TRPV: An emerging target in glaucoma and optic nerve damage.

Transient receptor potential vanilloid (TRPV) channels are members of the TRP channel superfamily, which are ion channels that sense mechanical and osmotic stimuli and participate in Ca2+ signalling across the cell membrane. TRPV channels play important roles in maintaining the normal functions of an organism, and defects or abnormalities in TRPV channel function cause a range of diseases, including cardiovascular, neurological and urological disorders. Glaucoma is a group of chronic progressive optic nerve diseases with pathological changes that can occur in the tissues of the anterior and posterior segments of the eye, including the ciliary body, trabecular meshwork, Schlemm's canal, and retina. TRPV channels are expressed in these tissues and play various roles in glaucoma. In this article, we review various aspects of the pathogenesis of glaucoma, the structure and function of TRPV channels, the relationship between TRPV channels and systemic diseases, and the relationship between TRPV channels and ocular diseases, especially glaucoma, and we suggest future research directions. This information will help to further our understanding of TRPV channels and provide new ideas and targets for the treatment of glaucoma and optic nerve damage.

Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity.

Glial reactivity is considered a hallmark of damage-induced innate immune responses in the central nervous system. In the visual system, unilateral optic nerve damage elicits dramatic glial reactivity in the retina directly affected by the lesion and a similar, albeit more modest, effect in the contralateral eye. Evaluation of astrocyte changes in a mouse model of optic nerve crush indicates that astrocyte reactivity, as a function of retinal coverage and cellular hypertrophy, occurs within both the experimental and contralateral retinas, although the hypertrophic response of the astrocytes in the contralateral eyes is delayed for at least 24 h. Evaluation of astrocytic reactivity as a function of Gfap expression indicates a similar, muted but significant, response in contralateral eyes. This constrained glial response is completely negated by conditional knock out of Panx1 in both astrocytes and Müller cells. Further studies are required to identify if this is an autocrine or a paracrine suppression of astroglial reactivity.

Non-Invasive Hybrid Ultrasound Stimulation of Visual Cortex In Vivo.

The optic nerve is the second cranial nerve (CN II) that connects and transmits visual information between the retina and the brain. Severe damage to the optic nerve often leads to distorted vision, vision loss, and even blindness. Such damage can be caused by various types of degenerative diseases, such as glaucoma and traumatic optic neuropathy, and result in an impaired visual pathway. To date, researchers have not found a viable therapeutic method to restore the impaired visual pathway; however, in this paper, a newly synthesized model is proposed to bypass the damaged portion of the visual pathway and set up a direct connection between a stimulated visual input and the visual cortex (VC) using Low-frequency Ring-transducer Ultrasound Stimulation (LRUS). In this study, by utilizing and integrating various advanced ultrasonic and neurological technologies, the following advantages are achieved by the proposed LRUS model: 1. This is a non-invasive procedure that uses enhanced sound field intensity to overcome the loss of ultrasound signal due to the blockage of the skull. 2. The simulated visual signal generated by LRUS in the visual-cortex-elicited neuronal response in the visual cortex is comparable to light stimulation of the retina. The result was confirmed by a combination of real-time electrophysiology and fiber photometry. 3. VC showed a faster response rate under LRUS than light stimulation through the retina. These results suggest a potential non-invasive therapeutic method for restoring vision in optic-nerve-impaired patients using ultrasound stimulation (US).

Neuroprotection by trans-resveratrol in rats with N-methyl-D-aspartate (NMDA)-induced retinal injury: Insights into the role of adenosine A1 receptors.

Adenosine A1 receptors (AA1R) have been shown to counteract N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitotoxicity. In the present study, we investigated the role of AA1R in neuroprotection by trans-resveratrol (TR) against NMDA-induced retinal injury. In total, 48 rats were divided into the following four groups: normal rats pretreated with vehicle; rats that received NMDA (NMDA group); rats that received NMDA after pretreatment with TR; and rats that received NMDA after pretreatment with TR and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), an AA1R antagonist. Assessment of general and visual behaviour was performed using the open field test and two-chamber mirror test, respectively, on Days 5 and 6 post NMDA injection. Seven days after NMDA injection, animals were euthanized, and eyeballs and optic nerves were harvested for histological parameters, whereas retinae were isolated to determine the redox status and expression of pro- and anti-apoptotic proteins. In the present study, the retinal and optic nerve morphology in the TR group was protected from NMDA-induced excitotoxic damage. These effects were correlated with the lower retinal expression of proapoptotic markers, lipid peroxidation, and markers of nitrosative/oxidative stress. The general and visual behavioural parameters in the TR group showed less anxiety-related behaviour and better visual function than those in the NMDA group. All the findings observed in the TR group were abolished by administration of DPCPX.

Research progress of ferroptosis in glaucoma and optic nerve damage.

Unlike other death forms, such as autophagy, necrosis, and apoptosis, ferroptosis is a novel type of programmed cell death with iron-dependent properties. Esteroxygenase affects the content of unsaturated fatty acids and promotes lipid peroxidation. In addition, GSH can cause the reduction of GPX4, which can cause ferroptosis. P53 and its signaling pathways also regulate ferroptosis. Recent studies have confirmed that ferroptosis also promotes the death of RGC. The progressive loss of RGC is one of the pathological features of glaucoma, indicating that ferroptosis may be related to the onset of glaucoma. Down-regulation of GPX4 leads to the loss of nerve cells, which suggests that ferroptosis may also be related to diseases related to optic nerve damage. At present, ferroptosis has been extensively researched and advanced in systemic diseases, such as cardiovascular diseases, gastrointestinal tumors such as stomach, liver, and pancreas, and brain diseases. This review focuses on the research progress of ferroptosis in ophthalmic diseases, especially glaucoma and optic nerve damage.

Global brain network modularity dynamics after local optic nerve damage following noninvasive brain stimulation: an EEG-tracking study.

Tightly connected clusters of nodes, called communities, interact in a time-dependent manner in brain functional connectivity networks (FCN) to support complex cognitive functions. However, little is known if and how different nodes synchronize their neural interactions to form functional communities ("modules") during visual processing and if and how this modularity changes postlesion (progression or recovery) following neuromodulation. Using the damaged optic nerve as a paradigm, we now studied brain FCN modularity dynamics to better understand module interactions and dynamic reconfigurations before and after neuromodulation with noninvasive repetitive transorbital alternating current stimulation (rtACS). We found that in both patients and controls, local intermodule interactions correlated with visual performance. However, patients' recovery of vision after treatment with rtACS was associated with improved interaction strength of pathways linked to the attention module, and it improved global modularity and increased the stability of FCN. Our results show that temporal coordination of multiple cortical modules and intermodule interaction are functionally relevant for visual processing. This modularity can be neuromodulated with tACS, which induces a more optimal balanced and stable multilayer modular structure for visual processing by enhancing the interaction of neural pathways with the attention network module.

Research progress of Posner-Schlossman syndrome / 国际眼科杂志(Guoji Yanke Zazhi)

Posner-Schlossman syndrome(PSS)is a sporadic and recurrent self-limiting anterior uveitis, and its pathogenesis remains unclear. It was considered to be a prostaglandin-mediated inflammatory response. In recent years, it has been found to be related to viral infection, immune genetics, vascular endothelial dysfunction, and other factors. Clinically, the disease is predominantly unilateral. The patients with PSS suffer from increased intraocular pressure, mild pain in the affected eye, as well as blurred vision, and irisopsia. Seldom damage to the optic nerve and visual field was reported. The commonly treatment of PSS is local medication, such as anti-inflammatory drugs and intraocular pressure lowering drugs; otherwise systemic medication can be employed in severe cases. Surgical treatment can be performed for PSS if uncontrolled intraocular pressure elevation, frequent attacks, and optic nerve damage and visual field defect due to prolonged disease course. Early diagnosis and treatment of PSS can effectively reduce glaucoma-related damages. This review discussed the research progress of PSS from various aspects, aiming to provide references for the etiology, pathogenesis, and clinical diagnosis and treatment of this disease.

Peripapillary Oxygenation and Retinal Vascular Responsiveness to Flicker Light in Primary Open Angle Glaucoma.

The aim of our study was to evaluate peripapillary oxygenation and its relationship to retinal vascular responsiveness to flicker light in patients with primary open angle glaucoma (POAG). Retinal vessel oxygen saturation was measured in 46 eyes of 34 Caucasian patients with POAG and in 21 eyes of 17 age-matched controls using the oximetry tool of Retinal Vessel Analyser (RVA: IMEDOS Systems UG, Jena, Germany). The mean oxygen saturation of the major arterioles (A-SO2; %) and venules (V-SO2; %), as well as the corresponding arterio−venular difference (A-V SO2; %), were calculated. We also measured retinal vascular responsiveness (RVR) to flicker light by means of RVA. Glaucoma patients were divided in two subgroups according to their median arteriolar and venular vascular responsiveness to flicker light (AFR and VFR). Glaucomatous damage was assessed by optical coherence tomography (Carl Zeiss Meditec, Dublin, CA, USA) and static automated perimetry (Octopus, program G2/standard strategy: Haag-Streit International, Köniz, Switzerland). In addition, we calculated the mean peripapillary oxygen exposure [ppO2E; %/µm] by dividing the mean A-V SO2 with the mean retinal nerve fibre layer (RNFL) thickness. In glaucoma patients, A-SO2 and V-SO2 values were significantly increased, and their difference decreased when compared to controls (p < 0.017; linear mixed-effects model). Grouped with respect to retinal vascular responsiveness to flicker light, subjects with reduced VFR (≤2.9%) had significantly higher ppO2E (0.49 ± 0.08%/µm, respectively, 0.43 ± 0.06%/µm; p = 0.027). Additionally, higher ppO2E in glaucoma patients correlated negatively with the neuroretinal rim area (p < 0.001) and the RNFL thickness (p = 0.017), and positively with the mean defect of the visual field (p = 0.012). Reduced venular vascular responsiveness in our glaucoma patients was associated with increased peripapillary oxygenation exposure. Thus, ganglion cells and their axons in glaucomatous eyes with reduced retinal vascular responsiveness are prone to be more exposed to higher oxidative stress, probably contributing to the further progression of glaucomatous damage.

Intravitreal Trans-Resveratrol Ameliorates NMDA-Induced Optic Nerve and Retinal Injury.

PURPOSE: Retinal and optic nerve damage in glaucoma involves excitotoxicity via N-methyl-D-aspartate (NMDA) receptors. Since, trans-resveratrol (TR) is known to provide neuroprotection, we investigated its protective effects against NMDA-induced retinal and optic nerve injury. METHODS: Sprague Dawley rats were divided into four groups which received vehicle (PBS), NMDA, and TR 0.4 or TR 4 nmol 24 h prior to NMDA, unilaterally and intravitreally. Seven days post-injection, rats were euthanized; eyeballs were enucleated and subjected to hematoxylin and eosin and terminal transferase dUTP nick end labeling staining while optic nerves were isolated for toluidine blue staining. RESULTS: Retinal morphometry showed that ganglion cell layer (GCL) layer thickness within inner retina (IR), retinal cell count (RCC) per 100-µm length of GCL, RCC per 100-µm2 area of GCL, and RCC per 100 µm2 of IR were significantly higher in both TR-treated groups compared to the NMDA group. No differences were observed between the two dose groups. Optic nerve morphology was in accordance with the retinal morphology whereby TR-treated groups showed significantly lesser degenerative changes compared to NMDA-treated group. CONCLUSIONS: TR protects against NMDA-induced changes in retinal and optic nerve morphology by preventing retinal cell apoptosis.

Retinal nerve fibre layer thickness in association with gamma zone width and disc-fovea distance.

PURPOSE: Previous studies have shown that the retinal nerve fibre layer (RNFL) thickness as surrogate of the optic nerve decreases with longer axial length. We explored which explanatory parameters might explain that association. METHODS: Participants of the population-based Beijing Eye Study 2011 without any retinal or optic nerve disease were selected based on a refractive error-based stratified randomization. RESULTS: The study included of 632 participants (age: 59.1 ± 7.3 years; axial length: 23.5 ± 1.2 mm; range: 20.88-28.68 mm). Thicker RNFL (mean: 101.0 ± 10.0 µm) was associated (multivariable analysis) with smaller parapapillary gamma zone (defined as Bruch's membrane-free parapapillary region) (standardized regression coefficient beta: -0.13; non-stadardized regression coefficient B: -0.008; 95% confidence interval (CI): -0.014, -0.003; p = 0.005) and shorter disc-fovea distance (beta: -0.15; B: -3.91; 95% CI: -6.60; -1.22; p = 0.004), after adjusting for age (beta: -0.22; B: -030; 95% CI: -0.41, -0.19; p < 0.001), gender (beta: 0.12; B: 2.37; 95% CI 0.77, 3.97; p = 0.004) and larger optic disc area (beta: 0.12; B: 0.12; 95% CI: 2.14; 95% CI: 0.54, 3.73; p = 0.009). RNFL thickness decreased by 8 µm (95% CI: 3, 14) for each mm increase in gamma zone width, and by 3.91 µm (95% CI: 1.22, 6.60) for each mm elongation of the disc-fovea distance. If disc-fovea distance and gamma zone width were replaced by axial length, the latter was correlated with RNFL thickness (beta: -0.37; B: -3.12; 95% CI: -3.88, -2.35; p < 0.001). Longer disc-fovea distance was directly associated with larger gamma zone (beta: 0.50; B: p < 0.001). CONCLUSIONS: The RNFL thickness decrease with longer axial length is associated with a longer optic disc-fovea distance and larger parapapillary gamma zone. Longer disc-fovea distance and larger gamma zone lead to an elongation and stretching of the retinal nerve fibres, potentially causing a thinning or loss of the nerve fibres. It may explain the occurrence of visual field defects in some non-glaucomatous highly myopic eyes without macular correlates of the perimetric defects.

Changes of Peripapillary Retinal Nerve Fiber Layer in Childhood Glaucoma: A Systematic Review and Meta-Analysis.

Objectives: Retinal nerve fiber layer (RNFL) thickness has been detected by numerous studies about alterations and abnormalities in childhood glaucoma, but these studies have yielded inconsistent results about the RNFL thinning region. The investigation of characteristics of RNFL in pediatric patients would contribute to the deep understanding of the neuropathic mechanisms of childhood glaucoma. Thus, the degree of thinning in different quadrants deserves further discussion and exploration. Method: A systematic literature search was conducted using the Cochrane Central Register of Controlled Trials, Medline, Embase, and PubMed databases to identify clinical studies published from inception to April 1, 2021. Results: Ten studies were included in this review with a total of 311 children with glaucoma and 444 in nonglaucomatous controls. The results revealed that average peripapillary RNFL (pRNFL) thickness was attenuated in pediatric patients with glaucoma [weighted mean difference (WMD) = -20.75; 95% CI -27.49 to -14.01; p < 0.00001]. Additionally, pRNFL thickness in eight quadrants (superior, inferior, temporal, nasal, superotemporal, inferotemporal, superonasal, and inferonasal) had different levels of reduction in the pediatric group of glaucoma. Conclusion: This study indicates that eight regions of RNFL thickness show various degrees of thinning in childhood glaucoma. However, caution is required in the interpretation of results due to marked heterogeneity. Future studies, especially larger samples and multicenter, need to confirm our results.

A meta-analysis of the rate and related factors of glaucomatous optic nerve damage in patients with Glaucomatocyclitic Crisis.

PURPOSE: To systematic analysis of domestic and foreign literature on the incidence and related factors of glaucomatous optic nerve damage (GOND) in patients with Glaucomatocyclitic Crisis (PSS). METHODS: A computerized literature search was carried out in PubMed database, Wanfang Medical Database, China National Knowledge Infrastructure to collected domestic and foreign research studies on the incidence and related factors of glaucomatous optic nerve damage of Glaucomatocyclitic Crisis. Using Stata 15.1 software, select the indicators: incidence, gender, age, single/double eyes, duration of disease, and intraocular pressure (IOP) at onset for meta-analysis. OR (odds risk) was used as the effect variable for the binary variables, and mean difference was used as the effect variable for the continuous variables. The results are expressed by each effect amount and its 95% Confidence interval (CI). If there was heterogeneity among the original studies, a random effects model was used; otherwise, a fixed effects model was used. RESULTS: A total of 13 studies were included. The incidence of GOND in PSS was 0.251 (95%CI: 0.175-0.327). Three studies include the relevant factor analysis and the results showed: there was a statistically significant difference in age, and duration of disease in PSS patients with/without GOND (p = 0.000, p = 0.000), there was no statistical difference between the two groups in gender, single /double eyes, and IOP at onset (p = 0.468, 0.053, 0.065). CONCLUSION: Glaucomatocyclitic Crisis can cause glaucomatous optic nerve damage. GOND is more likely to occur in patients who are older, and have a long course of the disease. For such patients, special attention should be paid to the detailed examination of visual function and follow-up.

Personality and stress influence vision restoration and recovery in glaucoma and optic neuropathy following alternating current stimulation: implications for personalized neuromodulation and rehabilitation.

PURPOSE: Identifying factors that affect recovery or restoration of neurological function is a key goal of rehabilitation in neurology and ophthalmology. One such factor can be prolonged mental stress, which may be not only the consequence of nervous system damage but also a major risk factor, or cause, of neural inactivation. Using the visual system as a model of neural injury, we wished to study how patients' stress and personality profiles correlate with vision recovery as induced by therapy with alternating current stimulation (ACS) in patients with optic nerve damage. METHODS: Personality and stress questionnaires were sent retrospectively to a clinical convenience sample of patients who suffer low vision due to optic nerve damage, which had previously been treated with ACS. The questionnaires included the NEO Five-Factor Inventory (NEO-FFI), the Trier Inventory of Chronic Stress (TICS), and the Flammer syndrome (FS) checklist, which probes signs of vascular dysregulation (VD). These scores were then correlated with the extent of ACS-induced vision restoration as recorded 1-3 years earlier by perimetric visual field tests. RESULTS: Two NEO-FFI personality factors (lower neuroticism, higher conscientiousness) and the presence of physiological Flammer signs were associated with greater recovery as were individual items of the factors openness and agreeableness. Single NEO-FFI item analysis revealed that recovery relates to greater extraversion (optimistic and happy), openness (less guided by authorities for decisions on moral issues), and agreeableness (argue less, like working with others, thoughtful, considerate) as well as the presence of FS signs (cold hands/feet, hypotension, slim body shapes, tinnitus). This suggests that patients with better recovery were more calm, peaceful and secure, hard-working, and reliable, and with high organizational skills. In contrast, patients with poor recovery had a tendency to be emotionally unstable, anxious, unhappy and prone to negative emotions, impulsive, careless, and unorganized. Chronic stress assessed with TICS did not correlate with recovery. CONCLUSION: Vision restoration induced by ACS is greater in patients with less stress-prone personality traits and those who show signs of VD. Prospective studies are now needed to determine if personality has (i) a causal influence, i.e., patients with less stress-prone personalities and greater VD signs recover better, and/or (ii) if personality changes are an effect of the treatment, i.e., successful recovery induces personality changes. Though the cause-effect relationship is still open, we nevertheless propose that psychosocial factors and VD contribute to the highly variable outcome of vision restoration treatments in low vision rehabilitation. This has implications for preventive and personalized vision restoration and is of general value for our understanding of outcome variability in neuromodulation and neurological rehabilitation.

Systems Genetics of Optic Nerve Axon Necrosis During Glaucoma.

In this study, we identify genomic regions that modulate the number of necrotic axons in optic nerves of a family of mice, some of which have severe glaucoma, and define a set of high priority positional candidate genes that modulate retinal ganglion cell (RGC) axonal degeneration. A large cohort of the BXD family were aged to greater than 13 months of age. Optic nerves from 74 strains and the DBA/2J (D2) parent were harvested, sectioned, and stained with p-phenylenediamine. Numbers of necrotic axons per optic nerve cross-section were counted from 1 to 10 replicates per genotype. Strain means and standard errors were uploaded into GeneNetwork 2 for mapping and systems genetics analyses (Trait 18614). The number of necrotic axons per nerve ranged from only a few hundred to more than 4,000. Using conventional interval mapping as well as linear mixed model mapping, we identified a single locus on chromosome 12 between 109 and 112.5 Mb with a likelihood ratio statistic (LRS) of ~18.5 (p genome-wide ~0.1). Axon necrosis is not linked to locations of major known glaucoma genes in this family, including Gpnmb, Tyrp1, Cdh11, Pou6f2, and Cacna2d1. This indicates that although these genes contribute to pigmentary dispersion or elevated IOP, none directly modulates axon necrosis. Of 156 positional candidates, eight genes-CDC42 binding protein kinase beta (Cdc42bpb); eukaryotic translation initiation factor 5 (Eif5); BCL2-associated athanogene 5 (Bag5); apoptogenic 1, mitochondrial (Apopt1); kinesin light chain 1 (Klc1); X-ray repair cross complementing 3 (Xrcc3); protein phosphatase 1, regulatory subunit 13B (Ppp1r13b); and transmembrane protein 179 (Tmem179)-passed stringent criteria and are high priority candidates. Several candidates are linked to mitochondria and/or axons, strengthening their plausible role as modulators of ON necrosis. Additional studies are required to validate and/or eliminate plausible candidates. Surprisingly, IOP and ON necrosis are inversely correlated across the BXD family in mice >13 months of age and these two traits share few genes among their top ocular and retinal correlates. These data suggest that the two traits are independently modulated or that a more complex and multifaceted approach is required to reveal their association.

Association Between BDNF Val66Met Polymorphism and Optic Neuritis Damage in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system (CNS). The purpose of the study was to examine the association between the brain-derived neurotrophic factor (BDNF) Val66Met genotype and structural and functional optic nerve damage in the eyes of NMOSD patients. A total of 17 NMOSD subjects (34 eyes) were included in the study and were divided into subgroups based on optic neuritis (ON) history and BDNF Val66Met polymorphisms. The mean (range) age was 47.8 (23-78) years, and the mean (SD) disease duration was 7.4 (2-39) years. All participants had undergone optical coherence tomography (OCT) scans for global retinal nerve fiber layer (gRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness and multifocal visual evoked potential (mfVEP) test for amplitude and latency. BDNF Val66Met polymorphisms were genotyped in all participants. OCT and mfVEP changes were compared between two genotype groups (Met carriers vs. Val homozygotes) by using the generalised estimating equation (GEE) models. The BDNF Val66Met polymorphism was significantly associated with more severe nerve fiber layer damage and axonal loss in ON eyes of NMOSD subjects. Met carriers had more significantly reduced GCIPL (P = 0.002) and gRNFL (P < 0.001) thickness as well as more delayed mfVEP latency (P = 0.008) in ON eyes. No association was found between Val66Met variants and non-ON (NON)-eye of the participants. These findings suggest that the BDNF Val66Met polymorphism may be associated with optic nerve damage caused by acute ON attacks in NMOSD patients.

Opportunities and challenges for glaucoma research / 中华实验眼科杂志

Elevation of intraocular pressure (IOP) is the most eminent risk factor for the presence and progression of glaucoma,which leads to optic nerve damages ultimately.With the advance of ocular imaging technology,several new structural and functional risk factors have been identified.The introduction of in vivo IOP measuring devices enables the real-time monitoring the IOP fluctuation.New anti-glaucoma drugs and surgical methodshave made more options for glaucoma treatment.Gene therapy and stem cell therapy have potential futures for glaucoma.Incorporation of imaging and deep learning techniques could enhance early detection and diagnosis of glaucoma.There were progresses in optic protection and regeneration.More studies are warrant to investigate the joint mechanism of gene,environment,anatomy and other factors,to develop new imaging techniques and artificial intelligence-assisted diagnostic software platform based on big data,to find new antihypertensive drugs based on different targets,and to assess the efficacy and safety of optic protection and regeneration therapies.

Effects of Pycnogenol on cisplatin-induced optic nerve injury: an experimental study.

AIM: To determine the effects of Pycnogenol on cisplatin-induced optic nerve damage. MATERIAL AND METHOD: Totally 18 albino Wistar male rats were assigned into three groups, with six rats in each group as follows: healthy controls (HC group), only cisplatin (2.5 mg/kg) administered group (CIS group) and Pycnogenol (40 mg/kg) + cisplatin (2.5 mg/kg) administered group (PYC group). We analyzed the levels of malondialdehyde (MDA) as a marker of lipid peroxidation and oxidative stress, total glutathione (tGSH) as a marker of antioxidant status, nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) as inflammatory markers, total oxidative status (TOS) and total antioxidant status (TAS) on eye tissue together with histopathological evaluation of optic nerve in an experimental model. RESULTS: In CIS group MDA, TOS, TNF-α and NF-κB levels were statistically significantly higher (p < 0.001) than HC group while tGSH and TAS levels were significantly lower (p < 0.001). On the other hand, in PYC group MDA, TOS, TNF-α and NF-κB levels were statistically significantly lower (p < 0.001) than CIS group while tGSH and TAS levels were significantly higher (p < 0.001). CONCLUSION: Pycnogenol pretreatment was highly effective in preventing augmentation of cisplatin-induced oxidative stress and inflammation in eye tissue.

Thin minimal rim width at Bruch's membrane opening is associated with glaucomatous paracentral visual field loss.

PURPOSE: To compare optic nerve head (ONH) measurements in glaucomatous eyes with paracentral visual field (VF) loss to eyes with peripheral VF loss and controls. METHODS: Open-angle glaucoma (OAG) patients with early paracentral VF loss or isolated peripheral VF loss as well as control subjects underwent ONH imaging with swept-source optical coherence tomography (OCT) and retinal nerve fiber layer (RNFL) imaging with spectral-domain OCT. Minimum rim width at Bruch's membrane opening (BMO-MRW), lamina cribrosa depth (LCD), and RNFL thickness were compared among the glaucoma and control groups with one-way analysis of variance, Kruskal-Wallis test, and multiple regression analysis. RESULTS: Twenty-nine eyes from 29 OAG patients (15 early paracentral and 14 isolated peripheral VF loss) and 20 eyes of 20 control subjects were included. The early paracentral and isolated peripheral VF loss groups had similar VF mean deviation (MD) (-5.3±2.7 dB and -3.7±3.0 dB, p=0.15, respectively). Global BMO-MRW was lower in OAG eyes than in controls (193.8±40.0 vs 322.7±62.2 µm, p<0.001), but similar between eyes with early paracentral VF loss and those with isolated peripheral VF loss (187.6±43.4 vs 200.6±36.3 µm; p>0.99). In contrast, the minimal BMO-MRW was lower in eyes with early paracentral loss (69.0±33.6 µm) than in eyes with isolated peripheral loss (107.7±40.2 µm; p=0.03) or control eyes (200.1±40.8 µm; p<0.001). Average and thinnest RNFL thickness did not differ between OAG groups (p=0.61 and 0.19, respectively). Horizontal and vertical LCD did not differ among the OAG groups and controls (p=0.80 and 0.82, respectively). Multivariable linear regression analysis among OAG cases confirmed the association between lower minimal BMO-MRW and early paracentral VF loss (ß=-38.3 µm; 95% confidence interval, -69.8 to -6.8 µm; p=0.02) after adjusting for age, gender, MD, and disc size. CONCLUSION: Thin minimal BMO-MRW may represent a new structural biomarker associated with early glaucomatous paracentral VF loss.

MR Imaging of the Anterior Visual Pathway in Primary Open-Angle Glaucoma: Correlation with Octopus 101 Perimetry and Spectralis Optical Coherence Tomography Findings.

PURPOSE: To investigate structural changes in the visual pathway measured by magnetic resonance imaging (MRI) and its relationship with the clinical severity of glaucoma in primary open-angle glaucoma (POAG) patients. MATERIALS AND METHODS: The study included 28 patients with POAG and 26 age- and sex-matched healthy volunteers. All the subjects underwent spectral domain optical coherence tomography (OCT) of the peripapillary retina nerve fiber layer (RNFL). The optic nerve diameter (OND), chiasma height (Ch), and lateral geniculate nucleus height (LGNh) were measured bilaterally using a 1.5-Tesla MRI system. RESULTS: The mean values of the OND and LGNh were significantly lower in the POAG group (OND: right p = 0.043 and left p = 0.048; LGNh: right p = 0.008 and left p = 0.025). The OND was not correlated with the clinical stage of glaucoma, but it was correlated with the ipsilateral RNFL thickness. The Ch was correlated with the ipsilateral clinical stage (right r = -0.536, p = 0.004; left r = -0.537, p = 0.004) and average RNFL thickness (RNFLav) (right r = 0.655, p < 0.001; left r = 0.626, p < 0.001). The sum of bilateral clinical stages and left clinical stages showed significant correlations with the right and left LGNh and the sum of both the right and left LGNh. The left RNFLav and the sum of the right-left RNFLav were significantly correlated with all LGNh measurements. CONCLUSIONS: 1.5-Tesla MRI can detect structural changes in the visual pathway early in the course of glaucoma. Thin optic nerve can be a risk factor for glaucoma. The Ch and LGNh seem to be correlated with the clinical stage of glaucoma and RNFL thickness. In particular, LGN can be a target of glaucomatous damage.

Alterations of the optic pathway between unilateral and bilateral optic nerve damage in multiple sclerosis as revealed by the combined use of advanced diffusion kurtosis imaging and visual evoked potentials.

OBJECTIVES: We investigated changes in the optic tract and optic radiation in patients with multiple sclerosis (MS) by comparing unilateral and bilateral optic nerve damage assessed based on visual evoked potentials (VEPs) using advanced diffusion MR metrics. METHODS: In 21 MS patients, diffusion MRI was performed. Maps of fractional anisotropy, apparent diffusion coefficient (ADC), and mean kurtosis (MK) were computed. On the basis of the P100 latency in VEPs, the MS patients were divided into three groups: bilateral (n=7), unilateral (n=7), and no abnormality (n=7). Their optic tracts and optic radiations were analyzed with diffusion MRI-based fiber tracking. We also investigated the correlations between diffusion parameters and VEPs (n=21). RESULTS: In the optic tract, the diffusion changes in each of the three groups showed step-like changes. The diffusion changes in the optic radiations of the unilateral group were similar to those in the normal VEP group. Only the bilateral group showed significantly higher ADC and lower MK relative to the other two groups (P<0.05, Steel-Dwass multiple-comparison test). A significant positive correlation between VEP latency and ADC and a significant negative correlation between VEP latency and MK were observed (P<0.01, Spearman's correction). CONCLUSIONS: We first evaluated the relationship between VEPs and DKI and concluded that the lateral geniculate nucleus may compensate for unilateral damage in the pre-geniculate optic pathway via neural plasticity.