Systemic Elevation of n-3 Polyunsaturated Fatty Acids (n-3-PUFA) Is Associated with Protection against Visual, Motor, and Emotional Deficits in Mice following Closed-Head Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration leading to various pathological complications such as motor and sensory (visual) deficits, cognitive impairment, and depression. N-3 polyunsaturated fatty acid (n-3 PUFA) containing lipids are known to be anti-inflammatory, whereas the sphingolipid, ceramide (Cer), is an inducer of neuroinflammation and degeneration. Using Fat1+-transgenic mice that contain elevated levels of systemic n-3 PUFA, we tested whether they are resistant to mild TBI-mediated sensory-motor and emotional deficits by subjecting Fat1-transgenic mice and their WT littermates to focal cranial air blast (50 psi) or sham blast (0 psi, control). We observed that visual function in WT mice was reduced significantly following TBI but not in Fat1+-blast animals. We also found Fat1+-blast mice were resistant to the decline in motor functions, depression, and fear-producing effects of blast, as well as the reduction in the area of oculomotor nucleus and increase in activated microglia in the optic tract in brain sections seen following blast in WT mice. Lipid and gene expression analyses confirmed an elevated level of the n-3 PUFA eicosapentaenoic acid (EPA) in the plasma and brain, blocking of TBI-mediated increase of Cer in the brain, and decrease in TBI-mediated induction of Cer biosynthetic and inflammatory gene expression in the brain of the Fat1+ mice. Our results demonstrate that suppression of ceramide biosynthesis and inflammatory factors in Fat1+-transgenic mice is associated with significant protection against the visual, motor, and emotional deficits caused by mild TBI. This study suggests that n-3 PUFA (especially, EPA) has a promising therapeutic role in preventing neurodegeneration after TBI.

New Insights into Diabetic and Vision-Threatening Retinopathy: Importance of Plasma Long Pentraxine 3 and Taurine Levels.

PURPOSE: To investigate diabetic retinopathy (DR), plasma long pentraxin-3 (PTX-3) and taurine levels, and systemic factors in patients with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: Patients with type 2 DM were categorized based on the presence of DR and maculopathy. Retinal findings (retinopathy, maculopathy, flame-shaped hemorrhage, intraretinal microvascular abnormalities, neovascularization of the optic disc, neovascularization elsewhere, and soft exudate); laboratory findings (fasting blood glucose, glycosylated hemoglobin [HbA1c], Taurine, PTX-3); systolic blood pressure (SBP) and diastolic blood pressure (DBP) were analyzed. RESULTS: In this study, 39 patients with a mean age of 59.5 ± 8.1 years were included. The mean taurine level was significantly lower (p = .025) and HbA1c values were significantly higher (p = .0001) in patients with and without DR, respectively. In patients with varying severity of DR, a significant difference in the plasma taurine level was found (p = .0001). The mean PTX-3 level decreased with the severity of retinopathy; however, there was no significant difference in levels among the grading groups (p = .732). Taurine and PTX-3 levels were significantly lower in patients with maculopathy (p = .001 and p = .022, respectively) and significantly higher in patients with grade 0 maculopathy than in those with grade 1, 2, or 3 maculopathy (p = .023, p = .01, and p = .01, respectively). Patients with flame-shaped hemorrhage had significantly lower PTX-3 levels (p = .009) and higher SBP and DBP levels (p = .003, p = .023) than those without the hemorrhage. CONCLUSIONS: No significant relation between PTX-3 level and severity of DR was found. HbA1c, taurine, and PTX-3 levels in patients with vision-threatening DR symptoms were significantly different from those without these symptoms. Management of systemic blood pressure and glycemic control is mandatory in the follow-up of DR, and increasing the plasma taurine levels can prevent vision loss.

Carotid artery intima-media thickness, HDL cholesterol levels, and gender associated with poor visual acuity in patients with branch retinal artery occlusion.

PURPOSE: To investigate factors associated with poor visual acuity (VA) in branch retinal artery occlusion (BRAO). METHODS: This was a retrospective cross-sectional study of 72 eyes with BRAO of 72 patients. For statistical comparison, we divided the patients into worse-VA (decimal VA < 0.5) and better-VA (decimal VA > = 0.5) groups. We examined the association of clinical findings, including blood biochemical test data and carotid artery ultrasound parameters, with poor VA. RESULTS: Median age, hematocrit, hemoglobin and high-density lipoprotein (HDL) differed significantly between the groups (P = 0.018, P < 0.01, P < 0.01, and P = 0.025). There was a tendency towards higher median IMT-Bmax in the worse-VA group (worse-VA vs. better-VA: 2.70 mm vs. 1.60 mm, P = 0.152). Spearman's rank correlation test revealed that logMAR VA was significantly correlated to IMT-Bmax (rs = 0.31, P < 0.01) and IMT-Cmax (rs = 0.24, P = 0.035). Furthermore, logMAR VA was significantly correlated to HDL level (rs = -0.33, P < 0.01). Multivariate logistic regression analysis revealed that IMT-Bmax (odds ratio [OR] = 2.70, P = 0.049), HDL level (OR = 0.91, P = 0.032), and female gender (OR = 15.63, P = 0.032) were independently associated with worse VA in BRAO. CONCLUSIONS: We found that increased IMT-Bmax, decreased HDL, and female sex were associated with poor VA in BRAO patients. Our findings might suggest novel risk factors for visual dysfunction in BRAO and may provide new insights into the pathomechanisms underlying BRAO.

Mechanisms Underlying Early-Stage Changes in Visual Performance and Retina Function After Experimental Induction of Sustained Dyslipidemia.

Visual and retinal function was measured in a mouse model of chemically induced, sustained dyslipidemia to determine the contribution of dyslipidemia to the pathogenesis of retinopathy in the context of metabolic syndrome. Fifteen male C57BL/6Crl mice were divided into three groups. Poloxamer 407 (P-407), 14.5% w/w was delivered at a rate of 6 µl/day by implanted osmotic mini-pumps either subcutaneously (P-407 SQ) or intraperitoneally (P-407 IP) to P-407-treated mice, whereas saline was administered at the same rate to control mice using only the subcutaneous route of administration. Total cholesterol (TC) and true triglyceride (TG) levels were quantified from plasma. Optomotor responses to stimuli of varying spatial frequency or contrast were used to measure visual acuity and contrast sensitivity. Retinal function was determined using Ganzfeld flash electroretinography (ERG). At 32 days, TC for the P-407 IP group was significantly elevated compared to saline controls (169.4 ± 16.5 mg/dl, 0.001 < P < 0.01). TG levels for both the P-407 SQ (59.3 ± 22.4 mg/dl, 0.01 < P < 0.05) and P-407 IP groups (67.7 ± 18.0 mg/dl, 0.001 < P < 0.01) were significantly elevated relative to controls. Electroretinography demonstrated a very significant decline in the b/a ratio (1.80 ± 0.11, P < 0.01) for the P-407 IP group. The b/a ratio exhibited a moderate, significant correlation with TC levels (r = - 0.4425, P = 0.0392) and a strong, very significant correlation with TG levels (r = - 0.6190, P = 0.0021). Delivery of P-407 via osmotic mini-pump resulted in the sustained, significant elevation of plasma TC and TG levels. This elevation in plasma lipid levels was correlated with a decline in inner retinal function.

Prenatal organophosphate insecticide exposure and infant sensory function.

BACKGROUND: Occupational studies suggest that exposure to organophosphate insecticides (OPs) can lead to vision or hearing loss. Yet the effects of early-life exposure on visual and auditory function are unknown. Here we examined associations between prenatal OP exposure and grating visual acuity (VA) and auditory brainstem response (ABR) during infancy. METHODS: 30 OPs were measured in umbilical cord blood using gas chromatography tandem mass spectrometry in a cohort of Chinese infants. Grating visual acuity (VA) (n = 179-200) and auditory brainstem response (ABR) (n = 139-183) were assessed at 6 weeks, 9 months, and 18 months. Outcomes included VA score, ABR wave V latency and central conduction time, and head circumference (HC). Associations between sensory outcomes during infancy and cord OPs were examined using linear mixed models. RESULTS: Prenatal chlorpyrifos exposure was associated with lower 9-month grating VA scores; scores were 0.64 (95% CI: -1.22, -0.06) points lower for exposed versus unexposed infants (p = 0.03). The OPs examined were not associated with infant ABR latencies, but chlorpyrifos and phorate were both significantly inversely associated with HC at 9 months; HCs were 0.41 (95% CI: 0.75, 0.6) cm and 0.44 (95% CI: 0.88, 0.1) cm smaller for chlorpyrifos (p = 0.02) and phorate (p = 0.04), respectively. CONCLUSIONS: We found deficits in grating VA and HC in 9-month-old infants with prenatal exposure to chlorpyrifos. The clinical significance of these small but statistically significant deficits is unclear. However, the disruption of visual or auditory pathway maturation in infancy could potentially negatively affect downstream cognitive development.

Glycemic Control and Quality of Life Following Cataract Surgery in Patients with Type 2 Diabetes and without Maculopathy.

OBJECTIVE: To assess whether cataract removal surgery will improve glycemic control and quality of life in patients with diabetes. METHODS: A prospective longitudinal study of 28 patients with type 2 diabetes and without diabetic retinopathy scheduled for cataract removal surgery. During the 4 months of follow-up, measurements of glycated hemoglobin (HbA1c) were obtained and assessment of quality of life was performed using two questionnaires: The EuroQoL 5-Dimension (EQ-5D®) and the Multidimensional Diabetes Questionnaire (MDQ). RESULTS: HbA1c values decreased by approximately 0.45% following surgery (7.24% to 6.78%, P = 0.009). Younger patients reduced HbA1c significantly more than older patients (0.73% vs. 0.03%, respectively, P = 0.043). Younger age also correlated with better visual acuity improvement (R = -0.44, P = 0.02). Poor glycemic control prior to surgery correlated with better HbA1c reductions, with a 42% chance for reduction of at least 0.5% HbA1c in patients with preoperative HbA1c values of 7.5% and a 72% chance for reduction in patients with preoperative HbA1c values of 8.5%. Quality of life was improved by 14% following surgery, as noted in the MDQ results (33.9-38.7, P = 0.034) only. CONCLUSIONS: Cataract removal surgery may positively influence glycemic control and quality of life in type 2 diabetic patients without maculopathy. Younger patients achieved superior improvement in visual and glycemic outcomes. The results of this study highlight the need for frequent inquiry regarding eyesight deterioration in patients with diabetes.

C-Reactive protein and progression of vision loss in retinitis pigmentosa.

PURPOSE: Chronic inflammation is involved in retinitis pigmentosa (RP). We demonstrated previously that intraocular inflammatory levels, as measured by slit-lamp ophthalmoscopy or laser flare photometry, are inversely correlated with central visual function in patients with RP. Here, we investigated the relationship between serum high-sensitivity C-reactive protein (hs-CRP) and visual parameters in RP. METHODS: We studied 58 consecutive typical patients with RP <40 years old and 29 age- and gender-matched controls. High-sensitivity C-reactive protein (hs-CRP) was detected by immunoturbidimetry. The relationships between hs-CRP and visual parameters including best-corrected visual acuity (BCVA), mean deviation (MD) of static perimetry tests (Humphrey Field Analyzer, the central 10-2 programme) and VA changes over the prior 5 years and MD changes over the prior 3 years were analysed in the patients with RP. RESULTS: The serum hs-CRP levels of the patients with RP were significantly higher than those of the controls (0.06 ± 0.08 versus 0.03 ± 0.04 mg/dl, p = 0.0119). In the patients with RP, there was no correlation of hs-CRP with cross-sectionally assessed VA or MD, but the baseline hs-CRP was significantly correlated with the MD deterioration (r = -0.4073, p = 0.0314). CONCLUSION: The average serum hs-CRP was significantly increased in the patients with RP, and higher hs-CRP was associated with faster deterioration of central visual function. These results suggest that the systemic inflammatory profile is altered and may be associated with disease progression in RP.

Risk factors of diabetic retinopathy and sight-threatening diabetic retinopathy: a cross-sectional study of 13 473 patients with type 2 diabetes mellitus in mainland China.

OBJECTIVE: To explore the risk factors of diabetic retinopathy (DR) and sight-threatening diabetic retinopathy (STDR) among Chinese patients with diabetes. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional investigation was performed in eight screening clinics in six provinces across mainland China. Information about the risk factors was recorded in screening clinics. Some risk factors (sex, age, diagnosis age, diabetes duration, systolic blood pressure (SBP), diastolic blood pressure, fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c)) were recorded in all eight clinics, while others were collected only in a subset of the clinics. The relationships between the risk factors and DR and between the risk factors and STDR were explored for the eight factors mentioned above and for all factors studied. MAIN OUTCOMES AND MEASURES: Risk factors of DR and STDR were assessed, and a nomogram of the results was produced. RESULTS: Younger age, longer diabetes duration, higher SBP, higher FBG and higher HbA1c were found to be independent risk factors for both DR and STDR in the eight-factor analyses. In the all-factor analysis, younger age, longer diabetes duration, higher SBP, oral medicine use and insulin use were independent risk factors for both DR and STDR; higher postprandial blood glucose (PBG), HbA1c, triglyceride andlow-density lipoprotein were independent risk factors for DR only, and higher FBG was a risk factor for STDR only. CONCLUSIONS: In this cross-sectional investigation, several risk factors were found for DR and STDR. Notably, FBG, PBG and HbA1c were all risk factors for DR or STDR, suggesting that stricter blood glucose control in clinical practice is required.

High serum creatinine is associated with reduction of vision impaired in patients with NMOSD.

Serum creatinine (SCR) has been found to be neuroprotective in neurodegenerative disease. However, whether SCR is a protective factor for vision impaired in neuromyelitis optica spectrum disorder (NMOSD) is unclear. This study to determine the relationship between SCR level and vision impaired in NMOSD patients through multivariate-adjusted linear regression analyses. Our result showed that high level of SCR was associated with a low occurrence of vision impaired, and the association was independent after adjustment for confounding risk factors and hierarchical analysis. Therefore, these results demonstrated that higher SCR level is a protective factor of vision impaired in male NMOSD patients.

Neonatal Hypoglycaemia and Visual Development: A Review.

BACKGROUND: Many newborn babies experience low blood glucose concentrations, a condition referred to as neonatal hypoglycaemia (NH). The effect of NH on visual development in infancy and childhood is of interest because the occipital lobes, which include the primary visual cortex and a number of extrastriate visual areas, may be particularly susceptible to NH-induced injury. In addition, a number of case series have suggested that NH can affect eye and optic nerve development. OBJECTIVE: To review the existing literature concerning the effect of NH on the visual system. METHODS: A PubMed, Embase, Medline, and Google Scholar literature search was conducted using prespecified MeSH terms. RESULTS: The literature reviewed revealed no clear evidence for an effect of NH on the development of the eye and optic nerve. Furthermore, occipital and occipital-parietal lobe injuries following NH often occurred in conjunction with comorbid conditions and were not clearly linked to subsequent visual dysfunction, possibly due to difficulties in measuring vision in young children and a lack of studies at older ages. A recent, large-scale, prospective study of NH outcomes at 2 years of age found no effect of mild-to-moderate NH on visual development. CONCLUSION: The effect of NH on visual development is unclear. It is currently unknown whether NH affects visual function in mid-to-late childhood when many visual functions reach adult levels.

Postnatal systemic inflammation and neuro-ophthalmologic dysfunctions in extremely low gestational age children.

AIM: Compared to infants born at term, children born very preterm are at increased risk of visual dysfunctions and neonatal systemic inflammation. Here, we explore whether these two propensities are related. METHODS: As part of the ELGAN study, the concentrations of 16 mediators of inflammation were measured in blood obtained on postnatal days 1, 7, 14, 21 and 28 from 1062 children born before the 28th week of gestation. Presence of visual field deficit, strabismus and/or impaired visual fixation was recorded at age two. The concentrations of each protein were divided into quartiles within gestational week categories. We calculated odds ratios with 99% confidence intervals for having each disorder comparing children with concentration in the top quartile of each protein to children whose concentration was in the lower quartiles on the corresponding day. Analyses were adjusted for gestational age and birth weight Z-score. RESULTS: Only one of 80 assessments (16 proteins on five different days) was significant for visual field deficit, and one for impaired fixation. No association was found between strabismus and any inflammatory mediator. CONCLUSION: None of the three neuro-ophthalmologic dysfunctions assessed at two years appears to be associated with systemic inflammation measured the first four postnatal weeks.

Different etiologies and prognoses of optic neuritis in demyelinating diseases.

We compared the clinical features of optic neuritis (ON) that are frequently observed in various central nervous system demyelinating diseases, including multiple sclerosis (MS), anti-aquaporin 4 (AQP4) antibody- and anti-myelin oligodendrocyte glycoprotein (MOG) autoantibody-related diseases. Almost all the AQP4-ON patients were female, whereas half of the MOG-ON patients were male. The ON-onset age was younger in MS-ON and was older in AQP4-ON. The ON-lesion detected using optic MRI in the acute phase was longer in MOG-ON and showed severe swelling and twisting. The worst visual acuity was similar between the diseases; however, the final visual acuity was significantly worse in AQP4-ON.

Visual Complications in Patients with Biopsy-proven Giant Cell Arteritis: A Population-based Study.

OBJECTIVE: To study the clinical and laboratory characteristics of patients with biopsy-proven giant cell arteritis (GCA) with visual complications, and to evaluate the incidence rate of visual complications in GCA compared to the background population. METHODS: Data from 840 patients with GCA in the county of Skåne, Sweden, diagnosed between 1997 and 2010, were used for this analysis. Cases with visual complications were identified from a diagnosis registry and confirmed by a review of medical records. The rate of visual complications in patients with GCA was compared with an age- and sex-matched reference population. RESULTS: There were 85 patients (10%) who developed ≥ 1 visual complication after the onset of GCA. Of the patients, 18 (21%) developed unilateral or bilateral complete visual loss. The mean age at diagnosis was 78 years (± 7.3); 69% were women. Compared with patients without visual complications, those with visual complication had lower C-reactive protein levels at diagnosis and were less likely to have headache, fever, and palpable abnormal temporal artery. The use of ß-adrenergic inhibitors was associated with visual complications. The incidence of visual complications among patients with GCA was 20.9/1000 person-years of followup compared to 6.9/1000 person-years in the reference population, resulting in a rate ratio of 3.0 (95% CI 2.3-3.8). CONCLUSION: Ten percent of patients with GCA developed visual complications, a rate substantially higher than that of the general population. Patients with GCA who had visual complications had lower inflammatory responses and were more likely to have been treated with ß-adrenergic inhibitors compared with patients without visual complications.

N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) Levels are Increased in Patients With Transient Ischemic Attack Accompanied by Nonfocal Symptoms.

BACKGROUND: Transient nonfocal neurological symptoms may serve as markers of cardiac dysfunction. We assessed whether serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, a biomarker of cardiac disease, are increased in patients with transient ischemic attack (TIA) accompanied by nonfocal symptoms and in patients with attacks of nonfocal symptoms (transient neurological attack [TNA]). METHODS AND RESULTS: We included 15 patients with TNA, 69 with TIA accompanied by nonfocal symptoms, 58 with large-vessel TIA, 32 with cardioembolic TIA, and 46 age- and sex-matched healthy control participants. Serum NT-proBNP levels were determined within 1 week after the attack. We compared log-transformed NT-proBNP levels of patients with cardioembolic TIAs and mixed or nonfocal TNAs, with those of patients with noncardioembolic TIAs as a reference group. Adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease were made with a multiple linear regression model. Compared with large-vessel TIA (mean 14.2 pmol/L), mean NT-proBNP levels were significantly higher in patients with TIA accompanied by nonfocal symptoms (40.5 pmol/L, P=0.049) and with cardioembolic TIA (123.5 pmol/L; P=0.004) after adjustments for age, sex, atrial fibrillation, and a history of nonischemic heart disease. Patients with TNA also had higher mean NT-proBNP levels (20.8 pmol/L, P=0.38) than those with large-vessel TIA, but this difference was not statistically significant. CONCLUSION: NT-proBNP levels are increased in patients with TIA accompanied by nonfocal symptoms.

Effects of Maternal Ω-3 Supplementation on Fatty Acids and on Visual and Cognitive Development.

OBJECTIVES: The aim of the present study was to elucidate whether a dairy drink enriched with ω-3 long-chain polyunsaturated fatty acid (LC-PUFA) could have an impact on the lipid profile of the mother and the newborn, and also whether this intervention could affect the newborns' visual and cognitive development. METHODS: A total of 110 pregnant women were randomly assigned to one of the following intervention groups: control group (n = 54), taking 400 mL/day of the control dairy drink, and supplemented group (fish oil [FO]) (n = 56), taking 400 mL/day of the fish oil-enriched dairy drink (including ∼400 mg eicosapentaenoic acid-docosahexaenoic acid [DHA]/day). During the study, the mothers' diets were supervised by a nutritionist to encourage compliance with present recommendations of FA intake. Blood fatty acid profiles were determined in the mother's (at enrollment, at delivery, and at 2.5 and 4 months) and newborn (at delivery and at 2.5 months) placenta and breast milk (colostrum and at 1, 2, and 4 months). Pattern reversal visual evoked potentials (VEPs) (at 2.5 and 7.5 months) and Bayley test (at 12 months) were recorded. RESULTS: DHA percentage was higher in plasma, erythrocyte membranes, and breast milk samples from the FO group. The ratio of nervonic acid was also higher in plasma and erythrocyte lipids of the mother and newborn's blood samples from the FO group. No differences were observed in the Bayley test. No differences were observed in VEPs between both groups. We observed a shorter latency, however, in the lower visual angle (7.5') in the boys of the supplemented group. CONCLUSIONS: Omega-3 LC-PUFA dietary supplement during pregnancy and lactation influenced the mother and newborn's fatty acid profile and nervonic acid content but did not show effects on visual and cognitive/psychomotor development.