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Biomedical subjects

K R Alexander

Publications and source records attributed to K R Alexander.

At least 55 records · Page 3Linked to original sources

Light adaptation, rods, and the human cone flicker ERG.

During the course of light adaptation, the amplitude and implicit time of the human cone ERG change systematically. In the present study, the effect of adapting field luminance on these ERG changes was assessed, and the hypothesis that light adaptation of the rod system is the primary determining factor was evaluated. Cone ERG responses, isolated through the use of 31.1-Hz flicker, were obtained from two visually normal subjects, initially under dark-adapted conditions and then repeatedly for 30 min following the onset of each of a series of ganzfeld adapting fields with luminances that ranged from -1.2 to 2.1 log cd/m2. The increase in flicker ERG amplitude and decrease in implicit time during light adaptation were greatest at the highest adapting field luminances. Photopically equivalent achromatic and long-wavelength adapting fields induced comparable increases in flicker ERG amplitude, while scotopically equivalent adapting fields had considerably different effects. This latter finding demonstrates that the rod system is not a major determinant of the adaptation-induced increase in cone ERG amplitude.

Adaptation, Ocular↗

Grating, vernier, and letter acuity in retinitis pigmentosa.

Grating, vernier, and letter acuities were compared in 25 patients with retinitis pigmentosa (RP), whose Snellen visual acuities were better than 20/40, to address the mechanism of visual acuity loss. For these patients with RP, all three types of visual acuity were reduced to an equivalent degree from those of a control group of 10 age-similar, visually normal subjects. The findings indicate that the visual acuity losses of these subjects with RP did not result from cone spatial undersampling (due, for example, to a random loss of foveal cones), from cone sampling irregularities (due to random alterations in foveal cone position), or from a selective loss of sensitivity to high spatial frequencies (as might result from changes in media transmission characteristics or a gain reduction in high spatial frequency mechanisms). In addition, previous studies have indicated that acuity losses in such patients with RP do not result from reductions in the quantum-catching ability of foveal cones. The most likely explanation for the equivalent losses in all three acuity types in these patients with RP appears to be an alteration in foveal spatial scale, consistent with a generalized increase in foveal intercone spacing.

Adult↗

'On' response defect in paraneoplastic night blindness with cutaneous malignant melanoma.

Response properties of rod and cone systems were assessed in a patient with an acquired form of night blindness associated with a metastatic cutaneous malignant melanoma. The night blindness, a sensation of shimmering lights, and selective reductions in the amplitudes of both rod and cone electroretinographic (ERG) b-waves were present before and after chemotherapy, confirming that this disorder was a paraneoplastic consequence of the melanoma rather than a response to chemotherapy. During ERG testing with flashes of extended duration, the cone b-wave abnormality was found to be a predominant loss of the cone ERG "on" response with relative preservation of the "off" response, similar to that observed in patients with congenital stationary night blindness. An impairment in signal transmission specific for retinal "on" pathways may be a primary defect in both of these forms of night blindness.

Adolescent↗

Contrast thresholds for letter identification in retinitis pigmentosa.

To assess mechanisms of foveal vision loss in retinitis pigmentosa (RP), contrast thresholds were measured for the identification of Sloan letters at four adapting field luminances (0.4, 1.4, 2.4, and 3.4 log td) in a group of 16 patients with RP who had best-corrected Snellen visual acuities of 20/30 or better, minimal or no posterior subcapsular cataracts, and no atrophic or cystic-appearing foveal lesions. Letter contrast sensitivities of the patients with RP were reduced below those of a group of ten subjects with normal vision for all letter sizes and at all adapting field luminances. The overall pattern of these results indicated that neither a reduced quantal absorption by foveal cones nor spatial undersampling from a loss of foveal cones accounted for the reductions in letter contrast sensitivities. The findings were most consistent with a uniform increase in intercone spacing in the foveas of this group of patients with RP and mild visual acuity loss.

Adaptation, Ocular↗

Effects of light adaptation on the response characteristics of human oscillatory potentials.

We have examined the response characteristics of the oscillatory potentials (OPs) of the human electroretinogram (ERG) obtained to ganzfeld flash stimuli presented against adapting fields. First, we determined the extent to which the OPs obtained to high luminance flashes change during the course of light adaptation to a cone-isolating adapting field. Regardless of the number of OP wavelets, the last OP wavelet increased in amplitude and decreased in implicit time to a greater extent than did the earlier wavelet(s). In addition, we examined the role of both flash and adapting field luminance in determining the wave form of the OPs. For each adapting field luminance that was tested, the number of OP wavelets increased as flash luminance increased, primarily resulting from the splitting of the last OP into 2 distinct wavelets. While the number of OP wavelets generally decreased as adapting field luminance increased, the amplitude of the last OP became larger. These functional distinctions between the last and the earlier wavelets are consistent with their representing the activity of different retinal generators.

Adult↗

Delayed rod dark adaptation in patients with Stargardt's disease.

Twelve patients with Stargardt's dystrophy were each found to have a prolongation in rod dark adaptation. All had a normal rate of recovery during the early portion of rod dark adaptation but a selective prolongation of the later segment of rod recovery. This observation was apparent in patients with limited fundus flecks and those with extensive fundus flecks, whether or not a dark choroid was observed and independent of the presence or absence of an atrophic-appearing macular lesion. A defect within retinal pigment epithelial cells of an enzyme or intracellular transport mechanism involved in the visual pigment regeneration cycle could account for these findings.

Adult↗

Peripheral vision screening for driving in retinitis pigmentosa patients.

The authors evaluated the test protocols used most frequently to screen the peripheral visual field of driving applicants to determine whether they are suitable for detecting peripheral field loss in patients with retinitis pigmentosa (RP). The peripheral vision tests available on the Keystone View Tester and the Titmus Vision Tester were administered to 23 subjects with RP, 3 subjects with Type 2 Usher's syndrome, and 1 subject who was a partially affected carrier of X-linked recessive RP. The subjects had varying degrees and types of visual field loss. Tests were administered using the standard protocol of the State of Illinois, which is a standard procedure used by state licensing bureaus nationwide. Results demonstrate that the screening protocols use stimulus conditions that are primarily sensitive only to appreciable field losses and examine locations that typically lie within an RP patient's remaining visual field rather than at locations that characteristically are scotomatous. The authors suggest that the current test protocols could determine peripheral field impairment more accurately by assessing additional locations in the visual field, and by introducing a background field and/or by reducing the luminance of the test targets.

Adult↗

Acuity-luminance and foveal increment threshold functions in retinitis pigmentosa.

Acuity-luminance functions and foveal increment threshold functions were measured in 20 subjects with retinitis pigmentosa (RP) who had Snellen acuities of 20/40 or better, minimal or no posterior subcapsular cataracts, and no atrophic-appearing foveal lesions. Compared with the results from ten normal subjects, the visual acuities of the RP subjects were reduced at all luminance levels; the acuity deficits were more pronounced at low luminances. Foveal detection thresholds of the RP subjects showed the greatest elevation at low background luminances and approached normal values at high adapting levels. There was a statistically significant correlation (r = 0.79, P less than 0.01) between the visual acuities and absolute thresholds of the RP subjects. The overall pattern of results cannot be explained by a reduced quantal absorption in foveal cones, but it is consistent with the hypothesis that a reduced cone spatial density is the primary mechanism of foveal visual loss in this group of RP subjects.

Adaptation, Ocular↗

Visual adaptation and the cone flicker electroretinogram.

This study examined the hypothesis that changes in the response properties of the human cone ERG during light adaptation represent the recovery of cone system responsiveness toward a dark-adapted value after an initial decrease in responsiveness at adapting field onset. The electroretinographic (ERG) responses to 31.1 Hz flicker were obtained under both dark-adapted and light-adapted conditions for stimulus luminances ranging from -1.42(-)+0.82 log cd sec/m2. At low stimulus luminances, flicker ERG amplitudes were larger under dark-adapted than under light-adapted conditions, consistent with the hypothesis. However, at high stimulus luminances, flicker ERG amplitudes obtained under light-adapted conditions were approximately double those recorded from the dark-adapted eye. Therefore, the increase in cone ERG amplitude that occurs during light adaptation at high stimulus luminances does not represent a return toward a dark-adapted level but instead entails a substantial enhancement above the dark-adapted value, by a mechanism that is presently unidentified.

Adult↗

Spatial properties of rod-cone interactions in flicker and hue detection.

Rod-cone interactions in flicker and hue detection were compared to examine the hypothesis that they are mediated by mechanisms with different spatial properties. Flicker and hue thresholds for a 1 deg test stimulus (TS) were measured as a function of background luminance and diameter. Flicker thresholds were reduced from their dark-adapted value by an 11 deg diameter background, but not by a 1 deg background. These results, in agreement with previous work, demonstrate that light adaptation of rods surrounding the TS is necessary to eliminate their effect on cone flicker thresholds. In contrast, hue thresholds were reduced from their dark-adapted value to a comparable degree by 1 and 11 deg backgrounds, indicating that light adaptation of the rods stimulated by the TS is sufficient to abolish the rod-cone hue interaction. Our results support the contention that the rod-cone flicker and hue interactions are mediated by different mechanisms. We also demonstrated that changing the detection task while keeping stimulus parameters constant is sufficient to shift between these two types of rod-cone interactions.

Adaptation, Ocular↗

A form of congenital stationary night blindness with apparent defect of rod phototransduction.

We report findings obtained from an individual with an unusual form of congenital stationary night blindness (CSNB). Although the rhodopsin density difference of this subject was normal, there was no evidence of rod-mediated visual function. Dark-adapted thresholds were cone-mediated, and dark-adapted electroretinograms (ERGs) represented activity of the cone system exclusively. ERG a- and b-waves obtained under light-adapted conditions were normal. The absence of a rod a-wave but the presence of normal rhodopsin density, in combination with normal cone function, indicates that this form of CSNB likely involves a defect of phototransduction that is limited to the rods. In addition, light-adapted b-wave responses to high luminance flashes were larger than dark-adapted responses, whereas a-wave amplitudes were reduced by light adaptation. These ERG results address proposed mechanisms by which light adaptation might enhance cone system responses.

Adolescent↗

Human macular pigment assessed by imaging fundus reflectometry.

A computerized, television-based, imaging fundus reflectometer was used to obtain estimates of the spatial distribution of macular pigment (xanthophylls) from seven normal subjects. Digitized images of the bleached macula of each subject were acquired at illuminating wavelengths from 462 to 697 nm. An analysis of spectral reflectances indicated that differences in short-wavelength reflectance between the foveal center and parafovea were influenced by spatial variations in melanin and oxyhemoglobin absorption as well as by the distribution of macular pigment. To provide an estimate of the spatial distribution of macular pigment alone, we have corrected fundus images obtained at 462 nm for the effect of melanin and oxyhemoglobin absorption. The spatial variation in macular pigment double density across the horizontal and vertical meridians of the retina was well described by Gaussian functions. The peak double densities for the individual subjects ranged from 0.22 to 0.45 and the standard deviations of the Gaussian functions averaged approx. 1 degree.

Adult↗

The luminance-response function of the dark-adapted human electroretinogram.

A hyperbolic equation of the form (R/Rmax) = Ln/(Ln + Kn) has been used to describe the b-wave luminance-response function of the dark-adapted human electroretinogram (ERG). However, this equation accurately describes the function only at low to moderate flash luminances. At high flash luminances, a second amplitude increase or "limb" appears in the function. The results of the present study demonstrate that this limb does not represent a cone system response. First, the spectral sensitivity of the entire luminance-response function is rod-determined in normal subjects. Second, the limb was present in a rod monochromat, in whom cone system ERGs were indistinguishable from noise. Instead, the nonmonotonic nature of the luminance-response function may result from a luminance-dependent algebraic summation of the components that underlie the ERG waveform of the rod system.

Color Vision Defects↗

Letter contrast sensitivity in retinitis pigmentosa patients assessed by Regan charts.

Regan Contrast Sensitivity Letter Charts were used to assess the effects of reduced contrast and luminance on visual acuity in retinitis pigmentosa (RP) patients. Letter acuity was measured monocularly in 17 RP patients and in 14 age-similar normals using charts of three different contrast levels presented at each of four levels of illumination. Despite visual acuities of 20/40 or better under standard clinical test conditions, an appreciable number of RP patients were unable to identify any letters on the intermediate- and/or low-contrast Regan charts. For example, even at the recommended test luminance, 5 patients could not read any letters on the intermediate (11%) contrast chart, and 9 could not be scored on the low (4%) contrast chart. Consequently, the Regan charts were found to have limited usefulness in quantifying the exact extent of visual impairment in this group of RP patients. Nevertheless, our results document the degree of visual acuity loss that can be experienced by RP patients under conditions of low contrast and luminance.

Adolescent↗

Mechanisms of rod-cone interaction: evidence from congenital stationary nightblindness.

The dark-adapted rod system can elevate cone-mediated thresholds for flicker detection as well as thresholds for the detection of hue. We examined these two types of rod-cone interactions in two individuals with congenital stationary nightblindness (CSNB), a retinal disorder in which rod outer segment function is intact, but in which a defect occurs in the transmission of rod signals within the retina. The two types of rod-cone interaction were differentially affected by the retinal pathology; the rod-cone flicker interaction was normal, but the rod-cone hue interaction was absent. These results provide evidence that, despite similarities in the adaptational properties of these two types of rod-cone interaction, they are mediated by different visual mechanisms.

Adolescent↗

Rod and cone dysfunction in carriers of X-linked retinitis pigmentosa.

Carriers of X-linked retinitis pigmentosa were studied using electroretinographic and psychophysical procedures. Under both dark- and light-adapted (cone-isolated) conditions, electroretinogram (ERG) a-waves of carriers were reduced in amplitude but normal in implicit time, whereas b-waves were reduced in amplitude and delayed in implicit time. Reductions in b-wave amplitudes of the carriers as a group were equivalent for the rod and cone systems. Luminance-response functions for both dark-adapted and cone-isolated b-waves were fit by the Naka-Rushton equation and demonstrated a selective reduction of Rmax; the semi-saturation constant (K) and the slope parameter (n) were normal. Electroretinograms recorded using the brightest stimulus flashes were most effective at distinguishing carriers from normals. Absolute thresholds of the carriers were elevated significantly across the central 40 degrees of the visual field. As a group, the threshold elevations of the carriers were approximately equal for the rod and cone systems.

Adult↗

Rod and cone system contributions to oscillatory potentials: an explanation for the conditioning flash effect.

The oscillatory potentials (OPs) of the human electroretinogram (ERG) are smaller in response to the initial flash of a series than to subsequent flashes. To investigate a possible rod system contribution to this "conditioning flash effect," we have examined OPs in normals and rod monochromats. The OPs recorded from rod monochromats were similar to those recorded from normals under test conditions that selectively stimulate rods. However, under conditions that in normals stimulate both rods and cones and that result in maximal amplitude of the OPs, the rod monochromats exhibit markedly reduced OPs. This finding suggests that the initial (conditioning) flash operates by adapting the rod system contribution to the OPs, so that the OPs in response to subsequent flashes result primarily from the cone system. In agreement with this hypothesis, the conditioning flash effect did not occur when flashes were presented against a background which eliminated the rod system response nor during the cone plateau phase of dark adaptation.

Color Vision Defects↗

Macular pigment and reduced foveal short-wavelength sensitivity in retinitis pigmentosa.

Some patients with retinitis pigmentosa (RP) show a reduced foveal short-wavelength sensitivity that cannot be attributed to a reduction in the sensitivity of the short-wavelength cone system. To determine whether an increased amount of macular pigment (xanthophyll) might account for this finding, we derived estimates of the two-way optical density of the macular pigment of five such RP patients as well as of five normals. The spectral reflectance of the foveal region of each subject was obtained from digitized images of the bleached fundus provided by a television-based reflectometer. The density spectra of the macular pigment, melanin, and oxygenated hemoglobin were fit by a least-squares procedure to the log of the ratio of parafoveal to foveal spectral reflectance in order to obtain a quantitative estimate of the contribution of each of these ocular pigments to foveal short-wavelength reflectance. By this analysis, the two-way densities of the macular pigment, melanin, and oxyhemoglobin of the RP patients were not significantly different from those of the normals. Therefore, the reduced foveal short-wavelength sensitivity of these patients was not due to an increased amount of macular pigment, but may result instead from morphological abnormalities in the foveal cones such that a normal amount of macular pigment screens the cones more effectively.

Adult↗