Ivan Bodis-Wollner

Abnormalities of Central Contrast Sensitivity in Glaucoma

The detectability of foveally presented low-contrast flickering stimuli was determined for glaucoma patients, ocular hypertensives, and normal control subjects. Two types of stimuli, a homogeneous flickering field, and a counterphase flickering grating of low spatial frequency, were presented on a screen subtending 4 degrees of visual angle. The average of the contrast sensitivities to these two simuli (defined as the dynamic response coefficient) was consistently lower in glaucomatous than in normotensive eyes. The dynamic response coefficient was also below normal in half the ocular hypertensive eyes.

Visual Acuity and Contrast Sensitivity in Patients with Cerebral Lesions

Spatial contrast sensitivity as a function of spatial frequency was measured in patients with cerebral lesions. In most of these patients visual acuity, as measured by the Snellen chart, was 20/30 or better, yet marked departures from normal contrast sensitivity were found. The greatest loss in contrast sensitivity occurred at high frequencies, but in one patient the loss was greatest in the midfrequency range. This finding lends support to the channel hypothesis of spatial contrast discrimination.

Pattern electroretinograms and visual-evoked potentials in glaucoma and multiple sclerosis.

Steady-state visual-evoked potentials and electroretinograms were simultaneously recorded in four patients with glaucoma and in five patients with multiple sclerosis. The stimuli included a homogenous field and a 2.3 cycles per degree sinusoidal grating that were counter-phase modulated at the rate of 7.5 Hz. We used narrow bandwidth spectral analysis to measure the response amplitudes and signal-to-noise ratios. Transient pattern visual-evoked potentials (1 Hz) were also measured for latency in each eye. We found abnormal pattern electroretinograms, based on the absence of a significant second harmonic component, in three of the four glaucomatous eyes although the homogenous field electroretinograms were normal. In the patients with multiple sclerosis, the pattern electroretinograms were abnormal in two eyes, but the transient visual-evoked potential latency had the highest diagnostic yield (seven of ten eyes).

Contrast sensitivity in retinal disease.

Central vision in patients with retinal disorders has been studied with sinusoidal grating patterns. Impaired detection of fine high-contrast gratings has been observed in patients with retinitis pigmentosa and glaucoma despite 20/20 vision. Abnormal contrast sensitivity to coarse gratings occurred in patients with certain macular disorders and occasional glaucoma patients, some with near-normal Snellen acuity. Thus, contrast sensitivity measurements demonstrate central visual deficits not apparent with Snellen testing.

Signs of early damage in glaucomatous monkey eyes: Low spatial frequency losses in the pattern ERG and VEP

Experimental glaucoma was created in one eye of three cynomolgus monkeys by argon laser application to the mid-trabecular meshwork. Simultaneous pattern electroretinograms (PERG) and pattern visual evoked potentials (PVEP) were measured in both control and glaucoma eyes to spatial frequencies of 0.5, 1.25, 2.5, and 3.5 cpd which were counterphase modulated at 6 Hz. The transient flash electroretinogram was also measured. While normal flash electroretinograms were recorded in all eyes both before and after the unilateral production of elevated intraocular pressure (IOP), reductions in PERG and PVEP amplitude were seen in the eyes with glaucoma as early as two weeks following a sustained increase of IOP, despite the absence of cupping of the optic nervehead judged by ophthalmoscopic examination and analysis of photograph by two observers. Optic nervehead abnormalities occurred subsequently. In glaucomatous monkey eyes, the earliest PERG and PVEP changes were most evident with lower spatial frequencies of stimulation. Our data suggest that the optimal stimulus parameters for the detection of early glaucoma are low spatial frequency patterns presented at a rapid rate of temporal modulation.

The effect of blur and contrast of VEP latency: comparison between check and sinusoidal grating patterns

Pattern defocusing was used to evaluate the contribution of different spatial frequency components in checks to VEP latency. Latency shifts with increasing blur (-2.5 to +2.5 diopters) were determined for sinusoidal grating and check patterns equated in fundamental spatial frequency. With both check and grating patterns, the effect of blur was greater the higher the spatial frequency. Given an equal fundamental spatial frequency, however, the latency of checks was more effected. This latency difference between check and sine patterns was pronounced at low fundamental spatial frequencies (large pattern) and decreased with higher spatial frequencies (small pattern). Latencies were then compared for patterns which were defocused vs. simply reduced in contrast. Results show that the increase in latency with defocused large checks is due to both fundamental and higher harmonic spatial components but with small checks, to the fundamental spatial frequency alone.

Systemic 1-methyl, 4-phenyl, 1-2-3-6-tetrahydropyridine (MPTP) administration decreases retinal dopamine content in primates

Following MPTP administration, 4 Cynomolgus monkeys developed a parkinsonian syndrome, accompanied by specific changes of both pattern visual evoked potential and electroretinogram. Retinal dopamine and dihydroxyphenylacetic acid contents were measured in the 4 MPTP-treated monkeys and in 3 normal monkeys. Dopamine and dihydroxyphenylacetic acid levels were significantly lower in the retinas of the MPTP-treated animals (p less than 0.001), suggesting that dopamine has a specific function in the visual system of primates.

Vulnerability of spatial frequency channels in cerebral lesions

QUANTITATIVE studies of vision in patients with cerebral lesions pose a challenge to purely topographical concepts of cerebral organisation. Pyschophysical measurements of the detectability of sinusoidal gratings (contrast sensitivity functions)1 established that in the majority of patients detection of high spatial frequencies suffers most. The spatial frequency of a grating is the number of its alternating bars subtended in 1° of visual angle; the higher the number, the finer the pattern. There seems to be no obvious correlation between this loss of fine pattern discrimination and the aetiology or the exact localisation of a cerebral lesion. The neural basis of this loss is unknown in vision as with the other senses. Is it the result of specific vulnerability of those neurones of the primary visual pathways which are optimally responding to high spatial frequencies or to some defect of high order cognitive functions? In this report I present data on three patients who recovered from cerebral blindness. Serial evoked potentials and psychophysical detection of gratings of high frequency showed concurrent changes throughout recovery in one patient in whom they could be measured. This suggests that structures of the central nervous system which determine evoked potentials and psychophysical responses to high frequency gratings are either identical or similarly vulnerable. These data also suggest why mid- and high-spatial frequency channels of the primary visual pathways may be especially vulnerable to cerebral lesions.

Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates

SummaryAcetyl-levo-carnitine (ALC) protects against 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in the nonhuman primate. ALC pretreated monkeys do not show signs of parkinsonism or electroretinographic changes typical of dopaminergic deficiency when given MPTP. In addition, pilot neurochemical and morphological data confirm a partial protection effect. While MAO-B inhibitors, like L-Deprenyl, are thought to protect dopaminergic neurons from MPTP-induced cell death by preventing the conversion of MPTP to its toxic metabolite MPP+, ALC is not known to have MAO-B affnity. Converging evidence suggests that ALC may affect directly mitochondrial respiration, which is known to be the target of MPP+ and affected in human neurodegenerative diseases, including Parkinsons disease. The results of this study point to new therapeutic avenues for the treatment of these nosologic entities.

A short latency cortical component of the foveal VEP is revealed by hemifield stimulation

Transient evoked potentials were recorded simultaneously over 5 electrodes placed in a horizontal row across the occiput. A range of spatial frequencies were presented as either full-field or hemifield stimuli. Subjects were 11 normal observers and 5 patients with lesions causing a homonymous hemianopic field defect. The shortest latency peak response was at approximately 70 msec, a negative potential (N70). For all spatial frequencies, full-field stimuli evoked a lower amplitude N70 at the midline than the sum of N70 amplitudes to two hemifield stimuli, suggesting partial cancellation. The latency and amplitude of N70 increased as spatial frequency increased. N70 and P100 differed in respect to their response to spatial frequency and field size, further suggesting that they may not be subsets of a unitary response. For hemifield stimulation, N70 had an ipsilateral maximum and attenuated or completely reversed in polarity across the midline. Consistent with the data of normals using hemifield stimuli, in 5 patients a full-field stimulus elicited an N70 lateralized contralaterally to the homonymous hemianopia, i.e., the ipsilateral N70 was absent. The absolute amplitude difference between the left and right electrodes was significant for hemifield stimulation in normals and full-field stimulation in the patients, but not for full-field stimulation in normals. Our results imply that the evaluation of N70 hemispheric distribution is useful for the evaluation of paramacular visual field defects.