Social history and glaucoma progression: the effect of body mass index, tobacco and alcohol consumption on the rates of structural change in patients with glaucoma.

BACKGROUND/AIMS: Although obesity, tobacco and alcohol consumption were linked to the progression of numerous chronic diseases, an association of these social history aspects with glaucoma progression is not yet determined. This study aims to investigate the effect of body mass index (BMI) and history of tobacco and alcohol use on the rates of retinal nerve fibre layer (RNFL) change over time in glaucoma patients. METHODS: 2839 eyes of 1584 patients with glaucoma from the Duke Ophthalmic Registry were included. Patients had at least two spectral-domain optical coherency tomography (SD-OCT) tests over a minimum 6-month follow-up. Self-reported history of alcohol and tobacco consumption was extracted from electronic health records and mean BMI was calculated. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on RNFL change over time. RESULTS: Mean follow-up time was 4.7±2.1 years, with 5.1±2.2 SD-OCT tests per eye. 43% and 54% of eyes had tobacco or alcohol consumption history, respectively, and 34% were classified as obese. Higher BMI had a protective effect on glaucoma progression (0.014 µm/year slower per each 1 kg/m2 higher; p=0.011). Tobacco and alcohol consumption were not significantly associated with RNFL change rates (p=0.473 and p=0.471, respectively). Underweight subjects presented significantly faster rates of structural loss (-0.768 µm/year; p=0.002) compared with normal weight. CONCLUSIONS: In a large clinical population with glaucoma, habits of tobacco and alcohol consumption showed no significant effect on the rates of RNFL change. Higher BMI was significantly associated with slower rates of RNFL loss.

Neurotoxin-Induced Rodent Models of Parkinson's Disease: Benefits and Drawbacks.

Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by cardinal motor impairments, including akinesia and tremor, as well as by a host of non-motor symptoms, including both autonomic and cognitive dysfunction. PD is associated with a death of nigral dopaminergic neurons, as well as the pathological spread of Lewy bodies, consisting predominantly of the misfolded protein alpha-synuclein. To date, only symptomatic treatments, such as levodopa, are available, and trials aiming to cure the disease, or at least halt its progression, have not been successful. Wong et al. (2019) suggested that the lack of effective therapy against neurodegeneration in PD might be attributed to the fact that the molecular mechanisms standing behind the dopaminergic neuronal vulnerability are still a major scientific challenge. Understanding these molecular mechanisms is critical for developing effective therapy. Thirty-five years ago, Calne and William Langston (1983) raised the question of whether biological or environmental factors precipitate the development of PD. In spite of great advances in technology and medicine, this question still lacks a clear answer. Only 5-15% of PD cases are attributed to a genetic mutation, with the majority of cases classified as idiopathic, which could be linked to exposure to environmental contaminants. Rodent models play a crucial role in understanding the risk factors and pathogenesis of PD. Additionally, well-validated rodent models are critical for driving the preclinical development of clinically translatable treatment options. In this review, we discuss the mechanisms, similarities and differences, as well as advantages and limitations of different neurotoxin-induced rat models of PD. In the second part of this review, we will discuss the potential future of neurotoxin-induced models of PD. Finally, we will briefly demonstrate the crucial role of gene-environment interactions in PD and discuss fusion or dual PD models. We argue that these models have the potential to significantly further our understanding of PD.

Polymyxin-Induced Cell Death of Human Macrophage-Like THP-1 and Neutrophil-Like HL-60 Cells Associated with the Activation of Apoptotic Pathways.

Innate immunity is crucial for the host to defend against infections, and understanding the effect of polymyxins on innate immunity is important for optimizing their clinical use. In this study, we investigated the potential toxicity of polymyxins on human macrophage-like THP-1 and neutrophil-like HL-60 cells. Differentiated THP-1 human macrophages (THP-1-dMs) and HL-60 human neutrophils (HL-60-dNs) were employed. Flow cytometry was used to measure the concentration-dependent effects (100 to 2,500 µM for THP-1-dMs and 5 to 2,500 µM for HL-60-dNs) and time-dependent effects (1,000 µM for THP-1-dMs and 300 µM for HL-60-dNs) of polymyxin B over 24 h. Effects of polymyxin B on mitochondrial activity, activation of caspase-3, caspase-8, and caspase-9, and Fas ligand (FasL) expression in both cell lines were examined using fluorescence imaging, colorimetric, and fluorometric assays. In both cell lines, polymyxin B induced concentration- and time-dependent loss of viability at 24 h with 50% effective concentration (EC50) values of 751.8 µM (95% confidence interval [CI], 692.1 to 816.6 µM; Hill slope, 3.09 to 5.64) for THP-1-dM cells and 175.4 µM (95% CI, 154.8 to 198.7 µM; Hill slope, 1.42 to 2.21) for HL-60-dN cells. A concentration-dependent loss of mitochondrial membrane potential and generation of mitochondrial superoxide was also observed. Polymyxin B-induced apoptosis was associated with concentration-dependent activation of all three tested caspases. The death receptor apoptotic pathway activation was demonstrated by a concentration-dependent increase of FasL expression. For the first time, our results reveal that polymyxin B induced concentration- and time-dependent cell death in human macrophage-like THP-1 and neutrophil-like HL-60 cells associated with mitochondrial and death receptor apoptotic pathways.

Highly specific Electrochemical Sensing of Pseudomonas aeruginosa in patients suffering from corneal ulcers: A comparative study.

Pseudomonas aeruginosa is the most common pathogenic gram-negative bacteria causing corneal ulcers globally. In severe cases, often after trauma and eye injury, corneal destruction progresses rapidly and may be completed within 24-48 h causing blindness. In our preliminary work, we have established an ultrasensitive polyaniline (PANI)/gold nanoparticles (Au NPs)/indium tin oxide (ITO) modified sensor for rapid detection of pyocyanin (PYO) in P. aeruginosa infections with a linear range from 238 µM to 1.9 µM and a detection limit of 500 nM. In the present study, we evaluated the efficiency of the established modified electrochemical sensor in the diagnosis of P. aeruginosa in 50 samples collected from patients suffering from corneal ulcers. The obtained results were compared with the results gained by the screen-printed electrode, conventional techniques, automated identification method, and the amplification of the 16 s rRNA gene by PCR as a gold standard test for P. aeruginosa identification. We have found that the electrochemical detection of PYO by square wave voltammetry technique using PANI/Au NPs modified ITO electrode was the only technique showing 100% agreement with the molecular method in sensitivity, specificity, positive and negative predictive values when compared with the SPE, conventional and automated methods.

Negative optokinetic afternystagmus in larval zebrafish demonstrates set-point adaptation.

Motor learning is essential to maintain accurate behavioral responses. We used a larval zebrafish model to study ocular motor learning behaviors. During a sustained period of optokinetic stimulation in 5-day-old wild-type zebrafish larvae the slow-phase eye velocity decreased over time. Then interestingly, a long-lasting and robust negative optokinetic afternystagmus (OKAN) was evoked upon light extinction. The slow-phase velocity, the quick-phase frequency, and the decay time constant of the negative OKAN were dependent on the stimulus duration and the adaptation to the preceding optokinetic stimulation. Based on these results, we propose a sensory adaptation process during continued optokinetic stimulation, which, when the stimulus is removed, leads to a negative OKAN as the result of a changed retinal slip velocity set point, and thus, a sensorimotor memory. The pronounced negative OKAN in larval zebrafish not only provides a practical solution to the hitherto unsolved problems of observing negative OKAN, but also, and most importantly, can be readily applied as a powerful model for studying sensorimotor learning and memory in vertebrates.

Relevance of Swept-Source Anterior Segment Optical Coherence Tomography for Corneal Imaging in Patients With Flap-Related Complications After LASIK.

PURPOSE: To evaluate the role of swept-source anterior segment optical coherence tomography (AS-OCT) in the diagnosis and management of laser in situ keratomileusis (LASIK) flap-related complications. METHODS: This prospective study included 25 eyes with LASIK flap-related complications imaged using swept-source AS-OCT between February and August 2016 at Alforsan Eye Centre, Assiut, Egypt. The images were acquired using a 6-mm line scan. RESULTS: Imaging of flap-related LASIK complications using AS-OCT revealed specific and nonspecific findings. Of note, epithelial ingrowth appeared as highly reflective lesions below the LASIK flap in the form of islands, nests, or a continuous sheet with or without changes in the overlying flap. Macrostriae manifested as dome-shaped irregularities on the stromal surface with regular overlying epithelium, whereas microstriae appeared as corrugations on the stromal surface with regular overlying epithelium. Less common complications included multiple flap macrostriae accompanied by a traumatic folded flap with a flap edge at the interface. Interface debris appeared as a highly reflective interface lesion with or without a surrounding reaction. One eye with a flap that was torn and lost intraoperatively showed epithelialization over a thin residual stroma underlying a contact lens with no stromal infiltration on the second postoperative day. AS-OCT was useful for the assessment of flap thickness and planning of the new flap thickness in the event of an incomplete cut. CONCLUSIONS: Swept-source AS-OCT is useful not only for diagnosis but also for management of eyes with LASIK flap-related complications by allowing noninvasive, noncontact, real-time acquisition of cross-sectional AS images.

Adenosine role in brain functions: Pathophysiological influence on Parkinson's disease and other brain disorders.

Although adenosine plays a key role in multiple motor, affective, and cognitive processes, it has received less attention in the neuroscience field compared to other neurotransmitters (e.g., dopamine). In this review, we highlight the role of adenosine in behavior as well as its interaction with other neurotransmitters, such as dopamine. We also discuss brain disorders impacted by alterations to adenosine, and how targeting adenosine can ameliorate Parkinson's disease motor symptoms. We also discuss the role of caffeine (as an adenosine antagonist) on cognition as well as a neuroprotective agent against Parkinson's disease (PD).

Effect of single subconjunctival injection of bevacizumab on primary pterygium: clinical, histopathological and immunohistochemical study.

AIM: To evaluate the effect (clinically, histopathologically and immunohistochemically) and safety of a single intra-pterygium injection of bevacizumab. METHODS: Prospective interventional study comprised 40 eyes of 40 patients with primary fleshy pterygia who attended the Outpatient Clinic of Department of Ophthalmology, Assiut University Hospitals, Egypt from May 2015 to May 2016. Patients were randomly classified into 2 groups: the first group received a single intralesional injection of bevacizumab (Avastin; Genentech, San Francisco, CA, USA); the second group comprised patients who did not receive subconjunctival bevacizumab. Excision of pterygium and conjunctival auto graft was done in both groups. The excised pterygium tissues were subjected to histopathological and immunohistochemical evaluation. RESULTS: The study comprised 40 eyes of 40 patients (33 men, 7 women) of age range from 31-58y. The study group included 22 eyes. The control group included 18 eyes. A decrease in the vascularity of the pterygium was noted in all injected cases. The mean vessel count was higher in non-injected pterygia than that in injected pterygia and the difference was statistically significant (P=0.001). Also, the mean vessel count in both groups was significantly higher than normal conjunctive (P=0.005 and 0.001). A statistically significant difference in vascular endothelial growth factor (VEGF) expression between injected and non-injected cases was detected in the epithelial, stromal and endothelial cells (P=0.0001, 0.016, 0.014). No serious intraoperative complications occurred in both groups. CONCLUSION: The use of single intra lesional injection of Avastin in pterygium decreased vascularity and decreased VEGF expression in injected pterygium after one month. Our study proved the effect of single intra lesional injection of Avastin on pterygium. Further studies may enable limiting the need for surgery and improve quality of life for patients with pterygia.

Refractive Lens Exchange Combined with Primary Posterior Vitrectorhexis in Highly Myopic Patients.

Purpose. To evaluate efficacy and safety of primary vitrectorhexis for posterior capsulotomy in highly myopic patients undergoing refractive lens exchange. Methods. The study is a prospective nonrandomized interventional study. The study comprised 60 eyes of 60 myopic patients. All patients underwent refractive lens exchange (RLE) and foldable IOL implantation combined with primary posterior capsulotomy. We used a 23-gauge vitrectomy probe for the creation of the posterior capsule opening. We followed the patients for one year. Results. During surgery, the IOLs remained well centered in the capsular bag after creation of the capsulotomy. Postoperatively, we did not report any complications related to lens centration or changes in the posterior capsulotomy size. No eye required YAG laser posterior capsulotomy and no cases of retinal detachment (RD) occurred during the follow-up period. Conclusion. Primary posterior vitrectorhexis during RLE is an efficient method in preventing the occurrence of posterior capsular opacification (PCO) and the need for YAG laser posterior capsulotomy with its possible complications.

Selective A2A receptors blockade reduces degeneration of substantia nigra dopamine neurons in a rotenone-induced rat model of Parkinson's disease: A histological study.

Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods. 32 male rats were randomly divided into 4 groups, 8 in each one: vehicle control (1ml/kg/48h), rotenone (1.5mg/kg/48h,s.c.), ZM241385 (3.3mg/kg/day, i.p) and 8-cyclopentyl-1,3-dipropylxanthine (5mg/kg/day, i.p). 24h after the last rotenone injection, animals were sacrificed and their brains were sectioned and prepared for histopathological staining with hematoxylin and eosin, cresyl violet for Nissl-staining, Mallory's phosphotungestic acid haematoxylin staining as well as for immunohistochemical staining for tyrosine hydroxylase. Our study showed that A2A-receptor blockade by ZM241385, but not A1 receptor blocking by 8-cyclopentyl-1,3-dipropylxanthine, decreased histopathological degeneration in SNpc neurons and hindered the reduction in dopamine levels caused by rotenone application. These results indicate that the selective A2A, but not A1 receptor blocking, has a neuroprotective effect, and may provide a more selective pharmacological strategy for the treatment of PD symptoms.

Dose-dependent neuroprotective effect of caffeine on a rotenone-induced rat model of parkinsonism: A histological study.

Several lines of evidence have demonstrated an inverse relationship between caffeine utilization and Parkinson's disease (PD) progression. Caffeine is a methylxanthine known as a non-specific inhibitor of adenosine (A2A and A1) receptors in the cerebrum and demonstrated to be a neuroprotective medication. In this study, the neuroprotective efficacy of two different doses of caffeine ranging above the usual consumption dose and below the toxic dose was investigated using histopathological and immunohistochemical methods. Thirty-two male rats were randomly divided into 4 groups, with 8 in each group: vehicle control (1ml/kg/48h for 12 days), rotenone (1.5mg/kg/48h, s.c. for 12 days), low-dose Caffeine-treated: (10mg/kg IP. daily for 12 days), high-dose Caffeine-treated (20mg IP daily for 12 days). Twenty-four hours after the last rotenone injection, animals were sacrificed and brains were sectioned and prepared for histopathological staining with hematoxylinand eosin, cresyl violet and Mallory's phosphotungestic acid haematoxylinand for immunohistochemical staining of tyrosine hydroxylase. Our study showed that the treatment with caffeine improved histopathological degeneration in the substantia nigra parts compacta (SNpc) neurons and hindered the reduction in dopamine concentration caused by rotenone. We also found that a higher dose of caffeine was more effective against histopathological degeneration. These results suggest that caffeine has a dose-dependent neuroprotective effect.

Adenosine A2A Receptor Blockade Prevents Rotenone-Induced Motor Impairment in a Rat Model of Parkinsonism.

Pharmacological studies implicate the blockade of adenosine receptorsas an effective strategy for reducing Parkinson's disease (PD) symptoms. The objective of this study is to elucidate the possible protective effects of ZM241385 and 8-cyclopentyl-1, 3-dipropylxanthine, two selective A2A and A1 receptor antagonists, on a rotenone rat model of PD. Rats were split into four groups: vehicle control (1 ml/kg/48 h), rotenone (1.5 mg/kg/48 h, s.c.), ZM241385 (3.3 mg/kg/day, i.p) and 8-cyclopentyl-1, 3-dipropylxanthine (5 mg/kg/day, i.p). After that, animals were subjected to behavioral (stride length and grid walking) and biochemical (measuring concentration of dopamine levels using high performance liquid chromatography, HPLC). In the rotenone group, rats displayed a reduced motor activity and disturbed movement coordination in the behavioral tests and a decreased dopamine concentration as foundby HPLC. The effect of rotenone was partially prevented in the ZM241385 group, but not with 8-cyclopentyl-1,3-dipropylxanthine administration. The administration of ZM241385 improved motor function and movement coordination (partial increase of stride length and partial decrease in the number of foot slips) and an increase in dopamine concentration in the rotenone-injected rats. However, the 8-cyclopentyl-1,3-dipropylxanthine and rotenone groups were not significantly different. These results indicate that selective A2A receptor blockade by ZM241385, but not A1 receptor blockadeby 8-cyclopentyl-1,3-dipropylxanthine, may treat PD motor symptoms. This reinforces the potential use of A2A receptor antagonists as a treatment strategy for PD patients.

Effect of intracameral triamcinolone acetonide on postoperative intraocular inflammation in pediatric traumatic cataract.

PURPOSE: To study the effect of a single intracameral injection of triamcinolone acetonide at the end of pediatric traumatic cataract surgery on postoperative inflammation. METHODS: This prospective interventional study comprised 40 eyes of children with unilateral traumatic cataract. Patients were classified into 2 groups: the study group, in which intraoperative intracameral triamcinolone acetonide (2 mg) was used at the end of surgery; and a control group, which did not receive intracameral triamcinolone acetonide. RESULTS: The study group included 20 eyes of patients with an average age of 6 ± 2.8 years. The control group included 20 eyes of patients with an average age of 6 ± 2.1 years. No serious intraoperative complications occurred. In the immediate postoperative period, 3 eyes of the control group (15.0%) developed a fibrinous anterior chamber reaction. None of the study group eyes developed a similar reaction. There were no cases of endophthalmitis. In addition, 3 eyes (15%) in the control group had obscuration of the visual axis at the last follow-up. This complication was not encountered in the study group. Posterior synechiae and cellular deposits were observed in 4 eyes (20%) in the study group and 8 eyes (40%) in the control group at 1 month and at the last follow-up. CONCLUSIONS: The use of intracameral triamcinolone decreased anterior segment inflammation postoperatively in children who had surgery for traumatic cataract.

Spectral domain anterior segment optical coherence tomography in microbial keratitis.

PURPOSE: To investigate the spectral domain anterior segment optical coherence tomography (SDAS-OCT) patterns in microbial keratitis (fungal and bacterial keratitis). DESIGN: Prospective, cross-sectional, observational study. METHODS: Twenty eyes of 20 patients with proven fungal and bacterial microbial keratitis, at different stages of the disease, underwent SDAS-OCT imaging. RESULTS: Eight eyes presented with proven bacterial keratitis (3 Staphylococcus Aureus, 2 Pseudomonas Aeruginosa and 3 Staphylococcus Epidermidis). Twelve eyes presented with proven fungal keratitis of Aspergillus species. Twelve different SDAS-OCT presentations of fungal and bacterial keratitis were found in this study. Our findings in fungal keratitis grasped two unique patterns of early localized and diffuse necrotic stromal cystic spaces. CONCLUSION: SDAS-OCT imaging provided a range of characteristic patterns that could be used as an additional tool in diagnosis and management of bacterial and fungal microbial keratitis.

Pediatric eye injuries in upper Egypt.

PURPOSE: To analyze the patterns, causes, and outcome of pediatric ocular trauma at Assiut University Hospital in Upper Egypt (South of Egypt). METHODS: All ocular trauma patients aged 16 years or younger admitted to the emergency unit of Ophthalmology Department of Assiut University between July 2009 and July 2010 were included in the study. The demographic data of all patients and characteristics of the injury events were determined. The initial visual acuity and final visual acuity after 3 months follow-up were recorded. RESULTS: One hundred and fifty patients were included. The majority of injuries occurred in children aged 2-7 years (50.7%). There were 106 (70.7%) boys and 44 (29.3%) girls. The highest proportion of injuries occurred in the street (54.7%) followed by the home (32.7%). Open globe injuries accounted for 67.3% of injuries, closed globe for 30.7%, and chemical injuries for 2%. The most common causes were wood, stones, missiles, and glass. LogMar best corrected visual acuity at 3 months follow-up was: 0-1 in 13.3%; <1-1.3 in 27.3%; <1.3-perception of light (PL) in 56%; and no perception of light (NPL) in 3.3%. CONCLUSIONS: Pediatric ocular trauma among patients referred to our tertiary ophthalmology referral center in Upper Egypt over a period of 1 year was 3.7%. Of these, 67.3% of cases had open globe injury, 30.7% had closed injury, and only 2% had chemical injury. In Upper Egypt, socioeconomic and sociocultural status, family negligence, and lack of supervision are important factors in pediatric eye injuries, as 92% of children were without adult supervision when the ocular trauma occurred. Nearly 86.6% of children with ocular trauma end up legally blind. Modification of these environmental risk factors is needed to decrease pediatric ocular morbidity.