Visual sensitivity to motion: age-related changes and deficits in senile dementia of the Alzheimer type.

To determine whether motion sensitivity varies with age, we measured motion discrimination in visual normals 25 to 80 years of age and found that motion thresholds increased linearly with age and were approximately two times higher in those 70 to 80 years old than in participants under thirty. This increase was not attributable to pupil size or retinal image distortion, but probably reflects neurodegeneration in the primary visual pathway. We compared the motion sensitivity of patients with senile dementia of the Alzheimer type (SDAT) with results from a subset of the visual normals of similar age. In SDAT patients, there were significant threshold elevations, which were more pronounced in the patients with more severe dementia. These findings confirm previous reports of visual system involvement in SDAT and indicate motion testing may reveal preclinical visual system involvement in SDAT.

Visual field loss in senile dementia of the Alzheimer's type.

BACKGROUND: Visual performance is impaired in patients with senile dementia of the Alzheimer's type (SDAT). We investigated the visual field topography of these deficits. METHODS: Humphrey automated perimetry (Program 30-2) was used to measure differential luminance sensitivity within the central 60 degrees of the visual field in SDAT patients (n = 61) and in visually and cognitively normal volunteer subjects of similar age (n = 61). Twenty-three SDAT patients were retested 18 months after the original examination. RESULTS: Reliable visual fields (by manufacturer's criteria) were obtained in 72.1% (44/61) of the control subjects and 55.7% (34/61) of the SDAT group. In the SDAT group, differential luminance sensitivity was significantly reduced relative to the control group. Visual sensitivity was reduced throughout the visual field, but deficits were most pronounced in the inferior visual field, where they presented most commonly as arcuate defects. Patients with more severe dementia exhibited greater reductions in visual sensitivity. On follow-up, 14 of 23 SDAT patients exhibited progression of visual field loss, whereas only two of 23 patients exhibited a regression of the visual field loss. CONCLUSIONS: Although automated perimetry requires considerable patient cooperation, many patients with SDAT can produce reliable visual field results. These patients exhibit significant reductions in global sensitivity. Visual field loss in SDAT is most pronounced in the inferonasal and inferotemporal arcuate regions of the visual field but also involves the central field.

Pattern electroretinograms and visual evoked potentials in HIV infection: evidence of asymptomatic retinal and postretinal impairment in the absence of infectious retinopathy.

Retinal microangiopathy associated with HIV infection is usually asymptomatic and escapes detection unless funduscopic examination is performed when evanescent cotton-wool spots are present. The aim of this study was to assess retinal and optic nerve/retrochiasmal function in HIV infection by means of electrophysiologic techniques that are sensitive to the detection of subclinical visual impairment. We studied transient and steady state pattern electroretinograms grams (PERGs) and pattern-reversal visual evoked potentials (PVEPs) in 21 HIV-negative controls and 33 HIV-positive subjects (16 with CD4 > or = 200/mL and 17 with CD4 < 200/mL) without visual symptoms or infectious retinopathy. HIV-positive subjects with CD4 > or = 200/mL had reduced amplitude of the transient PERG P1 potential, but no other latency or amplitude abnormalities. The HIV-positive group with CD4 < 200/mL had reduced P1 transient PERG amplitude, as well as latency delay of the transient PVEP. These findings suggest that HIV infection is associated with subclinical retinopathy and that, when severe immunosuppression occurs, both retinopathy and optic nerve/retrochiasmal dysfunction are present. Transient PERGs are more sensitive measures of visual system disease in HIV infection than are steady state responses.

PRRP abnormalities in glaucoma and ocular hypertension.

The human-pattern reversal retinal potential (PRRP) is a bioelectrical response that reflects neural activity generated in the proximal retina. Visual diseases which affect the retinal ganglion cells and the optic nerve often produce significant reductions in the amplitude of the PRRP. PRRP amplitude reductions are frequently observed in patients with primary open-angle glaucoma (POAG). This investigation was designed to determine whether patients with ocular hypertension (OHT) who are at risk of developing POAG also exhibit PRRP amplitude reductions. High contrast (76%), rapidly counterphasing (16 rps), phase alternating checkerboard patterns (15-120 min checks) were used to elicit PRRPs from patients with POAG (n = 12) and OHT (n = 24), as well as age-matched visual normals (n = 11). The patients with OHT were selected to be either at high or low risk of developing POAG. The results indicate that PRRP amplitude reductions similar to those exhibited by POAG patients do occur in some OHT patients. However, many other ocular hypertensives, particularly those at low risk of developing POAG, do not exhibit PRRP abnormalities.

Retinal potentials in patients with primary open-angle glaucoma: physiological evidence for temporal frequency tuning deficits.

The pattern-reversal retinal potential is a bio-electrical signal which can be recorded from the cornea of the human eye when a phase-alternating (contrast-reversing) pattern is viewed. The PRRP is correlated with activity of the retinal ganglion cells and visual diseases which affect the proximal retinal layers (such as optic atrophy and optic neuritis) and cause significant alterations in the waveform of the human PRRP. This study examined the PRRP in 32 patients with primary open-angle glaucoma (POAG) and 32 age-matched visual normals (AMVNs). Counterphasing (2, 4, 8 and 16 reversals/sec) checkerboard patterns (15', 30', 60', and 120' checks) were used as visual stimuli. PRRP amplitude was significantly reduced in patients with POAG. When temporal frequency was held constant, the magnitude of the observed PRRP amplitude reductions was identical for all check sizes. However, the magnitude of the observed amplitude reductions increased as temporal frequency increased. Therefore, in patients with POAG, the shape of the PRRP spatial tuning function was normal (although uniformly reduced for all check sizes), while the temporal tuning function was attenuated for high frequencies. Statistically significant increases in PRRP latency were also observed in the POAG patients, but these increases were quite small (mean = 3.6 ms).

Spatial and temporal frequency tuning of pattern-reversal retinal potentials.

Pattern-reversal retinal potentials (PRRPs) are electrical signals generated within the human retina, possibly by the retinal ganglion cells, when a phase-alternating checkerboard pattern (or grating) is viewed. This study systematically examined the effects of varying the spatial and/or temporal frequency of the stimulus pattern on the resulting PRRP. A significant variation in PRRP amplitude, which was dependent on both the spatial and temporal frequency of the stimulus, was observed. Optimum response amplitude was obtained with a low spatial frequency (0.250 cy/deg) at intermediate temporal frequencies (3.75 or 7.50 Hz). A linear regression, fit to the average PRRP amplitude vs. spatial frequency data for either the 1.88 or 3.75 Hz conditions, appears to predict average subjective visual acuity.

Altering body position affects intraocular pressure and visual function.

Intraocular pressure (IOP) can be altered by changing body position. This report describes two experiments evaluating variations in IOP, as well as neural functioning of the retina and visual cortex (as measured by pattern-reversal electroretinogram and visual evoked potential), associated with whole-body, head-down tilt. The subjects, ten per experiment, were visually normal with IOP less than 19. In the first experiment, IOP elevations were induced by varying the angle of tilt in discrete steps between +90 degrees (upright) and -90 degrees (inverted). In each position IOP was measured and significant elevations (up to 3x baseline) were noted. These elevations were maintained for 1 min during which simultaneous retinal and cortical biopotentials were measured. In the second experiment, 6 degrees head-down tilt was maintained for 2 hr during which time the IOP and both biopotentials were measured repeatedly. Our findings confirm the effect of body position of IOP, while also revealing that head-down tilt produces significant reductions in neurophysiological function at both the retinal and cortical levels. The neural effect is maximized when 6 degrees head-down tilt is maintained for 20 min.

Improved electrode for electroretinography.

Corneal electrodes useful for clinical electroretinography require topical anesthesia, interfere with vision, can abrade, and are not well accepted by most children and many adults. A low mass conductive thread, corneal (DTL) electrode is described and comparatively tested against the Burian-Allen electrode. The DTL electrode was found to have few of the limitations of the hard contact lens electrode. Furthermore, the DTL electrode signal quality was comparable to that of the Burian-Allen electrode and provided less between-patient variability.

Motion perception is abnormal in primary open-angle glaucoma and ocular hypertension.

Several lines of evidence suggest that the large optic nerve fibers, which form the magnocellular retinocortical pathway, are preferentially susceptible to early glaucomatous damage. It is evident from studies of the functional architecture of the visual system that the magnocellular pathway underlies the global perception of motion. Therefore, we have developed a psychophysical technique for assessing motion detection thresholds in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG). For this purpose we employed a dynamic random dot display that contained varying degrees of a coherent motion signal embedded within a background of random motion noise. We used this technique to measure motion thresholds in POAG patients (n = 37), OHT patients (n = 14), and age-matched controls (n = 39). Motion thresholds were elevated by 70% for the POAG group and 44% for the OHT group relative to controls. In the same patients, no significant deficit in form discrimination was found as measured by Pelli-Robson charts. Our results demonstrate that significant motion perception deficits are evident in POAG and OHT. These findings support the suggestion that significant and selective damage to the magnocellular pathway occurs in OHT and POAG and indicate that motion threshold testing may reveal preclinical optic nerve disease in early POAG.

Quantitative evaluation of papilledema in pseudotumor cerebri.

PURPOSE: To determine the feasibility of adapting confocal scanning laser (CSL) tomography of the optic disc for quantitative evaluation of papilledema in pseudotumor cerebri (PTC). METHODS: Confocal scanning laser tomography of the optic disc was performed in 11 patients with diagnosed PTC and 12 visually normal control subjects of similar age. In five patients with active papilledema, CSL tomography was performed serially over several months. To quantify optic disc characteristics, surface topography was measured in 0.1-mm steps along the horizontal and vertical meridians and four oblique meridians. Best fit polynomial functions, describing surface topography along each meridian, were derived using linear regression analysis. RESULTS: Third-order polynomials provided excellent fits (significantly better than the second-order functions) to the surface topography for all meridians in the control subjects and patients with PTC. In control subjects and PTC patients an asymmetry in the slope of the optic disc contours was evident along the horizontal but not the vertical meridian. In patients with active papilledema a significant elevation of the center of the disc was accompanied by a change in overall surface topography. Each of the PTC patients followed up serially had a pronounced posterior deformation of the disc (i.e., a reduction in papilledema) that was initially apparent in the temporal meridian and did not proceed uniformly across all meridians. CONCLUSIONS: Confocal scanning laser tomography can quantify the magnitude and monitor the resolution of papilledema in PTC. Studies of optic nerve head topography may provide further insight into optic nerve compliance with elevated intracranial pressure.

Interocular luminance differences and the binocular pattern-reversal visual-evoked response.

Although the visual-evoked response (VER) is frequently used to assess binocularity, the contribution of the monocular components to the binocular VER is poorly understood. To more fully elucidate this relationship, we examined checkerboard (14 min arc checks) pattern-reversal (3.75 Hz) VERs evoked from observers with normal binocularity, with conditions in which interocular luminance differences (from 0.3 to 2.0 log units) were established. When compared with monocular VERs obtained with similar luminances, the binocular response was always less than the sum of the component monocular responses. In addition, the amplitude of the binocular signal was dependent on the amount of interocular luminance the difference. For interocular luminance differences of less than 0.6 log units the amplitude of the binocular response was consistently greater than either corresponding monocular VER. When the interocular luminance difference was 1.3 log units or greater the amplitude of the binocular response fell below the level of either corresponding monocular response. Furthermore, it does not appear that these results can be attributed to a passive spread of electrical potentials from monocular cortical cell populations. We therefore suggest that these results indicate the activity of a binocular neural process.

Dissociation of visual deficits in ocular hypertension.

Both acquired color vision deficiencies and abnormal pattern electroretinograms (PERGs) are observed in patients with ocular hypertension (OHT) as well as in patients with glaucoma. In the present study we determined the prevalence of both of these functional deficits in a large group of OHT patients (N = 130). Color vision was tested with the desaturated D-15 and a color confusion score was used to quantitatively assess the magnitude of the color vision deficiency. Steady-state PERGs were evoked with rapidly alternating high contrast checkerboard patterns. Color vision deficits were detected in 23% of OHTs while 11.5% of the patients exhibited significant PERG amplitude reductions. Only 2.3% exhibited both abnormalities. The results suggest that although color vision deficiencies and PERG abnormalities are both evident in OHT, they are often dissociated findings.

Glaucomatous visual field damage. Luminance and color-contrast sensitivities.

Using a modified Humphrey perimeter, we evaluated 16 eyes with primary open-angle glaucoma and visual field loss (defects 0.5-3.0 log units in depth), and 14 normal eyes. Each eye was tested twice in random order with conventional luminance-increment static perimetry and with the perimeter modified to produce a high-luminance yellow adapting background and a blue test stimulus. The background was a broad-spectrum light of 500 nm and above (yellow), while the stimulus was a broad-spectrum light of 500 nm and below (blue). Paired comparisons were made between conventional and blue/yellow sensitivities for every point examined (1184 points in 16 diseased eyes and 1036 points in 14 normal eyes). Defect depths were determined by using the age-corrected norms distributed in the Humphrey Statpac software. In glaucomatous eyes, blue/yellow sensitivity showed greater impairment than did conventional perimetric sensitivity, in which defect depths were less than 1.0 log unit. However, for defects greater than 1.0 log unit in depth, conventional perimetric sensitivity and blue/yellow sensitivity showed equivalent degrees of damage. Receiver operating characteristic (ROC) analysis was used to compare the ability of blue/yellow and of conventional perimetry in distinguishing between glaucomatous and normal eyes. Results indicated that although blue/yellow color-contrast perimetry may be more sensitive for the detection of incipient glaucomatous damage, in the manifest stages of visual field damage blue/yellow color-contrast perimetry is no more sensitive than is conventional (luminance-increment) perimetry for defining the extent of glaucomatous visual field defects.

Motion perception deficits in glaucomatous optic neuropathy.

The mechanisms mediating impaired motion perception in glaucoma were investigated. Direction discrimination thresholds for low (4.2 deg/sec) and high (12.5 deg/sec) velocity random-dot kinematograms were measured in controls and patients with glaucoma or ocular hypertension. Thresholds were elevated significantly in glaucoma patients and individual ocular hypertensives. Threshold elevations were not due to blur or pupil size. After compensating for motion reversals, high but not low velocity thresholds remained elevated. Only high velocity thresholds correlated with differential luminance sensitivity. A hypothesis that different mechanisms mediate glaucoma-induced deficits at high and low velocities is presented.

Altered pattern evoked retinal and cortical potentials associated with human senescence.

Physiologically healthy elderly individuals often exhibit visual deficits which result from age-related changes in both the transmission characteristics of the ocular media and the functional properties of the neural elements in the visual pathway. Many of the age-related changes in the optical quality of the ocular media have been identified, but the age-dependent variations in visual neurophysiology have not been clearly delineated. This investigation examined age-related alterations in pattern-specific biopotentials generated in the human retina and visual cortex. Counterphasing (2.0 and 7.5 rps) patterns (7.5', 15', 30' and 60' checks) were used to simultaneously monitor pattern-reversal visual evoked potentials (PRVEPs). Young visual normals (20-30 years of age) and healthy elderly observers (70-80 years of age) with visual acuity of 20/30 or better were studied. All data were corrected for the effects of senile miosis on retinal illumination. Significant variations in the waveform characteristics of both biopotentials were noted for the elderly individuals. PRRP amplitude was uniformly reduced for all stimulus conditions. PRVEP amplitude reductions were also noted but were more stimulus specific than the PRRP amplitude reductions. No significant PRVEP or PRRP latency changes were observed. These results suggest that alterations in the physiological properties of neural elements in both the retina and visual cortex are associated with normal aging.

Pattern reversal electroretinogram (PRERG) abnormalities in ocular hypertension: correlation with glaucoma risk factors.

The indices employed commonly for the diagnosis of glaucoma (tonometry, ophthalmoscopy and perimetry) do not always identify which patients with ocular hypertension (OHT) will develop primary open-angle glaucoma (POAG) before irreversible visual field loss is manifest (1). The human pattern reversal electroretinogram (PRERG) is a bioelectric response reflecting neural activity of the proximal retina. PRERG amplitude reductions have been observed in POAG and other diseases affecting the optic nerve and retinal ganglion cells. This study was designed to determine whether OHT patients exhibit PRERG amplitude reductions and whether PRERG results are correlated with routinely evaluated clinical parameters. Steady-state PRERG (16 rps) were elicited by high contrast (76%), phase alternating checkerboard patterns (15-20 min checks) from one eye of 130 patients with ocular hypertension and 47 age matched visual normals (AMVNs). A significant (p less than 0.05) reduction in PRERG amplitude was noted for the OHT patients and 11.5% of those patients exhibited PRERG amplitudes more than 2.0 standard deviations below the AMVN mean. PRERG amplitude was found to be positively correlated with diastolic blood pressure (DBP) and negatively correlated with age, but no correlation between PRERG amplitude and either IOP, C/D ratio, or systolic blood pressure was evident. The lack of correlation between PRERG amplitude and the commonly used clinical indices may suggest a complementary role for this neurophysiologic test in determining which OHT patients will develop glaucoma.

Power spectral analysis of visual evoked potentials in multiple sclerosis.

Power spectral analysis (PSA) was performed on the visual evoked potentials (VEPs) to counterphased checkerboard stimuli from 98 eyes in 49 patients with multiple sclerosis (MS) and 54 eyes of 27 normal volunteers. Attenuation of high frequency components of the transient visual evoked potential was found in 53% of MS patients and 4% of controls. Loss of high frequency components was poorly correlated with prolonged latency (r = 0.346). The consideration of both PSA and latency of the VEP increased the percentage of MS patients exhibiting visual pathway conduction abnormalities from 61% to 86%. The use of PSA in the diagnosis of MS is useful in increasing detection especially in cases where deformed waveforms preclude a reliable estimation of latency.

The relationship of retrobulbar hematomas to vision in cynomolgus monkeys.

An experimental model has been developed to measure the effect of retrobulbar hematomas on functional vision in cynomolgus monkeys. In this model, functional vision was quantitated using flashed evoked visual potentials in five monkeys following creation of retrobulbar hematomas. In one monkey used as a control, functional vision remained impaired for 180 minutes following induction of retinal ischemia by increased intraorbital pressure. In two monkeys in which increased intraorbital pressure was relieved by anterior chamber paracentesis following 15 minutes of retinal ischemia, flashed evoked visual potential promptly returned to baseline level. In two additional monkeys in which increased intraorbital pressure was relieved following 30 minutes of retinal ischemia, flashed evoked visual potentials improved but never returned to baseline levels. This study demonstrates the usefulness of flashed evoked visual potentials in measuring functional vision in cynomolgus monkeys. This experimental model should prove useful in evaluating the effects of increased intraorbital pressure on functional vision and the effect of intervention on impaired vision due to retrobulbar hematomas. Further studies with larger numbers of animals are needed to clarify these preliminary studies and document longer-term effects of retinal ischemia secondary to retrobulbar hematomas.

Simulation of spaceflight with whole-body head-down tilt: influence on intraocular pressure and retinocortical processing.

Cephalad fluid shifts occur in the microgravity environment of spaceflight. Whole-body head-down tilt was used to simulate the influence of these fluid shifts upon intraocular pressure (IOP) and the bioelectrical activity of neural elements in the retinocortical pathway. Noninvasive techniques were used to monitor IOP, pattern reversal electroretinograms (prERGs), and pattern reversal visual evoked cortical potentials (prVEPs) when subjects were oriented either upright or in a head-down position (6 degrees or 90 degrees). The results indicate that there is a significant elevation in IOP when an individual is oriented in a head-down position. Significant alterations of neurophysiological processing in the retinocortical pathway also occur when individuals are oriented in a head-down position.