Ted Maddess

Testing for Glaucoma with the spatial frequency doubling illusion

We examined the performance of tests for glaucoma based on the spatial frequency doubling (FD) illusion. Contrast thresholds for seeing the FD illusion in four large visual field regions were measured from 340 subjects who were tested up to seven times over 2 years. Median sensitivities of 91% at specificities of 95% were obtained. Test-retest variability for the worst hemifield thresholds averaged 2.22 db +/- 0.09 S.E. for all tested groups, and significant progression was observed for glaucoma suspects over the seven visits, indicating that tests based on the FD illusion can detect diffuse early glaucomatous loss.

Evidence for spatial aliasing effects in the Y-like cells of the magnocellular visual pathway

Several lines of evidence are provided indicating that our visual percept can be dominated by spatial aliasing for viewing conditions near those needed to see the spatial frequency doubled illusion. The apparent aliasing effect indicates that the underlying sampling array has a density 15-30% of that of M-cells, in agreement with the known proportion of Y-like M-cells (M(y)-cells). The presence of aliasing indicates, that there is a separate irregular array of M(y)-cells, and that their role is to rapidly convey information on retinal gain control to the brain rather than to act primarily as inputs to image motion computation.

Effect of temporal sparseness and dichoptic presentation on multifocal visual evoked potentials

Multifocal VEP (mfVEP) responses were obtained from 13 normal human subjects for nine test conditions, covering three viewing conditions (dichoptic and left and right monocular), and three different temporal stimulation forms (rapid contrast reversal, rapid pattern pulse presentation, and slow pattern pulse presentation). The rapid contrast reversal stimulus had pseudorandomized reversals of checkerboards in each visual field region at a mean rate of 25 reversals/s, similar to most mfVEP studies to date. The rapid pattern pulse presentation had pseudorandomized presentations of a checkerboard for one frame, interspersed with uniform grey frames, with a mean rate of 25 presentations/s per region per eye. The slow pattern pulse stimulus had six presentations/s per region per eye. Recording time was 5.3 min/condition. For dichoptic presentation slow pattern pulse responses were 4.6 times larger in amplitude than the contrast reversal responses. Binocular suppression was greatest for the contrast reversal stimulus. Consideration of the signal-to-noise ratios indicated that to achieve a given level of reliability, slow pattern pulse stimuli would require half the recording time of contrast reversal stimuli for monocular viewing, and 0.4 times the recording time for dichoptically presented stimuli. About half the responses to the slow pattern pulse stimuli had peak value exceeding five times their estimated standard error. Responses were about 20% smaller in the upper visual field locations. Space-time decomposition showed that responses to slow pattern pulse were more consistent across visual field locations. We conclude that the pattern pulse stimuli, which we term temporally sparse, maintain the visual system in a high contrast gain state. This more than compensates for the smaller number of presentations in the run, and provides signal-to-noise advantages that may be valuable in clinical application.

Sparse multifocal stimuli for the detection of multiple sclerosis

We compared the diagnostic capabilities of contrast reversal and sparse pattern pulse stimulation for dichoptic multifocal visual evoked potentials (mfVEPs) measured in normal subjects and multiple sclerosis (MS) patients. Multifocal responses were obtained from 27 normal subjects and 50 relapsing‐remitting patients, 26 of whom had experienced optic neuritis (ON+). The patient groups were matched for length of disease and number of clinical attacks. Compared with the responses of normal subjects those of MS patients had significantly smaller response amplitudes, lower signal‐to‐noise ratios, more complex response waveforms, and longer response delays. The effects were larger for sparser stimuli. Sensitivities and specificities for the different stimulus types were estimated from receiver operator characteristic (ROC) plots. Bootstrap estimates of the accuracies of the ROCs for the most promising measure, the template delays, indicated the sparsest stimulus would deliver 92% sensitivity at a false‐positive rate of 0%. In contrast, at 92% sensitivity the conventional mfVEP stimulus misdiagnosed more than 20% of the normal population. The results were similar for patients with no history of ON (ON−). In performing well in patients with no history of ON, the sparse mfVEPs seem to measure progressive damage associated with axon and gray matter losses rather than damage associated with a history of serious inflammation. Ann Neurol 2005;57:904–913

Contrast response of temporally sparse dichoptic multifocal visual evoked potentials

Temporally sparse stimuli have been found to produce larger multifocal visual evoked potentials than rapid contrast-reversal stimuli. We compared the contrast-response functions of conventional contrast-reversing (CR) stimuli and three grades of temporally sparse stimuli, examining both the changes in response amplitude and signal-to-noise ratio (SNR). All stimuli were presented dichoptically to normal adult human subjects. One stimulus variant, the slowest pattern pulse, had interleaved monocular and binocular stimuli. Response amplitudes and SNRs were similar for all stimuli at contrast 0.4 but grew faster with increasing contrast for the sparser stimuli. The best sparse stimulus provided an SNR improvement that corresponded to a recording time improvement of 2.6 times relative to that required for contrast reversing stimuli. Multiple regression of log-transformed response metrics characterized the contrast-response functions by fitting power-law relationships. The exponents for the two sparsest stimuli were significantly larger (P < 0.001) than for the CR stimuli, as were the mean response amplitudes and signal-to-noise ratios for these stimuli. The contrast-dependent response enhancement is discussed with respect to the possible influences of rapid retinal contrast gain control, or intracortical and cortico-geniculate feedback.

Dichoptic multifocal pupillography reveals afferent visual field defects in early type 2 diabetes.

PURPOSE Multifocal pupillographic perimetry was used to examine differences in the visual fields of 23 subjects with early type 2 diabetes (T2D) and 23 age- and sex-matched control subjects. METHODS Independent stimuli were delivered to 44 regions of each eye while pupil responses were recorded with infrared cameras. The stimuli were presented in 8 segments of 30 seconds, and both eyes of each subject were tested twice. The direct and consensual responses provided 88 responses per eye. The diagnostic power of the method was then examined by applying receiver operator analysis to the peak regional contraction amplitudes, time to peaks, and linear combinations of those. RESULTS Dichoptic multifocal pupillography provided response amplitudes with a median z-score of 2.63 +/- 0.26 (SE). The diagnostic performance (expressed as areas under ROC plots) of the eight subjects (32 fields) who had had T2D for at least 10 years was 0.87 +/- 0.06 (mean +/- SE) for response amplitude deviations from normative data, rising to 0.95 +/- 0.04 when between-eye symmetry was considered. Mean pupil size did not have diagnostic power. Comparison of direct and consensual response fields indicated that the observed localized field defects were afferent. CONCLUSIONS Reasonable diagnostic power was obtained, especially for the 16 eyes that had had T2D for more than 10 years, inferring that even in the near absence of visible diabetic retinopathy, some retinal damage had been sustained. This result, if confirmed in a wider group, suggests the that the method may be clinically useful in screening for early damage to the retina in T2D diabetes.

Multifocal pupillographic visual field testing in glaucoma

Purpose:  This preliminary study investigated a means of concurrently assessing the visual field defects of both eyes by recording pupillary responses to multifocal stimuli.

A system of insect neurons sensitive to horizontal and vertical image motion connects the medulla and midbrain

SummaryThe response properties and gross morphologies of neurons that connect the medulla and midbrain in the butterfly Papilio aegeus are described. The neurons presented give direction-selective responses, i.e. they are excited by motion in the preferred direction and the background activity of the cells is inhibited by motion in the opposite, null, direction. The neurons are either maximally sensitive to horizontal motion or to slightly off-axis vertical upward or vertical downward motion, when tested in the frontal visual field. The responses of the cells are dependent on the contrast frequency of the stimulus with peak values at 5–10 Hz. The receptive fields of the medulla neurons are large and are most sensitive in the frontal visual field. Examination of the local and global properties of the receptive fields of the medulla neurons indicates that (1) they are fed by local elementary motion-detectors consistent with the correlation model and (2) there is a non-linear spatial integration mechanism in operation.

Spectral sensitivity of photoreceptors in an Australian marsupial, the tammar wallaby (Macropus eugenii )

Microspectrophotometric measurements on the rod photoreceptors of the tammar wallaby showed that they have a peak absorbance at 501 nm. This indicates that macropod marsupials have a typical mammalian rhodopsin. An electroretinogram-based study of the photoreceptors confirmed this measurement and provided clear evidence for a single middle wavelength-sensitive cone pigment with a peak sensitivity at 539 nm. The electroretinogram did not reveal the presence of a short-wavelength-sensitive cone pigment as was expected from behavioural and anatomical data. Limitations of the electroretinogram in demonstrating the presence of photopigments are discussed in relation to similarly inconsistent results from other species.

The influence of sampling errors on test-retest variability in perimetry.

PURPOSE To determine whether visual fields measured by standard automated perimetry (SAP) can be distorted by higher-spatial-frequency image components and, in particular, whether test-retest variability of SAP fields can be explained by the combination of small scale fixational drift, small stimulus size, and coarse spatial sampling of the visual fields. METHODS Standard SAP test patterns have points 6° apart. The amplitude spectra of the perimeters 10-2 fields (model 511 Humphrey Field Analyser [HFA]; Carl Zeiss Meditec, Inc., North Ryde, NSW, Australia) were assessed to see whether their finer grained sampling revealed spatial frequencies that could cause distortions of standard fields because of undersampling. Model visual fields were then constructed whose spectra were similar to the 10-2 fields, and test-retest variability was examined for Goldmann sizes III to VI stimuli and Gaussian fixational drift with standard deviations of 0.075° to 0.3°. RESULTS The 10-2 fields showed significant spatial frequency content up to 0.25 cyc/deg, three times the highest frequency that a 30-2 or 24-2 sample grid can resolve. As reported for SAP, test-retest variability increased with scotoma depth, and increasing the stimulus size from III to VI caused a reduction in test-retest variability, as did reduced fixation jitter. CONCLUSIONS With fixation drift half the size of that exhibited by good fixators, many of the features of SAP test-retest variability were reproduced. Reducing test-retest variability may therefore involve using large test stimuli that are blurry in appearance and that overlap somewhat when placed on the perimetric test grid. Overlap across the meridians should perhaps be avoided.