Deficits In Visual Function Research Articles

Visual function deficits in eyes with resolved endophthalmitis

To evaluate the changes in functional vision in patients with resolved endophthalmitis. This was a cross-sectional study. The study included 20 patients with resolved endophthalmitis and best-corrected visual acuity of 20/100 or better. Visual acuity (VA), contrast threshold (CT), red/green (RG) and yellow/blue (YB) colour vision and 15 Hz flicker modulation threshold (FMT) were assessed using standard psychophysical techniques. The median age was 54 years. The median visual acuity was 0.27 (~ 20/40—Snellen Equivalent) ((interquartile range [IQR]), 0.30) logMAR). The median log contrast threshold (CT) was − 1.13 (IQR, 0.36) log units (normative value for age-matched CT: − 1.61 log units). The median red/green (RG) and yellow/blue (YB) thresholds were 11.52 (IQR, 26.19) and 9.45 (IQR, 16.20) CAD units respectively, which were at least 5 times higher than age-matched normative RG and YB thresholds. The median central cone- mediated FMT was 17.64% (IQR, 23.40%), which was much higher compared to age-matched FMT (5.48% [IQR, 3.47]). Linear regression revealed significant relationship between contrast thresholds and foveal thickness (y = 0.001x−1.47, R2 = 0.20, p = 0.048). Though endophthalmitis may resolve with a good visual acuity, deficits in visual functions like chromatic discrimination, cone-mediated flicker and contrast sensitivity persist.

Loss of endocytosis-associated RabGEF1 causes aberrant morphogenesis and altered autophagy in photoreceptors leading to retinal degeneration.

Rab-GTPases and associated effectors mediate cargo transport through the endomembrane system of eukaryotic cells, regulating key processes such as membrane turnover, signal transduction, protein recycling and degradation. Using developmental transcriptome data, we identified Rabgef1 (encoding the protein RabGEF1 or Rabex-5) as the only gene associated with Rab GTPases that exhibited strong concordance with retinal photoreceptor differentiation. Loss of Rabgef1 in mice (Rabgef1-/-) resulted in defects specifically of photoreceptor morphology and almost complete loss of both rod and cone function as early as eye opening; however, aberrant outer segment formation could only partly account for visual function deficits. RabGEF1 protein in retinal photoreceptors interacts with Rabaptin-5, and RabGEF1 absence leads to reduction of early endosomes consistent with studies in other mammalian cells and tissues. Electron microscopy analyses reveal abnormal accumulation of macromolecular aggregates in autophagosome-like vacuoles and enhanced immunostaining for LC3A/B and p62 in Rabgef1-/- photoreceptors, consistent with compromised autophagy. Transcriptome analysis of the developing Rabgef1-/- retina reveals altered expression of 2469 genes related to multiple pathways including phototransduction, mitochondria, oxidative stress and endocytosis, suggesting an early trajectory of photoreceptor cell death. Our results implicate an essential role of the RabGEF1-modulated endocytic and autophagic pathways in photoreceptor differentiation and homeostasis. We propose that RabGEF1 and associated components are potential candidates for syndromic traits that include a retinopathy phenotype.

Retinal inhibition of glycogen synthase kinase 3 beta protects against tau phosphorylation and stabilises microtubule assembly

AbstractBackgroundThe microtubule associated protein tau is known to have several important functions like assembly and stabilisation of microtubules, axonal transport and neurite outgrowth in neurodegenerative diseases. Gsk3β, glycogen synthase kinase, plays a key role in regulating tau protein activity. There is little understanding of tau and Gsk3β association in the neurogenerative disorders affecting retina. Shp2, the mitogenic phosphatase, is associated with regulation of growth factor signalling pathways in the central nervous system. In this study we demonstrate that Gsk3β inhibition can suppress tau hyperphosphorylation and rescue the inner retinal degenerative changes induced by Shp2 overexpression (OE).MethodsAdult Sprague‐Dawley rats were subjected to intravitreal injection of adeno‐associated viral vector (AAV2) overexpressing either Shp2 or eGFP alone (3.4x1012 GC/ml; n=8). These animals were also subjected to weekly (8 weeks) intravitreal injections of Gsk3β inhibitor (10 nM) and control. Electrophysiology and positive scotopic threshold response (pSTR) (‐4.3 log cd s/m2) were measured using Phoenix Ganzfield two months following intra‐ocular injections. The amplitude of each component was measured and analysed. Immunohistochemistry (IHC) and Western blot (WB) were performed for pTau Ser404, Tau, pGsk3β Ser9, Gsk3β, Ac‐tubulin and Tyr‐tubulin.ResultsShp2OE in the rat eye significantly reduced the pSTR amplitudes (44%±3.1%) compared to PBS and GFP control. However, animals treated with Gsk3β inhibitor in Shp2OE retina demonstrated significant protection of pSTR amplitudes (81±5 % protection; n=32, p<0.05). IHC analysis demonstrated increased pTau Ser404 and decreased pGsk3β Ser9 immunoreactivity in the Shp2OE RGCs whereas pharmacological inhibition of Gsk3β for 8 weeks reversed the phosphorylation status of tau and Gsk3β in animals recieving AAV‐Shp2. We found that Shp2OE led to a markedly reduced expression of Ac‐tubulin (stable microtubules) and increased expression of Tyr‐tubulin (unstable microtubules) compared with control retina. Remarkably, the effects of Shp2OE on microtubules assembly was reversed upon Gsk3β inhibitor administration.ConclusionShp2OE in the retina led to abnormal tau hyperphosphorylation via Gsk3β activation causing deficits in RGCs visual function through the disruption of microtubular assembly. Shp2 may thus be an attractive therapeutic target to counter RGC neurodegeneration by reducing tau hyperphosphorylation in Alzheimer’s disease.

How to assess visual function in acquired brain injury-Asking is not enough.

BackgroundAcquired brain injury affects many brain areas and causes a range of dysfunctions including vision‐related issues. These issues can have negative impacts on rehabilitation progress and activities of daily life but may easily be overlooked. There is no common recommendation about how to assess visual impairments after ABI. The purpose of this study was to estimate the frequency of objectively measures oculomotor dysfunctions, and also how these findings are related to two inventories intended to support detection of visual impairment.MethodsThe study was cross‐sectional and included 73 outpatients. In addition to the standard evaluation program, the patients went through a comprehensive optometric examination. The inventories used were the Vision Interview (VI) and the Convergence Insufficiency Symptom Survey (CISS).ResultsAll three types of examinations showed a high proportion vision‐related symptoms. Fusion vergence was the most common objectively measured finding, 83%. There were seven statistically significant associations between five VI items and five visual deficits. The strength of associations was moderate (Phi 0.261–0.487, p < .05). The sensitivity and specificity of the CISS were moderate.ConclusionWe found high percentages of the patients with visual symptoms and dysfunctions. Due to the complexity of visual symptoms and functional deficits in ABI, we find it necessary to combine both symptom assessment and vision examination in order to capture visual function issues.

Methods of visual assessment in children with cortical visual impairment.

Cortical visual impairment (CVI) is the leading cause of pediatric visual impairment in developed countries. Currently, there is no standardized method of visual assessment in these children, who usually cannot participate in tests designed for typically developing children. A reproducible method of visual assessment that accurately reflects the multitude of visual deficits in CVI is critical to evaluate proposed therapies for this disorder. This review analyzes current research on methods of visual assessment in children with CVI. Earlier studies focused on measuring visual acuity in children with CVI. More recent studies have emphasized other aspects of visual function, such as contrast sensitivity, motion detection, and visual search. Current research topics include questionnaires, functional vision assessment (CVI Range), neuropsychological tests of visual perception, and eye tracking. Eye tracking shows promise for visual assessment in both clinical and research settings because it is objective and quantitative, with the ability to assess diverse visual parameters. Current research on visual assessment in children with CVI focuses on measuring deficits of visual function beyond visual acuity. This research represents an important step toward designing clinical trials to identify effective therapeutics for this increasingly prevalent disorder with heterogeneous manifestations.

English

BACKGROUND The prevalence of refractive errors is reported to be higher in children born preterm. Factors like gestational age, birth weight and retinopathy of prematurity status have a significant impact on the refractive development in preterm infants. Population based long term follow up studies on the refractive status in preterm infants are limited. We designed this study to assess whether prematurity is a risk factor for refractive errors in children. METHODS This study was conducted among children aged 5 - 16 years who participated in the school vision screening program over a period of one year. All children underwent detailed ocular examination including measurement of best corrected visual acuity, cycloplegic refraction and fundoscopy. Visual acuity was assessed using an internally illuminated Snellen’s chart at 6 meters. Objective refraction by streak retinoscopy after instilling 1 % cyclopentolate eye drops was done in all children with visual acuity ≤ 6 / 9. Children were divided into two groups based on their gestational age at birth - preterm group and full-term group. Preterm birth was defined as childbirth before 37 completed weeks of gestation. Children were enrolled in the study only if the hospital birth document showing gestational age and birth weight was available. Children with co-existing organic disease affecting the eye contributing to the diminished visual acuity such as congenital cataract, glaucoma, and corneal opacities were excluded from the study. Those who had undergone any ocular surgery were also excluded. RESULTS One thousand two hundred and ninety-five children were enrolled in the study of which 700 (54.1 %) were boys and 595 (45.9 %) were girls. Median age of the enrolled children was 12 years. The number of pre-term births was 287 (22.2 %). Of the 1295 students screened, 273 (21 %) had refractive errors. Among the children with refractive errors, astigmatism was the most common refractive error (10.6 %), followed by myopia (8.5 %) and hypermetropia (1.9 %). Refractive errors were statistically more prevalent in preterm group (34.1 %), when compared with term born children (17.3 %), p = &lt; 0.001. Compared to the term born children, preterm group had significantly higher prevalence of myopia; 16.4 % vs 6.3 % (p = &lt; 0.001) and astigmatism; 15.3 % vs 9.3% (p = 0.003). There was no statistically significant difference in the prevalence of hypermetropia among the two groups; 2.4 vs. 1.8 (p = 0.477). CONCLUSIONS There is strong association between prematurity and refractive errors. These findings prompt long term monitoring of the refractive and visual outcome in preterm infants for diagnosing refractive errors at the earliest. This helps to prevent the consequent amblyopia and the ensuing permanent visual function deficits. KEYWORDS Prematurity, Refractive Error, Myopia, Hypermetropia, Astigmatism

Assessment of Visual and Retinal Function Following In Vivo Genipin-Induced Scleral Crosslinking.

PurposeGenipin has been proposed as a possible neuroprotective therapy in myopia and glaucoma. Here, we aim to determine the effects of prolonged genipin-induced scleral stiffening on visual function.MethodsEyes from Brown Norway rats were treated in vivo with either a single 15 mM genipin retrobulbar injection or sham retrobulbar injection and were compared to naïve eyes. Intraocular pressure, optomotor response, and electroretinograms were repeatedly measured over 4 weeks following retrobulbar injections to determine visual and retinal function. At 4 weeks, we quantified retinal ganglion cell axon counts. Finally, molecular changes in gene and protein expression were analyzed via real-time polymerase chain reaction (RT-PCR) and proteomics.ResultsRetrobulbar injection of genipin did not affect intraocular pressure (IOP) or retinal function, nor have a sustained impact on visual function. Although genipin-treated eyes had a small decrease in retinal ganglion cell axon counts compared to contralateral sham-treated eyes (−8,558 ± 18,646; mean ± SD), this was not statistically significant (P = 0.206, n = 9). Last, we did not observe any changes in gene or protein expression due to genipin treatment.ConclusionsPosterior scleral stiffening with a single retrobulbar injection of 15 mM genipin causes no sustained deficits in visual or retinal function or at the molecular level in the retina and sclera. Retinal ganglion cell axon morphology appeared normal.Translational SignificanceThese results support future in vivo studies to determine the efficacy of genipin-induced posterior scleral stiffening to help treat ocular diseases, like myopia and glaucoma.

The influence of sociodemographic characteristics on vision-related quality of life in visually impaired patients

Objectives: Self-reported vision-related quality of life (VRQOL) allows us to assess the effect of disease and treatments from the patient’s perspective, focusing on an individual’s subjective satisfaction and functional ability. The previous studies mostly focused on the impact of visual function deficits on VRQOL in patients with visual impairment. This study seeks to investigate the influence of sociodemographic characteristics on VRQOL in visually impaired patients. Material and Methods: This prospective cross-sectional study included consecutive adult patients with visual impairment at the University of Calabar Teaching Hospital eye clinic. All patients had presenting visual acuity worse than 6/18 in the better eye. VRQOL was assessed by the validated English version 25-item National Eye Institute Visual Functioning Questionnaire. Sociodemographic characteristics and ocular parameters were recorded. Sociodemographic characteristics were evaluated based on age, sex, area of residence, marital status, religion, educational attainment, and monthly income. Each characteristic was stratified into groups or levels. Analysis of variance, including post hoc analysis was used to evaluate the association between sociodemographic characteristics and VRQOL. Results: A total of 270 patients were enrolled. After adjustments for category and causes of visual impairment, older age (P &lt; 0.001), rural dwellers (P &lt; 0.001), widowhood (P = 0.006), and no formal education (P &lt; 0.001) were significantly associated with low mean visual function (VF) scores. Similarly, older age (P &lt; 0.001), rural dwellers (P &lt; 0.001), widowhood (P = 0.003), and no formal education (P &lt; 0.001) were significantly associated with low mean QOL scores. The difference in the mean score of VF and QOL by religion, sex, and monthly income was not statistically significant. Conclusion: Besides the degree of visual impairment, the interplay of certain social and demographic factors plays a remarkable role in determining the QOL in visually impaired patients. Therefore, an individualized management plan, including psychosocial therapy is imperative in the care of visually impaired patients.

Vegetable Freshness Perception in Dementia with Lewy Bodies and Alzheimer’s Disease

Introduction: Although various visual function deficits have been reported in patients with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), vegetable freshness perception has not been thoroughly examined. Objective: To investigate vegetable freshness perception in patients with AD and DLB and to clarify the relationship between vegetable freshness perception and various visuoperceptual functions. Methods: We enrolled 37 patients with probable DLB, 58 patients with probable AD, and 32 age-matched healthy controls. We assessed vegetable freshness perception and visuoperceptual functions, including vegetable brightness perception, contrast sensitivity, color perception, and stereopsis. Patients with DLB showed disproportionate deficits in vegetable freshness perception and vegetable luminance perception compared to patients with AD and controls. Analyses of the groups with higher and lower vegetable freshness perceptions revealed significant differences in contrast sensitivity and visual texture recognition. Results: In the vegetable freshness test, we found significant differences among the 3 groups (F = 30.029, p < 0.0001); the extent of impairment in patients with DLB was greater than that in patients with AD. In patients with DLB, the vegetable freshness judgments were significantly correlated with texture judgment scores and contrast sensitivity. Conclusion: Our findings revealed significantly impaired vegetable freshness perception in patients with DLB. Vegetable freshness perception may be related to visual texture recognition in patients with DLB.

Long-Term Impact of Mild Traumatic Brain Injuries on Multiple Functional Outcomes and Epigenetics: A Pilot Study with College Students

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely assess long-term complications. This pilot study assessed and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated, including 14 healthy controls (64.3% females; mean age of 22.0) and 11 mTBI cases (27.3% females; mean age of 28.7 years) who self-reported mTBI history (63.6% multiple; 2.5 ± 1.29 injuries) with 7.1 years on average elapsed following the last injury. Every participant was assessed for cognitive (executive function, memory, and processing speed), psychological (depression, anxiety, and sleep disturbances), and visual function (by King–Devick and binocular accommodative tests); force-plate postural balance performance; and blood 5-mC% levels. Students with mTBI showed poorer episodic memory, severe anxiety, and higher blood 5-mC% ratio, compared to controls (all p’s &lt; 0.05), which were still significant after adjusting for age. No differences were detected in sleep problems (after adjusting for age), visual function, and postural balance. These findings identified changes in multiple functions and peripheral epigenetics long after mTBI.

Paroxetine can improve primary visual cortex activity in a high-risk mouse model of schizophrenia

Visual cortex functional deficits can be observed in schizophrenia patients and in individuals at high risk of schizophrenia. However, to date, few studies have investigated methods to improve these functional deficits. This study aimed to investigate the pathological change in the primary visual cortex of a prenatal MK-801-induced high-risk mouse model of schizophrenia (HRMMS) and to test the effect of paroxetine on visual cortex activity. Pregnant mice were given a systemic injection of MK-801, and male offspring that did not present schizophrenia-like behaviors in early adulthood were defined as HRMMS. Some of the HRMMS mice were treated with pharmacological agents beginning at 4 weeks of age. After 4 weeks of treatment with risperidone and/or paroxetine, two-photon calcium imaging was performed to analyze the primary visual cortex activity. The sucrose preference test and the prepulse inhibition (PPI) apparatus test were used to assess the cognitive and behavioral performance. HRMMS mice with or without risperidone treatment had impairments in the primary visual cortex as observed by reduced neuronal calcium activity. Risperidone plus paroxetine and paroxetine alone treatments increased the neuronal calcium activity in the primary visual cortex. Notably, the neuronal calcium activity was higher in mice treated with paroxetine alone. Treatment with paroxetine alone also improved the cognitive and behavioral performance better than treatment with risperidone plus paroxetine. Our pioneering animal model showed that treatment with paroxetine alone improves visual cortex impairments in HRMMS mice better than treatment with risperidone plus paroxetine, indicating that antipsychotics cannot normalize visual cortex impairments.

Galantamine protects against synaptic, axonal, and vision deficits in experimental neurotrauma

Our goal was to investigate the neuroprotective effects of galantamine in a mouse model of blast-induced indirect traumatic optic neuropathy (bITON). Galantamine is an FDA-approved acetylcholinesterase inhibitor used to treat mild-moderate Alzheimer's disease. We exposed one eye of an anesthetized mouse to repeat bursts of over-pressurized air to induce traumatic optic neuropathy. Mice were given regular or galantamine-containing water (120 mg/L) ad libitum, beginning immediately after blast and continuing for one month. Electroretinograms and visual evoked potentials were performed just prior to endpoint collection. Histological and biochemical assessments were performed to assess activation of sterile inflammation, axon degeneration, and synaptic changes. Galantamine treatment mitigated visual function deficits induced by our bITON model via preservation of the b-wave of the electroretinogram and the N1 of the visual evoked potential. We also observed a reduction in axon degeneration in the optic nerve as well as decreased rod bipolar cell dendritic retraction. Galantamine also showed anti-inflammatory and antioxidant effects. Galantamine may be a promising treatment for blast-induced indirect traumatic optic neuropathy as well as other optic neuropathies.

COMPLEMENT CONTRIBUTES TO ALZHEIMER’S DISEASE-INDUCED SYNAPSE DECLINE IN THE MURINE RETINA

Alzheimer's disease (AD) is among the most debilitating form of cognitive impairment in aged patients. Synapse deficits are thought to be a central trigger of neural miswiring and brain dysfunction in AD. However, the pathways that control synapse connectivity remain largely unknown. The retina is an easily accessible system with two distinct synapse layers and three cellular layers comprised of distinct neural types. In this study, we leveraged this system to assess synapse and cell integrity in the APPNLGF amyloid-beta AD mouse model. We showed that the expression of the complement component C3 is significantly increased in APPNLGF retina synapses, and that there is a significant decline of several synapse-associated markers by RT-PCR. These mice also display disorganized horizontal cell processes and visual function deficits. These results suggest that complement may drive AD-related changes in the synaptic and functional properties of the retina, which could serve as assessable preclinical biomarkers for AD. In ongoing studies, we are testing whether and how complement regulates synapse refinement and shapes retina synapse specificity in AD.

No Alteration of Optical Coherence Tomography and Multifocal Visual Evoked Potentials in Eyes With Symptomatic Carotid Artery Disease.

Background: Symptomatic carotid artery disease (CAD) may cause modified blood supply to the retina possibly leading to retinal structure changes. Results of previous studies in asymptomatic CAD were heterogeneous in retinal layer changes measured by OCT. The objectives of this prospective, non-interventional study were to investigate if structural retinal changes occur in symptomatic CAD patients with macroangiopathic ischemic stroke or transient ischemic attack (TIA).Methods: We used spectral-domain optical coherence tomography (SD-OCT) to cross-sectionally and longitudinally analyze the retinal morphology of CAD patients with macroangiopathic ischemic stroke or TIA not permanently affecting the visual pathway. We employed semi-automated segmentation of macular volume scans to assess the macular retinal layers' thickness and peripapillary ring scans to determine the peripapillary retinal nerve fiber layer thickness using the contralateral eye and eyes of microangiopathic ischemic stroke patients with matched age, gender, and vascular risk factors as control. Visual function and visual field deficits were assessed by multifocal visual evoked potentials (mfVEP).Results: Neither the thickness of retinal layers measured by SD-OCT in 17 patients nor the mfVEP latency or amplitude in 10 patients differed between the symptomatic stenotic, the contralateral internal carotid artery (ICA) side and the control group of 17 microangiopathic stroke patients at baseline. Furthermore, longitudinal investigations of 10 patients revealed no significant changes of any retinal layer 4 months after ischemic stroke or TIA.Conclusion: In conclusion, our study revealed no evidence for an impact of symptomatic carotid artery disease on retinal structure or functional impairment of the visual pathway.

The predictive potential of altered spontaneous brain activity patterns in diabetic retinopathy and nephropathy.

The amplitude of low-frequency fluctuation (ALFF) fMRI technique was used to study the changes of spontaneous brain activity in patients with diabetic retinopathy and nephropathy (DRN), and to explore the application of ALFF technique in the potential prediction and the targeted prevention of diabetic microangiopathy. Nineteen patients with diabetic retinopathy and nephropathy and 19 healthy controls (HCs) were matched for age and gender. Spontaneous cerebral activity variations were investigated using the ALFF technique. The average ALFF values of the DRN patients and the HCs were classified utilizing receiver operating characteristic (ROC) curves. In contrast to the results in the HCs, the patients with DRN had significantly higher ALFF values in the cerebellum (bilaterally in the posterior and anterior lobes) and the left inferior temporal gyrus, but the ALFF values of the bilateral medial frontal gyrus, right superior temporal gyrus, right middle frontal gyrus, left middle/inferior frontal gyrus, bilateral precuneus, and left inferior parietal lobule were lower. ROC curve analysis of each brain region showed the accuracy of AUC was excellent. However, the mean ALFF values in the different regions did not correlate with clinical performance. The subjects showed abnormal neuronal synchronization in many areas of the brain, which is consistent with cognitive and visual functional deficits. Abnormal spontaneous activity was detected in many areas of the brain, which may provide useful information for understanding the pathology of DRN. Abnormal ALFF values of these brain regions may be of predictive value in the development of early DRN and be a targeted intervention indicator for individualized treatment of diabetic microvascular diseases.

Impact of Dry Eye on Visual Acuity and Contrast Sensitivity: Dry Eye Assessment and Management Study.

Identification of the association of specific signs of dry eye disease with specific visual function deficits may allow for more targeted approaches to treatment. The purpose of this study was to explore the association of dry eye signs and symptoms with visual acuity (VA) and contrast sensitivity in the Dry Eye Assessment and Management study. Baseline data from participants in the Dry Eye Assessment and Management study were used in this secondary cross-sectional analysis. Standardized procedures were used to obtain results on the Ocular Surface Disease Index (OSDI), high-contrast logMAR VA, contrast sensitivity, tear film debris, tear breakup time (TBUT), corneal fluorescein staining, meibomian gland evaluation, conjunctival lissamine green staining, and Schirmer test scores. Generalized linear models that included age, refractive error status, and cataract status were used to assess the association between VA and contrast sensitivity with OSDI score and each dry eye sign. The Hochberg procedure was used to account for multiple comparisons. Among 487 participants (974 eyes), worse VA was associated with worse mean score on the OSDI vision subscale (39.4 for VA 20/32 or worse vs. 32.4 for VA 20/16 or better; adjusted linear trend, P = .02); scores were not associated with contrast sensitivity. Severe meibomian gland plugging and abnormal secretions were associated with worse mean log contrast sensitivity (1.48 for severe vs. 1.54 for not plugged [P = .04] and 1.49 for obstructed vs. 1.57 for clear [P = .002], respectively). Longer TBUT was associated with better mean log contrast sensitivity (1.57 for TBUT >5 seconds and 1.51 for TBUT ≤2 seconds, P < .0001). Worse VA rather than worse contrast sensitivity drives vision-related symptoms in dry eye. Greater tear film instability was associated with worse contrast sensitivity.

Decreased Amplitude of the Photopic Negative Response (PhNR) in the Ins2Akita Mouse Model of Type 1 Diabetes Mellitus

Diabetic retinopathy (DR) is a common, severe complication of diabetes mellitus. Current clinical detection of DR is based primarily on visible retinal vascular damage, and earlier detection of impending DR might allow earlier treatment to protect function. Recent studies in both animal models and humans with diabetes have shown that degradation of retinal ganglion cell (RGC) function occurs at an early stage, before visible vascular complications and before significant RGC loss. The photopic negative response (PhNR), obtained from full‐field electroretinogram (ERG) with photopic stimuli is thought to arise directly from RGC activity. Here, we hypothesized that PhNR amplitudes are reduced in a type 1 diabetic mouse model, the Ins2Akita mouse, which develops hyperglycemia by 5 weeks of age and visual function and ocular blood flow deficits early in the disease progression, before overtly visible vascular damage. Diabetic (male heterozygotes) and control (male WT littermates) mice were grouped according to age: young, adult, and old (5–6, 9–11, and 12–14 months of age, respectively). ERG recording was performed with 1.62 log cd/m2 white flashes over a constant 40 cd.s/m2 green background (Diagnosys Espion and ColorDome ganzfeld system) using gold ring contact lens electrodes (LKC Techniologies) under isoflurane anesthesia. Following 1 hour adaptation to the green background illumination, PhNR, a‐wave, and b‐wave amplitudes and implicit times were measured in response to 25 10‐msec flashes.The mean PhNR amplitude of the adult diabetic mice was 36% of their age‐matched controls (p &lt; 0.01). For the old diabetic group, the mean PhNR amplitude was 49% of their age‐matched controls (p &lt; 0.05). However, no significant difference was found in the young group. A‐wave amplitudes were decreased in the diabetic adult group, to a value only 41% of their age‐matched controls (p &lt; 0.05). B‐wave amplitudes were decreased in the diabetic old group, to 35% of their age‐matched controls (p &lt; 0.05). However, no significant difference was found among groups for PhNR, a‐wave, or b‐wave implicit times. Our results suggest that PhNR amplitude is altered relatively early in the Ins2Akita mouse model of diabetes. This suggests PhNR measurements could be used to detect diabetic retinopathy at earlier stages than the current clinical standard.Support or Funding InformationNIH R01 EY023290 and UIWRSO Faculty Development GrantThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Microperimetry for geographic atrophy secondary to age-related macular degeneration

Geographic atrophy (GA) is a progressive, advanced form of age-related macular degeneration leading to visual function impairment and irreversible vision loss. Standard clinical tests to evaluate visual function in patients with GA provide poor anatomic-functional correlation, whereas fundus imaging does not assess the visual function deficit. Microperimetry is a psychophysical visual function test that spatially maps retinal sensitivity and allows for identification of correlation of anatomic features with visual function. In this review, we present an overview of mesopic microperimetry for GA, including commercially available microperimetry devices, strategies to capture a mesopic microperimetry test, and strategies to assess and interpret microperimetry data in patients with GA. We demonstrate the importance of microperimetry data for assessing GA progression and for evaluating visual function loss through anatomic-functional correlations. Although valuable, current microperimetry tests require an extensive time commitment from the patient and examiner, and the development of faster, more reproducible and accessible methods is important to enable broader use of microperimetry in both clinical and research settings.

Cognitive Profiles of Developmental Dysgraphia.

Developmental dysgraphia is a disorder of writing/spelling skills, closely related to developmental dyslexia. For developmental dyslexia, profiles with a focus on phonological, attentional, visual or auditory deficits have recently been established. Unlike for developmental dyslexia, however, there are only few studies about dysgraphia, in particular about the variability of its causes. Research has demonstrated high similarity between developmental dyslexia and dysgraphia. Thus, the aim of the study was to investigate cognitive deficits as potential predictors of dysgraphia, analogously to those for dyslexia, in order to identify dysgraphia profiles, depending on the particular underlying disorder. Different tests were carried out with 3rd and 4th grade school children to assess their spelling abilities, tapping into phonological processing, auditory sound discrimination, visual attention and visual magnocellular functions as well as reading. A group of 45 children with developmental dysgraphia was compared to a control group. The results showed that besides phonological processing abilities, auditory skills and visual magnocellular functions affected spelling ability, too. Consequently, by means of a two-step cluster analysis, the group of dysgraphic children could be split into two distinct clusters, one with auditory deficits and the other with deficits in visual magnocellular functions. Visual attention was also related to spelling disabilities, but had no characteristic distinguishing effect for the two clusters. Together, these findings demonstrate that a more fine-grained diagnostic view on developmental dysgraphia, which takes the underlying cognitive profiles into account, might be advantageous for optimizing the outcome of individuum-centered intervention programs.

Effects of Deepwater Horizon crude oil on ocular development in two estuarine fish species, red drum (Sciaenops ocellatus) and sheepshead minnow (Cyprinodon variegatus)

Polycyclic aromatic hydrocarbons (PAHs) present in crude oil have been shown to cause the dysregulation of genes important in eye development and function, as well as morphological abnormalities of the eye. However, it is not currently understood how these changes in gene expression are manifested as deficits in visual function. Embryonic red drum (Sciaenops ocellatus) and sheepshead minnow (Cyprinodon variegatus) were exposed to water accommodated fractions (WAFs) of weathered crude oil and assessed for visual function using an optomotor response assay in early life-stage larvae, with subsequent samples taken for histological analysis of the eyes. Larvae of both species exposed to increasing concentrations of oil exhibited a reduced optomotor response. The mean diameters of retinal layers, which play an important role in visual function and image processing, were significantly reduced in oil-exposed sheepshead larvae, though not in red drum larvae. The present study provides evidence that weathered crude oil has a significant effect on visual function in early life-stage fishes.