Non-invasive electrical brain stimulation for vision restoration after stroke: An exploratory randomized trial (REVIS).

BACKGROUND: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke. OBJECTIVE: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke. METHODS: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm. RESULTS: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well. CONCLUSIONS: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials.NCT01418820 (clinicaltrials.gov).

Crystalline Wax Esters Regulate the Evaporation Resistance of Tear Film Lipid Layers Associated with Dry Eye Syndrome.

Dry eye syndrome (DES), one of the most common ophthalmological diseases, is typically caused by excessive evaporation of tear fluid from the ocular surface. Excessive evaporation is linked to impaired function of the tear film lipid layer (TFLL) that covers the aqueous tear film. The principles of the evaporation resistance of the TFLL have remained unknown, however. We combined atomistic simulations with Brewster angle microscopy and surface potential experiments to explore the organization and evaporation resistance of films composed of wax esters, one of the main components of the TFLL. The results provide evidence that the evaporation resistance of the TFLL is based on crystalline-state layers of wax esters and that the evaporation rate is determined by defects in the TFLL and its coverage on the ocular surface. On the basis of the results, uncovering the nonequilibrium spreading and crystallization of TFLL films has potential to reveal new means of treating DES.

Ocular trauma in the Finnish elderly - Helsinki Ocular Trauma Study.

PURPOSE: To describe epidemiology, causes, treatments and outcomes of all ocular injuries in southern Finland among people aged 61 and older. METHODS: All new ocular trauma patients, admitted to the Helsinki University Eye Hospital, during 1 year in 2011-2012. The data were from hospital records and prospectively from patient questionnaires. The follow-up time was 3 months. RESULTS: The incidence for ocular injuries among the elderly was 38/100 000/year. From 118 patients 69% were men. The mean age was 70.9 years old (median 67). The hospitalization rate was 14%. Injury types were minor traumas (48%), contusions (22%), chemical injuries (10%), eyelid wounds (8%), open globe injuries (OGI; 7%) and orbital fractures (5%). The injuries occurred at home (58%), institutions (12%) and in other public places (12%). The main causes of ocular injury were falls (22%), sticks (19%), superficial foreign bodies (18%) and chemicals (12%). All OGI and 88% of contusions needed a lifelong follow-up. A permanent visual or functional impairment occurred in 15 (13%) patients. Of these 53% were OGI, 40% contusions and 7% chemical injuries. The causes of permanent injuries were falls (seven cases, 47%), work tools, sports equipment, sticks, chemicals and eyeglasses. The incidence for legal blindness was 2.3/100 000. CONCLUSION: Minor trauma was the most frequent type, and home was the location of the most occurred eye injuries. Falls were the most frequent and serious cause, but behavioural causes were not significant. Preventive measures should be directed towards the main identified causes and risk factors of the eye injuries in the elderly.

Relevance of Lipid-Based Products in the Management of Dry Eye Disease.

Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.

Pure Glaucoma Drugs Are Toxic to Immortalized Human Corneal Epithelial Cells, but They Do Not Destabilize Lipid Membranes.

PURPOSE: Most pure glaucoma drugs (pGDs) are hydrophobic substances intended to reduce elevated intraocular pressure. The aims of our study were to determine the toxicity of pGDs (brimonidine tartrate, brinzolamide, latanoprost, timolol maleate, and pilocarpine hydrochloride) on ocular surface cells and to establish whether their toxicity is subsequent to cellular membrane destabilization. METHODS: The toxicity of clinically efficient doses of pGDs was measured at different time points in a cell culture of human corneal epithelial cells using a redox indicator. pGD interaction with the plasma membrane was analyzed using a hemolysis assay and liposome electrokinetic chromatography. The capacity of pGDs to induce endoplasmic reticulum stress was investigated by immunoblotting. RESULTS: The toxicity assay showed that all pGDs decrease the viability of the epithelial cells to variable degrees. Early toxicity was measured for 4% pilocarpine and 0.15% brimonidine with 60% cell death at 4 hours, whereas 2% pilocarpine and 0.005% latanoprost showed almost 100% toxicity but only after 16 hours. The hemolysis assay and liposome electrokinetic chromatography experiments suggested that interaction between pGDs and lipid membranes is weak and cannot explain cell death through lysis. Immunoblotting revealed that the drugs activate endoplasmic reticulum stress and, with the exception of pilocarpine, have the capacity to induce apoptosis through upregulation of C/EBP homologous protein. CONCLUSIONS: Our study indicates that all studied pGDs decrease the viability of the corneal epithelial cells, but none of the tested compounds were able to destabilize cellular membranes. The pGDs seem to be internalized and can induce apoptosis through C/EBP homologous protein recruitment.

TFOS DEWS II Tear Film Report.

The members of the Tear Film Subcommittee reviewed the role of the tear film in dry eye disease (DED). The Subcommittee reviewed biophysical and biochemical aspects of tears and how these change in DED. Clinically, DED is characterized by loss of tear volume, more rapid breakup of the tear film and increased evaporation of tears from the ocular surface. The tear film is composed of many substances including lipids, proteins, mucins and electrolytes. All of these contribute to the integrity of the tear film but exactly how they interact is still an area of active research. Tear film osmolarity increases in DED. Changes to other components such as proteins and mucins can be used as biomarkers for DED. The Subcommittee recommended areas for future research to advance our understanding of the tear film and how this changes with DED. The final report was written after review by all Subcommittee members and the entire TFOS DEWS II membership.

The Effect of Phospholipids on Tear Film Lipid Layer Surface Activity.

Purpose: We illustrate the importance of small quantities (<10 mol%) of polar phospholipids on the surface-active behavior of meibum-like lipid compositions. Methods: Artificial meibum-like lipid mixture containing cholesteryl and wax esters was mixed with differing amounts of phosphatidylcholine (PC). The surface activity of these mixtures was investigated at the air-water interface by recording surface pressure created by the lipid layer as a function of molecular area at 37°C. The PC proportion in the mixtures was 0, 2.5, 5, 7.5, or 10 mol%, and the remaining proportion in the mixture was 50:50 (mol/mol) of cholesteryl oleate (CO) and behenyl oleate (BO). Also, the effect of temperature was investigated. Results: The surface activity of the mixtures increased in a very predictable and consistent fashion as a function of the PC proportion. The lipid mixture containing only CO and BO showed miniscule surface activity. However, already 2.5% PC mixed with the nonpolar CO and BO generated considerable increase in surface pressure. At small surface areas, the behavior of 7.5% and 10% PC compositions started to approach that of a pure PC monolayer. The temperature did not have a considerable impact on the surface-active behavior of the PC-containing compositions. Conclusions: The polar phospholipids have a considerable effect on the surface-active properties of artificial tear film lipid layer (TFLL) compositions. Surprisingly, this takes place already at very low and physiologically relevant PC proportions. The effect is more dependent on the actual amount of the phospholipids at the air-tear interface than on the relative amount of these lipids in TFLL.

Ocular traumas in working age adults in Finland - Helsinki Ocular Trauma Study.

PURPOSE: To describe epidemiology, causes, treatments and outcomes of ocular injuries in adults aged 17 to 60 in southern Finland. METHODS: All new ocular trauma patients admitted to the Helsinki University Eye Hospital (HUEH), during 1 year in 2011-2012. The data were from hospital records and prospectively from patient questionnaires. The follow-up time was 3 months. RESULTS: The incidence for ocular injury was 88/100 000/year. From 831 trauma patients, 80% were men, 34% were work-related injuries, and 11% were assaults. Most of the injuries were minor traumas (54%). Contusions (22.5%) and chemical injuries and burns (13%) were common. Fractures (5%), lid wounds (3%), open globe injuries (OGI, 2%) and optic nerve injuries (0.5%) were rare. The main causes of ocular injury were superficial foreign bodies (33%), chemicals (13%), body parts (13%) and sports equipment (10%). The most dangerous objects were needles, stones, pellet guns, tools and guns. No patient with OGI used protective eyewear. All OGI and most of contusions needed a lifelong follow-up. Permanent impairment (73 patients, 9%) was caused most often by body parts, sports equipment and work tools. CONCLUSION: A typical ocular trauma patient was a man aged 31-45 with a minor trauma caused by a foreign body at work and a final visual acuity of 20/20. Most common serious injuries were contusion, OGI or fracture at home or at work and were caused by a body part, sport equipment or work tool. Factors causing common and serious eye injuries provide the targets for protective measures.

Distribution of local anesthetics between aqueous and liposome phases.

Liposomes were used as biomimetic models in capillary electrokinetic chromatography (EKC) for the determination of distribution constants (KD) of certain local anesthetics and a commonly used preservative. Synthetic liposomes comprised phosphatidylcholine and phosphatidylglycerol phospholipids with and without cholesterol. In addition, ghost liposomes made from red blood cell (RBC) lipid extracts were used as pseudostationary phase to acquire information on how the liposome composition affects the interactions between anesthetics and liposomes. These results were compared with theoretical distribution coefficients at pH 7.4. In addition to 25°C, the distribution constants were determined at 37 and 42°C to simulate physiological conditions. Moreover, the usability of five electroosmotic flow markers in liposome (LEKC) and micellar EKC (MEKC) was studied. LEKC was proven to be a convenient and fast technique for obtaining data about the distribution constants of local anesthetics between liposome and aqueous phase. RBC liposomes can be utilized for more representative model of cellular membranes, and the results indicate that the distribution constants of the anesthetics are greatly dependent on the used liposome composition and the amount of cholesterol, while the effect of temperature on the distribution constants is less significant.

Paediatric eye injuries in Finland - Helsinki eye trauma study.

PURPOSE: To determine the current population-based epidemiology, treatment, use of resources and outcomes of children's eye injuries in Finland. METHODS: The study included all new patients, 16 years of age or under, with ocular or orbital traumas taken into care to the Helsinki University Eye Hospital (population base 1.5 million people) in 1 year. The follow-up period was 3 months. RESULTS: Two hundred and two children's eye injuries were treated. The eye injury incidence was 5.2-8.3 per 10 000 per year, including all minor and major eye traumas. Eye injury most likely occurred at the junior high school age (13-16 years). Thirty-three percentage of accidents took place at home and 24% at school or in day care. The most common causes were sports equipment (15%), contact with human body (12%) and superficial foreign bodies (11%). Excluding minor injuries, contusion was the most common diagnosis (n = 60, 30%). Eighty-seven percentage of contusion patients were estimated to need lifelong follow-up due to elevated glaucoma risk. Nine percentage of all patients had a permanent disability. Guns, fireworks, tools and pellet guns were relatively the most dangerous objects. Pellet guns caused 6% of eye injuries, 36% of them causing permanent impairment. The number of outpatient visits was altogether 443, inpatient days were 49, and 60 children had major surgeries. CONCLUSIONS: Use of protective eyewear would have prevented or diminished eye traumas caused by pellet gun, floorball, most of the firework and in many superficial foreign body. The use of pellet guns and protective eyewear should be more supervised. Fireworks and tools are not suitable toys for children.

Bilateral Ectasia After Femtosecond Laser-Assisted Small Incision Lenticule Extraction (SMILE).

PURPOSE: To describe a case of bilateral ectasia after small incision lenticule extraction (SMILE) in a patient with early keratoconus. METHODS: Case report. RESULTS: Bilateral SMILE was performed on a patient even though preoperative topographies showed changes indicating early keratoconus. The right eye underwent further photorefractive keratectomy enhancement 18 months later. The patient developed a bilateral corneal ectasia. CONCLUSIONS: This case underlines the importance of thorough preoperative assessment for possible keratoconus suspect changes with corneal topography to avoid postoperative ectasia. [J Refract Surg. 2016;32(7):497-500.].

Matrix Regeneration Therapy: A Case Series of Corneal Neurotrophic Ulcers.

PURPOSE: Treating corneal neurotrophic ulcers is challenging. Topical application of matrix regeneration therapy (RGTA), which is a dextran derivative polymer and heparan sulfate analog, is a promising regenerative therapy and an alternative or additional therapeutic regimen when corneal healing is compromised. The aim of this study was to evaluate the efficacy of RGTA (Cacicol) in the treatment of 6 patients with severe neurotrophic ulcers. METHODS: We present an uncontrolled prospective case series of 6 patients (6 eyes) with severe corneal neurotrophic ulcers. Patients were treated with topical RGTA at a dose of 1 drop every second day. The main outcome measure was complete corneal epithelialization. We measured corneal thickness by anterior segment swept-source optical coherence tomography. RESULTS: Two patients (33%) showed complete corneal healing, one at 6 weeks and the other at 10 weeks. Treatment was considered failure in 4 patients (67%), and 1 patient had corneal perforation. None of the patients showed improvement in best-corrected visual acuity. There were no RGTA-related local or systemic side effects. CONCLUSIONS: Based on previous studies, RGTA seems to be a promising therapeutic agent for controlling ocular surface inflammation and promoting corneal healing. In this study, the efficacy of RGTA did not match the encouraging results from previous reports.

[Amnion in the treatment of ocular diseases]. / Amnionkalvo silmäsairauksien hoidossa.

Amnion is the innermost membrane of the structural layers of the placenta. It has been utilized both as tissue transplant and biological wound dressing in the treatment of cutaneous and mucosal injuries already for more than a century. It can be attached onto various tissue and wound surfaces even without sutures, if necessary. The amnion can also be utilized in the treatment of ocular diseases; and it has been shown to promote healing of the cornea in various ways. In this review we discuss the use of amnion in ophthalmology and in the treatment of ocular diseases.

Femtosecond Laser-Assisted Intrastromal Relaxing Incisions After Penetrating Keratoplasty: Effect of Incision Depth.

PURPOSE: To correlate the efficacy of femtosecond laser-assisted intrastromal relaxing incisions after penetrating keratoplasty with the posterior depth of corneal incisions. METHODS: Twenty eyes of 20 patients were treated for regular postoperative penetrating keratoplasty astigmatism. Sutures had been removed and refraction had stabilized. Ultrasound pachymetry was used to calculate incisional depth. Femtosecond laser-assisted paired arcuate incisions were made inside the graft stroma, leaving 90 µm of intact anterior cornea including epithelium. The intact posterior corneal margin was 10% of the measured corneal thickness for 10 patients (10% group) and 125 µm for the remaining 10 patients (125-µm group). Follow-up visits consisted of biomicroscopy, intraocular pressure measurement, fundus examination, and topographic evaluation using anterior segment optical coherence tomography at 1 and 3 months. Postoperative corneal thickness and the depth of incisions were measured with optical coherence tomography. RESULTS: Corrected distance visual acuity improved from 0.5 to 0.3 logMAR (Snellen: 20/63 to 20/40, P < .05) in the 10% group and remained constant in the 125-µm group. The refractive cylinder decreased by 34% in the 10% group (range: 0% to 60%), but did not change in the 125-µm group. The topographic anterior cylinder decreased in both groups by 48% (range: 0% to 67%) and 13% (range: 0% to 38%), respectively. The smaller the posterior intact corneal margin, the higher the surgically induced astigmatism (P < .05). CONCLUSIONS: Efficacy of femtosecond laser-assisted intrastromal relaxing incisions is correlated with the posterior depth of the incisions. The deeper incisions were more effective.

The genetic variant rs4073 A→T of the Interleukin-8 promoter region is associated with the earlier onset of exudative age-related macular degeneration.

PURPOSE: To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. METHODS: Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. RESULTS: Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. CONCLUSION: Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD.

Traffic and Criminal Behavior of Adults with Attention Deficit-Hyperactivity with a Prospective Follow-Up from Birth to the Age of 40 Years.

OBJECTIVE: The purpose of this study was to investigate whether individuals with attention deficit-hyperactivity disorder (ADHD) followed up to age 40 have a higher mortality, more involvement in criminal behavior, increased traffic accidents, and frequency or registered violations against traffic rules or whether they have been more frequently victims to crimes. METHODS: The ADHD cohort (N = 122) born in 1971-1974 was isolated at the age of 9 years from the base cohort of 865 children who had known risk factors at birth and were still alive at the age of 5 years. Ninety-four healthy individuals born during the same years served as control subjects. None of the individuals with ADHD had used psychostimulants before their adolescence. The follow-up data were available from the newborn period until the ages of 5 and 9 years. At the ages of 16 and 30, the data were collected via questionnaire. For this study, the national police registers (last 5 years) were examined for traffic violations, crimes, or being an object of a criminal act when the persons reached the age of 40 years. RESULTS: Ten men and one woman with ADHD but none of the controls had died by the age of 40. Three died of disease-related incidents, and 8 (13%) died of abnormal causes such as suicide (3), traffic accident (2), substance abuse (2), or violence (1). During the follow-up period, individuals with ADHD had been involved in violent behavior or economic criminality more frequently than the control subjects. They were also more commonly victims of criminal acts. No difference was found in traffic citations between those with ADHD and control subjects (at 35-40 years) when all traffic crimes were considered. A difference was not observed in the frequency of traffic accidents. However, there was a significant difference in drunk driving (at the ages of 30 and 35-40) and the number of persons without a driver's license. DISCUSSION: Subjects with ADHD showed an elevated risk of being involved in criminality and had a higher risk of dying before the age of 40 years. The early detection of ADHD in childhood and appropriate treatments and family support may decrease criminality and save both money and human distress.

Impact of amphiphilic biomass-dissolving ionic liquids on biological cells and liposomes.

The toxicity of some promising biomass-dissolving amidinium-, imidazolium-, and phosphonium-based ionic liquids (ILs), toward two different cell lines, human corneal epithelial cells and Escherichia coli bacterial cells, was investigated. In addition, dynamic light scattering (DLS) and ζ potential measurements were used to study the effect of the ILs on the size and surface charge of some model liposomes. Capillary electrophoresis (CE) was used for determination of the electrophoretic mobilities of the liposomes and for determination of the critical micelle concentration (cmc) of the ILs. The toxicity of the phosphonium ILs was highly dependent on the longest linear chain of the IL, due to increasing hydrophobicity, with the long-chain phosphonium ILs being toxic while the shorter-chain versions were significantly less toxic or not toxic at all. Amidinium and imidazolium ILs showed no significant effect on the cells, within the concentration range used. Moreover, the more hydrophobic ILs were found to have a major effect on the surface charges and size distributions of the model liposomes, which can lead to disruption of the lipid bilayer. This indicates that the cytotoxicity is at least to some extent dependent on direct interactions between ILs and the biomembrane.