Karen S Holopigian, Ph.D.

A primer on common statistical errors in clinical ophthalmology
Holopigian, Karen; Bach, Michael
2010 Dec;121(3):215-222, Documenta ophthalmologica
Although biomedical statistics is part of any scientific curriculum, a review of the current scientific literature indicates that statistical data analysis is an area that frequently needs improvement. To address this, we here cover some of the most common problems in statistical analysis, with an emphasis on an intuitive, tutorial approach rather than a rigorous, proof-based one. The topics covered in this manuscript are whether to enter eyes or patients into the analysis, issues related to multiple testing, pitfalls surrounding the correlation coefficient (causation, insensitivity to patterns, range confounding, unsuitability for method comparisons), and when to use standard deviation (SD) versus standard error of the mean (SEM) 'antennas' on graphs
— id: 114196, year: 2010, vol: 121, page: 215, stat: Journal Article,

Scotopic sensitivity and color vision with a blue-light-absorbing intraocular lens
Greenstein, Vivienne C; Chiosi, Flavia; Baker, Paul; Seiple, William; Holopigian, Karen; Braunstein, Richard E; Sparrow, Janet R
2007 Apr;33(4):667-672, Journal of cateract & refractive surgery
PURPOSE: To investigate possible adverse effects of a yellow-tinted intraocular lens (IOL) on scotopic sensitivity and hue discrimination. SETTING: Departments of Ophthalmology, Columbia University and New York University School of Medicine, New York, New York, USA. METHODS: Nine patients with a yellow-tinted IOL in 1 eye and a colorless ultraviolet IOL in the fellow eye and 9 young phakic subjects with and without a yellow-tinted clip-on lens were tested. Hue discrimination was measured with the Farnsworth-Munsell (FM) 100-hue test. Dark-adapted thresholds to 440 nm, 500 nm, and 650 nm lights were measured at 23 locations using a modified Humphrey perimeter, and dark-adapted thresholds to white light were measured at 15 degrees temporal retina. RESULTS: In the 9 patients, there were no significant differences in dark-adapted sensitivities to 440, 500, 650 nm, or white-light stimuli and no differences in FM 100-hue error scores between eyes with yellow-tinted IOLs and those with colorless IOLs. Similarly, in young phakic subjects, there were no significant differences in FM 100-hue error scores or dark-adapted sensitivity to the white light with and without the yellow-tinted clip-on lens. However, with the clip-on lens, mean sensitivities to the 440 nm, 500 nm, and 650 nm stimuli were significantly decreased by 2.7 to 2.8 dB, 0.7 to 1.0 dB, and 0 to 1.2 dB, respectively. CONCLUSION: Results suggest that implantation of a yellow-tinted IOL has non-significant effect on scotopic sensitivity and hue discrimination
— id: 71300, year: 2007, vol: 33, page: 667, stat: Journal Article,

Eccentricity-dependent changes in local onset and offset responses in patients with progressive cone dystrophy
Holopigian, K; Wynn, P; Seiple, W; Carr, R E; Hood, D C
2007 Aug;47(17):2297-2304, Vision research
Shinoda and colleagues hypothesized that patients with cone dystrophy (CD) might suffer from a selective ON-system deficit, based on the local nature of the disease [Shinoda, K, Ohde, H, Inoue, R, Ishida, S, Mashima, Y, & Oguchi, Y (2002). ON-pathway disturbance in two siblings. Acta Ophthalmologica Scandinavica, 80, 219-223]. The purpose of the current study was to test this hypothesis by examining onset and offset responses as a function of eccentricity in a group of patients with CD using long-duration LED stimuli. Nine patients with CD participated in this study (mean age of 36.1 years and visual acuity 20/200). For this study, the following measures were obtained: Humphrey threshold visual fields, standard multifocal ERGs (mfERGs) as well as mfERGs to long duration stimuli recorded using the Retiscan stimulator (Roland Instruments). This display contained 61 scaled hexagons and the LEDs were on for 100ms (180cd/m(2)) and off for 100ms. In addition, standard full-field photopic and flicker ERGs using Ganzfeld stimulation were obtained. For the control subjects, the onset responses were larger than the offset responses at all eccentricities; whereas for the patients, there was overlap between the amplitudes of the onset and offset responses. For the patients, the amplitude ratios (relative to the control data) indicated that the difference between the onset and offset responses was greatest for the central-most ring and this difference decreased with increasing eccentricity. For the onset responses, Humphrey thresholds and mfERG amplitudes, performance was poorest for the center ring and best for the most peripheral ring; for the offset responses, the opposite pattern of results was obtained. The differences in the pattern of results in the long duration mfERG data are consistent with a selective loss of the onset responses in our patient population
— id: 73870, year: 2007, vol: 47, page: 2297, stat: Journal Article,

A prospective study of rod and cone function in patients with dominantly inherited, progressive cone dystrophy
Holopigian, K; Greenstein, VC; Seiple, W; Gallardo, JM; Noble, KG; Carr, RE
2005 ;46(Suppl S):4086-4086, Investigative ophthalmology & visual science. IOVS
— id: 56199, year: 2005, vol: 46, page: 4086, stat: Journal Article,

Multifocal visual evoked potentials to cone specific stimuli in patients with retinitis pigmentosa
Holopigian, K; Shuwairi, S M; Greenstein, V C; Winn, B J; Zhang, X; Carr, R E; Hood, D C
2005 Nov;45(25-26):3244-3252, Vision research
Our aim was to determine whether patients with retinitis pigmentosa show differences in L- and M-cone multifocal visual evoked potential (mfVEP) responses that are eccentricity dependent, as has been shown for control subjects. Second, we compared the losses for mfVEPs to losses on achromatic visual field and multifocal electroretinogram (mfERG) measures in the patients. Monocular mfVEPs were recorded to a pattern reversing display that modulated only the L- or M-cones. Also, standard automated achromatic visual fields and mfERGs were obtained. For the control subjects, the ratio of L-cone to M-cone mfVEP amplitudes increased as a function of retinal eccentricity. For the patients, the ratio did not vary with eccentricity. For all measures, responses were least affected for the first ring (central 2.4 degrees ) and most affected for the third ring (11.6 degrees - 44.4 degrees ). For the first ring, mfERG amplitudes were more impaired than were the mfVEPs or the visual field thresholds. For most of the patients, there was local response correspondence among our measures of visual function
— id: 61418, year: 2005, vol: 45, page: 3244, stat: Journal Article,

The multifocal visual evoked potential: an objective measure of visual fields?
Seiple, William; Holopigian, Karen; Clemens, Colleen; Greenstein, Vivienne C; Hood, Donald C
2005 Apr;45(9):1155-1163, Vision research
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
— id: 51786, year: 2005, vol: 45, page: 1155, stat: Journal Article,

Reliability of multifocal electroretinograms and Humphrey visual field thresholds in patients with retinitis pigmentosa
Clemens, CJ; Seiple, W; Holopigian, K; Carr, RE
2004 APR ;45(9):U577-U577, Investigative ophthalmology & visual science. IOVS
— id: 48934, year: 2004, vol: 45, page: U577, stat: Journal Article,

Atypical multifocal ERG responses in patients with diseases affecting the photoreceptors
Greenstein, V C; Holopigian, K; Seiple, W; Carr, R E; Hood, D C
2004 Nov;44(25):2867-2874, Vision research
The purpose of this study was to investigate atypical multifocal ERG (mfERG) responses for patients with diseases that can affect the photoreceptors. MfERGS were obtained from seven patients with retinitis pigmentosa (RP), three with progressive cone dystrophy (CD) and eight with diabetic retinopathy (DR). Both first- and second-order kernel responses were analyzed. The amplitudes and implicit times of the first-order responses were compared to those obtained from age-similar controls. For the first slice of the second-order response, the root-mean-square (RMS) and the signal-to-noise ratio (SNR) of each response were calculated. Achromatic visual fields were also obtained from each subject. For the three groups of patients, first-order responses with relatively large amplitudes, broad-shaped waveforms and markedly increased implicit times had non-measurable second-order responses. These responses were associated with areas of decreased visual field sensitivity. As RP, CD and DR affect the outer retina, the results are consistent with damage to the outer plexiform layer rather than damage to the inner retina
— id: 92140, year: 2004, vol: 44, page: 2867, stat: Journal Article,

An examination of local ON- and OFF-System responses in patients with progressive cone dystrophy using long duration LED stimulation
Holopigian, K; Wynn, P; Clemens, CJ; Seiple, W; Carr, RE; Hood, DC
2004 APR ;45(9):U586-U586, Investigative ophthalmology & visual science. IOVS
— id: 48935, year: 2004, vol: 45, page: U586, stat: Journal Article,

Rod and cone photoreceptor function in patients with cone dystrophy
Holopigian, Karen; Greenstein, Vivienne C; Seiple, William; Hood, Donald C; Carr, Ronald E
2004 Jan;45(1):275-281, Investigative ophthalmology & visual science. IOVS
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
— id: 42630, year: 2004, vol: 45, page: 275, stat: Journal Article,

Test-retest reliability of the multifocal electroretinogram and humphrey visual fields in patients with retinitis pigmentosa
Seiple, William; Clemens, Colleen J; Greenstein, Vivienne C; Carr, Ronald E; Holopigian, Karen
2004 Nov;109(3):255-272, Documenta ophthalmologica
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
— id: 55997, year: 2004, vol: 109, page: 255, stat: Journal Article,

Multidimensional visual field maps: Relationships among local psychophysical and local electrophysiological measures
Seiple, William; Holopigian, Karen; Szlyk, Janet P; Wu, Carolyn
2004 May;41(3A):359-372, Journal of rehabilitation research & development
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
— id: 46898, year: 2004, vol: 41, page: 359, stat: Journal Article,

A comparison of multifocal and full-field photopic electroretinograms in patients with retinitis pigmentosa
Wynn, P; Holopigian, K; Carr, RE; Hood, DC
2004 APR ;45(9):U576-U576, Investigative ophthalmology & visual science. IOVS
— id: 48933, year: 2004, vol: 45, page: U576, stat: Journal Article,

M-versus P-function: Relationship to visual field loss in patients with open angle glaucoma
Badr, AA; Zemon, VM; Greenstein, VC; Clemens, CJ; Holopigian, K; Seiple, W
2003 MAY ;44(3):U5-U5, Investigative ophthalmology & visual science. IOVS
— id: 55412, year: 2003, vol: 44, page: U5, stat: Journal Article,

Local ON and OFF system responses in patients with progressive cone dystrophy
Holopigian, K; Seiple, W; Clemens, CJ; Rozenbaum, I; Carr, RE
2003 MAY ;44(3):U105-U105, Investigative ophthalmology & visual science. IOVS
— id: 55417, year: 2003, vol: 44, page: U105, stat: Journal Article,

Electrophysiology
Holopigian, Karen; Hood, Donald C
2003 Jun;16(2):237-251, Ophthalmology clinics of North America
Numerous electrophysiologic tests are available for use in the clinic. When properly recorded and analyzed, these tests provide important diagnostic and prognostic information about the site and nature of the disease process. If the results from these tests are combined with psychophysical findings (color vision, acuity, visual fields), their usefulness in defining disease can be further extended
— id: 93711, year: 2003, vol: 16, page: 237, stat: Journal Article,

The retinotopic distribution of localized attention assessed using the multifocal visual evoked potential
Kirzhner, M; Nam, JN; Clemens, CJ; Holopigian, K
2003 MAY ;44(19):U447-U447, Investigative ophthalmology & visual science. IOVS
— id: 55466, year: 2003, vol: 44, page: U447, stat: Journal Article,

The effect of variably tinted spectacle lenses on visual performance in cataract subjects
Naidu, Srilata; Lee, Jason E; Holopigian, Karen; Seiple, William H; Greenstein, Vivienne C; Stenson, Susan M
2003 Jan;29(1):17-20, Eye & contact lens
PURPOSE: A body of clinical and laboratory evidence suggests that tinted spectacle lenses may have an effect on visual performance. The aim of this study was to quantify the effects of spectacle lens tint on the visual performance of 25 subjects with cataracts. METHODS: Cataracts were scored based on best-corrected acuity and by comparison with the Lens Opacity Classification System (LOCS III) plates. Visual performance was assessed by measuring contrast sensitivity with and without glare (Morphonome software version 4.0). The effect of gray, brown, yellow, green and purple tinting was evaluated. RESULTS: All subjects demonstrated an increase in contrast thresholds under glare conditions regardless of lens tint. However, brown and yellow lens tints resulted in the least amount of contrast threshold increase. Gray lens tint resulted in the largest contrast threshold increase. CONCLUSIONS: Individuals with lenticular changes may benefit from brown or yellow spectacle lenses under glare conditions
— id: 39215, year: 2003, vol: 29, page: 17, stat: Journal Article,

Reliability of perimetry: Measures of acuity, contrast sensitivity, and luminance detection
Nam, JN; Kirzhner, M; Clemens, CJ; Holopigian, K; Seiple, W
2003 MAY ;44(19):U671-U671, Investigative ophthalmology & visual science. IOVS
— id: 55467, year: 2003, vol: 44, page: U671, stat: Journal Article,

Multifocal electroretinography as a function of age: the importance of normative values for older adults
Seiple, William; Vajaranant, Thasarat S; Szlyk, Janet P; Clemens, Colleen; Holopigian, Karen; Paliga, Jennifer; Badawi, David; Carr, Ronald E
2003 Apr;44(4):1783-1792, Investigative ophthalmology & visual science. IOVS
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
— id: 39262, year: 2003, vol: 44, page: 1783, stat: Journal Article,

Test-retest reliability of psychophysical and electrophysiological perimetric measures in patients with retinitis pigmentosa
Clemens, CJ; Kirzhner, M; Holopigian, K; Seiple, W; Greenstein, VC; Carr, RE
2002 MAY ;43(3):U254-U254, Investigative ophthalmology & visual science. IOVS
— id: 55483, year: 2002, vol: 43, page: U254, stat: Journal Article,

Local cone and rod system function in progressive cone dystrophy
Holopigian, Karen; Seiple, William; Greenstein, Vivienne C; Hood, Donald C; Carr, Ronald E
2002 Jul;43(7):2364-2373, Investigative ophthalmology & visual science. IOVS
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
— id: 39621, year: 2002, vol: 43, page: 2364, stat: Journal Article,

Effect of variable tinted spectacle lenses on visual performance in control subjects
Lee, Jason E; Stein, Jonathan J; Prevor, Meredith B; Seiple, William H; Holopigian, Karen; Greenstein, Vivienne C; Stenson, Susan M
2002 Apr;28(2):80-82, CLAO journal (Contact Lens Association of Ophthalmologists)
PURPOSE: To evaluate quantitatively the effects of tinted spectacle lenses on visual performance in individuals without visual pathology. METHODS: Twenty-five subjects were assessed by measuring contrast sensitivity with and without glare. Gray, brown, yellow, green, purple, and blue lens tints were evaluated. Measurements were repeated with each lens tint and with a clear lens, and the order was counterbalanced within and between subjects. Glare was induced with a modified brightness acuity tester. RESULTS: All subjects demonstrated an increase in contrast thresholds under glare conditions for all lens tints. However, purple and blue lens tints resulted in the least amount of contrast threshold increase; the yellow lens tint resulted in the largest contrast threshold increase. CONCLUSIONS: Purple and blue lens tints may improve contrast sensitivity in control subjects under glare conditions
— id: 37709, year: 2002, vol: 28, page: 80, stat: Journal Article,

Relationships among luminance, acuity, contrast, and electrophysiological perimetry in patients with retinitis pigmentosa
Seiple, WH; Clemens, C; Holopigian, K; Greenstein, V; Carr, R
2002 MAY ;43(3):U254-U254, Investigative ophthalmology & visual science. IOVS
— id: 55482, year: 2002, vol: 43, page: U254, stat: Journal Article,

The spatial distribution of selective attention assessed using the multifocal visual evoked potential
Seiple, William; Clemens, Colleen; Greenstein, Vivienne C; Holopigian, Karen; Zhang, Xian
2002 Jun;42(12):1513-1521, Vision research
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
— id: 39622, year: 2002, vol: 42, page: 1513, stat: Journal Article,

A method for comparing psychophysical and multifocal electroretinographic increment thresholds
Seiple, William; Greenstein, Vivienne C; Holopigian, Karen; Carr, Ronald E; Hood, Donald C
2002 Jan;42(2):257-269, Vision research
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
— id: 39725, year: 2002, vol: 42, page: 257, stat: Journal Article,

Multifocal visual evoked potentials to cone specific stimuli in patients with retinitis pigmentosa (RP)
Shuwairi, SM; Holopigian, K; Greenstein, VC; Zhang, X; Hood, DC
2002 MAY ;43(3):U271-U271, Investigative ophthalmology & visual science. IOVS
— id: 55484, year: 2002, vol: 43, page: U271, stat: Journal Article,

Localized attention assessed using the multifocal visual evoked potential
Clemens, CJ; Seiple, W; Holopigian, K; Greenstein, VC; Zhang, X
2001 MAR 15 ;42(4):S408-S408, Investigative ophthalmology & visual science. IOVS
— id: 54975, year: 2001, vol: 42, page: S408, stat: Journal Article,

An examination of visual evoked potential increment thresholds as a function of retinal eccentricity
Donsoff, I; Holopigian, K; Rubbani, S; Seiple, W
2001 MAR 15 ;42(4):S789-S789, Investigative ophthalmology & visual science. IOVS
— id: 54990, year: 2001, vol: 42, page: S789, stat: Journal Article,

Local cone and rod system function in patients with retinitis pigmentosa
Holopigian K; Seiple W; Greenstein VC; Hood DC; Carr RE
2001 Mar;42(3):779-788, Investigative ophthalmology & visual science. IOVS
PURPOSE. To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using electrophysiological and psychophysical techniques. METHODS. Cone-mediated multifocal electroretinograms (M-ERGs), cone system threshold visual fields, rod-mediated M-ERGs, and rod system threshold visual fields were measured in seven patients with RP. RESULTS. All the patients had normal cone system visual field thresholds and normal cone-mediated M-ERG implicit times within the central 5 degrees. Both cone-mediated responses were abnormal at some peripheral retinal locations. There were significant correlations among cone system amplitude, timing, and visual field loss. All the patients had some retinal areas where the rod-mediated M-ERG amplitudes were not measurable. In areas where they were measurable, these rod-mediated M-ERG responses were often within normal limits for amplitude and timing. In contrast to the cone system data, there were no significant relationships between rod-mediated M-ERG measures and rod system threshold elevations. The cone and rod system psychophysical thresholds showed regional correspondence; the amplitude-scale and time-scale measures of the M-ERG did not. CONCLUSIONS. The results indicate that there was better local correspondence between psychophysical and electrophysiological measures in the cone system than in the rod system in patients with RP. In addition, the psychophysical measures of cone and rod system function showed better correspondence than did the electrophysiological measures
— id: 26783, year: 2001, vol: 42, page: 779, stat: Journal Article,

Sites of cone and rod system loss in patients with progressive cone dystrophy
Holopigian, K; Greenstein, VC; Wu, C; Seiple, W; Hood, DC; Carr, RE
2001 MAR 15 ;42(4):S71-S71, Investigative ophthalmology & visual science. IOVS
— id: 54969, year: 2001, vol: 42, page: S71, stat: Journal Article,

Variable tinted spectacle lenses: a comparison of aesthetics and visual preference
Huang L; Seiple W; Park RI; Greenstein VC; Holopigian K; Naidu SS; Stenson SM
2001 Jul;27(3):121-124, CLAO journal (Contact Lens Association of Ophthalmologists)
PURPOSE: To determine the correlation between the aesthetics of lens tints preferred for cosmesis and lens tints preferred for viewing. METHODS: Thirty-five subjects (mean age: 25; 49% male, 51% female) with no significant ocular pathology participated in the study. Median visual acuity was 20/20. Color vision testing was performed on each subject using Ishihara plates, and those with abnormal scores were excluded from the study. Subjects were shown nine pre-selected tinted lenses (50% transmittance) of variable wavelengths. These lenses were mounted on two separate color backgrounds, one white and the other approximating their skin tone. Subjects were asked to choose from each background which tinted lens they would most prefer to wear and which lens they would least prefer to wear. The subjects were then shown a series of eight pictures (four nature photographs and four paintings) with different dominant wavelengths. Subjects were asked to grade the aesthetic effect of a clear lens and each of the nine tinted lenses on the appearance of the pictures. Chromaticity coordinates were calculated for each lens and picture. RESULTS: The blue lens was the most frequently chosen preferred lens to wear, followed by green, purple, and gray. The least preferred lenses were yellow, brown, and pink. For viewing the nature photographs, the clear lens was preferred over any of the tinted lenses. For viewing the paintings, the purple lens was most preferred. The yellow lens was least preferred for both photographs and paintings. CONCLUSIONS: Younger individuals with no significant ocular pathology preferred viewing both nature photographs and paintings through tinted lenses that did not, or only slightly, altered the chromaticity of the image. Whereas a clear lens was favored over the tinted lenses for viewing the photographs, some tinted lenses (purple and pink) were preferred for viewing paintings. There was no correlation between the most favored lens tint chosen based purely on cosmesis and the most favored lens tint based on viewing preference. However, the least preferred lens tint for cosmesis and viewing was yellow
— id: 26629, year: 2001, vol: 27, page: 121, stat: Journal Article,

Duration thresholds for target detection and identification in the peripheral visual field
Seiple W; Holopigian K; Shnayder Y; Szlyk JP
2001 Mar;78(3):169-176, Optometry & vision science
PURPOSE: In the current study, we measured threshold duration required to perform the tasks of letter identification, letter detection, grating orientation discrimination, and symmetry detection of targets presented as a function of retinal eccentricity. METHODS: Targets were presented in the nasal visual field on the horizontal meridian at eccentricities ranging from 0 degree to 22 degrees. Threshold duration was calculated using a modified staircase procedure. RESULTS: We found that for the task of letter identification, the rate of duration sensitivity loss was independent of the letter size. In contrast, for the tasks of letter detection, grating discrimination, and symmetry detection, the rate of loss was greater for smaller targets than for larger targets. CONCLUSION: At equivalent target sizes, letter identification always demonstrated the steepest decline in duration sensitivity with increasing eccentricity. This might be the case if the final stages of the identification process are rate limiting. It was hoped that by quantifying duration sensitivity of the peripheral retina, more appropriate temporal stimuli could be used in rehabilitation programs that train reading using eccentric preferred retina loci in patients with advanced macular disease
— id: 20698, year: 2001, vol: 78, page: 169, stat: Journal Article,

Retinal function in diabetic macular edema after focal laser photocoagulation
Greenstein VC; Chen H; Hood DC; Holopigian K; Seiple W; Carr RE
2000 Oct;41(11):3655-3664, Investigative ophthalmology & visual science. IOVS
PURPOSE: To assess the effects of focal photocoagulation on retinal function in the macular and perimacular areas in patients with diabetes who have clinically significant macular edema. METHODS: Eleven patients were assessed after focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques were used to evaluate the effects of treatment on macular, paramacular, and peripheral retinal function. A modified visual field technique was used to obtain local threshold fields. The posttreatment results were compared with pretreatment results. Changes in local ERG response amplitudes and implicit times were calculated for each patient and presented as difference fields. The changes in local ERG responses were compared with the changes in local field sensitivity. RESULTS: After treatment, the results of the psychophysical tests suggested little or no change in visual function, but changes in retinal function were observed with the multifocal ERG technique. Local ERG responses showed increases in implicit time and decreases in amplitude, compared with pretreatment values. Timing was affected more than amplitude. CONCLUSIONS: The results suggest that focal treatment produces changes in retinal function, and these changes are not restricted to the treated macular area
— id: 39554, year: 2000, vol: 41, page: 3655, stat: Journal Article,

The nature and extent of retinal dysfunction associated with diabetic macular edema
Greenstein VC; Holopigian K; Hood DC; Seiple W; Carr RE
2000 Oct;41(11):3643-3654, Investigative ophthalmology & visual science. IOVS
PURPOSE: To evaluate the nature and extent of retinal dysfunction in the macular and surrounding areas that occurs in patients with diabetes with clinically significant macular edema (CSME). METHODS: Eleven patients were evaluated before focal laser treatment. Multifocal electroretinogram (ERG) and full-field ERG techniques were used to assess the effects of diabetic retinopathy and CSME on macular, paramacular, and peripheral retinal function. A modified visual field technique was used to obtain local threshold fields. The relationship between local sensitivity changes and local ERG changes was determined. RESULTS: Local ERG responses were significantly delayed and decreased in amplitude, and timing changes were observed in a larger area of the retina than amplitude changes. Visual field deficits were similarly widespread with marked sensitivity losses occurring in retinal areas with normal ERG amplitudes and in areas that appeared to be free of fundus abnormalities. Despite this similarity and the finding that retinal areas with elevated thresholds have timing delays, timing delays were not good predictors of the degree of threshold elevation. CONCLUSIONS: The results demonstrate the widespread nature of timing deficits and visual field deficits that are associated with CSME
— id: 39555, year: 2000, vol: 41, page: 3643, stat: Journal Article,

Electrophysiologic assessment of photoreceptor function in patients with primary open-angle glaucoma
Holopigian K; Greenstein VC; Seiple W; Hood DC; Ritch R
2000 Apr;9(2):163-168, Journal of glaucoma
PURPOSE: Electroretinograms to high-intensity flashes were obtained to determine the extent of rod and cone photoreceptor and postreceptor dysfunction in patients with primary open-angle glaucoma. METHODS: Full-field flash electroretinograms were obtained using brief high-intensity flashes. Dark-adapted (rod-dominated) and light-adapted (cone-dominated) electroretinogram responses were recorded to a 'white' light as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of log Rmax (the maximum response) and log S (sensitivity). Oscillatory potentials were measured to the cone-dominated high-intensity flashes. Standard clinical 30 Hz flicker electroretinogram responses were recorded using a Grass photostimulator. RESULTS: Analysis of rod and cone a-wave data showed that log Rmax and log S values were within the normal range in nearly all of the patients. For some patients, oscillatory potentials were delayed beyond the normal range. CONCLUSION: Our results provide little evidence for widespread photoreceptor abnormalities in primary open-angle glaucoma
— id: 11735, year: 2000, vol: 9, page: 163, stat: Journal Article,

Are the differences between threshold visual fields and multifocal ERGs due to adaptation level?
Holopigian, K; Seiple, W; Greenstein, VC; Hood, DC; Carr, RE
2000 MAR 15 ;41(4):S892-S892, Investigative ophthalmology & visual science. IOVS
— id: 54624, year: 2000, vol: 41, page: S892, stat: Journal Article,

An attempt to detect glaucomatous damage to the inner retina with the multifocal ERG
Hood, D C; Greenstein, V C; Holopigian, K; Bauer, R; Firoz, B; Liebmann, J M; Odel, J G; Ritch, R
2000 May;41(6):1570-1579, Investigative ophthalmology & visual science. IOVS
PURPOSE: To detect glaucomatous damage to the inner retina using the multifocal electroretinogram (mERG). METHODS: The stimulus array consisted of 103 hexagons with a mean luminance of 100 cd/m2 and a contrast of 50%. The mERG was recorded from 13 control subjects, 18 patients with open-angle glaucoma (OAG), 4 glaucoma suspects, and one patient with ischemic optic neuropathy (ION). Individual responses, as well as responses summed within quadrants or across the entire array, were measured in a number of ways. Humphrey visual fields were obtained for all patients, and the mean total deviation (MD) values for the 18 patients with OAG ranged from -2.2 to -18.2 with a mean (SD) of -7.3 (4.5). RESULTS: The mERG measure that best discriminated between the patients and the control subjects was the ratio of the amplitude at 8 msec after the peak response to the amplitude at the peak. Although the value of this ratio fell below the median of the control group for 16 of the 18 OAG patients, only 6 of these patients had ratios that fell below the normal range. Other measures of first- and second-order kernels did not do as well. Both within and across patients, the correlation between local field loss and the mERG ratio measure was poor. Furthermore, although in some patients the mERG waveform is clearly different from normal, in other patients (including the patient with ION) the waveform approximates the normal even in visual field areas with substantial sensitivity loss. CONCLUSIONS: Because glaucomatous damage is known to affect the ganglion cell axon, these data suggest that damage to ganglion cell axons is not a sufficient condition to produce changes in the mERG as measured here and that in patients with clear changes in mERG waveforms, these changes do not appear to be well localized and local waveforms are poorly correlated with local changes in field sensitivity
— id: 93712, year: 2000, vol: 41, page: 1570, stat: Journal Article,

A comparison of psychophysical and multifocal electroretinographic increment thresholds as a function of retinal location
Seiple, W; Holopigian, K; Greenstein, VC; Hood, DC
2000 MAR 15 ;41(4):S496-S496, Investigative ophthalmology & visual science. IOVS
— id: 54616, year: 2000, vol: 41, page: S496, stat: Journal Article,

Functional peripheral visual performance in patients with RP
Holopigian, K; Seiple, W; Wu, C; Carr, RE
1999 May 9-14;40(4):S718-S718, Investigative ophthalmology & visual science. IOVS
— id: 34141, year: 1999, vol: 40, page: S718, stat: Journal Article,

Identifying inner retinal contributions to the human multifocal ERG
Hood, D C; Greenstein, V; Frishman, L; Holopigian, K; Viswanathan, S; Seiple, W; Ahmed, J; Robson, J G
1999 Jun;39(13):2285-2291, Vision research
Contributions to the multifocal electroretinogram (ERG) from the inner retina (i.e. ganglion and amacrine cells) were identified by recording from monkeys before and after intravitreal injections of n-methyl DL aspartate (NMDLA) and/or tetrodotoxin (TTX). Components similar in waveform to those removed by the drugs were identified in the human multifocal ERG if the stimulus contrast was set at 50% rather than the typically employed 100% contrast. These components were found to be missing or diminished in the records from some patients with glaucoma and diabetes, diseases which affect the inner retina
— id: 93713, year: 1999, vol: 39, page: 2285, stat: Journal Article,

Retinotopic distribution of the temporal aspects of letter identification
Seiple, W; Wu, C; Holopigian, K; Szlyk, J; Shnayder, Y; Chen, H
1999 May 9-14;40(4):S34-S34, Investigative ophthalmology & visual science. IOVS
— id: 34142, year: 1999, vol: 40, page: S34, stat: Journal Article,

Multifocal rod electroretinograms
Hood DC; Wladis EJ; Shady S; Holopigian K; Li J; Seiple W
1998 Jun;39(7):1152-1162, Investigative ophthalmology & visual science. IOVS
PURPOSE: To assess the feasibility of obtaining reliable multifocal rod electroretinograms (ERGS) and to compare them to full-field ERGs. METHODS: Multifocal rod ERGs were recorded using a stimulus array of 61 hexagons. The minimum number of dark, blank frames between flashes was varied from 0 (a minimum of 13.3 msec between flashes) to 21 (a minimum of 293 msec between flashes). Full-field ERGs were obtained using trains of flashes designed to simulate the multifocal sequences. Flashes were blue (W47B), except in a few cases in which red (W26) was used to check for cone intrusion. Flash intensities varied from -1 to 1.7 log scot td-s. RESULTS: Dark-adapted, multifocal ERGs to blue flashes had a small, early component followed by a larger, late component. The early component showed little change in amplitude with increasing intensity. Comparisons with the full-field ERGs indicated that the early component was the focal response. The larger, late component was the response to stray light, and it can be suppressed with the addition of a surround. The focal response was from a relatively circumscribed retinal region. This is shown by comparing the multifocal rod responses from a patient with retinitis pigmentosa to her behaviorally measured rod visual field. CONCLUSIONS: By choosing conditions (namely, flashes of moderate intensity with a surround) to minimize the effects of stray light, multifocal rod ERGs can be recorded with sufficient localization to be clinically useful. However, the signal-to-noise ratio of these multifocal rod ERGs was poorer than for multifocal cone responses for comparable recording periods because of the need for blank frames and the slower recovery of the rods to successive presentations
— id: 57168, year: 1998, vol: 39, page: 1152, stat: Journal Article,

Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique
Hood, D C; Holopigian, K; Greenstein, V; Seiple, W; Li, J; Sutter, E E; Carr, R E
1998 Jan;38(1):163-179, Vision research
To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and local thresholds (static visual fields) were obtained on eight RP patients with visual acuities of 20/25 or better. All eight patients showed multi-focal responses with normal timing within the central 5 deg. However, there were few responses with normal timing in the areas outside the central 7.5 deg, except in the case of the only patient with a 30 Hz full-field response with normal timing. Since full-field ERGs are dominated by responses from the periphery, this finding supplies a foundation for the commonly observed delays in the full-field cone ERGs of patients with RP. With respect to amplitude, only two patients showed multi-focal responses with near normal amplitudes anywhere in the field. The loss of amplitude at any point was not a good predictor of visual sensitivity in the Humphrey visual field. On the other hand, all areas with normal timing had near normal sensitivity. Timing changes appear to be an early indication of local retinal damage to the cone system. Nearly all areas with sensitivity losses greater than 0.5 log unit, and some areas with near normal sensitivity, showed significantly delayed multi-focal ERGs. Finally areas with extreme sensitivity loss show multi-focal responses with a wide range of amplitudes and implicit times across patients, suggesting different mechanisms of disease action in different patients
— id: 92135, year: 1998, vol: 38, page: 163, stat: Journal Article,

Multi-focal ERGs and visual fields in diabetic patients with macular edema
Greenstein, VC; Holopigian, K; Seiple, W; Kahanowicz, R; Katz, A
1997 MAR 15 ;38(4):3548-3548, Investigative ophthalmology & visual science. IOVS
— id: 53242, year: 1997, vol: 38, page: 3548, stat: Journal Article,

Evidence for photoreceptor changes in patients with diabetic retinopathy
Holopigian K; Greenstein VC; Seiple W; Hood DC; Carr RE
1997 Oct;38(11):2355-2365, Investigative ophthalmology & visual science. IOVS
PURPOSE: To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy. METHODS: Twelve patients with diabetes and varying levels of retinopathy and nine age-similar control observers participated in this study. Two-color (500 versus 650 nm) dark-adapted thresholds were measured as a function of retinal eccentricity. Full-field flash electroretinograms were obtained using brief, high-intensity flashes. Dark-adapted rod-isolated (Wratten 47B filter) and light-adapted cone-isolated (Wratten 26 filter) electroretinographic responses were measured as a function of flash intensity. The a-wave data were fitted with a model based on photopigment transduction to obtain values for the parameters of Rmax (the maximal response) and log S (sensitivity). Standard clinical 30-Hz flicker electroretinographic responses were also measured. RESULTS: Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. Analysis of rod and cone a-wave data showed that Rmax was normal in most of the patients, but log S was reduced. Analysis of b-wave and oscillatory potential parameters showed rod and cone postreceptoral abnormalities, including changes in the rod-isolated semisaturation constant (log k), cone-mediated 30-Hz flicker, and cone-isolated oscillatory potentials. The electrophysiological results were not significantly correlated with blood glucose or glycosylated hemoglobin level. CONCLUSIONS: The results provide evidence for rod and cone receptoral and postreceptoral deficits in patients with diabetic retinopathy. The photoreceptor changes are primarily in the log S (sensitivity) parameter and are attributed to transduction abnormalities
— id: 12264, year: 1997, vol: 38, page: 2355, stat: Journal Article,

Relative effects of aging and age-related macular degeneration on peripheral visual function
Holopigian K; Seiple W; Greenstein V; Kim D; Carr RE
1997 Mar;74(3):152-159, Optometry & vision science
The purpose of this study was to determine the extent of peripheral visual deficits in patients with early age-related macular degeneration (ARMD) using electrophysiological and psychophysical techniques. Dark-adaptation curves, electro-oculograms (EOGs), and electroretinograms (ERGs) were obtained from patients with early ARMD and from normally sighted control subjects. The control subjects' data were used to calculate age-dependent 95% confidence intervals for each measure of visual function. For the control subjects, performance on all our measures of visual function decreased with age. For the patients with early ARMD, the cone system absolute thresholds, EOG ratios, and cone-dominated ERG amplitudes and implicit times were within the range of normal age-related changes. Rod system absolute thresholds, cone-rod break times, and rod-dominated electroretinographic measures were abnormal in some patients. These results suggest that when the effects of aging are taken into account, some patients classified as early ARMD may not show significant changes in peripheral retinal function with standard clinical tests
— id: 56952, year: 1997, vol: 74, page: 152, stat: Journal Article,

A comparison of the components of the multifocal and full-field ERGs
Hood, D C; Seiple, W; Holopigian, K; Greenstein, V
1997 May-Jun;14(3):533-544, Visual neuroscience
The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs. The purpose here was to compare the components of this multifocal ERG to the components of the standard, full-field ERG. To record multifocal ERGs, an array of 103 hexagons was displayed on a monitor. Full-field (Ganzfeld) ERGs were elicited by flashes presented upon steady background fields. The latencies of two prominent subcomponents of the full-field ERG were altered by varying the intensity of the incremental flash or the intensity of the background field. By showing that similar manipulations of the multi-input parameters produce similar changes in latency, we were able to relate the components of the multifocal ERG to the components of the full-field ERG. The biphasic responses of the multifocal ERG appear to be generated by the same cells generating the a-wave and positive peaks of the full-field cone ERG
— id: 93714, year: 1997, vol: 14, page: 533, stat: Journal Article,

Rod multi-focal ERGs
Hood, DC; Wladis, EJ; Shady, S; Holopigian, K; Li, J; Seiple, W
1997 MAR 15 ;38(4):4121-4121, Investigative ophthalmology & visual science. IOVS
— id: 53243, year: 1997, vol: 38, page: 4121, stat: Journal Article,

Electroretinographic and psychophysical findings during early and late stages of human immunodeficiency virus infection and cytomegalovirus retinitis
Latkany PA; Holopigian K; Lorenzo-Latkany M; Seiple W
1997 Mar;104(3):445-453, Ophthalmology
PURPOSE: The authors examined electrophysiologic and psychophysical measures of retinal function in patients infected with human immunodeficiency virus (HIV) at different stages of infection, including patients with cytomegalovirus retinitis (CMVR). METHODS: All patients had complete ophthalmologic examinations. Rod-mediated psychophysical thresholds were measured using a modified two-color dark-adapted perimetry technique. Rod-dominated full field flash electroretinograms (ERGs) were obtained as a function of flash intensity, followed by cone-dominated ERGs. The 26 patients infected with HIV (26 eyes) were categorized into three groups. Six patients were infected with HIV but had not progressed to acquired immunodeficiency syndrome (AIDS), and 14 had AIDS. Six patients had CMVR with less than 10% of the retina involved. The data were compared with results from age-similar control subjects. RESULTS: Psychophysical thresholds as a function of retinal eccentricity were elevated for each of the three stages of HIV infection. The group of patients with CMVR had the greatest amount of threshold elevation and threshold elevation increased with retinal eccentricity. In addition, all three patient groups had abnormal electroretinographic findings. Patients with CMVR were affected more severely on all measures than were the other HIV-infected groups. CONCLUSIONS: Results reveal that a diffuse functional retinal pathology exists in eyes with the funduscopic appearance of localized peripheral CMVR. Additionally, patients infected with HIV, including those without cotton wool spots, may have abnormal retinal function
— id: 12368, year: 1997, vol: 104, page: 445, stat: Journal Article,

Rates of change differ among measures of visual function in patients with retinitis pigmentosa
Holopigian K; Greenstein V; Seiple W; Carr RE
1996 Mar;103(3):398-405, Ophthalmology
PURPOSE: To assess changes in measures of visual function in patients with retinitis pigmentosa (RP) over time. METHODS: Patients with RP and visual acuity of 20/40 or better and central visual fields of 10 degrees or larger were enrolled in a 9-year prospective study. The following measures of visual function were obtained annually over the follow-up period: visual acuity, Goldmann visual fields (V4e target), focal electroretinograms, and hue discrimination. RESULTS: Over the follow-up period, the averaged group data showed changes in all measures of visual function. The smallest amount of change occurred for visual acuity and hue discrimination, and the greatest amount of change occurred for visual field area. Examination of individual patient data over the follow-up period indicated that the rates of change varied among patients and that losses in function for one measure did not correlate well with losses on other measures. CONCLUSIONS: These results stress that although visual function deteriorated over time for this group of patients with RP, there were differences among our measures of visual function. Measures that primarily assess central retinal function change relatively slowly compared with measures that assess more peripheral retinal function
— id: 7005, year: 1996, vol: 103, page: 398, stat: Journal Article,

Assessment of receptoral and post-receptoral changes in primary open-angle glaucoma
Holopigian, K; Pollack, A; Greenstein, VC; Seiple, W; Hood, DC; Ritch, R
1996 FEB 15 ;37(3):2343-2343, Investigative ophthalmology & visual science. IOVS
— id: 53023, year: 1996, vol: 37, page: 2343, stat: Journal Article,

Do the delays in the cone ERG from patients with RP indicate global retinal damage?
Hood, DC; Holopigian, K; Greenstein, VC; Seiple, W; Carr, RE; Sutter, EE
1996 FEB 15 ;37(3):1558-1558, Investigative ophthalmology & visual science. IOVS
— id: 53022, year: 1996, vol: 37, page: 1558, stat: Journal Article,

Outer-retina locus of increased flicker sensitivity of the peripheral retina
Seiple W; Holopigian K
1996 Mar;13(3):658-666, Journal of the Optical Society of America. Pt. A. Optics & image science
We tested alternative hypotheses concerning the locus of enhanced flicker sensitivity observed in response to stimuli presented to the peripheral retina. The first hypothesis attributes increased temporal frequency sensitivity to ganglion cell and higher-order neural processing, whereas the second hypothesis states that the locus of these temporal effects is at the cone photoreceptors. To test these alternative hypotheses we measured retinal electrophysiological and psychophysical temporal modulation thresholds. We found that sensitivity for temporal frequencies < 30 Hz did not vary as a function of retinal location for either the focal electroretinogram (ERG) or the psychophysical measure. However, for both measures, sensitivity for temporal frequencies > or = 30 Hz was greater in the peripheral retina than in the central retina. In addition, critical flicker frequency for the central retina was linear as a function of retinal illuminance for both the psychophysical and the electrophysiological measures. For the peripheral retina the slopes of critical flicker frequency versus log illuminance functions were steeper than the central slopes for both threshold measures. Eccentrically measured focal ERG and psychophysical critical flicker frequency values showed a relative saturation, deviating from the linear slope above 3.5 log Td. The findings of similar focal ERG and psychophysical temporal sensitivity changes with eccentricity support an outer retinal origin of this phenomenon
— id: 7046, year: 1996, vol: 13, page: 658, stat: Journal Article,

Age-related functional field losses are not eccentricity dependent
Seiple W; Szlyk JP; Yang S; Holopigian K
1996 Jun;36(12):1859-1866, Vision research
Previous studies have found an increase in peripheral target localization errors in normally sighted older adults. These results have been interpreted as indicative of a constriction of the 'useful field of view'. In the present study, we parametrically manipulated masking, distractors and stimulus luminance and examined the relationships between peripheral target localization and age. We found that backward masking and/or flashed distractors increased error rates. This decrement in performance was larger for more peripherally located targets and largest for the older subjects at all stimulus locations. Stimulus luminance (either 2 or 78 cd/m2) had no effect on peripheral localization performance at any age. We also demonstrated that all subjects, regardless of age, had higher localization error rates to more peripherally located targets. In older subjects, error rates increased equally at all eccentricities; that is, there was an eccentricity independent increase in the number of target localization errors as a function of age. This finding does not support the interpretation of a selective constriction of the functional visual field in older subjects
— id: 56990, year: 1996, vol: 36, page: 1859, stat: Journal Article,

ROD AND CONE PHOTORECEPTOR ANALYSIS IN PATIENTS WITH DIABETIC-RETINOPATHY
HOLOPIGIAN, K; KELLY, R; GREENSTEIN, VC; SEIPLE, W; HOOD, DC
1995 MAR 15 ;36(4):S480-S480, Investigative ophthalmology & visual science. IOVS
— id: 87337, year: 1995, vol: 36, page: S480, stat: Journal Article,

The effects of random element loss on letter identification: implications for visual acuity loss in patients with retinitis pigmentosa
Seiple W; Holopigian K; Szlyk JP; Greenstein VC
1995 Jul;35(14):2057-2066, Vision research
The hypothesis that reductions in Snellen acuities in patients with retinitis pigmentosa are due solely to losses of photoreceptors was tested by measuring the effects of random losses of sampling elements on letter identification. Sampling element losses were mimicked by setting the luminance of randomly selected pixels equal to the luminance of the surround. The amount of pixel blanking ranged from 0 to 90%. Letters varying in retinal subtense from 5 to 17 min arc were presented for 500 msec. Although letter identification accuracy decreased with increasing pixel blanking for all letter sizes, performance remained relatively high even when a majority of the pixels was blanked. The data suggest that unless the loss of cone photoreceptors in greater than 80%, loss of sampling elements alone can not account for letter acuities poorer than 20/40. In addition to loss of cone photoreceptors in patients with RP, there are histological reports of photoreceptor abnormalities and psychophysical studies of visual sensory deficits. It is conceivable that these alone, or in combination with losses of photoreceptors, could account for decreased visual acuity. In a series of experiments, stimulus parameters were manipulated in order to mimic the effects of some of these abnormalities and deficits and the effects on letter identification were examined. The results of these experiments demonstrated that sampling element loss interacts with sensory factors (e.g. luminance and contrast sensitivity) and perceptual factors (e.g. set size and letter orientation) to reduce letter identification accuracy. The implication of these results is that decreases in letter acuity observed in patients with retinitis pigmentosa cannot be attributed solely to a random loss of sampling elements in the underlying retina, but may be due to the combination of photoreceptor degeneration and other sensory and perceptual factors
— id: 56847, year: 1995, vol: 35, page: 2057, stat: Journal Article,

Comparison of visual evoked potential and psychophysical contrast sensitivity
Seiple W; Kupersmith MJ; Holopigian K
1995 ;80(1-4):173-180, International journal of neuroscience
We measured contrast processing as a function of spatial and temporal frequency using three measurement techniques: psychophysical thresholds, visual evoked potential (VEP) thresholds and VEP amplitudes. Measurements were made using the same stimulus parameters and on the same group of subjects. The agreement among these functions depended upon the particular spatio-temporal stimulus employed and in general, there were more differences than similarities among these measures. For example, VEP derived functions (both amplitude and threshold) peaked at 4 c/deg, whereas, the psychophysical functions peaked at 1 c/deg. VEP amplitude functions were maximum at > or = 3.5 Hz, whereas both psychophysical and VEP sensitivity were maximum at < or = 2.5 Hz. VEP thresholds were broad and low pass in shape and in contrast, the psychophysical and VEP amplitude functions were band pass. In summary, comparisons among these measures of contrast processing must be made with caution
— id: 12835, year: 1995, vol: 80, page: 173, stat: Journal Article,

The effects of dopamine blockade on the human flash electroretinogram
Holopigian K; Clewner L; Seiple W; Kupersmith MJ
1994 ;86(1):1-10, Documenta ophthalmologica
Single-cell electrophysiologic studies have shown that dopamine modulates retinal activity, but its role in human retinal processing is unclear. We investigated the effects of short-term oral administration of dopaminergic receptor blocking agents on the flash electroretinogram in humans. Both chlorpromazine (25 and 50 mg) and fluphenazine (1 and 2 mg) significantly reduced electroretinogram b-wave amplitudes and also selectively reduced the amplitude of the first oscillatory potential. Implicit times were not altered. Metoclopramide (10 and 20 mg) had no effect on any electroretinographic variable. Our study indicates that dopamine receptor blocking agents with both D-1 and D-2 receptor affinities reduce the amplitude of the electroretinogram in humans
— id: 57469, year: 1994, vol: 86, page: 1, stat: Journal Article,

DECREASED RETINAL FUNCTION IN HIV AIDS PATIENTS WITH AND WITHOUT CMV RETINITIS
LATKANY, P; FROST, K; HOLOPIGIAN, K; PAK, SM; LORENZO, M; SEIPLE, W
1994 MAR 15 ;35(4):1310-1310, Investigative ophthalmology & visual science. IOVS
— id: 52541, year: 1994, vol: 35, page: 1310, stat: Journal Article,

VISUAL-LOSS CAUSED BY RETINAL CHOROIDAL LESIONS ASSOCIATED WITH CAVERNOUS SINUS REGION AV SHUNTS
PAK, S; KUPERSMITH, MJ; HOLOPIGIAN, K; SEIPLE, W
1994 MAR 15 ;35(4):1374-1374, Investigative ophthalmology & visual science. IOVS
— id: 52543, year: 1994, vol: 35, page: 1374, stat: Journal Article,

The 'OFF' response of the human electroretinogram does not contribute to the brief flash 'b-wave'
Seiple W; Holopigian K
1994 Jul-Aug;11(4):667-673, Visual neuroscience
It has been assumed that the 'ON' and 'OFF' responses of the human electroretinogram (ERG) interact to produce a single waveform when brief flashes are used. To test this assumption, we examined the separate effects of stimulus intensity, the level of retinal illuminance and stimulus duration on the ERG. Both 'ON' and 'OFF' response amplitude decreased as stimulus intensity was decreased and as the level of retinal illumination was reduced. When stimulus duration was reduced, the amplitude of the 'OFF' response decreased; however, the amplitude of the 'ON' response increased. Summing of the 'ON' and 'OFF' response waveforms could not account for the increased amplitude in response to brief stimuli or for the changes in ERG wave shape. These results indicate that there is not a significant corneally recordable 'OFF' response elicited by brief stimuli, such as those commonly used to record the flash ERG
— id: 6746, year: 1994, vol: 11, page: 667, stat: Journal Article,

Visual evoked potentials following abrupt contrast changes
Xin D; Seiple W; Holopigian K; Kupersmith MJ
1994 Nov;34(21):2813-2821, Vision research
The timing of visual evoked potential (VEP) amplitude and phase changes following abrupt increases or decreases in contrast was examined. Gratings (1 c/deg) were presented at a low contrast for 8 sec, increased to a higher contrast for 8 sec, and then decreased to the initial lower contrast for another 8 sec. Second harmonic VEP amplitude and phase were recorded continuously and averaged in 1 sec epochs. Both amplitude and phase exhibited delays in reaching a stable level following the contrast change. For amplitude, the length of the delay was dependent on the magnitude and direction of the contrast step and on the spatial frequency of the stimulus. Time constants for the change in amplitude following step increases in contrast ranged from 0.2 sec for a 12% contrast step to 1.34 sec for a 37% contrast step. The timing of phase changes, however, was independent of the size of the contrast increases (tau = 0.7 sec). For step decreases in contrast, both amplitude and phase were relatively independent of the size of the change (tau = approx. 0.9 sec for amplitude and tau = 0.15 sec for phase). Amplitude time constants also increased with increasing spatial frequency (tau = 1.2 sec for 1 c/deg, tau = 1.6 sec for 4 c/deg and tau = 2.3 sec for 8 c/deg); phase time constants, however, did not change as a function of spatial frequency (tau = 0.7 for all spatial frequencies). These findings demonstrate that a unitary process may not always be tapped by signal averaging techniques. Additionally, swept stimulus VEP techniques may produce considerable errors in threshold estimation depending on the stimulus spatial frequency and on the slope and direction of the contrast change
— id: 56731, year: 1994, vol: 34, page: 2813, stat: Journal Article,

INCREMENT THRESHOLD CURVES - THE EFFECTS OF PERIODIC AND APERIODIC STIMULI
YANG, S; HU, HP; GREENSTEIN, VC; HOLOPIGIAN, K; SEIPLE, W
1994 MAR 15 ;35(4):1835-1835, Investigative ophthalmology & visual science. IOVS
— id: 52556, year: 1994, vol: 35, page: 1835, stat: Journal Article,

PROSPECTIVE-STUDY OF CENTRAL VISUAL FUNCTION IN RETINITIS-PIGMENTOSA
CARR, R; HOLOPIGIAN, K; GREENSTEIN, V; KY, W; HALEVY, D; SEIPLE, W
1993 MAR 15 ;34(4):1369-1369, Investigative ophthalmology & visual science. IOVS
— id: 54327, year: 1993, vol: 34, page: 1369, stat: Journal Article,

The effects of acetazolamide on visual function in retinitis pigmentosa
Greenstein VC; Holopigian K; Siderides E; Seiple W; Carr RE
1993 Jan;34(1):269-273, Investigative ophthalmology & visual science. IOVS
PURPOSE. To study the effects of acetazolamide on central and peripheral visual function in patients with retinitis pigmentosa (RP) who showed no evidence of macular edema. METHODS. Thirteen patients with retinitis pigmentosa participated in a preliminary study. Measures of central and peripheral visual function were obtained before and after an 8 wk period on acetazolamide. An additional 10 patients participated in a cross-over study. They were placed on a placebo for an 8 wk period, then on acetazolamide for a second 8 wk period. RESULTS. None of the patients in the preliminary study showed significant changes in visual acuity, color vision, foveal cone pathway sensitivities, focal electroretinogram (ERG) amplitudes, or in any ERG parameter. Three patients, however, showed significant changes in visual field area and in dark-adapted thresholds. None of the patients in the cross-over study showed significant increases in visual field area. CONCLUSIONS. Given the results and the reports of side-effects, it is difficult to justify using acetazolamide to improve retinal function in RP patients who show no evidence of cystoid macular edema
— id: 13297, year: 1993, vol: 34, page: 269, stat: Journal Article,

ELECTROPHYSIOLOGICAL EVIDENCE FOR OUTER RETINAL DEFICITS IN PRIMARY OPEN ANGLE GLAUCOMA
HOLOPIGIAN, K; SEIPLE, W; GREENSTEIN, VC
1993 MAR 15 ;34(4):1269-1269, Investigative ophthalmology & visual science. IOVS
— id: 54326, year: 1993, vol: 34, page: 1269, stat: Journal Article,

Electro-oculogram changes in patients with ocular hypertension and primary open-angle glaucoma
Mehaffey L; Holopigian K; Seiple W
1993 ;83(2):103-110, Documenta ophthalmologica
Recent evidence suggests that retinal hypoxia and ischemia affect the standing potential of the eye and the activity of the photoreceptors. To test whether chronically elevated intraocular pressure would produce similar effects, we measured electro-oculograms in two groups of patients: ocular hypertensive patients and patients with primary open-angle glaucoma. There were significant differences among the average electro-oculogram ratios of these groups compared to age-similar controls. The control observers had an average light-peak/dark-trough ratio of 2.86, the ocular hypertensive patients had an average ratio of 2.44, and the patients with primary open-angle glaucoma had an average ratio of 2.07. This indicates that long-term elevations in intraocular pressure can decrease the light peak of the electro-oculogram, even in patients with no other evidence of glaucomatous damage. This deficit may have its origins in the sensitivity of the outer retina to choroidal ischemia
— id: 57458, year: 1993, vol: 83, page: 103, stat: Journal Article,

Comparison of P100 and P300 cortical potentials in spatial frequency discrimination
Mehaffey, L 3rd; Seiple, W; Holopigian, K
1993 ;85(2):173-183, Documenta ophthalmologica
The P300 cortical evoked potential was compared to the P100 wave of the visual evoked potential by means of appearance/disappearance gratings. The spatial frequency of the novel stimulus was varied to compare the effect of task sensory difficulty on both P100 and P300 potentials. The P100 showed a steady increase in latency with the spatial frequency of the uncommon stimulus, and a degree of amplitude tuning consistent with the contrast sensitivity function. The P300 showed marked changes in both amplitude and latency dependent almost wholly on the proximity of the uncommon stimulus spatial frequency to that of the common stimulus. Motor reaction time showed elements of both the P100 and P300 response patterns. The results are consistent with a model in which, after visual information arrives at the visual cortex, processing is parallel and interdependent. In this model, the amplitude and latency of the P100 cortical evoked potential are governed solely by properties intrinsic to the stimulus, whereas the amplitude and latency of the P300 are functions of the degree of stimulus mismatch
— id: 93715, year: 1993, vol: 85, page: 173, stat: Journal Article,

Sites of cone system sensitivity loss in retinitis pigmentosa
Seiple WH; Holopigian K; Greenstein VC; Hood DC
1993 Aug;34(9):2638-2645, Investigative ophthalmology & visual science. IOVS
PURPOSE. To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing focal electroretinographic and psychophysical modulation thresholds. METHODS. Both psychophysical and electrophysiologic increment threshold curves were obtained in retinitis pigmentosa patients and a group of age-matched, normally-sighted adults. RESULTS. The majority of the retinitis pigmentosa data could be accounted for by a vertical displacement of the normal curve. The retinitis pigmentosa patients showed similar patterns of cone sensitivity losses using both techniques. CONCLUSIONS. The combined electrophysiologic and psychophysical results provide support for an outer retina locus for these cone sensitivity losses. The data suggest that these deficits may be caused by a spatially independent loss of cone photoreceptors with normal adaptation properties in the remaining photoreceptors
— id: 56588, year: 1993, vol: 34, page: 2638, stat: Journal Article,

INDEPENDENCE OF SAMPLING DENSITY AND VISUAL RECOGNITION
SEIPLE, W; HOLOPIGIAN, K; SZLYK, JP
1993 MAR 15 ;34(4):777-777, Investigative ophthalmology & visual science. IOVS
— id: 54317, year: 1993, vol: 34, page: 777, stat: Journal Article,

SUPRATHRESHOLD VEP EVIDENCE OF MERIDIONAL AMBLYOPIA
XIN, D; KUPERSMITH, MJ; SEIPLE, W; HOLOPIGIAN, K
1993 MAR 15 ;34(4):864-864, Investigative ophthalmology & visual science. IOVS
— id: 54318, year: 1993, vol: 34, page: 864, stat: Journal Article,

THE EFFECTS OF ACETAZOLAMIDE ON CENTRAL AND PERIPHERAL VISUAL FUNCTION IN RETINITIS-PIGMENTOSA
CARR, R; GREENSTEIN, V; HOLOPIGIAN, K; SEIPLE, W
1992 MAR 15 ;33(4):1072-1072, Investigative ophthalmology & visual science. IOVS
— id: 52049, year: 1992, vol: 33, page: 1072, stat: Journal Article,

A comparison of photopic and scotopic electroretinographic changes in early diabetic retinopathy
Holopigian K; Seiple W; Lorenzo M; Carr R
1992 Sep;33(10):2773-2780, Investigative ophthalmology & visual science. IOVS
Previous studies of early diabetic retinopathy have shown that oscillatory potential (OP) amplitudes are reduced in many diabetic patients. OP amplitude is believed to be a more sensitive indicator of the development of future retinopathy than b-wave amplitude of the scotopic electroretinogram (ERG). Because OPs measured to a bright white flash reflect both rod and cone system activity, it is important to compare OP amplitudes to photopic ERG measures as well as scotopic measures in early diabetic retinopathy. In this study, OPs and ERG responses were measured under photopic and scotopic conditions in a group of diabetic patients. Although OPs were reduced in amplitude in the diabetic group, several other parameters of the scotopic and photopic b-waves were impaired. The results indicate that b-wave activity may indicate retinal changes in early diabetic retinopathy in the same manner as the OPs
— id: 57456, year: 1992, vol: 33, page: 2773, stat: Journal Article,

ANALYSIS OF ROD SYSTEM ACTIVITY IN DIABETES-MELLITUS
HOLOPIGIAN, K; GREENSTEIN, V; SEIPLE, W; WEINER, M; HOOD, D
1992 MAR 15 ;33(4):1365-1365, Investigative ophthalmology & visual science. IOVS
— id: 52056, year: 1992, vol: 33, page: 1365, stat: Journal Article,

ELECTROPHYSIOLOGICAL AND PSYCHOPHYSICAL ASSESSMENT OF AGE-RELATED MACULAR DEGENERATION
KIM, D; DUBOVY, S; HOLOPIGIAN, K; GREENSTEIN, V; SEIPLE, W; CARR, R
1992 MAR 15 ;33(4):1231-1231, Investigative ophthalmology & visual science. IOVS
— id: 52053, year: 1992, vol: 33, page: 1231, stat: Journal Article,

OPTIC ATROPHY FAILS TO ALTER THE FLASH ELECTRORETINOGRAM
KUPERSMITH MJ; GUPTA K; SEIPLE WH; HOLOPIGIAN K
1992 MAY ;7(3):247-250, Clinical vision sciences
Seven patients with longstanding monocular optic atrophy had normal flash electroretinograms when compared to the results from control observers or when compared to the results from their own unaffected eye, or the eyes of control observers. These findings are contrasted with prior investigations that report either depression or augmentation of ERG amplitudes. We found that optic nerve damage does not cause trans-synaptic changes in the retina, or loss of efferent inhibition that can be measured by electroretinography
— id: 130408, year: 1992, vol: 7, page: 247, stat: Journal Article,

Maculopathy caused by intra-arterially administered cisplatin and intravenously administered carmustine
Kupersmith MJ; Seiple WH; Holopigian K; Noble K; Hiesiger E; Warren F
1992 Apr 15;113(4):435-438, American journal of ophthalmology
Eight patients with malignant gliomas were monitored with clinical examinations to study the effects of the combination of intravenous administration of carmustine and infraophthalmic intra-arterial administration of cisplatin on retinal and optic nerve function. Three patients developed a severe macular retinal pigment abnormality in the eye ipsilateral to the intra-arterial infusion. Electrophysiologic studies disclosed no evidence of a generalized disturbance in the photoreceptors, middle retinal layers, or retinal pigment epithelium. In contrast to previous studies involving patients whose visual loss was caused by vaso-occlusive lesions in the retina and optic nerve, our study involved patients with clinically significant maculopathy, that was not vascular in origin and that developed after treatment with carmustine and cisplatin. We suggest that the deficit may result from a localized retinal pigment disturbance in the macula
— id: 13630, year: 1992, vol: 113, page: 435, stat: Journal Article,

Temporal frequency dependent adaptation at the level of the outer retina in humans
Seiple W; Holopigian K; Greenstein V; Hood DC
1992 Nov;32(11):2043-2048, Vision research
The focal electroretinogram (FERG) was used to examine temporal frequency tuning at the outer retinal level in humans by measuring temporal modulation thresholds. Changes in FERG thresholds as a function of ambient light level were compared to temporal modulation thresholds obtained psychophysically using the same stimuli. At lower temporal frequencies, both FERG and psychophysical thresholds changed sensitivity proportional to the mean illuminance level. At higher illuminance levels, both threshold measures were relatively independent of illuminance. The comparison of the FERG to the behavioral data suggest that most of the adaptation-dependent changes in temporal sensitivity in humans occur at the level of the photoreceptor complex
— id: 57457, year: 1992, vol: 32, page: 2043, stat: Journal Article,

ERG FLICKER SENSITIVITY AS A FUNCTION OF RETINAL ECCENTRICITY AND ADA
SEIPLE, W; HOLOPIGIAN, K; LORENZO, M
1992 MAR 15 ;33(4):837-837, Investigative ophthalmology & visual science. IOVS
— id: 52045, year: 1992, vol: 33, page: 837, stat: Journal Article,

VEP AMPLITUDE AND PHASE-CHANGES FOLLOWING DISCRETE CONTRAST STEPS
XIN, DY; KUPERSMITH, M; HOLOPIGIAN, K; SEIPLE, W
1992 MAR 15 ;33(4):833-833, Investigative ophthalmology & visual science. IOVS
— id: 52044, year: 1992, vol: 33, page: 833, stat: Journal Article,

DOPAMINE BLOCKADE HAS NO EFFECT ON THE HUMAN FLASH ERG
CLEWNER, L; HOLOPIGIAN, K; SEIPLE, W; ANGRIST, B; KUPERSMITH, M
1991 MAR 15 ;32(4):1229-1229, Investigative ophthalmology & visual science. IOVS
— id: 51686, year: 1991, vol: 32, page: 1229, stat: Journal Article,

SEPARATION OF ON AND OFF RESPONSES IN THE HUMAN ERG
HOLOPIGIAN, K; SEIPLE, W; HAN, S; CINCIRIPINI, G; CARR, R
1991 MAR 15 ;32(4):1229-1229, Investigative ophthalmology & visual science. IOVS
— id: 51685, year: 1991, vol: 32, page: 1229, stat: Journal Article,

VEP THRESHOLD AND SUPRATHRESHOLD DEFICITS IN AMBLYOPIA
Holopigian, K; Seiple, W; Kupersmith, M
1991 Apr;6(2):109-117, Clinical vision sciences
1. Strabismic and anisometropic amblyopes typically have elevated contrast thresholds. Despite these threshold losses, previous research has shown that some amblyopic observers demonstrate normal suprathreshold contrast matching. 2. One explanation for these contrasting results is a differential impairment of independent contrast mechanisms. 3. We used a swept visual evoked potential threshold technique to electrophysiologically isolate and compare absolute and suprathreshold contrast mechanisms in a group of strabismic and anisometropic amblyopes. 4. For both groups of amblyopes, the sensitivities of the absolute and the suprathreshold mechanisms were equally elevated. 5. These results indicate that, in these amblyopes, both threshold and suprathreshold mechanisms of the VEP are impaired
— id: 32189, year: 1991, vol: 6, page: 109, stat: Journal Article,

MACULOPATHY CAUSED BY CHEMOTHERAPY
KUPERSMITH, M; SEIPLE, W; HOLOPIGIAN, K; NOBLE, K; HIESIGER, E; WARREN, F
1991 MAR 15 ;32(4):690-690, Investigative ophthalmology & visual science. IOVS
— id: 51673, year: 1991, vol: 32, page: 690, stat: Journal Article,

NONLINEARITIES IN THE FOCAL ELECTRORETINOGRAM
SEIPLE, W; HOLOPIGIAN, K
1991 JAN ;6(6):413-421, Clinical vision sciences
1. At stimulation frequencies near 10 Hz, the focal electroretinogram (FERG) is non-linear, containing significant second harmonic amplitude. 2. We performed a series of experiments directed at identifying the origin of this nonlinearity. Three hypotheses were tested: (a) The frequency doubling reflects the summed contribution of responses to stimulus onset and offset. (b) The frequency doubling reflects interactions between the responses of different cone systems. (c) The frequency doubling is due to temporally separated contributions from the rod and cone systems. 3. The results of the present experiments did not support either the first (off response) or the second hypothesis (cone difference signal). The third hypothesis received the most support
— id: 52118, year: 1991, vol: 6, page: 413, stat: Journal Article,

Electrophysiological and psychophysical flicker sensitivity in patients with primary open-angle glaucoma and ocular hypertension
Holopigian, K; Seiple, W; Mayron, C; Koty, R; Lorenzo, M
1990 Sep;31(9):1863-1868, Investigative ophthalmology & visual science. IOVS
Temporal sensitivity was assessed in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Three measures of flicker sensitivity were obtained: psychophysical modulation thresholds, visual-evoked potentials (VEPs), and focal electroretinograms (FERGs). We found elevated psychophysical thresholds at higher temporal frequencies (30-50 Hz) in patients with POAG, relative to thresholds for age-matched controls. The OHT patients had elevated psychophysical thresholds only at 50 Hz. On the other hand, VEP amplitudes in POAG patients were reduced at all temporal frequencies, with the magnitude of the loss increasing with temporal frequency. The OHT patients, however, showed no reductions in VEP amplitude at any temporal frequency. Finally, POAG patients' FERG amplitudes were reduced at 30-50 Hz; whereas FERG amplitudes in the OHT patients were normal at all temporal frequencies. These results indicate that OHT patients can exhibit psychophysical threshold losses at high temporal frequencies which are not observed in the suprathreshold electrophysiological amplitude measures. On the other hand, patients with POAG show both psychophysical and VEP losses across a range of temporal frequencies. In addition, the decreases in FERG amplitudes in POAG patients suggest changes in the functioning of the outer retina in this disease
— id: 93716, year: 1990, vol: 31, page: 1863, stat: Journal Article,

Clinical suppression and binocular rivalry suppression: the effects of stimulus strength on the depth of suppression
Holopigian, K
1989 ;29(10):1325-1333, Vision research
In observers with abnormal binocular vision (such as strabismics or anisometropes) one eye's view is often suppressed. This clinical suppression serves to eliminate binocular diplopia and confusion. Suppression may also occur in observers with normal binocular vision, when the two eyes view disparate retinal images, a phenomenon known as binocular rivalry. When the image in an eye is suppressed, it is possible to determine the amount by which that suppressed stimulus is below the visibility threshold, or the depth of suppression. In the experiments presented here, the depth of suppression in an eye was measured as the strength of the stimulus in the contralateral eye (the stimulus inducing suppression) was varied. This was done for both clinical suppressors and normal observers undergoing binocular rivalry suppression. Independent changes were made to the contrast, the luminance, and the spatial frequency of the inducing stimulus. For both clinical suppression and binocular rivalry suppression, the depth of suppression was constant, regardless of the changes to the inducing stimulus
— id: 93717, year: 1989, vol: 29, page: 1325, stat: Journal Article,

An examination of VEP response phase
Seiple W; Holopigian K
1989 Dec;73(6):520-531, Electroencephalography & clinical neurophysiology
The accuracy of phase sensitive signal detection (PSD) as applied to swept visual evoked potential retrieval depends upon phase stability. If large phase shifts occur over the course of a swept run, amplitude will be lost in any one PSD channel and threshold estimation may be inaccurate. We were able to demonstrate large latency shifts in the conventional computer averaged VEP and phase shifts in the Fourier-analyzed steady-state VEP, as a function of contrast and spatial frequency. However, the phase changes observed over the portion of a sweep where there is a visually driven response are much smaller than obtained from averaged VEPs to a series of fixed stimulus values. The difference between the observed phase shifts may be caused by a delay in phase response when stimuli are swept. This hypothesis was supported by the finding that the phase of the steady-state VEP response requires from 1 to 2 sec to stabilize following a change in contrast. Sweeping contrast or spatial frequency results in a physiologically different response than when averaged VEP responses are measured to discrete changes in stimulus parameters
— id: 10425, year: 1989, vol: 73, page: 520, stat: Journal Article,

Variability of the pattern electroretinogram
Holopigian K; Snow J; Seiple W; Siegel I
1988 Sep;70(1):103-115, Documenta ophthalmologica
Conflicting results have been obtained concerning the parametric properties of the pattern electroretinogram. These discrepancies may be due to the large amount of variability inherent in recording amplitudes. We have found the variability within a single stimulus condition to be so large (ranging from 30% to 67% of the mean value) that it could mask any underlying spatial frequency tuning. Changing the stimulus conditions failed to significantly reduce the observed variability, although changing recording conditions produced some reduction. The use of a narrower rejection band, a greater number of sweeps, and placement of the reference electrode on the ipsilateral ear (as opposed to the ipsilateral temple) combined to decrease variability of the pattern electroretinogram within a single recording session; however, intersession variability remained high. Therefore one must be careful in evaluating data from this technique, and caution is advised in its clinical use
— id: 10972, year: 1988, vol: 70, page: 103, stat: Journal Article,

Clinical suppression and amblyopia
Holopigian, K; Blake, R; Greenwald, M J
1988 Mar;29(3):444-451, Investigative ophthalmology & visual science. IOVS
In individuals with abnormal binocular vision, such as strabismics and anisometropes, it is common for all or part of one eye's view to be suppressed so binocular confusion and diplopia are eliminated. We examined the relation between the depth of suppression (the amount by which the monocular contrast increment threshold for an eye was elevated by stimulation in the contralateral eye) and the degree of amblyopia (difference in monocular contrast thresholds for the two eyes). There was a significant negative correlation between suppression and amblyopia, so that clinical suppressors with no amblyopia exhibited deep suppression (ie, large threshold elevation) while observers with amblyopia exhibited weaker or no suppression. This negative correlation was found when the two eyes viewed orthogonally oriented contours as well as identically oriented contours. These results suggest that when an eye is amblyopic there is no longer a need for strong suppression of that eye by the contralateral eye
— id: 93718, year: 1988, vol: 29, page: 444, stat: Journal Article,

Changes in the focal electroretinogram with retinal eccentricity
Seiple W; Greenstein V; Holopigian K; Carr R
1988 Sep;70(1):29-36, Documenta ophthalmologica
Flicker sensitivity increases in the peripheral retina when relatively large targets are used. This enhancement of cone system-mediated temporal sensitivity persists even when corrections are made for cortical magnification factors. It has been suggested that the differences in temporal frequency response characteristics across the retina are based on differences in receptor morphology between the peripheral and central cones. We have examined a possible retinal origin of this phenomenon by obtaining psychophysical and electroretinographic data at a variety of locations on the temporal retina. Psychophysical results show an increased sensitivity for high temporal frequency stimuli (above 30 Hz) with retinal eccentricity whether or not the stimulus size was scaled. Focal electroretinograms recorded with a constant size stimulus did not show an increase in amplitude with eccentricity. However, when an equal number of receptors were stimulated by scaling the target size, focal amplitudes were larger in the periphery. The electrophysiological findings are consistent with a possible retinal origin for this flicker enhancement phenomenon
— id: 10971, year: 1988, vol: 70, page: 29, stat: Journal Article,

Spatial-frequency discrimination in cats
Blake, R; Holopigian, K; Wilson, H R
1986 Sep;3(9):1443-1449, Journal of the Optical Society of America. Pt. A. Optics & image science
Spatial-frequency discrimination thresholds were measured in two cats by using a two-alternative forced-choice procedure. A range of standard spatial frequencies centered around the peak of the cat's contrast-sensitivity function was sampled. For comparison, discrimination thresholds were also measured in two human observers at spatial frequencies centered around the peak of the human contrast-sensitivity function. For the humans, spatial-frequency discrimination thresholds averaged 4%, while for cats discrimination thresholds averaged 50%. The relatively poorer performance of the cats cannot be entirely explained on the basis of the larger sample spacing of the feline retinal mosaic. More accurate predictions can be obtained from a model that assumes that the cat bases its discrimination performance on the level of activity within that mechanism maximally activated by the standard spatial frequency
— id: 93719, year: 1986, vol: 3, page: 1443, stat: Journal Article,

Selective losses in binocular vision in anisometropic amblyopes
Holopigian, K; Blake, R; Greenwald, M J
1986 ;26(4):621-630, Vision research
Human anisometropic amblyopes typically exhibit reduced contrast sensitivity in the amblyopic eye, especially at higher spatial frequencies. We determined whether this spatial frequency selective loss in contrast sensitivity is accompanied by selective losses in binocular function. Binocular summation (the improvement in one eye's detection performance produced by a subthreshold pattern presented to the fellow eye) was measured at several spatial frequencies. Normal observers exhibited equivalent binouclar summation at all spatial frequencies, whereas all anisometropic amblyopes exhibited normal summation at low spatial frequencies but none at high spatial frequencies. Stereoacuity (minimum resolvable disparity) was also measured as a function of spatial frequency. For normal observers, stereoacuity was best at the highest spatial frequency; for anisometropes stereoacuity was normal at low spatial frequencies, subnormal at intermediate spatial frequencies, and unmeasurable at higher spatial frequencies. Anisometropia may represent a form of selective binocular deprivation that affects neural mechanisms underlying binocular summation and stereopsis
— id: 93720, year: 1986, vol: 26, page: 621, stat: Journal Article,

Orientation selectivity in cats and humans assessed by masking
Blake, R; Holopigian, K
1985 ;25(10):1459-1467, Vision research
A two-alternative, spatial forced-choice procedure was used to measure contrast thresholds for detection of sinusoidal gratings that appeared within one-dimensional random noise. The orientation of the noise was symmetrically varied relative to the orientation of the test grating to derive estimates of orientation tuning at two spatial frequencies for both cats and humans. For cats, orientation tuning (half-width at half-strength) averaged 23 deg while for humans tuning averaged 28 deg. Both species displayed narrower tuning at the higher spatial frequency. In addition, evidence is presented that estimates of orientation tuning may be narrower when only one orientation of noise is presented, due to 'off-channel' detection strategies. These estimates of orientation tuning are discussed in terms of the orientation selectivity of cortical neurons
— id: 93722, year: 1985, vol: 25, page: 1459, stat: Journal Article,

Another visual illusion involving orientation
Blake, R; Holopigian, K; Jauch, M
1985 ;25(10):1469-1476, Vision research
The orientation of a grating may be misperceived when that grating appears superimposed within one-dimensional visual noise of a different orientation. An adjustment procedure was employed to measure the size of this tilt illusion and its dependence on noise orientation. The illusion is maximum when the noise and test differ by 20 to 40 deg, depending on the spatial frequency of the test grating. Noise composed of spatial frequencies several octaves removed from the test spatial frequency can still cause illusory tilt, although the degree of tilt under these conditions depends on test spatial frequency. This orientation illusion, like the tilt aftereffect, simultaneous tilt illusion and angle expansion illusion, may reflect inhibitory interactions between orientation selective neurons in human vision
— id: 93721, year: 1985, vol: 25, page: 1469, stat: Journal Article,

Abnormal spatial frequency channels in esotropic cats
Holopigian, K; Blake, R
1984 ;24(7):677-687, Vision research
A noise masking paradigm was used to measure spatial tuning for the deviating and nondeviating eyes of two esotropic cats and for one eye of a control cat. With increasing noise contrast, masking grew more slowly for both the deviating and the nondeviating eyes of the esotropic cats than for the control cat; apparently, contrast coding is impaired for both eyes of the esotropic cats. Masking with band-reject filtered noise indicated that detection channels for either eye of the esotropic cats were twice as broadly tuned as those for the control cat. In a subsequent experiment, the spatial tuning characteristics of two human esotropes were found to be normal, indicating a fundamental difference between human esotropia and esotropia induced in cats by the section of an eye muscle
— id: 93723, year: 1984, vol: 24, page: 677, stat: Journal Article,

Spatial vision in strabismic cats
Holopigian, K; Blake, R
1983 Jul;50(1):287-296, Journal of neurophysiology
Contrast thresholds for detection of stationary and flickering gratings were measured behaviorally for each eye of cats raised with induced convergent strabismus. The performance of the deviating eye was inferior to that of the nondeviating eye when test patterns were stationary. Flicker served to reduce the performance difference between the eyes in two cats but not in a third. These results suggest that strabismus amblyopia may not result from deficits within a single class of neurons. In all strabismic cats the contrast sensitivity of the nondeviating eye was significantly reduced relative to normal cats. These behavioral findings, including the deficits found bilaterally, correspond very well with results from cortical recordings from these and other strabismic cats presented in the preceding paper (7)
— id: 93724, year: 1983, vol: 50, page: 287, stat: Journal Article,