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.

This study investigated multifocal pupillographic objective perimetry (mfPOP) stimuli that target the intrinsic photosensitivity of melanopsin retinal ganglion cells. The diagnostic potential for glaucoma is compared between stimuli biased toward either cone input to these cells or their melanopsin response. Nineteen glaucoma patients and 24 normal subjects were tested using mfPOP stimulus protocols with either 33-ms yellow or 750-ms blue stimuli. Subjects' color discrimination was assessed using the Farnsworth 100-hue test. Pupillary responses were measured, and mixed-effects regression was used to quantify results. Diagnostic accuracy was assessed using receiver operating characteristic (ROC) analysis. The mean reduction in moderate to severe glaucoma pupil responses using blue mfPOP stimuli was larger but more variable than that of the shorter yellow stimuli (blue: -1.32 dB [t(40) = -2.29; P = 0.027]; yellow: -0.93 dB [t(40) = -3.13; P = 0.003]). Color discrimination decreased significantly with age and glaucoma, with type III blue-yellow anomalies dominating. ROC analysis revealed similar diagnostic accuracies (AUC for eyes classified as moderate to severe; blue: 81.7%, yellow: 83.7). Slightly higher sensitivity and specificity were obtained using blue stimuli in mild disease (AUCs blue: 71.1, cf. yellow: 67.7), although this difference was not significant. In moderate to severe glaucoma, diagnostic accuracy of yellow and blue was similar, but blue stimuli showed limited ability to resolve scotomas. Blue mfPOP stimuli, however, may have advantages over yellow in detecting early glaucoma.

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.

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.