Haidinger's brushes: Psychophysical analysis of an entoptic phenomenon.

Entoptic phenomena are visual artifacts arising from the interaction of light with the specific anatomic structure of the human eye. While they are usually too subtle to actually enable additional visual abilities, their perception can provide indirect information on the physiological conditions of the visual system. Among the most famous ones, Haidinger's brushes consist in the appearance of a yellowish bow tie perceived in the presence of linearly polarized white light and originate from the particular spatial distribution of dichroic carotenoid molecules forming a sort of embedded radial polarizer in the foveal region. In this work, we develop a compact and versatile optical setup for the psychophysical analysis of the perceptual threshold of such entoptic effect. The tests performed on a group of 113 healthy individuals under conditions of maximum contrast (blue light) reveal the capability to perceive an average polarization degree around 16%. The developed prototype outlines a new optical platform to train the users in the perception of the phenomenon and infer information on the polarization-degree sensitivity of the human visual system.

Neural evidence for lexical parafoveal processing.

In spite of the reduced visual acuity, parafoveal information plays an important role in natural reading. However, competing models on reading disagree on whether words are previewed parafoveally at the lexical level. We find neural evidence for lexical parafoveal processing by combining a rapid invisible frequency tagging (RIFT) approach with magnetoencephalography (MEG) and eye-tracking. In a silent reading task, target words are tagged (flickered) subliminally at 60 Hz. The tagging responses measured when fixating on the pre-target word reflect parafoveal processing of the target word. We observe stronger tagging responses during pre-target fixations when followed by low compared with high lexical frequency targets. Moreover, this lexical parafoveal processing is associated with individual reading speed. Our findings suggest that reading unfolds in the fovea and parafovea simultaneously to support fluent reading.

Human Eye Optics within a Non-Euclidian Geometrical Approach and Some Implications in Vision Prosthetics Design.

An analogy with our previously published theory on the ionospheric auroral gyroscope provides a new perspective in human eye optics. Based on cone cells' real distribution, we model the human eye macula as a pseudospherical surface. This allows the rigorous description of the photoreceptor cell densities in the parafoveal zones modeled further by an optimized paving method. The hexagonal photoreceptors' distribution has been optimally projected on the elliptical pseudosphere, thus designing a prosthetic array counting almost 7000 pixel points. Thanks to the high morphological similarities to a normal human retina, the visual prosthesis performance in camera-free systems might be significantly improved.

Locus-Level Changes in Macular Sensitivity in Patients with Retinitis Pigmentosa Treated with Oral N-acetylcysteine.

PURPOSE: To identify characteristics of loci associated with locus-level sensitivity loss or improvement during treatment with N-acetylcysteine (NAC) in retinitis pigmentosa (RP). DESIGN: Retrospective analysis of prospectively collected data in the FIGHT RP clinical trial. METHODS: Patients (n = 30) were treated with 600, 1,200, or 1,800 mg of NAC twice daily for 3 months and then 3 times/day for 3 months. Microperimetry locus-level changes between baseline and month 6 were correlated with baseline characteristics of loci using regression models. The main outcome measurement was locus-level sensitivity change ≥6 dB. RESULTS: Baseline mean sensitivity (3,468 loci; 51 evaluable eyes) was 7.7 dB and for foveal, parafoveal, and perifoveal loci were 20.2, 11.8, and 5.8 dB. During treatment, 287 loci (8.28%) increased ≥6 dB, and 119 of 1,613 loci with baseline sensitivity ≥6 dB decreased ≥6 dB (7.38%). A higher dose of NAC was associated with lower likelihood of sensitivity loss ≥6 dB (P = .033). Loci with low baseline sensitivity were more likely to decrease ≥6 dB (P = .034) but also more likely to increase ≥6 dB (P < .001). Foveal versus perifoveal loci (P < .001) and superior versus inferior loci (P = .005) were more likely to increase ≥6 dB. CONCLUSIONS: Higher doses of NAC reduced risk of macular loci sensitivity loss in RP. Greater sensitivity depression reversibility in the fovea during treatment suggests that high foveal cone density protects cones from irreversible loss of function in RP making them more likely to show improved function during NAC treatment.

Individual differences in visual function.

A significant proportion of research on the visual system focuses on general principles that apply to samples and/or populations. Many questions, however, are more suited to the specific characteristics of an individual. The visual system, like most systems of the body, is extremely variable with respect to function and susceptibility to disease. Understanding this variation is an important avenue to better measurement, disease prevention and treatment.

In vivo assessment of foveal geometry and cone photoreceptor density and spacing in children.

The fovea undergoes significant developmental changes from birth into adolescence. However, there is limited data examining cone photoreceptor density, foveal pit shape, and foveal avascular zone (FAZ) size in children. The purpose of this study was to determine whether overall foveal structure differs as a function of age and refractive status in children. Forty-eight healthy children (ages 5.8 to 15.8 years) underwent optical coherence tomography imaging to quantify foveal point thickness and foveal pit diameter, depth, and slope. Adaptive optics scanning laser ophthalmoscope (AOSLO) images of foveal capillaries and cone photoreceptors were acquired in a subset of children to quantify FAZ metrics and cone densities at 0.2, 0.3, and 0.5 mm eccentricities. Results show that foveal pit and FAZ metrics were not related to age, axial length, or refractive status. However, linear cone density was lower in myopic versus non-myopic children at eccentricities of 0.2 mm (mean ± SD = 50,022 ± 5,878 cones/mm2 vs 58,989 ± 4,822 cones/mm2, P < 0.001) and 0.3 mm (43,944 ± 5,547 cones/mm2 vs 48,622 ± 3,538 cones/mm2, P < 0.001). These results suggest FAZ and foveal pit metrics do not systematically differ with age in children, while myopic eyes have decreased linear cone density near the foveal center. Significance Statement: The development of the fovea begins prior to birth and continues through the early teenage years until it reaches adult-like properties. Although the majority of changes during childhood are related to the maturation and migration of cone photoreceptors, in vivo data describing cone packing in children is limited. We assessed overall foveal structure in children as young as 5.8 years old by quantifying cone density and spacing, foveal avascular zone size, and foveal pit morphometry to investigate potential structural differences as a function of age and refractive status. While foveal avascular zone and foveal pit metrics did not significantly differ with age, results indicate that myopic children have lower linear cone densities close to the foveal center compared to non-myopic children.

Macular Ganglion Cell-Inner Plexiform Layer as a Marker of Cognitive and Sensory Function in Midlife.

BACKGROUND: Neurodegenerative diseases are public health challenges in aging populations. Early identification of people at risk for neurodegeneration might improve targeted treatment. Noninvasive, inexpensive screening tools are lacking but are of great potential. Optical coherence tomography (OCT) measures the thickness of nerve cell layers in the retina, which is an anatomical extension of the brain and might be indicative of common underlying neurodegeneration. We aimed to determine the association of macular ganglion cell-inner plexiform layer (mGCIPL) thickness with cognitive and sensorineural function in midlife. METHOD: This cross-sectional study included 1,880 Beaver Dam Offspring Study participants (aged 27-93 years, mean 58) who participated in the 10-year follow-up examination. We assessed cognitive function and impairment, hearing sensitivity thresholds and impairment, central auditory processing, visual impairment, and olfactory impairment. We measured mGCIPL using the Cirrus 5000 HD-OCT Macular Cube Scan. Multivariable linear and logistic regression models adjusted for potential confounders were used to determine associations between mGCIPL thickness and cognitive and sensorineural functions, as well as for comparing participants with a thin mGCIPL (1 SD below average) to the remainder in those functions. RESULTS: Thinner mGCIPL was associated with worse cognitive function, worse central auditory function, and visual impairment. We found an association of mGCIPL thickness with hearing sensitivity in women only and no association with impairment in hearing, olfaction, and cognition. Results on the thin group comparisons were consistent. CONCLUSIONS: mGCIPL thickness is associated with cognitive and sensorineural function and has the potential as a marker for neurodegeneration in middle-aged adults.

Posterior vitreous detachment and macular microvasculature in the elderly.

PURPOSE: To investigate the association between different stages of posterior vitreous detachment (PVD) and macular microvasculature in the elderly. METHODS: Swept-source optical coherence tomography (OCT), OCT angiography, and color fundus images of 490 eyes without retinal pathologies of 322 participants aged ≥65 years were evaluated. PVD was classified using enhanced vitreous visualization mode as no apparent PVD (stage 0/1), vitreous adhesions at the fovea and optic disc (stage 2), adhesion at the optic disc (stage 3), or complete PVD (stage 4). Microvascular parameters, including foveal avascular zone (FAZ) and vessel density (VD), were analyzed for their associations with complete PVD. Additionally, the association between PVD and central retinal thickness (CRT) was also addressed. RESULTS: Overall, 80, 31, 31, and 349 eyes were categorized into stages 0/1, 2, 3, and 4, respectively. Using multivariate mixed-effects model, the mean superficial FAZ area was smaller in stage 4 compared with stages 0-3 (0.29 vs. 0.32 mm2; P = 0.014), and the mean superficial VD was lower in stage 4 compared with stages 0-3 (34.96% vs. 35.24%; P = 0.0089). However, PVD was not significantly associated with deep macular microvascular parameters or CRT. CONCLUSIONS: Complete PVD was associated with smaller FAZ area and lower VD in superficial macular microvasculature, while it was not associated with central retinal thickness.

Quantitative assessment of the effect of acute anaerobic exercise on macular perfusion via swept-source optical coherence tomography angiography in young football players.

AIM: To evaluate the effect of acute anaerobic exercise on macular perfusion measured by swept-source optical coherence tomography angiography (SS-OCTA) in young football players. MATERIALS AND METHODS: Football players with ages between 18 and 20 years were included into the study. After a detailed ophthalmological examination, physiological parameters including height (cm), body weight (kg), body fat percentage (%), systemic blood pressure (BP) (mmHg), hematocrit values (%), oxygen saturation pO2 (%) and heart rate (bpm) were recorded. Intraocular pressure (IOP) (mmHg) and SS-OCTA using DRI OCT Triton (Topcon, Tokyo, Japan) were measured immediately before and after Wingate test. RESULTS: Out of 20, 16 participants completed the study. All participants were males with a mean age of 18.12 ± .34 years. Systolic BP, hematocrit and heart rate increased, while pO2 and IOP decreased remarkably after Wingate test (p < .01). After anaerobic exercise, there was an increase in mean FAZ area in superficial capillary plexus (FAZs) which was not significant (p = .13), while decrease in FAZ area in deep capillary plexus (FAZd) (mm2) was remarkable (p = .04). No changes were observed in mean vessel density (VD) (%) in superficial capillary plexus (VDs), deep capillary plexus (VDd), choriocapillaris (VDcc), central macular thickness (CMT) (µm) and subfoveal choroidal thickness (SFCT) (µm) after Wingate test (p > .05). FAZd and some of the VD parameters showed a significant correlation with BP (p < .05). CONCLUSION: Acute anaerobic exercise seems not to alter either mean VD in retina and choroid or CMT and SFCT. Among OCTA parameters, only FAZd decreased remarkably.

Polarization perception in humans: on the origin of and relationship between Maxwell's spot and Haidinger's brushes.

Under specific conditions of illumination and polarization, differential absorption of light by macular pigments is perceived as the entoptic phenomena of Maxwell's spot (MS) or Haidinger's brushes (HB). To simulate MS and HB, an existing computational model of polarization-dependent properties of the human macula was extended by incorporating neuronal adaptation to stabilized retinal images. The model predicted that polarized light modifies the appearance of MS leading to the perception of a novel phenomenon. The model also predicted a correlation between the observed diameters of MS and HB. Predictions were tested psychophysically in human observers, whose measured differences in the diameters of each entoptic phenomenon generated with depolarized and linearly polarized light were consistent with the model simulations. These findings support a common origin of each phenomenon, and are relevant to the clinical use of polarization stimuli in detecting and monitoring human eye disorders, including macular degeneration. We conclude: (i) MS and HB both result from differential light absorption through a radial diattenuator, compatible with the arrangement of macular pigments in Henle fibres; (ii) the morphology of MS is dependent on the degree of linear polarization; (iii) perceptual differences between MS and HB result from different states of neural adaptation.

A co-registration investigation of inter-word spacing and parafoveal preview: Eye movements and fixation-related potentials.

Participants' eye movements (EMs) and EEG signal were simultaneously recorded to examine foveal and parafoveal processing during sentence reading. All the words in the sentence were manipulated for inter-word spacing (intact spaces vs. spaces replaced by a random letter) and parafoveal preview (identical preview vs. random letter string preview). We observed disruption for unspaced text and invalid preview conditions in both EMs and fixation-related potentials (FRPs). Unspaced and invalid preview conditions received longer reading times than spaced and valid preview conditions. In addition, the FRP data showed that unspaced previews disrupted reading in earlier time windows of analysis, compared to string preview conditions. Moreover, the effect of parafoveal preview was greater for spaced relative to unspaced conditions, in both EMs and FRPs. These findings replicate well-established preview effects, provide novel insight into the neural correlates of reading with and without inter-word spacing and suggest that spatial selection precedes lexical processing.

Topographic correlation and asymmetry analysis of ganglion cell layer thinning and the retinal nerve fiber layer with localized visual field defects.

PURPOSE: To evaluate the accuracy of the measurement of the ganglion cell layer (GCL) of the posterior pole analysis (PPA) software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, Germany), the asymmetry of paired GCL sectors, the total retinal thickness asymmetry (RTA), and the peripapillary retinal nerve fiber layer (pRNFL) test to discriminate between healthy, early and advanced glaucoma eyes. METHODS: Three hundred eighteen eyes of 161 individuals with reliable visual fields (VF) were enrolled in this study. All participants were examined using the standard posterior pole and the pRNFL protocols of the Spectralis OCT device. VF impairment was graded in hemifields, and the GCL sectors were correlated with this damage. Thicknesses of each GCL, the GCL map deviation asymmetry and the pRNFL were compared between control and glaucomatous eyes. The area under the receiver operating characteristic curve (AUC) of these analyses was assessed. RESULTS: Fourteen of the 16 sectors of the GCL and pRNFL were significantly thinner in eyes with glaucoma than in control eyes (p<0.006). Similarly, the GCL map deviation showed a significant difference between these eyes and both the control eyes as well as the eyes with early glaucoma (p = 0.001 and p = 0.039, respectively). The highest values of AUC to diagnose both early and advanced glaucoma corresponded to the average pRNFL analysis and the GCL map deviation (AUC>0.823, p<0.040 and AUC>0.708, p<0.188, respectively). CONCLUSIONS: Although 16 central sectors of the GCL observed with PPA showed good correlation with VF damage, the pRNFL and the GCL map deviation were more effective for discrimination of glaucomatous damage.

Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment.

BACKGROUNDS: To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS: Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS: Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS: Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.

Parafoveal vessel loss and correlation between peripapillary vessel density and cognitive performance in amnestic mild cognitive impairment and early Alzheimer's Disease on optical coherence tomography angiography.

PURPOSE: Patients with Alzheimer's Disease (AD) exhibit decreased retinal blood flow and vessel density (VD). However, it is not known whether these changes are also present in individuals with early AD (eAD) or amnestic type mild cognitive impairment (aMCI), an enriched pre-AD population with a higher risk for progressing to dementia. We performed a prospective case-control clinical study to investigate whether optical coherence tomography angiography (OCTA) parameters in the macula and disc are altered in those with aMCI and eAD. METHODS: This is a single center study of 32 participants. Individuals with aMCI/eAD (n = 16) were 1:1 matched to cognitively normal controls (n = 16). We evaluated OCTA images of the parafoveal superficial capillary plexus (SCP) and two vascular layers in the peripapillary region, the radial peripapillary capillary (RPC) and superficial vascular complex (SVC). Outcome vascular and structural parameters included VD, vessel length density (VLD), adjusted flow index (AFI) and structural retinal nerve fiber layer (RNFL) thickness. We compared these parameters between the two groups and examined the correlation between OCTA parameters and cognitive performance on the Montreal Cognitive Assessment (MoCA). RESULTS: Cognitively impaired participants demonstrated statistically significant decrease in parafoveal SCP VD and AFI as compared to controls, but no statistically significant difference in peripapillary parameters. Furthermore, we found a significant positive correlation between MoCA scores for the entire study cohort and both the parafoveal SCP VD and peripapillary RPC VLD. CONCLUSION: OCTA shows significant decline in parafoveal flow and VD in individuals with early cognitive impairment related to AD, suggesting that these parameters could have potential utility as early disease biomarkers. In contrast, the presence of larger vascular channels in the peripapillary region may have obscured subtle capillary changes in that region. Overall, the correlation between vascular OCTA parameters and cognitive performance supports further OCTA studies in this population.

Hemodynamic Response of the Three Macular Capillary Plexuses in Dark Adaptation and Flicker Stimulation Using Optical Coherence Tomography Angiography.

Purpose: To assess retinal microvascular reactivity during dark adaptation and the transition to ambient light and after flicker stimulation using optical coherence tomography angiography (OCTA). Methods: Fifteen eyes of 15 healthy participants were dark adapted for 45 minutes followed by OCTA imaging in the dark-adapted state. After 5 minutes of normal lighting, subjects underwent OCTA imaging. Participants were then subjected to a flashing light-emitting diode (LED) light and repeat OCTA. Parafoveal vessel density and adjusted flow index (AFI) were calculated for superficial (SCP), middle (MCP), and deep capillary plexuses (DCP), and then compared between conditions after adjusting for age, refractive error, and scan quality. SCP vessel length density (VLD) was also evaluated. Between-condition capillary images were aligned and subtracted to identify differences. We then analyzed images from 10 healthy subjects during the transition from dark adaptation to ambient light. Results: SCP vessel density was significantly higher while SCP VLD was significantly lower during ambient light and flicker compared to dark adaptation. There was a significant positive mean value for DCP "flicker minus dark or light," suggesting more visible vessels during flicker due to changes in flow, dilation, or vessel recruitment. We found a significant, transient increase in SCP and decrease in both MCP and DCP vessel density during the transition from dark to light. Conclusions: We show evidence suggesting constriction of deeper vessels and dilation of large SCP vessels during the transition from dark to light. This contrasts to redistribution of blood flow to deeper layers during dark adaptation and flicker stimulation.

Genome-wide association analyses identify 139 loci associated with macular thickness in the UK Biobank cohort.

The macula, located near the center of the retina in the human eye, is responsible for providing critical functions, such as central, sharp vision. Structural changes in the macula are associated with many ocular diseases, including age-related macular degeneration (AMD) and glaucoma. Although macular thickness is a highly heritable trait, there are no prior reported genome-wide association studies (GWASs) of it. Here we describe the first GWAS of macular thickness, which was measured by spectral-domain optical coherence tomography using 68 423 participants from the UK Biobank cohort. We identified 139 genetic loci associated with macular thickness at genome-wide significance (P < 5 × 10-8). The most significant loci were LINC00461 (P = 5.1 × 10-120), TSPAN10 (P = 1.2 × 10-118), RDH5 (P = 9.2 × 10-105) and SLC6A20 (P = 1.4 × 10-71). Results from gene expression demonstrated that these genes are highly expressed in the retina. Other hits included many previously reported AMD genes, such as NPLOC4 (P = 1.7 × 10-103), RAD51B (P = 9.1 × 10-14) and SLC16A8 (P = 1.7 × 10-8), further providing functional significance of the identified loci. Through cross-phenotype analysis, these genetic loci also exhibited pleiotropic effects with myopia, neurodegenerative diseases (e.g. Parkinson's disease, schizophrenia and Alzheimer's disease), cancer (e.g. breast, ovarian and lung cancers) and metabolic traits (e.g. body mass index, waist circumference and type 2 diabetes). Our findings provide the first insight into the genetic architecture of macular thickness and may further elucidate the pathogenesis of related ocular diseases, such as AMD.

The effect of fish consumption on macula structure and function of healthy individuals: an OCT and mfERG study.

OBJECTIVE: The study was designed to investigate the potential effect of fish consumption on macular structure and function of healthy individuals. PATIENTS AND METHODS: The participants were Greek, who used to consume less than one portion of fish per week since their childhood. All participants underwent body mass index (BMI) measurements and ophthalmological examination. At their first examination, they were asked to consume at least 2 portions of fish per week over a period of 8 weeks, after which all the measurements were repeated. RESULTS: Eighteen healthy individuals (36 eyes) participated in this study. The central macular thickness was reduced, while the amplitudes in the foveal and parafoveal area were increased after the fish consumption. However, all measurements remained within the normal range at both visits. CONCLUSIONS: Regular fish consumption could enhance the structural and functional status of the macula.

Relationship of Macular Thickness and Function to Optical Microangiography Measurements in Glaucoma.

PURPOSE: The purpose of this article was to evaluate the relationship between macular optical microangiography (OMAG), ganglion cell-inner plexiform layer (GCIPL) thickness, and visual sensitivity measurements of different macular sectors in primary open-angle glaucoma. METHODS: In a cross-sectional study, 39 eyes of 26 primary open-angle glaucoma patients underwent optical coherence tomography imaging and 10-2 visual field examination of the macula in the same session. Linear regression models were used to evaluate the relationships between OMAG, GCIPL thickness, and visual sensitivity measurements in different macular sectors. Strength of relationship was reported as coefficient of determination (R). RESULTS: R values for the associations between OMAG and GCIPL thickness measurements ranged from 0.37 in the temporal sector to 0.56 in the inferior macular sector. R values for the association between OMAG and visual sensitivity measurements ranged from 0.23 in the superior to 0.53 in the inferior macular sector. R values for the association between GCIPL thickness and visual sensitivity measurements ranged from 0.15 in the superior to 0.62 in the temporal sector. CONCLUSIONS: The strongest associations between OMAG, GCIPL thickness, and visual sensitivity measurements were found in the inferior macular sector. The association of OMAG with GCIPL thickness measurements was as strong as the association between OMAG and visual sensitivity measurements in the inferior macular sector.

Vitreomacular Changes after Intravitreal Gas Injection for Idiopathic Impending or Early Macular Hole: An Optical Coherence Tomography Study.

PURPOSE: To study the early changes of vitreomacular microstructure by optical coherence tomography (OCT) after intravitreal gas injection for the treatment of idiopathic impending or early full-thickness macular hole (FTMH). METHODS: A retrospective, interventional case series. RESULTS: A total of 21 eyes were included. In the impending macular hole, 8/8 achieved vitreomacular traction (VMT) release, while a macular hole developed in 1 case. On postoperative day 1, the vitreomacular configuration by OCT showed either a flattening (n = 3) or elevation (n = 1) pattern. In early FTMH, vitreomacular separation was achieved in 10/13 cases, but macular hole closure was only observed in 3 cases. On postoperative day 1, only flattening of the vitreomacular configuration was observed (n = 5). Enlargement of the macular hole was found in 4 cases. CONCLUSIONS: VMT separation can be achieved with intravitreal gas injection by mechanically stretching the posterior vitreous cortex, causing either flattening or steepening of the vitreomacular configuration. However, it did not always result in macular hole closure.