Corinne F. Carle

High resolution multifocal pupillographic objective perimetry in glaucoma

PURPOSE The recent development of an objective and noninvasive perimetric technique using pupillary responses to sparse multifocal visual stimuli shows promise for the assessment of visual function in glaucoma. This study assesses the sensitivity and specificity of four variants of dichoptic multifocal pupillographic objective perimetry (mfPOP) with a high-resolution, 40-region/field stimulus. METHODS Nineteen normal subjects and 17 with open-angle glaucoma were tested with four 4-minute stimulus protocols, presented in eight segments of 30 seconds each. Achromatic multifocal stimuli comprised 40 test regions per eye arranged in a four-ring dartboard layout subtending 60° of visual field. Background luminance was 10 cd/m² with active stimulus regions displaying steady or flickered stimuli at 290 cd/m². Stimulus durations were between 33 and 150 ms, mean intervals between presentations to each test region ranged from 1 to 16 seconds. Fixation was monitored in real time. RESULTS Longer mean intervals and durations resulted in better diagnostic performance. Best results were obtained with 150-ms flickered stimuli and a discriminant function that incorporated both amplitude and width of responses: ROC area under the curve 0.86 ± 0.05 (mean ± SE) across all visual field severities, (n = 34) and 1.00 ± 0.00 for moderate and severe fields (n = 10). CONCLUSIONS mfPOP produces separate information on response delay and afferent and efferent defects at every point in the field. The diagnostic accuracy of the 40-region, 150-ms stimulus is comparable to that of commonly used subjective perimeters and encourages further investigation of this technique.

Contraction anisocoria: Segregation, summation, and saturation in the pupillary pathway

PURPOSE To investigate the neural basis of contraction anisocoria and any implications for assessments using pupillary responses, through analysis of topographic variation in amplitudes of direct and consensual pupil responses. METHODS Direct and consensual pupillary contraction amplitudes were analyzed from six studies in which 120 normal subjects were tested with 24 different stimulus variants. The dichoptically presented multifocal stimulus arrays subtended ± 30° of visual field but varied in color (achromatic or yellow), number of test regions (24 to 60/eye), mean regional presentation interval (0.25 to 16 s), and pulse time-course (33 to 150 ms, flickered or steady). The 290 cd/m(2) test-regions were displayed on a 10 cd/m(2) background. Ratios between mean direct and consensual responses were calculated for each region. Results were quantified using multivariate linear analysis. RESULTS Direct responses within the temporal hemifield were significantly larger than consensual for all stimulus protocols. Across the 24 protocols these differences ranged between 13.8% (t(1415)=3.06, P<0.01) and 27.0% (t(990)=5.72, P<0.0001). Differences in the nasal field were mostly non-significant. Contraction amplitudes varied systematically across the visual field. By contrast, direct/consensual ratios were markedly uniform within each hemifield. CONCLUSIONS The distribution of signal from the pretectal olivary nuclei to each Edinger-Westphal nucleus differs depending on the hemifield being stimulated. A simple model incorporating segregation and summation of afferent signals, and differing saturation of midbrain pathways is proposed. This appears to explain inconsistent observations in the literature and predicates the need for separate assessment of direct and consensual responses at hemifield or better resolution.

The pupillary response to color and luminance variant multifocal stimuli.

PURPOSE We are developing multifocal pupillographic objective perimetry (mfPOP) to assess localized changes in function within visual pathways. In this study, we investigate novel mfPOP stimuli designed to target neural components from either or both the sub-cortical pupillary luminance response and the cortically driven color response. METHODS Pupillary responses of 12 subjects were recorded to eight mfPOP stimulus variants (protocols). Forty-eight visual field test-regions (24/eye) were stimulated concurrently with uncorrelated sequences of either high or low luminance-contrast, luminance- plus color-contrast, or equiluminant color-exchange stimuli. Stimulus pulses were of 50 ms duration and were presented at mean intervals of 4 seconds/region. Test durations were 4 or 8 minutes; therefore, estimated responses were derived from 60 or 120 stimulus presentations to each test region. RESULTS Pupillary response amplitudes were more influenced by luminance-contrast than the color-contrast of stimuli; response delays, however, were more closely linked to the proportion of color- versus luminance-contrast in each protocol. Significant differences (P < 0.05) in amplitudes but not delays were present between all three high luminance-contrast protocols and a low luminance-contrast luminance protocol, regardless of color content. The reverse pattern was observed between the equiluminant color exchange protocol and this same low luminance-contrast luminance protocol. Only the low luminance-contrast plus color exchange protocol differed significantly from the low luminance-contrast luminance protocol in both measures. CONCLUSIONS Two protocols, utilizing low and high luminance-contrast plus color exchange, were identified as likely to incorporate both cortical and subcortical response components, and were deemed potential candidates for further investigation in clinical studies.

Multifocal pupillography in early age-related macular degeneration.

Purpose To investigate the potential of multifocal pupillographic objective perimetry to assess changes in retinal function with clinical severity of age-related macular degeneration (AMD). Methods Pupil responses were recorded from 40 subjects with AMD and 23 normal control subjects (mean ± SD age, 71.3 ± 5.1 years). Age-related macular degeneration subjects were classified according to the Age-Related Eye Disease Study (AREDS) classification system and allocated into one of four AMD severity groups. Three multifocal pupillographic objective perimetry stimulus variants that were identical in luminance but varied in spatiotemporal sequence were used. In one of the three protocols, stimuli were presented with a pedestal flicker for 266 milliseconds at 15 Hz. Results On average, response amplitudes demonstrated a significant change in sensitivity with progression from early-stage (0.32 ± 0.08 dB, t = 3.88) to late-stage (−1.60 ± 0.12 dB, t = −12.7) age-related macular degeneration. Response delays followed a similar trend with the longest delays in AREDS4 (57.2 ± 1.9 milliseconds, t = 29.5). Ring analysis identified the largest mean effect on responses within the central 6 degrees of fixation. The NewStimuli protocol achieved the best diagnostic accuracy across all severity groups with area under the curve values of 0.85 ± 0.066 (AREDS1), 0.908 ± 0.085 (AREDS2), 0.929 ± 0.040 (AREDS3), and 1.0 ± 0.0 (AREDS4). Conclusions The mean effect of AMD on contraction amplitudes and response delays reflected the severity of disease, and the NewStimuli protocol achieved good diagnostic accuracy across all AMD severity groups. Multifocal pupillographic objective perimetry may potentially be a useful method in monitoring progression of AMD and assessing change in retinal function with novel interventions in early AMD. Longitudinal studies are required to identify biomarkers that predict eyes at risk of progression.

High‐ versus low‐density multifocal pupillographic objective perimetry in glaucoma

Multifocal pupillographic objective perimetry was compared using 24 and 44 regions per visual field.

Luminance and colour variant pupil perimetry in glaucoma.

This study investigated the diagnostic utility for glaucoma of multifocal pupillographic objective perimetry stimuli targeting different components of the pupillary response: cortically derived colour responses and subcortical luminance responses.

Comparing multifocal pupillographic objective perimetry (mfPOP) and multifocal visual evoked potentials (mfVEP) in retinal diseases

Multifocal pupillographic objective perimetry (mfPOP) shows regions of slight hypersensitivity away from retinal regions damaged by diabetes or age-related macular degeneration (AMD). This study examines if such results also appear in multifocal visual evoked potentials (mfVEPs) recorded on the same day in the same patients. The pupil control system receives input from the extra-striate cortex, so we also examined evidence for such input. We recruited subjects with early type 2 diabetes (T2D) with no retinopathy, and patients with unilateral exudative AMD. Population average responses of the diabetes patients, and the normal fellow eyes of AMD patients, showed multiple regions of significant hypersensitivity (p < 0.05) on both mfPOP and mfVEPs. For mfVEPs the occipital electrodes showed fewer hypersensitive regions than the surrounding electrodes. More advanced AMD showed regions of suppression becoming centrally concentrated in the exudative AMD areas. Thus, mfVEP electrodes biased towards extra-striate cortical responses (surround electrodes) appeared to show similar hypersensitive visual field locations to mfPOP in early stage diabetic and AMD damage. Our findings suggest that hypersensitive regions may be a potential biomarker for future development of AMD or non-proliferative diabetic retinopathy, and may be more informative than visual acuity which remains largely undisturbed during early disease.

Retinotopic effects of visual attention revealed by dichoptic multifocal pupillography

Multifocal pupillographic objective perimetry (mfPOP) has recently been shown to be able to measure cortical function. Here we assessed 44 regions of the central 60 degrees of the visual fields of each eye concurrently in 7 minutes/test. We examined how foveally- and peripherally-directed attention changed response sensitivity and delay across the 44 visual field locations/eye. Four experiments were completed comparing white, yellow and blue stimulus arrays. Experiments 1 to 4 tested 16, 23, 9 and 6 subjects, 49/54 being unique. Experiment 1, Experiments 2 and 3, and Experiment 4 used three variants of the mfPOP method that provided increasingly improved signal quality. Experiments 1 to 3 examined centrally directed attention, and Experiment 4 compared effects of attention directed to different peripheral targets. Attention reduced the sensitivity of the peripheral locations in Experiment 1, but only for the white stimuli not yellow. Experiment 2 confirmed that result. Experiment 3 showed that blue stimuli behaved like white. Peripheral attention showed increased sensitivity around the attentional targets. The results are discussed in terms of the cortical inputs to the pupillary system. The results agree with those from multifocal and other fMRI and VEP studies. mfPOP may be a useful adjunct to those methods.

Learning Complex Texture Discrimination

Di erent isotrigon texture types are only discriminable from random binary patterns and each other by their third and higher-order spatial correlations. Their mean contrast and spatial frequency content is identical to random noise. Our ability to make these discriminations has be proposed to be innate. We previously investigated learning of 17 isotrigon types in seven naïve subjects, where each type was tested in 14 sessions over 6 weeks. Signi cant learning was observed. Here we examined if 7 learning sessions conducted every 30 minutes on one day achieved similar learning. We also tested participants at a recall session, 2.5 months later. We used 11 naïve subjects with normal vision. We examined discrimination from random patterns of a subset of 5 of the original texture types, with 16 4AFC repeats/texture/session (5*11*8*16=7040 discriminations). Learning was similar to that achieved in the 6-week sessions. Two of the textures showed signi cant learning with mean discrimination improvement in probability of correct discrimination of 0.125 ± 0.058 to 0.244 ± 0.089 (p = 0.03 and 0.01). The textures that showed signi cant learning were the Cross-Even and Wolf-Odd type. However, both of these textures showed a reduction in learning at the nal recall session. It appears that the number of discriminations, rather than the duration of the This ite uses cooki s. By continuing to use our website, you re agreeing to o r privacy policy. | Accept 7/31/2019 Learning Complex Texture Discrimination | JOV | ARVO Journals https://jov.arvojournals.org/article.aspx?articleid=2699253&resultClick=1 2/2 learning period is the key factor in learning di erences in texture appearance based upon higher order spatial correlations. Initial performance was not chance so there appears to be some innate ability in naïve subjects. Meeting abstract presented at VSS 2018

47. : Effects of stimulating melanopsin-containing retinal ganglion cells in migraine patients using multifocal objective pupillometry

Recent evidence has linked intrinsically-photosensitive retinal ganglion cells (ipRGC) to photosensitivity in migraine. It is possible that multifocal pupillographic objective perimetry (mfPOP) might exacerbate migraine and the response to mfPOP might be different in migraineurs. This study aimed to establish the effects of stimulating ipRGC using mfPOP on migraine severity parameters and pupillary response characteristics. A randomized case-control crossover study tested migraineurs and normal controls using mfPOP utilising a blue protocol to target the intrinsic melanopsin response of the ipRGC and a yellow protocol to stimulate cone photoreceptors. Migraine diaries were obtained a week prior to and a week after each testing. Responses were analysed according to response time-to-peak and standardised amplitude (AmpStd). The percentage area under the receiver operator characteristic curve (%AUC) was used to predict migraine status. Thirty-eight migraineurs and 24 normal controls were enrolled. There was no significant difference in the mean number of migraine attacks/subject in the weeks prior to, or following, testing with either protocol. The AmpStds (in dB) were lower for migraineurs than controls, though these differences did not reach statistical significance. A migraine attack occurring in the 2 weeks prior to testing had a significant independent effect in lowering AmpStd while a history of triptan use increased AmpStd. Time-to-peak was shorter in yellow protocol, probably related to differences in the stimuli. The %AUC was highest for AmpStd. Stimulating ipRGC did not affect migraine severity. Pupillary response characteristics were influenced by recent attacks of a migraine and a history of triptan use.