Loss Of Contrast Sensitivity Research Articles

A chart-based test of contrast sensitivity in noise: reference ranges, effects of age and optical abnormality

ABSTRACT Clinical relevance Contrast sensitivity plays an important role in the comprehensive assessment of visual function; however, measurement with standard eye charts can be affected by age and optical abnormality. Background This study describes a novel chart-based test of letter contrast sensitivity (CS) in luminance noise (the Illinois Eye and Ear Noise CS test), defines normal reference ranges, estimates test-retest repeatability, and assesses the effects of age and simulated optical abnormalities. Methods Seventy-five individuals with normal visual function (age 18–85 years) participated. Subjects identified letter optotypes that spanned a broad contrast range (0.9% to 59.6%) printed in a book-based test. Letters were presented against a grey background (no-noise condition) and in luminance noise that consisted of light and dark checks (noise condition). A subset of 10 subjects repeated the test to define short-term variability and performed the test under three additional conditions: simulated cataract, +2.00D defocus, and low room illuminance. Results In the no-noise condition, CS was independent of age (mean log CS of 1.74) until approximately 54 years, and declined for older subjects (CS loss of 0.1 log unit/decade). CS measured in noise was independent of age across the range of ages tested (mean log CS of 0.91). The 95% limits of agreement for test-retest repeatability was 0.19 log units. Simulated cataract, +2.00D defocus, and reduced illumination significantly reduced CS in the no-noise condition (F = 102.6, p < 0.001), whereas these optical manipulations did not significantly affect CS in noise (F = 2.58, p = 0.074). Conclusions Measurements of CS in luminance noise may be valuable, as these measures are largely independent of age and certain forms of optical degradation. CS measurements in noise may provide useful insight into visual function in patients who have combined neural and optical abnormality, as noise minimises CS loss from optical defects.

Update on Clinical Trial Endpoints in Gene Therapy Trials for Inherited Retinal Diseases.

Inherited retinal diseases (IRDs) encompass a wide spectrum of rare conditions characterized by diverse phenotypes associated with hundreds of genetic variations, often leading to progressive visual impairment and profound vision loss. Multiple natural history studies and clinical trials exploring gene therapy for various IRDs are ongoing. Outcomes for ophthalmic trials measure visual changes in three main categories-structural, functional, and patient-focused outcomes. Since IRDs may range from congenital with poor central vision from birth to affecting the peripheral retina initially and progressing insidiously with visual acuity affected late in the disease course, typical outcome measures such as central visual acuity and ocular coherence tomography (OCT) imaging of the macula may not provide adequate representation of therapeutic outcomes including alterations in disease course. Thus, alternative unique outcome measures are necessary to assess loss of peripheral vision, color vision, night vision, and contrast sensitivity in IRDs. These differences have complicated the assessment of clinical outcomes for IRD therapies, and the clinical trials for IRDs have had to design novel specialized endpoints to demonstrate treatment efficacy. As genetic engineering and gene therapy techniques continue to advance with growing investment from industry and accelerated approval tracks for orphan conditions, the clinical trials must continue to improve their assessments to demonstrate safety and efficacy of new gene therapies that aim to come to market. Here, we will provide an overview of the current gene therapy approaches, review various endpoints for measuring visual function, highlight those that are utilized in recent gene therapy trials, and provide an overview of stage 2 and 3 IRD trials through the second quarter of 2024.

Subgroup Analysis from a Phase 1/2 Randomized Clinical Trial of 2.6% EDTA Ophthalmic Solution in Patients with Age-Related Cataract

To explore the efficacy of topical 2.6% EDTA ophthalmic solution (C-KAD) as a treatment to improve visual function for the subgroup of patients with loss of contrast sensitivity (CS) due to early-stage age-related cataract. Subgroup analysis of randomized, double-blinded, placebo-controlled, multicenter phase 1/2 clinical trial data. Both eyes of subjects in the intent-to-treat population, with mesopic CS scores between 1 and 7 grating patches (range 0-9, each patch representing 0.15 logCS), at baseline in all five frequencies, were included. The proportion of eyes with clinically significant mesopic CS improvement and mean changes in mesopic CS at spatial frequencies between 1.5 to 18 cycles per degree (cpd), and summary metrics of area under the log CS function (AULCSF), were analyzed. Other exploratory outcomes analyzed included best-corrected visual acuity (BCVA) and lens density for a smaller subgroup of eyes for which Scheimpflug images were available. Forty-one subject eyes were included in the subgroup analysis (C-KAD n = 21, placebo n = 20). The primary endpoint of the proportion of eyes with mesopic CS improvements ≥ 0.30 logCS (equivalent to 100% CS improvement) in at least two of the five spatial frequencies was significantly greater for C-KAD (66.7% vs. 35.0% for placebo, P = .043) at Day 120. C-KAD met the primary protocol endpoint in this subgroup analysis. The proportion of eyes achieving ≥ 0.30 logCS improvement (mesopic) as measured in AULCSF was also significantly greater for C-KAD, with 42.9% compared to 15.0% for placebo (P = .050) at Day 120. The mean change in AULCSF (mesopic) was significantly larger for C-KAD, with 0.25 logCS improvement, versus placebo with 0.06 logCS improvement (P = .020) at Day 120. C-KAD also showed significant mesopic CS improvements at spatial frequencies 3 and 6 cpd, with 0.28 logCS (P = .004) and 0.31 logCS (P = .047) versus placebo at Day 120. Positive BCVA trends and statistical significance in lens density were also observed. A significant treatment effect of C-KAD in visual function and vision quality was observed consistently. These promising results suggest a novel, noninvasive pharmacological treatment to improve vision in patients with early-stage cataract.

Hazard Perception in Visually Impaired Drivers Who Use Bioptic Telescopes.

Bioptic telescopic spectacles can allow individuals with central vision impairment to obtain or maintain driving privileges. The purpose of this study was to (1) compare hazard perception ability among bioptic drivers and traditionally licensed controls, (2) assess the impact of bioptic telescopic spectacles on hazard perception in drivers with vision impairment, and (3) analyze the relationships among vision and hazard detection in bioptic drivers. Visual acuity, contrast sensitivity, and visual field were measured for each participant. All drivers completed the Driving Habits Questionnaire. Hazard perception testing was conducted using commercially available first-person video driving clips. Subjects signaled when they could first identify a traffic hazard requiring a change of speed or direction. Bioptic drivers were tested with and without their bioptic telescopes in alternating blocks. Hazard detection times for each clip were converted to z-scores, converted back to seconds using the average response time across all videos, and then compared among conditions. Twenty-one bioptic drivers and 21 normally sighted controls participated in the study. The hazard response time of bioptic drivers was improved when able to use the telescope (5.4 ± 1.4 seconds vs 6.3 ± 1.8 seconds without telescope); however, it remained significantly longer than for controls (4.0 ± 1.4 seconds). Poorer visual acuity, contrast sensitivity, and superior visual field sensitivity loss were related to longer hazard response times. Drivers with central vision loss had improved hazard response times with the use of bioptic telescopic spectacles, although their responses were still slower than normally sighted control drivers. The use of a bioptic telescope by licensed, visually impaired drivers improves their hazard detection speed on a video-based task, lending support to their use on the road.

Contrast sensitivity is resilient to induced fast periodic defocus oscillations.

This study investigates the potential effects of periodic defocus oscillations on contrast sensitivity. Sinusoidal fluctuations at 5, 15, and 25 Hz, with defocus peak-to-valley values ranging from 0.15 to 3 D, were induced by means of a focus-tunable lens after calibrating its dynamic behavior. Monocular contrast sensitivity was measured on five young emmetropic subjects. The experimental data shows that contrast sensitivity loss due to defocus fluctuations is low for a wide range of frequencies and amplitudes. Only for the more severe case studied (25 Hz, ± 1.5 D) contrast threshold showed a clear increase in most subjects. Qualitative comparison of the empirical data with a simulation of modulation loss due to time integration of defocused retinal point spread functions, suggests a short integration time by the eye for defocus blur, around or even below a hundredth of a second.

POU6F2, a risk factor for glaucoma, myopia and dyslexia, labels specific populations of retinal ganglion cells

Pou6f2 is a genetic connection between central corneal thickness (CCT) in the mouse and a risk factor for developing primary open-angle glaucoma. POU6F2 is also a risk factor for several conditions in humans, including glaucoma, myopia, and dyslexia. Recent findings demonstrate that POU6F2-positive retinal ganglion cells (RGCs) comprise a number of RGC subtypes in the mouse, some of which also co-stain for Cdh6 and Hoxd10. These POU6F2-positive RGCs appear to be novel of ON–OFF directionally selective ganglion cells (ooDSGCs) that do not co-stain with CART or SATB2 (typical ooDSGCs markers). These POU6F2-positive cells are sensitive to damage caused by elevated intraocular pressure. In the DBA/2J mouse glaucoma model, heavily-labeled POU6F2 RGCs decrease by 73% at 8 months of age compared to only 22% loss of total RGCs (labeled with RBPMS). Additionally, Pou6f2−/− mice suffer a significant loss of acuity and spatial contrast sensitivity along with an 11.4% loss of total RGCs. In the rhesus macaque retina, POU6F2 labels the large parasol ganglion cells that form the magnocellular (M) pathway. The association of POU6F2 with the M-pathway may reveal in part its role in human glaucoma, myopia, and dyslexia.

Ocular toxicity of psychotropic medications in a tertiary hospital in Lagos, Nigeria.

Objective: This study aimed to determine the ocular toxicity of the psychotropic drugs used by patients and to proffer suggestions on how to prevent visual impairment or blindness in patients on antipsychotics. Methodology: This was a prospective, hospital-based cross-sectional study. Participants were adult patients between 18 and 70 years, diagnosed with psychosis, and who had been on antipsychotic medications for at least one year. All the recruited participants had an examination of the anterior and posterior segments of the eyes done. Schirmer's test, Tear film Break-up time (TBUT), Central Corneal thickness (CCT), Colour vision test, and Contrast sensitivity test were done. The collected data was analyzed using IBM SPSS 28.0. Results: The study enrolled patients who were mainly females (55.1%). The highest age group of the cases was 29-38 years (29.7%). The examination of the eyes and investigations revealed that 10.2% of the respondents on antipsychotics had color vision deficiency and 25.4% - loss of contrast sensitivity. Lid pigmentation was observed in 20.3% and cataract in 32.2%. Degeneration of the peripheral retina was observed in 4.2% of patients on antipsychotic medication. Schirmer's test showed mild, moderate, and severe dry eyes in 11%,17.8%, and 20.3% of the participants respectively. The test for Central Corneal Thickness (CCT) showed 50.0% of the respondents had a thin cornea and 24.6% had a thick cornea. 17.8% of the surveyed respondents manifested high eye pressure. Discussion: Psychotropics are the gold standard for the treatment of psychotic episodes and disorders. The choice of drug, dosing, and mode of administration depends on the severity of the psychotic disorder. Higher doses of psychotropics were reported to cause toxicity in different organs in the body including the eyes, especially on long-term use and high dosage and this can affect the quality of life of the individual negatively. Conclusion: The earliest and most prominent side effect seen in patients on psychotic medication was dry eyes. There were a few cases of blinding eye diseases like glaucoma, and cataract. For these reasons, ophthalmic assessments should be included as part of the management of psychiatric patients early at the start of antipsychotic treatment. Abbreviations: FGA = First Generation Antipsychotics, SGA = Second Generation Antipsychotics, TCAs = Tricyclic Antidepressants, CCT = Central Corneal Thickness, IOP = Intraocular Pressure, TBUT =Tear film Break-up Time, BIO = Binocular Indirect Ophthalmoscope.

Significant loss of retinal nerve fibre layer and contrast sensitivity in people with well controlled HIV disease: implications for aging with HIV.

Antiretroviral therapy has decreased the prevalence of retinal opportunistic infections in people living with HIV (PLWH). However, abnormalities in visual function are evident and may be associated with an early onset of aging in PLWH. In this study, we examined the Retinal Nerve Fibre Layer (RNFL) thickness and visual function in PLWH and HIV non-infected controls in Malaysia. Cross-sectional study. Two hundred and two (202) PLWH without retinal opportunistic infection and 182 age-matched, HIV seronegative individuals were enrolled. PLWH were recruited from the Infectious Disease clinic at the University Malaya Medical Centre. Controls were recruited among the hospital staff and community volunteers. RNFL thickness was measured with spectral domain optical coherence tomography (SDOCT). Visual functions include visual acuity using LogMAR chart and contrast sensitivity using Pelli- Robson Chart. All PLWH (mean age 46.1 years ± 9.9 years) in the study were on ART and 61.2% had a CD4+ T-cell count more than 500 cell/μl. The mean visual acuity was similar between the two groups (LogMAR 0.05 vs. 0.07, p = 0.115). Contrast sensitivity was lower in PLWH compared to HIV seronegative individuals (1.90 vs 1.93, p = 0.032). RNFL thickness was significantly thinner in the temporal quadrant for PLWH compared to controls (68.89 μm vs 74.08 μm, p = 0.001). Changes in RNFL thickness and contrast sensitivity were seen in PLWH despite their relatively young age and well controlled HIV disease. The changes reflect structural and functional deficits, and could have long-term implications on their health trajectory.

Mechanical Regulation of Retinal Vascular Inflammation and Degeneration in Diabetes.

Vascular inflammation is known to cause degeneration of retinal capillaries in early diabetic retinopathy (DR), a major microvascular complication of diabetes. Past studies investigating these diabetes-induced retinal vascular abnormalities have focused primarily on the role of molecular or biochemical cues. Here we show that retinal vascular inflammation and degeneration in diabetes are also mechanically regulated by the increase in retinal vascular stiffness caused by overexpression of collagen-crosslinking enzyme lysyl oxidase (LOX). Treatment of diabetic mice with LOX inhibitor β-Aminopropionitrile (BAPN) prevented the increase in retinal capillary stiffness, vascular ICAM-1 overexpression, and leukostasis. Consistent with these anti-inflammatory effects, BAPN treatment of diabetic mice blocked the upregulation of proapoptotic caspase-3 in retinal vessels, which concomitantly reduced retinal capillary degeneration, pericyte ghost formation, and the diabetes-induced loss of contrast sensitivity in these mice. Finally, our in vitro studies indicate that retinal capillary stiffening is sufficient to increase the adhesiveness and neutrophil elastase-induced death of retinal endothelial cells. By uncovering a link between LOX-dependent capillary stiffening and the development of retinal vascular and functional defects in diabetes, these findings offer a new insight into DR pathogenesis that has important translational potential.

Population prevalence of dual sensory loss in community-dwelling US adults 71 years and older: Evidence from the National Health and Aging Trends Study.

Existing estimates for the prevalence of dual sensory loss (vision and hearing) among older adults are either based on self-reported measures or aggregated for older age groups. Current and detailed estimates based on objective measures are needed for public health, clinical, and policy decision-making. We estimated the prevalence of dual sensory loss (DSL) using National Health Aging Trends Study (NHATS) Round 11 data (2021). We restricted to community-dwelling adults aged ≥71 years with complete sensory testing data (N = 2579). Hearing loss was defined by a 4-frequency (0.5, 1, 2 and 4 kHz) pure tone average for the better-hearing ear (>25 decibel hearing level). Vision loss was defined by the presence of distance, near (logarithm of the minimum angle of resolution >0.30), or contrast sensitivity loss (log contrast sensitivity <1.55). Participants were categorized into three groups: no sensory loss, single sensory loss (vision or hearing loss), and DSL (hearing and vision). Sensory loss prevalence was estimated by age group and sociodemographic characteristics. In weighted analyses, among older Medicare beneficiaries (53% female, 7% Black, 6% Hispanic), 28% had no sensory loss and 22% had DSL. Prevalence of DSL increased with age. Most adults aged ≥90 years experienced DSL (59%), as opposed to single (39%) or no sensory loss (2%). DSL prevalence was greater among older adults with low education attainment (34%) and household income (43%). A higher proportion of older adults with a college education (17%), or from wealthier households (16%), had no sensory loss. One in 5 community-dwelling Medicare beneficiaries aged ≥71 years have DSL, increasing to 3 in 5 for those aged ≥90 years. Prevalence is higher among older adults with low education attainment and from low-income households, characteristics associated with low treatment. Policies increasing access and affordability of vision and hearing care could benefit millions of older Americans experiencing sensory loss.

Contour integration deficits at high spatial frequencies in children treated for anisometropic amblyopia.

This study was conducted to reexamine the question of whether children treated for anisometropic amblyopia have contour integration deficits. To do so, we used psychophysical methods that require global contour processing while minimizing the influence of low-level deficits: visibility, shape perception, and positional uncertainty. Thirteen children with anisometropic amblyopia (age: 10.1 ± 1.8 years) and thirteen visually normal children (age: 10.8 ± 2.0 years) participated in this study. The stimuli were closed figures made up of Gabor patches either in noise or on a blank field. The contrast thresholds to detect a circular contour on a blank field, as well as the thresholds of aspect ratio and contour element number to discriminate a circular or elliptical contour in noise, were measured at Gabor spatial frequencies of 1.5, 3, and 6 cpd for amblyopic eyes (AEs), fellow eyes (FEs), and normal control eyes. Visual acuities and contrast sensitivity functions for AEs and FEs and the Randot stereoacuity were measured before testing. The AEs showed contrast deficits and degraded shape perception compared to the FEs at higher spatial frequencies (6 cpd). When the influence of abnormal contrast sensitivity and shape perception were minimized, the AEs showed contour integration deficits at spatial frequencies 3 and 6 cpd. These deficits were not related to basic losses in contrast sensitivity and acuity, stereoacuity, and visual crowding. Besides, no significant difference was found between the fellow eyes of the amblyopic children and the normal control eyes in the performance of contour integration. After eliminating or compensating for the low-level deficits, children treated for anisometropic amblyopia still show contour integration deficits, primarily at higher spatial frequencies, which might reflect the deficits in global processing caused by amblyopia. Contour integration deficits are likely independent of spatial vision deficits. Refractive correction and/or occlusion therapies may not be sufficient to fully restore contour integration deficits, which indicates the need for the development of clinical treatments to recover these deficits.

Central Visual Attention in Primary Open-angle Glaucoma

SIGNIFICANCE To better understand the implication of a potential cognitive change in glaucoma, patients were stimulated in central visual areas considered functionally normal to discard an effect due to the loss of vision during an attentional task. The outcome might improve the follow-up on the impact of the pathology. PURPOSE This study aimed to evaluate the effect of primary open-angle glaucoma on the visual attention system by recording responses of behavioral and oculomotor strategies. METHODS We included 20 individuals with primary open-angle glaucoma (62.1 ± 7.2 years old), 18 age-matched control subjects (58.4 ± 7.2 years old), and 20 young control subjects (25.7 ± 3.5 years old). The procedure consisted of visual (eye-tracking recordings) and manual detection of a target. All participants had to detect a square with a vertical bar within distractors (squares, triangles, and circles with a horizontal or vertical bar) of identical size of 1.6 × 1.6° visual angle. The shapes were displayed concentrically on a radius of 5° of visual angle. All participants were tested to ensure that their visual field sensitivity was normal within ±5° central vision. RESULTS In responding manually, glaucoma participants were slower than age-matched control subjects (1723 ± 488 vs. 1263 ± 385 milliseconds; P &lt; .01). Eye-tracking recordings showed that glaucoma participants found the target within the same time frame as age-matched control subjects. Compared with the young group, the scanpath length and average fixation duration on distractors were significantly longer for the glaucoma patients (+235 pixels, +104 milliseconds) and the age-matched control participants (+120 pixels, +39 milliseconds). Impaired contrast sensitivity was correlated with longer response time, longer scanpath, and longer fixation on distractors. CONCLUSIONS Glaucoma affects the manual response times in a visual attention task, but patients can visually detect the target as quickly as age-matched control subjects. Different clinical factors predicted the performances. The age of the patients was associated with longer scanpath. The visual field loss (mean deviation) was linked with longer visual response time. The loss of contrast sensitivity predicted the behavioral change on fixation duration to the distractors, global response time, visual response time, and scanpath length.

Absolute prediction of relative changes in contrast sensitivity with aberrations using a single metric of retinal image quality.

Metrics of retinal image quality predict optimal refractive corrections and correlate with visual performance. To date, they do not predict absolutely the relative change in visual performance when aberrations change and therefore need to be a-posteriori rescaled to match relative measurements. Here we demonstrate that a recently proposed metric can be used to predict, in an absolute manner, changes in contrast sensitivity measurements with Sloan letters when aberrations change. Typical aberrations of young and healthy eyes (for a 6 mm pupil diameter) were numerically introduced, and we measured the resulting loss in contrast sensitivity of subjects looking through a 2 mm diameter pupil. Our results suggest that the metric can be used to corroborate measurements of visual performance in clinical practice, thereby potentially improving patient follow-ups.

Effects of short-term -30° HDT on contrast sensitivity.

Potential cognitive and physiological alterations due to space environments have been investigated in long-term space flight and various microgravity-like conditions, for example, head-down tilt (HDT), confinement, isolation, and immobilization. However, little is known about the influence of simulated microgravity environments on visual function. Contrast sensitivity (CS), which indicates how much contrast a person requires to see a target, is a fundamental feature of human vision. Here, we investigated how the CS changed by 1-h -30° HDT and determined the corresponding mechanisms with a perceptual template model. A quick contrast sensitivity function procedure was used to assess the CS at ten spatial frequencies and three external noise levels. We found that (1) relative to the + 30° head-up tilt (HUT) position, 1-h -30° HDT significantly deteriorated the CS at intermediate frequencies when external noise was present; (2) CS loss was not detected in zero- or high-noise conditions; (3) HDT-induced CS loss was characterized by impaired perceptual template; and (4) self-reported questionnaires indicated that subjects felt less pleasure and more excitement, less comfort and more fatigued by screen light, less comfort in the area around the eye, and serious symptoms such as piercing pain, blur acid, strain, eye burning, and dizziness after HDT. These findings improve our understanding of the negative effects of simulated microgravity on visual function and elucidate the potential risks of astronauts during space flight.

Visual Characteristics of Adults with Long-Standing History of Dietary Exposure to Mercury in Grassy Narrows First Nation, Canada.

Since the 1960s, Grassy Narrows First Nation (Ontario, Canada) has been exposed to methyl mercury (Hg) through fish consumption, resulting from industrial pollution of their territorial waters. This cross-sectional study describes the visual characteristics of adults with documented Hg exposure between 1970 and 1997. Oculo-visual examinations of 80 community members included visual acuity, automated visual fields, optical coherence tomography [OCT], color vision and contrast sensitivity. Median age was 57 years (IQR 51-63) and 55% of participants were women. Median visual acuity was 0.1 logMAR (Snellen 6/6.4; IQR 0-0.2). A total of 26% of participants presented a Visual Field Index inferior to 62%, and qualitative losses assessment showed concentric constriction (18%), end-stage concentric loss (18%), and complex defects (24%). On OCT, retinal nerve fiber layer scans showed 74% of participants within normal/green range. For color testing with the Hardy, Rand, and Rittler test, 40% presented at least one type of color defect, and with the Lanthony D-15 test, median color confusion index was 1.59 (IQR 1.33-1.96). Contrast sensitivity showed moderate loss for 83% of participants. These findings demonstrate important loss of visual field, color vision, and contrast sensitivity in older adults in a context of long-term exposure to Hg in Grassy Narrows First Nation.

Objective cataract grading methods and expected contrast sensitivity reestablishment with multifocal intraocular lenses.

To determine the cut-off points for age and metrics provided by cataract grading objective systems for which a reestablishment in contrast sensitivity(CS) is expected after multifocal intraocular lens(MIOL) implantation. One hundred seven subjects were included in this retrospective analysis carried out during the screening for presbyopia and cataract surgery. Monocular distance corrected contrast sensitivity defocus curve (CSDC) and visual acuity were measured, and crystalline lens sclerosis was graded with three objective metrics: Ocular Scatter Index(OSI), Dysfunctional Lens Index(DLI) and Pentacam Nucleus Staging(PNS). A CS value of 0.8 logCS at far distance, following published literature on this matter, was selected to compute the cut-off that maximized the detection of eyes exceeding this value at the preoperative screening, either for age or objective metrics. The CDCS showed a stronger correlation than CDVA with objective grading methods, whereas all objective metrics were significantly correlated between them (p < 0.05). The cut-offs for age, OSI, DLI and PNS were ≤ 62, ≤ 1.25, ≥ 7.67 and ≤ 1, respectively. The OSI provided the highest area under the receiver operating characteristic curve (0.85) followed by the age (0.84), DLI (0.74) and PNS (0.63). Surgeons conducting clear lens exchange should communicate the possible distance CS loss after surgery with MIOL implantation according to the previous described cut-offs points. Age in combination with any cataract grading objective system is recommended to detect possible inconsistencies.

Effect of glare on contrast sensitivity at various external noise levels

BackgroundGlare can reduce a driver's visual performance, increasing the risk of traffic accidents. The ability of the visual system to process spatial information can be assessed with the contrast sensitivity function (CSF); the CSF is decreased by glare. ObjectiveThe current study had three key aims: to examine whether and how glare-induced contrast sensitivity (CS) loss is modulated by spatial frequency (between 0.5 and 16 cycles per degree) and external noise (zero, low, or high); to evaluate subjective feelings of discomfort under different glare conditions; and to investigate the underlying mechanisms with a perceptual template model (PTM). MethodsParticipants completed a contrast detection task with quick CSF algorithm and reported their subjective feelings under nonglare, steady-glare, and transient-glare conditions. ResultsSteady and transient glare both reduced CS to comparable degrees. When external noise was absent, the CS reduction was largely dependent on spatial frequency, with a larger amount of CS loss at lower spatial frequencies. When external noise was present, the CS reduction was independent of spatial frequency. In addition, the reduction in the area under the log CS function (AULCSF) under steady-glare condition was roughly the same as that under transient-glare condition, regardless of external noise. However, participants reported greater discomfort under transient-glare condition than under steady-glare condition. Moreover, the AULCSF was reduced more under the zero-noise condition than under noise conditions. The PTM suggested that an increase in internal noise and an impaired perceptual template explained the glare-induced CS loss. ConclusionThe glare-induced CS loss was modulated by spatial frequency and external noise. Steady glare and transient glare affect CS to a similar extent, but steady glare produces less discomfort. Glare attenuates signals and weakens noise exclusion ability. ApplicationThis study advances our knowledge on glare-induced CS loss and its underlying mechanisms. The qCSF procedure with external noise should be utilized in future studies to investigate the effect of various light sources on visual function.

Mitochondrial optic neuropathies (MON)

AbstractWhen we first proposed the term, Mitochondrial Optic Neuropathies (MON) (Sadun AA. Mitochondrial optic neuropathies. J Neurol Neurosurg Psychiatry. 2002 Apr;72(4):423–5.), it may have seemed odd. The paradigm before then was that many things could injure the optic nerves, and genetic, nutritional and many toxic causes made the list alongside tumours, infections, inflammations, etc. Our experiences in Cuba changed this mode of thinking. There, an epidemic of optic neuropathy (CEON) was found to exist among those consuming small amounts of methanol in the presence of folic acid deficiency. This demonstrated the convergence of toxic and nutritional causes that affected the same (oxidative‐phosphorylation) systems. Several publications have demonstrated that certain metabolic optic neuropathies are more likely in the setting of genetic predispositions. In short, asymptomatic carriers of well characterized genetic disorders such as Leber's Hereditary Optic Neuropathy (LHON), may lose vision when additionally stressed by exposures to certain drugs like ethambutol or to nutritional deficiencies. Several studies have revisited the original diagnosis of tobacco‐alcohol amblyopia (their term) and found about 20% harboured LHON mtDNA mutations (Cullom, et al., Arch Ophthalmol. 1993 Nov;111(11):1482–5).We hereby present a framework for seeing many forms of metabolic (hereditary, nutritional and toxic) optic neuropathies as related. One unifier is the stereotypic clinical presentation. These patients have, after a while, very symmetric visual losses. The loss of visual acuity, colour vision, and high spatial frequency contrast sensitivity, reflects a pair of symmetrical central or cecocentral scotomas. These aforementioned functional defects are to be expected by the equally characteristic anatomical loss of the small fibres of the papillo‐macular bundle (PMB) which also explains the temporal optic disc pallor. The other unifier is that the molecular injuries cause impairments of mitochondria, and specifically oxidative phosphorylation (Ox‐Phos). We and others have further demonstrated that this especially entails the accumulation of reactive oxygen species (ROS) more than a problem with bioenergetics. This also explains the particular predilection for injury of the smallest and unmyelinated fibres of the PMB.Several drugs are causes or additional risk factors in MON. Remarkably, most drugs that are best demonstrated to injure the optic nerve are also understood to impair mitochondria and Ox‐Phos. These include ethambutol and linezolid, chloramphenicol, streptomycin, and some antivirals (Wang and Sadun, J Neuroophthalmol. 2013 Jun;33(2):172–8). These drugs can also be regarded, in addition to heavy smoking and binge drinking of alcohol, as exogenous sources of ROS that are likely to bring out Type II LHON (vs Type I LHON which is apt to be genetic/genetic, and occurs at an early age more acutely).In general, MON represent the unique susceptibility of the optic nerve, and most specifically, the small fibres of the PMB, to the ROS that are generated when mitochondrial Ox‐Phos is defective. When the ROS threshold is exceeded, these fibres are the first to decompensate and this leads to a remarkably consistent phenotype.

Achromatic and chromatic perceived contrast are reduced in the visual periphery.

The loss of contrast sensitivity with eccentricity is well documented, and is steeper for higher spatial frequencies, and for L/M cone-opponent stimuli compared to achromatic or S-cone-opponent. Here, we ask how perceived contrast depends on eccentricity when stimuli are presented at suprathreshold contrasts, and test two opposing predictions. Contrast constancy predicts no loss in perceived contrast across the visual field regardless of changes in detection threshold - appearance depends only on physical contrast. Conversely, perceived contrast may be scaled in the same way as detection threshold, reflecting the proportional increase in stimulus contrast above threshold. We measured perceived contrast for L/M cone-opponent, S-cone opponent, and Ach stimuli up to 18 degrees of eccentricity using a 2AFC contrast matching method between fovea and periphery. We tested a range of reference contrasts from low (close to detection threshold) to high suprathreshold contrasts and we relate suprathreshold perceived contrast to measured detection thresholds. We find evidence for a hybrid model in which apparent contrast is reduced with eccentricity for stimuli in the low and mid contrast range, with contrast constancy only attained at the highest contrasts. When equated for similar sensitivity losses, we find no difference between chromatic and Ach contrast responses.

Tandem pore domain acid-sensitive K channel 3 (TASK-3) regulates visual sensitivity in healthy and aging retina.

Retinal ganglion cells (RGCs) not only collect but also integrate visual signals and send them from the retina to the brain. The mechanisms underlying the RGC integration of synaptic activity within retinal circuits have not been fully explored. Here, we identified a pronounced expression of tandem pore domain acid-sensitive potassium channel 3 (TASK-3), a two–pore domain potassium channel (K2P), in RGCs. By using a specific antagonist and TASK-3 knockout mice, we found that TASK-3 regulates the intrinsic excitability and the light sensitivity of RGCs by sensing neuronal activity–dependent extracellular acidification. In vivo, the blockade or loss of TASK-3 dampened pupillary light reflex, visual acuity, and contrast sensitivity. Furthermore, overexpressing TASK-3 specifically in RGCs using an adeno-associated virus approach restored the visual function of TASK-3 knockout mice and aged mice where the expression and function of TASK-3 were reduced. Thus, our results provide evidence that implicates a critical role of K2P in visual processing in the retina.