RESUMEN
PURPOSE: Pseudomonas aeruginosa-induced keratitis is one of the most severe and challenging forms of corneal infection, owing to its associated intense inflammatory reactions leading to corneal necrosis and dense corneal scar with loss of vision. Since mesenchymal stem cells (MSCs) are reported to possess antimicrobial and immunomodulatory properties, they can be tested as an adjuvant treatment along with the antibiotics which are the current standard of care. This study aims to investigate the anti-bacterial and immunomodulatory roles of human bone marrow MSC-derived conditioned medium (MSC-CM) in P. aeruginosa-infected human corneal epithelial cells (HCECs) in vitro. METHODS: The effect of MSC-CM on the growth of clinical isolates of P. aeruginosa was evaluated by colony-forming unit assay. The expression of inflammatory cytokines (IL-6 and TNF-α) and an antimicrobial peptide (Lipocalin 2) in lipopolysaccharide-treated MSCs and HCECs was analyzed through ELISA. Corneal epithelial repair following infection with P. aeruginosa was studied through scratch assay. RESULTS: Compared to control (P. aeruginosa (5*105) incubated in DMEM (1 ml) at 37 °C for 16 h), MSC-CM significantly: i) inhibits the growth of P. aeruginosa (159*109 vs. 104*109 CFU/ml), ii) accelerates corneal epithelial repair following infection with P. aeruginosa (9% vs. 24% closure of the wounded area after 12 h of infection), and iii) downregulates the lipopolysaccharide-induced expression of IL-6, TNF-α and Lipocalin 2 in HCECs. A combination of MSC-CM with an antibiotic, Ciprofloxacin moderately regulated the expression of IL-6, TNF-α, and Lipocalin 2. CONCLUSION: MSC-CM holds promise as an adjunctive therapeutic approach for P. aeruginosa-induced corneal epithelial damage.
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Ensayo de Inmunoadsorción Enzimática , Infecciones Bacterianas del Ojo , Células Madre Mesenquimatosas , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/metabolismo , Infecciones Bacterianas del Ojo/patología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/terapia , Infecciones por Pseudomonas/tratamiento farmacológico , Células Madre Mesenquimatosas/metabolismo , Epitelio Corneal/microbiología , Epitelio Corneal/patología , Epitelio Corneal/metabolismo , Células Cultivadas , Queratitis/microbiología , Queratitis/metabolismo , Queratitis/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Medios de Cultivo Condicionados/farmacología , Prueba de Estudio Conceptual , Interleucina-6/metabolismo , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/metabolismo , Úlcera de la Córnea/patología , Úlcera de la Córnea/tratamiento farmacológico , Lipocalina 2/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
This retrospective study evaluated tear film (TF) interferometry on horses examined in Northern Italy in 2019-2021. The objectives were to evaluate horses affected by keratitis, and to describe TF values in horses with no evidence of ocular disease. All horses received a complete ophthalmic examination and were examined with the Ocular Surface Analyser, Veterinary-setting, prior to eye manipulation, staining and sample collection. Eighteen horses with no evidence of ocular disease were included in the comparison group. Additionally, 46 horses displaying signs of keratitis (neovascularization, corneal opacities, ulceration, epithelial and subepithelial infiltrates) were evaluated. These horses were divided into presumed non-infectious and infectious or presumed infectious keratitis groups (one with proven bacterial origin, and the others with diagnosed or presumptive keratomycosis) with the former including immune-mediated keratitis. From the observations of TF interferometry in the comparison population the authors concluded that for non-invasive break-up time (NIBUT), the estimated preliminary reference interval was 10.4-31.2s, and for tear meniscus height (TMH), it was 0.215-0.457mm. Moreover, within the keratitis population, from an interferometric point of view punctate lesions of the ocular surface were present in all cases of active diagnosed or presumptive subepithelial keratomycosis but not in any of the non-infectious cases, either non-ulcerative or ulcerative. Limitations of the study include a relatively low number of horses examined and the fact that the diagnosis of infectious keratitis was presumptive and based on clinical improvement after treatment in some cases. To the authors' knowledge, this is the first report of TF interferometry performed in horses.
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Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Enfermedades de los Caballos , Queratitis , Animales , Caballos , Estudios Retrospectivos , Enfermedades de los Caballos/tratamiento farmacológico , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/patología , Úlcera de la Córnea/veterinaria , Queratitis/patología , Queratitis/veterinaria , Infecciones Fúngicas del Ojo/epidemiología , Infecciones Fúngicas del Ojo/patología , Infecciones Fúngicas del Ojo/veterinariaRESUMEN
Exposure to mustard agents, such as sulfur mustard (SM) and nitrogen mustard (NM), often results in ocular surface damage. This can lead to the emergence of various corneal disorders that are collectively referred to as mustard gas keratopathy (MGK). In this study, we aimed to develop a mouse model of MGK by using ocular NM exposure, and describe the subsequent structural changes analyzed across the different layers of the cornea. A 3 µL solution of 0.25 mg/mL or 5 mg/mL NM was applied to the center of the cornea via a 2-mm filter paper for 5 min. Mice were evaluated prior to and after exposure on days 1, 3, 7, 14, and 28 for 4 weeks using slit lamp examination with fluorescein staining. Anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) tracked changes in the epithelium, stroma, and endothelium of the cornea. Histologic evaluation was used to examine corneal cross-sections collected at the completion of follow-up. Following exposure, mice experienced central corneal epithelial erosion and thinning, accompanied by a decreased number of nerve branches in the subbasal plexus and increased activated keratocytes in the stroma in both dosages. The epithelium was recovered by day 3 in the low dose group, followed by exacerbated punctuate erosions alongside persistent corneal edema that arose and continued onward to four weeks post-exposure. The high dose group showed persistent epitheliopathy throughout the study. The endothelial cell density was reduced, more prominent in the high dose group, early after NM exposure, which persisted until the end of follow-up, along with increased polymegethism and pleomorphism. Microstructural changes in the central cornea at 4 weeks post-exposure included dysmorphic basal epithelial cells and reduced epithelial thickness, and in the limbal cornea included decreased cellular layers. We present a mouse model of MGK using NM that successfully replicates ocular injury caused by SM in humans who have been exposed to mustard gas.
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Enfermedades de la Córnea , Edema Corneal , Úlcera de la Córnea , Gas Mostaza , Humanos , Animales , Ratones , Gas Mostaza/toxicidad , Mecloretamina/toxicidad , Córnea/patología , Enfermedades de la Córnea/inducido químicamente , Enfermedades de la Córnea/patología , Úlcera de la Córnea/patología , Trastornos de la Visión/patología , Microscopía ConfocalRESUMEN
This case series describes the use of in vivo confocal microscopy in the diagnosis and treatment of mycotic keratitis in two owls (one Bubo scandiacus, one Strix varia) and one woodcock (Scolopax minor). Each bird was at increased risk of fungal infection due to recent injury or stress. Ophthalmic findings in all birds included blepharospasm, ocular discharge, ulcerative keratitis, white or yellow corneal plaques, and anterior uveitis. Fungal hyphae were identified in corneal samples from all three eyes examined cytologically and in all three eyes by using in vivo confocal microscopy. Aspergillus fumigatus was isolated from a corneal culture in one bird. Despite medical treatment, progressive ocular disease prompted enucleation in two birds. Fungal hyphae were detected by histopathology in one of the two enucleated eyes. In vivo confocal microscopy aided the diagnosis of fungal keratitis in all birds and was the only diagnostic method that allowed immediate, real-time quantification of the extent (area and depth) and severity of mycotic keratitis.
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Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Queratitis , Animales , Úlcera de la Córnea/veterinaria , Úlcera de la Córnea/patología , Queratitis/diagnóstico , Queratitis/veterinaria , Queratitis/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/veterinaria , Infecciones Fúngicas del Ojo/microbiología , Córnea , Microscopía Confocal/veterinariaRESUMEN
OBJECTIVE: The aim of this study was to describe placement of a nictitating membrane flap as a treatment for corneal ulceration and bullous keratopathy in two horses. ANIMALS STUDIED: A 13-year-old American Saddlebred mare presented for severe corneal edema, superficial stromal ulceration, and a central bulla of the left eye. A 4-year-old Trakhener stallion also presented with a large axial bulla of the left eye with concurrent severe corneal edema and a deep stromal ulcer. PROCEDURE: A complete ophthalmic examination was performed. Samples were obtained for corneal cytology, and both horses were started on aggressive medical therapy. Both underwent general anesthesia for placement of a nictitating membrane flap and a subpalpebral lavage system (SPLS). RESULTS: Corneal cytology for each horse revealed a mixed bacterial population. Moderate Pseudomonas aeruginosa was cultured from the mare, while Aspergillus species and a few Enterococcus gallinarum were cultured from the stallion. The bullae in both horses resolved at 3 and 4 weeks and vision returned in the affected eye 4.5 and 3 months postoperatively at the last follow-up, respectively. CONCLUSION: Aggressive medical management with concurrent placement of a nictitating membrane flap is effective to treat bullous keratopathy in two horses. The described treatments could be used to treat horses that develop severe or progressive bullous corneal lesions.
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Edema Corneal , Úlcera de la Córnea , Caballos , Animales , Masculino , Femenino , Edema Corneal/veterinaria , Membrana Nictitante/patología , Vesícula/patología , Vesícula/veterinaria , Córnea/patología , Úlcera de la Córnea/cirugía , Úlcera de la Córnea/veterinaria , Úlcera de la Córnea/patologíaAsunto(s)
Úlcera de la Córnea , Infecciones Fúngicas del Ojo , Enfermedades de los Caballos , Caballos , Animales , Córnea , Técnicas Citológicas/veterinaria , Citodiagnóstico/veterinaria , Úlcera de la Córnea/patología , Úlcera de la Córnea/veterinaria , Infecciones Fúngicas del Ojo/patología , Infecciones Fúngicas del Ojo/veterinaria , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/patologíaRESUMEN
BACKGROUND: Knowledge on possible delaying effects of topical ciprofloxacin on corneal ulcer healing is scarce in avian patients. OBJECTIVES: The study evaluates effects of different dosage regimens of topical ciprofloxacin on healing of corneal ulcer in an avian model. METHODS: One hundred and fifty adult layers were randomly allocated into two equal categories each consisted of 5 groups (n = 15): 1, negative control (NC, normal cornea); 2, positive control (PC) (birds with experimental corneal ulcer); and 3, 4 and 5, birds with corneal injury that received ciprofloxacin 0.3% topically q6h, q8h and q12h, respectively for 3 (category 1) or 5 days (category 2). Corneas were excised for histopathological evaluation and determination of MMP-9 expression. RESULTS: While no significant difference was observed in daily-measured fluorescein-stained ulcer size among ciprofloxacin-treated birds and PC group in category 1, birds in PC group of category 2 had significantly smaller ulcers as compared to antibiotic-treated birds at the end of experiment (p < 0.01 for all cases). Histopathological evaluations at the end of the experiment showed no significant difference among PC and ciprofloxacin-treated birds of both categories for almost all of the assayed parameters. Over expression of MMP-9 mRNA was observed in PC group after 3 and 5 days of ulcer induction compared to NC groups. Its expression in ciprofloxacin-treated birds of both categories remained close to PC groups. CONCLUSIONS: While ciprofloxacin administration for 3 days does not affect ulcer healing, it delays healing process at the end of 5 days of treatments in an avian model of corneal ulcer injury. This delaying effect is not associated with a drastic change in MMP-9 expression.
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Úlcera de la Córnea , Animales , Úlcera de la Córnea/tratamiento farmacológico , Úlcera de la Córnea/veterinaria , Úlcera de la Córnea/patología , Ciprofloxacina/uso terapéutico , Ciprofloxacina/farmacología , Úlcera/veterinaria , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/farmacología , Córnea/patologíaRESUMEN
Mooren's ulcer (MU) is a chronic and painful ulcerative keratitis that is difficult to diagnose, especially when concealed beneath the pterygium, which is a common, benign, wedge-shaped, fleshy tissue growth of the conjunctiva extending onto the cornea. The coexistence of MU and pterygium is extremely rare. A 41-year-old man presented with a 2-month history of unprovoked redness, pain, and blurred vision in the right eye. Corneal epithelial defects around the pterygium head were noted upon slit-lamp examination and fluorescein staining. The patient was initially misdiagnosed with a corneal epithelial defect and pterygium. The initial treatments with anti-inflammatory and corneal epithelial growth promotion tear agents failed. Anterior segment optical coherence tomography (AS-OCT) showed corneal stromal lysis thinning, and in vivo confocal microscopy (IVCM) revealed marked inflammatory cell infiltration and stromal degeneration. We suspected the pathology was an immune-related or tumor-related corneal ulcer. The MU concealed beneath the pterygium was diagnosed by histopathological examination of a biopsy specimen that presented typical localized loss of the corneal epithelium and Bowman's layer, stromal degeneration, and inflammatory cell infiltration. Finally, we performed lamellar keratoplasty (LKP) combined with pterygium excision surgery. The patient recovered with no complications or recurrence during the 1-year follow-up period. Few cases of MU concealed beneath the pterygium have been reported. It is beneficial to rule out the pathological changes concealed beneath the pterygium, combined with multiple means of examination such as slit-lamp examination, AS-OCT, and IVCM. A histopathological examination should be performed to establish a diagnosis.
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Úlcera de la Córnea , Pterigion , Masculino , Humanos , Adulto , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/patología , Úlcera de la Córnea/cirugía , Pterigion/diagnóstico , Pterigion/patología , Úlcera/diagnóstico , Úlcera/patología , Conjuntiva/patología , Conjuntiva/cirugíaRESUMEN
PURPOSE: The purpose of this study was to evaluate the incidence and epidemiology of recurrent corneal erosion within a clinical population using standard diagnostic techniques and a new technique called the corneal sweep test (CST). METHODS: A retrospective chart review was conducted on 58 eyes of 51 patients with the diagnosis of recurrent corneal erosion from July 2018 to June 2020. All underwent a thorough history and physical examination. The CST was performed as a confirmatory test and on any patient who lacked visible corneal pathology. RESULTS: The CST was necessary on 49 of the 58 eyes to help confirm the diagnosis of a corneal erosion. Among them, 34 had an occult corneal erosion, which is defined as having a normal-appearing cornea on slitlamp examination but found to have loose corneal epithelium with the CST. Clear corneal cataract surgery (28 eyes, 48.2%) was the most common presumed mechanism of injury, with 20 (71.4%) developing symptoms only after cataract surgery. All 20 eyes had an erosion located directly over a clear corneal cataract incision. CONCLUSIONS: The CST is a new and effective technique to help diagnose corneal erosions in the absence of visible corneal findings. Clear corneal cataract surgery is an under-recognized but important risk factor to consider because the incision can be the source for an erosion. Using the CST could lead to a paradigm shift in the way clinicians approach RCEs and patients with a persistent ocular pain syndrome.
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Catarata , Distrofias Hereditarias de la Córnea , Edema Corneal , Úlcera de la Córnea , Epitelio Corneal , Catarata/complicaciones , Córnea/patología , Distrofias Hereditarias de la Córnea/diagnóstico , Edema Corneal/patología , Úlcera de la Córnea/patología , Epitelio Corneal/patología , Humanos , Estudios RetrospectivosRESUMEN
OBJECTIVES: To assess the inter-rater agreement of corneal cytology findings in canine ulcerative keratitis by veterinary surgeons of different training levels and the agreement of corneal cytology with culture. MATERIALS AND METHODS: Dogs with progressive ulcerative keratitis were prospectively recruited for corneal cytology and culture. Corneal cytology slides were reviewed by veterinary surgeons of different training levels (three general practitioners, three ophthalmologists and three pathologists). The inter-rater agreement of cytology findings and agreement of cytology with culture was assessed using the kappa measure of agreement. RESULTS: The study included 145 corneal cytology samples from 143 dogs (145 eyes) with progressive ulcerative keratitis. Positive cultures were obtained from 81 of 145 (56%) eyes. The most commonly isolated pathogens were Streptococcus canis, Pseudomonas aeruginosa and Staphylococcus pseudintermedius. The results demonstrated increased inter-rater agreement of corneal cytology and increased agreement with culture with increased ocular pathology expertise (pathologists > ophthalmologists > general practitioners). CLINICAL SIGNIFICANCE: This study provides important information about the diagnostic value of corneal cytology in canine ulcerative keratitis and the most common pathogens involved in such cases in the UK. Based on the results of this study, cytology findings should be interpreted in conjunction with the expertise of the observer. For maximal pathogen identification, both cytology and culture should be considered.
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Úlcera de la Córnea , Enfermedades de los Perros , Animales , Córnea/patología , Úlcera de la Córnea/diagnóstico , Úlcera de la Córnea/patología , Úlcera de la Córnea/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , PerrosRESUMEN
PURPOSE: To describe the corneal calcification of acellular porcine corneal stroma (APCS) following lamellar keratoplasty (LKP) and identify risk factors. METHODS: Two cases of APCS calcification were evaluated by slit-lamp photography and anterior segment optical coherence tomography (AS-OCT). von Kossa staining and scanning electron microscope/energy-dispersive spectrometry (SEM/EDS) were performed on pathologic tissue. Associated graft and postoperative risk factors were analysed. Acellular porcine corneal stroma (APCS) cleanliness and element content after rinsing with sterilized water were observed by SEM/EDS and inductively coupled plasma mass spectrometry. Calcium metabolism-related proteins were analysed by protein mass spectrometry. Corneal epithelial defects and postoperative medications were reviewed. RESULTS: Two cases of APCS calcification occurred at 23 and 22 days postoperatively. Anterior segment optical coherence tomography (AS-OCT) and von Kossa staining demonstrated calcium deposition in the superficial stroma composed of calcium, phosphorus and oxygen conforming to the Ca/P ratio of hydroxyapatite. Phosphate crystals were present on the APCS surface and decreased with number of rinsing times. The phosphorus content of APCS was minimal after rinsing 10 times and avoiding excessive corneal swelling. Calcium metabolism-related proteins were downregulated in APCS. Patients with corneal calcification had 1-week postoperative corneal epithelial defects and were treated with three types of phosphorous eyedrops. CONCLUSIONS: Acellular porcine corneal stroma (APCS) calcification occurs in the superficial corneal stroma about 1 month after LKP. The application of AS-OCT, von Kossa staining and SEM/EDS provides a basis for the clinical and pathological diagnosis of corneal calcification. The associated risk factors were mainly high phosphorus content and downregulated calcium metabolism-related proteins in APCS. Postoperative epithelial defects, inflammation and use of phosphorous eyedrops may promote corneal calcification.
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Calcinosis/metabolismo , Sustancia Propia/trasplante , Trasplante de Córnea/métodos , Úlcera de la Córnea/cirugía , Anciano , Animales , Úlcera de la Córnea/patología , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Porcinos , Tomografía de Coherencia Óptica , Trasplante HeterólogoRESUMEN
BACKGROUND: Cornea is a composite tissue exhibiting nonlinear and time-dependent mechanical properties. Corneal ulcers are one of the main pathologies that affect this tissue, disrupting its structural integrity and leading to impaired functions. In this study, uniaxial tensile and stress-relaxation tests are developed to evaluate stress-strain and time-dependent mechanical behaviour of porcine corneas. RESULTS: The samples are split in two groups: some corneas are analysed in an unaltered state (healthy samples), while others are injured with alkaline solution to create an experimental ulcer (lesioned samples). Furthermore, within each group, corneas are examined in two conditions: few hours after the enucleation (fresh samples) or after 7 days in a specific culture medium for the tissue (cultured samples). Finally, another condition is added: corneas from all the groups undergo or not a cross-linking treatment. In both stress-strain and stress-relaxation tests, a weakening of the tissue is observed due to the imposed conditions (lesion, culture and treatment), represented by a lower stiffness and increased stress-relaxation. CONCLUSIONS: Alkali-induced corneal stromal melting determines changes in the mechanical response that can be related to a damage at microstructural level. The results of the present study represent the basis for the investigation of traditional and innovative corneal therapies.
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Córnea/efectos de los fármacos , Córnea/fisiología , Úlcera de la Córnea/veterinaria , Técnicas de Cultivo de Órganos/veterinaria , Enfermedades de los Porcinos/patología , Animales , Úlcera de la Córnea/inducido químicamente , Úlcera de la Córnea/patología , Porcinos , Enfermedades de los Porcinos/inducido químicamenteRESUMEN
Parry-Romberg´s syndrome is a rare clinical entity characterized by progressive hemifacial atrophy associated with several systemic manifestations including ophthalmologic, neurologic, maxillofacial symptoms whose treatment should be multidisciplinary. We here report a case of Parry-Romberg´s syndrome diagnosed in a patient referred for management of chronic corneal ulcer following hypoesthesia, characterized by rare and difficult-to-treat features.
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Úlcera de la Córnea/etiología , Hemiatrofia Facial/diagnóstico , Adulto , Enfermedad Crónica , Úlcera de la Córnea/patología , Hemiatrofia Facial/complicaciones , Humanos , MasculinoRESUMEN
Fungal keratitis (FK) pathology is driven by both fungal growth and inflammation within the corneal stroma. Standard in vitro infection models ̶ involving co-culture of the pathogen and the corneal cells in tissue culture medium ̶ are sufficient to probe host responses to the fungus; however, they lack the physiological structure and nutrient composition of the stroma to accurately study fungal invasiveness and metabolic processes. We therefore sought to develop a culture model of FK that would allow for both host and fungal cell biology to be evaluated in parallel. Towards this end, we employed a previously described system in which primary human cornea fibroblasts (HCFs) are cultured on transwell membranes, whereupon they secrete a three-dimensional (3D) collagen matrix that resembles the human stroma. We demonstrated that two common mold agents of FK, Fusarium petroliphilum and Aspergillus fumigatus, penetrated into these constructs and caused a disruption of the collagen matrix that is characteristic of infection. HCF morphology appeared altered in the presence of fungus and electron microscopy revealed a clear internalization of fungal spores into these cells. Consistent with this apparent phagocyte-like activity of the HCFs, mRNA and protein levels for several pro-inflammatory cytokines/chemokines (including TNFα, IL-1ß, IL-6, and IL-8) were significantly upregulated compared to uninfected samples. We similarly found an upregulation of several HCF metalloproteases (MMPs), which are enzymes that breakdown collagen during wound healing and may further activate pro-inflammatory signaling molecules. Finally, several fungal collagenase genes were upregulated during growth in the constructs relative to growth in tissue culture media alone, suggesting a fungal metabolic shift towards protein catabolism. Taken together, our results indicate that this 3D-stromal model provides a physiologically relevant system to study host and fungal cell pathobiology during FK.
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Aspergilosis/microbiología , Queratocitos de la Córnea/microbiología , Úlcera de la Córnea/microbiología , Infecciones Fúngicas del Ojo/microbiología , Fusariosis/microbiología , Interacciones Huésped-Patógeno/fisiología , Animales , Aspergilosis/metabolismo , Aspergilosis/patología , Aspergillus fumigatus/fisiología , Técnicas de Cultivo de Célula , Queratocitos de la Córnea/metabolismo , Sustancia Propia/metabolismo , Sustancia Propia/microbiología , Sustancia Propia/ultraestructura , Úlcera de la Córnea/metabolismo , Úlcera de la Córnea/patología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Infecciones Fúngicas del Ojo/metabolismo , Infecciones Fúngicas del Ojo/patología , Fusariosis/metabolismo , Fusariosis/patología , Fusarium/fisiología , Humanos , Masculino , Metaloproteinasas de la Matriz/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Electrónica de Transmisión , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Streptococcus pneumoniae endophthalmitis is clinically more severe, more difficult to treat, and carry a higher risk of vision loss, evisceration, or enucleation. This study is to investigate the clinical settings, antibiotic susceptibility, and visual outcomes of S. pneumoniae endophthalmitis at a tertiary referral center in Taiwan. S. pneumoniae endophthalmitis was diagnosed in 38 eyes of 38 patients. The main clinical features were postcataract endophthalmitis (n = 13, 34%) and endophthalmitis associated with corneal ulcer (n = 12, 32%), trauma (n = 6, 16%), endogenous etiology (n = 4, 11%), trabeculectomy (n = 2, 5%), and pterygium excision-related scleral ulcer (n = 1, 3%). Presenting visual acuity ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics was performed in 17 eyes (39%) in primary or secondary treatments. S. pneumoniae isolates were susceptible to vancomycin (38/38, 100%), penicillin (37/38, 97%), ceftriaxone (37/38, 97%), cefuroxime (12/15, 80%), levofloxacin (13/15 ,87%), and moxifloxacin (15/17, 88%). Final visual acuity was better than 20/400 in 3 of 38 eyes (8%), 5/200 to hand motions in 3 eyes (8%), and light perception to no light perception in 32 eyes (84%). Ten eyes (26%) underwent evisceration or enucleation. Although S. pneumoniae isolates were susceptible to vancomycin, S. pneumoniae endophthalmitis had a very poor visual prognosis.
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Antibacterianos/uso terapéutico , Endoftalmitis/patología , Infecciones Neumocócicas/patología , Streptococcus pneumoniae/patogenicidad , Vitrectomía/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Catarata/complicaciones , Catarata/microbiología , Catarata/patología , Extracción de Catarata/efectos adversos , Ceftriaxona/uso terapéutico , Cefuroxima/uso terapéutico , Úlcera de la Córnea/complicaciones , Úlcera de la Córnea/microbiología , Úlcera de la Córnea/patología , Endoftalmitis/etiología , Endoftalmitis/microbiología , Enucleación del Ojo/métodos , Enucleación del Ojo/estadística & datos numéricos , Lesiones Oculares/complicaciones , Lesiones Oculares/microbiología , Lesiones Oculares/patología , Femenino , Humanos , Levofloxacino/uso terapéutico , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Moxifloxacino/uso terapéutico , Penicilinas/uso terapéutico , Infecciones Neumocócicas/etiología , Infecciones Neumocócicas/microbiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/crecimiento & desarrollo , Taiwán , Centros de Atención Terciaria , Trabeculectomía/efectos adversos , Resultado del Tratamiento , Vancomicina/uso terapéutico , Vitrectomía/métodosRESUMEN
A 34year-old man presented with diminution of vision, pain and whitish opacity in both eyes (right eye followed by left eye) since 1 week. He is a known case of chronic alcoholic abuse. He had multiple episodes of haemoptysis in the past. On general physical examination, he was severely malnourished with multiple oral ulcers. Visual acuity at presentation was light perception in both eyes with projection of rays accurate in all quadrants. Slit-lamp biomicroscopy revealed bilateral total corneal melt with diffuse conjunctival congestion. Corneal scrapings and blood investigations were done and he was started on empirical topical and systemic therapy followed by surgical intervention, with large corneal grafts in both the eyes (right eye followed by left eye) with 1 day interval. The visual gain in both the eyes were 20/400 at first postoperative day. The right eye developed severe fibrinous reaction on the second postoperative day which resolved with topical antibiotics, topical steroids and systemic steroids. The patient was followed up via telemedicine (due to COVID-19 outbreak) and he is able to carry out his daily routine work independently.
Asunto(s)
Alcoholismo/complicaciones , Úlcera de la Córnea/etiología , Desnutrición Proteico-Calórica/complicaciones , Deficiencia de Vitamina A/complicaciones , Adulto , Antibacterianos/uso terapéutico , Avitaminosis/diagnóstico , Avitaminosis/tratamiento farmacológico , Trasplante de Córnea , Úlcera de la Córnea/patología , Úlcera de la Córnea/terapia , Intervención Médica Temprana , Humanos , Masculino , Necrosis , Microscopía con Lámpara de Hendidura , Vitamina A/uso terapéutico , Deficiencia de Vitamina A/diagnóstico , Deficiencia de Vitamina A/tratamiento farmacológico , Vitaminas/uso terapéuticoRESUMEN
Forkhead box C1 (FOXC1) is required for neural crest and ocular development, and mutations in FOXC1 lead to inherited Axenfeld-Rieger syndrome. Here, we find that FOXC1 and paired box 6 (PAX6) are co-expressed in the human limbus and central corneal epithelium. Deficiency of FOXC1 and alternation in epithelial features occur in patients with corneal ulcers. FOXC1 governs the fate of the corneal epithelium by directly binding to lineage-specific open promoters or enhancers marked by H3K4me2. FOXC1 depletion not only activates the keratinization pathway and reprograms corneal epithelial cells into skin-like epithelial cells, but also disrupts the collagen metabolic process and interferon signaling pathways. Loss of interferon regulatory factor 1 and PAX6 induced by FOXC1 dysfunction is linked to the corneal ulcer. Collectively, our results reveal a FOXC1-mediated regulatory network responsible for corneal epithelial homeostasis and provide a potential therapeutic target for corneal ulcer.
Asunto(s)
Úlcera de la Córnea/metabolismo , Células Epiteliales/metabolismo , Epitelio Corneal/metabolismo , Factores de Transcripción Forkhead/deficiencia , Células Cultivadas , Úlcera de la Córnea/genética , Úlcera de la Córnea/patología , Células Epiteliales/patología , Epitelio Corneal/patología , Factores de Transcripción Forkhead/metabolismo , Humanos , Factor de Transcripción PAX6/genética , Factor de Transcripción PAX6/metabolismoRESUMEN
The purpose of this study was to explore the potential of formulating hesperetin into an ophthalmic solution with dipotassium glycyrrhizinate (DG) as a micelle nanocarrier. A DG-based micelle ophthalmic solution encapsulating hesperetin (DG-Hes) was developed and its in vitro/in vivo characterizations were evaluated. The optimal formulation featured a DG/hesperetin (Hes) weight ratio of 12:1 and an encapsulation efficiency of 90.4 ± 1.7%; The optimized DG-Hes was characterized as small uniform spheres with an average micelle size of 70.93 ± 3.41 nm, a polydispersity index of 0.11 ± 0.02, and an electrically negative surface (-36.12 ± 2.79 mV). The DG-Hes ophthalmic solution had good tolerance in rabbit eyes. DG-Hes significantly improved the in vitro passive permeation, ex vivo corneal permeation, and in vivo ocular bioavailability of Hes. DG-Hes showed markedly increases in in vitro antioxidant activity. In vitro antibacterial activity tests revealed a lower minimum inhibitory concentration and lower minimum bactericidal concentration for DG-Hes ophthalmic solution were lower than for free Hes. DG-Hes ophthalmic solution also significantly reduced symptoms of eye infection in the rabbit bacterial keratitis model when compared to a Hes suspension. These results suggest that DG-Hes eye drops may be useful as a new ophthalmic preparation for the treatment of ocular diseases, especially bacterial ophthalmopathy.