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2.
EBioMedicine ; 99: 104911, 2024 Jan.
Article En | MEDLINE | ID: mdl-38168585

BACKGROUND: The high variability in clinical and metabolic presentations of inborn errors of cobalamin (cbl) metabolism (IECM), such as the cblC/epicblC types with combined deficits in methylmalonyl-coA mutase (MUT) and methionine synthase (MS), are not well understood. They could be explained by the impaired expression/activity of enzymes from other metabolic pathways. METHODS: We performed metabolomic, genomic, proteomic, and post-translational modification (PTM) analyses in fibroblasts from three cblC cases and one epi-cblC case compared with three cblG cases with specific MS deficits and control fibroblasts. FINDINGS: CblC patients had metabolic profilings consistent with altered urea cycle, glycine, and energy mitochondrial metabolism. Metabolomic analysis showed partial disruption and increased glutamate/ketoglutarate anaplerotic pathway of the tricarboxylic acid cycle (TCA), in patient fibroblasts. RNA-seq analysis showed decreased expression of MT-TT (mitochondrial tRNA threonine), MT-TP (mitochondrial tRNA proline), OXCT1 (succinyl CoA:3-oxoacid CoA transferase deficiency), and MT-CO1 (cytochrome C oxidase subunit 1). Proteomic changes were observed for key mitochondrial enzymes, including NADH:ubiquinone oxidoreductase subunit A8 (NDUFA8), carnitine palmitoyltransferase 2 (CPT2), and ubiquinol-cytochrome C reductase, complex III subunit X (UQCR10). Propionaldehyde addition in ornithine aminotransferase was the predominant PTM in cblC cells and could be related with the dramatic cellular increase in propionate and methylglyoxalate. It is consistent with the decreased concentration of ornithine reported in 3 cblC cases. Whether the changes detected after multi-omic analyses underlies clinical features in cblC and cblG types of IECM, such as peripheral and central neuropathy, cardiomyopathy, pulmonary hypertension, development delay, remains to be investigated. INTERPRETATION: The omics-related effects of IECM on other enzymes and metabolic pathways are consistent with the diversity and variability of their age-related metabolic and clinical manifestations. PTMs are expected to produce cumulative effects, which could explain the influence of age on neurological manifestations. FUNDING: French Agence Nationale de la Recherche (Projects PREDICTS and EpiGONE) and Inserm.


Multiomics , Vitamin B 12 , Humans , Vitamin B 12/metabolism , Proteomics , Oxidoreductases/metabolism , Fibroblasts/metabolism , RNA, Transfer/metabolism
3.
Clin Epigenetics ; 15(1): 158, 2023 10 05.
Article En | MEDLINE | ID: mdl-37798757

BACKGROUND: MTR gene encodes the cytoplasmic enzyme methionine synthase, which plays a pivotal role in the methionine cycle of one-carbon metabolism. This cycle holds a significant importance in generating S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), the respective universal methyl donor and end-product of epigenetic transmethylation reactions. cblG type of inherited disorders of vitamin B12 metabolism due to mutations in MTR gene exhibits a wide spectrum of symptoms, including a retinopathy unresponsive to conventional therapies. METHODS: To unveil the underlying epigenetic pathological mechanisms, we conducted a comprehensive study of epigenomic-wide alterations of DNA methylation by NGS of bisulfited retinal DNA in an original murine model with conditional Mtr deletion in retinal tissue. Our focus was on postnatal day 21, a critical developmental juncture for ocular structure refinement and functional maturation. RESULTS: We observed delayed eye opening and impaired visual acuity and alterations in the one-carbon metabolomic profile, with a notable dramatic decline in SAM/SAH ratio predicted to impair DNA methylation. This metabolic disruption led to epigenome-wide changes in genes involved in eye development, synaptic plasticity, and retinoid metabolism, including promoter hypermethylation of Rarα, a regulator of Lrat expression. Consistently, we observed a decline in cone photoreceptor cells and reduced expression of Lrat, Rpe65, and Rdh5, three pivotal genes of eye retinoid metabolism. CONCLUSION: We introduced an original in vivo model for studying cblG retinopathy, which highlighted the pivotal role of altered DNA methylation in eye development, cone differentiation, and retinoid metabolism. This model can be used for preclinical studies of novel therapeutic targets.


Retinal Cone Photoreceptor Cells , Retinal Diseases , Mice , Animals , Retinal Cone Photoreceptor Cells/metabolism , Mice, Transgenic , Epigenome , DNA Methylation , S-Adenosylmethionine/metabolism , Retinal Diseases/metabolism , Carbon/metabolism , Retinoids/metabolism
4.
Cells ; 12(9)2023 04 27.
Article En | MEDLINE | ID: mdl-37174668

Impairment of one-carbon metabolism during pregnancy, either due to nutritional deficiencies in B9 or B12 vitamins or caused by specific genetic defects, is often associated with neurological defects, including cognitive dysfunction that persists even after vitamin supplementation. Animal nutritional models do not allow for conclusions regarding the specific brain mechanisms that may be modulated by systemic compensations. Using the Cre-lox system associated to the neuronal promoter Thy1.2, a knock-out model for the methionine synthase specifically in the brain was generated. Our results on the neurobehavioral development of offspring show that the absence of methionine synthase did not lead to growth retardation, despite an effective reduction of both its expression and the methylation status in brain tissues. Behaviors were differently affected according to their functional outcome. Only temporary retardations were recorded in the acquisition of vegetative functions during the suckling period, compared to a dramatic reduction in cognitive performance after weaning. Investigation of the glutamatergic synapses in cognitive areas showed a reduction of AMPA receptors phosphorylation and clustering, indicating an epigenomic effect of the neuronal deficiency of methionine synthase on the reduction of glutamatergic synapses excitability. Altogether, our data indicate that cognitive impairment associated with methionine synthase deficiency may not only result from neurodevelopmental abnormalities, but may also be the consequence of alterations in functional plasticity of the brain.


Amino Acid Metabolism, Inborn Errors , Cognitive Dysfunction , Mice , Pregnancy , Animals , Female , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/metabolism , Vitamin B 12
5.
Front Mol Biosci ; 8: 709395, 2021.
Article En | MEDLINE | ID: mdl-34277711

The last two decades have seen the discovery of novel retroviruses that have resulted in severe negative consequences for human health. In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged with a high transmission rate and severe effects on human health, with 5% infected persons requiring hospitalisation and 3.81 million deaths to date globally. Aerosol particles containing virions are considered the main source of SARS CoV-2 transmission in this pandemic, with increased infection rates in confined spaces. Consequently, public and private institutions had to institute mitigation measures including the use of facial masks and social distancing to limit the spread of the virus. Moreover, the role of air purification and bio-decontamination is understood as being essential to mitigate viral spread. Various techniques can be applied to bio-decontaminate the air such as the use of filtration and radiation; however, these methods are expensive and not feasible for home use. Another method of air purification is where indoor plants can purify the air by the removal of air pollutants and habituated airborne microbes. The use of indoor plants could prove to be a cost-efficient way of indoor air-purification that could be adapted for a variety of environments with no need for special requirements and can also add an aesthetic value that can have an indirect impact on human health. In this review, we discuss the emergence of the COVID-19 pandemic and the currently used air purification methods, and we propose the use of indoor plants as a new possible eco-friendly tool for indoor air purification and for reducing the spread of COVID-19 in confined places.

6.
Ocul Immunol Inflamm ; 29(6): 1090-1101, 2021 Aug 18.
Article En | MEDLINE | ID: mdl-32130054

Purpose: To find immunomediator combinations which could sensitively indicate keratoconus progression.Methods: Tear samples of 42 patients with keratoconus were collected at baseline and at the end of a one-year follow-up. The concentrations of 13 mediators were measured by CBA. Based on Pentacam HR examination, eyes were divided into a non-progressive and a progressive group.Results: At the end of the follow-up, significant differences were observed in the release of IFNγ, IL-13, IL-17A, CCL5, MMP-13 and PAI-1 between the two groups. Changes in five Pentacam parameters correlated positively with changes in IFNγ, IL-13, IL-17A, CXCL8, CCL5, TIMP-1 and t-PA. We found that tear level of IL-13 in combination with NGF can predict the progression of keratoconus with 100% specificity and 80% sensitivity.Conclusion: The findings of our longitudinal study may underscore the importance of NGF and IL-13 tear levels in the prediction of keratoconus progression.


Eye Proteins/metabolism , Interleukin-13/metabolism , Keratoconus/diagnosis , Nerve Growth Factor/metabolism , Tears/metabolism , Adolescent , Adult , Aged , Disease Progression , Female , Humans , Keratoconus/metabolism , Longitudinal Studies , Male , Middle Aged , Slit Lamp Microscopy , Visual Acuity/physiology , Young Adult
7.
Int J Ophthalmol ; 13(9): 1443-1450, 2020.
Article En | MEDLINE | ID: mdl-32953585

AIM: To evaluate detailed anterior segment parameters of patients with idiopathic inflammatory myopathies (IIM), including polymyositis (PM), and dermatomyositis (DM), and to clarify the associations between these data and clinical variables of IIM. METHODS: Totally 57 PM, 41 DM patients and 62 controls were enrolled in this cross-sectional, observational, case-control study. All study participants underwent Pentacam evaluation. Laboratory investigations consisted of different antibody assays, while extramuscular clinical assessments included Raynaud's phenomenon, dysphagia, interstitial lung disease, arthritis/arthralgia, and weight loss. Objective signs and subjective symptoms of dry eye disease (DED) were also evaluated. RESULTS: All pachymetric parameters [center, apex, thinnest and maximal keratometry (Kmax)] and corneal volume (CV) of both sides of PM patients proved to be significantly lower. Some pachymetric data were also noticed as significantly decreased compared to those of controls. Several significant differences were traced between anterior segment values and extramuscular manifestations of myositis, largely in case of arthritis/arthralgia and weight loss, whereas associations between anterior segment parameters and antibodies were weak. Objective clinical tests of DED were also significantly decreased in IIM patients. CONCLUSION: The results suggest that all IIM patients have thinner corneas compared with those of controls, and decreased corneal parameters are significantly associated with the occurrence of some extramuscular manifestations. In addition, IIM patients tend to develop objective signs of DED.

8.
Hum Mol Genet ; 29(12): 1969-1985, 2020 07 29.
Article En | MEDLINE | ID: mdl-32068834

Vitamin B12 or cobalamin (Cbl) metabolism can be affected by genetic defects leading to defective activity of either methylmalonyl-CoA mutase or methionine synthase or both enzymes. Patients usually present with a wide spectrum of pathologies suggesting that various cellular processes could be affected by modifications in gene expression. We have previously demonstrated that these genetic defects are associated with subcellular mislocalization of RNA-binding proteins (RBP) and subsequent altered nucleo-cytoplasmic shuttling of mRNAs. In order to characterize the possible changes of gene expression in these diseases, we have investigated global gene expression in fibroblasts from patients with cblC and cblG inherited disorders by RNA-seq. The most differentially expressed genes are strongly associated with developmental processes, neurological, ophthalmologic and cardiovascular diseases. These associations are consistent with the clinical presentation of cblC and cblG disorders. Multivariate analysis of transcript processing revaled splicing alterations that led to dramatic changes in cytoskeleton organization, response to stress, methylation of macromolecules and RNA binding. The RNA motifs associated with this differential splicing reflected a potential role of RBP such as HuR and HNRNPL. Proteomic analysis confirmed that mRNA processing was significantly disturbed. This study reports a dramatic alteration of gene expression in fibroblasts of patients with cblC and cblG disorders, which resulted partly from disturbed function of RBP. These data suggest to evaluate the rescue of the mislocalization of RBP as a potential strategy in the treatment of severe cases who are resistant to classical treatments with co-enzyme supplements.


5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics , Oxidoreductases/genetics , Vitamin B 12 Deficiency/genetics , Vitamin B 12/genetics , Alternative Splicing/genetics , Cell Line , ELAV-Like Protein 1/genetics , Fibroblasts/metabolism , Gene Expression Regulation/genetics , Humans , Proteomics , RNA-Binding Proteins/genetics , Ribonucleoproteins/genetics , Vitamin B 12/metabolism , Vitamin B 12 Deficiency/pathology
9.
Int J Mol Sci ; 20(22)2019 Nov 14.
Article En | MEDLINE | ID: mdl-31739389

Deficiencies in methyl donors, folate, and vitamin B12 are known to lead to brain function defects. Fetal development is the most studied but data are also available for such an impact in elderly rats. To compare the functional consequences of nutritional deficiency in young versus adult rats, we monitored behavioral outcomes of cerebellum and hippocampus circuits in the offspring of deficient mother rats and in adult rats fed a deficient diet from 2 to 8 months-of-age. We present data showing that the main deleterious consequences are found in young ages compared to adult ones, in terms of movement coordination and learning abilities. Moreover, we obtained sex and age differences in the deleterious effects on these functions and on neuronal layer integrity in growing young rats, while deficient adults presented only slight functional alterations without tissue damage. Actually, the cerebellum and the hippocampus develop and maturate according to different time lap windows and we demonstrate that a switch to a normal diet can only rescue circuits that present a long permissive window of time, such as the cerebellum, whereas the hippocampus does not. Thus, we argue, as others have, for supplements or fortifications given over a longer time than the developmental period.


Brain/metabolism , Brain/physiopathology , Deficiency Diseases/complications , Deficiency Diseases/metabolism , Fetal Development , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/metabolism , Animals , Cognition , Deficiency Diseases/etiology , Diet , Disease Models, Animal , Female , Folic Acid Deficiency/complications , Folic Acid Deficiency/metabolism , Hippocampus/metabolism , Hippocampus/physiopathology , Male , Maze Learning , Rats
10.
Sci Rep ; 9(1): 3419, 2019 03 04.
Article En | MEDLINE | ID: mdl-30833606

Our purpose was to prospectively analyze the age-related changes of corneal Scheimpflug parameters in healthy subjects. Thirty-five eyes of 35 volunteers (age 14-67 years) were investigated with an average interval of 3.6 years. Changes of corneal parameters (flattest keratometric reading at anterior (K1F) and posterior surface (K1B), steepest keratometric reading at anterior (K2F) and posterior surface, anterior astigmatism, posterior astigmatism (AstigB), flat axis of anterior and posterior astigmatism (AxisB), thinnest pachymetric value (PachyMin), corneal volume (CV10-mm)) were analyzed. K1F and K2F decreased significantly during observation and showed stronger decrease in younger than in older individuals. Higher values proved to be more stable. K1B decreased significantly and the degree of decrease was dependent on its baseline value and age: in young subjects low values increased, high values decreased. AstigB decreased significantly and showed a baseline-dependent significant increase from lower and a significant decrease from higher initial values. Over time, the mean AxisB shifted significantly. PachyMin and CV decreased significantly with age, especially from higher baseline values in younger subjects. The results of this longitudinal study suggest that both corneal surfaces change significantly with age. We demonstrate for the first time that age and baseline values influence age-related changes of corneal parameters.


Aging/physiology , Cornea/physiology , Adolescent , Adult , Aged , Astigmatism/diagnostic imaging , Astigmatism/physiopathology , Cornea/diagnostic imaging , Female , Healthy Volunteers , Humans , Longitudinal Studies , Male , Middle Aged , Young Adult
11.
Curr Eye Res ; 43(1): 18-26, 2018 01.
Article En | MEDLINE | ID: mdl-29111836

PURPOSE: Our aim was to compare densitometry data between keratoconus and normal corneas and to assess the long-term changes in corneal backscattered light values after corneal collagen cross-linking (CXL) treatment. MATERIAL AND METHODS: Retrospective analysis was performed on 26 eyes of normal patients (age: 32.71 ± 12.68 years) and 39 eyes of keratoconus patients (28.93 ± 7.59 years) using the Pentacam HR corneal densitometry module before CXL and during the postoperative period, which lasted a mean of 2.53 years (range: 1-4 years). Corneal backscattered light values in grey scale unit (GSU) were recorded for the anterior 120 µm, the center layer, and the posterior 60 µm of the cornea in four concentric, central rings. An additional calculation was performed with converting GSU values to GSU/cubic millimeters (mm3) with surface area calculations and using corneal thickness data. RESULTS: Statistically significant differences were observed between normal and keratoconus group densitometry values (in GSU/mm3) in all annuli of the center layer; all, but anterior layer of the 10-12 annuli; all annuli of the total thickness and in all values of the total diameter. In all these cases, the normal cornea showed higher GSU/mm3 values compared to keratoconus corneas (p < 0.05). One month after the CXL treatment, the GSU/mm3 data increased significantly in the anterior, the center, and the posterior zone (p < 0.05), followed by its slow decrease. At the end of the follow-up period, the GSU/mm3 values were significantly higher in all three zones compared to those before the CXL treatment (p < 0.01). CONCLUSION: Densitometry measurements can reflect the changes of optical quality of the cornea. These measurements may play a valuable role in assessing keratoconus and optical changes of the corneas after CXL treatment.


Collagen/therapeutic use , Cornea/pathology , Cross-Linking Reagents/therapeutic use , Densitometry/methods , Keratoconus/drug therapy , Light , Adolescent , Adult , Cornea/drug effects , Cornea/physiopathology , Corneal Topography , Female , Follow-Up Studies , Humans , Keratoconus/diagnosis , Keratoconus/physiopathology , Male , Middle Aged , Retrospective Studies , Scattering, Radiation , Time Factors , Young Adult
12.
Int J Ophthalmol ; 10(2): 217-222, 2017.
Article En | MEDLINE | ID: mdl-28251079

AIM: To analyze the correlations between ocular biomechanical and biometric data of the eye, measured by Scheimpflug-based devices on healthy subjects. METHODS: Three consecutive measurements were carried out using the corneal visualization Scheimpflug technology (CorVis ST) device on healthy eyes and the 10 device-specific parameters were recorded. Pentacam HR-derived parameters (corneal curvature radii on the anterior and posterior surfaces; apical pachymetry; corneal volume; corneal aberration data; depth, volume and angle of the anterior chamber) and axial length (AL) from IOLMaster were correlated with the 10 specific CorVis ST parameters. RESULTS: Measurements were conducted in 43 eyes of 43 volunteers (age 61.24±15.72y). The 10 specific CorVis ST data showed significant relationships with corneal curvature radii both on the anterior and posterior surface, pachymetric data, root mean square (RMS) data of lower-order aberrations, and posterior RMS of higher-order aberrations and spherical aberration of the posterior cornea. Anterior chamber depth showed a significant relationship, but there were no significant correlations between corneal volume, anterior chamber volume, mean chamber angle or AL and the 10 specific CorVis ST parameters. CONCLUSIONS: CorVis ST-generated parameters are influenced by corneal curvature radii, some corneal RMS data, but corneal volume, anterior chamber volume, chamber angle and AL have no correlation with the biomechanical parameters. The parameters measured by CorVis ST seem to refer mostly to corneal properties of the eye.

13.
Cornea ; 36(4): 434-439, 2017 Apr.
Article En | MEDLINE | ID: mdl-28079690

PURPOSE: To study the reliability and repeatability of anterior segment measurements in patients who underwent penetrating keratoplasty with swept light source Fourier domain anterior segment optical coherence tomography (SS-OCT) in comparison with a high-resolution Scheimpflug camera. METHODS: Keratometry (K) and elevation data of the anterior and posterior corneal surfaces, central corneal thickness, and anterior chamber depth were determined in 56 postkeratoplasty eyes (mean age: 59.6 ± 16.5 yrs) with SS-OCT (CASIA SS-1000; Tomey) followed by Scheimpflug photography (Pentacam High Resolution; Oculus). Examinations were also performed on 48 right eyes of 48 age-matched healthy subjects (mean age: 66.3 ± 7.0 yrs). RESULTS: A statistically significant difference was detected between both tomographers in anterior flat K [1.7 ± 4.92 diopters (D)], posterior astigmatism (1.32 ± 5.7 D) and elevation (6.65 ± 14.07 µm), and central corneal thickness (27.39 ± 90.81 µm) and anterior chamber depth values (0.14 ± 0.66 mm) in patients who had undergone corneal transplantation (P < 0.05). In the postkeratoplasty group, repeatability of SS-OCT was higher for every anterior segment parameter in comparison with the Pentacam. In corneal grafts, the variability between 3 consecutive measurements on the same subject was remarkably lower for every parameter while using SS-OCT. CONCLUSIONS: In patients who had undergone corneal transplantation, SS-OCT provided more reliable and repeatable anterior segment evaluations when compared with the rotating Scheimpflug system. Our findings suggested that the tested high-resolution swept-source OCT system is a comprehensive and precise diagnostic tool for postoperative follow-up of patients who have undergone penetrating keratoplasty.


Cornea/pathology , Keratoplasty, Penetrating , Photography , Tomography, Optical Coherence , Aged , Anterior Eye Segment/pathology , Corneal Diseases/surgery , Corneal Pachymetry , Female , Fourier Analysis , Healthy Volunteers , Humans , Male , Middle Aged , Reproducibility of Results
14.
Eur J Ophthalmol ; 27(3): 301-307, 2017 May 11.
Article En | MEDLINE | ID: mdl-27646325

PURPOSE: To analyze the effect of the accommodation on the anterior segment data (corneal and anterior chamber parameters) induced by short-time reading in a healthy, nonpresbyopic adult patient group. METHODS: Images of both eyes of nonpresbyopic volunteers were captured with a Scheimpflug device (Pentacam HR) in a nonaccommodative state. Fifteen minutes of reading followed and through fixation of the built-in target of Pentacam HR further accommodation was achieved and new images were captured by the device. Anterior segment parameters were observed and the differences were analyzed. RESULTS: Fifty-two healthy eyes of 26 subjects (range 20.04-28.58 years) were analyzed. No significant differences were observed in the keratometric values before and after the accommodative task (p = 0.35). A statistically significant difference was measured in the 5.0-mm-diameter and the 7.0-mm-diameter corneal volume (p = 0.01 and p = 0.03) between accommodation states. Corneal aberrometric data did not change significantly during short-term accommodation. Significant differences were observed between nonaccommodative and accommodative states of the eyes for all measured anterior chamber parameters. CONCLUSIONS: Among the parameters of the cornea, only corneal volume changed during the short-term accommodation process, showing some fine changes with accommodation of the cornea in young, emmetropic patients. The position of the pupil and the anterior chamber parameters were observed to change with accommodation as captured by a Scheimpflug device.


Accommodation, Ocular/physiology , Anterior Chamber/diagnostic imaging , Diagnostic Techniques, Ophthalmological , Emmetropia/physiology , Photography/methods , Reading , Adult , Anterior Chamber/physiology , Female , Healthy Volunteers , Humans , Male , Pupil/physiology , Young Adult
15.
PLoS One ; 11(4): e0153186, 2016.
Article En | MEDLINE | ID: mdl-27074131

PURPOSE: To compare the concentrations of 11 tear mediators in order to reveal the biochemical difference between pellucid marginal degeneration (PMD) and keratoconus (KC). METHODS: We have designed a cross-sectional study in which patients with corneal ectasia based on slit-lamp biomicroscopy and Pentacam HR (keratometry values (K1, K2, Kmax), astigmatism, minimal radius of curvature (Rmin), corneal thickness (Apex and Min), indices (surface variation, vertical asymmetry, keratoconus, central keratoconus, height asymmetry and decentration)) were enrolled. Eyes of keratoconic patients were similar to the PMD patients in age and severity (K2, Kmax and Rmin). Non-stimulated tear samples were collected from nine eyes of seven PMD patients, 55 eyes of 55 KC patients and 24 eyes of 24 healthy controls. The mediators' (interleukin -6, -10, chemokine ligand 5, -8, -10, matrix metalloproteinase (MMP) -9, -13, tissue inhibitor of metalloproteinases (TIMP)-1, tissue plasminogen activator, plasminogen activator inhibitor, nerve growth factor) concentrations were measured using Cytometric Bead Array. RESULTS: MMP-9 was the only mediator which presented relevant variances between the two patient groups (p = 0.005). The ratios of MMP-9 and TIMP-1 were 2.45, 0.40 and 0.23 in PMD, KC and the controls, respectively. CONCLUSION: As far as we are aware, this is the first study that aims to reveal the biochemical differences between PMD and KC. Further studies of biomarkers to investigate the precise role of these mediators need to be defined, and it is important to confirm the observed changes in a larger study to gain further insights into the molecular alterations in PMD.


Cornea/metabolism , Corneal Diseases/diagnosis , Keratoconus/diagnosis , Tears/metabolism , Adult , Aged , Corneal Diseases/metabolism , Corneal Topography , Cross-Sectional Studies , Diagnosis, Differential , Female , Humans , Keratoconus/metabolism , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged , Tissue Inhibitor of Metalloproteinase-1/metabolism
16.
Int J Ophthalmol ; 9(2): 235-8, 2016.
Article En | MEDLINE | ID: mdl-26949641

AIM: To analyse ocular biomechanical properties, central corneal thickness (CCT) and intraocular pressure (IOP) in post-keratoplasty eyes, as compared to normal subjects, with a new Scheimpflug-based technology. Moreover, biomechanical data were correlated with the size and age of the donor and recipient corneas. METHODS: Measurements were conducted on 46 eyes of 46 healthy patients without any corneal pathology (age: 53.83±20.8y) and 30 eyes of 28 patients after penetrating keratoplasty (age: 49.43±21.34y). Ten biomechanical parameters, the CCT and IOP were recorded by corneal visualization scheimpflug technology (CorVis ST) using high-speed Scheimpflug imaging. Keratometry values were also recorded using Pentacam HR system. Scheimpflug measurements were performed after 43.41±40.17mo (range: 11-128mo) after the keratoplasty and after 7.64±2.34mo (range: 5-14mo) of suture removal. RESULTS: Regarding the device-specific biomechanical parameters, the highest concavity time and radius values showed a significant decrease between these two groups (P=0.01 and P<0.001). None of other biomechanical parameters disclosed a significant difference. The CCT showed a significant difference between post-keratoplasty eyes as compared to normal subjects (P=0.003) using the CorVis ST device. The IOP was within the normal range in both groups (P=0.84). There were no significant relationships between the keratometric data, the size of the donor and recipient, age of the donor and recipient and biomechanical properties obtained by CorVis ST. CONCLUSION: The ocular biomechanics remain stable after penetrating keratoplasty according to the CorVis ST measurements. Only two from the ten device-specific parameters have importance in the follow-up period after penetrating keratoplasty.

17.
J Ophthalmol ; 2016: 9392640, 2016.
Article En | MEDLINE | ID: mdl-26881061

Purpose. To determine associations between mediators in tears in the whole spectrum of keratoconus (KC); to explore connections between mediators and Scheimpflug parameters; to examine correlations between Scheimpflug parameters and bronchial asthma. Methods. Tear samples were collected from 69 patients and 19 controls. Concentrations of mediators-IL-6, -10; CXCL8, CCL5; MMP-9, -13; TIMP-1; t-PA, PAI-1-were measured by Cytometric Bead Array. Measured Pentacam parameters include keratometry values (K 1, K 2, K max), corneal thickness (Pachy Pupil, Apex, Min), and elevations and indices (including Belin-Ambrósio deviation (BAD-D)). Results. A number of significant positive associations were observed between pairs of mediator concentrations. Significant positive correlations were found between BAD-D and CXCL8/MMP-9 and K 2 and MMP-9. Significant negative associations were explored between Pachy Min and CXCL8/t-PA. Significant associations were found between pairs of mediators (IL-6 and CXCL8; CCL5 and CXCL8/MMP-9; TIMP-1 and MMP-9/-13/t-PA; t-PA and CXCL8/CCL5/PAI-1) and the severity of KC. Significant positive correlation between asthma and the severity of KC was explored. Conclusion. Cooperation of different mediators in tears all taking part in the complex pathomechanism of keratoconus was revealed. Our research verifies that inflammation plays a crucial role in the pathogenesis of KC. Additionally this study confirms the effect of bronchial asthma on keratoconus.

18.
J Refract Surg ; 31(5): 333-7, 2015 May.
Article En | MEDLINE | ID: mdl-25974973

PURPOSE: To analyze the repeatability of keratometric and white-to-white (WTW) distance measurements with the VERION Measurement Module (Alcon Laboratories, Inc., Fort Worth, TX) and to compare the measured data to the results of the IOLMaster (Carl Zeiss Meditec, Jena, Germany). METHODS: Three images were captured with the VERION and the flattest and steepest keratometric data, the astigmatism axis, and the WTW distance were recorded. Subsequently, the axial length, the keratometric data with axis, and the WTW distance were measured with an IOLMaster. The repeatability data of the keratometric value of the VERION System, converted to cross cylinder J0 and J45 vector components, were analyzed. The agreement data for keratometry obtained by the VERION System and the differences regarding keratometric data and WTW distance compared to IOLMaster were calculated. RESULTS: The measurements were conducted in 50 eyes of 50 healthy volunteers (median age: 50.32 years, range: 19.34 to 85.3 years). The flattest and the steepest keratometric data, the diopter of astigmatism, the J0 and J45 vector components, and WTW distance did not differ significantly between devices (P > .05). Intraclass correlation coefficients (range: 0.863 to 0.994) and Cronbach's alpha values (range: 0.950 to 0.998) were high for all parameters measured by the VERION System. CONCLUSIONS: The VERION System has high repeatability and agreement with the IOLMaster, making it suitable as an alternative tool in clinical practice.


Cornea/anatomy & histology , Diagnostic Techniques, Ophthalmological/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Astigmatism/diagnosis , Axial Length, Eye/anatomy & histology , Axial Length, Eye/pathology , Biometry/instrumentation , Female , Healthy Volunteers , Humans , Male , Middle Aged , Reproducibility of Results
19.
Cornea ; 33(11): 1214-8, 2014 Nov.
Article En | MEDLINE | ID: mdl-25162757

PURPOSE: Our aim was to assess the corneal power, axis, and age dependence of the anterior and posterior corneal surfaces with Scheimpflug imaging. METHODS: Patients older than 10 years without a history of ocular surgery, corneal diseases, contact lens wearing, or severe dry eye were enrolled. Data regarding the anterior and posterior cornea were analyzed by means of Scheimpflug imaging (Pentacam HR). RESULTS: The median age was 46.8 years (range: 10.0-90.3), and involved 827 eyes of 827 patients. Posterior corneal astigmatism was a median of -0.30 diopters (D) and exceeded 0.50 D in 12.56%. The ratio of the anterior-to-posterior corneal radius was a median of 1.217 (range: 1.021-1.402). The correlation between this ratio and age was significant (r = -0.219; P < 0.001). The correlation between anterior and posterior corneal astigmatism and age was significant. At the anterior surface, the ratio of with-the-rule astigmatism was 80.0% for the age range 10 to 20, decreasing to 36.0% for those aged over 81 years, whereas the ratio of against-the-rule astigmatism increased from 7.1% to 44.0%. At the posterior surface, the ratio of with-the-rule astigmatism was 94.3% for the age range 10 to 20 years, decreasing to 84.0% for those aged over 81 years, whereas the ratio of against-the-rule astigmatism increased from 1.4% to 8.0%. CONCLUSIONS: The posterior cornea significantly influences corneal astigmatism. Its power value and orientation are much more stable with advancing age compared with anterior surface values.


Astigmatism/diagnosis , Cornea/pathology , Diagnostic Imaging/methods , Diagnostic Techniques, Ophthalmological , Adolescent , Adult , Aged , Aged, 80 and over , Aging/physiology , Child , Corneal Pachymetry , Female , Healthy Volunteers , Humans , Male , Middle Aged
20.
J Refract Surg ; 30(9): 604-8, 2014 Sep.
Article En | MEDLINE | ID: mdl-25068890

PURPOSE: To measure surgically induced astigmatism (SIA) on the posterior surface of the cornea using Scheimpflug-based keratometry on eyes with with-the-rule astigmatism. METHODS: Repeated Scheimpflug-based keratometry was obtained preoperatively and a mean of 8.65 weeks postoperatively following superior clear corneal incisions. Differences in the keratometric values and SIA were determined on the anterior and posterior surfaces separately and the data were analyzed. RESULTS: The study included 88 eyes of 88 patients (age range: 46.4 to 87.5 years), with the steepest total corneal meridian between 75° and 105°. Preoperatively, the magnitude of the anterior and posterior corneal astigmatism was 0.74 ± 0.44 and 0.29 ± 0.14 diopters (D), respectively, which was greater than 0.5 D in 10 eyes (11.36%). The difference between preoperative and postoperative keratometric data on the posterior surface was significant, as was the difference between the preoperative and postoperative posterior astigmatism. The mean magnitude of posterior corneal SIA was 0.32 ± 0.29 D, which was 0.5 D or greater in 22 eyes (25.00%). A statistically significant correlation was observed between the diopter of the preoperatively measured posterior corneal astigmatism and the postoperative SIA on the posterior surface (r = 0.34, P = .001). The correlation was not significant between SIA on the anterior and posterior surfaces (r = 0.10, P = .36). CONCLUSIONS: SIA on the posterior surface of the cornea may have a significant role, especially in cases of toric intraocular lens implantation. Posterior corneal astigmatism and SIA may have a significant clinical impact on more precise planning of cataract surgeries.


Astigmatism/etiology , Astigmatism/physiopathology , Cornea/physiopathology , Phacoemulsification/adverse effects , Aged , Aged, 80 and over , Cataract/complications , Cornea/surgery , Corneal Pachymetry , Corneal Topography , Humans , Lens Implantation, Intraocular , Middle Aged , Phacoemulsification/methods
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