ARVO

Online Abstract: ARVO-2011-5491/A292
ARVO 2011, Ft. Lauderdale, Florida, May 1-5, 2011

Authors

Corinne F. Carle¹, Andrew C. James¹, Maria Kolic¹, Rohan W. Essex², Ted L. Maddess^1
1 ARC Centre of Excellence in Vis. Science, Australian National University, Canberra, Australia
² Dept of Ophthalmology, The Canberra Hospital, Canberra, Australia

Purpose

This study investigated the utility of multifocal Pupillographic Objective Perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. These cells comprise the afferent arm of the subcortical pupillary pathway and exhibit differing dynamics dependent on the initiator of their response. The diagnostic potential for glaucoma is compared between protocols that favored either excitatory cone input to these cells or their intrinsic melanopsin response.

Methods

19 glaucoma and 24 normal subjects were tested using mfPOP stimulus protocols with either 33 ms yellow or 750 ms blue stimuli, Subjects’ color sensitivity was assessed using the Farnsworth 100-Hue Test (F100). Pupillary responses were recorded and multivariate linear regression used to quantify results. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis.

Results

Pupillary responses to the slow blue stimuli were highly suggestive of melanopsin involvement. F100 error scores increased significantly with age and were higher in glaucoma. The predominant errors in both groups were Type III blue/yellow anomalies. The mean reduction in patients’ pupillary response amplitudes to blue stimuli (-0.57dB (t(7490) = -7.2, p=8.4×10^-13) was substantially less than that of yellow (-1.25dB (t(6749) = -10.9, p=1.6×10^-27). ROC analysis revealed similar diagnostic accuracy: area under the curve, Blue: 100% for eyes classified as severe, 79.4% for moderate, Yellow: 100% for severe, 78.8% for moderate. The yellow protocol demonstrated much greater sensitivity to localized visual field damage, diagnostic power for the blue protocol however, was largely reliant on measures equivalent to the mean defect.

Conclusion

The blue protocol did not proffer any diagnostic advantage over the yellow protocol and appeared prone to confounding factors related to aging and the disease process.

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Online Abstract: ARVO-2011-3890/D1122
ARVO 2011, Ft. Lauderdale, Florida, May 1-5, 2011

Authors

Faran Sabeti¹, Ted Maddess¹, Rohan W. Essex², Andrew James^1
1 Vision Science, Australian National University, Canberra, Australia
² Ophthalmology, Canberra Hospital, Canberra, Australia.

Purpose

To investigate the efficacy of intravitreal ranibizumab injection for choroidal neovascularization (CNV) secondary to exudative Age-related Macular Degeneration (AMD) by evaluation of multifocal pupillographic objective perimetry (mfPOP).

Methods

Pupil responses from 20 exudative AMD patients treated unilaterally with intravitreal ranibizumab were recorded before treatment and after 3 months treatment and compared with 30 normal subjects. Two multifocal stimulus ensembles consisting of 44 or 24 independent stimulus regions per eye with a mean presentation interval at each region of 1 second was presented dichoptically. Pupil responses were recorded with video cameras under infrared illumination. The stimulus layout extended from fixation to 15° eccentricity and presented stimuli at a luminance of 250 cd/m² and a background of 10 cd/m². A multivariate linear model was fitted to contraction amplitudes and time to peak responses to determine the independent effects of exudative AMD at pre and post-treatment.

Results

Mean additional response delays for the 24 region stimulus improved significantly from a mean delay of 18.82 ± 3.0 ms (P < 0.0001) at baseline to 6.47 ± 3.13 ms (P < 0.05) after 3 months treatment. The mean effect of exudative AMD at baseline decreased constriction amplitudes by 1.3 times (-1.00 ± 0.23 µm, P < 0.0001). After 3 months of treatment exudative AMD produced smaller responses than normals by a multiplicative loss of 1.15 times (-0.63 ± 0.17 µm, P < 0.0005). Diagnostic performance was greater at baseline achieving an ROC area under the curve (AUC) of 100% ± 0.0 (mean ± SE) than at post-treatment (96.1% ± 3.8%).

Conclusion

This study demonstrates the ability of mfPOP to detect functional improvements in eyes treated with intravitreal ranibizumab for exudative AMD and may assist in detecting progression or monitoring the effect of treatment. The 44 region stimulus ensemble demonstrated greater sensitivity for the diagnosis of exudative AMD at baseline than at post-treatment examination.

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Online Abstract: ARVO-2011-3890/D1122

Online Abstract: ARVO2001-267-D647
ARVO 2011, Ft. Lauderdale, Florida, May 1-5, 2011

Authors

Ted Maddess¹, Christian J. Lueck^1,2, Cristian Voicu¹, Andrew C. James^1
1 ARC CoE Vision Science, CVS, Australian National University, Canberra, Australia;
² Neurology, The Canberra Hospital, Canberra, Australia.

Purpose

To examine the diagnostic power of a multifocal pupillographic perimeter, the TrueField Analyzer (TFA), in multiple sclerosis (MS) patients who had different histories of acute neuritis.

Methods

35 normal (47.9 ± 16.8 yr, 22 women) and 85 MS subjects (49.8 ± 11.3 yr, 62 women) were enrolled; including 2 primary and 11 secondary progressives (PS), the remainder relapsing remitting (RR). EDSS scores for RR patients were 3.53 ± 1.04 (mean ± SD), and 5.90 ± 1.43 for PS. The TFA stimuli tested 44 regions/eye within the central 60 deg. The dichoptic sparse stimuli were delivered at a mean rate of 1/s/visual field region and each persisted for 33 ms on each presentation. Stimulus duration was 4 min divided into 8 intervals of 30 s.

Results

ROC plots revealed that the percent area under ROC plots (%AUC) for the 144 RR eyes was 75.0 ± 3.31 (mean ± SE) and for the 26 PS eyes 94.8 ± 3.55 (mean EDSS 5.90 ± 1.43). %AUC for RRMS with EDSS >= 5 (5.29 ± 0.57) was 91.4 ± 8.1. For RR patients that had or had not experienced ON %AUC was 75.7 ± 4.48 and 75.4 ± 3.84 respectively.

Conclusion

Neither ON, nor a history of RR attacks had a significant effect on diagnostic power: and both RR and PS patients had %AUC consistent with EDSS scores. Take together these results suggested that the results were more dependent on “secondary” degeneration than inflammation history. Since both visual fields were examined concurrently separate direct and consensual fields are obtained for both eyes in 2 min/eye. This can permit afferent and efferent defects to be discriminated.

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Presentation: 1822/D674
ARVO 2010 Annual Meeting, Ft. Lauderdale FL, 2-6 May 2010

Presentation: Monday, May 03, 2010, 1:45 PM – 3:30 PM

Authors

Y. Rosli^1,2, T.L. Maddess¹, Y. Ho¹, C. Carle¹, M. Kolic¹, A.C. James¹.
¹ ARC Centre of Excellence in Vision Science & Centre for Visual Science, Australian National University, Canberra, Australia;
² Department of Biomedical Science, FSKB, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Purpose

Multifocal pupillography perimetry has recently been developed and refined for visual field assessment of glaucoma. This study explored for the first time the possible presence of attention-related changes to the amplitudes of pupillary constriction.

Methods

Two experiments were carried out: the second to verify the findings of the first. In both experiments both white and yellow stimuli were examined. In Experiment 1 (19 subjects) the stimuli had a maximum luminance of 288cd/m2. Other experiments showed that those stimuli might drive the pupillary responses into a saturating range so in Experiment 2 (22 subjects) the stimuli had maximum luminance of 150 cd/m2 stimuli. In the attention task noted changes in the shape of the fixation target pressing a button whenever a change occurred. In all experiments the multifocal array contained 44 stimulus regions extending to 30 deg eccentricity; the stimulus elements were presented for 33 ms at a mean rate of 44/s/eye. Each protocol was divided into eight segments of 30s.

Results

Attention reduced the amplitude of the transient pupil responses to white stimuli (Exp 1: -1.58dB, p=0.0001; Exp 2: -0.20dB p=0.021) but increased responses to yellow stimuli (Exp 1: 1.15dB, p=0.006; Exp 2: 1.71dB p=0.054). A naso-temporal bias was possibly shown in Exp 2, in which at the ( p<=0.1) level 6 nasal regions, as opposed to one temporal region, had their responses suppressed during attention protocols using white stimuli.

Conclusion

Pupillary responses were found to be significantly influenced by attention, albeit equivocally, as contrasting reactions were obtained in response to white and coloured stimuli. The result was verified in the second experiment.

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Program/Poster: 5513/A568
ARVO 2010 Annual Meeting, Ft. Lauderdale FL, 2-6 May 2010

Presentation: Thursday, May 06, 2010, 8:30 AM -10:15 AM

Authors

Maria Kolic¹, Ted Maddess¹, Rohan Essex², Andrew C James¹.
¹ ARC Centre of Excellence in Vision Science & Centre for Visual Science, Australian National University, Canberra, Australia;
² Department of Ophthalmology, Canberra Hospital & Australian National University, Canberra, Australia.

Purpose

To investigate the effect of intra ocular lens implants (IOLs) on the diagnostic performance of 4 variants of multifocal Pupil Objective Perimetry (mfPOP) in glaucoma.

Methods

We tested 77 normal subjects (age 62.7 ± 8.9SD), including 34 IOL eyes. The glaucoma group consisted of 87 subjects (age 67.9 ± 9.8SD), with 40 IOL eyes. Glaucoma subjects had moderate to severe visual fields in at least one eye. 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 24 test regions/eye, extending to 30 deg eccentricity, were presented concurrently to both eyes using a prototype of the TrueField Analyzer. Recording duration was 4 minutes, divided into 8 segments of 30 s. Segments were repeated if more than 15% of the data was lost due to blinks or fixation losses, monitored in real time under infrared illumination. Four stimulus protocols were examined which differed in mean presentation rate (4/s or 2/s) and flicker rate (15Hz or 30Hz). Peak stimulus luminance of 290 cd/m2 and background of 10 cd/m2 were used. The measure of diagnostic performance was area under the curve (AUC) of receiver operator characteristics (ROC) plots and the method used to determine the effect of IOLs on pupil responses for both groups was multiple regression analysis.

Results

The best diagnosticity was achieved with the 4/s and 15 Hz protocol, with 94.98% AUC in subjects with IOLs and 94.48% AUC in subjects without IOLs. As might be expected changes to response amplitudes although significant were small. The diagnostically best protocol produced the largest effect of IOLs on pupil constriction: a response reduction of -0.33 dB, tstat = 7.27, p = 3.66e-13.

Conclusion

This study of 328 eyes demonstrates that IOLs have only a small effect on pupillary responses and diagnostic performance in glaucoma subjects and that this can be compensated for by a small bias term on the normative data of about 0.3 dB.

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Program/Poster: 2794/D832
ARVO 2010 Annual Meeting, Ft. Lauderdale FL, 2-6 May 2010

Presentation: Tuesday, May 04, 2010, 8:30 AM -10:15 AM

Authors

Faran Sabeti, Ted Maddess, Andrew James. ARC Centre of Excellence in Vision Science, and Centre for Visual Science, Australian National University, Canberra, Australia.

Purpose

To explore the use of multifocal pupillography in detecting functional changes associated with early age-related macular degeneration (AMD).

Methods

Pupillary contraction amplitudes and time to peak contractions of 19 early AMD eyes (mean age 69.6 ± 4.3) showing retinal drusen or irregular fundus pigmentation with mildly decreased visual acuity were examined and compared with 28 normal (mean age 68.5 ± 7.9) subjects with 3 different stimulus protocols. Stimuli were presented dichoptically and both pupil responses were measured concurrently. All protocols presented multifocal stimulus arrays subtending ±15° of visual field. A dart board layout having 44 independent test regions/eye with a mean presentation interval of 4 s/region and a duration of 33 ms on each presentation was employed. One protocol with peak test luminance of 288 cd/m2 employed a luminance balancing strategy designed to make responses more even across the visual field [ARVO (2009) E-Abstract 5281]. The non-balanced protocols had peak test luminance’s of 210 cd/m2 and 288 cd/m2 with a 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.

Results

Unbalanced stimuli with a peak luminance of 210 cd/m2 achieved the largest decrease in mean response amplitude of -2.22 dB (t = 14.82, p <.00001); however this was found to be the least diagnostic. Balanced stimuli produced the largest delay in time to peak of 61.9 ms (t = 14.87, p <.00001). A linear discriminant model incorporating contraction amplitude and time to peak found the balanced protocol to be the most diagnostic achieving an AUC of 94.05%.

Conclusion

Clinical signs of early AMD produced significant abnormality in amplitude and latency of pupillary responses. Balancing stimuli to reduce the effects of response saturation produced ROC AUC of 94%, suggesting that multifocal pupillography is a sensitive tool in detecting early macular abnormalities in AMD.

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