Multifocal pupillography identifies retinal dysfunction in early age-related macular degeneration

ARC Centre of Excellence in Vision Science, John Curtin School of Medical Research, Australian National University, Building 131, Garran Road, Acton, Canberra, ACT, 0200, Australia, .
Albrecht von Graæes Archiv für Ophthalmologie (Impact Factor: 1.91). 02/2013; 251(7). DOI: 10.1007/s00417-013-2273-z
Source: PubMed


Early age-related macular degeneration (AMD) is common among the elderly. While only a small number progress to sight-threatening stages of AMD, identifying prognostic functional markers remains paramount. Here, we objectively evaluate retinal function in patients with large drusen by multifocal pupillographic objective perimetry (mfPOP). Different temporal presentation rates and luminances were compared to optimize parameters for high signal to noise ratios (SNR) and diagnosticity for early AMD.

Pupil responses were recorded from 19 early AMD patients (30 eyes) and 29 age-matched control subjects. We compared a luminance-balanced stimulus ensemble and two unbalanced stimulus variants, each consisting of 44 independent stimulus regions per eye extending from fixation to 15˚ eccentricity. Video cameras recorded pupil responses for each eye under infrared illumination. The amplitudes and delays of the peak responses were analysed by multivariate linear models. The diagnostic accuracy of the stimulus variants was compared using areas under the curve (AUC) of receiver operator characteristic (ROC) plots.

Early AMD eyes differed significantly from normal in their mean constriction amplitudes (-2.22 ± 0.15 dB, t = -14.8) and delays (17.92 ± 1.2 ms, t = 14.9). The brightest stimulus ensembles produced the highest median SNRs of 3.45 z-score units; however, the balanced method was found to be the most diagnostic. AUC values of 0.95 ± 0.03 (mean ± SE) for early AMD were obtained when the asymmetry of response amplitudes between eyes was considered.

The mfPOP responses of early AMD eyes showed significant abnormality in response amplitudes and peak time. The ROC AUCs of 95 % suggest that mfPOP is a sensitive tool for detecting early abnormalities in AMD and longitudinal studies measuring progression of retinal dysfunction are warranted.

Download full-text


Available from: Ted Maddess, Mar 11, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We compared photopic and scotopic multifocal pupillographic stimuli in age-related macular degeneration (AMD). Both eyes of 18 normal and 14 AMD subjects were tested with four stimulus variants presented at photopic and 126 times lower luminances. The multifocal stimuli presented 24 test regions/eye to the central 60°. The stimulus variants had two different check sizes, and when presented either flickered (15Hz) for 266ms, or were steady for 133ms. Mean differences from normal of 5 to 7dB were observed in the central visual field for both photopic and scotopic stimuli (all p<0.00002). The best areas under receiver operating characteristic plots for exudative AMD in the photopic and scotopic conditions were 92.9±8.0 and 90.3±5.7% respectively, and in less severely affected eyes 83.8±9.7% and 76.9±8.2%. Damage recorded at photopic levels was possibly more diffusely distributed across the visual field. Sensitivity and specificity was similar at photopic and scotopic levels.
    Vision research 08/2012; 69:42-8. DOI:10.1016/j.visres.2012.07.019 · 1.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multifocal pupillographic objective perimetry was compared using 24 and 44 regions per visual field. Experimental design in a university setting. Twenty-seven normal control and 36 age-matched glaucoma patients. The four test variants differed in the mean interval between stimuli: 4, 1 or 0.25 s; and the number of visual field regions tested within the central 60 degrees: 24 or 44. All subjects had their diagnostic status confirmed by optical coherence tomography, two forms of perimetry and slit-lamp biomicroscopy. Both eyes were measured concurrently in 2.73 ± 0.45 min/eye (mean ± standard deviation), and tests were repeated about 2 weeks apart. The main outcome measures were: (i) mean change in light sensitivity due glaucoma; and (ii) areas under Receiver Operator Characteristic plots for detecting glaucoma. For all four variants, consensual responses, female gender and age produced small but significant sensitivity differences, and sensitivity declined with age by ≤−0.27 dB/decade (all P < 0.0003). The best diagnostic accuracy (area under curve 93.2 ± 3.89%) was produced by the one-presentation/s 44-region protocol. Across the four protocols, the effect of repeat testing was small (all methods ≤0.15 dB). Presentation rate had little effect, but increasing the tested density from 24 to 44 regions/field improved diagnostic power. Given that multifocal pupillographic objective perimetry also provides information on response delay and afferent versus efferent defects at every visual field region, it may be a useful adjunct to perimetry.
    Clinical and Experimental Ophthalmology 01/2013; 41(2):140-7. DOI:10.1111/ceo.12016 · 2.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study investigated the diagnostic utility for glaucoma of multifocal pupillographic objective perimetry (mfPOP) stimuli targeting different components of the pupillary response: cortically-derived colour responses, and subcortical luminance responses. Observational cross-sectional study undertaken at the Australian National University. Thirty-five eyes of 24 glaucoma subjects and 46 eyes of 23 normal subjects. Subjects were tested with three mfPOP stimulus variants. The luminance-only variant (YYbal) utilised yellow stimuli on a yellow background; mixed colour and luminance protocols utilised green stimuli on a red background (RGbal, RG). Stimuli of 33 ms duration were presented at mean intervals of 4 s / region. Pupil constriction amplitude and time to peak. Area under the receiver operating characteristic curve (ROC AUC) was the main measure of sensitivity and specificity for glaucoma. Colour and luminance protocols were more accurate at differentiating glaucoma subjects from normal subjects than the luminance-only protocol, and produced the largest reductions in amplitudes. This type of protocol also produced the highest overall sensitivity and specificity for glaucoma (ROC percent AUC Severe: 100%, Moderate: 94.4%, Mild: 71.0%). Pattern deviations tended to produce higher ROC AUCs in eyes classified as Mild. Significant differences in the means of the 6-worst amplitude deviations were observed between normal and severe glaucoma subjects only. Stimuli targeting both cortical pupillary colour response and sub-cortical pupillary luminance response components produced higher diagnostic accuracy than stimuli targeting sub-cortical pupillary luminance responses alone. Inclusion of constriction latencies further improved accuracy.
    Clinical and Experimental Ophthalmology 04/2014; 42(9). DOI:10.1111/ceo.12346 · 2.35 Impact Factor
Show more