Multifocal pupillography identifies Ranibizumab-induced changes in retinal function for exudative age-related macular degeneration

PURPOSE. To investigate the efficacy of multifocal pupillographic objective perimetry (mfPOP) to quantify the effects of intravitreal ranibizumab injection for choroidal neovascularization (CNV) secondary to exudative age-related macular degeneration (AMD). METHODS. mfPOP visual fields from 20 patients with unilateral exudative AMD treated with intravitreal ranibizumab were measured before and after 3 months of treatment and were compared with that in 30 normal subjects. Two stimulus types consisting of ensembles of 24 or 44 independent stimuli per eye had a mean presentation interval at each region of 1 second. Pupil responses were recorded with video cameras under infrared illumination. Multiple linear models were fitted to contraction amplitudes and delay to peak responses, to determine the independent effects of exudative AMD before and after ranibizumab therapy. RESULTS. After 3 months of treatment, mean additional response delays compared to normal subjects for the 24-region stimulus improved significantly (P < 5 × 10 -9) from a mean of 18.82 ± 3.0 ms at baseline to 7.45 ± 3.15 ms. The mean effect of exudative AMD at baseline decreased constriction amplitude by -1.11 ± 0.24 dB (P < 0.00001) with little improvement after ranibizumab therapy. Small pretreatment elevations of extrafoveal sensitivity correlated with improvements in central retinal thickness (CRT) after treatment (P < 0.0005). CONCLUSIONS. Improvements in mfPOP contraction amplitudes and time to peak responses were measured in eyes treated with intravitreal ranibizumab; however, response delays appeared to be the most indicative of functional improvement. Confirmation of hypersensitivity in the extrafoveal field in a larger group may support this finding as a prognostic marker for good treatment outcomes

Multifocal pupillography identifies changes in visual sensitivity according to severity of diabetic retinopathy in type 2 diabetes

PURPOSE. Retinal light sensitivity loss has been shown to occur prior to other signs of retinopathy and may predict the sight-threatening sequelae. A rapid, objective perimetric test could augment diabetes care. We investigated the clinical use of multifocal pupillographic objective perimetry (mfPOP) to identify patients with and without diabetic retinopathy. METHODS. Retinopathy severity was determined using the Early Treatment of Diabetic Retinopathy Study (ETDRS) standard for fundus photography. Pupillary responses were measured from both eyes of 25 adults with none to moderate diabetic retinopathy and 24 agematched controls, using three mfPOP stimulus variants. Multifocal pupillographic objective perimetry stimulus variants tested 44 regions per eye arranged in a five-ring dartboard layout presented within either the central 300 or 600 of fixation. Receiver operator characteristic (ROC) curves were produced from contraction amplitudes and time to peak responses. RESULTS. Regression analysis revealed that mean amplitude deviations were larger with severity of early retinopathy. On average, the longest delays were measured in patients with no retinopathy. The brightest wide-field stimuli produced the highest area under the ROC curve for differentiating eyes with no retinopathy from nonproliferative diabetic retinopathy (NPDR) and from healthy eyes (100 ± 0.0%, mean ± SE). The asymmetry in local delay deviations between eyes tended to produce higher sensitivity and specificity than amplitude deviations. CONCLUSIONS. Asymmetry in local response delays measured by mfPOP may provide useful information regarding the severity of diabetic retinopathy and may have clinical use as a rapid, noninvasive method for identifying functional loss even in the absence of NPDR

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

The experience of visual art for people living with mild-to-moderate vision loss

Background: Visual art can enhance wellbeing and quality-of-life; however, the experience of visual art for people with mild-to-moderate vision loss has not been examined. Methods: Eight participants (6 females, 2 males; Mean age = 81 years, SD = 7.9, range 70–91 years; 4 with mild vision loss and 4 with moderate vision loss based on binocular visual acuity) completed a mixed-methods study comprising: a semi-structured interview on visual art experience; an eye examination; and questionnaires about visual functioning and quality-of-life. Results: Various themes were identified: visual perception of art (e.g. altered colours, visual distortions, etc.), viewing conditions, elements of art, personal preference, deriving meaning, appreciation of art, impact of impaired visual perception, and social aspects of art. Conclusions: The overall experience of art is influenced by how an individual sees, perceives, and makes meaning from art. Even mild vision loss can impair this experience and impact emotional and social wellbeing.</p

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 diseas

Discriminating early-stage diabetic retinopathy with subjective and objective perimetry

Introduction: To prevent progression of early-stage diabetic retinopathy, we need functional tests that can distinguish multiple levels of neural damage before classical vasculopathy. To that end, we compared multifocal pupillographic objective perimetry (mfPOP), and two types of subjective automated perimetry (SAP), in persons with type 2 diabetes (PwT2D) with either no retinopathy (noDR) or mild to-moderate non-proliferative retinopathy (mmDR). Methods: Both eyes were assessed by two mfPOP test methods that present stimuli within either the central ±15° (OFA15) or ±30° (OFA30), each producing per-region sensitivities and response delays. The SAP tests were 24-2 Short Wavelength Automated Perimetry and 24-2 Matrix perimetry. Results: Five of eight mfPOP global indices were significantly different between noDR and mmDR eyes, but none of the equivalent measures differed for SAP. Per-region mfPOP identified significant hypersensitivity and longer delays in the peripheral visual field, verifying earlier findings. Diagnostic power for discrimination of noDR vs. mmDR, and normal controls vs. PwT2D, was much higher for mfPOP than SAP. The mfPOP per-region delays provided the best discrimination. The presence of localized rather than global changes in delay ruled out iris neuropathy as a major factor. Discussion: mfPOP response delays may provide new surrogate endpoints for studies of interventions for early-stage diabetic eye damage.</p

Rapid Objective Testing of Visual Function Matched to the ETDRS Grid and Its Diagnostic Power in Age-Related Macular Degeneration

Purpose: To study the power of an 80-second multifocal pupillographic objective perimetry (mfPOP) test tailored to the ETDRS grid to diagnose age-related macular degeneration (AMD) by Age-Related Eye Disease Study (AREDS) severity grade. Design: Evaluation of a diagnostic technology. Methods: We compared diagnostic power of acuity, ETDRS grid retinal thickness data, new 80-second M18 mfPOP test, and two wider-field 6-minute mfPOP tests (Macular-P131, Widefield-P129). The M18 stimuli match the size and shape of bifurcated ETDRS grid regions, allowing easy structure–function comparisons. M18, P129, and P131 stimuli test both eyes concurrently. We recruited 34 patients with early-stage AMD with a mean ± standard deviation (SD) age of 72.6 ± 7.06 years. The M18 and P129 plus P131 stimuli had 26 and 51 control participants, respectively with mean ± SD ages of 73.1 ± 8.17 years and 72.1 ± 5.83 years, respectively. Multifocal pupillographic objective perimetry testing used the Food and Drug Administration-cleared Objective FIELD Analyzer (OFA; Konan Medical USA). Main Outcome Measures: Percentage area under the receiver operator characteristic curve (AUC) and Hedge's g effect size. Results: Acuity and OCT ETDRS grid thickness and volume produced reasonable diagnostic power (percentage AUC) for AREDS grade 4 eyes at 83.9 ± 9.98% and 90.2 ± 6.32% (mean ± standard error), respectively, but not for eyes with less severe disease. By contrast, M18 stimuli produced percentage AUCs from 72.8 ± 6.65% (AREDS grade 2) to 92.9 ± 3.93% (AREDS grade 4), and 82.9 ± 3.71% for all eyes. Hedge's g effect sizes ranged from 0.84 to 2.32 (large to huge). Percentage AUC for P131 stimuli performed similarly and for P129 performed somewhat less well. Conclusions: The rapid and objective M18 test provided diagnostic power comparable with that of wider-field 6-minute mfPOP tests. Unlike acuity or OCT ETDRS grid data, OFA tests produced reasonable diagnostic power in AREDS grade 1 to 3 eyes.</p

Objective Perimetry in Sporting-Related Mild Traumatic Brain Injury

Supported by National Health and Medical Research Council Project Grant APP1063458 and Rebecca Cooper Medical Foundation Grant PG2018040