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To examine corneal subbasal nerve changes in patients who received vaccination against SARS-CoV-2 virus and underwent COVID-19 infection compared to infected non-vaccinated patients and healthy controls. Twenty-nine eyes of 29 vaccinated patients (mean age: 36.66 ± 12.25 years) within six months after PCR or Ag test proven COVID-19 infection and twenty-eight eyes of 28 age-matched infected, non-vaccinated patients (mean age: 42.14 ± 14.17 years) were enrolled. Twenty-five age-matched healthy individuals (mean age: 47.52 ± 18.45 years) served as controls. In vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module, Germany) was performed in each group. Corneal subbasal nerve plexus morphology and corneal dendritic cells (DC) were evaluated. Significantly higher corneal nerve fiber density (P < 0.001), nerve branch density (P < 0.001), nerve fiber length (P < 0.001), total branch density (P = 0.007), nerve fiber area (P = 0.001) and fractal dimension (P < 0.001) values were observed in vaccinated patients after COVID-19 infection compared to the non-vaccinated group. Significantly higher DC density was observed in the non-vaccinated group compared to the control group (P = 0.05). There was a statistically significant difference in the size of mature DCs (P < 0.0001) but the size of immature DCs did not differ significantly among the 3 groups (P = 0.132). Our results suggest that SARS-CoV-2 vaccination may have a protective effect against the complications of COVID-19 disease on the corneal subbasal nerve fibers.
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COVID-19 , Córnea , Fibras Nervosas , SARS-CoV-2 , Vacinação , Humanos , COVID-19/virologia , COVID-19/patologia , COVID-19/prevenção & controle , Masculino , Feminino , Córnea/virologia , Córnea/patologia , Córnea/inervação , Adulto , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Fibras Nervosas/virologia , SARS-CoV-2/isolamento & purificação , Vacinas contra COVID-19/administração & dosagem , Microscopia Confocal , Células Dendríticas/imunologiaRESUMO
OBJECTIVE: To assess the efficacy of myopia control spectacle lenses (defocus incorporated multiple segments/DIMS) in slowing myopia progression among a diverse Central European paediatric population and investigate the contribution of baseline parameters on treatment outcomes. METHODS AND ANALYSIS: This retrospective observational study included 62 individuals aged 4-17 years (mean±SD: 10.21±2.70) with progressing myopia but without ocular pathology with a range of -0.88 to -8.25 D spherical equivalent refraction (SER) (-3.73±1.56), coupled with astigmatism up to -3.25 D cylindrical. All participants were prescribed DIMS (Hoya MiyoSmart) spectacles. Key outcome variables were cycloplegic SER, measured for all participants and axial length (AL), assessed in a subset of patients, recorded at baseline, 6 months and 12 months. Quality of life assessments were conducted at baseline, at 2 weeks, and 3, 6, 9 and 12 months. Additionally, parental myopic dioptre was recorded when applicable. RESULTS: At the 12-month mark, myopia progression in patients (mean±SE: -0.40±0.05) mirrored findings from prior European DIMS studies, but with 50% of patients showing no progression. A multivariate analysis of covariance model revealed that baseline astigmatism and younger age adversely affected therapy outcomes in both SER and AL, while severe maternal myopia led to greater SER progression. In contrast, only young age but not astigmatism was associated with AL increase in a comparable group of children with myopia, part of the LIFE Child Study, wearing single-vision spectacles. Patients reported consistent satisfaction with treatment, with minimal side effects, which diminished over the year. CONCLUSION: In the European population, astigmatism, young age and severe maternal myopia are risk factors for suboptimal outcomes following DIMS therapy. Further research is necessary to elucidate the impact of astigmatism on myopic defocus therapy.
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Astigmatismo , Miopia , Criança , Humanos , Astigmatismo/terapia , Miopia/terapia , Qualidade de Vida , Refração Ocular , Resultado do Tratamento , Pré-Escolar , AdolescenteRESUMO
AIM: Migraine is a chronic neurovascular disease that affects the trigeminovascular system. The purpose of this study was to evaluate corneal subbasal nerve fibers, dendritic cells and to measure tear film parameters in migraine. PATIENTS AND METHODS: 87 eyes of 44 patients suffering from migraine with a mean age of 33.23 ± 11.41 years were included in our study. 25 age-matched controls (mean age of 30.16 ± 12.59 years; P = 0.162) were recruited. The corneal subbasal plexus and the dendritic cells (DC) were analyzed using in vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module; Heidelberg Engineering GmbH), and the tear film was imaged using LacryDiag (Quantel Medical, France). RESULTS: Regarding the subbasal nerve fibers of the cornea, none of the examined parameters differed significantly in migraine patients from controls. We found a significant increase in the corneal DC density (P < 0.0001) and DC area (P < 0.0001) in migraine patients compared to healthy volunteers. DC density showed a positive correlation with the monthly attack frequency (r = 0.32, P = 0.041) and the DC area a negative correlation with corneal nerve branch density (r = -0.233, P = 0.039), nerve fiber length (r = -0.232, P = 0.04) and total branch density (r = -0.233, P = 0.039). Using LacryDiag a significant loss of Meibomian gland area could be detected on the superior eyelid (P = 0.005) in migraine. CONCLUSIONS: Our results suggest the presence of neuroinflammation in the cornea of migraine patients affecting the peripheral trigeminal system. Dendritic cells surrounding the subbasal plexus may be involved in the activation and modulation of pain in migraine.
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Diabetes mellitus affects carbohydrate homeostasis but also influences fat and protein metabolism. Due to ophthalmic complications, it is a leading cause of blindness worldwide. The molecular pathology reveals that nuclear factor kappa B (NFκB) has a central role in the progression of diabetic retinopathy, sharing this signaling pathway with another major retinal disorder, glaucoma. Therefore, new therapeutic approaches can be elaborated to decelerate the ever-emerging "epidemics" of diabetic retinopathy and glaucoma targeting this critical node. In our review, we emphasize the role of an improvement of lifestyle in its prevention as well as the use of phytomedicals associated with evidence-based protocols. A balanced personalized therapy requires an integrative approach to be more successful for prevention and early treatment.
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Diabetes Mellitus , Retinopatia Diabética , Glaucoma , Humanos , Retinopatia Diabética/tratamento farmacológico , Retina , Cegueira/complicações , Cegueira/prevenção & controle , Glaucoma/complicaçõesRESUMO
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
OBJECTIVE: To compare the efficacy and safety of two fixed combination, preservative-free eye drops (bimatoprost 0.01% in combination with either timolol 0.1% or 0.5%) in a gel formulation, with bimatoprost 0.03%/timolol 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Phase II, randomized, investigator-masked, multicenter, 3-arm parallel group (Eudract No. 2017-002823-46). Eighty-six patients aged ≥18 years with OAG or OHT, with intraocular pressure (IOP) initially controlled for at least 6 months by a combination therapy of a dual prostaglandin and timolol or insufficiently controlled by first-line monotherapy were included. Patients were randomized to receive T4030a (bimatoprost 0.01%/timolol 0.1%; N = 29), T4030c (bimatoprost 0.01%/timolol 0.5%; N = 29) or bimatoprost 0.03%/timolol 0.5% (N = 28), administered once daily in the evening for 12 weeks. Primary endpoint was defined as change in IOP from day 1 to week 12 measured at 08:00 (±1 h). Further efficacy, safety and pharmacokinetic endpoints were assessed as secondary outcomes. RESULTS: The mean change in IOP from baseline to week 12 was -9.8 ± 2.1 mmHg for T4030a, -10.1 ± 2.5 mmHg for T4030c and -10.0 ± 2.8 mmHg for bimatoprost 0.03%/timolol 0.5%. All treatments were well tolerated with no safety issues identified in any group. In patients treated with T4030a, the systemic concentration of timolol was significantly lower after 12 weeks than in patients treated with T4030c or bimatoprost 0.03%/timolol0.5%. CONCLUSIONS: These study results suggest that the preservative-free ophthalmic formulation of T4030a (bimatoprost 0.01%/timolol 0.1%) can be regarded as a useful tool in the therapeutic management of OAG and OHT.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Humanos , Adolescente , Adulto , Bimatoprost/efeitos adversos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Timolol/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Cloprostenol/efeitos adversos , Amidas/efeitos adversos , Hipertensão Ocular/tratamento farmacológico , Pressão Intraocular , Combinação de Medicamentos , Resultado do TratamentoRESUMO
Purpose: The purpose of this study was to assess whether retinal microvascular or corneal nerve abnormalities occur earlier in diabetes mellitus (DM) and to identify imaging biomarkers in order to help prevent the subsequent irreversible retinal and corneal complications. Methods: The study comprised 35 eyes of 35 healthy volunteers and 52 eyes of 52 patients with type 1 and type 2 DM. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal sub-basal nerve plexus and vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were evaluated. Results: All corneal sub-basal nerve fiber parameters were decreased in patients with DM compared with healthy subjects and the difference was significant for each result except for nerve fiber width (P = 0.586). No significant correlation was obtained between any nerve fiber morphology parameters and disease duration or HbA1C. VD in SCP was significantly decreased in the superior (P < 0.0001), temporal (P = 0.001), and nasal quadrant (P = 0.003) in the diabetes group. In DCP, only superior VD (P = 0.036), decreased significantly in the diabetes group. Ganglion cell layer thickness in the inner ring showed a significantly lower value in patients with DM (P < 0.0001). Conclusions: Our results implicate a more pronounced and earlier damage to the corneal nerve fibers compared to the retinal microvasculature in patients with DM. Translational Relevance: In DM, an earlier and more pronounced damage to the corneal nerve fibers was observed compared to the retinal microvasculature.
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Diabetes Mellitus Tipo 2 , Vasos Retinianos , Humanos , Retina , Diabetes Mellitus Tipo 2/complicações , Angiografia , Tomografia de Coerência Óptica/métodos , BiomarcadoresRESUMO
Introduction: Hurler-Scheie syndrome is a type of mucopolysaccharidosis I (MPS). In MPS I the decreased activity of alpha-L-iduronidase lysosomal enzyme leads to glycosaminoglycan (GAG) deposition in the intra- and extracellular matrix. Excessive amounts of GAG can accumulate in most layers of the cornea, including epithelial cells, stromal keratocytes, and endothelial cells. Case Presentation: A 25-year-old female patient suffering from Hurler-Scheie syndrome with multiple ocular manifestations is reported. Due to significant bilateral corneal opacification, penetrating keratoplasty was performed on both eyes. Histopathologic examination of the corneal buttons showed disorganized collagen fibers with heterogenous thickness and many granule-containing keratocytes with excessive cytoplasm. Despite receiving enzyme replacement therapy, in vivo confocal microscopy revealed characteristic vacuoles in the basal epithelium and corneal stroma 96 months after transplantation. High resolution anterior segment optical coherence tomography demonstrated hyperreflective opacities superficial and deeper in the stroma which was consistent with recurrence of host disease in the graft. Conclusion: To the best of our knowledge, this is the first documented Hurler-Scheie syndrome case of recurrence after penetrating keratoplasty demonstrated by in vivo confocal microscopy. Additionally, this patient manifested severe ocular involvement of MPS which might be an explanation of the progressive course of corneal opacification after transplantation.
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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
Glucocorticosteroids are key anti-inflammatory agents in the treatment of ophthalmic and systemic inflammatory diseases. However, prolonged use may result in an increase in intraocular pressure followed by a potentially vision -threatening ocular complication as glaucomatous neuropathy ultimately leading to blindness. Steroid therapy can increase intraocular pressure not only with ophthalmic preparations, but also with other routes of administration such as inhalational, intranasal and systemic. The aim of this paper is to provide a summary of the etiology, diagnosis, and treatment options for steroid-induced iatrogenic glaucoma, based on key literature findings and our own clinical experience, with a detailed comparison of different corticosteroid treatments. The application of steroid therapy can be avoided in a small number of medical fields, so it is crucial that where prolonged steroid therapy is required, all physicians should consider the intraocular pressure-enhancing effects of steroids. The intraocular pressure-increasing effect of steroids depends on the type of active substance, the route of administration and the time of administration. Regardless of the application of a certain medical field, regular ophthalmic examination is necessary, especially with a history of glaucoma, as persistent elevations in intraocular pressure can cause irreversible damage to ganglion cells and optic nerve fibers, ultimately leading to blindness. The difficulty in recognizing the complication is exacerbated by the fact that the intraocular pressure usually rises asymptomatically and painlessly. When steroid therapy cannot be avoided, the least possible intraocular pressure-increasing agent should be selected for the shortest possible dosage at the lowest possible dose. If the increase in intraocular pressure cannot be controlled conservatively, a surgical solution may be considered.
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Glaucoma , Pressão Intraocular , Cegueira , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Humanos , Fibras Nervosas , Nervo ÓpticoRESUMO
Metabolomics strategies are widely used to examine obesity and type 2 diabetes (T2D). Patients with obesity (n = 31) or T2D (n = 26) and sex- and age-matched controls (n = 28) were recruited, and serum and tear samples were collected. The concentration of 23 amino acids and 10 biogenic amines in serum and tear samples was analyzed. Statistical analysis and Pearson correlation analysis along with network analysis were carried out. Compared to controls, changes in the level of 6 analytes in the obese group and of 10 analytes in the T2D group were statistically significant. For obesity, the energy generation, while for T2D, the involvement of NO synthesis and its relation to insulin signaling and inflammation, were characteristic. We found that BCAA and glutamine metabolism, urea cycle, and beta-oxidation make up crucial parts of the metabolic changes in T2D. According to our data, the retromer-mediated retrograde transport, the ethanolamine metabolism, and, consequently, the endocannabinoid signaling and phospholipid metabolism were characteristic of both conditions and can be relevant pathways to understanding and treating insulin resistance. By providing potential therapeutic targets and new starting points for mechanistic studies, our results emphasize the importance of complex data analysis procedures to better understand the pathomechanism of obesity and diabetes.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Insulina , Metabolômica , ObesidadeRESUMO
PURPOSE: The purpose of this study was to evaluate corneal cellular and ultrastructural changes and to quantify the neuroinflammatory process in patients after mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Thirty patients after SARS-CoV-2 infection and 41 age-matched controls were examined. All subjects underwent in vivo confocal microscopy of the corneal cell layers and subbasal nerve fibers with the Heidelberg Retina Tomograph II. Semiautomated analysis of basal epithelial, anterior and posterior stromal keratocyte, and endothelial cell density was performed. Dendritic cell (DC) density and area were also calculated, and subbasal nerve plexus morphology was analyzed. RESULTS: The posterior stromal keratocyte density was significantly lower in patients after SARS-CoV-2 infection ( P = 0.0006). DC density in the central cornea was significantly higher in patients after SARS-CoV-2 infection ( P = 0.0004). There was a significant difference in the DC area between the 2 groups ( P < 0.0001). Significantly altered subbasal nerve fiber morphology was detected in patients after SARS-CoV-2 infection compared with healthy volunteers ( P < 0.05). CONCLUSIONS: Corneal cellular and ultrastructural changes demonstrated in this study suggest neuroinflammatory consequences of COVID-19 in the cornea in the absence of ophthalmoscopic alterations.
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COVID-19 , Contagem de Células , Córnea/inervação , Ceratócitos da Córnea , Humanos , Microscopia Confocal , SARS-CoV-2RESUMO
PURPOSE: To examine retinal and corneal neurodegenerative and retinal microvascular changes in patients after mild or asymptomatic COVID-19 disease compared to age-matched controls. METHODS: Thirty-five (35) patients after PCR-proven SARS-CoV-2 infection and 28 age-matched controls were enrolled. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal subbasal nerve plexus was quantified. Vessel density for superficial (SCP) and deep capillary plexus (DCP) and structural OCT parameters were recorded. RESULTS: Significantly lower nerve branch density (P = 0.0004), nerve fiber area (P = 0.0001), nerve fiber density (P = 0.0009), nerve fiber length (P < 0.0001), and total nerve branch density (P = 0.002) values were observed in patients after COVID-19 compared to healthy controls. VD of the temporal SCP was significantly different between the two groups (P = 0.019). No other SCP and DCP vessel density parameter differed significantly between the two groups. CONCLUSIONS: Our results suggest that peripheral neurodegenerative changes may occur even after mild or asymptomatic SARS-CoV-2 infection. No relevant microvascular changes were seen with OCT angiography and structural OCT parameters did not show any signs of optic neuropathy in post-COVID patients. In vivo confocal microscopy seems to be an important tool in monitoring peripheral neuropathy in patients after COVID-19.
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COVID-19 , Vasos Retinianos , COVID-19/complicações , COVID-19/diagnóstico , Angiofluoresceinografia/métodos , Humanos , SARS-CoV-2 , Tomografia de Coerência Óptica/métodosRESUMO
PURPOSE: To study the reproducibility of measurements performed with a recently developed multimodal high resolution swept source optical coherence tomography (SSOCT) and to make comparisons with a partial coherence interferometry (PCI) biometer. METHODS: One hundred and fifty-two eyes of 152 subjects were involved in this study with a mean age of 65.71 ± 13.86 years (26-85 years). Anterior surface keratometry (K), anterior chamber depth (ACD), white-to-white (WTW) and axial length (AL) values were recorded by the SSOCT (ANTERION, Heidelberg Engineering Ltd, Germany) and PCI (IOLMaster 500, version 5.5, Carl Zeiss Meditec, Germany). Intraocular lens (IOL) power was calculated based on ANTERION and IOLMaster keratometry values by using five traditional vergence formulas. RESULTS: Anterior surface simulated keratometry values did not differ significantly between the IOLMaster and ANTERION (P > 0.05). AL measurements were successful in 95% of the cases both with the SSOCT and PCI. No significant difference was disclosed between the two instruments (P = 0.229). For WTW measurements, a significant difference was observed between the two optical biometers (P < 0.0001). The difference between PCI and SSOCT in IOL powers was statistically significant for SRK/T, Hoffer and Holladay formulas (P < 0.001). CONCLUSION: Our results implicated an overall good reproducibility of anterior keratometry, AL, ACD and WTW measurements for IOLMaster and ANTERION. The discrepancies between their measurements resulted in significant difference in the calculated IOL power for SRK/T, Hoffer and Holladay formulas, but not for Haigis formula.
Assuntos
Lentes Intraoculares , Tomografia de Coerência Óptica , Idoso , Câmara Anterior/anatomia & histologia , Comprimento Axial do Olho , Biometria/métodos , Humanos , Interferometria , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tomografia de Coerência Óptica/métodosRESUMO
Összefoglaló. Az agy és a szem vascularis katasztrófái számos esetben egymáshoz társuló vagy egymást elore jelzo kórképek. Az arteria centralis retinae occlusio az ér rekanalizációjának hiányában a retina szöveteinek irreverzibilis károsodását okozza. Sem a nemzetközi, sem a hazai stroke-irányelvek nem foglalkoznak az ocularis stroke problémakörével, annak ellenére, hogy az arteria centralis retinae occlusio okozta retinalis ischaemia minden tekintetben megfelel az akut ischaemiás stroke definíciójának. Az eddig rendelkezésre álló irodalmi adatok alapján arteria centralis retinae occlusio esetén az intravénás thrombolysis 4,5 órán belül alkalmazva növeli a szignifikáns mértéku visusjavulás esélyét. Az országban jelenleg 4 centrum (Pécsi Tudományegyetem, Szegedi Tudományegyetem, Debreceni Egyetem, Semmelweis Egyetem) tervezi az ocularis stroke kezelésében a thrombolysis bevezetését. A maradandó látásromlás és a szekunder cerebrovascularis események megelozése érdekében elengedhetetlen az alapellátásban és a társszakmákban dolgozó kollégákkal való szoros együttmuködés. Orv Hetil. 2021; 162(47): 1871-1875. Summary. Vascular events of the brain and the eye may occur concomitantly or sequentially. In the absence of recanalization, central retinal artery occlusion causes irreversible damage to the retinal tissues. Even though retinal ischemia secondary to central retinal artery occlusion meets the definition of acute ischemic stroke, neither the international nor the Hungarian stroke guidelines mention ocular stroke. Based on the available literature, intravenous thrombolysis of the central retinal artery within 4.5 hours of occlusion can increase the odds of significant vision improvement. Currently 4 centers (University of Pécs, Debrecen, Szeged, and Semmelweis University) are planning to introduce thrombolysis in the treatment of ocular stroke. To prevent permanent visual loss and secondary cerebrovascular events, timely intervention requires the collaboration between general practitioners and other specialties. Orv Hetil. 2021; 162(47): 1871-1875.
Assuntos
Isquemia Encefálica , Oclusão da Artéria Retiniana , Acidente Vascular Cerebral , Olho , Face , Humanos , Oclusão da Artéria Retiniana/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
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.