Investigating the pathogenesis of vitreous in postmortem COVID patients via untargeted metabolomics based bioinformatics model.

SARS-CoV-2 virus has become a worldwide pandemic causing millions of death. This severe disaster lead to a immense panic and stress all over the world. Several studies were dedicated to understand its mechanism, pathogenesis and spreading characteristics. By this way, scientists try to develop different therapy and diagnose strategies. For these reasons, several metabolomics, proteomics and genomics studies were also carried out to improve knowledge in this newly identified virus. In this study, we are aimed to explain the pathogenesis of SARS-CoV-2 exposure on postmortem COVID (+) patients via untargeted metabolomics analysis. To carry out this study, a Data Independent Acquisition SWATH method is optimized and performed. Vitreous samples were analyzed in both MS1 and MS2 ESI(+) mode. An orthogonal Partial Least Square Discriminant Analysis were performed for classification. It was observed that lipid metabolism, several amino acids and oxidative stress biomarkers were strongly affected due to high inflammation and possible cytokine storm.

Retinal Nerve Fiber Layer Thickness in Prediabetic Patients.

OBJECTIVE: Diabetic retinopathy is a leading cause of blindness. Diabetic retinopathy is not only seen in diabetic patients with the clinical diagnosis but also in prediabetic patients. The aim of this study is to evaluate the RNFL thickness in prediabetic patients. MATERIALS AND METHODS: In this study, 50 prediabetic patients and 50 healthy individuals were included. RNFL measurements were performed with SD-OCT in patients with prediabetes and healthy controls. RESULTS: The mean RNFL thickness for the prediabetic group was 94.7 ± 6.3 µm, inferior quadrant (120 ± 11.6), superior quadrant (112.3 ± 14.13), nasal quadrant (71 ± 12.9), and temporal quadrant (65.3 ± 9.2 µm). The mean RNFL thickness for the control group was 98.9 ± 7.5 µm, inferior quadrant (128 ± 14.7), superior quadrant (116.3 ± 15.12), nasal quadrant (77 ± 15.8), and temporal quadrant (71.2 ± 10.3 µm). Variance analysis demonstrated that the RNFL thickness difference between the groups was significant in all quadrants (P < .001). CONCLUSION: RNLF thinning can be seen in prediabetic patients before obvious vascular damage has occurred, and it may present in prediabetic patients not only in the temporal quadrant but also in all quadrants. The early retinal neural changes shown in this study in prediabetic patients may help to better understand the process leading to diabetic overt retinopathy.

Does Intravitreal Dopamine Agonist and Antagonist Administration Have Effects on the Brain? An Experimental Study in Rats.

OBJECTIVE: There might be dopaminergic connections between the retina and the brain. In this context, the study was aimed to investigate the possible interaction between the retina and basal ganglia through the dopaminergic system. MATERIALS AND METHODS: In total, 32 healthy rats were randomized into 4 groups: healthy, Sham, dopamine antagonist injected group (risperidone, 0.04 mg/kg intravitreally), and dopamine agonist injected group (apomorphine, 0.4 mg/kg intravitreally). The locomotor activity and Morris water maze tests were applied to all rats twice, before the injection and 28 days after, to detect changes in movement, memory, and attention. Histopathologically, the basal ganglia and hippocampus regions were removed and examined. RESULTS: In the locomotor activity test, a statistical significance was found between the first and last measurement values of the apomorphine group and a decrease in activities and an increase in resting times (P < .05). In the Morris water maze test, a statistical significance was detected between the first and last tests of the control group and the apomorphine groups and showed significantly shorter learning times (P < .05). Histological analyses of the substantia nigra and hippocampus were noteworthy in that the number of damaged neurons in the risperidone group was considerably higher than the other groups. The number of damaged neurons in the apomorphine group was significantly lower than in the healthy group. CONCLUSION: Intravitreal administration of dopamine agonists and antagonists has given rise to alterations in the cerebral dopaminergic system, leading to changes in locomotor activity and memory and histopathological changes.

Differential Diagnosis of Ischemic Vertigo by Optical Coherence Tomography.

OBJECTIVE: This study aimed to evaluate the differences in the mean retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) in patients with early stage central vertigo with or without vertebrobasilar stenosis detected by Doppler ultrasound. MATERIALS AND METHODS: A total of 50 patients with ischemic vertigo and 50 healthy individuals were included in the study. The distinction between central and peripheral vertigo was determined by physical and neurological examinations and the Dix-Hallpike maneuver. For all patients, the mean RNFL thickness was determined using OCT performed by 2 independent ophthalmologists. RESULTS: There were no significant differences between the groups in terms of age and sex distribution (p>0.05). On average, in superior, inferior, and temporal quadrants, there was a statistically significant difference between the control and patient groups (p<0.001). CONCLUSION: The retina may be affected in patients with ischemic vertigo because of atherosclerotic ischemic lesions in the carotid and vertebral arteries. Neuroimaging methods and OCT were evaluated together to develop a new diagnostic approach. With OCT, which is a non-invasive method, early and more objective differential diagnosis will be possible.

Nifedipine-loaded polymeric nanoparticles: Preparation and in vitro characterization.

The purpose of the current study was to prepare nifedipine (NF) loaded-PLGA nanoparticles (NPs) using two different methods (nanoprecipitation method (N-2) and emulsion-solvent evaporation method (N-4)) to achieve the sustained release of NF and to reduce its side effects, and also to investigate the in vitro characteristics of NPs (surface morphology, particle size and size distribution, encapsulation efficiency and in vitro release characteristics). SEM images of nanoparticles revealed their approximate spherical shape. The mean particle sizes of the prepared nanoparticles ranged from 294.27±7.93 to 424.92±4.96 nm with almost neutral zeta potential values (close to 0 mV). The percent encapsulation efficiency values of N-2 and N-4 formulations 13.03±1.82% and 18.96±1.95% (p=0.05), respectively. The extents of cumulative drug release from N-2 and N-4 in PB pH 7.4 medium were up to about 100 % in 38 days and 22 days, respectively (when comparing two formulations, p<0.05). PLGA nanoparticles are useful systems for the sustained release of NF, and hence for reducing its side-effects and increasing patient compliance.

Intravitreal Infliximab Injection to Treat Experimental Endophthalmitis.

OBJECTIVE: The purpose of this study was to compare the use of an intravitreal injection of infliximab and of dexamethasone combined with vancomycin to treat experimental endophthalmitis induced by Staphylococcus epidermidis. MATERIALS AND METHODS: The study was conducted between March 25 and April 13, 2012. Twenty-five six-month-old healthy rabbits were used, each weighing 2.5-3 kg. The rabbits were randomized into five groups with five animals per group. Endophthalmitis was induced by 0.1 mL (103 colony-forming units) S. epidermidis in all groups. In group 1, injection was not implemented after the occurrence of endophthalmitis. In groups 2, 3, and 4, the following intravitreal injections were given 24 h after the occurrence of endophthalmitis: group 2, 0.1 mg/0.1 mL vancomycin; group 3, 1 mg/0.1 mL vancomycin and 1 mg/0.1 mL dexamethasone; and group 4, 1 mg/0.1 mL vancomycin and 2 mg/0.1 mL infliximab. Group 5 was the control/uninfected group. The rabbits were clinically assessed each day for seven days. On day 9, a histopathologic evaluation was performed after enucleation. RESULTS: After a clinical evaluation, no statistically significant difference was found between the vancomycin+infliximab and vancomycin+dexamethasone groups (p>0.05). The difference was significant when both groups were compared with the vancomycin group (p<0.001). After the histopathologic evaluation, no statistically significant difference was found among the three groups (p>0.05). CONCLUSION: An intravitreal injection of infliximab and of dexamethasone combined with vancomycin have similar clinical and histopathologic effects. To supplement the antibiotic treatment of endophthalmitis, infliximab in a safe dose range can be used as an alternative to dexamethasone to suppress inflammation and prevent ocular damage.

Phacoemulsification and Core Vitrectomy in Fuchs' Heterochromic Uveitis.

OBJECTIVE: To evaluate the efficacy of phacoemulsification combined with posterior capsulorhexis, core vitrectomy and ciliary sulcus intraocular lens (IOL) implantation in patients with Fuchs' heterochromic uveitis (FHU). MATERIALS AND METHODS: A total of 18 eyes of 18 patients with FHU underwent cataract surgery were included in the study. 18 eyes with FHU underwent posterior capsulorhexis, core vitrectomy and poly (methyl methacrylate) (PMMA) IOL implantation in the ciliary sulcus. Subjects were chosen for this procedure based on an intraoperative vitreous haziness assessment, performed by indirect ophthalmoscopy. Patients with +2 or more vitreous haziness qualified for this procedure. RESULTS: Of the 83 eyes with FHU that underwent cataract surgery, 18 eyes (21.6%) of 18 patients were employed in the study. There were 11 (61.1%) men and 7 (38.9%) women in the study; ages ranged from 23 to 47, with a mean of 32.06 years. Follow-up ranged from 8 months to 49 months. There were no intraoperative complications except for peripheral iris bleeding in 7 eyes. There was no severe intraocular inflammation in any patient postoperatively. All patients had 0.05 or better logMAR visual acuity after corneal suture removal. Glaucoma developed in 2 patients. For the short term period, the main vision threatening problem was suture-induced astigmatism. CONCLUSION: Cataract surgery combined with posterior capsulorhexis, core vitrectomy and IOL implantation in the ciliary sulcus is safe and leads to good visual outcome due to the removal of the hazy vitreous in patients with FHU.

Endocan Measurement for Active Behçet Disease.

OBJECTIVES: This study aims to investigate the relationships between serum endocan, vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-α) levels in active Behçet disease. PATIENTS AND METHODS: Forty patients with active Behçet disease (24 males, 16 females; mean age 37.6±8.7 years; range 20 to 50 years) and 40 healthy controls (22 males, 18 females; mean age 38.8±7.9 years; range 21 to 52 years) were included in this study. Both patient and control groups underwent a complete systemic and ophthalmic examination by the same specialist. Endocan, VEGF, and TNF-α levels were measured with an enzyme-linked immunosorbent assay kit in all subjects. RESULTS: Serum endocan levels were 775.2±479.3 ng/mL and 275.8±145.8 ng/mL in the patient and control groups, respectively. VEGF levels were 1768.2±900.5 pg/mL and 980.2±135.3 pg/mL in the patient and control groups, respectively. TNF-α levels were 22.4±74.3 pg/mL-1 and 11.4±16.9 pg/mL-1 in the patient and control groups, respectively. There was a statistically significant difference between groups in terms of serum endocan, VEGF, and TNF-α levels. There was a significant positive correlation between serum endocan and VEGF levels in the patient group (r=0.630; p<0.001). Also, there was a significant positive correlation between serum endocan and TNF-α levels in the patient group (r=0.713; p<0.001). CONCLUSION: Serum endocan level may be a new marker in evaluation of both the prognosis and activity of Behçet disease.

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma.

To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development.

Effects of immunosuppressive drugs on oral mucosa in patients with Behçet's disease: cytomorphological and cytopathological assessment.

BACKGROUND/AIM: The aim of this study was to investigate cytomorphological and cytopathological changes in oral exfoliated smears collected from immunosuppressed patients with Behçet's disease (BD) using stereological methods. MATERIALS AND METHODS: For cytomorphometric analysis, mucosal cell smears were obtained from the buccal mucosa and the floor of the mouths of BD patients treated with immunosuppressive drugs and from healthy volunteers. All mucosal smears from the patients and the healthy volunteers were stained using the Papanicolaou method and examined cytopathologically under light microscopy and cytomorphologically via the stereological nucleator method. RESULTS: The cytomorphological analysis revealed 3 types of mucosal cells, with numbers of particularly pink cells lower in the aphthous areas of the patients with BD compared to the healthy controls (P < 0.05). The nuclear volumes (NVs) and cytoplasmic volume (CVs) were significantly higher in the BD patients (P < 0.05), but the NV/CV ratio was higher only in the drug-use patient groups (P > 0.05). There was lower apoptotic activity in the nondrug-use patients with BD and in the immunosuppressive-taking BD patients. CONCLUSION: The findings suggest that quantifiably morphological and morphometric changes in oral mucosa can be detected by stereological techniques. Changes in these parameters may indicate malignant transformation in the oral mucosa.

Visual Hallucinations in an Old Patient after Cataract Surgery and Treatment.

Sensory visual pathologies, accompanying simple or complex visual hallucinations that occur in visually-impaired individuals due to ophthalmologic or brain pathologies related to visual pathways in patients without mental disorders, are defined as Charles Bonnet syndrome. Between 10% and 60% of the patients having age-related eye diseases involving retina, cornea and the lens, commonly with macular degeneration experience complex visual hallucinations depending on the severity of visual problems. The neurophysiology of the visual hallucinations in Charles Bonnet Syndrome is not clearly known, and they may differ in content and severity over time. In differential diagnoses of Charles Bonnet Syndrome, many aetiologies (drugs, uraemia, exposure to toxic materials, neurodegenerative and psychiatric conditions) need to be ruled out. In the treatment of Charles Bonnet syndrome, first the management of the reason of visual loss should be clarified if possible. If needed, neuroleptics, anticonvulsants, antidepressants, benzodiazepines, cognitive enhancer agents such as cholinesterase inhibitors can be used also. In this case, an 83-year-old female patient experiencing visual hallucinations as burning candles in both eyes' visual field after left eye cataract surgery, treated with 0.5 milligram/day risperidone will be presented.

Retinal Nerve Fiber Layer Thickness in Early-Stage Diabetic Retinopathy With Vitamin D Deficiency.

PURPOSE: To evaluate retinal nerve fiber layer (RNFL) thickness in early-stage diabetic retinopathy (DR) patients with and without vitamin D deficiency (VDD). METHODS: This study compared 50 early-stage DR patients with VDD (group 1) and 50 early-stage DR patients without VDD (group 2). All patients were examined by the same ophthalmologist. Mean RNFL thickness was determined by optical coherence tomography (OCT) performed by the two independent ophthalmologists for all subjects. Vitamin D levels were measured by using a radioimmunoassay. Vitamin D deficiency was defined, in accordance with the general standards, as a 25-hydroxyvitamin D (25(OH)D) level lower than 20 ng/mL. RESULTS: There were no significant differences between the groups in terms of age and sex distribution (P > 0.05). The mean serum 25(OH)D concentration of group 1 was significantly lower than that of group 2 (P < 0.001). The mean RNFL thickness of group 1 was significantly reduced compared to that of group 2 (P < 0.001). A significant relationship between the mean RNFL thickness and serum 25(OH)D concentrations was observed in group 1 (P < 0.001). CONCLUSIONS: The results indicate that vitamin D functions as a neuroprotective component for optic nerves. Low serum 25(OH)D concentrations contribute to RNLF thinning in early-stage DR patients with VDD.

Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration.

AIM: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA), and nitric oxide (NO), as well as activity of endothelial NO synthase (eNOS), in patients with age-related macular degeneration (AMD). METHODS: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30) were compared to a control group with no retinal pathology (n=30). RESULTS: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001), whereas NO levels and eNOS activity were higher in the control group (P<0.001). In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively. CONCLUSION: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD.

Protective effect of L-carnitine in a rat model of retinopathy of prematurity.

AIM: To investigate the effects of L-carnitine (LC) on rats with oxygen-induced retinopathy. MATERIALS AND METHODS: The study was conducted on 40 Sprague Dawley rat pups. The rat pups were randomly divided into 4 groups: group 1 (n = 10) the healthy control group with intraperitoneal 0.1 mL/day physiological saline injection; group 2 (n = 10), exposed to hyperoxygen, did not receive LC but received 0.1 mL/day physiological saline intraperitoneally; group 3 (n = 10), exposed to hyperoxygen and received 100 mg/kg/day LC intraperitoneally; group 4 (n = 10), exposed to hyperoxygen and received 200 mg/kg/ day LC intraperitoneally. After postnatal day 20, the rat pups were killed and an histological examination was performed on the eyes, in addition to the detection of plasma malondialdehyde (MDA) levels. RESULTS: The retinal and choroidal histopathological changes due to hyperoxygen were less in group 3 and minimal in group 4 compared with group 2. Compared with the healthy control group, the increase in the MDA levels in group 2 was significant (P <0.05). Compared with group 2 there was a significant (P < 0.05) decrease in the MDA levels in groups 3 and 4. CONCLUSION: LC has beneficial effects on oxygen-induced retinopathy in rats in terms of histopathological changes and MDA levels.

Plasma coenzyme Q10 levels in type 2 diabetic patients with retinopathy.

AIM: To determine the relationship between proliferative diabetic retinopathy (PDRP) and plasma coenzyme Q10(CoQ10) concentration. METHODS: Patients with type 2 diabetes and PDRP were determined to be the case group (n=50). The control group was consist of healthy individuals (n=50). Plasma CoQ10 and malondialdehyde (MDA) levels were measured in both groups. RESULTS: Ubiquinone-10 (Coenzyme Q10) levels in PDRP and control subjects are 3.81±1.19µmol/L and 1.91±0.62µmol/L, respectively. Plasma MDA levels in PDRP and control subjects were 8.16±2µmol/L and 3.44±2.08µmol/L, respectively. Ratio of Ubiquinol-10/ubiquinone-10 in PDRP and control subjects were 0.26±0.16 and 1.41±0.68, respectively. CONCLUSION: The ratio of ubiquinol-10/ubiquinone-10 is found lower in patients with PDRP. High levels of plasma ubiquinol-10/ubiquinone-10 ratio indicate the protective effect on diabetic retinopathy.

Better surgical method for removing perfluorocarbon liquids from the anterior chamber.

PURPOSE: To describe a surgical method for removing perfluorocarbon liquids from the anterior chamber. METHODS: Perfluorodecalin was noted in the anterior chamber in 2 patients after a vitreoretinal surgery was performed. We removed the perfluorodecalin by using a Rycroft cannula mounted on the tip of a tuberculin syringe with continued irrigation by means of an anterior chamber maintainer. RESULTS: The perfluorodecalin was removed using a single intervention. We did not observe any perfluorodecalin residue in subsequent postoperative examinations in either patient. CONCLUSIONS: The method is simple and safe, and it allows the complete removal of perfluorocarbon liquids from the anterior chamber using a single intervention.

Comparison of the efficacy of topical N-acetyl-cysteine and a topical steroid-antibiotic combination therapy in the treatment of meibomian gland dysfunction.

PURPOSE: This study aimed to compare the efficacy of topical N-acetyl-cysteine (NAC) with a topical steroid-antibiotic combination, betamethasone-sulfacetamide sodium therapy in patients with meibomian gland dysfunction (MGD). METHODS: Twenty patients with MGD were prospectively randomized and assigned into 2 groups. The patients were instructed to use either NAC 5% or a topical steroid-antibiotic combination, betamethasone 0.1%-sulfacetamide sodium 10%, topically 4 times a day for a month. All patients were instructed to apply lid hygiene once daily. RESULTS: One month of topical therapy provided statistically significant improvements in fluorescein break-up time and Schirmer scores as compared with the initial study visit in both groups (P≤0.001). Significant improvements for the symptoms of ocular burning, itching, and intermittent filmy or blurred vision were noted in both groups at 1 month as compared with 1 day (P<0.05). Considering these rates, there was no significant difference between the groups (P>0.05). None of the patients developed an allergic reaction to the medications, and intraocular pressure measurements were within the normal limits in both groups. CONCLUSION: When used in conjunction with eyelid hygiene, topical administration of NAC appears to be as effective as a topical steroid-antibiotic combination, betamethasone-sulfacetamide sodium therapy in patients with MGD.

Carbonic anhydrase activities from the rainbow trout lens correspond to the development of acute gas bubble disease.

Dissolved gas supersaturation is hazardous to fish and can result in gas bubble disease (GBD). Signs of GBD typically include bubbles in the eyes, fins, skin, lateral line, and gill filaments. Ocular abnormalities in diseased salmonids typically occur after aberrant gas production in the eyes. In this study, freshwater rainbow trout Oncorhynchus mykiss were exposed experimentally to percent total gas pressure (TGP%) levels of 104% (control) and 115%. No mortalities occurred during the 7-d experimental period. Effects of GBD were observed externally as a darkened skin, exophthalmia, localized hemorrhage in the eye, and gas bubbles on the operculum. Additional signs included increased swimming activity and, more frequently, panic episodes. Carbonic anhydrase (CA) enzyme activities from the lens and retina were determined at days 0, 1, 3, 5, and 7 of the study. Venous blood gases were also measured on day 7. Retinal pH did not differ between normal and affected fish, but blood characteristics such as the partial pressure of O2, partial pressure of CO2, carboxyhemoglobin level, and bicarbonate ion concentration were significantly elevated in affected fish relative to normal fish. Venous blood pH and oxyhemoglobin levels were not significantly different between affected and normal fish. Patterns of response to total dissolved gas levels differed between the lens and the retina. Mean CA activities in the lenses of fish exposed to a TGP% level of 115% were significantly below those of control fish. However, retinal CA activities did not significantly differ between the two groups over the course of the experiment. These findings show that dissolved gas supersaturation reduces CA activity in the rainbow trout lens.

Oxidative DNA damage in patients with cataract.

PURPOSE: This study examines the levels of oxidative damage in patients with cataract. METHODS: Blood samples were collected from 60 patients with cataract and 60 age- and gender-matched healthy individuals to measure 8-hydroxy 2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) levels. RESULTS: A significant difference was observed in leukocyte 8-OHdG levels in patients with cataract in comparison with healthy persons (p < 0.001). Similarly, a significant difference was observed in plasma MDA levels in patients with cataract in comparison with healthy persons (p<0.001). In addition, a significant correlation was found between levels of 8-OHdG in leukocyte DNA and plasma MDA (r = 0.859, p < 0.001). CONCLUSION: This study measured the oxidative DNA damage by measuring the 8-OHdG in the leukocyte DNA in patients with cataract. In addition, the level of MDA - a marker for lipid peroxidation - was measured to determine lipid peroxidation.