Mechanisms Mediating Visual Detection in Static Perimetry

Transcription

1 Mechanisms Mediating Visual Detection in Static Perimetry Ronald S. Harwerth,* Earl L. Smith III* and Louis DeSantis\ Purpose. The usual stimuli in static perimetry are white-light luminance increments. However, the specific visual detection mechanisms involved in perimetry are unknown because all classes of neural mechanisms are sensitive to spectrally broadband stimuli. The objective of this study was to determine the relative sensitivities of nonopponent and opponent detecting mechanisms under standard perimetry test conditions. Methods. Using trained rhesus monkey subjects, the relative sensitivities of the vision mechanisms for the detection of perimetry test stimuli were determined through psychophysical measurements of spectral sensitivity at each of the test field locations of the C24-2 threshold program on the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA). The spectral sensitivity functions were analyzed by a three-channel model that incorporated independent short-wavelength-sensitive, nonopponent (luminance), and opponent (chromatic) spectral sensitivity mechanisms. Results. The visual detection mechanisms for perimetry thresholds varied as a function of the size and wavelength of the test field. With the perimeter's standard stimulus (Goldmann Size III) and bowl illumination (31.5 asb), the presence of a short-wavelength-sensitive mechanism was clearly evident at all field locations, but its relative sensitivity systematically declined with eccentricity. Under these conditions, the sensitivities of the opponent and nonopponent mechanisms were approximately equal at most field locations. With a larger stimulus (Goldmann Size V), however, the contribution of the opponent spectral sensitivity mechanism was more apparent over most of the central field and the alterations of sensitivity with eccentricity were less pronounced. In contrast, a small test field (Goldmann Size II) appeared to bias detection toward nonopponent mechanisms. Conclusion. The results of these investigations indicate that detection thresholds during perimetry can be effectively biased toward different photopic, visual processing channels through the appropriate selection of size and wavelength of the test stimulus. Invest Ophthalmol Vis Sci. 1993;34: Computerized light-sense perimetry is an important component in the diagnosis of ocular disorders affecting peripheral vision as, for instance, in the differentiation of glaucoma from ocular hypertension. 1 It has, however, been demonstrated that standard perimetric methods (white-light test stimuli superimposed on a white-light adaptation field) are not always sensitive From the *College of Optometry; University of Houston, Houston, and falcon Laboratories, Inc., Fort Worth, Texas. This study was supported in part by research funds from Alcon Laboratories, Inc., Fort Worth, Texas and Public Health Service research giants EY-OJ139 and EY , and core grant EY from the National Eye Institute, Bethesda, Maryland. Presented in part at the annual meeting of the Association for Research in Vision and Ophthalmology, Sarasola, Florida, May 2, Submitted for publication f une 8, 1992; accepted February 10, Proprietary interest category: N. Reprint requests: Ronald S. Harwerth, College of Optometry, University of Houston, Houston, Texas measures of the state of the underlying retinal neurology. For example, Quigley et al 2 reported that perimetric visual field defects are poorly correlated with neural damage in retinas of glaucoma patients. It has been suggested that static perimetry thresholds are insensitive to early neural damage because white-light test stimuli can be detected by retinal mechanisms that are not affected early in the disease process. 3 ' 4 The validity of this type of explanation must be based on a knowledge of the detection mechanisms involved in perimetry thresholds and the alterations of these specific visual mechanisms by glaucoma. Neither is known, but such information would be of considerable value for the evaluation of perimetry with conventional testing parameters and/or to provide a rational basis for the development of alternative testing strategies. Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10 Copyright Association for Research in Vision and Ophthalmology 3011

2 3012 Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10 The visual sensitivities of neural mechanisms can be classified by their spectral response properties as broadband (nonopponent) or chromatic (opponent) mechanisms. 5 These two classes of response properties are considered to originate from different neural combinations of the three cone types. 56 Because either of the two channels could be primary in the detection of perimetry stimuli, the general purpose of our experiments was to describe the relative sensitivities of color vision mechanisms in standard, clinical perimetry. Specifically, the sensitivities of detection mechanisms were assessed by an analysis of their contributions to the increment-threshold spectral sensitivity functions of observers with normal vision, under standard perimetry test conditions. Increment-threshold spectral sensitivity under white-light adaptation seems to depend on the sensitivities of several channels or mechanisms derived from either independent responses or interactions between the responses of retinal cones. 7 " 12 Although there are alternative models, 1314 the three photopic mechanisms most often considered to underlie the increment-threshold spectral sensitivity functions are: an independent short-wavelength-sensitive (SWS) mechanism reflecting the sensitivity of the SWS cones; a color-opponent (chromatic) mechanism derived from differential inputs of the middle-wavelength-sensitive and long-wavelength-sensitive cone classes; and a color nonopponent (luminance) mechanism derived from undifferentiated middle-wavelength-sensitive and long-wavelength-sensitive cone inputs. 8 " 12 It might be presumed that the luminance contrast of a white test field superimposed on a white background would be detected by the nonopponent.mechanisms. However, achromatic light could be detected by either opponent or nonopponent channels 1516 and factors other than the spectral composition of the test and background fields can influence the relative sensitivities of these channels. For example, the intensity of the adaptation field, 12 the size of the test field with respect to the size of the background, 17 the exposure duration of the test field, 1819 and the retinal location of the test field 20 are all factors that affect the balance of sensitivities between opponent and nonopponent channels. Some of the stimulus parameters used in conventional perimetry would cause a bias toward opponent channel detection, but others would bias detection toward nonopponent channels. Considering perimetry with the Humphrey Field Analyzer (Allergan Humphrey, San Leandro, CA) as a specific example, the moderately intense bowl illumination (31.5 asb; 10 cd/m 2 ) and relatively long stimulus duration (200 msec) would seem to favor detection by opponent mechanisms, while the relatively small test field (0.43 degrees for the standard Goldmann Size III stimulus) and extensive adaptation field probably favor detection by the nonopponent mechanisms. In addition, the relative weights of these various factors undoubtedly vary across the visual field. 21 Therefore, it is apparent that the relative roles of these mechanisms in lightsense perimetry must be assessed empirically. SUBJECTS AND METHODS Subjects The subjects for the current experiments were three 5-year-old, male rhesus monkeys (Macaca mulatto) who had been the subjects of our previous comparisons of the normal visualfieldsof humans and monkeys. 22 The monkey subjects were used in anticipation of studies of experimentally-induced ocular disorders and because the experimental requirements for these investigations would have been formidable for human observers. The complete series of experiments actually required more than 150 visual field measurements involving approximately 125,000 behavioral trials for each subject and were only practical by using surrogate human observers. Conversely, the use of monkeys as alternative subjects has little consequence for the general applicability of the findings because the visual capabilities of macaque monkeys, including perimetric thresholds, match those of human beings. 22 " 25 All of the experimental and animal care procedures adhered to the ARVO statement for the Use of Animals in Ophthalmic and Vision Research. Apparatus The visual fields of the monkeys were measured with a modified Humphrey Visual Field Analyzer that was attached to a small primate testing cubicle (BRS/LVE, Laurel, MD). The principal modifications of the perimeter, which did not alter the standard threshold procedures or data analysis programs, included the following: (1) A light-emitting diode fixation stimulus was placed in Maxwellian view to control the monkeys' head and eye positions. A luminance increment of the light-emitting diode was the test stimulus in at least 30% of the session trials. (2) A microcomputer eye-position monitor (Micromeasurements System 2000, Micromeasurements, Inc., Berkeley, CA), aligned with the fixation stimulus, caused an interruption of the behavioral paradigm if an eye movement greater than approximately 5 occurred during a trial. Infrared light for the eye-position monitor was provided by filtered tungsten lamps (Schott glass RG-715; Jenaer Glaswerk Schott and Gen., Mainz, Germany) mounted to the wall of the primate cubicle. (3) Custom readonly memory computer chips were provided by the perimeter's manufacturer that delayed movement of the projector for 2 seconds after the presentation of

3 Detection Mechanisms in Perimetry WAVELENGTH (NM) FIGURE l. Absorption spectra for the crystalline lenses of the three monkeys. The solid line, representing the absorption spectra of the monkeys' lenses, was derived from a modification of the absorption spectrum of lenses of human subjects of approximately 20 years of age (see references 29 and 30). The absorption spectra were obtained by determining the multiplication factor needed to scale the function for human subjects to fit the difference spectrum between the shortwavelength-sensitive photopigment and the monkey's spectral sensitivity for wavelengths between 420 and 480 nm (shown by the data symbols). The data represented by squares are on a true scale, the the other functions have been displaced upward (circles) or downward (triangles) by 1.0 log unit for clarity of presentation. the visual field stimuli and modified the testing protocol to necessitate discrete behavioral responses for each trial. (4) The timing of the perimeter's testing sequence was controlled and synchronized with the other events of the behavioral procedure by an external laboratory computer. (5) Narrow-band, monochromatic test stimuli were produced by interference filters with 10 nm half-band widths (Oriel Corp., Stratford, CT) located in the optical pathway for the test stimulus, between the light source and the field stop that sets the test field size. It was necessary to calibrate the monochromatic stimuli from measurements of light energy (EG&G model 550 radiometer/photometer, Salem, MA) ahead of the field stop. As a result, the relative stimulus intensities were accurately defined,but it was not possible to obtain absolute calibration of the visual stimuli on the surface of the perimeter bowl. Therefore, the light energies were converted to relative quantum values and, for convenience, an arbitrary constant was used to adjust the monkeys' threshold values into a range compatible with previous experiments using an optical system with more precise calibration. 12 However, because a single value was used for all of the data, the calibration factor does not alter the relative sensitivities across animals,fieldsizes, retinal eccentricity, or adaptation level. (6) In the series of experiments on the effects of retinal adaptation, the bowl illumination was lowered by reducing the lamp voltage through the perimeter's set-up menu. Although the variation in lamp voltage changed the color temperature of the bowi illumination, the adaptation data (see Fig. 7) did not show wavelength-specific effects. Thus, the changes in the color temperature of the adapting illuminance did not cause significant chromatic adaptation. The perimeter bowl illuminance levels, calibrated with the EG&G radiometer/ photometer system, covered the range of asb (10 to 0.6'cd/m 2 ). The monkeys' pupils varied from approximately 6 to 9 mm in diameter over this adaptation range resulting in a variation in retinal illuminance of troland. During the experimental sessions, the monkeys were placed in a custom-made primate chair that provided adjustments for alignment of their eyes at the correct viewing position for the perimeter and allowed access to the juice reward delivery spout. A behavioral response lever was mounted at a convenient waist level. Methods Psychophysical increment thresholds for the central fixation stimulus and the peripheral visual field stimuli were measured with an adaptation of the criterion response-time paradigm used in our previous studies of visual functions in monkeys. 26 The essential components of the procedures for visual field measurements with monkeys, which have been described in more detail, 22 were as follows: the monkeys were trained to press and hold down their response lever to initiate a trial and, subsequently, to release the lever in the presence of a visual stimulus. Because the time of the appearance of the stimulus within a trial was randomly varied, the monkey's responses that were closely correlated with the visual stimulus presentation (i.e., within the 900 msec response interval) were operationally defined as true-positive responses and they were rewarded. Alternatively, lever releases beyond the response interval were defined as false-negative responses. The test stimulus in any trial could be either a luminance increment of the central, fixation stimulus or of a peripheral field stimulus. The locations and intensities of the peripheral test stimuli were determined by the Humphrey Field Analyzer's C24-2 fullthreshold program. The Humphrey Field Analyzer's C24-2 program consists of 54 test field locations in the central visual field that are placed at 6-degree intervals (horizontally and vertically) on Cartesian coordinates. The most central testfieldlocations are at an eccentricity of 3 degrees (on a 45-degree angle into each quad-

4 3014 Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10 SPECTRAL SENSITIVITY MECHANISMS 1) SW-mech = LOG{SWS}+ SS1 2) NOPP-mech = LOG{LWS + (MWS * K2)} + SS2 3) OPP-mech = LOG{LWS - (MWS * K3)} + SS " WAVELENGTH (nm) WAVENUMBER (I/cm) WAVELENGTH (nm) WAVENUMBER -(I/cm) FIGURE 2. Examples of increment-threshold spectral sensitivity functions (mean ± 1 SD) from a central (left panel) and a peripheral (right panel) visualfieldlocation. The curves superimposed on the data represent the: best-fitting color vision mechanisms derived from the spectral sensitivity model presented at the top of thefigure (see text for details). rant) and the most peripheral locations are at 27 degrees, in the nasal field, or 21 degrees, in the superior, inferior, and temporal fields. Visual field data with monochromatic test stimuli of a single wavelength were obtained in each daily session. On successive days, data were collected for pseudo-randomly ordered wavelengths between 420 and 680 nm, in 20-nm intervals, until two sets of data were acquired for each subject at each wavelength. The mean threshold value from the two sets of data was taken as the attenuation factor for calculating of the relative quantum threshold value. The logarithm of the reciprocal of the quantum threshold (log sensitivity) as a function of the reciprocal of the wavelength of the monochromatic stimulus (wave number) represented the increment-threshold spectral sensitivity function. Data Analysis The relative sensitivities of the color vision mechanisms mediating detection at each field location were determined by a specific curve-fitting analysis based on Stiles' proposition that spectral sensitivity functions represent the upper envelope of multiple independent detection mechanisms. 27 It was assumed that although there may be several potential detection mechanisms at every site in the retina, the mechanism most sensitive to a specific stimulus independently determined the monkey's visual threshold. The empirical spectral sensitivity functions were therefore used to define the mechanisms mediating detection by fitting separate portions of the function from a set of three underlying spectral sensitivity mechanisms, that is, i.e., an SWS mechanism (SWS-mech), a nonopponent mechanism (NOPP-mech), and an opponent mechanism (OPP-mech). Of course, this upper envelope, curve fitting procedure by itself is not sufficient to define the stimulus detection mechanisms. However, extensive investigations of spectral sensitivity functions for foveal vision of monkeys 12 have verified the existence of these three underlying mechanisms and it seems logical to extend the analysis to peripheral retinal locations. In addition, the form of incrementthreshold spectral sensitivity in perimetry is important in understanding the procedure, regardless of the underlying detection mechanisms. Quantitative descriptions for the three spectral sensitivity mechanisms 12 used in the analysis of the increment-threshold functions are presented at the top of Figure 2. Each mechanism was based on one or two cone photopigment absorption functions, but the general conclusions of the analysis are not dependent on

5 Detection Mechanisms in Perimetry 3015 FIGURE 3. The relative sensitivities of the opponent and nonopponent visual detection mechanisms as a function of field location with the Goldmann Size III stimulus and the Humphrey Field Analyzer standard bowl illumination (31.5 asb). The cells of the data matrix represent the 54 test locations of the Humphrey Field Analyzer C24-2 threshold program; the small numbers in the upper left corner of each cell correspond to the perimeter's designation of field locations, that is, spaced at 6-degree intervals (horizontally and vertically) on cartesian coordinates with the most central test field locations at an eccentricity of 3 degrees (on a 45-degree angle into each quadrant) and the most peripheral locations are 27 degrees, in the nasal field, or 21 degrees, in the superior, inferior, and temporal fields. At each field location an "N" or an "O" designates whether the spectral sensitivity data at that location were better fitted (minimum chi-square) with the nonopponent mechanism or opponent mechanism and the statistically significant cases (P < 0.05) are labeled by an asterisk. Examples of the spectral sensitivity data (mean ± 1SD) and best-fitting mechanisms from four representative field locations are also presented. specific cone fundamentals. For ease of computation, the cone functions were derived from the polynomial expressions of Baylor et al 28 with compensation for the spectral absorption of the animal's crystalline lens. Corrections for macular pigment were not included because even the most central test fields were located at an eccentricity (3 degrees) where absorption by the macula lutea approaches nonsignificance The correction for the spectral absorption of each animal's lens was based on the finding by Savage et al 31 that individual variations in the optical density of human lenses differ by a multiplicative factor. Assuming that the same is true for monkeys, the average lens absorption function for human subjects aged approximately 20 years was modified to fit the monkey's spectral sensitivity function. Because the SWS-mech

6 3016 Investigative Ophthalmology 8c Visual Science, September 1993, Vol. 34, No. 10 z w in -6 WAVENUMBER (I/cm) WAVENUMBER (I/cm) FIGURE 4. The relative sensitivities of the opponent and nonopponent visual detection mechanisms as a function of field location with the Goldmann Size V stimulus and the Humphrey Field Analyzer standard bowl illumination (31.5 asb). Other details as in Figure 3. represents the sensitivity of a single class of cones, the lens absorption for wavelengths between 420 and 480 nm should be proportional to the difference spectrum between the sensitivity of the SWS photopigment and the subject's spectral sensitivity at these wavelengths. The spectral sensitivity of the SWS-mech was determined by the average data from ten field locations approximating a 12-degree arc around fixation, but excluding points near the blind spot. The difference spectrum data and the modified absorption spectrum for the lens of each of the monkeys are presented in Figure 1. The lens optical densities at 415 nm (0.98, 1.13, and 1.45, for the 3 monkeys) represent only minor modifications of the data for 20-year-old humans, which can be considered the approximate human age-equivalent of the monkeys. 33 The three cone photopigment functions, corrected for absorption by the lens, were used as constants (SWS, middle-wavelength-sensitive, and long-wavelength-sensitive) in the descriptive spectral sensitivity model (shown in Fig. 2). The interaction values (K2 and K3) and the sensitivity values (SSI, SS2, and SS3) of the photopigment functions that provided the bestfit of the model to the spectral sensitivity data were determined by a Chi-square minimizing routine. In addition, using a reduced Chi-square statistic that compensated for the number of fitting parameters, 34 the algorithm evaluated the total fit to determine the minimum number of mechanisms required to describe the spectral sensitivity function. The differences produced by fitting the data with different numbers of parameters were then assessed from the F-ratios of the reduced Chi-square values, 35 with statistical significance set at a level of P < 0.05.

7 Detection Mechanisms in Perimetry WAVELENGTH (nm) WAVENUMBER (I/cm) WAVENUMBER (I/cm) WAVENUMBER (I/Cm) FIGURE 5. The relative sensitivities of the opponent and nonopponent visual detection mechanisms as a function of field location with the Goldmann Size II stimulus and the Humphrey Field Analyzer standard bowl illumination (31.5 asb). Other details as in Figure 3. RESULTS The data from the three monkeys were in agreement across all of the experimental conditions and therefore were averaged across animals. Examples of the spectral sensitivity data for a central and a peripheral field location, selected to illustrate differences in the forms of the functions, are presented in Figure 2. The data from a central field location {left panel) were bestfit with three mechanisms; the SWS-mech to fit the sensitivity peak in the short wavelength region of the spectrum, the OPP-mech to fit the majority of the data across the two sensitivity peaks in the middle and longer wavelength region, and the NOPP-mech to fit the few data points in the nm region that are not accounted for by the OPP-mech. In contrast, for the peripheral field location {right panel), the spectral sensitivity function was better described by just two mechanisms, the SWS-mech and the NOPP-mech. In both of these cases, the correlation between the fitted functions and the data provided an indication of the mechanisms mediating detection. These examples also illustrate the two aspects of the data analysis that were considered separately for each field location: (1) the sensitivity and category (opponent or nonopponent interactions) of the mechanism that mediated detection over the middle- and long-wavelength regions of the spectrum (520 to 680 nm); and (2) the sensitivity of the independent SWS-mech that mediated detection over the short-wavelength region of the spectrum ( nm). The results of the analysis of the relative sensitivities of opponent versus nonopponent mechanisms, as a function of perimetric field location, are presented

8 3018 Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10 BBS ES9 B EB3 BBS! WEI j MjHM WBil BEfll CO jh laajj 2'J i ESI BSI HSi Epi j EB1 EfSI Ed ES9 ESS ESI 1ES3 FIGURE 6. The relative sensitivity of the short-wavelenth-sensitive mechanism as a function of field location. The cells of the data matrix represent the 54 test locations of the Humphrey Field Analyzer C24-2 threshold program; the small numbers in the upper left corner of each cell correspond to the perimeter's designations of field location. The sensitivity data have been normalized to the most central field location in the inferior, nasal visual field and displayed as a gray scale proportional to the relative sensitivity. The numeric relative sensitivity values for each field location are also presented in the corresponding cells of the matrix. (A) Relative sensitivity of the short-wavelenth-sensitive mechanism with the Goldmann Size III test field. (B) Relative sensitivity for white-light stimuli with the Goldmann Size III test stimulus. (C) Relative sensitivity of the short-wavelength mechanism with the Goldmann Size V test stimulus. in Figures 3-5 and 8). The cells of the data matrices represent the 54 test field locations of the Humphrey Field Analyzer C24-2 program. For each field location, an "N" or an "O" designates whether the spectral sensitivity data were better fitted with the NOPPmech or OPP-mech (minimum Chi-square value) and the statistically significant cases (P < 0.05) are labeled by an asterisk. Although the relative contributions of the SWS-mech have not been presented in these matrices, its inclusion as a fitting parameter provided a significantly better description of the functions with Goldmann Size III or V stimuli at all field locations. These properties are also illustrated by the representative examples of the spectral sensitivity data (mean ± 1

9 Detection Mechanisms in Perimetry 3019 LOG BOWL LUMINANCE (ASB) FIGURE 7. Detection thresholds (mean ± 1 SD) as a function of perimeter bowl illuminance for monochromatic test stimuli (Goldmann Size V). Functions are presented for four wavelengths, (A) 460 nm, (B) 520 nm, (C) 580 nm, and (D) 620 nm, at test field coordinates of: 9 degrees, 9 degrees in superior-temporal quadrant (triangles); 9 degrees, 15 degrees in the superior-nasal quadrant {squares); 15 degrees, 15 degrees in the inferior-nasal quadrant {circles); and 3 degrees, 3 degrees in the inferior-temporal quadrant (diamonds)). Data for the most peripheral visual field location (circles) are on a true scale, the other data has been displaced upward by 6.5 log units for clarity of presentation. SD) and the best-fitting spectral sensitivity mechanisms at four field locations. With the standard test stimulus (Goldmann Size III; 0.43 degrees) and bowl luminance (31.5 asb), the spectral sensitivity functions in the central visual field tended to be better described by opponent mechanisms whereas the functions in more peripheral field locations were generally better described by nonopponent mechanisms (Fig. 3). However, the distinctions between mechanisms were hot often statistically significant and, under these conditions, the sensitivities of NOPP-mech and OPP-mech were nearly equal across the whole visual field. Based on these results, it is not possible to specify the detection mechanisms that are most sensitive for a Goldmann Size III test target or to propose a monochromatic stimulus that would bias detection toward a certain mechanism. Visual field measurements with a larger test stimulus, a Goldmann Size V (1.72 degrees), resulted in a somewhat clearer separation of detection mechanisms and the peak in short-wavelength sensitivity was more obvious at all field locations. In the longer wavelength regions of the spectrum, opponent color mechanisms were more sensitive than nonopponent mechanisms over most of the visual field with a substantial proportion being statistically better described by OPP-mech than NOPP-mech functions (Fig. 4). Under these conditions, the separation of color vision mechanisms was sufficiently clear to demonstrate that the sensitivities of the opponent mechanisms were higher than the nonopponent mechanisms for long wavelength stimuli over the majority of the visual field locations. In distinction, with a smaller perimetry test field (Goldmann Size II; 0.21 degrees), the best descriptions of the spectral sensitivity functions at most test locations required an additive combination of the middle- and long-wavelength-sensitive photopigment functions. An additive combinations of cone functions defines a nonopponent mechanism and, as shown by the data of Figure 5, also defined the predominant detection mechanism with this small test field. Interestingly, the majority of the field locations (19 of 29) that were significantly better fitted with the N-OPP function were in the nasal hemifield (Fig. 5). In contrast, with the largest test field (Goldmann Size V) the majority of the significant cases for the OPP function (16 of 25) were in the temporal hemifield (Fig. 4). In our analysis of the spectral sensitivity functions, the sensitivity of the SWS-mech was considered to be an independent detection process (Fig. 2). The SWSmech was not evident with the 0.21-degree test field, even for the most central field locations (Fig. 5), but its inclusion significantly improved the descriptive fits of the data for all field locations, with either the or 1.72-degree test fields. Nevertheless, as illustrated by the insets of Figure 3, the SWS-mech sensitivity with the 0.43-degree test field was quite low at the more eccentric field locations. To illustrate the SWS-mech sensitivity as a function of field location, the data were normalized at the most central field location (3 degrees, 3 degrees) in the inferior, nasal field and are displayed in Figure 6 using a gray scale that was proportional to the logarithm of the relative sensitivity. The numeric relative sensitivity values for the individual field locations are also presented in the cells of the data matrix. As shown in panel A of Figure 6, with the perimeter's standard stimulus size (0.43 degrees) the SWS-mech sensitivity rapidly declined as a function of eccentricity. The decline in SWS-mech sensitivity was, in fact, more rapid than with a white-light stimulus of

10 3020 Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No WAVELENGTH (nm) FIGURE 8. The relative sensitivities of the opponent and nonopponent visual detection mechanisms as a function of field location with the Goldmann Size V stimulus and a Humphrey Field Analyzer bowl illumination of 4 asb. Other details as in Figure 3. the same size {panel B). In contrast, the change in SWS-mech sensitivity with eccentricity was smaller and similar to the function with the white light stimulus when the SWS-mech sensitivity was measured with a larger diameter test field (1.72 degrees, panel C). The variations in SWS-mech sensitivity as a function of field location (Fig. 6C) indicated that the SWS-mech was reasonably well isolated with the larger test field at all eccentricities within, at least, the centra] 48 degrees of the visual field. For instance, at the most peripheral field locations, the sensitivity of the SWS-mech at 460 nm was approximately 1.0 log unit higher than the sensitivity of either the OPP-mech or NOPP-mech (see Fig. 4). Previous studies 12 have shown that the relative balance in the sensitivities of the three color vision mechanisms are dependent on the level of white-light adaptation. Therefore, to determine how the detection mechanisms were affected by the state of adaptation provided by the bowl illumination, threshold-versusintensity functions were derived for wavelengths of 460, 520, 580, and 620 nm (panels A-D, Fig. 7) using a Goldmann Size V test stimulus. The results from each of the field locations, illustrated by the four examples in Figure 7, were similar in showing a linear relationship between threshold and adaptation level over the range of asb, regardless of the stimulus wavelength. The slopes of the functions, which varied between 0.56 and 0.84 on the log-log coordinate system, did not vary systematically with wavelength, but they are somewhat more shallow than has been found for foveal vision. 12 The linearity of the threshold-versus-intensity relationships indicates that alterations in the adaptation level did not change the detection mechanisms for a Goldmann Size V test stimulus. This outcome is also

11 Detection Mechanisms in Perimetry 3021 demonstrated by a comparison of the data shown in Figure 4, which were obtained for a 31.5-asb adaptation level to those for a lower adaptation level (4 asb) presented in Figure 8. With the lower level of adaptation, the SW-mech was isolated for test wavelengths below 500 nm, even at the most peripheral field locations, and the opponent mechanisms tended to dominate detection at the longer wavelengths throughout most of the central visual field. On the basis of these results, it may be concluded that, with the 1.72-degree test stimulus, the relative balance of the visual detection mechanisms are consistent across adaptation states, down to very low levels of photopic vision. DISCUSSION The results of these experiments have demonstrated that the visual detection mechanisms in static perimetry vary as a function of the size and wavelength of the test field. Whether any of these variations are applicable to the improvement of diagnostic procedures for ocular disorders would depend on the specific effects of the disease process and the goals of the perimetric measurement. For example, under the standard testing conditions of the Humphrey Field Analyzer (Goldmann Size III test field superimposed on a 31.5-asb background), specific detection mechanisms cannot be specified because the sensitivities of all of the detection mechanisms are approximately equal (Fig. 2). It therefore is unlikely that very selective deficits would alter visual thresholds under these standard conditions, but they are probably optimal for the assessment of deep scotorrias because any of the mechanisms would be effective in detecting the test stimulus. As demonstrated by the spectral sensitivity functions with larger and smaller stimulus field diameters, static perimetry thresholds may be differentially biased toward specific detection mechanisms by the appropriate selection of test field wavelength and/or test field size. These procedures could, therefore, be used to develop testing strategies for the specific neural deficits associated with various retinal diseases. In this respect, it is apparent that any single set of standard test parameters designed to bias detection toward a single mechanism would not be appropriate for general use because specific defects in each of the three color vision mechanisms have been associated with retinal diseases of one form or another. For example, evidence has been presented for specific deficits in the sensitivity of the SWS-mech in many retinal diseases of the inner and outer retina, 36 ' 3 ' including glaucoma. 38 " 41 Alternatively, psychophysical and morphologic data have been reported that suggest that the nonopponent or luminance mechanisms are differentially affected in incipient glaucoma. 42 " 44 Other diseases, especially optic neuritis, have been shown, however, to cause selective losses in the opponent or chromatic mechanisms. 45 ' 46 A selective vulnerability of the SWS-mech in early glaucoma has been suggested by several recent demonstrations that perimetry with monochromatic, blue light can reveal glaucomatous field defects that were not present with standard white light stimuli. 39 " 41 In each case, isolation of the SWS-mech was accomplished by auxiliary lighting of the perimeter bowl to provide a relatively intense yellow or orange adaptation field. However, the results of the present experiments (Figs 4 and 7B) indicate that, with the largest test field diameter, adequate isolation of the shortwavelength-mechanism can be achieved with the standard white light background. The use of achromatic, white adaptation is an advantage because factors that affect the overall level of adaptation, such as senile miosis, would uniformly affect the entire sensitivity function and, therefore, maintain a constant isolation of the short-wavelength-sensitive mechanism (Figs 7 and 8). On the other hand, color specific effects of the crystalline lens from aging or disease will affect the accuracy of sensitivity measurements with short wavelength light and the lens absorption of each patient should be empirically determined. 3 li32 ' 40>47 In this report, we described a new method of determining the optical density of the lens that takes advantage of the relative isolation of the SWS-mech with the standard white-light adaptation used in perimetry. The procedure used standard perimetry thresholds with liionochromatic blue light and an analysis procedure that provided a spectral correction factor for sensitivity measurements with any monochromatic stimulus. The visual detection mechanisms with a small diameter perimetric test field (Goldmann Size II; 0.21 degrees) could be described as nonopponent channels at essentially all field eccentricities (Fig. 5). The nonopponent nature of the spectral sensitivity mechanisms was defined by the additive combination of the middle- and long-wavelength-sensitive photopigment functions needed to obtain the best fit of the psychophysical functions. However, in contrast to opponent mechanisms, the shape of a spectral sensitivity function may not be sufficient to identify nonopponent mechanisms 48 or even a specific part of the geniculostriate pathway. Nonopponent neurons have been identified in both the magnocellular and parvocellular divisions of the lateral geniculate nucleus 15 ' 49 and within the parvocellular pathway, neurons with nonopponent response characteristics can be either unitary or associated with the short- wavelength-sensitive mechanism in the blue/yellow opponent channels. 50 The stimulus conditions and methods of data analysis in the current experiments were not specific enough to assume that detection would be confined to any one of these channels and, consequently, it is not certain

12 3022 Investigative Ophthalmology & Visual Science, September 1993, Vol. 34, No. 10 that the use of small monochromatic test fields in perimetry would bias detection toward the broadband or M-pathway mechanisms. Isolation of the opponent-color vision channels, using a large test field and monochromatic light, is straightforward. The findings of the current experiments are in agreement with a large number of previous investigations 7 " 1217 ~ 20>51 that have demonstrated opponent channel spectral sensitivity for middle- to long-wavelength stimuli, in the presence of white-light adaptation. It was also expected that large test fields would be more effective than small stimuli for achieving a distinct isolation of these channels at peripheral retinal locations. 20 In fact, the failure to attain unequivocal isolation of the opponent mechanisms at the most peripheral field locations was probably because the 1.72-degree (Goldmann Size V) test field was not large enough at these eccentricities. In any case, the use of the largest of the perimeter's test fields, in conjunction with a monochromatic test light of nm, apparently would provide independent detection by opponent mechanisms over the major portion of the central visual field. Therefore, it would be expected that diseases of the retina or optic nerve that preferentially affect neurons in the red/green chromatic channels would show selective deficits under these test conditions. Overall, the results of these experiments have suggested testing conditions that may have application in the development of methodology for perimetry that is more sensitive to the effects of early disease states than the current, standard procedures. Of course, the validity of each of the sets of conditions must be subjected to further investigations in defined disease states. For example, the correlations of specific testing strategies could be determined throughout the natural timecourse of induced pathology, such as experimental glaucoma in monkeys. Nevertheless, even procedures developed through investigations of valid monkey models will need to be subjected to investigations on human patients to define their clinical efficacy. 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