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Biomedical subjects

William Seiple

Publications and source records attributed to William Seiple.

At least 19 recordsLinked to original sources

Multifocal ERG findings in carriers of X-linked retinoschisis.

PURPOSE: To determine whether retinal dysfunction in obligate carriers of X-linked retinoschisis (XLRS) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). METHODS: Nine obligate carriers of XLRS (mean age, 46.2 years) were examined for the study. Examination of each carrier included an ocular examination and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 degrees in diameter. The amplitudes and implicit times in each location for the mfERG were compared with the corresponding values determined for a group of 34 normally-sighted, age-similar control subjects. RESULTS: Mapping of 103 local electroretinographic response amplitudes and implicit times within a central 40 degrees area with the mfERG showed regions of reduced mfERG amplitudes and delayed implicit times in two of nine carriers. CONCLUSIONS: The mfERG demonstrated areas of retinal dysfunction in two carriers of XLRS. When present, retinal dysfunction was evident in the presence of a normal-appearing fundus. Multifocal ERG testing can be useful for identifying some carriers of XLRS.

Adult↗

Perifoveal function in patients with North Carolina macular dystrophy: the importance of accounting for fixation locus.

PURPOSE: To quantify the extent of visual function losses in patients with North Carolina Macular Dystrophy (NCMD) and to demonstrate the importance of accounting for eccentric fixation when making comparisons with normal data. METHODS: Five patients with NCMD who were from a single family were examined. Multifocal electroretinograms (mfERGs) and psychophysical assessments of acuity and luminance visual field sensitivities were measured throughout the central retina. Comparisons of responses from equivalent retinal areas were accomplished by shifting normal templates to be centered at the locus of fixation for each patient. RESULTS: Losses of psychophysically measured visual function in patients with NCMD extend to areas adjacent to the locations of visible lesions. The multifocal ERG amplitude was reduced only within the area of visible lesion. Multifocal ERG implicit times were delayed throughout the entire central retinal area assessed. CONCLUSIONS: ERG timing is a sensitive assay of retinal function, and our results indicate that NCMD has a widespread effect at the level of the mid and outer retina. The findings also demonstrated that it is necessary to account for fixation locus and to ensure that equivalent retinal areas are compared when testing patients with macular disease who have eccentric fixation.

Adult↗

Comprehensive functional vision assessment of patients with North Carolina macular dystrophy (MCDR1).

PURPOSE: Previous studies indicated abnormal development of fixation toward the optic nerve head in patients with the inherited retinal disease North Carolina macular dystrophy (NCMD). The implication of this development on functional vision and structural characteristics has not been described. METHODS: The anatomical characteristics of five NCMD-affected individuals were assessed by measuring the retinal thickness of the macula using optical coherence tomography. The underlying physiologic health of the retina was assessed using the multifocal ERG. Psychophysical assessment of remaining vision in the affected areas was done with a new microperimetry system that measures functional visual acuity at 27 discrete locations and the Humphrey visual field analyzer. RESULTS: All patients had better areas of visual sensitivity toward the nasal macula. Follow-up examination showed no changes in the clinical appearance of the retina. Visual acuities ranged from -0.10 logMAR (Snellen equivalent, approximately 20/16) to 0.50 logMAR (Snellen equivalent, approximately 20/63) in the better eye. No significant changes in visual acuity were found over time. Local multifocal electroretinogram deficits were found in all patients. Patients with grade 2 or 3 disease had large patches of decreased amplitudes and delayed implicit times. Results of the anatomical, electrophysiological, and psychophysical tests were consistent. CONCLUSION: The electrophysiological and psychophysical deficits found in patients with more severe disease were consistent with an abnormal development of fixation from the anatomical fovea toward the optic nerve head with the placement of the lesion temporal to fixation (into the nasal visual field).

Adult↗

Driving performance of glaucoma patients correlates with peripheral visual field loss.

PURPOSE: To identify clinical vision measures that are associated with the driving performance of glaucoma patients who have visual field loss and visual acuity better than 20/100 and to compare the driving performance of glaucoma patients with the driving performance of a group of age- and sex-equivalent individuals without eye disease. PATIENTS: Forty patients with glaucoma and 17 normally sighted control subjects participated in this study. METHODS: Clinical vision data, consisting of visual acuity, letter contrast sensitivity, and visual fields, were collected. Driving performance was assessed by (1) an interactive driving simulator that measured 7 indices of performance (including number of accidents) and (2) the self-reported accident involvement for the past 5 years. MAIN OUTCOME MEASURES: Driving simulator performance and real-world, self-reported accident involvement. RESULTS: The number of accidents as measured on the driving simulator in the glaucoma group was significantly correlated with three Goldmann visual field measures: combined horizontal extent (rho = -0.47, P = 0.01), total horizontal extent (rho = -0.49, P = 0.007), and total peripheral extent (rho = -0.55, P = 0.002). There were no statistically significant correlations between the driving performance of the glaucoma group and the visual acuity or contrast sensitivity measures. When compared with the control group, a significantly greater proportion of the glaucoma group reported having at least one real-world accident within the past 5 years (Fisher exact test, P = 0.005). CONCLUSIONS: Visual field reduced to less than 100 degrees of horizontal extent may place patients with peripheral field loss at greater accident risk. A higher incidence of real-world and simulator accidents was found for the group with glaucoma.

Adult↗

Use of prisms for navigation and driving in hemianopic patients.

PURPOSE: (1) To compare the outcomes of orientation and mobility and driving training with Fresnel prisms and the Gottlieb Visual Field Awareness System for patients with homonymous hemianopsia, and (2) To determine whether the patients continue to use the optical enhancement devices at a 2-year follow-up point. METHODS: Patients with homonymous hemianopsia were provided with a rehabilitation program where they were fitted with prism lenses and trained to use them for navigation and driving. Telephone interviews were used to obtain information about device usage 2 years following the completion of the training program. RESULTS: Patients' performance was compared with a test-retest criterion in the visual skills areas of recognition, mobility, peripheral detection, scanning, tracking, and visual memory. Patients with hemianopic loss showed improvements in all of the visual skills categories, ranging from the highest improvements of 26% of tasks improved in the mobility category to 13% in the recognition category. The majority of the hemianopic patients reported using the devices at the 2-year follow-up interview. CONCLUSIONS: The patients with homonymous hemianopsia showed improvements in visual functioning using prism lenses, although these improvements were smaller than those found in previous studies with central or bilateral peripheral vision loss groups who were trained to use other optical enhancement devices for navigation and driving using a similar curriculum. However, given the evidence of increased risk of accidents for patients with peripheral vision loss, the safety of peripheral enhancement devices for driving must be thoroughly evaluated before their impact on public safety is known.

Adult↗

Eye-movement training for reading in patients with age-related macular degeneration.

PURPOSE: To determine whether training oculomotor control, without direct practice in reading sentences, could increase reading speed in patients with age-related macular degeneration (AMD). METHODS: Sixteen patients with AMD participated in the study (age range, 65-87 years; mean, 77). The training program consisted of a series of exercises that were designed to allow the patients to practice eye movements. At the beginning of training, the subjects practiced small horizontal saccades in response to cognitively easy stimuli (e.g., dots). The training then progressed to practicing larger eye movements and then to practicing saccades with single letters, pairs of letters, and three-letter words. Reading of sentences was practiced in only one exercise, during the last session of the 8-week training. RESULTS: The difference between average reading speeds before and after training was 24.7 wpm (difference between medians, 17.9 wpm). The increase in speed was statistically significant (Wilcoxon signed rank test = 124.0, P < 0.001). There was no significant relationship between change in maximum reading speed and ETDRS (Early Treatment Diabetic Retinopathy Study) acuity (r = -0.14, P = 0.76) or between change in maximum reading speed and age (r = 0.25, P = 0.45). CONCLUSIONS: The results indicate that a training curriculum that concentrates on eye-movement control can increase reading speed in patients with AMD. This finding is especially interesting, because the training involved little direct practice in reading sentences but instead concentrated on having subjects practice control of eye positions and eye movements.

Aged↗

Contrast response properties of magnocellular and parvocellular pathways in retinitis pigmentosa assessed by the visual evoked potential.

PURPOSE: To evaluate the contrast response of the visual system in retinitis pigmentosa (RP) under conditions designed to emphasize the parvocellular (PC) and magnocellular (MC) pathways. METHOD: Visual evoked potentials (VEPs) were measured in 10 patients with RP and in 10 age-equivalent control subjects with normal visual acuity and color vision, by using an array of isolated checks that were presented against a steady yellow background. The checks were modulated sinusoidally, either in isoluminant chromatic contrast (5.6 Hz), to favor the chromatic PC pathway, or in luminance contrast (5.6 and 11.2 Hz), to favor the MC pathway. Response amplitude and phase at the stimulus (fundamental) frequency were derived from Fourier analysis, and contrast response functions were fit with a Michaelis-Menten equation to derive R(max), the maximum response amplitude, and sigma, the contrast necessary to produce R(max)/2. RESULTS: In the control subjects, the mean amplitude function for chromatic modulation increased approximately linearly with increasing contrast, whereas the function for luminance modulation increased sharply at low contrasts and saturated at contrasts above approximately 30% for both temporal frequencies, as expected. The patients with RP showed primarily a reduction in R(max) with little change in sigma in all testing conditions. The reduction in R(max) was equivalent for chromatic modulation and luminance modulation at 5.6 Hz, but was substantially lower for luminance modulation at 11.2 Hz. CONCLUSION: Contrast processing was impaired within both the MC and PC pathways in these patients with RP, but the degree of impairment within the MC pathway depended on temporal frequency. These VEP results are in general agreement with recent psychophysical studies of contrast sensitivity losses in patients with RP, and further they characterize contrast processing deficits in these patients at suprathreshold levels.

Adult↗

The multifocal visual evoked potential: an objective measure of visual fields?

We examined the effects of inter-modal attention and mental arithmetic on Humphrey visual field sensitivity and multifocal visual evoked potential (mfVEP) amplitude. Four normally sighted subjects (ages ranging from 24 to 58 years) participated in this study. Monocular visual field sensitivity was measured under two conditions: (1) standard testing condition and (2) while the subject performed a Paced Auditory Serial Addition Task (PASAT). Monocular mfVEPs were recorded in response to a 60-sector stimulus. The checkerboard pattern in each sector was contrast reversed according to a binary m-sequence. mfVEPs were recorded under two conditions: (1) standard testing conditions and (2) while the subject performed a PASAT. We found that, when compared to the no-task condition, all subjects had locations of significantly reduced Humphrey visual field sensitivities when performing the PASAT. In contrast, there were no significant decreases in mfVEP amplitude in any sector for any of the subjects while performing the PASAT. Our findings indicate that divided attention and ongoing mental processes did not affect the mfVEP. Therefore, the mfVEP provides an objective measure of visual field function that may be useful for some patients with unreliable automated static perimetry results.

Adult↗

Test-retest reliability of the multifocal electroretinogram and humphrey visual fields in patients with retinitis pigmentosa.

We examined the reliability of Humphrey visual field thresholds and multifocal electroretinogram (mfERG) amplitudes and timing in a group of patients with Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were tested five times: at baseline (visit #0), at three weekly follow-up visits (visits #1 - #3), and at three months (visit #4). For the Humphrey thresholds, differences between dB values on repeat visits were obtained. Differences between log values on repeat visits were calculated for mfERG amplitude and implicit time. We used the standard deviations of these difference scores as a measure of reliability and the means of the difference scores as a measure of progression. We found that the majority of the patients' repeat data were more variable than that of the control subjects for both the Humphrey and mfERG. We found no single factor that predicted the magnitude, or the variance, of the SD of differences scores for the patients. We recommend that each patient's reliability be assessed individually. Ultimately, the choice of an outcome measure must be guided by its reliability, as well as its ability to assess the visual function of interest.

Adult↗

Rod and cone photoreceptor function in patients with cone dystrophy.

PURPOSE: To determine the extent of rod and cone photoreceptor dysfunction in patients with cone dystrophy using psychophysical and electrophysiological tests. METHODS: Ten patients with cone dystrophy participated. Rod and cone system psychophysical thresholds were measured as a function of retinal eccentricity. Bright-flash full-field electroretinograms were obtained under dark-adapted (rod-mediated) and light-adapted (cone-mediated) conditions. The a-wave data were fitted with a model based on photopigment transduction to obtain values for log Rmax (maximum response) and log S (sensitivity). b-Wave parameters were also examined by fitting a nonlinear, saturating function (the Naka-Rushton equation) to the rod-mediated responses. Oscillatory potentials were measured to the cone-mediated high-intensity flashes. RESULTS: On average, the rod-mediated psychophysical thresholds were elevated by 0.5 log unit. These threshold elevations did not differ significantly with retinal eccentricity. In contrast, cone-mediated psychophysical thresholds were elevated up to 3.0 log units. Threshold elevation was greatest in the central retinal locations. For rod-mediated conditions, the a-wave Rmax parameter was significantly reduced in three patients; the a-wave log S parameter was within normal limits. The rod-mediated b-wave Rmax parameter was reduced in six patients; log k was abnormal in one patient. For cone-mediated conditions, the a-wave Rmax parameter was reduced in six patients and the a-wave log S parameter was reduced in two patients. The cone system oscillatory potentials were abnormal in nine patients. CONCLUSIONS: Patients with cone dystrophy show different patterns of psychophysical rod versus cone system sensitivity losses with retinal eccentricity. The full-field electrophysiological data indicate that most of the patients had abnormal cone photoreceptor function. Some patients also showed rod photoreceptor abnormalities. The rod system changes were smaller than the cone system changes.

Adult↗

Relationship of retinal structural and clinical vision parameters to driving performance of diabetic retinopathy patients.

This study identifies clinical vision measures or retinal structural measures associated with the driving performance of diabetic retinopathy patients. Twenty-five licensed drivers with diabetic retinopathy (median age, 53 years; range, 34-72 years) completed clinical tests (visual acuity, letter contrast sensitivity, and Humphrey 30-2 visual fields) and structural examinations (retinal thickness analysis and fundus photograph grading of retinopathy and laser scarring). Driving performance was assessed with an interactive driving simulator and a driving history questionnaire. Increased retinal thickness was significantly correlated with a higher frequency of simulator accidents and near accidents. Laser scar grades significantly correlated with steeper brake-response slopes, increased brake-pressure standard deviation (SD), and longer response times. Subjects with focal laser scars had significantly higher average brake-pedal pressure and brake-pressure SD than subjects without focal laser scars. Retinal thickness and laser scarring correlated with driving simulator performance in subjects with diabetic retinopathy.

Accidents, Traffic↗

Multidimensional visual field maps: relationships among local psychophysical and local electrophysiological measures.

Multidimensional psychophysical and electrophysical maps of the central retina are essential for assessing the functioning of the diseased retina. In this study, grating acuity, contrast sensitivity, duration for letter identification, multifocal electroretinograms, and Humphrey visual field thresholds were measured at equivalent positions throughout the central 20 degrees. We found that the rates of sensitivity loss were not equivalent for all psychophysical measures. The rate of loss in the duration required for letter identification as a function of eccentricity was the steepest, followed by acuity and contrast sensitivity. The rate of loss in luminance sensitivity as measured in the Humphrey visual field was the shallowest. The pattern of losses also varied across meridians. Specifically, the rate of loss as a function of eccentricity was highest in the vertical meridian and lowest in the horizontal meridian. These maps and the correlations among measures as a function of retinal position serve as a baseline so that we can examine disease effects throughout the retina. In addition, the development of vision rehabilitation programs focused on eccentric viewing training should consider the differential sensitivities of the peripheral retina.

Adult↗

Multifocal electroretinography as a function of age: the importance of normative values for older adults.

PURPOSE: To determine the influence of age on local electroretinographic responses in humans. METHODS: Multifocal electroretinograms (mfERGs) were obtained from 62 normally sighted subjects ranging in age from 21 to 81 years. A stimulus array of 103 scaled hexagons was used to measure electrical signals within a retinal area approximately 46 degrees in diameter. Commonly reported mfERG methods were used to quantify the responses: peak-to-peak amplitudes and implicit times, scalar product amplitude, and amplitude and time scales derived from the algorithm of Hood and Li, published in 1997. RESULTS: Regression analysis showed significant linear relationships of amplitude and timing measures with age. The rates of losses were 10.5% per decade for peak-to-peak amplitude, 11.7% per decade for scalar product amplitude, and 9.5% per decade for a-scale. The rate of amplitude reduction was highest in the central 3 degrees. Age had less influence on implicit time measures. The rates of timing losses were 1.4% per decade for the N1 component and 1.0% per decade for both the P1 component and the t-scale measure. Using predicted interval ranges, the age was calculated at which 50% of the expected values would fall below the lower 95% prediction interval band of younger subjects. CONCLUSIONS: The age-associated mfERG alterations are presented to emphasize the importance of appropriate normative data in interpretation of mfERGs.

Adult↗

A method for comparing psychophysical and multifocal electroretinographic increment thresholds.

The multifocal electroretinogram (mfERG) has been commonly used as a method for obtaining objective visual fields. Although qualitative comparisons have been good, quantitative comparisons between the results from mfERG and the results from Humphrey Visual Field Analyser (HVFA) have found variable degrees of agreement depending upon the mfERG response parameter examined and/or the disease studied. Lack of agreement may be due to differences in methodology, differences in the sites of response generation, and/or differences derived from comparing suprathreshold versus threshold responses. In addition, the two procedures are performed at different levels of adaptation. We developed an approach for matching stimulus parameters and compared mfERG and psychophysical thresholds to assess the effects of technique and level of adaptation on the two responses. Psychophysical and mfERG thresholds were obtained as a function of the adaptation level (1.5-4.0 log td) and retinal location. The derived increment threshold-versus-intensity functions for both measures were fitted using the equation logT=logT(0)+log((A+A(0))/A(0))(n). We found that the values of A(0) for the mfERG data were one log unit higher than those for the psychophysical data. In addition, the value of the slope (n) for the mfERG data was shallower (0.8) than that of the psychophysical data (1.0). Predictions were made about comparisons of HVFA threshold and mfERG amplitude data in patients with retinal disease based upon a two-site model of adaptation. The data for some groups of patients could be best-fitted with a model of a disease acting at a site distal to all gain changes, whereas data from other patients were best fitted with a model of a disease acting at a site proximal to all retinal gain. The relationship between the Humphrey visual field threshold losses and mfERG amplitude reductions depends upon the site and mechanism of a particular disease process and the model of retinal gain assumed. In no case is a one-to-one relationship between the losses in the two measures predicted.

Adaptation, Ocular↗

The spatial distribution of selective attention assessed using the multifocal visual evoked potential.

To determine the manner in which attention is distributed among numerous locations in the visual space, we used a multifocal recording technique that allowed simultaneous recordings of evoked cortical activity from 12 visual field areas out to 23.6 degrees. We found that multifocal visual evoked potential (mfVEP) amplitude was larger when a region of visual space was attended than when it was not attended. The magnitude of this effect was inversely related to visual field eccentricity and there was no attention-related modulation of VEP amplitude for the most eccentric region. In addition, we found that mfVEP amplitudes in the regions contiguous to the attended region could also be larger, depending upon their spatial relationship to the attended region. Specifically, amplitudes in more central regions on the 'meridian of attention' were larger when the subject attended anywhere along that meridian.

Attention↗

Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of X-linked retinitis pigmentosa.

PURPOSE: To examine whether a mosaic pattern of retinal dysfunction in obligate carriers of X-linked retinitis pigmentosa (XLRP) could be observed in local electroretinographic responses obtained with the multifocal electroretinogram (mfERG). DESIGN: Prospective observational case series. PARTICIPANTS: Five obligate carriers of XLRP (mean age, 53.2 years) were recruited into the study. METHODS: Examination of each subject included a complete ocular examination, Humphrey visual field, standard full-field electroretinogram (ERG), and mfERG testing. For the mfERG, we used a 103-scaled hexagonal stimulus array that subtended a retinal area of approximately 40 in diameter. The amplitudes and implicit times in each location for the mfERG was compared with the corresponding value determined for a group of normally sighted, age-corrected control subjects. MAIN OUTCOME MEASURES: Mapping of 103 local electroretinographic response amplitudes and implicit times within the central 40 with the multifocal electroretinogram. RESULTS: Localized regions of reduced mfERG amplitudes and/or delayed implicit times were found in four of five carriers. In one of these four carriers, a mosaic pattern of mfERG dysfunction was present even in the absence of any clinically apparent retinal changes, retinal sensitivity losses on Humphrey field testing, or abnormal full-field cone ERG responses. However, one carrier with a typical tapetal-like reflex demonstrated no deficit on any functional tests. CONCLUSIONS: The mfERG demonstrated patchy areas of retinal dysfunction in some carriers of XLRP. This mosaic pattern of dysfunction may be observed in some patients with a normal-appearing fundus, normal psychophysical thresholds, and normal amplitude and implicit time full-field ERG cone responses.

Adult↗

Localized retinal dysfunction in central serous chorioretinopathy as measured using the multifocal electroretinogram.

PURPOSE: To determine the extent of electrophysiologic dysfunction in patients with central serous chorioretinopathy (CSC). DESIGN: Prospective observational case series. PARTICIPANTS: Six patients with unilateral CSC (mean age, 40 years) were recruited into the study. METHODS: Six patients with CSC underwent multifocal electroretinogram (mfERG) testing on both their clinically affected and opposite uninvolved eyes using the VERIS System, with a stimulus array of 103 scaled hexagons. The first positive peak responses were analyzed within six concentric ring annuli centered on the fovea. Amplitudes and implicit times were compared with those of an age-similar control group. MAIN OUTCOME MEASURES: Local electroretinographic response amplitudes and implicit times within the central 40 degrees with the mfERG. RESULTS: All the clinically uninvolved eyes showed mfERG amplitudes and implicit times within the normal range throughout the central 40 degrees of the retina. All six eyes with CSC showed reduced amplitudes and/or delayed implicit times that were limited to the regions of the macula in which clinical changes associated with CSC were apparent. CONCLUSIONS: We observed electroretinographic changes only in the clinically affected eyes, and these were limited to regions with ophthalmoscopically apparent fundus changes. Our findings do not support the conclusion that functional impairment, as measured by the mfERG, in eyes with CSC extends beyond clinically observed fundus changes. We did not observe abnormal mfERG responses in the clinically normal eyes of such patients.

Adult↗

Local cone and rod system function in progressive cone dystrophy.

PURPOSE: To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques. METHODS: Local cone system function was assessed by measuring cone system thresholds (visual fields) and cone-mediated multifocal electroretinograms (mfERGs). Rod system function was assessed by measuring rod system thresholds (visual fields) and rod-mediated mfERGs. The results in a group of eight patients with CD were compared with those in an age-similar control group. RESULTS: All the patients had abnormal cone system visual field thresholds and cone-mediated mfERGs. Cone system psychophysical thresholds were elevated for targets presented within the central 10 degrees, but were within normal limits for targets at peripheral locations. Cone-mediated mfERG measures of amplitude scale and time scale were abnormal for most of the hexagons tested. Most of the rod-mediated psychophysical thresholds and mfERGs were within normal limits. Rod system losses tended to be patchy and scattered throughout the area tested. CONCLUSIONS: There was poor correspondence among local measures of cone and rod system losses in these patients with CD. The results suggest that the spatial pattern of cone system losses in this disease differs from the spatial pattern of rod system losses.

Adolescent↗