. These commonly used clinical examinations lack standardization, as ambient light, distance, and dimensions of the hand and fingers, as well as the brightness of the light source may be subject to considerable variations.

There is a need for more sensitive and more standardized methods for evaluating these very low visual functions. In analogy to clinical testing we propose a computerized test that is capable of assessing four basic visual qualities. These are light perception, temporal resolution, location of light, and detection of motion. We developed a software and a technical setup, called the “Basic Light and Motion (BaLM) test,” that will be described later on in detail.

With increasing visual performance, additional tests assessing resolution of the visual system are needed. As can be seen in Table 5.3, we propose a three-level procedure. The very basic routine is provided by the BaLM test (level 1) and higher performances can be tested with standardized techniques for determining visual acuity (level 3). However, there might be a gap between these two levels, leaving an area of uncertainty in the case where a patient easily passes the BaLM test, but cannot recognize correctly even large optotypes. This scenario is not unlikely, as various situations can be imagined when resolution gained with artificial vision is sufficient for determining a large optotype, but the patient is

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Table 5.3. Elements of psychophysical testing.

still not able to recognize it. Distortion due to various reasons might be one obstacle. Another possible situation that must be considered in which resolution and recognition do not match is the generation of a patchy visual impression. AVDs do not necessarily create a visual image that covers one contiguous area. Rather a kind of patchwork of seeing and not-seeing areas may be present within a certain area with restituted functions. Nevertheless, it is important even in these situations to gain valid information about the resolution and visual acuity an AVD could provide under optimal conditions.

For this reason we suggest a grating acuity test as a second level of psychophysical testing. These tests are well known for determining optical transfer functions of optical devices and use patterns with black and white lines with different spatial frequencies. Certain limitations of this test method in the human visual system are well known and will be discussed later on in detail.

Psychophysical testing can be completed by a standardized test for measuring visual acuity, as in the Freiburg visual acuity and contrast test (FrACT) (see <http://www.michaelbach.de/fract.html>. This is a fully computerized test to estimate the psychometric threshold.

All three of these tests can be performed sequentially, using one common platform, i.e. a computer with a customized display.

Electrophysiological tests in clinical trials of AVDs are of limited value. Their principal application is in experimental animal testing. Measuring the ERG may demonstrate the ability of an AVD to generate electrical potentials at a retinal level or prove function and integrity of the device by recording electrical pulses delivered by an AVD under biological conditions. This is suitable only for retinal prostheses, and even in this case the conclusions from these results may be of limited value.

The VEP can measure activation of the visual cortex after stimulation by an AVD. However, this examination is not necessarily correlated with a useful visual impression. For this reason we expect electrophysiological tests to be of low validity and relevance in clinical trials and would not suggest using them as a tool to determine the efficacy of such devices.

Technical Setup for Psychophysical Testing

All three psychophysical tests mentioned above are computerized tests. Herein we describe a technical implementation as it has been used for evaluating Basic