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Presentation: Australian Neurological Society Annual Meeting, Sydney, Australia, 31 January – 3 Feb 2010.
Corinne Carle, Andrew James, Ted Maddess.
Eccles Institute of Neuroscience, ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia;
To assess the effect of stimulus luminance and duration on pupillary responses of normal subjects using blue multifocal pupillographic objective perimetry (mfPOP).
World Glaucoma Congress 2009, Boston MA, 8-11 July 2009
T. Maddess(1), M. Kolic(1), RW Essex(2), A.C. James(1).
(1) ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia.
(2) Dept. Ophthalmology, Australian National University, Canberra, Australia.
To investigate the diagnostic power and repeatability of 8 variants of multifocal pupillographic perimetry in open angle glaucoma.
Experimental design.
Eight stimulus protocols were examined in two blocks of experiments. Block 1 contained 40 normal and 39 glaucoma subjects; block two: 41 normal and 47 glaucoma subjects. Diagnosis was confirmed by examining all subjects with HFA achromatic, and Matrix 24-2 perimetry, Stratus OCT, slit lamp and tonometry. Informed written consent was obtained from all subjects under ANU ethics approval 238/04.
Independent multifocal stimuli were presented concurrently to both eyes with a dartboard layout, having 44 independent test regions/eye extending to 30 deg eccentricity. The recording duration for 5 protocols was 4 min., divided into 8 segments of 30 s each, and for the other 3 was 6 min. divided into 9 segments of 40 s. Stimuli in each protocol could differ in the presentation rate per stimulus region (0.25, 1, presentations/s), or luminosity (150, 180, 290 or 340 cd/m²). Background luminance was 10 cd/m². Since both pupils responded to stimuli from both eyes, 88 responses/eye were obtained giving 176 contraction amplitudes and 176 delays per protocol, with SE for all 352 measures. Retest was done within 4 weeks. Visual fields were classified by HFA mean defects: moderate: 6 to 12 dB, severe: >12 dB.
The relative diagnostic power of the 8 protocols was examined using areas under receiver operator plots (AUC). The signal qualities were quantified as the median t-static across regions and subjects for peak (relative) constriction amplitude. Test-rest quality was quantified by the width of the 25th to 75th and 5th to 95th percentiles on plots of visit 1 versus visit 2 defects.
In Block 1 for severe fields the mean of the 20 regional amplitudes that most deviated from the normative data gave an AUC of 0.98 ± 0.01 (mean ± SE), and for combined moderate and severe fields 0.86 ± 0.04. The median t-stat for that protocol was 2.79 ± 0.29. That protocol had a mean presentation rate of 0.25/s and luminance of 150 cd/m2. These results were reproduced in Block 2 and a 6 min. version of the best protocol of Block 1 had a median t-stat of 3.26 ± 0.45, with a concomitant improvement in test-test variability.
This study indicates that multifocal pupil perimetry can yield acceptable diagnostic power, excellent median signal quality and test-retest variability comparable to the Matrix perimeter using a test duration equivalent to 3 min/eye. Data on efferent and afferent defects is obtained for all regions and data from blinks and fixation losses are automatically discarded. That protocol had a mean presentation rate of 0.25/region/s and luminance of 150 cd/m2. These results were reproduced in Block 2 and a 6 min. version of the best protocol of Block 1 had a median t-stat of 3.26 ± 0.45, with a concomitant improvement in test-test variability.
Program/Poster: 5282/A212
Poster Session: 513 – Visual Fields and Electrophysiology I
ARVO 2009 Annual Meeting, Ft. Lauderdale FL, 3-7 May 2009
Presentation: Thursday, May 07, 2009, 8:30 AM -10:15 AM
A.C. James, X.-L. Goh, M. Kolic, R.W. Essex, T. Maddess. Centre of Excellence in Vision Science, Australian National University, Canberra, Australia.
To investigate 4 variants of multifocal pupillographic perimetry using a prototype of the TrueField Analyser, which objectively assesses both visual fields concurrently.
We tested 35 normal and 44 glaucoma subjects. All eyes were examined with HFA achromatic, SWAP and Matrix 24-2 perimetry, Stratus OCT. Visual fields were classified by HFA mean defects: moderate: 6 to 12 dB, severe: >12 dB. Glaucoma subjects had a moderate to severe visual field in at least one eye. All subjects gave informed written consent. Multifocal stimuli of 4 min. duration, divided into 8 segments of 30s, were presented dichoptically with 24 or 44 regions/eye extending to 30o eccentricity. Individual 30s segments were only repeated if more than 15% of the data was lost due to blinks or fixation losses, both automatically monitored in real time. Mean presentation intervals (MPI) per region were 0.25, 1, or 4s. Most subjects were tested twice with each of the 4 stimuli. The background luminance was 10cd/m2 , and the maximum luminance of all stimuli was the same at 290cd/m2. The stimuli were thus not balanced for visual field sensitivity as in our more recent experiments.
44 region, 1 MPI stimuli gave the best diagnostic efficiency, providing area under ROC plots for severe fields of 0.92 ± 0.03 (mean ± SE) and for combined moderate and severe fields of 0.80 ± 0.04.
Good diagnostic accuracy for test duration of 2 min/eye was obtained from this new binocular method. The new method resolves many of the problems of subjective perimetry.
Program/Poster: 5281/A211
Poster Session: 513 – Visual Fields and Electrophysiology I
ARVO 2009 Annual Meeting, Ft. Lauderdale FL, 3-7 May 2009
Presentation: Thursday, May 07, 2009, 8:30 AM -10:15 AM
T.L. Maddess(1A), M. Kolic(1A), R.W. Essex(1B), A.C. James(1A).
(A) ARC CoE Vision Science, CVS, (B) Dept of Ophthalmology, CVS, (1) Australian National University, Canberra, Australia.
To investigate 4 variants of multifocal pupillographic perimetry in glaucoma to further explore the effects of balancing the stimulus luminances across the visual field to match the sensitivity of the pupillary field.
Following a smaller scale experiment (Kolic et al. ARVO 2009 submitted) we tested 40 normal and 39 glaucoma subjects to further explore the effects of luminance balancing. All eyes were examined with HFA achromatic, SWAP and Matrix 24-2 perimetry and Stratus OCT. Visual fields were classified by HFA mean defects: moderate: 6 to 12 dB, severe: >12 dB. Glaucoma subjects had a moderate or severe visual field in at least one eye. All subjects gave informed written consent. Multifocal stimuli having 44 test regions/eye, extending to 30 deg eccentricity, were presented concurrently to both eyes using a prototype of the TrueField Analyser. Recording duration was 4 minutes, divided into 8 segments of 30 s. Pupil diameter was monitored under infrared illumination. The 4 stimulus protocols examined differed in terms of mean presentation intervals (MPI) of 1 or 4 s per region, and balancing strategy. The balancing strategies assumed stimulus/response functions of the form R=Sz where z was 0.5 or 0.66. The peak test luminances were 150, 290 or 340 cd/m2. The backgrounds were 10 cd/m2. Almost all subjects were tested twice with the 4 stimulus variants. Diagnostic performance was assessed by areas under ROC curves (AUCs) for the N-worst response amplitudes.
For all visual field severities the best AUCs were produced by a stimulus having MPI=4 s, luminance 150 cd/m2 and z=0.5. For severe fields the mean of the 20 regional amplitudes that most deviated from the normative data gave an AUC of 0.978 ± 0.012 (mean ± SE), and for combined moderate and severe fields 0.862 ± 0.038.
Careful balancing of the stimuli to cater to differences in field sensitivity, minimized the effects of response saturation, as characterised by the exponent z, and improved the diagnostic efficiency of pupillographic multifocal perimetry. The pupillographic method eliminates several problems associated with conventional subjective perimetry.
Program/Poster: 5280/A210
Poster Session: 513 – Visual Fields and Electrophysiology I
ARVO 2009 Annual Meeting, Ft. Lauderdale FL, 3-7 May 2009
Presentation: Thursday, May 07, 2009, 8:30 AM -10:15 AM
M. Kolic(1), T. Maddess(1), R.W. Essex(2), A.C. James(1).
(1) ARC CoE in Vision Science, CVS, Australian National University, Canberra, Australia; (2) Department of Ophthalmology, Canberra Hospital, Canberra, Australia.
To investigate 4 variants of multifocal pupillographic perimetry in glaucoma to test the effects of balancing luminances across the field to match the sensitivity of the pupillary field.
We tested 21 normal and 21 glaucoma subjects. Glaucoma subjects had moderate to severe visual fields in at least one eye. All subjects were examined with HFA achromatic, SWAP and Matrix 24-2 perimetry, Stratus OCT. Visual fields were classified according to their HFA mean defects: mild <=6 dB, moderate 6 to 12 dB, severe > 12 dB. Informed written consent was obtained from all subjects. Multifocal stimuli having 44 test regions/eye, extending to 30 deg eccentricity, were presented concurrently to both eyes using a prototype of the TrueField Analyser. Recording duration was 4 minutes, divided into 8 segments of 30 s. Individual 30 s segments were repeated if more than 15% of the data was lost due to blinks of fixation losses, both automatically monitored in real time. Pupil diameter was monitored under infrared illumination. Four stimulus protocols were examined which differed in terms of mean presentation intervals (MPI) of 1 or 4 s per region. One each of the 1 and 4 MPI stimuli had their luminances balanced so that responsive field regions received less light than less responsive regions. The mean test luminances were 210 cd/m2, and the background was at 10 cd/m2. Measures of field loss included the N-worst amplitudes, response delays, or pair-wise linear combinations of those.
Diagnostic performance was assessed by areas under ROC curves (AUCs). For all visual field severities the best AUCs were produced by the balanced 1 s MPI stimulus protocol. For severe fields the mean of the 3 regional amplitudes that most deviated from the normative data gave an AUC of 1.0 ± 0.0 (mean ± SE), the corresponding AUCs for moderate and mild fields were 0.82 ± 0.11 and 0.764 ± 0.06.
In this preliminary study balancing seemed to improve diagnostic accuracy. The pupillographic method eliminates several problems associated with subjective testing as employed in conventional perimetry.
Program/Poster: 1332/A71, Poster Session: 217 – Diabetic Retinopathy I
ARVO 2009 Annual Meeting, Ft. Lauderdale FL, 3-7 May 2009
Presentation: Monday, May 04, 2009, 8:30 AM -10:15 AM
A. Bell, A.C. James, M. Kolic, T. Maddess. ARC Centre of Excellence in Vision Science, Australian National University, Canberra, Australia
We sought to derive perimetric measures from the responses of pupils to novel spatial and temporal patterns of dichoptic multifocal visual stimuli; we then investigated whether the measures could distinguish 23 subjects in the early stages of type 2 diabetes from 23 normal subjects.
We used a prototype of the TrueField Analyzer to deliver a multifocal sequence of flashed stimuli to both eyes at the same time. This device uses a stereoscopic pair of LCD displays to deliver pseudorandomly modulated arrays of light stimuli to multiple regions of each retina while pupil responses are recorded with infrared cameras. The multifocal stimuli covered 44 regions per eye and induced variations in pupil diameter which were measured across 8 segments of 30 s. The method was largely immune to the effects of blinks and fixation losses. Applying receiver operator analysis, we then examined whether the pupil responses of the diabetic patients could be reliably discriminated from those of normal subjects. We examined the n-worst constriction amplitudes, time to peak, and linear combinations of those.
Dichoptic multifocal pupillometry provided robust plots of pupil contraction versus post-stimulus time for each stimulus region. These region-by-region constrictions were reliable, giving median z-scores of 2 to 3. Responses of the normal and diabetic subjects were statistically different when region-by-region effects were considered (p<0.0005), but not when aggregated (p=0.07). The diagnostic performance (expressed as areas under ROC plots) for the 8 subjects who had been diagnosed with type 2 diabetes for at least 10 years was 0.89 ± 0.06 (mean ± SE), rising to 0.97 ± 0.03 when between-eye asymmetry was considered.
In a pilot study of 23 patients diagnosed with type 2 diabetes, dichoptic multifocal pupillography produced perimetric measures that were statistically different to those seen in 23 matched controls, especially for those who had had the disease for more than 10 years. This result, if confirmed in a wider group, suggests that the method may be clinically useful.
Program/Poster: 730/D784, Poster Session: 130 – AMD Clinical II
ARVO 2009 Annual Meeting, Ft. Lauderdale FL, 3-7 May 2009
Presentation: Sunday, May 03, 2009, 11:15 AM – 1:00 PM
F. Sabeti(1A), T.L. Maddess(1A), R.W. Essex(1B), A.C. James(1A)
(1) Australian National University, Canberra, Australia, (A) ARC Centre of Excellence in Vision Science, Centre for Visual Sciences, (B) College of Medicine, Biology and Environment, Department of Ophthalmology Canberra Hospital
To investigate the sensitivity and specificity of 4 stimulus variations of multifocal pupillographic perimetry in unilateral exudative macular degeneration (MD).
Pupillary contraction amplitudes and time to peak contraction were analysed for 29 normal (mean age 70.9 ±6.0) and 20 unilateral exudative MD (mean age 78.0 ±5.3) subjects with 4 different stimulus protocols. Stimuli were presented dichoptically and pupil responses were measured concurrently. All protocols presented multifocal stimulus arrays subtending ±15° of visual field. A dart board layout having 24 or 44 independent test regions/eye with a mean presentation interval of 1 or 4 s/region and a presentation duration of 33 ms on each presentation was employed. Luminance of the stimulus regions was 250 cd/m2 and background 10 cd/m2. Test duration was 4 minutes separated into 8 segments of 30 second recording intervals. Cameras under infrared illumination monitored pupil responses. Data during blinks and fixation losses were excluded to a maximum of 15% of responses beyond which a segment was repeated.
Stimuli presented in a 24 region layout with a 4 s/region presentation rate achieved the largest responses by a factor of 2.3 (b = 3.63 dB, t = 3.57, p <.00001); however this was not found to be most diagnostic, achieving an ROC area under the curve (AUC) of 83.31%. A linear discriminant model incorporating contraction amplitude and time to peak found the 44 region layout with 4 s/region presentation rate to be the most diagnostic achieving an AUC of 89.51%.
The clinical application of multifocal pupillography utilizing a 44 region stimulus with a slow presentation rate can produce ROC AUC of 89% in the diagnosis of unilateral exudative MD. Further investigation into the assessment of non-exudative MD through pupillography may facilitate early diagnosis and therapeutic intervention.
Poster #1099/D1042, ARVO 2008 Annual Meeting, Fort Lauderdale, 27-30 April 2008
T Maddess, AC James, CF Carle, M Kolic, XL Goh. ARC Centre of Excellence in Vision Science, Centre for Visual Sciences, Australian National University, Canberra, Australia.
To investigate 4 variants of multifocal pupillographic perimetry in glaucoma. Our previous studies have used 24 test regions per eye, here 40 regions per eye were used.
We tested 20 normal and 20 glaucoma subjects, that were tightly age and sex matched. Glaucoma patients had moderate to severe fields in at least one eye. All subjects were examined with HFA achromatic, SWAP and Matrix 24-2 perimetry, Stratus OCT, slit lamp and tonometry. Informed written consent was obtained from all subjects under ANU ethics approval 238/04. Multifocal stimuli were presented concurrently to both eyes with a dartboard layout, having 40 independent test regions/eye extending to 30 deg. Eccentricity (Fig). Four stimulus variants were examined in which stimuli were presented at 1/s, 1/4s, or 1/16s per region and either flickered at 20 Hz for 100 ms, or had a single 33 ms pulse. Recording duration was 4 minutes, divided into 8 segments of 30s. Pupil diameter was monitored by video cameras under infrared illumination. Data from fixation losses and blinks was
automatically excluded. Up to 15% data loss from blinks and fixation losses were permitted by our regressive analysis method, which produced error estimates for each region. Measures of field loss examined the N worst amplitudes, areas under the response, delays, or pairwise linear combinations of those.
Discriminant functions including response amplitude, or area, and time to peak had area under ROC curves (AUCs) of 0.89 to 0.93 for the short pulse, 1/s, stimulus. The very slow stimulus had the worst diagnostic performance. Whichever of the direct or consensual responses gave the lowest median error was used, hence only one pupil need function.
Including more test regions provided AUCs of up to 0.93. The method eliminates problems associated with false positive and negative errors, and fixation losses found in conventional perimetry, all of which effectively lower sensitivity and specificity. Having 40 regions per eye may improve the scope for detecting clusters of damage.
Poster #1100/D1043, ARVO 2008 Annual Meeting, Fort Lauderdale, 27-30 April 2008
AC James, T Maddess, M Kolic, XL Goh. ARC Centre of Excellence in Vision Science, Centre for Visual Sciences, Australian National University, Canberra, Australia.
To investigate 4 variants of multifocal pupillographic perimetry in glaucoma.
We tested 4 normal and 82 glaucoma subjects. All subjects were examined with HFA achromatic, SWAP and Matrix 24-2 perimetry, Stratus OCT, slit lamp and tonometry. Informed written consent was obtained from all subjects under ANU ethics approval 238/04. Multifocal stimuli were presented concurrently to both eyes with a dartboard layout, having 24 independent test regions/eye extending to 30 deg eccentricity. Each subject was tested with 4 stimulus sets which adopted either 2 or 4/s/region, and a flicker rate on each presentation of 15, or 30Hz. Recording duration was 4 minutes, divided into 8 segments of 30s. Pupil diameter was monitored by video cameras under infrared illumination. Data from fixation losses and blinks was automatically excluded. Up to 15% data loss from blinks, fixation losses were permitted by our regressive analysis method, which produced error estimates for each region. Measures of field loss examined the N worst amplitudes, response areas, delays or pairwise linear combinations of those.
Since some blinks and fixation losses were permitted only 1 in 45 of the 30s test segments had to be repeated. The simple N-worst region method, based upon the area of the pupillary responses and delay for the 2/s, 30Hz test, produced the best areas under ROC curves, which ranged from 67% for moderate fields to 94% for severe fields. The largest age effect was -0.10 um×s per decade (p<0.0001). Whichever of the direct or consensual responses gave the lowest error was used, hence only one pupil need function.
The results suggest that this form of objective test for glaucoma may be practical for test durations equivalent to 2 min/eye. The method eliminates problems associated with false positive and negative errors, and fixation losses found in conventional perimetry, all of which effectively lower sensitivity and specificity. Consideration of clusters of damage or between eye comparisons, and or using more regions may improve sensitivity and specificity.
Poster #098. AAO 2007 Annual Meeting, New Orleans, 10-13 November 2007
AC James, XL Goh, T Maddess. ARC Centre of Excellence in Vision Science, Centre for Visual Sciences, Australian National University, Canberra, Australia.
To investigate 10 variants of multifocal pupillographic perimetry in glaucoma.
We tested 22 normal and 23 glaucoma subjects. Multifocal stimuli of four-minute duration were presented dichoptically with 24 regions/eye extending to 30 degrees eccentricity. Stimulus sets differed in the presentation rate per region (0.25, 1, 4, presentations/sec.), stimulus duration/presentation (66, 133, or 266 ms), flicker rate on each presentation (0, 15, or 30 Hz), and peak luminosity (80, 150, and 290 cd/m2).
The brightest, four presentation/sec. stimuli, with 30Hz flicker gave sensitivities and specificities of 95.5% using response amplitude and delay.
Good accuracy for test durations of two minutes/eye could be obtained from this objective method.
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