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Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 µm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 µm after epithelial debridement and 375 µm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 µm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 µm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 µm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 µm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness. IMPORTANCE: This study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with.
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COVID-19 , RNA Viral , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , COVID-19/diagnóstico , COVID-19/virologia , RNA Viral/genética , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Teste de Ácido Nucleico para COVID-19/métodos , Propídio/análogos & derivados , Azidas , Sensibilidade e Especificidade , Teste para COVID-19/métodosRESUMO
PURPOSE: Stevens-Johnson syndrome (SJS) is characterised as an immuno-inflammatory condition with potentially blinding ocular sequelae. Therefore, we have investigated the ocular surface immune cell profile and correlated it with secreted tear molecular factors and clinical ocular sequelae in SJS patients. METHODS: 21 patients (42 eyes) with chronic ocular SJS and 16 healthy controls (20 eyes) were included in the study. Severity, types of keratopathies and ocular surface (OS) manifestations were determined. OS wash samples from study subjects were used to determine the status of 13 immune cell subsets using flow cytometry. Levels of 42 secreted immuno-inflammatory factors were measured by flow cytometry-based multiplex ELISA in tear samples. RESULTS: Neutrophils (Total, activated), neutrophils/NK cells ratio, neutrophils/T cells ratio were significantly (p < 0.05) elevated in SJS, while, proportions of T cells and NKT cells were significantly lower in SJS patients. Positive association between neutrophils and chronic ocular surface complication score (COCS) was observed, whereas, a negative association was noted between NK cells and COCS. Tear fluid levels of IL-6, IL-8, IL-18, IFNα/ß/γ, TNFα, LIF, IL-8, HGF, sTNFR-I, NGAL, Granzyme, Perforins, MMP9/TIMP1 ratio were significantly higher in SJS. Loss of Limbal niche correlated significantly with immune profile and clinical sequelae. Increased neutrophils, decreased NK cells and specific set of altered secreted immuno-inflammatory mediators including bFGF, and IL-8 were observed in SJS patients with different types of keratopathies compared to those without keratopathy. CONCLUSION: Distinct ocular surface immune profile variations were observed to correlate with clinical stages of chronic ocular SJS. Our findings uncover novel mechanisms and potential for targeted therapy in chronic ocular SJS patients.
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The conjunctival epithelium covering the eye contains two main cell types: mucus-producing goblet cells and water-secreting keratinocytes, which present mucins on their apical surface. Here, we describe long-term expanding organoids and air-liquid interface representing mouse and human conjunctiva. A single-cell RNA expression atlas of primary and cultured human conjunctiva reveals that keratinocytes express multiple antimicrobial peptides and identifies conjunctival tuft cells. IL-4/-13 exposure increases goblet and tuft cell differentiation and drastically modifies the conjunctiva secretome. Human NGFR+ basal cells are identified as bipotent conjunctiva stem cells. Conjunctival cultures can be infected by herpes simplex virus 1 (HSV1), human adenovirus 8 (hAdV8), and SARS-CoV-2. HSV1 infection was reversed by acyclovir addition, whereas hAdV8 infection, which lacks an approved drug therapy, was inhibited by cidofovir. We document transcriptional programs induced by HSV1 and hAdV8. Finally, conjunctival organoids can be transplanted. Together, human conjunctiva organoid cultures enable the study of conjunctival (patho)-physiology.
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Túnica Conjuntiva , Células Caliciformes , Humanos , Camundongos , Animais , Túnica Conjuntiva/metabolismo , Células Caliciformes/metabolismo , Epitélio , Interleucina-13 , Homeostase , OrganoidesRESUMO
The intraoperative optical coherence tomography (iOCT) is recently introduced in Descemet membrane endothelial keratoplasty (DMEK) surgery, which aims to increase clinical performance and surgery safety. However, the acquisition of this modality is a substantial investment. The objective of this paper is to report on the cost-effectiveness of an iOCT-protocol in DMEK surgery with the Advanced Visualization in Corneal Surgery Evaluation (ADVISE) trial. This cost-effectiveness analysis uses data 6 months postoperatively from the multicentre prospective randomized clinical ADVISE trial. Sixty-five patients were randomized to usual care (n = 33) or the iOCT-protocol (n = 32). Quality-Adjusted Life Years (EQ-5D-5L), Vision-related Quality of Life (NEI-VFQ-25) and self-administered resources questionnaires were administered. Main outcome is the incremental cost-effectiveness ratio (ICER) and sensitivity analyses. The iOCT protocol reports no statistical difference in ICER. For the usual care group compared with the iOCT protocol, respectively, the mean societal costs are 5027 compared with 4920 (Δ107). The sensitivity analyses report the highest variability on time variables. This economic evaluation learned that there is no added value in quality of life or cost-effectiveness in using the iOCT protocol in DMEK surgery. The variability of cost variables depends on the characteristics of an eye clinic. The added value of iOCT could gain incrementally by increasing surgical efficiency, and aiding in surgical decision-making.
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Análise de Custo-Efetividade , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Análise Custo-Benefício , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Endotélio Corneano , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tomografia de Coerência Óptica/métodosRESUMO
Purpose: Keratoconus is characterized by the progressive thinning of the cornea, which leads to a cone-like appearance of the eye over time. Although conventionally defined as a noninflammatory condition, a number of recent studies have associated keratoconus (KC) with allergic conjunctivitis (AC) based on clinical parameters. This study aimed to consolidate this association by performing a proteomic analysis of tear fluid from patients with keratoconus and/or allergic conjunctivitis. Methods: Of 51 patients, 17 were diagnosed with KC, 17 were diagnosed with AC, and 17 were diagnosed with both KC and AC (combined). Nine of 34 patients with KC had a progressive form of the disease. Tear fluid samples (n = 51, one eye per patient) were collected by the Schirmer's strips. Tear proteins were extracted from the Schirmer's strips. Proteomic profiling of 384 inflammatory proteins was assessed by a multiplex proximity extension assay (Olink Explore 384 Inflammation Panel I). Results: A total of 384 inflammatory proteins were measured. Two hundred seventy-two of the 384 proteins passed stringent data cleaning and were compared among the patient groups. Compared to the 2 other groups, LGALS9 was upregulated uniquely in KC, whereas FGF19, PDGFB, HPCAL1, OSM, and FCAR were downregulated in KC. Similarly, TNFRSF4 and CCL13 were specifically upregulated in AC, whereas ectodysplasin A receptor (EDAR) was uniquely downregulated in AC. Conclusions: High-throughput proteomic profiling of tear fluid confirms the association between KC and AC on a molecular level and raise the importance of redefining KC as an inflammatory condition.
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Conjuntivite Alérgica , Ceratocone , Humanos , Ceratocone/diagnóstico , Ceratocone/metabolismo , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/metabolismo , Proteoma/metabolismo , Proteômica , Córnea/metabolismo , Lágrimas/metabolismoRESUMO
PURPOSE: To compare the prediction accuracy of toric intraocular lens calculations using estimated vs measured posterior corneal astigmatism (PCA). DESIGN: Retrospective case series. METHODS: A total of 110 eyes of 110 patients with uncomplicated toric intraocular lens implantation were included in this study. Predicted postoperative refractive astigmatism was calculated with the Barrett Toric Calculator using the estimated PCA (E-PCA), the measured IOLMaster 700 PCA (I-PCA), and the measured Pentacam PCA (P-PCA). Refractive astigmatism prediction errors (RA-PEs), including their trimmed (tr-) centroid (mean vector), spread (precision), tr-mean absolute RA-PE (accuracy), and percentage within a certain threshold, were determined using vector analysis and compared between groups. SETTING: University Eye Clinic, Maastricht University Medical Center+, the Netherlands. RESULTS: The tr-centroid RA-PEs of the E-PCA (0.02 diopter [D] at 82.2°), the I-PCA (0.08 D at 35.5°), and the P-PCA (0.09 D at 69.1°) were significantly different from each other (P < .01), but not significantly different from zero (P = .75, P = .05, and P = .05, respectively). The E-PCA had the best precision (tr-mean 0.40 D), which was not significantly lower than the I-PCA (0.42 D, P = .53) and P-PCA (0.43 D, P = .06). The E-PCA also had the best accuracy (0.40 D), which was not significantly different from the I-PCA (0.42 D, P = .26) and significantly better than the P-PCA (0.44 D, P < .01). The precision and accuracy of the I-PCA did not significantly differ from those of the P-PCA. There were no statistically significant differences in the percentage of eyes within a certain absolute RA-PE threshold. CONCLUSIONS: The Barrett Toric Calculator using the E-PCA, I-PCA, or P-PCA showed a comparable prediction of postoperative refractive astigmatism in standard clinical practice.
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BACKGROUND: Keratoconus remains difficult to diagnose, especially in the early stages. It is a progressive disorder of the cornea that starts at a young age. Diagnosis is based on clinical examination and corneal imaging; though in the early stages, when there are no clinical signs, diagnosis depends on the interpretation of corneal imaging (e.g. topography and tomography) by trained cornea specialists. Using artificial intelligence (AI) to analyse the corneal images and detect cases of keratoconus could help prevent visual acuity loss and even corneal transplantation. However, a missed diagnosis in people seeking refractive surgery could lead to weakening of the cornea and keratoconus-like ectasia. There is a need for a reliable overview of the accuracy of AI for detecting keratoconus and the applicability of this automated method to the clinical setting. OBJECTIVES: To assess the diagnostic accuracy of artificial intelligence (AI) algorithms for detecting keratoconus in people presenting with refractive errors, especially those whose vision can no longer be fully corrected with glasses, those seeking corneal refractive surgery, and those suspected of having keratoconus. AI could help ophthalmologists, optometrists, and other eye care professionals to make decisions on referral to cornea specialists. Secondary objectives To assess the following potential causes of heterogeneity in diagnostic performance across studies. ⢠Different AI algorithms (e.g. neural networks, decision trees, support vector machines) ⢠Index test methodology (preprocessing techniques, core AI method, and postprocessing techniques) ⢠Sources of input to train algorithms (topography and tomography images from Placido disc system, Scheimpflug system, slit-scanning system, or optical coherence tomography (OCT); number of training and testing cases/images; label/endpoint variable used for training) ⢠Study setting ⢠Study design ⢠Ethnicity, or geographic area as its proxy ⢠Different index test positivity criteria provided by the topography or tomography device ⢠Reference standard, topography or tomography, one or two cornea specialists ⢠Definition of keratoconus ⢠Mean age of participants ⢠Recruitment of participants ⢠Severity of keratoconus (clinically manifest or subclinical) SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), Ovid MEDLINE, Ovid Embase, OpenGrey, the ISRCTN registry, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 29 November 2022. SELECTION CRITERIA: We included cross-sectional and diagnostic case-control studies that investigated AI for the diagnosis of keratoconus using topography, tomography, or both. We included studies that diagnosed manifest keratoconus, subclinical keratoconus, or both. The reference standard was the interpretation of topography or tomography images by at least two cornea specialists. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the study data and assessed the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When an article contained multiple AI algorithms, we selected the algorithm with the highest Youden's index. We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included 63 studies, published between 1994 and 2022, that developed and investigated the accuracy of AI for the diagnosis of keratoconus. There were three different units of analysis in the studies: eyes, participants, and images. Forty-four studies analysed 23,771 eyes, four studies analysed 3843 participants, and 15 studies analysed 38,832 images. Fifty-four articles evaluated the detection of manifest keratoconus, defined as a cornea that showed any clinical sign of keratoconus. The accuracy of AI seems almost perfect, with a summary sensitivity of 98.6% (95% confidence interval (CI) 97.6% to 99.1%) and a summary specificity of 98.3% (95% CI 97.4% to 98.9%). However, accuracy varied across studies and the certainty of the evidence was low. Twenty-eight articles evaluated the detection of subclinical keratoconus, although the definition of subclinical varied. We grouped subclinical keratoconus, forme fruste, and very asymmetrical eyes together. The tests showed good accuracy, with a summary sensitivity of 90.0% (95% CI 84.5% to 93.8%) and a summary specificity of 95.5% (95% CI 91.9% to 97.5%). However, the certainty of the evidence was very low for sensitivity and low for specificity. In both groups, we graded most studies at high risk of bias, with high applicability concerns, in the domain of patient selection, since most were case-control studies. Moreover, we graded the certainty of evidence as low to very low due to selection bias, inconsistency, and imprecision. We could not explain the heterogeneity between the studies. The sensitivity analyses based on study design, AI algorithm, imaging technique (topography versus tomography), and data source (parameters versus images) showed no differences in the results. AUTHORS' CONCLUSIONS: AI appears to be a promising triage tool in ophthalmologic practice for diagnosing keratoconus. Test accuracy was very high for manifest keratoconus and slightly lower for subclinical keratoconus, indicating a higher chance of missing a diagnosis in people without clinical signs. This could lead to progression of keratoconus or an erroneous indication for refractive surgery, which would worsen the disease. We are unable to draw clear and reliable conclusions due to the high risk of bias, the unexplained heterogeneity of the results, and high applicability concerns, all of which reduced our confidence in the evidence. Greater standardization in future research would increase the quality of studies and improve comparability between studies.
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Inteligência Artificial , Ceratocone , Humanos , Ceratocone/diagnóstico por imagem , Estudos Transversais , Exame Físico , Estudos de Casos e ControlesRESUMO
INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.
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Transplante de Córnea , Cirurgiões , Humanos , Endotélio Corneano/cirurgia , Células Endoteliais , Estudos de Coortes , Azul Tripano , Transplante de Córnea/efeitos adversos , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVES: We aimed to assess Long COVID sexual dysfunction among both sexes. PATIENTS AND METHODS: A cross-sectional study at a multidisciplinary COVID clinic. Consecutive patients answered a symptom-based questionnaire, which included sexual dysfunction. Individuals reporting any degree of sexual dysfunction were compared with those who denied. A multivariable logistic regression was conducted to identify risk factors. A principal component analysis was implemented to explore other symptoms associated with sexual dysfunction. RESULTS: All in all, 391 individuals recovering from COVID-19 completed the questionnaire, 211 women and 180 men. Mean age was 45.2 (SD 15.4) years. Most (280, 85.9%) had mild COVID-19, assessed at a median of 3.8 (IQR 2.0) months from diagnosis. Sexual dysfunction was reported by 55 (36%) of the men and 48 (28%) of the women. Increased age [per year; men OR 1.05 (95% CI 1.02-1.08)], long COVID cough [men 2.58 (1.05-6.32)], chest pain [women 3.54 (1.28-9.80)], irritability [women 3.45 (1.28-9.29)], paresthesia [men 4.23 (1.55-10.44); women 3.08 (1.14-8.32)], and emotional distress [men 3.26 (1.36-7.82); women 4.29 (1.65-11.18)] were significantly associated with sexual dysfunction. In women, sexual dysfunction was part of the emotional pattern, while among men, it was part of the emotional and pulmonary patterns. CONCLUSION: Sexual dysfunction is a common manifestation of long COVID in both men and women. Presence of other long COVID symptoms, and older age, are associated with this phenomenon. Further studies should explore the mechanisms for long COVID sexual dysfunction in both men and women, as well as strategies for prevention and treatment.
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The cornea is a transparent and avascular tissue located in front of the eye. Its inner surface is lined by a monolayer of corneal endothelial cells (CECs), which maintain the cornea transparency. CECs remain arrested in a non-proliferative state and damage to these cells can compromise their function leading to corneal opacity. The primary culture of donor-derived CECs is a promising cell therapy. It confers the potential to treat multiple patients from a single donor, alleviating the global donor shortage. Nevertheless, this approach has limitations preventing its adoption, particularly culture protocols allow limited expansion of CECs and there is a lack of clear parameters to identify therapy-grade CECs. To address this limitation, a better understanding of the molecular changes arising from the primary culture of CECs is required. Using single-cell RNA sequencing on primary cultured CECs, we identify their variable transcriptomic fingerprint at the single cell level, provide a pseudo-temporal reconstruction of the changes arising from primary culture, and suggest markers to assess the quality of primary CEC cultures. This research depicts a deep transcriptomic understanding of the cellular heterogeneity arising from the primary expansion of CECs and sets the basis for further improvement of culture protocols and therapies.
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Células Endoteliais , Endotélio Corneano , Humanos , Análise da Expressão Gênica de Célula Única , Córnea , Células CultivadasRESUMO
Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.
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Aniridia , Doenças da Córnea , Humanos , Doenças da Córnea/etiologia , Doenças da Córnea/terapia , Aniridia/complicações , Aniridia/terapia , Aniridia/genética , Córnea/patologia , Transtornos da Visão , PrevisõesAssuntos
Ceratocone , Lentes Intraoculares , Humanos , Ceratocone/cirurgia , Olho , Refração Ocular , Estudos RetrospectivosRESUMO
BACKGROUND: Keratoconus is a degenerative disorder of the cornea leading to a protrusion and thinning with loss of visual acuity. The only treatment to halt the progression is corneal crosslinking (CXL), which uses riboflavin and UV-A light to stiffen the cornea. Recent ultra-structural examinations show that the disease is regional and does not affect the entire cornea. Treating only the affected zone with CXL could be as good as the standard CXL, that treats the entire cornea. METHODS: We set up a multicentre non-inferiority randomized controlled clinical trial comparing standard CXL (sCXL) and customized CXL (cCXL). Patients between 16 and 45 years old with progressive keratoconus were included. Progression is based on one or more of the following changes within 12 months: 1 dioptre (D) increase in keratometry (Kmax, K1, K2); or 10% decrease of corneal thickness; or 1 D increase in myopia or refractive astigmatism, requiring corneal crosslinking. DISCUSSION: The goal of this study is to evaluate whether the effectiveness of cCXL is non-inferior to sCXL in terms of flattening of the cornea and halting keratoconus progression. Treating only the affected zone could be beneficial for minimalizing the risk of damaging surrounding tissues and faster wound healing. Recent non-randomized studies suggest that a customized crosslinking protocol based on the tomography of the patient's cornea may stop the progression of keratoconus and result in flattening of the cornea. TRIAL REGISTRATION: This study was prospectively registered at ClinicalTrials.gov on August 31st, 2020, the identifier of the study is NCT04532788.
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Ceratocone , Fotoquimioterapia , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Colágeno/uso terapêutico , Córnea , Refração Ocular , Riboflavina/uso terapêutico , Fotoquimioterapia/métodos , Reagentes de Ligações Cruzadas/uso terapêutico , Topografia da Córnea/métodos , Raios Ultravioleta , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
Purpose: Dry eye disease (DED) is characterized by altered ocular surface proinflammatory and antiinflammatory factors. Interferons (IFNs) are a class of pleiotropic cytokines well known for their antimicrobial, inflammatory, and immunomodulatory roles. Hence, this study investigates the ocular surface expression of different types of IFNs in patients with DED. Methods: The cross-sectional, observational study included patients with DED and normal subjects. Conjunctival impression cytology (CIC) samples were obtained from the study subjects (controls, n = 7; DED, n = 8). The mRNA expression levels of type 1 IFN (IFNα, IFNß), type 2 IFN (IFNγ), and type 3 IFN (IFNλ1, IFNλ2, IFNλ3) were measured by quantitative PCR (polymerase chain reaction) in CIC samples. IFNα and IFNγ expression under hyperosmotic stress was also studied in human corneal epithelial cells (HCECs) in vitro. Results: The mRNA expression levels of IFNα and IFNß were significantly lower and that of IFNγ was significantly higher in DED patients compared to healthy controls. The mRNA levels of IFNα, IFNß, and IFNλ were significantly lower compared to IFNγ in DED patients. An inverse association between tonicity-responsive enhancer-binding protein (TonEBP; hyperosmotic stress maker) and IFNα or IFNß expression and a positive association between TonEBP and IFNγ expression was observed in CIC samples. The expression of IFNα was lower than IFNγ in HCECs undergoing hyperosmotic stress compared to HCECs without the stress. Conclusion: The presence of an imbalance between type 1 and type 2 IFNs in DED patients suggests newer pathogenic processes in DED, plausible ocular surface infection susceptibility in DED patients, and potential therapeutic targets in the management of DED.
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Citocinas , Síndromes do Olho Seco , Humanos , Estudos Transversais , Citocinas/metabolismo , Interferon-alfa , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/genética , Síndromes do Olho Seco/metabolismo , Células Epiteliais/metabolismoRESUMO
The regenerative capacity of corneal endothelial cells (CECs) differs between species; in bigger mammals, CECs are arrested in a non-proliferative state. Damage to these cells can compromise their function causing corneal opacity. Corneal transplantation is the current treatment for the recovery of clear eyesight, but the donor tissue demand is higher than the availability and there is a need to develop novel treatments. Interestingly, rabbit CECs retain a high proliferative profile and can repopulate the endothelium. There is a lack of fundamental knowledge to explain these differences. Gaining information on their transcriptomic variances could allow the identification of CEC proliferation drivers. In this study, human, sheep, and rabbit CECs are analyzed at the transcriptomic level. To understand the differences across each species, a pipeline for the analysis of pathways with different activities is generated. The results reveal that 52 pathways have different activity when comparing species with non-proliferative CECs (human and sheep) to species with proliferative CECs (rabbit). The results show that Notch and TGF-ß pathways have increased activity in species with non-proliferative CECs, which might be associated with their low proliferation. Overall, this study illustrates transcriptomic pathway-level differences that can provide leads to develop novel therapies to regenerate the corneal endothelium.
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PURPOSE: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands. METHODS: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors. RESULTS: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001). CONCLUSIONS: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome.
Assuntos
Ceratite por Acanthamoeba , Transplante de Córnea , Infecções Oculares Virais , Humanos , Estudos Prospectivos , Ceratoplastia Penetrante/métodos , Resultado do Tratamento , Acuidade Visual , Ceratite por Acanthamoeba/cirurgia , Sistema de Registros , Sobrevivência de Enxerto , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate the performance of different probabilistic classifiers to predict posterior capsule rupture (PCR) prior to cataract surgery. METHODS: Three probabilistic classifiers were constructed to estimate the probability of PCR: a Bayesian network (BN), logistic regression (LR) model, and multi-layer perceptron (MLP) network. The classifiers were trained on a sample of 2 853 376 surgeries reported to the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO) between 2008 and 2018. The performance of the classifiers was evaluated based on the area under the precision-recall curve (AUPRC) and compared to existing scoring models in the literature. Furthermore, direct risk factors for PCR were identified by analysing the independence structure of the BN. RESULTS: The MLP network predicted PCR overall the best (AUPRC 13.1 ± 0.41%), followed by the BN (AUPRC 8.05 ± 0.39%) and the LR model (AUPRC 7.31 ± 0.15%). Direct risk factors for PCR include preoperative best-corrected visual acuity (BCVA), year of surgery, operation type, anaesthesia, target refraction, other ocular comorbidities, white cataract, and corneal opacities. CONCLUSIONS: Our results suggest that the MLP network performs better than existing scoring models in the literature, despite a relatively low precision at high recall. Consequently, implementing the MLP network in clinical practice can potentially decrease the PCR rate.