Michael E. Breton

Nimodipine, a centrally active calcium antagonist, exerts a beneficial effect on contrast sensitivity in patients with normal-tension glaucoma and in control subjects

BACKGROUND/PURPOSE The use of calcium antagonists in patients with normal-tension glaucoma (NTG) currently is under investigation. The aim of this study is to evaluate the effect of an acute dose of oral nimodipine, a centrally active calcium antagonist, on spatial contrast sensitivity in patients with NTG and in age-matched control subjects. METHODS Spatial contrast sensitivity was measured using the Pelli-Robson and the Vistech 6000 charts in 14 patients with NTG and in 17 control subjects. Testing was performed at baseline and at two subsequent sessions. Measurements were recorded 2 hours after oral administration of either nimodipine or placebo in a randomized, double-masked manner. Data were analyzed using unpaired, two-tailed Students t test for between-group comparisons and repeated measures analysis of variance for within-group comparisons. RESULTS Using the Pelli-Robson charts, baseline contrast sensitivity was significantly lower in patients with NTG compared with control subjects (P < 0.05, unpaired Students t test). There was a significant increase in log contrast sensitivity after administration of nimodipine compared with baseline and placebo in patients with NTG (baseline, 1.39 +/- 0.38; placebo, 1.41 +/- 0.40; nimodipine, 1.51 +/- 0.39) and in control subjects (baseline, 1.62 +/- 0.11; placebo, 1.64 +/- 0.10; nimodipine, 1.81 +/- 0.14) (P < 0.05, repeated measures analysis of variance). A similar trend was observed using the Vistech charts. CONCLUSION These results suggest that central visual function as measured by Pelli-Robson and Vistech contrast sensitivity is impaired in eyes with NTG. An acute, oral administration of nimodipine, a calcium antagonist, improved contrast sensitivity in patients with NTG and in control subjects. The mechanism of this improvement is not fully understood. Further studies are needed to evaluate the effect of long-term administration in glaucoma.

Normative Values for Visual Fields in 4- to 12-Year-Old Children Using Kinetic Perimetry/Normative Values for Visual Fields in 4- to 12-Year-Old Children Using Kinetic Perimetry: Discussion

We report normative data for 4- to 12-year-old children using a kinetic perimetry technique that employs a double arc perimeter with a 6-degree target designed for use with infants and children. The subject population consisted of 84 children in four age groups (4, 5, 7, and 10 yrs) and 21 adults as comparison subjects. Individuals had eye examinations to rule out causes of abnormal visual fields. Mean visual field size was determined separately for the right and left eyes in each age group. In the 4-year-old group, the mean extent of visual field along each of the four meridians for the right eye was 59, 48, 52, and 85 degrees of arc for radial meridians orientation set at 45, 135, 225, and 315 meridians, respectively. The visual field extent in each quadrant generally increased with age. The overall extent of field as measured along the four meridians for all subject groups increased significantly with the age, indicating a continued growth of visual field size in older children. These data suggest that adult visual field size is achieved at about 11.6 years of age.

Empiric limits of rod photocurrent component underlying a-wave response in the electroretinogram*

The corneally recorded rod photocurrent component (photoresponse) underlying the a-wave feature of the electroretinogram was analyzed. The results set empiric limits on critical photoresponse variables. Measurements were obtained from four normal adult subjects on a-wave amplitude, a-wave velocity, b-wave amplitude, b-wave implicit time and b-wave height above baseline. At high intensity, interference from the b-wave component was minimized and the amplitude of the saturated photoresponse component was approximated by the a-wave feature. At lower intensities, the a-wave feature represented progressively less of the underlying photoresponse amplitude. Photoresponse amplitude saturation was signaled by the abrupt slowing of the rate of decline of b-wave peak latency and occurred at an intensity about 2.5 log units above the first appearance of the b-wave. At the intensity of photoresponse saturation, the peak amplitude of the a-wave feature was only about 25% of the maximum amplitude of the underlying photoresponse component. A-wave leading edge velocity was found to increase up to 3 log units above the intensity of photoresponse amplitude saturation and to provide a good estimate of photoresponse velocity at higher intensities. A cascaded low-pass filter model with modifications to accommodate amplitude and timing nonlinearities was used to generate a set of probable underlying photoresponses from the analysis of a-wave amplitude and velocity. Movement of the a-wave leading edge to the left at higher intensities in algebraic combination with a static b-wave leading edge above the intensity of photoresponse amplitude saturation was found to explain the second rise of the b-wave amplitude function and the decline of b-wave amplitude above baseline at high intensities. This analysis provides a basis for modeling the underlying photoresponse on a biochemical level and for interpreting photoreceptor damage in disease states.

Electroretinogram b-Wave Implicit Time and b/a Wave Ratio as a Function of Intensity in Central Retinal Vein Occlusion

The ability of electroretinogram (ERG) b-wave implicit time and b/a wave ratio to predict iris neovascular response was analyzed as a function of stimulus intensity over a 3.6 log unit intensity range in 39 patients with central retinal vein occlusion (CRVO). Predictive power for CRVO patients was evaluated using ROC area at intensities of 1.23, 1.83, 2.43, and 3.03 effective log quanta/rod, where reliable data for both parameters were obtainable from most patients. The relative predictive power of b-wave implicit time and b/a wave ratio were shown to vary with stimulus intensity. The predictive power of b-wave implicit time, as measured by ROC area, declined to below significance at high intensity (above 1.83 log quanta/rod), while b/a wave ratio performed best at middle intensities (1.83 and 2.43 log quanta/rod) and not as well at high and low intensities. Further analysis of statistical behavior of both ERG parameters was obtained from the t statistic. Insight into the mechanism influencing predictive power of b-wave implicit time was derived from measurements on normal adults and CRVO patients with response data taken at high intensities. These results suggest that an optimal stimulus intensity range can be found for these ERG parameters in the evaluation of CRVO.

Selective loss of pattern discrimination in early glaucoma

A new perimetric pattern discrimination test was compared with conventional automated perimetry (Humphrey program 30-2 or Octopus program 32) in glaucoma patients, glaucoma suspects, and control subjects. The new test is based on the rationale that a greater percentage of retinal ganglion cells should be needed to detect a stimulus by its shape, or pattern, than by its brightness. The pattern discrimination stimulus was apatch of nonrandom dots embedded in a surrounding random dot field of the same average density. Pattern discrimination thresholds were measured by changing the degree of regularity, or coherence, of the stimulus dots. The fully coherent target was a static, 1-s duration, 20 x 20-dot checkerboard. Using a criterion-free relative operating characteristic analysis, we estimated the ability of both the pattern discrimination and conventional tests to distinguish the normal data distribution from the suspect and glaucoma distributions. The pattern discrimination test appeared to produce separations greater than conventional perimetry for glaucoma suspects and separations equivalent to conventional perimetry for glaucoma patients.

The Visual-evoked Response in Infants With Central Visual Impairment

We studied ten children with central visual impairment with a known neurologic defect and an abnormal visual-evoked response who had results of repeat electrophysiologic testing evaluated at the Childrens Hospital of Philadelphia from December 1989 through July 1991. Central visual impairment is defined as poor visual function with a normal anterior visual pathway. Age at first examination ranged from 5 to 48 months with a followup of two to 31 months. Repeat visual-evoked response testing showed improvement in seven patients and no change in three. Grating acuity as measured by the Teller acuity card procedure, performed in nine of ten patients, improved in seven, showed no change in one, and declined in one. We found a potentially favorable prognosis for those infants with central visual impairment, despite an initially abnormal visual-evoked response. We used a clinical approach to this disorder to improve diagnostic categorization and prognostic capabilities in central visual impairment.

Pattern discrimination perimetry: a new concept in visual field testing

The subject’s task in conventional perimetry is to detect an incremental spot of light on a uniform background. Recent evidence indicates that, at least in glaucoma, this task can be insensitive to large amounts of neural damage. In an attempt to find more effective ways to detect early glaucomatous damage, we are developing alternative perimetric techniques that are based on pattern discrimination rather than light detection. The subject fixates a small square at the center of a large field of dynamic random dots and tries to detect a patch of non-random, or coherent, dots embedded in the background. The stimuli are displayed on a projection CRT, and all test target parameters, including position, size, shape, exposure duration, dot density, dot arrangement and dot dynamics, are under computer control. In particular, spatial and temporal coherence parameters are defined in terms of the spacing and motion of the target dots.

Electroretinogram Interpretation in Central Retinal Vein Occlusion

The authors report electroretinogram (ERG) data from the initial clinic visit of 39 patients with central retinal vein occlusion (CRVO). No patient had signs of neovascular complications or had received treatment at the time of the ERG examination. Area under the receiver operating characteristic (ROC) curve was used to compare effectiveness of the 4 ERG parameters (Rmax, Log K, b/a wave ratio, and 30 Hz implicit time) in separating those patients who went on to iris neovascularization from those who did not. Rmax is the maximum saturated b-wave amplitude and Log K is the half saturation constant of the Naka-Rushton curve fit to the intensity response data. Discriminant scores, derived using multiple discriminant analysis, were calculated for the total patient groups, CRVO eye alone, and intereye difference. These scores also were compared with the four individual ERG parameters using ROC analysis. Parameters based on amplitude of ERG response, Rmax, and b/a wave ratio are as effective predictors of neovascular response as those interpreted as indicators of retinal sensitivity, such as 30Hz implicit time or Log K. The authors present evidence that loss of b-wave amplitude is not necessarily associated with irreversible loss of inner retinal function.

Influence of serial practice on Farnsworth-Munsell 100-hue scores: the learning effect

Clinical application of the Farnsworth-Munsell 100-hue test may be compromised by uncontrolled sources of psychophysical fluctuation such as a serial practice effect. Although the literature does not report a substantial practice effect for the 100-hue test, we have measured significant improvement in performance extending over at least four test repetitions for a group of twenty-six normal naive subjects. Analysis of test taking strategy identified the most likely source of improvement as cognitive in nature and not related to the availability of the peripheral color signal. An extended training procedure was devised to minimize the serial practice effect which included intensive instruction with illustrations of correct and incorrect cap sequences and practice with verbal feedback on performance using a subset of ten 100-hue caps. Administration of the pretest training was found to minimize the practice effect in an additional group of thirty initially naive subjects. Using pretest training, we were also able to record consistent 100-hue intensity-response functions over five illumination levels.

Evaluation of a CRT-Based Test of Saturation Discrimination Using a Discrete Matching Technique

A computer controlled color CRT system was used to present color test stimuli varying in saturation along R-G and B-Y lines through the white point in color space. Subjects ordered stimuli according to color and saturation. Normals ordered the R-G series with few errors but showed a tendency toward increasing errors with increasing age on the B-Y series. Dichromat error scores showed a sensitivity to the exact orientation of the R-G stimulus line. The maximum rate of stimulus presentation was too slow to allow exploitation of color choice.