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

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The software developed for this test is based on Macromedia Flash 7.0, allowing for usage on Macintosh, Linux, and Windows systems. It is designed to run self-paced, meaning that a sequence of tests runs automatically, advanced by the reaction of the patient. This minimizes bias due to interactions between investigator and patient.

Software Solutions: 1. BaLM Test

This test consists of a battery of four modules for perception of light, time, location, and motion. In a preferences screen, the variables of the four tests can be determined and the test can be calibrated to projecting distance and image size.

Upon starting the first subtest the program runs self-paced, requiring the patient to enter an alternative choice response via a numeric keypad. Most visually impaired subjects are familiar with a numeric keypad, and the central key is marked with a tactile prominence, so that this task can be handled easily. At the beginning of each test there is a short sound to prompt a patient’s response. After the patient has pressed the corresponding key, two different sounds are played to indicate either a right or a wrong response.

In the first test module the ability of detecting a single flash of maximal brightness is tested. After the initial sound a full-field flash appears, or the display stays black in a random fashion (maximal screen luminance in our setup is 5100 cd/m2, Michelson contrast of 99.5%). The patient has to indicate whether he has seen a flash or not. The duration of the flashes can be adjusted in the preferences screen. As some AVDs may perform better when stimulated with a high contrast pattern instead of a homogenous Ganzfeld-flash, there is an option to create a black-and-white checkerboard (3 check size). Luminance is varied using neutral density filters to estimate the individual threshold. Hit rate at different brightness as well as the stimulation parameters (Ganzfeld or checkerboard, number of trials) are recorded.

The second module is designated to test temporal resolution. After an auditory prime, one or two flashes are presented in a random fashion with constant timeintegrated energy. The patient indicates the number of flashes perceived. The duration of the flashes and the interval between them can be varied. The duration of the single flash is automatically adapted in accordance to the duration of the two flashes. This is necessary to avoid patients solving the test by determining the duration of the total light–dark–light phase rather than by actually detecting two single flashes. Hit rates and stimulation parameters (flash duration, interstimulation interval, Ganzfeld or checkerboard, brightness, and number of trials) are recorded.

Recognition of the localization of a light can be tested in the third module. A fixation target appears in the middle of the display, followed after a few seconds by a wedge-shaped bright field with its tip on the central fixation dot. The base is oriented in one of eight directions (up, down, left, right, and four obliques). Figure 5.3 shows a screenshot. The patient is asked to enter the direction, then a randomly chosen new direction is presented. The number of possible directions can also be limited to four (up, down, left, and right). Hit rates and stimulation

Figure 5.3. Example image of the localization test: First the fixation spot appears in the middle and will stay for the entire test. After a few seconds a wedge-shaped bright stimulus appears at one of eight directions, in this example on the upper left side.

parameters (size of fixation target, eccentricity of the wedge, brightness, number of trials, and number of choices) are recorded.

The fourth module tests the ability to detect motion (Figure 5.4). A random pattern of white and black hexagons is moving in one of eight directions (up, down, left, right, and oblique); again, the patient has to indicate the direction of movement. The size of the hexagons, the speed of movement, and contrast of the checkerboard can be adjusted. The black and white patterns are designed as hexagons to create a smooth appearance of motion even for oblique directions.

Figure 5.4. Example image of the motion test: random pattern of white and black hexagon moving to the right.

Figure 5.6. Gratings as seen by amblyopic patients. With increasing spatial frequency there is considerable distortion, but the main orientation can still be determined [18].

cortex responsible for detection of lines. Despite this distortion, these patients are able to detect the gross direction of the pattern, but they may not be able to detect single optotypes of a similar spatial frequency. Single optotypes bear only one discriminating characteristic that is related to a certain spatial frequency, e.g. the gap in a Landolt C, whereas in gratings this characteristic is repeated several times.

In testing visual functions in patients with retinal prostheses precisely, this feature of grating acuity can be valuable. Grating acuity can provide an estimate of the theoretical resolution that an AVD can provide, even if the individual black and white bars might appear to be distorted or interrupted. As mentioned before, these devices have a limited amount of stimulation electrodes and may create a field of view that is relatively small and possibly non-coherent or even patchy. In this case, single optotypes may not be well identified as they are distorted or might even not be seen as a whole entity.

We have developed a standardized computerized grating acuity test. The test is called “Basic Grating Acuity (BaGA) Test” and presented with the same setup described for the BaLM Test. A round pattern of variable size is presented on the display with a sine-wave grating with a spatial frequency of 0.1, 0.33, 1.0, or 3.3 cycles per degree (Figure 5.7). By using adequate gamma correction an equal mean luminosity of the test pattern and the background is assured. The grating is presented with random orientation in one of four directions and the patient is asked to indicate the orientation via the keypad.

Software Solutions: 3. Freiburg Visual Acuity and Contrast Test (FrACT)

The “Freiburg Visual Acuity & Contrast Test” (FrACT) assesses visual acuity and contrast sensitivity. It is a free computer program that uses dithering, anti-aliasing, and psychometric methods to provide automated, selfpaced measurement of visual acuity [19, 20]. It is used by many vision

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Figure 5.7. Main screen of the BaGA Test. Four different spatial frequencies (0.1; 0.33; 1.0, and 3.3 cycles/degree) can be chosen. In a preferences screen (not shown) stimulus distance, image size and gamma value can be adjusted. After each test hit rates and reaction times are displayed.

labs, optometrists, and ophthalmologists worldwide. FrACT complies with the European Norm for acuity testing EN ISO 8596. It is well established and has recently been demonstrated to provide accurate data even in patients with very low vision [21].

Analysis of Test Results

The BaLM and BaGA tests automatically calculate percentages of correct responses of each test, as well as mean reaction times for each test.

When analyzing individual performance in a psychophysical test, the psychometric function has to be considered [22, 23]. This function describes the correlation between rate of perception of a certain stimulus and strength of that stimulus. For the BaGA test this could be the number of correct responses as it correlates with the spatial frequency of the grating (compare Figure 5.8).

With increasing spatial frequency the number of correct responses will decrease until a basic plateau is reached. This plateau equals the guessing probability.

The psychometric function shows a turning point at which the slope of the curve is steepest. This means that at the turning point changes in the number of correct responses correlate to very small changes in spatial frequency. This is

Figure 5.8. Psychometric function. The rate of correct responses to a visual test in response to increasing demands like higher spatial frequency is shown. The curve demonstrates that there is no sharp transition between seeing and not seeing but rather an area of uncertainty. The inflection point of the curve where the slope is highest should be defined as the psychometric threshold.

the most sensitive point of the test. For this reason this point should be used to determine a psychometric threshold, as it ensures a good reliability of this test.

The psychometric threshold can be estimated as the mean between guessing probability and 100% correct responses. It can be calculated as follows:

Psychometric Threshold % = 100/nc + 100 − 100/nc/2 where nc = Number of choices

Accordingly the psychometric threshold for an eight-alternative forced choice, like in the grating test, is 56.25%; for a four-alternative forced choice it would be 62.5%.

As the psychometric threshold is approached, there is increasing uncertainty and the patient has to guess. This is rather uncomfortable for the tested individual and he will tend to give up before actually reaching the threshold. Canceling the test at this point would lead to an underestimation of the psychometric threshold. To avoid this, the BaLM test applies the forced choice principle, in which the patient is required to make a decision even if uncertain. In this way the influence of different criteria (“personalities”) can be minimized and the interindividual reproducability of the test can be increased.

Test Battery Pillar Two: Testing Activities of Daily Living and Orientation

Visual prostheses will be available in first clinical trials only to severely visually impaired or completely blind subjects. These people have adopted

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specialized coping strategies to manage the various tasks of daily living and to maintain autonomy. Restoring basic visual functions by visual prostheses will not necessarily improve these patients’ ability to master everyday tasks. However, improvement in the ability to pursue such activities would be a valuable endpoint in determining the efficacy of a visual prosthesis and could turn out to be more relevant than mere visual resolution values.

Therefore, a standardized method of testing performance in everyday activities is needed. In order to avoid as many uncontrollable biases as possible, the test must be carried out under well-defined, slightly artificial conditions. Nevertheless, actual situations encountered in daily life must be represented. In cooperation with an experienced mobility trainer, we have developed a setup for testing activities connected with daily life and orientation.

The test consists of two basic parts. The first one represents tasks in familiar surroundings, like sitting at a dining table and finding the plate, the glass, the cutlery, and other typical objects. The second part tests orientation and the ability to detect prominent markers or obstacles in a new surrounding when moving in public areas.

All tests are performed under the guidance of a mobility trainer. The time needed to fulfill a task is recorded, as is the patient’s subjective impression about the difficulty of the tasks. In addition, the trainer records his or her subjective assessment of the performance of the patient.

This test is highly subjective by nature. To achieve the greatest possible objectivity and reliability, a well-planned test design is obligatory. Thus, these tests should be carried out strictly under blinded and controlled conditions to be able to detect even slight improvements in activities of daily living and orientation (ADL/O) as an endpoint of a clinical trial.

The two parts of testing ADL/O are described in detail below.

Testing ADL: the Dining Table Scenery

The patient is seated at a table next to the mobility trainer. The setup is standardized with respect to ambient light and contrast as bright items are used on a black cloth on the surface of the table and ambient light is measured before each session. The patient is informed about the presence of several typical items like a plate, a knife, a spoon, a fork, or a cup in front of him on the table. He is asked to identify these items and to indicate the location of these items according to the hours on a clock face without touching or moving them. It is noted whether the patient can manage this task, and the time needed is recorded. In a second step, he is asked to change the position of certain items (eye–hand coordination). For example, he could be asked to move the cup to 2 o’clock position and the knife to the 3 o’clock position. Again, the time needed is noted. Applying real objects rather than standardized videotapes allows to account for tactile abilities which these patients are trained in very well and to test for eye–hand coordination which could be a demanding task for these patients. This might give a more realistic assessment of the benefit of an AVD in daily living.

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evaluating quality of life in patients suffering from eye diseases, like the National Eye Institute – Visual Function Questionnaire-25 (NEI-VFQ25, <http://www.proqolid.org/public/nei-vfq25.html>). However, most of these tests are of limited value in severely visually impaired or even blind patients. To be suitable for evaluating the psychological condition in blind patients during first clinical trials, possibly facing tremendous expectations and dissapointments, such tests must meet special requirements. We suggest using the “Brief Symptom Inventory (BSI)” test by L.R. Derogatis (Pearson Assessments) because it is capable of detecting even short-term fluctuations [24–26].

The BSI is a 53-item self-report scale used to measure 9 primary symptom dimensions (somatization, obsessive–compulsive behavior, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism), and 3 global indices (a Global Severity Index to measure overall psychological distress level, a Positive Symptom Distress Index to measure the intensity of symptoms, and the Positive Symptom Total to report the number of self-reported symptoms). The BSI is a shortened version of the Symptom Check List-90 (SCL-90 [27]), a widely used scale assessing current psychological distress and symptoms in both patient and non-patient populations. The BSI measures the experience of symptoms in the preceding seven days including the day the BSI was completed. Responses are on a 5-point scale, from 0 = “not at all” to 4 = “extremely.” Raw scores are converted to T-scores using ageand sex-appropriate non-patient norms. The BSI has high scale-by-scale correlations with the SCL-90. The BSI also has high internal consistency (Cronbach’s alpha: 0.71–0.85), test–retest reliability, and convergent, discriminant, and construct validity.

Conclusion

The suggested test battery, consisting of a set of psychophysical tests, tests for assessing performance in everyday activities and questionnaires to evaluate personality and psychological condition as well as novel sensation, while using an AVD allows for standardized estimation of the efficacy of the AVD under investigation. The entire test battery is needed to get a meaningful estimation of patient benefit and visual functions, using well-controlled prospective study designs.

References

1.Ricci F, Cedrone C, and Cerulli L: “Standardized measurement of visual acuity” Ophthalmic Epidemiol. Mar 1998; 5(1):41–53

2.Kniestedt C and Stamper RL: “Visual acuity and its measurement” Ophthalmol Clin North Am. Jun 2003; 16(2):155–170

3.Tamai M, Kunikata H, Itabashi T, Kawamura M, Saigo Y, Sato H, Wada Y, and Nakagawa Y.: “An instrument capable of grading visual function: results from patients with retinitis pigmentosa.” Tohoku J Exp Med. 2004 Aug; 203(4):305–312.

4.Marmor MF, Holder GE, Seeliger MW, and Yamamoto S: “Standard for clinical electroretinography” Doc Ophthalmol 2004; 108:107–114

5.Bach M, Hawlina M, Holder GE, Marmor M, Meigen T, Vaegan, and Miyake Y: “Standard for Pattern Electroretinography” Doc Ophthalmol 2000; 101:11–18

6.Odom JV, Bach M, Barber C, Brigell M, Marmor MF, Tormene AP, Holder GE, and Vaegan: “Visual Evoked Potentials Standard” Doc Ophthalmol 2004; 108:115–123

7.Kersten D and Yuille A: “Bayesian models of object perception” Curr Opin Neurobiol. Apr 2003; 13(2):150–158

8.Albright TD and Stoner GR: “Contextual influences on visual processing” Annu Rev Neurosci. 2002; 25:339–379

9.Hayes JS, Yin VT, Piyathaisere D, Weiland JD, Humayun MS, and Dagnelie G: “Visually guided performance of simple tasks using simulated prosthetic vision” Artif Organs. Nov 2003; 27(11):1016–1028

10.Thompson RW Jr, Barnett GD, Humayun MS, and Dagnelie G: “Facial recognition using simulated prosthetic pixelized vision.” Invest Ophthalmol Vis Sci. Nov 2003; 44(11):5035–5042

11.Hossain P, Seetho IW, Browning AC, and Amoaku WM: “Artificial means for restoring vision” BMJ. 1 Jan 2005; 330(7481):30–33

12.Alteheld N, Roessler G, Vobig M, and Walter P: “The retina implant–new approach to a visual prosthesis” Biomed Tech (Berl). Apr 2004; 49(4):99–103

13.Loewenstein JI, Montezuma SR, and Rizzo JF 3rd: “Outer retinal degeneration: an electronic retinal prosthesis as a treatment strategy” Arch Ophthalmol. Apr 2004; 122(4):587–596

14.Chow AY, Chow VY, Packo KH, Pollack JS, Peyman GA, and Schuchard R: “The artificial silicon retina microchip for the treatment of vision loss from retinitis pigmentosa” Arch Ophthalmol. Apr 2004; 122(4):460–469.

15.Zrenner E: “Will retinal implants restore vision?” Science 8 Feb 2002;295(5557):1022–1025.

16.Stanley OH: “Cortical development and visual function” Eye. 1991; 5 (Pt 1):27–30

17.Gwiazda JE: “Detection of amblyopia and development of binocular vision in infants and children” Curr Opin Ophthalmol. Dec 1992;3(6):735–740

18.Hess RF: “Assessment of stimulus field size for strabismic amblyopes” Am J Optom Physiol Opt. May 1977; 54(5):292–299.

19.Bach M: “The ‘Freiburg Visual Acuity Test’ – Automatic measurement of visual acuity” Optometry and Vision Science 1996; 73:49–53

20.Dennis RJ, Beer JM, Baldwin JB, Ivan DJ, Lorusso FJ, and Thompson WT: “Using the Freiburg Acuity and Contrast Test to measure visual performance in USAF personnel after PRK” Optom Vis Sci 2004; 81:516–524

21.Schulze-Bonsel K, Feltgen N, Burau H, Hansen LL, and Bach M: “Visual acuities ‘Hand Motion’ and ‘Counting Fingers’ can be quantified using the Freiburg Visual Acuity Test.” Invest Ophthalmol Vis Sci 2006; 47:1236–1240

22.Green DM andSwets JA (1966) Signal detection theory and psychophysics. New York, Wiley

23.Harvey LO: “Efficient estimation of sensory thresholds” Behavior Research Methods, Instruments, Computers 1986; 18:623–632

24.Alagappan K, Steinberg M, MancherjeN, Pollack S, and Carpenter K: “The psychological effects of a four-week emergency medicine rotation on residents in training” Academic Emergency Medicine 1996; 3(12): 1131–1135