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It is of interest to determine how patients’ performance on clinical tests relates to their ability to conduct tasks of daily life.

The electroretinogram (ERG) elicited by a flickering stimulus has become a useful clinical test for monitoring the progression of retinal disease and for inferring the pathophysiology of the disease process. In the clinical setting, the flicker ERG is usually obtained using a train of strobe flashes. The effect of the disease process is then either derived from an examination of the characteristics of the flicker ERG waveform, such as peak amplitude and implicit time, or from narrow-band filtering of the ERG at the stimulating frequency. However, the interpretation of the flicker ERG can be problematic in cases of retinal disease in which patients have unusual waveform shapes. An example is the double-peaked 30 Hz flicker ERG waveform reported by Miyake et al. (1987) in patients with "incomplete" congenital stationary night blindness (CSNB). We recently identified two patients with typical retinitis pigmentosa (RP) who showed also showed a double-peaked flicker ERG waveform, indicating that this response abnormality may be found in other types of retinal disorders besides incomplete CSNB. The purpose of the present study was to characterize the harmonic components of the flicker ERG in these RP patients in order to better understand the origin of this anomalous flicker response as well as the flicker ERG of normals.

Retinitis pigmentosa (RP) refers to a group of retinal dystrophies that are characterized typically by night blindness, peripheral visual field restrictions and/or scotomas, abnormalities in the electroretinogram (ERG), intraretinal bone spicule-like pigmentation, and narrowing of the retinal vessels. While functional abnormalities are usually most apparent in the peripheral visual field, foveal function can often be impaired as well. Previous studies have suggested that not only can foveal visual acuity be reduced in RP patients, but foveal contrast sensitivity for relatively large targets can also be decreased.1-4 The purpose of this study was to examine the quantitative relationship between the loss of foveal visual acuity and the reduction in foveal letter contrast sensitivity in subjects with RP in order to provide further information about the nature of the foveal dysfunction. Acuity and contrast sensitivity were assessed both by means of a computerized display system and by commercially available chart tests.

Spatial sampling of visual targets results in a reduction in effective stimulus contrast and a loss of information.1 To determine the contribution of these two factors to grating resolution and to letter identification, we measured visual acuity and contrast thresholds for spatially sampled gratings and letters.

Evidence indicates that the spatial tuning properties of luminance increments and decrements may not be equivalent and that stimulus onset-offset characteristics can differentially affect contrast thresholds. The present study investigated whether this is the case for letter identification. Individual Sloan letters were presented as luminance increments or decrements on a gray-scale display of a Macintosh IIfx computer, with contrasts controlled by an ISR video attenuator. The temporal mode of presentation was either a rapid onset with a Gaussian offset, or the reverse. Contrast sensitivity for letter identification was measured with a forced-choice staircase procedure. When plotted in Rayleigh (Michelson) units, contrast sensitivity was higher for letters of positive than of equivalent negative contrast, and the contrast sensitivity function for letters of positive contrast extended to smaller letter sizes. In Weber units, however, contrast sensitivity was equivalent for increments and decrements of equal magnitudes. Performance at Weber contrasts greater than unity was predictable from a negative exponential fit to the letter contrast sensitivity functions. Onset-offset characteristics had no differential effect on letter contrast sensitivity. These results indicate that the Weber definition provides the better metric for specifying letter contrast, and the findings provide a framework for predicting the effect of contrast polarity on tasks that involve letter identification.

In the study of visual disorders, contrast sensitivity has been measured with both windowed sinusoidal gratings and with letters. It has been suggested that contrast sensitivity functions for both types of stimuli are quite similar (e.g., Legge et al., 1987; Herse and Bedell, 1989), although comparisons have not been made under comparable conditions. While sinusoidal stimuli are advantageous for studying spatial mechanisms, letters are more familiar to patients, contain multiple orientations, are less subject to spurious resolution and are more affected by sampling irregularity than are gratings (Herse and Bedell, 1989), all of which suggest that the measurement of contrast sensitivity for letters may have an advantage in detecting visual abnormalities. However, letters contain a broad range of spatial frequencies (Parish and Sperling, 1991) which potentially complicates the interpretation of test results using these stimuli.

Patients with retinitis pigmentosa (RP) not infrequently exhibit reductions in foveal visual acuity in addition to night blindness and peripheral visual field restrictions. Measurement of visual acuity in RP subjects has typically been made with an extended duration of target presentation. Since there is evidence of abnormal temporal processing in some RP subjects (e.g., Tyler et al., 1984; Dagnelie and Massof, 1990), it is possible that such long-duration viewing of acuity targets underestimates the degree of acuity loss under conditions of briefer target duration. To address this issue, we have examined the temporal properties of foveal vision in RP subjects using Sloan letter identification. First, we measured log MAR (minimum angle of resolution) as a function of stimulus duration to determine whether RP subjects demonstrate a greater degree of acuity loss at short durations. Second, we measured contrast thresholds as a function of stimulus duration at a fixed letter size to determine whether temporal summation for letter identification is abnormal.

Following adapting field onset, the amplitude of the cone-system electroretinogram (ERG) b-wave increases systematically over several minutes, a finding that has been assumed to represent a partial return of the ERG response toward the dark-adapted value. To examine the validity of this assumption, we have measured luminance-response functions of the cone-system ERG, isolated using 31-Hz flicker, in normal subjects under both dark-adapted and light-adapted conditions. Our findings show that the increase in amplitude of the cone-system flicker ERG that occurs during light adaptation does not represent a return toward a dark-adapted baseline but, instead, entails a substantial enhancement above the dark-adapted value. It is likely that this is also the case for the single-flash ERG, as evidenced by our findings relating to a subject with an unusual form of night blindness, in whom the absence of rod-mediated vision allowed the recording of single-flash cone system ERG responses in the dark-adapted state. Preliminary evidence suggests that selective alterations in ERG off-components may contribute to this phenomenon.

Because of the possible role of melanin in various ocular pathologies, it is important to develop a noninvasive objective measurement of this ocular pigment. We have used imaging fundus reflectometry to assess the spatial distribution of melanin within the macular region. A microchannel plate-intensifier solid-state video camera viewed an area of the fundus (21° horizontally by 16° vertically) through the optics of a modified Zeiss fundus camera. A fiber-optic lightguide illuminated by a computer-controlled optical system replaced the normal Zeiss light source. Images of the unbleached and bleached fundus were obtained at thirteen wavelengths (460-700 nm). For the present study, digitally processed images of the bleached fundus obtained at long wavelengths (>620 nm) were used to provide an estimate of the spatial distribution of melanin in the macular region. In three Caucasian subjects, our measurements show a region of lower reflectance in these long wavelengths that is ~10° in diameter and centered on the fovea. This result is consistent with previous anatomic studies reporting that the melanin optical density is higher in the central macula than in the surrounding region.

Retinitis pigmentosa (RP) is a group of genetic retinal dystrophies characterized by nightblindness, visual field depression, intraretinal bone-spicule-like pigmentation, narrowing of the retinal vessels, and a reduction in the amplitude of the electroretinogram. Usher's syndrome is a variant of RP in which there is also a congenital neurosensory hearing defect. Although the loss of visual function in RP typically is more severe in the retinal periphery, there is ultimately a reduction in foveal function in a substantial number of RP patients.

Recent measurements of the dark-adapted foveal spectral sensitivity of retinitis pigmentosa (RP) patients have shown that some patients have a considerably reduced sensitivity at short wavelengths (Alexander, Hutman and Fishman, 1985). Moreover, there is an inverse correlation between the relative sensitivity at short wavelengths and the absolute sensitivity at longer wavelengths, such that patients with the best overall sensitivity show the greatest reduction in short-wavelength sensitivity.

Psychophysical studies have shown that the rod system can reduce the flicker sensitivity of the cone system at temporal frequencies near 10 Hz, apparently through the interference of out-of-phase rod and cone signals. Light-adapting or bleaching the rod system improves flicker sensitivity. We have examined an electrophysiological correlate of this rod-cone interaction by measuring ERG responses to a long-wavelength (Wratten No. 23A) Ganzfeld stimulus flickering at 10 Hz, either in the dark-adapted eye, against a steady Ganzfeld background, or following a Ganzfeld bleach. Consistent with the psychophysical finding, the amplitude of the cone component of the b wave is larger if the eye is moderately light-adapted or partially bleached rather than completely dark-adapted. A comparison of the ERG responses to scotopically matched short- and long-wavelength Ganzfeld flickering stimuli shows that in the dark-adapted eye, a negative-going rod response subtracts from the positive cone b-wave response, reducing its amplitude. Light adaptation shortens the implicit time of the rod response and reduces its amplitude, so that its negative influence on the cone b wave is reduced. The effect of light adaptation on the cone flicker ERG is therefore predictable from the algebraic summation of phase-shifted rod and cone ERG subcomponents.

Luminance-response functions of the dark-adapted ERG b-wave have been previously described by the Naka-Rushton equation R/R max = L n /(L n + K n ), in which R is the response to a stimulus of luminance L, R max is the maximum response amplitude, K is the luminance required to achieve a response one-half the amplitude of R max , and n is a dimensionless slope constant (1,2). However, when recording from normal observers and from patients with retinal disorders, we have observed that the Naka-Rushton equation does not represent the entire b-wave luminance-response function. Instead, our functions are composed of two distinct limbs. One limb appears to saturate at the luminance levels reported previously (1). However, as flash luminance increases above this level, a second limb appears. In the present report, we document the non-monotonic nature of the b-wave luminance-response function and examine possible explanations for the high luminance limb by recording ERGs from selected patients.

Xanthophyll, a short-wavelength absorbing, non-bleaching macular pigment consisting primarily of lutein and zeaxanthin (Bone et al., 1985), may partially protect the foveal photoreceptors from light damage (Kirschfeld, 1982). For example, it has been suggested that the characteristic fundus pattern of bull’s eye maculopathies may be the clinical expression of this relative photoprotective effect (Weiter and Delori, 1986). It is of interest, therefore, to develop an objective, noninvasive technique for estimating the optical density of the macular pigment in the human eye.

Optotype acuity was measured as a function of chart illumination in patients with retinitis pigmentosa (RP) to characterize more completely the degree of foveal impairment in this night-blinding disorder. Acuity-luminance functions were obtained from twenty RP patients who had 20/40 or better Snellen acuity, minimal or no posterior subcapsular cataracts, and no observable foveal lesions, as well as from ten age-similar normal observers. Subjects viewed modified Bailey-Lovie charts through an artificial pupil and an appropriate correction in a phoropter with illumination ranging from −1.1 to 5.2 log Td. Results were analyzed with a hyperbolic equation: in which MAR is the measured minimum angle of resolution, A is the asymptotic value of MAR, I is the chart retinal illuminance, s is a semisaturation parameter, and m is a slope parameter. The RP patients showed normal values of logs but had increases in logA and logm that were correlated significantly (r = 0.65). These findings indicate that (1) the greater the acuity loss of the RP patients at high luminances, the proportionately greater their acuity deficit at low luminances; (2) the patient’s acuity reductions result from a mechanism other than a decreased quantal catch.

In normal observers the rod system influences both cone-mediated flicker thresholds and thresholds for color (Lie specific threshold). Both types of thresholds become elevated as rods recover sensitivity after a bleach and both are reduced by light adapting the rod system. We have compared these two types of rod–cone interaction in two patients with congenital stationary night blindness (CSNB). Evidence suggests that in this condition the rod outer segments function normally (e.g., the a-wave of the scotopic ERG was normal) but there is a defect in the transmission of rod signals within the retina (rod absolute thresholds were elevated at least three log units and the scotopic ERG showed a markedly reduced b-wave). Thresholds for detecting flicker (white, 25 Hz, 1.7°, 3-s test) or color (525 nm, 1.7°, 500-ms test) were measured with a Tubinger perimeter in dark-adapted conditions, following a bleach and against a rod-desensitizing background. The rod–cone flicker interaction was normal in the two CSNB patients, but the rod influence on color thresholds was absent. These results indicate that the two types of rod–cone interaction are mediated by different neural pathways and provide additional constraints about the locus of the visual defect in these two CSNB patients.