A neural signature of the unique hues

Since at least the 17th century there has been the idea that there are four simple and perceptually pure “unique” hues: red, yellow, green, and blue, and that all other hues are perceived as mixtures of these four hues. However, sustained scientific investigation has not yet provided solid evidence for a neural representation that separates the unique hues from other colors. We measured event-related potentials elicited from unique hues and the ‘intermediate’ hues in between them. We find a neural signature of the unique hues 230 ms after stimulus onset at a post-perceptual stage of visual processing. Specifically, the posterior P2 component over the parieto-occipital lobe peaked significantly earlier for the unique than for the intermediate hues (Z = -2.9, p = .004). Having identified a neural marker for unique hues, fundamental questions about the contribution of neural hardwiring, language and environment to the unique hues can now be addressed

Oral Omega-3 Supplementation Lowers Intraocular Pressure in Normotensive Adults

Purpose: Elevated intraocular pressure (IOP) is the major modifiable risk factor for the sight-threatening eye disease, glaucoma. We investigated whether oral omega-3 supplements affect IOP in normotensive adults. Methods: We undertook a pooled analysis of data from two double-masked, placebo-controlled randomized trials (Australian New Zealand Clinical Trials Registry, ACTRN12614001019695, ACTRN12615000173594) that investigated the efficacy and safety of oral omega-3 supplementation for treating ocular surface inflammation. Recruitment involved adults (n = 105) with IOP <21 mm Hg, and without a current or prior glaucoma diagnosis. Participants were randomly allocated to either an oral omega-3 (∼1000 mg/day eicosapentaenoic acid + ∼500 mg/day docosahexaenoic acid ± 900 mg/day α-linolenic acid) or placebo (olive oil, 1500 mg/day) supplement. IOP was quantified at baseline and after 3 months of supplementation (day 90). Change in IOP, relative to baseline, was compared between groups. Results: At baseline, participants were of similar age (omega-3/placebo groups: mean ± SEM, 33.7 ± 1.7, n = 72/35.6 ± 3.0 years, n = 33), sex (65%/79% female), and had similar IOP (14.3 ± 0.3/13.8 ± 0.5 mm Hg). At day 90, IOP was reduced to 13.6 ± 0.3 mm Hg in the omega-3 group; controls had a slight IOP increase to 14.2 ± 0.4 mm Hg (P < 0.05). Conclusions: Oral omega-3 supplementation for 3 months significantly reduced IOP in normotensive adults. To our knowledge, this is the first study to report that omega-3 fatty acids lower IOP in humans. Translational Relevance: These findings justify further investigation into the therapeutic potential of omega-3 supplementation for reducing IOP, to prevent and/or treat conditions with IOP elevation, including ocular hypertension and glaucoma

Simultaneous retinal and cortical visually evoked electrophysiological responses in between migraine attacks

PURPOSE: People with migraine often report aversion to flickering lights and show abnormal results on behavioural tasks that require the processing of temporal visual information. Studies have reported that the cortically evoked electrophysiological response to a flickering visual stimulus is abnormal; however, none have considered whether there is an underlying pre-cortical abnormality. In this cross-sectional study, we consider whether people with migraine have retinal and cortical electrophysiological abnormalities to flickering stimuli. METHODS: Monocular transient (1 Hz) and steady-state (8.3 Hz) pattern reversal electroretinograms (PERGs) and pattern visual evoked responses (PVERs) were measured simultaneously in 45 people with migraine (26 without aura, 19 with aura) and 30 non-headache controls at a time between migraine attacks. RESULTS: PERG amplitude and timing did not differ significantly between groups. Transient PVER amplitude was significantly reduced (28%) in the migraine with aura group compared to the controls F(2,72) = 3.6, p = 0.03). Both migraine groups showed significant reductions (32%, 39%) in steady-state PVER amplitude relative to controls (F(2,70) = 4.3, p = 0.02). CONCLUSIONS: This study finds normal retinal processing of flickering stimuli in the presence of abnormal cortical function between migraine attacks

Abnormal inhibition-excitation imbalance in migraine

BACKGROUND: People with migraine show increased surround suppression of perceived contrast, a perceptual analogue of centre-surround antagonistic interactions in visual cortex. A proposed mechanism is that cortical 'hyperexcitability' or 'hyperresponsivity', a prominent theory in the migraine literature, drives abnormal excitatory-inhibitory balance to give increased local inhibition. The purpose of this cross-sectional study was to determine whether cortical hyperresponsivity and excitatory-inhibitory imbalance manifests in the visual cortical response of migraine sufferers. METHODS: Interictal steady-state visual evoked potentials (VEPs) in response to 0 to 97% contrast were recorded in 30 migraine participants (15 without aura, 15 with aura) and 21 non-headache controls. Monotonicity indices were calculated to determine response saturation or supersaturation. Contrast gain was modelled with a modified saturating hyperbolic function to allow for variation in excitation and inhibition. RESULTS: A greater proportion of migraine participants (43%) than controls (14%) exhibited significant VEP supersaturation at high contrast, based on monotonicity index (chi-square, p = 0.028). Supersaturation was also evident by the trend for greater suppressive exponent values in migraine compared to control individuals (Mann-Whitney rank sum, p = 0.075). CONCLUSIONS: Supersaturation in migraine is consistent with excess excitation (hyperresponsivity) driving increased network inhibition and provides support for excitatory-inhibitory imbalance as a pathophysiological disturbance in migraine

The effect of duration post-migraine on visual electrophysiology and visual field performance in people with migraine

PURPOSE: In between migraine attacks, some people show visual field defects that are worse when measured closer to the end of a migraine event. In this cohort study, we consider whether electrophysiological responses correlate with visual field performance at different times post-migraine, and explore evidence for cortical versus retinal origin. METHODS: Twenty-six non-headache controls and 17 people with migraine performed three types of perimetry (static, flicker and blue-on-yellow) to assess different aspects of visual function at two visits conducted at different durations post-migraine. On the same days, the pattern electroretinogram (PERG) and visual evoked response (PVER) were recorded. RESULTS: Migraine participants showed persistent, interictal, localised visual field loss, with greater deficits at the visit nearer to migraine offset. Spatial patterns of visual field defect consistent with retinal and cortical dysfunction were identified. The PERG was normal, whereas the PVER abnormality found did not change with time post-migraine and did not correlate with abnormal visual field performance. CONCLUSIONS: Dysfunction on clinical tests of vision is common in between migraine attacks; however, the nature of the defect varies between individuals and can change with time. People with migraine show markers of both retinal and/or cortical dysfunction. Abnormal visual field sensitivity does not predict abnormality on electrophysiological testing

Clinical impact of migraine for the management of glaucoma patients

Migraine is a common and debilitating primary headache disorder that affects 10-15% of the general population, particularly people of working age. Migraine is relevant to providers of clinical eye-care because migraine attacks are associated with a range of visual sensory symptoms, and because of growing evidence that the results of standard tests of visual function necessary for the diagnosis and monitoring of glaucoma (visual fields, electrophysiology, ocular imaging) can be abnormal due to migraine. These abnormalities are measureable in-between migraine events (the interictal period), despite patients being asymptomatic and otherwise healthy. This picture is further complicated by epidemiological data that suggests an increased prevalence of migraine in patients with glaucoma, particularly in patients with normal tension glaucoma. We discuss how migraine, as a co-morbidity, can confound the results and interpretation of clinical tests that form part of contemporary glaucoma evaluation, and provide practical evidence-based recommendations for the clinical testing and management of patients with migraine who attend eye-care settings

Acquired Visual Deficits Independent of Lesion Site in Acute Stroke

Most clinical diagnoses of stroke are based on the persistence of symptoms relating to consciousness, language, visual-field loss, extraocular movement, neglect (visual), motor strength, and sensory loss following acute cerebral infarction. Yet despite the fact that most motor actions and cognition are driven by vision, functional vision per se is seldom tested rigorously during hospitalization. Hence we set out to determine the effects of acute stroke on functional vision, using an iPad application (Melbourne Rapid Field-Neural) that can be used to assess vision (visual acuity and visual field sensitivity) at the bedside or in the emergency ward in about 6 min per eye. Our convenience sample comprised 60 (29-88 years, 65 ± 14 years, 33 males) of 160 sequentially presenting first episode, acute (<7 days) ischemic stroke patients at Sunshine Hospital, Melbourne. One hundred patients were excluded due to existing eye disease, inadequate radiological confirmation, inability to comply with English directions or too ill to participate. Stroke cases were compared with 37 (29-85 years, 64 ± 12 years,14 males) similar-aged controls using a Mann-Whitney U-test. A significant loss in visual field sensitivity was measured in 68% of stroke cases (41/60, Mean Deviation: Stroke: -5.39 ± 6.26 dB, Control: 0.30 ± 0.60 dB, MWU = 246, p < 0.0001). Surprisingly, 44% (18/41) of these patients were unaware of their field loss. Although high contrast visual acuity was unaffected in most (55/60) patients, visual acuity-in-noise was reduced in 62% (37/60, Stroke: mean 6/12-2, log MAR 0.34 ± 0.21 vs. Control: mean 6/7·5-2, log MAR 0.14 ± 0.10; MWU = 470, p < 0.0001). Visual field defects were associated with all occipital, parietal and posterior cerebellar artery strokes while 9/15 middle cerebral artery lesions and 11 lesions in other brain regions were also associated with visual field defects. Our findings demonstrate that ~2/3 of acute first episode ischemic stroke patients experience acquired vision deficits, often unrelated to the confirmed lesion site. Our results also imply that visual dysfunction may be associated with a more generalized cerebral dysfunction while highlighting the need for bedside testing of vision for every stroke patient and demonstrating the translational clinical value of the "Melbourne Rapid Field- Neural" iPad application. Clinical Trial: http://www.ANZCTR.org.au/ACTRN12618001111268.aspx

Uptake, Persistence, and Performance of Weekly Home Monitoring of Visual Field in a Large Cohort of Patients With Glaucoma

PURPOSE: This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients. DESIGN: Single-center, observational, longitudinal, compliance study. METHODS: Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean ± [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap. RESULTS: We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing ≥1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85). CONCLUSIONS: VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance

An Electrophysiological Comparison of Contrast Response Functions in Younger and Older Adults, and Those With Glaucoma

Purpose: Aging and glaucoma both result in contrast processing deficits. However, it is unclear the extent to which these functional deficits arise from retinal or post-retinal neuronal changes. This study aims to disentangle the effects of healthy human aging and glaucoma on retinal and post-retinal contrast processing using visual electrophysiology. Methods: Steady-state pattern electroretinograms (PERG) and pattern visual evoked potentials (PVEP) were simultaneously recorded across a range of contrasts (0%, 4%, 9%, 18%, 39%, 73%, 97%; 0.8° diameter checks, 31° diameter checkerboard) in 13 glaucoma patients (67 ± 6 years), 15 older (63 ± 8 years) and 14 younger adults (27 ± 3 years). PERG and PVEP contrast response functions were fit with a linear and saturating hyperbolic model, respectively. PERG and PVEP magnitude, timing (phase), and model fit parameters (slope, semi-saturation constant) were compared between groups. Results: PERG responses were reduced and delayed in older adults relative to younger adults, and further reduced and delayed in glaucoma patients across all contrasts. PVEP signals were also reduced and delayed in glaucoma patients, relative to age-similar (older) controls. However, despite having reduced PERG magnitudes, older adults did not demonstrate reduced PVEP magnitudes. Conclusions: Older adults with healthy vision demonstrate reduced magnitude and delayed timing in the PERG that is not reflected in the PVEP. In contrast, glaucoma produces functional deficits in both PERG and PVEP contrast response functions. Our results suggest that glaucomatous effects on contrast processing are not a simple extension of those that arise as part of the aging process

Optical Coherence Tomography Reveals Changes to Corneal Reflectivity and Thickness in Individuals with Tear Hyperosmolarity

PURPOSE: To investigate whether tear hyperosmolarity, a feature of dry eye disease (DED), affects central corneal thickness (CCT), corneal light reflectivity, and/or tear film reflectivity. METHODS: This prospective, cross-sectional study involved 48 participants (38 with hyperosmolar tears and 10 controls with normo-osmolar tears). Symptoms and signs of DED (tear osmolarity, sodium fluorescein tear break-up time, ocular surface staining, Schirmer test) were assessed. CCT, and the reflectivity of the cornea and the tear-epithelial interface were quantified relative to background noise using Fourier-domain optical coherence tomography (FD-OCT). RESULTS: CCT of eyes with severe tear hyperosmolarity, defined as eyes in the upper quartile of the hyperosmolar group, was less than control eyes (539.1 ± 7.4 vs. 583.1 ± 15.0 μm, P = 0.02) and eyes with less severe tear hyperosmolarity, defined as hyperosmolar eyes in the lower quartile (622.7 ± 5.8 μm, P < 0.0001). CCT showed a negative linear relationship with tear osmolarity for values above 316 mOsmol/L (R2 = 0.17, P = 0.01). Central corneal reflectivity was lower in hyperosmolar eyes than normo-osmolar eyes (45.1 ± 0.3 vs. 48.1 ± 0.6 pixels, P = 0.02); the greatest relative difference was in the anterior stroma, where corneal reflectivity was 4.7 ± 1.9% less in hyperosmolar eyes (P < 0.01). Peak reflectivity of the tear-epithelial interface was 4.8% ± 3.5% higher in the hyperosmolar group than the normo-osmolar tear group (P = 0.04). CONCLUSION: Individuals with significant tear hyperosmolarity and clinical signs of symptoms of DED show reduced CCT and altered corneal reflectivity. TRANSLATIONAL RELEVANCE: Anterior segment FD-OCT provides novel insight into corneal microstructural differences in individuals with DED