Clinical course of Acanthamoeba keratitis by genotypes T4 and T8 in Hungary.

Genus Acanthamoeba is an opportunistic protozoan that is widely distributed in the environment. Within this genus, numerous species are recognized as human pathogens, potentially causing Acanthamoeba keratitis (AK). AK is a corneal disease, associated predominantly with contact lens (CL) wear; its epidemiology is related to the specific Acanthamoeba genotypes. This study reports seven CL wearer, Acanthamoeba PCR-positive patients with AK, diagnosed between January 2015 and 2018. Patients had the diagnosis of AK 1.36 months after first symptoms. Genotyping allowed the identification of six isolates of the T4 and one of the T8 genotypes. At first presentation, pseudendritiformic epithelopathy/dirty epithelium (four eyes, 57.1%), multifocal stromal infiltrates (five eyes, 71.4%), ring infiltrate (three eyes, 42.8%), and perineuritis (one eye, 14.3%) were observed. AK was healed without later recurrence in two eyes (28.5%) using triple-topical therapy, in three eyes (42.8%) following additional penetrating keratoplasty. In one patient (14.3%), AK recurred following successful application of triple-therapy and was treated successfully with repeated triple-topical therapy and in one patient (14.3%), no follow-up data were available after diagnosis. We could not observe correlation of genotype and clinical course or the necessity of corneal transplantation in our case series.

[Evaluation of free radical quantity in the anterior chamber following femtosecond laser-assisted capsulotomy]. / Szabadgyök-felszabadulás vizsgálata femtoszekundum lézerrel asszisztált capsulotomiát követoen.

INTRODUCTION: Femtosecond laser is a revolutionary, innovative treatment method used in cataract surgery. AIM: To evaluate free radical quantity in the anterior chamber of the eye, during femtosecond laser assisted capsulotomy, in a porcine eye model. METHOD: Seventy fresh porcine eyes were collected within 2 hours post mortem, were transported at 4 ºC and treated within 7 hours. Thirty-five eyes were used as control and 35 as femtosecond laser assisted capsulotomy group. A simple luminol-dependent chemiluminescence method was used to measure the total scavenger capacity in the aqueous humour, as an indicator of free radical production. The emitted photons were expressed in relative light unit %. RESULTS: The relative light unit % was lower in the control group (median 1%, interquartile range [0.4-3%]) than in the femtosecond laser assisted capsulotomy group (median 4.4%, interquartile range [1.5%-21%]) (p = 0.01). CONCLUSIONS: Femtosecond laser assisted capsulotomy decreases the antioxidant defense of the anterior chamber, which refers to a significant free radical production during femtosecond laser assisted capsulotomy. Orv. Hetil., 2016, 157(47), 1880-1883.

[Results of femtosecond laser-assisted cataract surgery using the new 2.16 software and the SoftFit® Patient Interface]. / A femtoszekundumlézer-asszisztált szürkehályog-mutét eredményei az új 2.16-os szoftverrel és a módosított SoftFit® páciensi felszínnel.

INTRODUCTION: Femtosecond laser-assisted cataract surgery improved the results of cataract surgeries. AIM: Outcome analysis of femtosecond laser-assisted cataract surgery using the novel 2.16 software and the SoftFit(®) Patient Interface. METHOD: The novel software and the newly developed Patient Interface were used in 100 eyes of 100 patients. RESULTS: Length of femtosecond laser pretreatment decreased to 45-60 seconds. The smaller size of the new patient interface resulted in easier docking even on pediatric eyes. Suction force used for docking decreased from 40-50 mmHg to 16-20 mmHg. Incidence rate of subconjunctival suffusion decreased from 40% to 15-20% and its clinical severity was reduced, too. No corneal microfolds evolved, thus the incidence rate of the free-floating capsulotomies increased from 30% to 97%. The total energy of femtosecond laser pretreatment was decreased by almost 50%. Corneal wounds had the desired structure, and they were easy to open and closed precisely. CONCLUSIONS: The SoftFit(®) patient interface and the novel software widened the possible uses of the femtosecond laser-assisted cataract surgery, e.g. in pediatric ophthalmology. Innovations improved the safety and the predictability of the method.

Retinal and choroidal thickness measurements using spectral domain optical coherence tomography in anterior and intermediate uveitis.

BACKGROUND: Macular edema is a common cause of visual loss at uveitic patients. The aim of our study was to investigate retinal and choroidal thickness at the macula in anterior (AU) and intermediate (IMU) uveitis and in healthy individuals using spectral domain optical coherence tomography (SD-OCT). METHODS: Case-control study of 21 patients with AU and 23 patients with IMU and 34 age-matched healthy controls was performed with Spectralis SD-OCT (Heidelberg Engineering, Germany). High resolution SD-OCT scans and macular mapping were applied for automated measurement of retinal thickness. Standardized, masked manual measurement of the choroidal thickness was performed in the center of the ETDRS fields on enhanced depth imaging (EDI) scans. Evaluation of central retinal subfield thickness, 3 mm and 6 mm perifoveal rings was performed in the corresponding ETDRS zones in patient groups. RESULTS: The mean central retinal subfield thickness was significantly higher in IMU (368.65 ± 115.88 µm, p = 0.0003), but not significantly different in AU (290.42 ± 26.37 µm p = 0.6617) compared to that of in controls (278.55 ± 18.31 µm). In both uveitis groups retina was significantly thicker in the 3 and 6 mm perifoveal rings than that of in controls (359 ± 15.24 µm in AU and 390.55 ± 70.90 µm in IMU vs 345,41 ± 15.28 µm in the control group, p = 0.0388 and p < 0.0001) in the 3 mm and (313.83 ± 16.63 µm in AU and 343.33 ± 57.29 µm in IMU vs 299 ± 13.82 µm in the control group, p = 0.0171 and p < 0.0001) in the 6 mm ring. Central choroidal thickness was 311.94 ± 60.48 µm in the control eyes, showed no significant difference in AU (312.61 ± 90.35 µm) and IMU (303.17 ± 93.66 µm) eyes, and was also similar at the perifoveal rings. CONCLUSION: Significant topographical changes could be detected in the macula of AU and IMU patients. Retinal thickness in the perifoveal rings was increased both in AU and IMU, but in the center only in IMU. Choroidal thickness seems to be unaffected by uveitis, even in the presence of macular edema, at least in the early stage of the inflammatory disease process.

Comparative Analysis of Clinical and Patient-Reported Outcomes of a New Enhanced Monofocal IOL and a Conventional Monofocal IOL.

Purpose: To compare the outcomes of the Tecnis Eyhance ICB00 IOL, designed to enhance intermediate vision, to a conventional Tecnis Monofocal ZCB00 IOL. Methods: This retrospective analysis compared two cohorts of patients undergoing lens replacement surgery with bilateral implantation of the Tecnis ICB00 or the Tecnis ZCB00 IOL (383 patients in each group). Monocular and binocular uncorrected distance (UDVA), intermediate (UIVA; 66cm), and near (UNVA; 40cm) visual acuities, refractive predictability, and patient-reported outcomes were compared. A sub-analysis of patients with the Eyhance IOL was performed to compare patients who achieved bilateral emmetropia to those with mini-monovision. One-month postoperative outcomes were analyzed. Results: Both groups had comparable UDVA outcomes. On average, both monocular and binocular UIVAs were approximately one Snellen line better in patients implanted with Eyhance IOL (monocular UIVA: ICB00 0.23 ± 0.18 logMAR, ZCB00 0.33 ± 0.19 logMAR; binocular UIVA: ICB00 0.18 ± 0.18 logMAR, ZCB00 0.26 ± 0.20 logMAR, p < 0.01). Likewise, the mean UNVA was also one Snellen line better with the ICB00 model (monocular UNVA: ICB00 0.51 ± 0.20 logMAR, ZCB00 0.61 ± 0.18 logMAR; binocular UNVA: ICB00 0.42 ± 0.19 logMAR, ZCB00 0.51 ± 0.22 logMAR, p < 0.01). There was no difference between the two groups in overall satisfaction or visual phenomena. A subgroup of patients who achieved mini-monovision with Eyhance IOL had, on average, one Snellen line better UIVA and UNVA compared to patients with bilateral emmetropia. Conclusion: Patients receiving the enhanced monofocal IOL had better intermediate and near vision compared to those receiving the conventional monofocal IOL, with similar levels of patient-reported photic phenomena in both groups.

Comparison of the 1st Generation and 3rd Generation Wavefront-Guided LASIK for the Treatment of Myopia and Myopic Astigmatism.

Purpose: To compare refractive, visual, and patient-reported outcomes associated with a 1st generation wavefront-guided (WFG) treatment with those associated with a 3rd generation WFG treatment. Patients and Methods: This retrospective study included patients who underwent femtosecond laser-assisted in situ keratomileusis (LASIK) for myopia/myopic astigmatism. Two random stratified samples of patients who underwent either 1stgeneration (WaveScan, Johnson & Johnson Vision, Santa Ana, CA) or 3rd generation (iDesign 2.0, Johnson & Johnson Vision, Santa Ana, CA) treatment matched on preoperative refraction were compared (4290 eyes of 2145 patients in each group). One-month postoperative visual, refractive, and patient-reported outcomes were analyzed. Refractive and monocular visual acuity analyses were performed using one random eye of each patient. Results: The percentage of eyes achieving 20/20 or better uncorrected vision was 91.3% (1958/2145) in the 1st generation group and 95.9% (2056/2145) in the 3rd generation group (p<0.01). Binocularly, the percentage of patients with 20/20 or better UDVA was 97.0% (2080/2145) and 99.2% (2127/2145) in the 1st and 3rd generation groups, respectively (p<0.01). The mean postoperative MSE was -0.01 ± 0.33 D in the 1st generation group and +0.19 ± 0.33 D in the 3rd generation group (p<0.01). Postoperative refractive astigmatism had a mean value of -0.20 ± 0.26 D and -0.18 ± 0.24 D in the 1st and 3rd generation groups, respectively (p<0.01). The mean correction index of refractive astigmatism was 1.09 ± 0.53 in the 1st generation group and 1.02 ± 0.38 in the 3rd generation group, p<0.01. The overall percentage of patients satisfied with vision was 92.8% (1991/2145 patients) in the 1st generation group and 97.3% (2087/2145 patients) in the 3rd generation group (p<0.01). Conclusion: For the majority of postoperative variables, there were significant differences between 1st and 3rd generation treatments. The 3rd generation treatments had better visual acuity outcomes and higher patient satisfaction.

Ageing as a price of cooperation and complexity: self-organization of complex systems causes the gradual deterioration of constituent networks.

The network concept is increasingly used for the description of complex systems. Here, we summarize key aspects of the evolvability and robustness of the hierarchical network set of macromolecules, cells, organisms and ecosystems. Listing the costs and benefits of cooperation as a necessary behaviour to build this network hierarchy, we outline the major hypothesis of the paper: the emergence of hierarchical complexity needs cooperation leading to the ageing (i.e. gradual deterioration) of the constituent networks. A stable environment develops cooperation leading to over-optimization, and forming an 'always-old' network, which accumulates damage, and dies in an apoptosis-like process. A rapidly changing environment develops competition forming a 'forever-young' network, which may suffer an occasional over-perturbation exhausting system resources, and causing death in a necrosis-like process. Giving a number of examples we demonstrate how cooperation evokes the gradual accumulation of damage typical to ageing. Finally, we show how various forms of cooperation and consequent ageing emerge as key elements in all major steps of evolution from the formation of protocells to the establishment of the globalized, modern human society.

Contrast independence of dynamic random dot correlogram evoked VEP amplitude.

Dynamic random dot correlograms (DRDCs) are binocular stimuli that evoke a percept and a visual evoked potential (VEP) only in case of a mature and functional binocular system. DRDC-VEP is a method extensively used to study cortical binocularity in human infants and nonverbal children. Although the DRDC-VEP was invented 3 decades ago, neither the fundamental parameters, including contrast, of the stimulation nor the cerebral processing mechanisms have been clarified. The objective of the present study was to investigate the variability and detectability of adults' VEPs to DRDC under different stimulus contrast conditions. DRDCs were presented on the red and green channels of a computer monitor and were viewed with red-green goggles. The steady state DRDC-VEPs were recorded in healthy adult volunteers, and response reliability was assessed by the T(circ)(2) statistic. DRDC-VEP amplitude was independent of contrast, while VEP phases showed a weak correlation with contrast. Contrast invariance of DRDC-VEP amplitude suggests a very high contrast gain and dominant magnocellular input to the binocular correlation processing system.

Comparison of visual and refractive outcomes between hydrophilic and hydrophobic trifocal intraocular lenses sharing the same optical design.

PURPOSE: To compare clinical outcomes between two trifocal intraocular lenses (IOLs): the new FineVision POD F GF trifocal IOL made of hydrophobic acrylic glistening-free material, and the FineVision POD F IOL made of hydrophilic acrylic material with 26% water uptake in patients undergoing routine cataract surgery using standard phacoemulsification. SETTING: Semmelweis University, Department of Ophthalmology, Budapest, Hungary. DESIGN: Prospective controlled randomized single-center single-surgeon study. METHODS: Each patient had the hydrophilic POD F IOL implanted in one eye and the hydrophobic POD F GF IOL in the contralateral eye, according to a randomization table. Clinical outcomes included distance (4 m), intermediate (70 cm), and near (35 cm) visual acuities, contrast sensitivity measured under photopic and mesopic conditions, and defocus curves under photopic conditions. The follow-up was 6 months. RESULTS: The study comprised 25 patients. Under photopic conditions, there was no statistically significant difference between POD F GF and POD F IOLs for uncorrected distance (UDVA) (P = .607), uncorrected intermediate (UIVA) (P = .491), and uncorrected near (UNVA) (P = .414) visual acuities. Under mesopic conditions, there was no statistically significant differences between the 2 IOLs for UDVA (P = 1.00), UIVA (P = .149), and UNVA (P = .551). No statistically significant differences in contrast sensitivity were found between the groups under photopic (P = .4347) and mesopic (P = .425) conditions. No safety issues were reported. CONCLUSION: The study demonstrated equally good visual and refractive outcomes for the POD F GF IOL and the POD F IOL, giving the surgeon the option to choose the preferred material for the individual patient without compromising clinical outcomes.

Corneal-PAMPA: A novel, non-cell-based assay for prediction of corneal drug permeability.

The present study was aimed to develop an in vitro non-cell-based method, for the measurement of corneal permeability. To this avail, the parallel artificial membrane permeability assay (PAMPA) was used for studying the effects of composition of the artificial lipid membrane, the DMSO cosolvent content of the donor phase as well as different buffer solutions in the model. Based on experimental corneal permeability values of 25 active pharmaceutical ingredients (APIs), a final model with good predictive ability (R2 = 0.880) was developed and validated. The optimized conditions for the Corneal-PAMPA were the following: iso-pH conditions using phosphate buffer saline (PBS pH 7.4) without cosolvent, phosphatidylcholine (10.7 w/v %; without cholesterol) dissolved in a mixture of hexane:dodecane:chloroform = 70:25:5 (v/v) as an artificial membrane, 4 h incubation of the PAMPA plates at 35 °C. The model's applicability in the case of diluted solutions of eye drops was also demonstrated.

First report of Acanthamoeba genotype T8 human keratitis.

Acanthamoeba has a worldwide distribution in the environment and it is capable of causing a painful sight-threatening disease of the cornea designated as Acanthamoeba keratitis (AK). Nowadays, the cases of AK have surged all over the world along with its disease burden due to increasing use of contact lenses used not only for optical correction but also for cosmetic purposes. In our present work, epithelial abrasion of a 27-year-old female soft contact lens wearer with keratitis was examined. Genotype identification was carried out with a real-time fluorescence resonance energy transfer polymerase chain reaction (PCR) assay based on sequence analysis of the 18S rRNA gene. Genotyping allowed the identification of a T8 group isolate. The analysis confirmed the importance of a complete diagnostic protocol, including a PCR assay, for the clinical diagnosis of AK from human samples. Acanthamoeba T8 should be considered as potential causative organism in keratitis in human.

The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

PURPOSE: To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. METHODS: Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. RESULTS: After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO2; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). CONCLUSION: Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.

One-Day Use of Preoperative Topical Nonsteroidal Anti-Inflammatory Drug Prevents Intraoperative Prostaglandin Level Elevation During Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To determine if pretreatment with topical nonsteroidal anti-inflammatory drug (NSAID) prior to femtosecond laser-assisted cataract surgery (FLACS) prevents intraoperative prostaglandin level elevation as a potential risk factor of postoperative complications. PATIENTS AND METHODS: Thirty-six patients with clinically significant cataract and without any concomitant general or ophthalmic disease were enrolled into the three age-matched groups of the study. The mean age of the patients was 62.3 ± 13.1 years. The first group of patients underwent traditional phacoemulsification (Control group), on the second group of patients FLACS was performed, and the third group of patients received topical 0.1% nepafenac pretreatment for 1one day prior to FLACS. Before the phacoemulsification part of the cataract surgery, approximately 110 µL of aqueous humor was collected in all groups. Total prostaglandin concentrations of the collected aqueous humor samples were evaluated by enzyme immunoassay (EIA). RESULTS: The mean of the total prostaglandin concentrations of the aqueous humor samples was 208.8 ± 140.5 pg/mL in patients in the control group, 1449.1 ± 1019.7 pg/mL in the FLACS group (p > 0.001), and 92.2 ± 51.7 pg/mL in the group pretreated with topical NSAID before the FLACS (p > 0.001 compared to FLACS; p > 0.01 compared to control), respectively. CONCLUSIONS: FLACS surgery increases intracameral prostaglandin concentration. However, using preoperative 1-day-long nonsteroid anti-inflammatory drops prior to FLACS, this intraoperative increase diminishes. Our study raises the possibility that NSAID pretreatment may be routinely administered before FLACS cataract surgeries to achieve a further decrease in the potential complications of increased total prostaglandin concentration during FLACS surgeries.

Isotonic Glycerol and Sodium Hyaluronate Containing Artificial Tear Decreases Conjunctivochalasis after One and Three Months: A Self-Controlled, Unmasked Study.

UNLABELLED: Dry eye complaints are ranked as the most frequent symptoms of patients visiting ophthalmologists. Conjunctivochalasis is a common dry eye disorder, which can cause an unstable tear film and ocular discomfort. The severe conjunctivochalasis characterized by high LId-Parallel COnjunctival Folds (LIPCOF) degree usually requires surgical intervention, where a conservative therapy would be highly desirable. Here we examined the efficacy of a preservative-free, inorganic salt-free unit-dose artificial tear, called Conheal containing isotonic glycerol and 0.015% sodium hyaluronate in a prospective, unmasked, self-controlled study involving 20 patients. The regular use of the glycerol/hyaluronate artificial tear in three months caused a significant improvement in the recorded parameters. Conjunctivochalasis decreased from a mean LIPCOF degree of 2.9 ± 0.4 on both eyes to 1.4 ± 0.6 on the right (median decrease of -2 points, 95% CI from -2.0 to -1.0), and to 1.4 ± 0.7 on the left eye (median decrease of -1 points, 95% CI from -2.0 to -1.0) (p<0.001 for both sides). The tear film breakup time (TFBUT) lengthened from 4.8 ± 1.9 seconds on both eyes to 5.9 ± 2.3 seconds (mean increase of 1.1 seconds, 95% CI from 0.2 to 2.0) and 5.7 ± 1.8 seconds (mean increase of 0.9 seconds, 95% CI from 0.3 to 1.5) on the right and left eyes, respectively (p(right eyes) = 0.020, p(left eyes) = 0.004). The corneal lissamine staining (Oxford Scheme grade) was reduced from 1.3 ± 0.6 on the right and 1.4 ± 0.6 on the left eye significantly (p<0.001) to 0.3 ± 0.4 and 0.2 ± 0.4 on the right and the left eyes. The Ocular Surface Disease Index (OSDI) questionnaire score indicating the subjective complaints of the patients also decreased from a mean value of 36.2 ± 25.3 to 15.6 ± 16.7 (p<0.001). In this study, the artificial tear, Conheal decreased the grade of the conjunctivochalasis significantly after one month of regular use already, from the LIPCOF degree 3, considered as indication of conjunctival surgery, to a LIPCOF degree 2 or lower requiring a conservative therapy. Our results raise the possibility that vision-related quality of life can be significantly improved by conservative therapies even in severe conjunctivochalasis. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN81112701 http://www.isrctn.com/ISRCTN81112701.

Corneal Sensitivity and Dry Eye Symptoms in Patients with Keratoconus.

PURPOSE: To investigate corneal sensitivity to selective mechanical, chemical, and thermal stimulation and to evaluate their relation to dry eye symptoms in patients with keratoconus. METHODS: Corneal sensitivity to mechanical, chemical, and thermal thresholds were determined using a gas esthesiometer in 19 patients with keratoconus (KC group) and in 20 age-matched healthy subjects (control group). Tear film dynamics was assessed by Schirmer I test and by the non-invasive tear film breakup time (NI-BUT). All eyes were examined with a rotating Scheimpflug camera to assess keratoconus severity. RESULTS: KC patients had significatly decreased tear secretion and significantly higher ocular surface disease index (OSDI) scores compared to controls (5.3±2.2 vs. 13.2±2.0 mm and 26.8±15.8 vs. 8.1±2.3; p<0.001). There was no significant difference in NI-BUT between the two groups (KC: 9.8±4.8 vs. control: 10.7±3.8; p>0.05). The mean threshold for selective mechanical (KC: 139.2±25.8 vs. control: 109.1±24.0 ml/min), chemical (KC: 39.4±3.9 vs. control: 35.2±1.9%CO2), heat (KC: 0.91±0.32 vs. control: 0.54±0.26 Δ°C) and cold (KC: 1.28±0.27 vs. control: 0.98±0.25 Δ°C) stimulation in the KC patients were significantly higher than in the control subjects (p<0.001, for all parameters). No correlation was found between age and mechanical, chemical, heat or cold thresholds in the patients with KC (p>0.05), whereas in the control subjects both mechanical (r = 0.52, p = 0.02), chemical (r = 0.47, p = 0.04), heat (r = 0.26, p = 0.04) and cold threshold (r = 0.40, p = 0.03) increased with age. In the KC group, neither corneal thickness nor tear flow, NI-BUT or OSDI correlated significantly with mechanical, chemical, heat or cold thresholds (p>0.05 for all variables). CONCLUSIONS: Corneal sensitivity to different types of stimuli is decreased in patients with keratoconus independently of age and disease severity. The reduction of the sensory input from corneal nerves may contribute to the onset of unpleasant sensations in these patients and might lead to the impaired tear film dynamics.

The Effect of Tear Supplementation on Ocular Surface Sensations during the Interblink Interval in Patients with Dry Eye.

PURPOSE: To investigate the characteristics of ocular surface sensations and corneal sensitivity during the interblink interval before and after tear supplementation in dry eye patients. METHODS: Twenty subjects (41.88±14.37 years) with dry eye symptoms were included in the dry eye group. Fourteen subjects (39.13±11.27 years) without any clinical signs and/or symptoms of dry eye were included in the control group. Tear film dynamics was assessed by non-invasive tear film breakup time (NI-BUT) in parallel with continuous recordings of ocular sensations during forced blinking. Corneal sensitivity to selective stimulation of corneal mechano-, cold and chemical receptors was assessed using a gas esthesiometer. All the measurements were made before and 5 min after saline and hydroxypropyl-guar (HP-guar) drops. RESULTS: In dry eye patients the intensity of irritation increased rapidly after the last blink during forced blinking, while in controls there was no alteration in the intensity during the first 10 sec followed by an exponential increase. Irritation scores were significantly higher in dry eye patients throughout the entire interblink interval compared to controls (p<0.004). NI-BUT significantly increased after HP-guar (p = 0.003) but not after saline drops (p = 0.14). In both groups, either after saline or HP-guar the shape of symptom intensity curves remained the same with significantly lower irritation scores (p<0.004), however after HP-guar the decrease was significantly more pronounced (p<0.004). Corneal sensitivity to selective mechanical, cold and chemical stimulation decreased significantly in both groups after HP-guar (p<0.05), but not after saline drops (p>0.05). CONCLUSION: Ocular surface irritation responses due to tear film drying are considerably increased in dry eye patients compared to normal subjects. Although tear supplementation improves the protective tear film layer, and thus reduce unpleasant sensory responses, the rapid rise in discomfort is still maintained and might be responsible for the remaining complaints of dry eye patients despite the treatment.

Structure and dynamics of molecular networks: a novel paradigm of drug discovery: a comprehensive review.

Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only give a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The "central hit strategy" selectively targets central nodes/edges of the flexible networks of infectious agents or cancer cells to kill them. The "network influence strategy" works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved by targeting the neighbors of central nodes/edges. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach.

Effects of luminance on dynamic random-dot correlogram evoked visual potentials.

Although dynamic random-dot correlogram evoked visual potentials (DRDC-VEPs) are a three-decade-old method to detect the cortical binocularity in humans and animals, our knowledge of the influence of fundamental stimulus parameters and the underlying cerebral processing mechanisms has remained limited. The purpose of this study was to evaluate the effect of luminance on DRDC-VEPs in adults. The variability and detectability of DRDC-VEPs were investigated under different stimulus luminance conditions with neutral density filters. Our results have demonstrated that DRDC-VEPs can be evoked in a wide luminance range, and the response amplitude was practically independent of luminance between 4.75 cd m(-2) and 0.015 cd m(-2), while DRDC-VEP latencies showed a strong linear correlation with log luminance. There is, however, a limit (0.06 cd m(-2)) below which DRDC-VEPs are not reliably recordable. Luminance reduction-induced delays in DRDC-VEP latencies cannot be explained simply by retinal mechanisms, since their regression slope does not follow the course of electroretinogram and cortical evoked potential latencies. Luminance independence of DRDC-VEP amplitude suggests that binocular correlation-processing cortical neurons receive input predominantly from the magnocellular visual pathway.

Disordered proteins and network disorder in network descriptions of protein structure, dynamics and function: hypotheses and a comprehensive review.

During the last decade, network approaches became a powerful tool to describe protein structure and dynamics. Here we review the links between disordered proteins and the associated networks, and describe the consequences of local, mesoscopic and global network disorder on changes in protein structure and dynamics. We introduce a new classification of protein networks into 'cumulus-type', i.e., those similar to puffy (white) clouds, and 'stratus-type', i.e., those similar to flat, dense (dark) low-lying clouds, and relate these network types to protein disorder dynamics and to differences in energy transmission processes. In the first class, there is limited overlap between the modules, which implies higher rigidity of the individual units; there the conformational changes can be described by an 'energy transfer' mechanism. In the second class, the topology presents a compact structure with significant overlap between the modules; there the conformational changes can be described by 'multi-trajectories'; that is, multiple highly populated pathways. We further propose that disordered protein regions evolved to help other protein segments reach 'rarely visited' but functionally-related states. We also show the role of disorder in 'spatial games' of amino acids; highlight the effects of intrinsically disordered proteins (IDPs) on cellular networks and list some possible studies linking protein disorder and protein structure networks.