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PURPOSE: To determine the correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis (OTB). METHODS: Vitreous fluid was analysed for cytokines in patients with OTB and non-OTB uveitis using multiplex fluorescent bead-based flow cytometric assay. The clinical phenotypes were recorded and correlated with vitreous biomarkers. RESULTS: Vitreous humour from OTB patients had elevated levels of interleukin-10 (IL-10), IL-17-A, interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α). Angiopoietin (Ang-2) levels were higher in the panuveitis phenotype. OTB posterior uveitis phenotype had relatively higher vascular endothelial growth factor (VEGF) levels and lower fibroblast growth factor (FGF) levels. Additionally, eyes with choroiditis and vasculitis had elevated levels of VEGF and Ang-2 with FGF downregulation. Both IFN-γ and IL-10 were upregulated in the choroiditis phenotype of OTB. CONCLUSION: Angiogenic growth factors and inflammatory cytokines were altered in the vitreous humour of OTB patients. IFN-γ, VEGF, and IL-10 levels are increased in choroiditis and vasculitis phenotypes. Receiver operating characteristic (ROC) curve analysis further emphasized the importance of the IFN-γ assay in the diagnosis of OTB.
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Coroiditis , Tuberculosis Ocular , Humanos , Citocinas/metabolismo , Interleucina-10 , Factor A de Crecimiento Endotelial Vascular , Tuberculosis Ocular/diagnóstico , Péptidos y Proteínas de Señalización Intercelular , Interferón gamma , FenotipoRESUMEN
PURPOSE: Posterior capsular opacification (PCO) accounts for the most significant and most challenging complication after successful cataract surgery in children. Our study aimed to investigate the levels of cytokines in the aqueous humor of children afflicted with congenital cataracts and their association with PCO. METHODS: This was an observational study conducted at a tertiary referral center in India. Consecutive children aged less than 5 years with unilateral/bilateral isolated idiopathic congenital cataracts and planned for cataract extraction with intraocular lens implantation were included. During cataract surgery, 100-500 µl of aqueous samples were collected and the levels of inflammatory cytokines were quantified in the aqueous humor. RESULTS: An analysis of 28 samples was done. The mean age of the patients was 16.7 ± 0.4 months (range 3-60 months) with a mean follow-up 14.2 ± 2.3 months. On binary logistic regression, the level of MCP-1 was significantly related to the development of PCO at 1 year (P = 0.0072). Levels of IL-6 and IL-8 were not associated with the development of PCO (P = 0.05 and P = 0.07, respectively). CONCLUSION: Inflammatory markers like IL-6 and IL-8 were raised in children with pediatric cataracts in our study. Chronic high levels of MCP-1-induced fibrosis may be associated with PCO.
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Knee osteoarthritis (OA) is the most documented form of OA and is accountable for about 80% of total OA cases worldwide [...].
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OBJECTIVE: To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). METHODS: This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups. RESULTS: Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. CONCLUSIONS: Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.
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Glaucoma , Humanos , Lactante , Recién Nacido , Citocromo P-450 CYP1B1/genética , Análisis Mutacional de ADN , Frecuencia de los Genes , Glaucoma/genética , Glaucoma/congénito , Mutación , Linaje , Estudios ProspectivosRESUMEN
Purpose: To evaluate the cytokine levels in tear samples of human leukocyte antigen B27 (HLA-B27)-associated uveitis.Methods: Twenty HLA-B27-associated uveitis patients and 10 non-HLA-B27 uveitis controls were enrolled for the estimation of interleukin-6 (IL-6) and IL-10 levels in the tear samples. The cytokine levels were determined by flow cytometry using a bead-based assay.Results: IL-6, and IL-10 levels and IL-6/IL-10 ratio were found to be higher in the tear samples of HLA-B27-associated uveitis patients as compared to controls. IL-6 levels were also elevated in the active disease as compared to the quiescent group; likewise, IL-6 levels were higher even in the quiescent phase in comparison to non-HLA-B27 disease control. Additionally, levels of IL-6 were significantly correlated with multiple disease episodes. Moreover, IL-6 showed a good area under the curve in receiver operating characteristic analysis.Conclusions: Elevated tear IL-6 levels were associated with active disease and multiple disease episodes and thus could be used as putative markers for disease episodes.
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Antígeno HLA-B27/inmunología , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lágrimas/metabolismo , Uveítis/inmunología , Enfermedad Aguda , Adulto , Biomarcadores/metabolismo , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Uveítis/metabolismo , Adulto JovenRESUMEN
Purpose: To evaluate the role of angiogenic growth factors in the pathogenesis of intraocular tuberculosis.Methods: Retinal Pigment Epithelium (RPE) cells were infected with varying dilution of Mycobacterium tuberculosis (MTB), ranging from several thousand to a few MTB bacilli to replicate paucibacillary conditions. Angiogenesis growth factors were evaluated using multiplex fluorescent bead based flow cytometry in the culture supernatant of RPE cells infected with MTB, vitreous fluids and tear samples of uveitis patients visiting retina clinic.Results: Vascular endothelial growth factor (VEGF) levels were elevated and fibroblast growth factors (FGFs) were down regulated in RPE-infected MTB cells. Similar pattern of VEGF and FGF was observed in the vitreous of IOTB patients. However, no changes were observed in tear samples.Conclusions: MTB exploits the angiogenesis growth factors for pathogenesis by decreasing FGF with concomitant surge of VEGF in MTB infected RPE as well in the vitreous of IOTB patients.
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Factores de Crecimiento de Fibroblastos/metabolismo , Mycobacterium tuberculosis/fisiología , Enfermedades de la Retina/metabolismo , Tuberculosis Ocular/metabolismo , Uveítis/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Anciano , Células Cultivadas , Niño , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades de la Retina/microbiología , Epitelio Pigmentado de la Retina/microbiología , Lágrimas/metabolismo , Tuberculosis Ocular/microbiología , Uveítis/microbiología , Cuerpo Vítreo/metabolismoRESUMEN
Background: Rapid and timely diagnosis of tubercular uveitis (TBU) is of paramount importance to save these eyes from blindness. The present study was, therefore, undertaken to carry out a comparative evaluation of Gene Xpert MTB/RIF (Xpert), MTBDRplus and Multiplex PCR (MPCR) for the diagnosis of TBU. These tests were performed on vitreous fluid of 110 patients with presumed TBU and 90 controls. rpoB gene sequencing confirmed Rifampicin resistance.Results: Xpert, MTBDRplus and MPCR were positive in 19(17.2%),38 (34.5%) and 79 (71.8 %) patients, respectively. All tests were negative in all controls. Rif resistance was detected in 3 by Xpert and 7 by MTBDRplus. MPCR followed by rpoB gene sequencing detected Rif resistance in 6 cases. One case of false Rif resistance was reported each by MTBDRplus and Xpert.Conclusion: MPCR followed by rpoB sequencing is a robust technique for the diagnosis of paucibacilliary condition like TBU and reliable detection of drug resistance.
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Infecciones Bacterianas del Ojo/diagnóstico , Rifampin/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/diagnóstico , Uveítis/diagnóstico , Adolescente , Adulto , Antibióticos Antituberculosos/farmacología , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , ADN Bacteriano/análisis , ARN Polimerasas Dirigidas por ADN/análisis , ARN Polimerasas Dirigidas por ADN/genética , Infecciones Bacterianas del Ojo/tratamiento farmacológico , Infecciones Bacterianas del Ojo/epidemiología , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/genética , Prevalencia , Estudios Retrospectivos , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Uveítis/tratamiento farmacológico , Uveítis/epidemiología , Adulto JovenRESUMEN
Purpose: To describe the distinguishing features of retinitis-like lesions seen in vitreoretinal lymphoma (VRL) from viral and toxoplasma retinitis.Methods: In this multicenter, retrospective study, we reviewed charts and imaging of consecutive patients with VRL. The associated features and the characteristics of retinitis-like lesions were assessed and compared with those of viral and toxoplasmic retinochoroiditis. Primary outcome measures were the unique features of VRL retinitis-like lesions.Results: Out of 76 eyes of 38 patients with VRL, retinitis-like lesions were identified in 6 eyes and confirmed on OCT. Distinctive features of VRL retinitis-like lesions were massive retinal thickening, associated sub-retinal pigment epithelium infiltrates and partial restoration of retinal layers after specific therapy.Conclusion: VRL can present with retinitis-like lesions that have distinctive OCT features on presentation as well as healing that can help to differentiate them from other lookalike etiologies and can guide further diagnostic and therapeutic interventions.
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Linfoma Intraocular/diagnóstico , Neoplasias de la Retina/diagnóstico , Retinitis/diagnóstico , Cuerpo Vítreo/patología , Anciano , Anciano de 80 o más Años , Infecciones Parasitarias del Ojo/diagnóstico , Infecciones Parasitarias del Ojo/parasitología , Infecciones Virales del Ojo/diagnóstico , Infecciones Virales del Ojo/virología , Femenino , Humanos , Linfoma Intraocular/parasitología , Linfoma Intraocular/virología , Masculino , Persona de Mediana Edad , Neoplasias de la Retina/parasitología , Neoplasias de la Retina/virología , Retinitis/parasitología , Retinitis/virología , Estudios Retrospectivos , Tomografía de Coherencia ÓpticaRESUMEN
Fungal endogenous endophthalmitis (EE) secondary to contaminated intravenous fluid infusion is frequently seen in developing countries. Molds and yeasts are commonly implicated as the causative agents. Dematiaceous fungi such as Lecythophora have been linked to exogenous endophthalmitis but have never been reported to cause EE. We report a case of Lecythophora EE that was successfully managed with pars plana vitrectomy along with intravitreal and systemic voriconazole. Endogenous endophthalmitis (EE) is a potentially devastating intraocular infection caused by intraocular spread of pathogens through blood stream. It generally accounts for 2%-16% of all reported endophthalmitis cases.[1] Predisposing risk factors include diabetes mellitus, malignancies, intravenous drug use, organ abscess, immunosuppressive therapy, indwelling catheters, urinary tract infection, organ transplant, end-stage renal or liver disease, and endocarditis.[2] It may occur in patients with no overt signs of systemic infection, particularly in the setting of contaminated intravenous fluid infusion in a rural setting.[3] Among the three broad categories of pathogens responsible for EE-bacteria, yeast, and molds, cases caused by molds are most infrequent and have the worst outcomes.[4] While Candida and Aspergillus are the most common species among fungal causes of EE, Lecythophora has been rarely reported as a cause of endophthalmitis due to exogenous causes.[5],[6],[7],[8] We, herein, report a case of EE caused by Lecythophora species.
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Endoftalmitis/diagnóstico , Infecciones Fúngicas del Ojo/diagnóstico , Cuerpo Vítreo/microbiología , Voriconazol/administración & dosificación , Adulto , Antifúngicos/administración & dosificación , Endoftalmitis/tratamiento farmacológico , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Humanos , Inyecciones Intravítreas , MasculinoRESUMEN
Atypical facial pain can be dreadful for the patient, and treating it can be an arduous task for the clinician, unless the diagnosis is constantly revisited.
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BACKGROUND/AIMS: To describe in vivo confocal microscopy (IVCM) features of microsporidial keratoconjunctivitis in immunocompetent adult patients. METHODS: Patients suspected clinically to be suffering from microsporidial keratoconjunctivitis (ie, presence of unilateral follicular and/or papillary conjunctivitis in conjunction with multifocal, coarse corneal epitheliopathy) were subjected to IVCM with the Rostock Cornea Module of the Heidelberg Retinal Tomograph 3, and combined potassium hydroxide and calcofluor white (KOH+CFW) staining of the corneal scrapings, to detect the microsporidial spores. Detection of spores in corneal scrapings was considered as being confirmatory for microsporidial infection. RESULTS: Of a total of 10 patients screened, 8 patients (7 male, 1 female) demonstrated the presence of oval, non-budding microsporidial spores which fluoresced bluish white on combined KOH+CFW staining. IVCM in seven of these eight patients demonstrated multiple rosette-like clusters/plaque of epithelial cells, within which hyper-reflective, pinpoint oval intracellular bodies (similar to the spores seen on microbiological staining) were present. One patient who had been on prolonged treatment with topical steroids showed the presence of the oval bright bodies scattered diffusely within the epithelial cells, without rosette formation. CONCLUSIONS: In microsporidial keratoconjunctivitis, IVCM is able to detect presence of bright, ovoid spore-like structures in the epithelial layers. Epithelial rosette formation is another characteristic feature seen in a majority of these patients. These features may be used as a reliable screening tool for starting therapy, precluding the need for corneal scrapings in a majority of patients.
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Infecciones Fúngicas del Ojo/diagnóstico por imagen , Inmunocompetencia , Queratoconjuntivitis/diagnóstico por imagen , Microscopía Confocal , Microsporidiosis/diagnóstico por imagen , Adolescente , Adulto , Antibacterianos/uso terapéutico , Antifúngicos/uso terapéutico , Quimioterapia Combinada , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Femenino , Fluoroquinolonas/uso terapéutico , Humanos , Queratoconjuntivitis/tratamiento farmacológico , Queratoconjuntivitis/microbiología , Masculino , Microsporidios/aislamiento & purificación , Microsporidiosis/tratamiento farmacológico , Microsporidiosis/microbiología , Moxifloxacino , Factores de Riesgo , Voriconazol/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND: We report unfavorable outcome in a patient with subretinal granuloma caused by dual infection of Mycobacterium tuberculosis complex with Mycobacterium fortuitum and Mycobacterium bovis in an immunosuppressed, non-HIV patient. We did a systematic review of literature on dual infection due to M. tuberculosis and M. fortuitum via MEDLINE and PUBMED and could not find any case reported of causing this kind of dual infection in the eye. RESULTS: A 38-year-old Indian male patient presented with decreased vision in the left eye for 3 months, diagnosed as tubercular choroidal granuloma with associated retinal angiomatosis proliferans (RAP) lesion. He also had multiple enlarged lymph nodes in the chest, and sternal pus sample was positive for acid-fast bacilli (AFB). M. tuberculosis complex was detected by gene expert. The patient was started on antitubercular treatment (ATT) whereby the lung lesions improved but the ocular lesion showed initial clinical improvement followed by worsening. Twenty-five-gauge diagnostic pars plana core vitreous surgery was done whereby sample demonstrated a large number of AFB on Ziehl-Neelsen stain and auramine-rhodamine stain. The vitreous sample showed growth on routinely inoculated mycobacteria growth indicator tube (MGIT) 960 tubes, and multiplex polymerase chain reaction (PCR), Gene Xpert MTB/ RIF assay (Cepheid, Sunnyvale, CA), and line probe assay (LPA) were positive for ocular tuberculosis. In view of nonresponse to conventional ATT, a suspicion of dual infection of M. tuberculosis complex with a nontubercular mycobacteria was kept and a subculture was made onto the solid Lowenstein-Jensen (LJ) medium from the positive MGIT 960 tubes. Two morphologically distinct types of colonies were obtained on LJ slopes. Subsequently, the two etiological agents were identified as M. fortuitum and M. bovis by PCR from the vitreous sample. CONCLUSIONS: Co-infection of M. tuberculosis complex with nontubercular mycobacterium (NTM) has never been reported from ocular tuberculosis before. In immunosuppressed individuals, who test positive for MTB, not responding to the standard ATT, one needs to have a high index of clinical suspicion to rule out associated NTM infection and initiate appropriate multidrug systemic antibiotic therapy early.