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Introduction: The aim of the study was to report a unique case with excellent clinical outcomes after late endophthalmitis following Descemet's membrane endothelial keratoplasty (DMEK) surgery requiring donor graft removal without replacement. Case Presentation: A 67-year-old female with a prior ocular history of bilateral cataract surgery, Fuchs endothelial dystrophy, and pseudophakic DMEK in the left eye presented with endophthalmitis 2 months after keratoplasty. DMEK graft removal without replacement with an intracameral washout, pars plana vitrectomy, intracameral, and intravitreal antibiotics resulted in an excellent visual outcome (20/25). Conclusion: This is a unique case of late endophthalmitis following DMEK surgery requiring graft removal and pars plana vitrectomy with excellent visual recovery without donor replacement.
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INTRODUCTION: Patients undergoing surgery due to hip fracture face an elevated risk of a subsequent fall during rehabilitation. An important contributing factor to this risk is deteriorated visual function, often responsive to intervention. This study aims to explore differences in visual acuity (VA) and stereovision (SV) between individuals with a history of fall-related hip injuries (study group) and age-matched controls, utilizing a mobile application (EuvisionTab, ET) to distinguish age-related visual decline from pathological vision. MATERIALS & METHODS: A total of 32 and 71 participants were enrolled in the study and control groups, respectively (mean age: 74.9 years, range: 60-96). Monocular logMAR VA was measured using a tablet by means of an adaptive threshold-search algorithm. SV was assessed using low-dot density static and dynamic random dot stereograms. An age-dependent reference limit for VA was established. For ET stereotests, the number of correctly identified optotypes out of 10 random presentations served as the measure for further comparisons. Visually impaired status in the study group was determined if patients failed either the VA threshold or the SV criteria. RESULTS: In the control group, an apparent but statistically nonsignificant decline in VA was observed, while stereovision remained stable and did not exhibit significant age-related variations based on ET stereotests. Conversely, the study group demonstrated significantly worse results in monocular VA (p = 0.0032) and for both stereotests (p = 0.018 for static, p = 0.036 for dynamic) according to paired samples t-test and chi-square test, respectively. Hip injuries were significantly associated with visual impairment (OR = 4.88, p = 0.0012). DISCUSSION: This study focuses on one possible risk factor of elderly falls, namely, vision impairment. Patients with visual decay present a higher incidence of hip injuries compared to age-matched controls. This data suggest that vision screening and, when feasible, restoration of visual function may contribute to the prevention of secondary falls, refractures, or contralateral fractures. A mobile-based screening protocol, executable as part of a postoperative bedside examination and independent of specialized eye care, can be proposed.
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Acidentes por Quedas , Fraturas do Quadril , Transtornos da Visão , Acuidade Visual , Humanos , Idoso , Masculino , Feminino , Acuidade Visual/fisiologia , Fraturas do Quadril/cirurgia , Fraturas do Quadril/fisiopatologia , Idoso de 80 Anos ou mais , Acidentes por Quedas/prevenção & controle , Transtornos da Visão/fisiopatologia , Transtornos da Visão/prevenção & controle , Pessoa de Meia-Idade , Aplicativos Móveis , Estudos de Casos e Controles , Testes Visuais , Percepção de Profundidade/fisiologiaRESUMO
Parkinson's disease is one of the most prevalent neurological disorders affecting millions of people worldwide. There is a growing demand for novel and natural substances as complementary therapies. Essential oils and their various compounds are highly investigated natural plant-based products as potential treatment options for common human diseases, such as microbial infections, chronic diseases, and neurodegenerative disorders. The present study focuses on the beneficial effects of linalool and geraniol, the major compounds of lavender (Lavandula angustifolia L.) and geranium (Pelargonium graveolens L'Hér. in Aiton) essential oils, on oxidative stress, inflammation, and iron metabolism of the rotenone and 6-hydroxydopamine-induced in vitro Parkinson's models. The experiments were carried out on all-trans retinoic acid differentiated SH-SY5Y cells. The effects of linalool and geraniol were compared to rasagiline, an MAO-B inhibitor. The results revealed that both essential oil compounds reduce the level of reactive oxygen species and alter the antioxidant capacity of the cells. They lower the secretion of IL-6, IL-8, and IL-1ß pro-inflammatory cytokines. Moreover, linalool and geraniol change the expression of iron-related genes, such as the iron importer transferrin receptor 1, heme-oxygenase-1, and ferroportin iron exporter, and influence the intracellular iron contents. In addition, it has been unveiled that iron availability is concatenated with the actions of the essential oil compounds. Based on the results, linalool and geraniol are vigorous candidates as an alternative therapy for Parkinson's disease.
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BACKGROUND/AIMS: To evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of SB15 versus reference aflibercept (AFL), and switching from AFL to SB15 in neovascular age-related macular degeneration (nAMD). DESIGN: Prospective, double-masked, randomised, phase 3 trial. METHODS: Participants with nAMD were randomised 1:1 to receive SB15 (N=224 participants) or AFL (N=225). At week 32, participants either continued on SB15 (SB15/SB15, N=219) or AFL (AFL/AFL, N=108), or switched from AFL to SB15 (AFL/SB15, N=111). This manuscript reports 1-year and switching results of secondary efficacy endpoints such as changes from baseline to week 56 in best-corrected visual acuity (BCVA), central subfield thickness (CST, from internal limiting membrane (ILM) to retinal pigment epithelium), and total retinal thickness (TRT, from ILM to Bruch's membrane). Additional endpoints included safety, PK and immunogenicity. RESULTS: Efficacy results were comparable between groups. The least squares mean (LSmean) change in BCVA from baseline to week 56 was 7.4 letters for SB15/SB15 and 7.0 letters for AFL/AFL (difference (95% CI)=0.4 (-2.5 to 3.2)). The LSmean changes from baseline to week 56 in CST and TRT were -119.2 µm and -132.4 µm for SB15/SB15 and -126.6 µm and -136.3 µm for AFL/AFL, respectively (CST: difference (95% CI)=7.4 µm (-6.11 to 20.96); TRT: difference (95% CI)=3.9 µm (-18.35 to 26.10)). Switched and non-switched participants showed similar LSmean changes in BCVA from baseline to week 56 (AFL/SB15, 7.9 letters vs AFL/AFL, 7.8 letters; difference (95% CI)=0.0 (-2.8 to 2.8)). Safety, PK and immunogenicity were comparable between groups. CONCLUSIONS: Efficacy, safety, PK and immunogenicity were comparable between SB15 and AFL and between switched and non-switched participants.
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Medicamentos Biossimilares , Degeneração Macular , Humanos , Inibidores da Angiogênese/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Estudos Prospectivos , Acuidade VisualRESUMO
Despite the high probability of glaucoma-related blindness, its cause is not fully understood and there is no efficient therapeutic strategy for neuroprotection. Vascular factors have been suggested to play an important role in glaucoma development and progression. Previously, we have proven the neuroprotective effects of pituitary adenylate-cyclase-activating polypeptide (PACAP) eye drops in an inducible, microbeads model in rats that is able to reproduce many clinically relevant features of human glaucoma. In the present study, we examined the potential protective effects of PACAP1-38 on the retinal vasculature and the molecular changes in hypoxia. Ocular hypertension was induced by injection of microbeads into the anterior chamber, while control rats received PBS. PACAP dissolved in vehicle (1 µg/drop) or vehicle treatment was started one day after the injections for four weeks three times a day. Retinal degeneration was assessed with optical coherence tomography (OCT), and vascular and molecular changes were assessed by immunofluorescence labeling. HIF1-α and VEGF-A protein levels were measured by Western blot. OCT images proved severe retinal degeneration in the glaucomatous group, while PACAP1-38 eye drops had a retinoprotective effect. Vascular parameters were deteriorated and molecular analysis suggested hypoxic conditions in glaucoma. PACAP treatment exerted a positive effect against these alterations. In summary, PACAP could prevent the severe damage to the retina and its vasculature induced by ocular hypertension in a microbeads model.
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Glaucoma , Hipertensão Ocular , Degeneração Retiniana , Animais , Ratos , Glaucoma/tratamento farmacológico , Hipóxia , Hipertensão Ocular/tratamento farmacológico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/uso terapêutico , Vasos RetinianosRESUMO
Importance: Aflibercept biosimilars can expand available treatment options in retinal diseases and have the potential to improve patient access to safe and effective therapy. Objective: To establish equivalence in efficacy and similarity in safety, pharmacokinetics, and immunogenicity of SB15 and reference aflibercept (AFL) in neovascular age-related macular degeneration (nAMD). Design, Setting, and Participants: This was a randomized double-masked parallel group phase 3 trial conducted at 56 centers in 10 countries from June 2020 to March 2022, including follow-up through 56 weeks. Of 549 screened participants, 449 participants 50 years and older with treatment-naive nAMD were included and randomly assigned to SB15 (n = 224) or AFL (n = 225). Key exclusion criteria included considerable scarring, fibrosis, atrophy, and hemorrhage. This report includes results up to the end of the parallel group period at week 32. Of the 449 randomized participants, 438 (97.6%) completed week 32 follow-up. Intervention: Participants were randomized 1:1 to receive 2 mg of SB15 or AFL every 4 weeks for the first 12 weeks (3 injections), followed by dosing every 8 weeks up to week 48, with final assessments at week 56. Main Outcomes and Measures: The primary end point was the change in best-corrected visual acuity (BCVA) from baseline to week 8 with predefined equivalence margins of -3 letters to 3 letters. Other key end points were changes in BCVA and central subfield thickness up to week 32, safety, pharmacokinetics, and immunogenicity. Results: The mean (SD) age among the 449 included participants was 74.0 (8.1) years, and 250 participants (55.7%) were female. Baseline demographic characteristics and most disease characteristics were comparable between treatment groups. The least squares mean change in BCVA from baseline to week 8 in the SB15 group was equivalent to that in the AFL group (6.7 letters vs 6.6 letters, respectively; difference, 0.1 letters; 95% CI, -1.3 to 1.4). Comparable efficacy between treatment groups was maintained up to week 32 (least squares mean change from baseline in BCVA: SB15, 7.6 letters vs AFL, 6.5 letters; least squares mean change from baseline in central subfield thickness: SB15, -110.4 µm vs AFL, -115.7 µm). No clinically relevant differences were observed in the incidence of treatment-emergent adverse events (TEAEs) (SB15, 107/224 [47.8%] vs AFL, 98/224 [43.8%]) and ocular TEAEs in the study eye (SB15, 41/224 [18.3%] vs AFL, 28/224 [12.5%]). The serum concentration profiles and cumulative incidences of overall antidrug antibody positive participants were comparable. Conclusions and Relevance: In this phase 3 randomized clinical trial, SB15 and AFL showed equivalent efficacy and comparable safety, pharmacokinetics, and immunogenicity in participants with nAMD. Trial Registration: ClinicalTrials.gov Identifier: NCT04450329.
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Medicamentos Biossimilares , Degeneração Macular , Degeneração Macular Exsudativa , Humanos , Feminino , Idoso , Masculino , Inibidores da Angiogênese/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Resultado do Tratamento , Acuidade Visual , Injeções Intravítreas , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/efeitos adversos , Degeneração Macular/tratamento farmacológico , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Degeneração Macular Exsudativa/induzido quimicamente , Ranibizumab/uso terapêuticoRESUMO
An imbalance of homeostasis in the retina leads to neuron loss and this eventually results in a deterioration of vision. If the stress threshold is exceeded, different protective/survival mechanisms are activated. Numerous key molecular actors contribute to prevalent metabolically induced retinal diseases-the three major challenges are age-related alterations, diabetic retinopathy and glaucoma. These diseases have complex dysregulation of glucose-, lipid-, amino acid or purine metabolism. In this review, we summarize current knowledge on possible ways of preventing or circumventing retinal degeneration by available methods. We intend to provide a unified background, common prevention and treatment rationale for these disorders and identify the mechanisms through which these actions protect the retina. We suggest a role for herbal medicines, internal neuroprotective substances and synthetic drugs targeting four processes: parainflammation and/or glial cell activation, ischemia and related reactive oxygen species and vascular endothelial growth factor accumulation, apoptosis and/or autophagy of nerve cells and an elevation of ocular perfusion pressure and/or intraocular pressure. We conclude that in order to achieve substantial preventive or therapeutic effects, at least two of the mentioned pathways should be targeted synergistically. A repositioning of some drugs is considered to use them for the cure of the other related conditions.
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Retinopatia Diabética , Glaucoma , Degeneração Retiniana , Humanos , Degeneração Retiniana/etiologia , Degeneração Retiniana/prevenção & controle , Degeneração Retiniana/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Retina/metabolismo , Retinopatia Diabética/metabolismo , Glaucoma/metabolismoRESUMO
Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.
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Carcinoma de Células Escamosas , Neoplasias da Túnica Conjuntiva , Neoplasias Oculares , Administração Tópica , Carcinoma de Células Escamosas/patologia , Neoplasias da Túnica Conjuntiva/tratamento farmacológico , Neoplasias da Túnica Conjuntiva/patologia , Neoplasias da Túnica Conjuntiva/cirurgia , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Fluoruracila , Humanos , Interferon alfa-2 , Mitomicina , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Glaucoma is associated with increased intraocular pressure (IOP), causing the apoptosis of retinal ganglion cells (RGCs) and the loss of their axons leading to blindness. Pituitary adenylate cyclase activating polypeptide (PACAP) is neuroprotective in several neural injuries, including retinopathies. The aim of this study was to investigate the effects of PACAP1-38 eye drops in a model of glaucoma. IOP was elevated bilaterally by injections of microbeads to block the aqueous humor outflow. The control groups received the same volume of saline. Animals were treated with PACAP1-38 (1 µg/drop, 3 × 1 drop/day) or vehicle for 4 weeks starting one day after the injections. Retinal morphology by histology and optical coherence tomography, function by electroretinography, and IOP changes were analyzed. Animals were sacrificed 8 weeks after the injections. Microbeads injections induced a significant increase in the IOP, while PACAP1-38 treatment lowered it to normal levels (~10 mmHg). Significant retinal degeneration and functional impairment were observed in the microbead-injected group without PACAP1-38 treatment. In the microbeads + PACAP1-38 group, the retinal morphology and functionality were close to the normal values. In summary, our results show that PACAP1-38, given in form of eye drops, is neuroprotective in glaucoma, providing the basis for potential future therapeutic administration.
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Modelos Animais de Doenças , Glaucoma/tratamento farmacológico , Microesferas , Fármacos Neuroprotetores/farmacologia , Soluções Oftálmicas/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/farmacologia , Degeneração Retiniana/prevenção & controle , Animais , Glaucoma/etiologia , Glaucoma/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Degeneração Retiniana/etiologia , Degeneração Retiniana/patologiaAssuntos
Neoplasias da Coroide/secundário , Imidazóis/administração & dosagem , Imunoterapia/métodos , Melanoma/secundário , Melanoma/terapia , Oximas/administração & dosagem , Piridonas/administração & dosagem , Pirimidinonas/administração & dosagem , Neoplasias Cutâneas/patologia , Corioide/patologia , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/terapia , Quimioterapia Combinada , Seguimentos , Humanos , Injeções Intralesionais , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/terapia , Tomografia de Coerência Óptica/métodos , Melanoma Maligno CutâneoRESUMO
PURPOSE: To compare vergence, artificial intelligence, and combined intraocular lens (IOL) calculation formulas using a new swept-source optical coherence tomographer (SS-OCT) and to analyze their performance based on manifest and estimated refractive outcomes of cataract surgery. SETTING: Department of Ophthalmology, University of Pécs Medical School, Pécs, Hungary. DESIGN: Retrospective data analysis. METHODS: Optical biometry readings of patients who underwent uneventful cataract removal and implantation of a monofocal acrylic IOL were used to predict IOL power with Barrett Universal II (BUII), Haigis, Hoffer Q, Holladay 1, Radial Basis Function (RBF) 2.0, Kane, Ladas Super Formula, and SRK/T. All the implanted IOLs were calculated by using the Haigis formula. The arithmetic prediction error and median and mean absolute refractive errors for all formulas were computed. The percentage of eyes within ±0.25 diopters (D), ±0.50 D, and ±1.0 D of prediction error was calculated. RESULTS: A total of 95 eyes of 95 patients with a mean age of 68.80 ± 7.57 years were included. There was a statistically significant difference in absolute prediction error across the 8 IOL calculation formulas (P < .0001). Haigis showed the lowest mean absolute error, and it differed significantly from the BUII, Hoffer Q, Holladay 1, Ladas, RBF 2.0, and SRK/T formulas (P < .05). In terms of eyes within ±0.25 D, ±0.50 D, and ±1.0 D of prediction error, the Haigis formula showed the overall best performance. CONCLUSIONS: The results indicated that a recently developed SS-OCT provided accurate ocular biometry measurements before cataract surgery, and the Haigis formula incorporated in its software enabled precise calculation of IOL refractive power.
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Lentes Intraoculares , Facoemulsificação , Idoso , Inteligência Artificial , Biometria , Humanos , Implante de Lente Intraocular , Pessoa de Meia-Idade , Óptica e Fotônica , Refração Ocular , Estudos RetrospectivosRESUMO
Tears are a constantly available and highly valuable body fluid collectable by non-invasive techniques. Although it can give information on ocular status and be used for follow-ups, tear analysis is challenging due to the low amount of sample that is available. Proximity extension assay (PEA) allows for a sensitive and scalable analysis of multiple proteins in a single run from a one-µL sample, so we applied this technique and examined the amount of 184 proteins in tears collected at different time points after trabeculectomy. The success rate of this surgical intervention highly depends on proper wound healing; therefore, information on the process is indispensable. We observed significantly higher levels of IL-6 and MMP1 at the early time points (day one, two, and four) following trabeculectomy, and the protein amounts went back to the level observed before the surgery three months after the intervention. Patients with or without complications were tested, and proteins that have roles in the immune response and wound healing could be observed with altered frequency and amounts in the cases of patients with complications. Our results highlight the importance of inflammation in wound-healing complications, and at the same time, indicate the utility of PEA in tear analysis.
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Glaucoma/genética , Inflamação/genética , Interleucina-6/genética , Metaloproteinase 1 da Matriz/genética , Lágrimas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Glaucoma/cirurgia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Inflamação/cirurgia , Interleucina-6/metabolismo , Masculino , Metaloproteinase 1 da Matriz/metabolismo , Pessoa de Meia-Idade , Trabeculectomia/métodos , Cicatrização/genéticaRESUMO
PURPOSE: Plasminogen activator activity (PAA) in tears of pregnant women was investigated at various gestation times to assess the availability of plasminogen activator for aiding potential corneal wound healing processes during pregnancy. METHODS: PAA was measured by a spectrophotometric method. The analysis used 91 tear samples from pregnant and non-pregnant women, supplemented with 10 additional tear PAA measurements from non-pregnant women obtained in a previous study. RESULTS: Tear levels of PAA in pregnant women formed a bimodal distribution. Either the tear PAA level was zero or non-zero during pregnancy. When non-zero, the tear PAA level was dissociated from gestation time and not different than non-pregnant and post-pregnant levels. The frequency of occurrence of zero level tear PAA increased with gestation: 16%, 17% and 46% had zero tear PAA in samples taken from women in the first, second and third trimester, respectively. CONCLUSIONS: Overall, of the tear samples taken from women during pregnancy, a total of 26% were at zero tear PAA. The remaining tear samples had non-zero tear PAA values throughout gestation equivalent to non-pregnant tear PAA values, suggesting local control of the source of PAA in tears. Given the importance of the plasminogen activator system in tears to wound healing in the cornea, and the high occurrence of zero tear PAA in our sample of pregnant women, elective corneal surgery would be contraindicated. If corneal surgery is nevertheless necessary, the tear PAA level would be worth checking and patients with low level should be closely observed during the postoperative period.
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Ativadores de Plasminogênio/metabolismo , Lágrimas/metabolismo , Adulto , Feminino , Humanos , Gravidez , Adulto JovemRESUMO
Background. It is estimated that 347 million people suffer from diabetes mellitus (DM), and almost 5 million are blind due to diabetic retinopathy (DR). The progression of DR can be slowed down with early diagnosis and treatment. Therefore our aim was to develop a novel automated method for DR screening. Methods. 52 patients with diabetes mellitus were enrolled into the project. Of all patients, 39 had signs of DR. Digital retina images and tear fluid samples were taken from each eye. The results from the tear fluid proteomics analysis and from digital microaneurysm (MA) detection on fundus images were used as the input of a machine learning system. Results. MA detection method alone resulted in 0.84 sensitivity and 0.81 specificity. Using the proteomics data for analysis 0.87 sensitivity and 0.68 specificity values were achieved. The combined data analysis integrated the features of the proteomics data along with the number of detected MAs in the associated image and achieved sensitivity/specificity values of 0.93/0.78. Conclusions. As the two different types of data represent independent and complementary information on the outcome, the combined model resulted in a reliable screening method that is comparable to the requirements of DR screening programs applied in clinical routine.
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Aneurisma/diagnóstico , Diabetes Mellitus/metabolismo , Retinopatia Diabética/diagnóstico , Fundo de Olho , Proteoma/metabolismo , Retina , Vasos Retinianos , Lágrimas/metabolismo , Idoso , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Fotografação , Proteômica , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To analyze the repeatability of a new device measuring ocular biomechanical properties, central corneal thickness (CCT), and intraocular pressure (IOP) and to investigate these parameters and their correlations in healthy eyes. METHODS: Three consecutive measurements were performed on each eye using the CorVis ST device (Oculus Optikgeräte, Inc., Wetzler, Germany). Ten specific parameters, CCT, and IOP were measured. Biometric data were recorded with IOLMaster (Carl Zeiss Meditec, Jena, Germany). RESULTS: This study comprised 75 eyes of 75 healthy volunteers (mean age: 61.24 ± 15.72 years). Mean IOP was 15.02 ± 2.90 mm Hg and mean CCT was 556.33 ± 33.13 µm. Intraclass correlation coefficient (ICC) was 0.865 for IOP and 0.970 for CCT, and coefficient of variation was 0.069 for IOP and 0.008 for CCT. ICC was 0.758 for maximum amplitude at highest concavity and 0.784 for first applanation time, and less than 0.6 for all other parameters. The device-specific data showed no significant relationship with age and axial length. Flattest and steepest keratometric values and IOP showed a significant correlation with the 10 device-specific parameters. CONCLUSIONS: The CorVis ST showed high repeatability for only IOP and pachymetric values. Single measurements are not reliable for the 10 device-specific parameters. The device allows for conducting clinical examinations and screening for surgeries altering ocular biomechanical properties with some form of averaging of multiple measurements.
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Córnea/fisiologia , Tonometria Ocular/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Córnea/diagnóstico por imagem , Desenho de Equipamento , Humanos , Pressão Intraocular , Microscopia Acústica , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Adulto JovemRESUMO
PURPOSE: To examine the effect of aprotinin eye drops on urokinase-type plasminogen activator (uPA) gene expression in rabbit corneal cells during wound healing after photorefractive keratectomy (PRK). METHODS: Both eyes of 22 rabbits were subjected to PRK. One eye of each rabbit was treated with antibiotic eye drops five times while the contralateral eye was treated at the same time with antibiotic eye drops and a serine protease inhibitor. The animals were sacrificed at different time frames, and 2-4 rabbits were used for each time point. Half of each cornea was used for the determination of the amount of uPA mRNA after reverse transcription and real-time quantitative polymerase chain reaction, while frozen sections were prepared from the other halves for in situ zymography to detect uPA activity. RESULTS: The level of uPA mRNA in corneal cells was markedly increased in corneal samples obtained hours after PRK. The time-dependent up-regulation of uPA mRNA was strongly dependent on the diameter of the area from which the epithelial cells were removed before the surgery. Independently of the time scale of uPA up-regulation, application of eye drops containing aprotinin significantly diminished the uPA expression. In situ zymography confirmed that aprotinin has also decreased overall uPA activity. CONCLUSIONS: Aprotinin down-regulates uPA gene expression in corneal cells during the wound-healing phase after PRK.
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Aprotinina/administração & dosagem , Córnea/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Ceratectomia Fotorrefrativa , Inibidores de Serina Proteinase/administração & dosagem , Ativador de Plasminogênio Tipo Uroquinase/genética , Cicatrização/efeitos dos fármacos , Animais , Córnea/enzimologia , Soluções Oftálmicas/administração & dosagem , RNA Mensageiro/genética , Coelhos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
PURPOSE: To determine the transcription pattern of Nod-like receptors (NLRs) and inflammasome components (apoptosis-associated speck-like protein containing a CARD [ASC], CARD inhibitor of NFkB-activating ligands [Cardinal], and caspase-1) in human corneal epithelial cells obtained from healthy individuals undergoing photorefractive keratectomy and in immortalized human corneal epithelial cells (HCE-T). METHODS: Human corneal epithelial cells were taken from the eyes of healthy individuals by epithelial ablation for photorefractive keratectomy (PRK). The SV-40 immortalized human corneal epithelial cell line (HCE-T) was cultured. mRNA obtained from the cells was reverse transcribed and subjected to quantitative real-time polymerase chain reaction (PCR) measurements. Protein obtained from HCE-T cells was studied using the western blot technique. HCE-T cells were irradiated by UV-B light or treated with ultrapure peptidoglycan, and the effects were studied at the mRNA and protein level while the supernatant of the cells was tested for the presence of various cytokines by using enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: mRNA levels of the studied proteins in the primary cells of the donors were similar in most cases. The transcription of Nod1, Nod2, NLRX1, Nalp1, and Cardinal was similar in the two cell types. While the expression of Nalp3 and Nalp10 was higher in HCE-T cells, ASC and caspase-1 showed higher transcription levels in the primary cells. NLRC5 and Nalp7 were hardly detectable in the studied cells. Functionality of the Nod1/Nod2 system was demonstrated by increased phosphorylation of IkB upon Nod1/Nod2 agonist ultrapure peptidoglycan treatment in HCE-T cells. While UV-B irradiation exerted a downregulation of both Nalp and Nod mRNAs as well as those of inflammasome components in HCE-T cells, longer incubation of the cells after exposure resulted in recovery or upregulation only of the Nalp sensors. At the protein level, we detected a short isoform of Nalp1 and its expression changed in a similar way as its RNA expression, but we could not detect Nalp3 protein. Among the studied cytokines, only IL-6 was detected in the supernatant of HCE-T cells. Its constitutively secreted level increased by only twofold after 24 h of UV-B irradiation. CONCLUSIONS: Based on our experiments, UV-B irradiation appears to exert an immunosilencing effect on the HCE-T cells by downregulating most of the sensor molecules as well as the components of the inflammasomes. Expression profiling of corneal epithelial cells suggested that the HCE-T cells may not serve as a good model for Nalp3 or Nalp1 inflammasome studies but it may be better suited for studies on the Nod1/Nod2 systems.
Assuntos
Células Epiteliais/metabolismo , Células Epiteliais/efeitos da radiação , Epitélio Corneano/citologia , Epitélio Corneano/metabolismo , Proteínas Adaptadoras de Sinalização NOD/genética , Transcrição Gênica/efeitos da radiação , Raios Ultravioleta , Linhagem Celular , Linhagem Celular Transformada , Células Epiteliais/enzimologia , Epitélio Corneano/enzimologia , Feminino , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Inflamação/enzimologia , Interleucina-6/metabolismo , Masculino , Proteínas Adaptadoras de Sinalização NOD/metabolismoRESUMO
PURPOSE: To observe levels of plasminogen activator inhibitor (PAI) in human tears after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). SETTING: University medical center eye clinic. METHODS: Tear samples were collected from 46 eyes having PRK and 13 eyes having LASIK immediately before and after surgery and on the first (LASIK), third (PRK), and fifth (PRK) postoperative days. Analyses used enzyme-linked immunoassay, yielding 61 PRK PAI-1 determinations and 146 PRK and 35 LASIK PAI-2 determinations. RESULTS: All determinations of PRK PAI-1 were below the detection limit of 1 ng/mL of the original tear sample. In the PRK eyes, the mean PAI-2 concentration was 19.8 ng/mL +/- 23.4 (SD) in preoperative tears, 112.7 +/- 60.5 ng/mL immediately postoperatively, 12.1 +/- 19.5 ng/mL after 3 days, and 15.5 +/- 20.4 ng/mL after 5 days. In the LASIK eyes, the mean PAI-2 concentration was 19.0 +/- 33.1 ng/mL preoperatively, 111.5 +/- 69.2 ng/mL immediately postoperatively, and 15.7 +/- 18.8 ng/mL after 1 day. CONCLUSIONS: The similarity in the general time pattern of PAI-2 after PRK and LASIK suggests commonality in the enzymatic control response to corneal surgical wounding. Taken in the context of previous work, the observed levels of PAI-2 concentration in eyes with and without opacification suggest that in the postsurgical period, PAI-2 is not the controlling mechanism for the later development of corneal opacification and haze.
Assuntos
Proteínas do Olho/metabolismo , Ceratomileuse Assistida por Excimer Laser In Situ , Ceratectomia Fotorrefrativa , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Inibidor 2 de Ativador de Plasminogênio/metabolismo , Lágrimas/metabolismo , Adulto , Ensaio de Imunoadsorção Enzimática , Humanos , Lasers de Excimer , Miopia/metabolismo , Miopia/cirurgia , Período Pós-Operatório , CicatrizaçãoRESUMO
Plasminogen activator is a normal component of tear fluid that plays a role in corneal wound healing processes. This work examines whether inhibitor-induced low levels of plasminogen activator activity (PAA) during corneal re-epithelialization after excimer laser photorefractive keratectomy (PRK) correlates with the eventual occurrence of haze in rabbit eyes. Tear samples were collected with glass capillaries from 16 eyes of eight New Zealand rabbits, using i.m. injection of pilocarpine hydrochloride for stimulation. Tears were collected before and after PRK surgery, and then daily for 5 days, and every fourth day thereafter for 3 months. Both eyes underwent PRK treatment. One eye of each rabbit was treated as a control while the contralateral eye was treated with aprotinin, a serine protease inhibitor, over the first 7 days. PAA in the tear samples was measured by a spectrophotometric method using human plasminogen and chromogenic peptide substrate S-2251. For the eight control eyes after PRK, the PAA values were significantly lower (day 1) and higher (days 2 and 3) than the equilibrium PAA (p<0.001). The corneas remained clear in each of these control eyes. For the eight contralateral aprotinin-treated eyes after PRK, the PAA values on days 1-7 were significantly lower than the equilibrium PAA (p<0.001). All eight of these aprotinin-treated eyes developed corneal haze after 2 months. There was no significant difference (p=0.06) between control and aprotinin-treated eyes for the equilibrium PAA after 19 days. We conclude that a corneal wound healing abnormality (haze) develops in rabbit eyes after PRK when PAA levels are reduced using aprotinin for a week following PRK.