Spacetime in the brain: rapid brain network reorganization in visual processing and recovery.

Functional connectivity networks (FCN) are the physiological basis of brain synchronization to integrating neural activity. They are not rigid but can reorganize under pathological conditions or during mental or behavioral states. However, because mental acts can be very fast, like the blink of an eye, we now used the visual system as a model to explore rapid FCN reorganization and its functional impact in normal, abnormal and post treatment vision. EEG-recordings were time-locked to visual stimulus presentation; graph analysis of neurophysiological oscillations were used to characterize millisecond FCN dynamics in healthy subjects and in patients with optic nerve damage before and after neuromodulation with alternating currents stimulation and were correlated with visual performance. We showed that rapid and transient FCN synchronization patterns in humans can evolve and dissolve in millisecond speed during visual processing. This rapid FCN reorganization is functionally relevant because disruption and recovery after treatment in optic nerve patients correlated with impaired and recovered visual performance, respectively. Because FCN hub and node interactions can evolve and dissolve in millisecond speed to manage spatial and temporal neural synchronization during visual processing and recovery, we propose "Brain Spacetime" as a fundamental principle of the human mind not only in visual cognition but also in vision restoration.

[Acupuncture prescription of "Wei's triple nine needling therapy" in the treatment of optic nerve disease].

"Wei 's triple nine needling therapy" is the crucial acupuncture prescription in treatment of eye diseases in Wei 's academic school of ophthalmology. "Wei 's triple nine needling therapy" includes the three points near to the eyes, the three groups of points for penetrating acupuncture around the eyes and the acupoint selection based on the general differentiation of syndrome. In this paper, the acupoint selection and the thinking of acupoint combination were introduced in the treatment of optic nerve disease on the base of the theory of "Wei 's triple nine needling" prescription. The specific needling manipulations at different regions involved in the triple needling procedure were explained in detail. It is proposed that the acupoints are combined and the correct needling manipulations selected rationally in compliance with the illness condition and the syndrome characteristics to ensure maximally the clinical effects of "Wei 's triple nine needling therapy".

Benefit of hyperbaric oxygen therapy treatment in direct traumatic optic neuropathy: case report.

Direct traumatic optic neuropathy (TON) is a devastating condition and clinical challenge. Its adequate treatment remains controversial. Hyperbaric oxygen (HBO2) therapy has been proposed as an adjunctive treatment for eye disease but has rarely been used in optic neuropathy. The patient was a 57-year-old woman who had direct TON and brain injury after contusion injury. After receiving delayed HBO2 therapy her visual acuity got better - from hand motion to 6/60 - along with improvement of visual field and color vision. She was treated at 2.5 atmospheres absolute for 100 minutes, five times a week, for a total of 61 sessions. Our case highlights that HBO2 may be beneficial as an alternative treatment for direct TON, particularly when combined with brain injury. Although this entity is promising, further randomized controlled trials will be needed to clarify the efficacy of HBO2 in the treatment of direct TON.

Electrical Stimulation as a Means for Improving Vision.

Evolving research has provided evidence that noninvasive electrical stimulation (ES) of the eye may be a promising therapy for either preserving or restoring vision in several retinal and optic nerve diseases. In this review, we focus on minimally invasive strategies for the delivery of ES and accordingly summarize the current literature on transcorneal, transorbital, and transpalpebral ES in both animal experiments and clinical studies. Various mechanisms are believed to underlie the effects of ES, including increased production of neurotrophic agents, improved chorioretinal blood circulation, and inhibition of proinflammatory cytokines. Different animal models have demonstrated favorable effects of ES on both the retina and the optic nerve. Promising effects of ES have also been demonstrated in clinical studies; however, all current studies have a lack of randomization and/or a control group (sham). There is thus a pressing need for a deeper understanding of the underlying mechanisms that govern clinical success and optimization of stimulation parameters in animal studies. In addition, such research should be followed by large, prospective, clinical studies to explore the full potential of ES. Through this review, we aim to provide insight to guide future research on ES as a potential therapy for improving vision.

Bilateral optic nerve edema presenting as initial manifestation of thyroid eye disease.

A 48-year-old smoker with a history of hyperthyroidism treated 10 years prior to presentation with radioactive iodine ablation of the thyroid gland presented to his ophthalmologist with a 2-week history of transient loss of vision in the right eye occurring for 1 to 2 hours each morning. He denied ocular pain, diplopia or change in the prominence of one or both eyes. Examination revealed 2 mm of relative proptosis on the right, bilateral temporal flare and lower lid retraction. There was minimal upper lid retraction and no evidence of lid lag. Ocular motility was full. Dilated fundoscopic examination revealed bilateral optic nerve edema, right more than left. CT of the orbit demonstrated enlargement of the extraocular muscles bilaterally with marked enlargement of the right medial rectus and left inferior rectus muscles resulting in crowding at the orbital apex bilaterally. Laboratory testing revealed the patient to be hyperthyroid. The patient was treated with high dose oral steroids followed by orbital radiation. Hyperthyroidism was managed by the patient's primary care physician. Visual symptoms rapidly improved with oral steroids and orbital radiation. Optic nerve edema completely resolved. Repeat CT imaging demonstrated a reduction in the enlargement of the extraocular muscles with relief of bilateral optic nerve compression.

Alternating Current Stimulation for Vision Restoration after Optic Nerve Damage: A Randomized Clinical Trial.

BACKGROUND: Vision loss after optic neuropathy is considered irreversible. Here, repetitive transorbital alternating current stimulation (rtACS) was applied in partially blind patients with the goal of activating their residual vision. METHODS: We conducted a multicenter, prospective, randomized, double-blind, sham-controlled trial in an ambulatory setting with daily application of rtACS (n = 45) or sham-stimulation (n = 37) for 50 min for a duration of 10 week days. A volunteer sample of patients with optic nerve damage (mean age 59.1 yrs) was recruited. The primary outcome measure for efficacy was super-threshold visual fields with 48 hrs after the last treatment day and at 2-months follow-up. Secondary outcome measures were near-threshold visual fields, reaction time, visual acuity, and resting-state EEGs to assess changes in brain physiology. RESULTS: The rtACS-treated group had a mean improvement in visual field of 24.0% which was significantly greater than after sham-stimulation (2.5%). This improvement persisted for at least 2 months in terms of both within- and between-group comparisons. Secondary analyses revealed improvements of near-threshold visual fields in the central 5° and increased thresholds in static perimetry after rtACS and improved reaction times, but visual acuity did not change compared to shams. Visual field improvement induced by rtACS was associated with EEG power-spectra and coherence alterations in visual cortical networks which are interpreted as signs of neuromodulation. Current flow simulation indicates current in the frontal cortex, eye, and optic nerve and in the subcortical but not in the cortical regions. CONCLUSION: rtACS treatment is a safe and effective means to partially restore vision after optic nerve damage probably by modulating brain plasticity. This class 1 evidence suggests that visual fields can be improved in a clinically meaningful way. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280877.

Reversible structural and functional changes after intraocular pressure reduction in patients with glaucoma.

PURPOSE: The aim of this study was to evaluate structural and functional improvement following intraocular pressure (IOP) reduction in patients with glaucoma using Spectral Domain Optical Coherence Tomography (SD-OCT), Visual Field (VF) testing, and Visual Evoked Potentials (VEP). METHODS: A total of 76 eyes from 61 patients underwent SD-OCT, VF and VEP testing. Sixty-two eyes were put in either an acutely high (group 1, IOP > 32 mmHg) or mildly high (group 2, IOP between 22 and 31 mmHg) IOP group and underwent a pressure-lowering intervention. Fourteen eyes with stable glaucoma were controls (group 3, IOP < 22 mmHg). SD-OCT, VF and VEP testing were subsequently performed on all patients at three follow-up visits. Results from these follow-up periods were analyzed for signs of functional and structural improvement. RESULTS: Both group 1 and group 2 patients demonstrated significant decrease in the average cup to disc ratio (p < 0.05) following the intervention. Post-interventional reduction of cup volume was also significant for group 2 patients (p < 0.05). RNFL thickness changes were insignificant. Qualitative grading of VFs by two observers showed improvement in group 1 patients' VFs (p = 0.021). VEP measurements were mostly insignificant, with the exception of High Contrast Latency (LHC) deteriorating for group 2 patients in the first follow-up visit (p = 0.025). CONCLUSIONS: This study provides evidence for structural disc cupping reversal following IOP lowering interventions. These changes were not related to the amount of pressure lowering. While there was evidence of functional improvement as measured by VF testing, VEP was unable to detect any reversible changes.

Management of Primary Angle-Closure Glaucoma.

Primary angle-closure glaucoma (PACG) is a progressive optic nerve degeneration and is defined as a glaucomatous optic neuropathy with associated characteristic enlargement of optic disc cupping and visual field loss that is secondary to ocular hypertension caused by closure of the drainage angle. Angle closure is caused by appositional approximation or adhesion between the iris and the trabecular meshwork. The main treatment strategy for PACG lies in the reduction of intraocular pressure, reopening of the closed angle, and possible prevention of further angle closure. There is no universally agreed best surgical treatment for PACG. Trabeculectomy, goniosynechialysis (GSL), glaucoma implant, and cyclodestructive procedures are effective surgical options. Each of them plays an important role in the management of PACG with its own pros and cons. Accumulating evidence is available to show the effectiveness of visually significant and visually nonsignificant cataract extraction in the treatment of PACG. Trabeculectomy and GSL are often combined with cataract extraction, which may offer additional pressure control benefits to patients with PACG. This review article will discuss laser peripheral iridotomy, argon laser peripheral iridoplasty, and surgeries such as GSL, phacoemulsification, and phaco plus glaucoma surgeries that lower intraocular pressure and also alter the anterior segment and/or drainage angle anatomy. Currently, glaucoma implants and cyclodestruction are mainly reserved for PACG patients who have failed previous filtering operations. Their role as initial surgical treatment for PACG will not be discussed.

[Improvement of visual functions after successful microsurgical exclusion of a giant aneurysm of the right internal carotid artery using revascularization techniques]. / Uluchshenie zritel'nykh funktsii posle uspeshnogo mikrokhirurgicheskogo vykliucheniia gigantskoi anevrizmy pravoi vnutrennei sonnoi arterii s primeneniem revaskuliariziruiushchikh metodik.

We describe a clinical case of successful treatment of a female patient with a giant paraclinoid aneurysm of the right ICA. The aneurysm had a pseudotumoral course and manifested as pronounced progressive visual impairments. The patient underwent microsurgery including trapping/clipping of the right ICA aneurysm after creation of an EICMA and a high-flow anastomosis between the ECA and the M2 segment of the MCA. The surgery enabled decompression of the optic nerves, avoiding their injury. Postoperatively, the patient underwent transcutaneous electrical stimulation of the optic nerves. The case feature was that the patient developed gradual restoration of the blind eye vision.

Cambridge community Optometry Glaucoma Scheme.

BACKGROUND: With a higher life expectancy, there is an increased demand for hospital glaucoma services in the United Kingdom. DESIGN: The Cambridge community Optometry Glaucoma Scheme (COGS) was initiated in 2010, where new referrals for suspected glaucoma are evaluated by community optometrists with a special interest in glaucoma, with virtual electronic review and validation by a consultant ophthalmologist with special interest in glaucoma. PARTICIPANTS: 1733 patients were evaluated by this scheme between 2010 and 2013. METHODS: Clinical assessment is performed by the optometrist at a remote site. Goldmann applanation tonometry, pachymetry, monoscopic colour optic disc photographs and automated Humphrey visual field testing are performed. A clinical decision is made as to whether a patient has glaucoma or is a suspect, and referred on or discharged as a false positive referral. The clinical findings, optic disc photographs and visual field test results are transmitted electronically for virtual review by a consultant ophthalmologist. MAIN OUTCOME MEASURES: The number of false positive referrals from initial referral into the scheme. RESULTS: Of the patients, 46.6% were discharged at assessment and a further 5.7% were discharged following virtual review. Of the patients initially discharged, 2.8% were recalled following virtual review. Following assessment at the hospital, a further 10.5% were discharged after a single visit. CONCLUSIONS: The COGS community-based glaucoma screening programme is a safe and effective way of evaluating glaucoma referrals in the community and reducing false-positive referrals for glaucoma into the hospital system.

The role of electrical stimulation therapy in ophthalmic diseases.

INTRODUCTION: Electrical stimulation therapy (EST) involves the use of a low-intensity electrical current in the treatment of neuromuscular conditions. During the recent two decades, EST has emerged as a potential neuroprotective strategy in certain ophthalmic diseases, aided by a lack of effective management for these conditions. PURPOSE: The aim of this review is to summarize and discuss current available evidence for the use of EST in ophthalmic diseases in the laboratory setting and in human trials. METHODS: The compilation and review of published English-language reports on the use of EST in human ophthalmic disease and animal models of ophthalmic disease. RESULTS: From published reports, research work on the use of EST in ophthalmic diseases began in the last 20 years. Different methods of electrical stimulation have been devised, with varying levels of invasiveness. Results from human trials have favored earlier and repeated treatment after insults to the optic nerve, while EST has shown transient effectiveness in degenerative diseases of photoreceptors. Patients also reported no serious adverse effects from EST in the clinical trials. Results from animal studies have further confirmed survival benefits of EST in retinal cell survival, with the underlying mechanism likely multifactorial, but involving Müller cell modulation. CONCLUSIONS: Results from human and animal studies have demonstrated the relevance and potential effectiveness of EST in ophthalmic disease. However, optimal disease and species-specific stimulation settings need to be defined.

Nutritional optic neuropathy.

Nutritional optic neuropathy (aka deficiency optic neuropathy) is a dysfunction of the optic nerve resulting from improper dietary content of certain nutrients essential for normal functioning of the nerve fibers. Most commonly, it results from folic acid and vitamin B complex deficiency associated with malnutrition or poor dietary habits, incorrectly applied vegetarian diet, or chronic alcohol abuse. Obese patients after bariatric surgery constitute another risk group of optic neuropathy. Nutritional optic neuropathy is characterized by painless, gradually progressing, bilateral and symmetrical decrease in visual acuity, which can be accompanied by the color vision dysfunction. Progression of the neuropathy is associated with optic nerve atrophy, manifesting as complete disc pallor. Treatment of nutritional neuropathy includes dietary supplementation, aimed at compensating for the deficient nutrients. The treatment is mostly based on folic acid, vitamin B complex, and protein replacement, as well as eliminating risk factors of neuropathy. Early treatment commencement, prior to irreversible optic nerve atrophy, is a prerequisite of effective treatment. We would like to highlight this problem by presenting the case of a young woman in whom chronic use "water-based" diet resulted in anemia and bilateral nutritional optic neuropathy.

Brain functional connectivity network breakdown and restoration in blindness.

OBJECTIVE: To characterize brain functional connectivity in subjects with prechiasmatic visual system damage and relate functional connectivity features to extent of vision loss. METHODS: In this case-control study, resting-state, eyes-closed EEG activity was recorded in patients with partial optic nerve damage (n = 15) and uninjured controls (n = 13). We analyzed power density and functional connectivity (coherence, Granger causality), the latter as (1) between-areal coupling strength and (2) individually thresholded binary graphs. Functional connectivity was then modulated by noninvasive repetitive transorbital alternating current stimulation (rtACS; 10 days, 40 minutes daily; n = 7; sham, n = 8) to study how this would affect connectivity networks and perception. RESULTS: Patients exhibited lower spectral power (p = 0.005), decreased short- (p = 0.015) and long-range (p = 0.033) coherence, and less densely clustered coherence networks (p = 0.025) in the high-alpha frequency band (11-13 Hz). rtACS strengthened short- (p = 0.003) and long-range (p = 0.032) alpha coherence and this was correlated with improved detection abilities (r = 0.57, p = 0.035) and processing speed (r = 0.56, p = 0.049), respectively. CONCLUSION: Vision loss in the blind is caused not only by primary tissue damage but also by a breakdown of synchronization in brain networks. Because visual field improvements are associated with resynchronization of alpha band coherence, brain connectivity is a key component in partial blindness and in restoration of vision.

Case report: hyperbaric oxygen and MRI findings in radiation-induced optic neuropathy.

Hyperbaric oxygen (HBO2) therapy has been utilized in conjunction with systemic corticosteroid administration for treating radiation-induced optic neuropathy (RON) with varying success. We present the case of a 78-year-old female with RON who received two courses of HBO2 (without corticosteroids) and also pre- and post-treatment magnetic resonance imaging (MRI) of her brain. Her visual acuity subjectively and functionally improved throughout her first course of 30 treatments, including regaining the ability to ambulate independently, but subsequently deteriorated following completion. A second course of 40 additional treatments was prescribed; the patient's visual symptoms subjectively improved once more, followed again with subsequent decline after treatment. Post-treatment MRI also showed resolution of previously visible optic nerve contrast enhancement. This patient represents the 27th reported case of RON treated with HBO2 and the first reported case of radiologic and transient symptomatic improvement without concomitant steroid use. Our case adds additional evidence to the limited anecdotal data supporting MRI correlation with RON symptoms and HBO2 in RON treatment as well.

Optic neuropathy, myelopathy, anemia, and neutropenia caused by acquired copper deficiency after gastric bypass surgery.

Malabsorptive bariatric surgery is rapidly becoming a major cause of copper deficiency given the increasing prevalence of these procedures for morbid obesity. Acquired copper deficiency can present with clinically significant hematologic and neurological manifestations. Although hematologic manifestations of copper deficiency are rapidly reversible, significant neurological improvement after copper supplementation therapy is unusual and many patients remain debilitated and may only experience, at best, stabilization of the neurological manifestations. Here we present a case of an undiagnosed copper deficiency several years after bariatric gastric bypass surgery, in a patient who concomitantly used zinc-containing denture cream for several years, associated with anemia, neutropenia, myelopathy, respiratory failure, and bilateral optic neuropathy, which caused major vision loss. This patient was also a heterozygote carrier of the 5,10-methylenetetrahydrofolate reductase A1298C gene polymorphism, which may affect copper metabolism. Intravenous copper repletion resulted in rapid correction of hematologic indices. However, neurological manifestations, including vision loss responded only modestly to copper supplementation, despite achieving normal blood copper concentrations. Clinicians should consider copper deficiency in patients at risk, as in this case, as a delayed diagnosis can lead to irreversible disability due to neurological manifestations.

Advanced glaucoma: management pearls.

A significant proportion of glaucoma patients present late, particularly in the developing world, and unfortunately, in an advanced stage of the disease. They are at imminent danger of losing remaining vision, and may also be afflicted with various socioeconomic and health challenges. The encounter with such a patient is typically characterized by anxiety/fear and sometimes hopelessness from the patient's perspective. The physician may also feel that they are in a difficult position managing the patient's disease. When dealing with such cases, we suggest a holistic, individualized approach taking into account the 'biopsychosociospiritual' (BPSS) profile of each patient. The BPSS model takes into account relevant ocular as well as systemic biology (factors such as the mechanism of glaucoma, level of intraocular pressure [IOP], rate of progression, life expectancy, general health), psychological considerations (e.g., fear, depression), socio-economic factors and spiritual/cultural values and beliefs before being able to decide with the patient and their care partner(s) what treatment goals should be and how they can best be approached. Treatment for advanced glaucoma can be highly effective, and patients and their care partners should be informed that aggressive IOP lowering to the low teens or even single digits offers the best chance of protecting remaining vision. This can be achieved safely and effectively in most cases with trabeculectomy (including an antimetabolite), and in some cases with medical and/or laser therapy. Vision rehabilitation and psychosocial support should also be considered in order to optimize remaining vision, replace fear with hope as appropriate, and thus improve the overall quality of life.

Late-onset radiation-induced optic neuropathy after radiotherapy for nasopharyngeal carcinoma.

Radiation-induced optic neuropathy (RION) is a rare but devastating late complication of radiotherapy, usually manifesting months to years after cancer treatment of the head and neck, resulting in rapidly progressive blindness in one or both eyes. The incidence of radiation-induced complications following radiotherapy, especially RION, is correlated with survival time of patients. Nasopharyngeal carcinoma (NPC), the most common type of cancer in southern China, has been primarily treated with radiotherapy, with associated neural injuries. To our knowledge, there are few reports of RION among patients with NPC who have undergone radiotherapy. To study this further, we reviewed nine patients with NPC and RION after radiotherapy and examined the clinical manifestations of RION, characteristics of the ophthalmologic examination, MRI results and the treatments used. Of the nine patients with RION, the most frequent clinical presentation was a decline of vision with visual field defects in one or both eyes. Ophthalmologic examinations showed flame hemorrhages in the retina, optic nerve atrophy and cotton wool spots. T1-weighted enhanced MRI showed enhancement of the optic nerve and optic chiasm in six patients. Treatment with corticosteroids, anticoagulation and hyperbaric oxygen (HBO) treatment did not reduce visual loss or blindness in patients.

The delayed cost of treatment.

A 78-year-old woman presented with acute decreased vision in both eyes. She had been treated for a pituitary mass with a total of 4,500 centigray of external beam radiation 8 months prior to presentation. She was diagnosed with radiation optic neuropathy. Treatment with hyperbaric oxygen and intravenous steroids were initiated but vision remained poor.