Vivienne Greenstein - Academia.edu (original) (raw)

Papers by Vivienne Greenstein

Research paper thumbnail of Repeat Reliability of the Multifocal Visual Evoked Potential in Normal and Glaucomatous Eyes

Journal of Glaucoma, 2003

To investigate the repeat reliability of the multifocal visual evoked potential (mfVEP). Fifteen ... more To investigate the repeat reliability of the multifocal visual evoked potential (mfVEP). Fifteen subjects with no known abnormalities of the visual system and 10 patients with glaucoma participated in the study. Monocular mfVEPs were recorded on two separate days, using a 60-sector, pattern-reversal dart board array. Within a single session, two 7-minute. recordings were obtained for each eye. The amplitude of each mfVEP response was obtained using a root mean square measure (RMS). An mfVEP ratio [10*log (RMS day 1 / RMS day 2)] provided a measure of the reproducibility of an individual response. The same calculations were performed for Run 1 compared with Run 2 within a day and Run 1 (Run 2) compared with Run 1 (Run 2) across days. For all 1800 mfVEP responses (60 sectors x 15 subjects x 2 eyes), the correlation between the amplitude on day 2 and the amplitude on day 1 was good (r = 0.85). The mean standard deviation (SD) of the 60 mfVEP ratios for the individual subjects was 1.63 dB for the 14-minute records (the combination of the two 7-minute recordings). On average for the 7-minute records, the mean SD across days was 1.77 dB while the mean SD within a day was 1.53 dB. The correlation within a day (r = 0.87) also was slightly larger than across days (r = 0.80). The mean SD decreased as the RMS amplitude increased. The patients' mean SD was 1.75 dB with r equal to 0.82. The repeat reliability of the mfVEP was good (approximately 1.6dB); in fact, it was better than that typically obtained with static automated perimetry (approximately 2.7dB). Repeat testing on separate days added surprisingly little to the variability seen with repeat testing within the same session.

Research paper thumbnail of The Enhanced S Cone Syndrome: An Analysis of Receptoral and Post-receptoral Changes

Vision Research, 1996

The purpose of the study was to test the hypothesis that the retinae of patients with enhanced S ... more The purpose of the study was to test the hypothesis that the retinae of patients with enhanced S cone syndrome (ESCS) have more S cones than the normal retina and these cones have replaced some of the L and M cones. Standard and spectral full-field electroretinograms, measurements of L, M, and S cone system sensitivities and S cone acuity were

Research paper thumbnail of The Pattern Electroretinogram in Glaucoma Patients with Confirmed Visual Field Deficits

PURPOSE. To better understand the relationship between the amplitude of the pattern electroretino... more PURPOSE. To better understand the relationship between the amplitude of the pattern electroretinogram (PERG) and visual loss, measured with static automated perimetry. METHODS. Transient PERGs were recorded in 15 patients (31-77 years) and 16 normal individuals (26 - 65 years). An eye was considered to have glaucomatous damage only if there was an abnormal disc, an abnormal 24-2 Humphrey visual

Research paper thumbnail of Test of the Decreased Responsiveness Hypothesis in Retinitis Pigmentosa

Optometry and Vision Science, 1986

Retinitis pigmentosa (RP) frequently leads to a decrease in cone system sensitivity. A number of ... more Retinitis pigmentosa (RP) frequently leads to a decrease in cone system sensitivity. A number of alternative explanations have been proposed for this decrease. Based on the results of a psychophysical technique, the probe-flash paradigm, the authors suggest that a decrease in responsiveness of retinal elements can account for much of this loss. In this paper the decreased responsiveness hypothesis is tested by obtaining data at two levels of steady adaptation. The results of the study indicate that sensitivity loss is greater for the dark adapted than the light adapted state. The data rule out the decreased responsiveness hypothesis coupled with a simple model of adaptation. More complicated adaptation models cannot be excluded. The importance of considering models of adaptation when testing models of disease-related sensitivity loss is underscored.

Research paper thumbnail of Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage

British Journal of Ophthalmology, 2007

confirmed glaucomatous damage coherence tomography accurately detects Retinal nerve fibre thickne... more confirmed glaucomatous damage coherence tomography accurately detects Retinal nerve fibre thickness measured with optical http://bjo.bmj.com/cgi/content/full/91/7/905

Research paper thumbnail of Near-infrared autofluorescence: its relationship to short-wavelength autofluorescence and optical coherence tomography in recessive stargardt disease

Investigative ophthalmology & visual science, 2015

We compared hypoautofluorescent (hypoAF) areas detected with near-infrared (NIR-AF) and short-wav... more We compared hypoautofluorescent (hypoAF) areas detected with near-infrared (NIR-AF) and short-wavelength autofluorescence (SW-AF) in patients with recessive Stargardt disease (STGD1) to retinal structure using spectral domain optical coherence tomography (SD-OCT). The SD-OCT volume scans, and SW-AF and NIR-AF images were obtained from 15 eyes of 15 patients with STGD1 and registered to each other. Thickness maps of the total retina, receptor-plus layer (R+, from distal border of the RPE to outer plexiform/inner nuclear layer boundary), and outer segment-plus layer (OS+, from distal border of the RPE to ellipsoid zone [EZ] band) were created from SD-OCT scans. These were compared qualitatively and quantitatively to the hypoAF areas in SW-AF and NIR-AF images. All eyes showed a hypoAF area in the central macula and loss of the EZ band in SD-OCT scans. The hypoAF area was larger in NIR than SW-AF images and it exceeded the area of EZ band loss for 12 eyes. The thickness maps showed pro...

Research paper thumbnail of Local cone and rod system function in progressive cone dystrophy

Investigative ophthalmology & visual science, 2002

To compare the patterns of local cone and rod system impairment in patients with progressive cone... more To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques. 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. 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 limit...

Research paper thumbnail of Local cone and rod system function in patients with retinitis pigmentosa

Investigative ophthalmology & visual science, 2001

To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using el... more To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using electrophysiological and psychophysical techniques. 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. 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 measur...

Research paper thumbnail of Retinal function in diabetic macular edema after focal laser photocoagulation

Investigative ophthalmology & visual science, 2000

To assess the effects of focal photocoagulation on retinal function in the macular and perimacula... more 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. 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. 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 increase...

Research paper thumbnail of Evidence for photoreceptor changes in patients with diabetic retinopathy

Investigative ophthalmology & visual science, 1997

To determine whether the rod and cone photoreceptors are affected in patients with diabetic retin... more To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy. 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. Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. An...

Research paper thumbnail of Relative effects of aging and age-related macular degeneration on peripheral visual function

Optometry and vision science : official publication of the American Academy of Optometry, 1997

The purpose of this study was to determine the extent of peripheral visual deficits in patients w... more 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 accou...

Research paper thumbnail of Sites of cone system sensitivity loss in retinitis pigmentosa

Investigative ophthalmology & visual science, 1993

To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing ... more To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing focal electroretinographic and psychophysical modulation thresholds. Both psychophysical and electrophysiologic increment threshold curves were obtained in retinitis pigmentosa patients and a group of age-matched, normally-sighted adults. 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. 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.

Research paper thumbnail of The effects of random element loss on letter identification: implications for visual acuity loss in patients with retinitis pigmentosa

Vision research, 1995

The hypothesis that reductions in Snellen acuities in patients with retinitis pigmentosa are due ... more 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 psychophys...

Research paper thumbnail of Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique

Vision Research, 1998

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and... more 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 e~ght 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. Ncarly 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. © 1997 Elsevier Science Ltd

Research paper thumbnail of New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11

Human molecular genetics, 2014

Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both ... more Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes and loci remain to be identified. We investigated three siblings, born to asymptomatic parents of Italian-American descent, who each presented with atypical RP with systemic features, including facial dysmorphologies, psychomotor developmental delays recognized since early childhood, learning disabilities and short stature. RP-associated ophthalmological findings included salt-and-pepper retinopathy, attenuation of the arterioles and generalized rod-cone dysfunction as determined by almost extinguished electroretinogram in 2 of 3 siblings. Atypical for RP features included mottled macula at an early age and peripapillary sparing of the retinal pigment epithelium. Whole-e...

Research paper thumbnail of Correlations among near-infrared and short-wavelength autofluorescence and spectral-domain optical coherence tomography in recessive Stargardt disease

Investigative ophthalmology & visual science, 2014

Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in ... more Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of E...

Research paper thumbnail of Functional Analysis of Retinal Flecks in Stargardt Disease

Journal of clinical & experimental ophthalmology, Jan 30, 2012

To evaluate visual function of flecked areas in a series of patients with Stargardt disease (STGD... more To evaluate visual function of flecked areas in a series of patients with Stargardt disease (STGD) and compare them with adjacent non flecked areas. Twenty-seven patients with STGD, ABCA4 mutations and yellowish retinal flecks at fundus examination were recruited. Microperimetry with the Nidek MP-1 and fundus autofluorescence imaging (FAF) were performed in all the patients (27 eyes) while spectral-domain optical coherence tomography (SD-OCT) was performed in a subgroup of patients (20 eyes). Visual sensitivity (in dB) for each hyperfluorescent flecked area on FAF was compared with the value of the nearest adjacent non-flecked area in the MP-1 grid and at approximately the same distance from the fovea. Retinal structure in some of the flecked areas tested by microperimetry was analysed with SD-OCT. All patients were screened for mutations in the ABCA4 gene by APEX array and direct sequencing. A total of 1836 locations (68 locations for each eye with the 10-2 program) were tested wit...

Research paper thumbnail of STRUCTURAL ASSESSMENT OF HYPERAUTOFLUORESCENT RING IN PATIENTS WITH RETINITIS PIGMENTOSA

Retina, 2009

Purpose-To analyze the retinal structure underlying the hyperautofluorescent ring visible on fund... more Purpose-To analyze the retinal structure underlying the hyperautofluorescent ring visible on fundus autofluorescence in patients with retinitis pigmentosa.

Research paper thumbnail of A comparison of the components of the multifocal and full-field ERGs

Visual Neuroscience, 1997

The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs. The purpose here ... more 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.

Research paper thumbnail of Identifying inner retinal contributions to the human multifocal ERG

Vision Research, 1999

Contributions to the multifocal electroretinogram (ERG) from the inner retina (i.e. ganglion and ... more 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.

Research paper thumbnail of Repeat Reliability of the Multifocal Visual Evoked Potential in Normal and Glaucomatous Eyes

Journal of Glaucoma, 2003

To investigate the repeat reliability of the multifocal visual evoked potential (mfVEP). Fifteen ... more To investigate the repeat reliability of the multifocal visual evoked potential (mfVEP). Fifteen subjects with no known abnormalities of the visual system and 10 patients with glaucoma participated in the study. Monocular mfVEPs were recorded on two separate days, using a 60-sector, pattern-reversal dart board array. Within a single session, two 7-minute. recordings were obtained for each eye. The amplitude of each mfVEP response was obtained using a root mean square measure (RMS). An mfVEP ratio [10*log (RMS day 1 / RMS day 2)] provided a measure of the reproducibility of an individual response. The same calculations were performed for Run 1 compared with Run 2 within a day and Run 1 (Run 2) compared with Run 1 (Run 2) across days. For all 1800 mfVEP responses (60 sectors x 15 subjects x 2 eyes), the correlation between the amplitude on day 2 and the amplitude on day 1 was good (r = 0.85). The mean standard deviation (SD) of the 60 mfVEP ratios for the individual subjects was 1.63 dB for the 14-minute records (the combination of the two 7-minute recordings). On average for the 7-minute records, the mean SD across days was 1.77 dB while the mean SD within a day was 1.53 dB. The correlation within a day (r = 0.87) also was slightly larger than across days (r = 0.80). The mean SD decreased as the RMS amplitude increased. The patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; mean SD was 1.75 dB with r equal to 0.82. The repeat reliability of the mfVEP was good (approximately 1.6dB); in fact, it was better than that typically obtained with static automated perimetry (approximately 2.7dB). Repeat testing on separate days added surprisingly little to the variability seen with repeat testing within the same session.

Research paper thumbnail of The Enhanced S Cone Syndrome: An Analysis of Receptoral and Post-receptoral Changes

Vision Research, 1996

The purpose of the study was to test the hypothesis that the retinae of patients with enhanced S ... more The purpose of the study was to test the hypothesis that the retinae of patients with enhanced S cone syndrome (ESCS) have more S cones than the normal retina and these cones have replaced some of the L and M cones. Standard and spectral full-field electroretinograms, measurements of L, M, and S cone system sensitivities and S cone acuity were

Research paper thumbnail of The Pattern Electroretinogram in Glaucoma Patients with Confirmed Visual Field Deficits

PURPOSE. To better understand the relationship between the amplitude of the pattern electroretino... more PURPOSE. To better understand the relationship between the amplitude of the pattern electroretinogram (PERG) and visual loss, measured with static automated perimetry. METHODS. Transient PERGs were recorded in 15 patients (31-77 years) and 16 normal individuals (26 - 65 years). An eye was considered to have glaucomatous damage only if there was an abnormal disc, an abnormal 24-2 Humphrey visual

Research paper thumbnail of Test of the Decreased Responsiveness Hypothesis in Retinitis Pigmentosa

Optometry and Vision Science, 1986

Retinitis pigmentosa (RP) frequently leads to a decrease in cone system sensitivity. A number of ... more Retinitis pigmentosa (RP) frequently leads to a decrease in cone system sensitivity. A number of alternative explanations have been proposed for this decrease. Based on the results of a psychophysical technique, the probe-flash paradigm, the authors suggest that a decrease in responsiveness of retinal elements can account for much of this loss. In this paper the decreased responsiveness hypothesis is tested by obtaining data at two levels of steady adaptation. The results of the study indicate that sensitivity loss is greater for the dark adapted than the light adapted state. The data rule out the decreased responsiveness hypothesis coupled with a simple model of adaptation. More complicated adaptation models cannot be excluded. The importance of considering models of adaptation when testing models of disease-related sensitivity loss is underscored.

Research paper thumbnail of Retinal nerve fibre thickness measured with optical coherence tomography accurately detects confirmed glaucomatous damage

British Journal of Ophthalmology, 2007

confirmed glaucomatous damage coherence tomography accurately detects Retinal nerve fibre thickne... more confirmed glaucomatous damage coherence tomography accurately detects Retinal nerve fibre thickness measured with optical http://bjo.bmj.com/cgi/content/full/91/7/905

Research paper thumbnail of Near-infrared autofluorescence: its relationship to short-wavelength autofluorescence and optical coherence tomography in recessive stargardt disease

Investigative ophthalmology & visual science, 2015

We compared hypoautofluorescent (hypoAF) areas detected with near-infrared (NIR-AF) and short-wav... more We compared hypoautofluorescent (hypoAF) areas detected with near-infrared (NIR-AF) and short-wavelength autofluorescence (SW-AF) in patients with recessive Stargardt disease (STGD1) to retinal structure using spectral domain optical coherence tomography (SD-OCT). The SD-OCT volume scans, and SW-AF and NIR-AF images were obtained from 15 eyes of 15 patients with STGD1 and registered to each other. Thickness maps of the total retina, receptor-plus layer (R+, from distal border of the RPE to outer plexiform/inner nuclear layer boundary), and outer segment-plus layer (OS+, from distal border of the RPE to ellipsoid zone [EZ] band) were created from SD-OCT scans. These were compared qualitatively and quantitatively to the hypoAF areas in SW-AF and NIR-AF images. All eyes showed a hypoAF area in the central macula and loss of the EZ band in SD-OCT scans. The hypoAF area was larger in NIR than SW-AF images and it exceeded the area of EZ band loss for 12 eyes. The thickness maps showed pro...

Research paper thumbnail of Local cone and rod system function in progressive cone dystrophy

Investigative ophthalmology & visual science, 2002

To compare the patterns of local cone and rod system impairment in patients with progressive cone... more To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques. 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. 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 limit...

Research paper thumbnail of Local cone and rod system function in patients with retinitis pigmentosa

Investigative ophthalmology & visual science, 2001

To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using el... more To compare local cone and rod system function in patients with retinitis pigmentosa (RP) using electrophysiological and psychophysical techniques. 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. 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 measur...

Research paper thumbnail of Retinal function in diabetic macular edema after focal laser photocoagulation

Investigative ophthalmology & visual science, 2000

To assess the effects of focal photocoagulation on retinal function in the macular and perimacula... more 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. 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. 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 increase...

Research paper thumbnail of Evidence for photoreceptor changes in patients with diabetic retinopathy

Investigative ophthalmology & visual science, 1997

To determine whether the rod and cone photoreceptors are affected in patients with diabetic retin... more To determine whether the rod and cone photoreceptors are affected in patients with diabetic retinopathy. 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. Psychophysically measured dark-adapted thresholds were elevated primarily at eccentricities of 5 degrees and 10 degrees from the fovea. An...

Research paper thumbnail of Relative effects of aging and age-related macular degeneration on peripheral visual function

Optometry and vision science : official publication of the American Academy of Optometry, 1997

The purpose of this study was to determine the extent of peripheral visual deficits in patients w... more 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 accou...

Research paper thumbnail of Sites of cone system sensitivity loss in retinitis pigmentosa

Investigative ophthalmology & visual science, 1993

To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing ... more To examine the sites of cone sensitivity loss in patients with retinitis pigmentosa by comparing focal electroretinographic and psychophysical modulation thresholds. Both psychophysical and electrophysiologic increment threshold curves were obtained in retinitis pigmentosa patients and a group of age-matched, normally-sighted adults. 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. 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.

Research paper thumbnail of The effects of random element loss on letter identification: implications for visual acuity loss in patients with retinitis pigmentosa

Vision research, 1995

The hypothesis that reductions in Snellen acuities in patients with retinitis pigmentosa are due ... more 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 psychophys...

Research paper thumbnail of Assessment of local retinal function in patients with retinitis pigmentosa using the multi-focal ERG technique

Vision Research, 1998

To assess local retinal function in patients with retinitis pigmentosa (RP), multi-focal ERGs and... more 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 e~ght 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. Ncarly 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. © 1997 Elsevier Science Ltd

Research paper thumbnail of New syndrome with retinitis pigmentosa is caused by nonsense mutations in retinol dehydrogenase RDH11

Human molecular genetics, 2014

Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both ... more Retinitis pigmentosa (RP), a genetically heterogeneous group of retinopathies that occur in both non-syndromic and syndromic forms, is caused by mutations in ∼100 genes. Although recent advances in next-generation sequencing have aided in the discovery of novel RP genes, a number of the underlying contributing genes and loci remain to be identified. We investigated three siblings, born to asymptomatic parents of Italian-American descent, who each presented with atypical RP with systemic features, including facial dysmorphologies, psychomotor developmental delays recognized since early childhood, learning disabilities and short stature. RP-associated ophthalmological findings included salt-and-pepper retinopathy, attenuation of the arterioles and generalized rod-cone dysfunction as determined by almost extinguished electroretinogram in 2 of 3 siblings. Atypical for RP features included mottled macula at an early age and peripapillary sparing of the retinal pigment epithelium. Whole-e...

Research paper thumbnail of Correlations among near-infrared and short-wavelength autofluorescence and spectral-domain optical coherence tomography in recessive Stargardt disease

Investigative ophthalmology & visual science, 2014

Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in ... more Short-wavelength (SW) fundus autofluorescence (AF) is considered to originate from lipofuscin in retinal pigment epithelium (RPE) and near-infrared (NIR) AF from melanin. In patients with recessive Stargardt disease (STGD1), we correlated SW-AF and NIR-AF with structural information obtained by spectral-domain optical coherence tomography (SD-OCT). Twenty-four STGD1 patients (45 eyes; age 8 to 61 years) carrying confirmed disease-associated ABCA4 mutations were studied prospectively. Short-wavelength AF, NIR-AF, and SD-OCT images were acquired. Five phenotypes were identified according to features of the central lesion and extent of fundus change. Central zones of reduced NIR-AF were typically larger than areas of diminished SW-AF and reduced NIR-AF usually approximated areas of ellipsoid zone (EZ) loss identified by SD-OCT (group 1; r, 0.93, P < 0.0001). In patients having a central lesion with overlapping parafoveal rings of increased NIR-AF and SW-AF (group 3), the extent of E...

Research paper thumbnail of Functional Analysis of Retinal Flecks in Stargardt Disease

Journal of clinical & experimental ophthalmology, Jan 30, 2012

To evaluate visual function of flecked areas in a series of patients with Stargardt disease (STGD... more To evaluate visual function of flecked areas in a series of patients with Stargardt disease (STGD) and compare them with adjacent non flecked areas. Twenty-seven patients with STGD, ABCA4 mutations and yellowish retinal flecks at fundus examination were recruited. Microperimetry with the Nidek MP-1 and fundus autofluorescence imaging (FAF) were performed in all the patients (27 eyes) while spectral-domain optical coherence tomography (SD-OCT) was performed in a subgroup of patients (20 eyes). Visual sensitivity (in dB) for each hyperfluorescent flecked area on FAF was compared with the value of the nearest adjacent non-flecked area in the MP-1 grid and at approximately the same distance from the fovea. Retinal structure in some of the flecked areas tested by microperimetry was analysed with SD-OCT. All patients were screened for mutations in the ABCA4 gene by APEX array and direct sequencing. A total of 1836 locations (68 locations for each eye with the 10-2 program) were tested wit...

Research paper thumbnail of STRUCTURAL ASSESSMENT OF HYPERAUTOFLUORESCENT RING IN PATIENTS WITH RETINITIS PIGMENTOSA

Retina, 2009

Purpose-To analyze the retinal structure underlying the hyperautofluorescent ring visible on fund... more Purpose-To analyze the retinal structure underlying the hyperautofluorescent ring visible on fundus autofluorescence in patients with retinitis pigmentosa.

Research paper thumbnail of A comparison of the components of the multifocal and full-field ERGs

Visual Neuroscience, 1997

The multi-input technique of Sutter and Tran (1992) yields multiple focal ERGs. The purpose here ... more 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.

Research paper thumbnail of Identifying inner retinal contributions to the human multifocal ERG

Vision Research, 1999

Contributions to the multifocal electroretinogram (ERG) from the inner retina (i.e. ganglion and ... more 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.