Fundus Albipunctatus Associated with Biallelic LRAT Gene Mutation: A Case Report with Long-Term Follow-Up.

This case report presents a 26-year-old female patient diagnosed with fundus albipunctatus (FAP), a rare form of congenital stationary night blindness. The patient's clinical history and retinal findings spanning 23 years are consistent with FAP. The patient has profound night blindness, photophobia, and mild color vision changes with preserved best-corrected visual acuity (BCVA). Small white dots are present throughout the fundus, sparing the central macula. Electroretinograms (ERG) are consistent with congenital stationary night blindness (CSNB) and suggest a lack of rod response. Ophthalmic imaging has remained stable over time. Genetic testing revealed two biallelic missense mutations in the LRAT gene, c.197G>A (p.Gly66Glu) and c.557A>C (p.Lys186Thr). LRAT mutations are known to contribute to other retinal conditions but have not been previously associated with FAP. While there are currently no available treatments for FAP, this report expands our understanding of the genetic landscape of FAP to include LRAT and provides clinical data to support this finding.

ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update).

This document developed by the International Society for Clinical Electrophysiology of Vision (ISCEV) provides guidance for calibration and verification of stimulus and recording systems specific to clinical electrophysiology of vision. This guideline provides additional information for those using ISCEV Standards and Extended protocols and supersedes earlier Guidelines. The ISCEV guidelines for calibration and verification of stimuli and recording instruments (2023 update) were approved by the ISCEV Board of Directors 01, March 2023.

New Insights Into Pentosan Polysulfate Maculopathy.

BACKGROUND AND OBJECTIVE: To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing. PATIENTS AND METHODS: Retrospective case-series of four patients from two academic centers evaluated with multimodal imaging, electrophysiology, dark adaptometry (DA), and genetic testing. RESULTS: Median age was 58 years, exposure to PPS was 18.5 years, and cumulative dose of was 2,025 grams. Seven of eight eyes had visual acuity of 20/40 or better. Optical coherence tomography (OCT) angiography demonstrated increased choriocapillaris flow voids (54.25%) in cases compared to controls (13.2%). Two subjects had abnormal foveal avascular zone configurations. Two subjects demonstrated collapse of the retinal pigment epithelium nodular excrescences and progressive retinal thinning over 4 to 5 years on OCT. Electrophysiology was normal (3/3 patients), but DA was delayed (2/2 patients). CONCLUSIONS: The authors describe novel findings of PPS maculopathy, including flow voids in the choriocapillaris. Progressive retinal thinning may suggest a secondary retinal effect. These findings may improve understanding of the pathophysiology. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:13-22.].

VEP estimation of visual acuity: a systematic review.

PURPOSE: Visual evoked potentials (VEPs) can be used to measure visual resolution via a spatial frequency (SF) limit as an objective estimate of visual acuity. The aim of this systematic review is to collate descriptions of the VEP SF limit in humans, healthy and disordered, and to assess how accurately and precisely VEP SF limits reflect visual acuity. METHODS: The protocol methodology followed the PRISMA statement. Multiple databases were searched using "VEP" and "acuity" and associated terms, plus hand search: titles, abstracts or full text were reviewed for eligibility. Data extracted included VEP SF limits, stimulus protocols, VEP recording and analysis techniques and correspondence with behavioural acuity for normally sighted healthy adults, typically developing infants and children, healthy adults with artificially degraded vision and patients with ophthalmic or neurological conditions. RESULTS: A total of 155 studies are included. Commonly used stimulus, recording and analysis techniques are summarised. Average healthy adult VEP SF limits vary from 15 to 40 cpd, depend on stimulus, recording and analysis techniques and are often, but not always, poorer than behavioural acuity measured either psychophysically with an identical stimulus or with a clinical acuity test. The difference between VEP SF limit and behavioural acuity is variable and strongly dependent on the VEP stimulus and choice of acuity test. VEP SF limits mature rapidly, from 1.5 to 9 cpd by the end of the first month of life to 12-20 cpd by 8-12 months, with slower improvement to 20-40 cpd by 3-5 years. VEP SF limits are much better than behavioural thresholds in the youngest, typically developing infants. This difference lessens with age and reaches equivalence between 1 and 2 years; from around 3-5 years, behavioural acuity is better than the VEP SF limit, as for adults. Healthy, artificially blurred adults had slightly better behavioural acuity than VEP SF limits across a wide range of acuities, while adults with heterogeneous ophthalmic or neurological pathologies causing reduced acuity showed a much wider and less consistent relationship. For refractive error, ocular media opacity or pathology primarily affecting the retina, VEP SF limits and behavioural acuity had a fairly consistent relationship across a wide range of acuity. This relationship was much less consistent or close for primarily macular, optic nerve or neurological conditions such as amblyopia. VEP SF limits were almost always normal in patients with non-organic visual acuity loss. CONCLUSIONS: The VEP SF limit has great utility as an objective acuity estimator, especially in pre-verbal children or patients of any age with motor or learning impairments which prevent reliable measurement of behavioural acuity. Its diagnostic power depends heavily on adequate, age-stratified, reference data, age-stratified empirical calibration with behavioural acuity, and interpretation in the light of other electrophysiological and clinical findings. Future developments could encompass faster, more objective and robust techniques such as real-time, adaptive control. REGISTRATION: International prospective register of systematic reviews PROSPERO ( https://www.crd.york.ac.uk/PROSPERO/ ), registration number CRD42018085666.

ISCEV extended protocol for VEP methods of estimation of visual acuity.

The International Society for Clinical Electrophysiology of Vision (ISCEV) standard for visual evoked potentials (VEPs) describes a minimum procedure for clinical VEP testing and encourages more extensive testing. This ISCEV extended protocol is an extension to the VEP standard. It describes procedures for recording multiple VEPs to a range of sizes of pattern stimuli to establish the VEP spatial frequency limit (threshold) and for relating this limit to visual acuity.

Giving Support and Suicidal Ideation in Older Adults with Vision-Related Diagnoses.

Objectives: Visual impairment in older adults may increase risk for depression and suicide. Research suggests that giving support to others may be associated with lower depressive symptoms in older adults, but much of the research has been in non-clinical populations. Furthermore, there is limited research on giving support and suicide risk.Methods: Using a sample of older adults with vision-related diagnoses (N = 101), this study investigated the association between informal support giving (unpaid support given to family, friends, or neighbors) and formal support giving (volunteering) on depressive symptoms and suicidal ideation. Linear regressions examined the relation between support giving and depression, and logistic regressions examined the relation between support giving and suicidal ideation.Results: Greater informal support giving was related to lower likelihood of reported suicidal ideation (OR: .82, 95% CI: .68-.99, p = .04), whereas volunteer activity was not significantly related to suicidal ideation. Neither volunteer behavior nor informal support giving was related to depressive symptoms.Conclusions: Providing informal support was associated with lower likelihood of endorsing suicidal ideation in older adults with vision impairment.Clinical Implications: Informal support giving may be a target for decreasing suicidal ideation among older adults with health impairments.

Predicting visual function after an ocular bee sting.

PURPOSE: To report a case of toxic optic neuropathy caused by an ocular bee sting. METHODS: Case report and literature review. RESULTS: A 44-year-old female presented with no light perception vision 2 days after a corneal bee sting in her right eye. She was found to have diffuse cornea edema with overlying epithelial defect and a pinpoint penetrating laceration at 6 o'clock. There was an intense green color to the cornea. The pupil was fixed and dilated with an afferent pupillary defect. A small hyphema was seen, and a dense white cataract had formed. A diagnosis of toxic endophthalmitis with associated toxic optic neuropathy was made. The patient underwent pars plana vitrectomy and lensectomy with anterior chamber washout. She was also placed on systemic broad-spectrum antibiotics. She had noted clinical improvement over the course of her hospitalization and was discharged with light perception vision. A corneal opacity precluded viewing of the fundus. We utilized ganzfeld electroretinography and flash visual evoked potentials (2 and 10 Hz) to assess the visual function. Both tests were normal and predicted improvement following restorative surgery. She underwent a secondary lens implantation with penetrating keratoplasty 7 months later. This was followed by an epiretinal membrane peel 1 year after the bee sting. Her best corrected visual acuity improved to 20/80. CONCLUSION: Toxic endophthalmitis and toxic optic neuropathy can be complications of ocular bee sting. We discuss the management of this rare occurrence and the role of electroretinographic testing and visual evoked potentials in predicting visual outcome.

Effects of Lighting on Reading Speed as a Function of Letter Size.

OBJECTIVE: We sought to determine under what conditions brighter lighting improves reading performance. METHOD: Thirteen participants with typical sight and 9 participants with age-related macular degeneration (AMD) read sentences ranging from 0.0 to 1.3 logMAR under luminance levels ranging from 3.5 to 696 cd/m². RESULTS: At the dimmest luminance level (3.5 cd/m²), reading speeds were slowest at the smaller letter sizes and reached an asymptote for larger sizes. When luminance was increased to 30 cd/m², reading speed increased only for the smaller letter sizes. Additional lighting did not increase reading speeds for any letter size. Similar size-related effects of luminance were observed in participants with AMD. CONCLUSION: In some instances, performance on acuity-limited tasks might be improved by brighter lighting. However, brighter lighting does not always improve reading; the magnitude of the effect depends on the text size and the relative changes in light level.

Efferent influences on the bioelectrical activity of the retina in primates.

PURPOSE: The existence of retinopetal (sometimes referred to as "efferent" or "centrifugal") axons in the mammalian optic nerve is a topic of long-standing debate. Opposition is fading as efferent innervation of the retina has now been widely documented in rodents and other animals. The existence and function of an efferent system in humans and non-human primates has not, though, been definitively established. Such a feedback pathway could have important functional, clinical, and experimental significance to the field of vision science and ophthalmology. METHODS: Following a comprehensive literature review (PubMed and Google Scholar, until July 2016), we present evidence regarding a system that can influence the bioelectrical activity of the retina in primates. RESULTS: Anatomical and physiological evidences are presented separately. Improvements in histological staining and the advent of retrograde nerve fiber tracers have allowed for more confidence in the identification of efferent optic nerve fibers, including back to their point of origin. CONCLUSION: Even with the accumulation of more modern anatomical and physiological evidence, some limitations and uncertainties about crucial details regarding the origins and role of a top-down, efferent system still exist. However, the summary of the evidence from earlier and more modern studies makes a compelling case in support of such a system in humans and non-human primates.

ISCEV standard for clinical visual evoked potentials: (2016 update).

Visual evoked potentials (VEPs) can provide important diagnostic information regarding the functional integrity of the visual system. This document updates the ISCEV standard for clinical VEP testing and supersedes the 2009 standard. The main changes in this revision are the acknowledgment that pattern stimuli can be produced using a variety of technologies with an emphasis on the need for manufacturers to ensure that there is no luminance change during pattern reversal or pattern onset/offset. The document is also edited to bring the VEP standard into closer harmony with other ISCEV standards. The ISCEV standard VEP is based on a subset of stimulus and recording conditions that provide core clinical information and can be performed by most clinical electrophysiology laboratories throughout the world. These are: (1) Pattern-reversal VEPs elicited by checkerboard stimuli with large 1 degree (°) and small 0.25° checks. (2) Pattern onset/offset VEPs elicited by checkerboard stimuli with large 1° and small 0.25° checks. (3) Flash VEPs elicited by a flash (brief luminance increment) which subtends a visual field of at least 20°. The ISCEV standard VEP protocols are defined for a single recording channel with a midline occipital active electrode. These protocols are intended for assessment of the eye and/or optic nerves anterior to the optic chiasm. Extended, multi-channel protocols are required to evaluate postchiasmal lesions.

Visual function affects prosocial behaviors in older adults.

Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

Health-related quality of life after surgical removal of an eye.

PURPOSE: This study compared the general health-related quality of life (HRQOL) and the vision-specific HRQOL in patients following the surgical removal of 1 eye who had good vision in the remaining eye to a group of binocular patients with good vision in OU. METHODS: The Medical Outcomes Study Short Form 12 and the National Eye Institute Visual Function Questionnaire HRQOL surveys were administered to 29 patients who had surgical removal of an eye who attended an ocular prosthetics clinic and to 25 binocular persons who accompanied a patient. All subjects in each group had best-corrected visual acuity of 20/40 or better. Overall statistical significance was tested using Cramer's V followed by individual t tests for independent groups for each of the scales on the 2 questionnaires to determine whether the means between the 2 groups differed statistically. RESULTS: The patient group had a mean age of 50.98 years (range, 19-76 years). The control group had a mean age of 49.46 years (range, 18-76 years). The mean time after loss of vision was 28.03 years (range, 1-71 years), and the mean time from surgical removal of the eye was 23.6 years (range, 0.5-59.5 years). There was an overall significant difference between the 2 groups on the 15 derived subscales of the 2 forms (Cramer's V, p = 0.0025). Three general HRQOL subscales (Short Form 12-mental component summary, Short Form 12 physical component summary, and National Eye Institute Visual Function Questionnaire-General Health) showed no differences between the 2 groups (p = 0.48, p = 0.81, and p = 0.78, respectively). Three of the 12 vision-specific National Eye Institute Visual Function Questionnaire subscales demonstrated statistically significant differences between the patient and control groups: peripheral vision (p = 0.0006), role difficulties (p = 0.015), and the composite score (p = 0.014). In addition, 2 monocular patients had given up driving compared with no binocular subjects (p = 0.056). CONCLUSIONS: This population of monocular patients had general physical and mental HRQOL equivalent to the normal binocular group despite the surgical removal of 1 eye. However, the reduced vision-specific HRQOL of monocular patients on the National Eye Institute Visual Function Questionnaire indicates that there are substantial residual visual deficits even after prolonged monocular status.

Bacterial biofilm diversity in contact lens-related disease: emerging role of Achromobacter, Stenotrophomonas, and Delftia.

PURPOSE: Multi-species biofilms associated with contact lens cases and lenses can predispose individuals to contact lens-related inflammatory complications. Our study used culture-independent methods to assess the relationship between the severity of contact lens-related disease and bacteria residing in biofilms of contact lens cases and lenses. METHODS: Contact lens cases and lenses from 28 patients referred to the West Virginia University Eye Institute and diagnosed as having mild keratitis, keratitis with focal infiltrates, or corneal ulcers were processed and evaluated for bacterial composition based on 16S ribosomal RNA gene sequencing. Cases and lenses from nine asymptomatic contact lens wearers were processed in a manner similar to controls. Relationships between disease severity, bacterial types, and bacterial diversity were evaluated statistically. RESULTS: Disease severity and presenting visual acuity correlated with an increase in the diversity of bacterial types isolated from contact lens cases. A significant difference also was observed in the number of bacterial types associated with the three clinical groups. Achromobacter, Stenotrophomonas, and Delftia were prevalent in all disease groups, and Achromobacter and Stenotrophomonas were present in one asymptomatic control. Scanning electron microscopy revealed that Achromobacter and Stenotrophomonas formed a biofilm on the surface of contact lenses. CONCLUSIONS: Culture-independent methods identified an association between disease severity and bacterial diversity in biofilms isolated from cases and lenses of patients with contact lens-related corneal disease. Achromobacter, Stenotrophomonas, and Delftia were predominant bacteria identified in our study, drawing attention to their emerging role in contact lens-related disease.

Relationship of chromatic visual-evoked potentials and the changes of foveal photoreceptor layer in central serous chorioretinopathy patients.

PURPOSE: To investigate the relative involvement of chromatic and achromatic visual subsystems in central serous chorioretinopathy, and to correlate the function changes with the changes of the foveal photoreceptor layer using Fourier domain optical coherence tomography (FD-OCT). METHODS: Central serous chorioretinopathy patients and control subjects were tested and compared. Equiluminant Chromatic sinusoidal gratings were presented in a pattern onset-offset mode. We measured the distance between the internal limiting membrane (ILM) and the external limiting membrane (ELM) on FD-OCT images. RESULTS: Visual evoked potential mean latency was delayed significantly in central serous chorioretinopathy patients compared to controls. The visual evoked potential delay was greater for chromatic than for achromatic stimuli. Retinal thickness from ILM to ELM was associated significantly and selectively with short-wavelength-sensitive (S) cone visual evoked potential latency (r = -0.40, p = 0.032). CONCLUSIONS: These results are consistent with data that indicate the loss of photoreceptors in central serous chorioretinopathy resulting in a reduced thickness of the outer nuclear layer. Additionally, they are consistent with data which indicate that the photoreceptor loss is relatively greater in cones. The S-cone pathway was affected the most.

ISCEV standard for clinical visual evoked potentials (2009 update).

Visual evoked potentials (VEPs) can provide important diagnostic information regarding the functional integrity of the visual system. This document updates the ISCEV standard for clinical VEP testing and supersedes the 2004 standard. The major change in this revision is that test parameters have been made more precise to achieve better consistency of results within and between test centers. The ISCEV standard VEP protocols are defined for a single recording channel with a midline occipital active electrode. These protocols are intended for assessment of prechiasmal function; additional electrode sites are recommended for evaluation of chiasmal and postchiasmal function. ISCEV has selected a subset of stimulus and recording conditions that provide core clinical information and can be performed by most clinical electrophysiology laboratories throughout the world. These are: 1. Pattern-reversal VEPs elicited by checkerboard stimuli with large 1 degrees (i.e., 60 min of arc; min) and small 0.25 degrees (15 min) checks. 2. Pattern onset/offset VEPs elicited by checkerboard stimuli with large 1 degrees (60 min) and small 0.25 degrees (15 min) checks. 3. Flash VEP elicited by a brief luminance increment, a flash, which subtends a visual field of at least 20 degrees.

Retinotopic maps and foveal suppression in the visual cortex of amblyopic adults.

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early-onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.

Monocular activation of V1 and V2 in amblyopic adults measured with functional magnetic resonance imaging.

PURPOSE: Although previous neuroimaging efforts clearly indicate visual cortical dysfunction in adults with amblyopia, the extent of abnormalities remains unclear. METHODS: This functional magnetic resonance imaging (fMRI) study directly compared activity in visual cortex produced by monocular stimulation in 18 adults (six esotropic strabismics, six anisometropes, and six controls). Measures were made in three cortical regions-of-interest, individually defined using standard retinotopic mapping techniques in the nonamblyopic eye, corresponding to extrafoveal V1, extrafoveal V2, and the foveal representation at the occipital pole. Fixation stability was monitored and found not to differ significantly between subject groups. RESULTS: Overall results showed depressed fMRI signal magnitude for amblyopic eyes compared with sound eyes, although a few subjects did not show this trend. Assessment of the spatial extent of activation using an ocular dominance index did show significantly larger interocular differences for both strabismics and anisometropes compared with control subjects for whom eye dominance was carefully defined. In addition, both amblyopic groups showed less cortical area able to be significantly driven by either eye. The magnitude of these effects was equivalent in V1, V2, and the foveal representation, as well as between amblyopic groups. No difference was detected in the strength of signal from the nasal versus temporal retina in either amblyopic group. CONCLUSIONS: Asymmetries in magnitude of monocular activation do occur in subjects with amblyopia, but these basic measures are limited in terms of sensitivity for mild to moderate amblyopia and for specificity between subtypes.

Texton-based segmentation of retinal vessels.

With improvements in fundus imaging technology and the increasing use of digital images in screening and diagnosis, the issue of automated analysis of retinal images is gaining more serious attention. We consider the problem of retinal vessel segmentation, a key issue in automated analysis of digital fundus images. We propose a texture-based vessel segmentation algorithm based on the notion of textons. Using a weak statistical learning approach, we construct textons for retinal vasculature by designing filters that are specifically tuned to the structural and photometric properties of retinal vessels. We evaluate the performance of the proposed approach using a standard database of retinal images. On the DRIVE data set, the proposed method produced an average performance of 0.9568 specificity at 0.7346 sensitivity. This compares well with the best-published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc. SPIE5370, 648 (2004)].

Voxel-based analysis of MRI detects abnormal visual cortex in children and adults with amblyopia.

Amblyopia, sometimes called "lazy eye," is a relatively common developmental visual disorder well characterized behaviorally; however, the neural substrates associated with amblyopia in humans remain unclear. We hypothesized that abnormalities in the cerebral cortex of subjects with amblyopia exist, possibly as a result of experience-dependent neuronal plasticity. Anatomic magnetic resonance imaging (MRI) and psychophysical vision testing was carried out on 74 subjects divided into two age ranges, 7-12 years and 18-35 years, and three diagnoses, strabismic amblyopia, anisometropic amblyopia, and normal vision. We report a behavioral impairment in contrast sensitivity for subjects with amblyopia, consistent with previous reports. When the high-resolution MRI brain images were analyzed quantitatively with optimized voxel-based morphometry, results indicated that adults and children with amblyopia have decreased gray matter volume in visual cortical regions, including the calcarine sulcus, known to contain primary visual cortex. This finding was confirmed with a separate region-of-interest analysis. For the children with amblyopia, additional gray matter reductions in parietal-occipital areas and ventral temporal cortex were detected, consistent with recent reports that amblyopia can result in spatial location and object processing deficits. These data are the first to provide possible neuroanatomic bases for the loss of binocularity and visual sensitivity in children and adults with amblyopia.