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Background: Microbial keratitis is one of the leading causes of blindness globally. An overactive immune response during an infection can exacerbate damage, causing corneal opacities and vision loss. This study aimed to identify the differentially expressed genes between corneal infection patients and healthy volunteers within the cornea and conjunctiva and elucidate the contributing pathways to these conditions' pathogenesis. Moreover, it compared the corneal and conjunctival transcriptomes in corneal-infected patients to cytokine levels in tears. Methods: Corneal and conjunctival swabs were collected from seven corneal infection patients and three healthy controls under topical anesthesia. RNA from seven corneal infection patients and three healthy volunteers were analyzed by RNA sequencing (RNA-Seq). Tear proteins were extracted from Schirmer strips via acetone precipitation from 38 cases of corneal infection and 14 healthy controls. The cytokines and chemokines IL-1ß, IL-6, CXCL8 (IL-8), CX3CL1, IL-10, IL-12 (p70), IL-17A, and IL-23 were measured using an antibody bead assay. Results: A total of 512 genes were found to be differentially expressed in infected corneas compared to healthy corneas, with 508 being upregulated and four downregulated (fold-change (FC) <-2 or > 2 and adjusted p <0.01). For the conjunctiva, 477 were upregulated, and 3 were downregulated (FC <-3 or ≥ 3 and adjusted p <0.01). There was a significant overlap in cornea and conjunctiva gene expression in patients with corneal infections. The genes were predominantly associated with immune response, regulation of angiogenesis, and apoptotic signaling pathways. The most highly upregulated gene was CXCL8 (which codes for IL-8 protein). In patients with corneal infections, the concentration of IL-8 protein in tears was relatively higher in patients compared to healthy controls but did not show statistical significance. Conclusions: During corneal infection, many genes were upregulated, with most of them being associated with immune response, regulation of angiogenesis, and apoptotic signaling. The findings may facilitate the development of treatments for corneal infections that can dampen specific aspects of the immune response to reduce scarring and preserve sight.
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Conjuntiva , Córnea , Citocinas , Queratitis , Lágrimas , Transcriptoma , Humanos , Lágrimas/metabolismo , Citocinas/metabolismo , Citocinas/genética , Córnea/metabolismo , Córnea/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Conjuntiva/metabolismo , Conjuntiva/inmunología , Queratitis/genética , Queratitis/inmunología , Queratitis/metabolismo , Anciano , Perfilación de la Expresión GénicaRESUMEN
CLINICAL RELEVANCE: The behaviour of human telomerase reverse transcriptase (hTERT) in tears reflects its role in maintaining the ocular surface homoeostasis, as it is increased after the initial fitting of contact lenses and post-overnight lid closure. BACKGROUND: hTERT has been shown to respond to cellular stress in neurodegenerative diseases and to enhance axonal regeneration after peripheral axotomy in an animal model. This work investigated whether the behaviour of hTERT in the tear film reflects ocular surface inflammation and neuronal changes in the presence of dry eye disease. METHODS: Flush tears were collected from 18 participants with dry eye disease (14 females, 4 males, mean age 34.7 ± 5.2 years) and from 18 healthy participants without dry eye disease (8 females, 10 males, mean age 31.9 ± 5.8 years). Dry eye disease status was defined using the TFOS DEWS II diagnostic criteria. hTERT levels in tears were measured using enzyme-linked immunosorbent assays. Confocal images were taken at the level of the subbasal nerve plexus at the central cornea and at the inferior whorl, and the densities of corneal immune cells were evaluated as well as corneal nerve morphology metrics using a fully automated technique (University of Manchester, United Kingdom). RESULTS: In participants with dry eye disease, hTERT levels were significantly higher compared to controls (median [interquartile range]: 434 [320-600] ng/ml, and 184 [42-390] ng/ml, respectively, p = 0.01). Increased nerve fibre width at the inferior whorl, was seen in those with dry eyes (0.0219 [0.0214-0.0236] mm/mm compared to controls 0.0217 [0.0207 0.0222] p < 0.001), but no significant differences were found in the density of corneal immune cells. CONCLUSIONS: hTERT levels were elevated in participants with dry eye disease, and this was accompanied by increased nerve thickness in the inferior cornea. The hTERT response may reflect the stress induced to the ocular surface and corneal nerves due to having dry eye disease.
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PURPOSE: To investigate the behaviour of telomerase reverse transcriptase (hTERT) in the tears of healthy neophyte contact lenses-wearing individuals during the sleep/wake cycle. A subsequent aim was to investigate whether hTERT behaviour was associated with inflammatory mediators interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in tears. METHODS: Flush tears were collected from 19 healthy, non-contact lens-wearing participants (11 males, 8 females, mean age 31.9 ± 5.7 years), before and during contact lens wear. Tears were collected at noon, before sleep and upon awakening and levels of hTERT, IL-6 and TNF-α, were determined using enzyme-linked immunosorbent assays (ELISA). RESULTS: hTERT levels (median [interquartile range]) during contact lens wear were significantly higher before sleep (436.5 (263.9 - 697.7) ng/ml compared to the same time point without contact lenses (256.1 (0.0 - 590.9) ng/ml (p = 0.01). There was no difference between contact lens wear (851.3 [353.2 - 2109.9]) ng/ml, and no wear (1091.0 [492.3 - 3045.4]) ng/ml, upon awakening (p = 0.94). A significant increase was found upon awakening compared to before sleep, irrespective of the presence of a contact lens (p = 0.02). IL-6 and TNF-α levels in tears were below the limit of detection. CONCLUSIONS: The study showed that hTERT increases after a contact lens is placed on the eye, but this change is small, compared to the impact of overnight eye closure. Taken together with the lack of responses of the inflammatory markers monitored at the same time points, this may suggest that hTERT can respond both to low-level stress stimuli acting on the ocular surface, and to situations where inflammation is a likely factor.
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Lentes de Contacto de Uso Prolongado , Lentes de Contacto Hidrofílicos , Lentes de Contacto , Masculino , Femenino , Humanos , Adulto , Interleucina-6 , Factor de Necrosis Tumoral alfa , Lentes de Contacto/efectos adversos , Sueño , LágrimasRESUMEN
The most common and chronic ocular problem of aging is dry eye disease (DED) and the associated condition of meibomian gland dysfunction (MGD). The resident ocular surface bacteria may have a role in maintaining homeostasis and perturbation may contribute to disease development. The aim of this study was to compare the microbiomes of the conjunctiva and eyelid margin in humans with mild and moderate DED and controls using 16 S rRNA gene sequencing. The conjunctiva and lid margin of three cohorts (N = 60; MGD, MGD with lacrimal dysfunction [MGD + LD] and controls) were swabbed bilaterally three times over three months. Microbial communities were analysed by extracting DNA and sequencing the V3-V4 region of the 16 S ribosomal RNA gene using the Illumina MiSeq platform. Sequences were quality filtered, clustered into amplicon sequence variants (ASVs) using UNOISE algorithm and taxonomically classified using a Bayesian Last Common Ancestor (BCLA) algorithm against the GTDB 2207 database. The overall microbial communities of the MGD, MGD + LD and control groups were significantly different from each other (P = 0.001). The MGD and MGD + LD dry eye groups showed greater variability between individuals compared to the control (PERMDISP, P < 0.01). There was decreased richness and diversity in females compared to males for the conjunctiva (P < 0.04) and eyelid margin (P < 0.018). The conjunctiva in the MGD + LD group had more abundant Pseudomonas azotoformans, P. oleovorans and Caballeronia zhejiangensis compared to MGD and control (P < 0.05), while the MGD group had more abundant Corynebacterium macginleyi and C. kroppenstedtii compared to control (P < 0.05). The lid margin in MGD was more abundant in C. macginleyi, C. accolens, and C. simulans compared to the MGD + LD and control (P < 0.05). There were differences in the overall microbial community composition and certain taxa, including increased levels of lipophilic bacteria, on the conjunctiva and eyelid margin in mild to moderate DED/MGD compared to controls. DED/MGD was also associated with a reduced bacterial richness and diversity in females.
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Síndromes de Ojo Seco , Enfermedades de los Párpados , Disfunción de la Glándula de Meibomio , Microbiota , Humanos , Masculino , Femenino , Glándulas Tarsales , Teorema de Bayes , Bacterias/genética , LágrimasRESUMEN
The human face/head supports a highly diverse population of microorganisms across a diverse range of microhabitats. This biogeographical diversity has given rise to selection pressure resulting in the formation of distinct bacterial communities between sites. This review investigates the similarity and differences of microbiomes across the different biogeographies of the human face and discusses a potential pathway for microbial circulation within individuals and within a population to maintain microbiome niches and diversity.
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Microbiota , Bacterias/genética , Ojo , Humanos , ARN Ribosómico 16SRESUMEN
Purpose: To measure variation in corneal dendritic cell density, and percentage of mature to total dendritic cells, in healthy individuals during the sleep/wake cycle.Methods: Using in vivo confocal microscopy, images of the subbasal nerve plexus were captured from 19 healthy, noncontact lens wearing participants. The central cornea and inferior whorl were imaged three times (midday, before sleep, upon awakening). Dendritic cell counts from the images were categorized according to perceived maturity (immature vs mature). Dendritic cell density and percentage of mature to total cells were compared between time points.Result: The median and interquartile range (IQR) of total dendritic cell density in the central cornea was 32.0 (7.0-131.3) cells/mm2 at midday, 37.1 (8.2-103.9) cells/mm2 before sleep, and 19.5 (7.0-83.2) cells/mm2 on awakening. Corresponding values for immature cells were 28.1 (5.8-112.5) cells/mm2, 22.3 (7.4-84.0) cells/mm2 and 18.0 (2.9-64.8) cells/mm2, and for mature cells, 3.1 (0.0-6.6) cells/mm2, 2.0 (0.8-16.8) cells/mm2, and 1.6 (0.2-8.2) cells/mm2. At the inferior whorl, total dendritic cell density was 38.5 (18.4-84.5) cells/mm2, 34.4 (9.4-82.3) cell/mm2, and 32.3 (15.2-96.1) cells/mm2. Immature cell density was 32.8 (18.4-80.9) cells/mm2, 34.4 (8.6-81.0) cells/mm2, and 32.3 (12.6-78.5) cells/mm2. Mature cell density was 1.6 (0.0-6.3) cells/mm2, 1.6 (0.0-3.1) cells/mm2, and 1.8 (0.0-6.3) cells/mm2. There was no significant difference between time points for total cell density (p > 0.05), but the percentage of mature cells upon awakening was significantly greater, compared to midday, at the central cornea (p = 0.02).Conclusion: In healthy individuals, overall corneal dendritic cell density is reasonably constant during the sleep/wake cycle, but the relative number of mature cells tends to increase overnight.
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Ritmo Circadiano , Córnea , Recuento de Células , Córnea/inervación , Células Dendríticas , Humanos , Microscopía Confocal/métodos , Nervio OftálmicoRESUMEN
The tear film is a thin, moist layer covering the ocular surface and is laden with proteins, peptides, lipids, mucins, electrolytes and cellular debris which function to maintain the healthy status of the ocular surface. In many cases of ocular or systemic disease, the integrity of this layer is changed and/or the balance of its constituents is disturbed. Since tears are easy and quick to collect and can be stored for long periods, they have the potential to be a valuable source of information relevant to many disease states. The purpose of this review is to collate information on the known biomarkers of systemic disease that have been identified in tears. The range of conditions covered includes diabetes mellitus, diabetic retinopathy, diabetic peripheral neuropathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, migraine, systemic sclerosis, cystic fibrosis, thyroid disorders and cancer.
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Enfermedades no Transmisibles , Biomarcadores/metabolismo , Ojo/metabolismo , Humanos , Mucinas/metabolismo , Lágrimas/metabolismoRESUMEN
PURPOSE: To determine if there is diurnal variation in gene expression in normal healthy conjunctival cells. METHODS: Bulbar conjunctival swab samples were collected from four healthy subjects in the morning and evening of the same day. The two swab samples were taken from one eye of each participant, with a minimum of five hours gap between the two samples. RNA was extracted and analysed using RNA sequencing (RNA-Seq). RESULTS: A total of 121 genes were differentially expressed between the morning and the evening conjunctival samples, of which 94 genes were upregulated in the morning, and 27 genes were upregulated in the evening. Many of the genes that were upregulated in the morning were involved in defence, cell turnover and regulation of gene expression, while the genes upregulated in the evening were involved in signalling and mucin production. CONCLUSIONS: This study has identified several genes whose expression changes over the course of the day. Knowledge of diurnal variations of conjunctival gene expression provides an insight into the regulatory status of the healthy eye and provides a baseline for examining changes during ocular surface disease.
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Conjuntiva , Mucinas , Ritmo Circadiano/genética , Expresión Génica , Humanos , Mucinas/metabolismoRESUMEN
Animal models are a critical element of ocular surface research for investigating therapeutic drops, surgical implants, and infection research. This study was a comparative analysis of the microbial communities on conjunctival tissue samples from humans compared to several commonly used laboratory animals (BALB/c mice, New Zealand white rabbits and IMVS colored stock guinea pigs). Microbial communities were analyzed by extracting total DNA from conjunctival tissue and sequencing the 16 S rRNA gene using the Illumina MiSeq platform. Sequences were quality filtered using the UNOISE pipeline in USEARCH and taxonomically classified using GTDB database. Sequences associated with blank extraction and sampling negative controls were removed with the decontam R software package prior to downstream analysis. There was a difference in the diversity measures of richness (P = 0.0124) and Shannon index (P = 0.0002) between humans and rabbits but not between human, mouse and guinea pigs. There was a difference between the human and any animal for bacterial community structure (P = 0.006). There was a higher degree of similarity between the bacterial composition of the human and mouse samples with each dominated by the phyla Proteobacteria and Firmicutes. The use of mouse models may be more appropriate for studies investigating changes to the ocular microbiome due to interventions such as application of antibiotics due to greater similarities in bacterial community structure and composition to humans.
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Bacterias/aislamiento & purificación , Conjuntiva/microbiología , ADN Bacteriano/genética , Microbiota/genética , Adolescente , Adulto , Animales , Femenino , Cobayas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Modelos Animales , ARN Ribosómico 16S/genética , Conejos , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
PURPOSE: The ocular surface microbiota are recognised as one of causative microorganisms in post-procedural endophthalmitis but in many cases the vitreous tap is culture negative. This study investigated bacterial contamination of intravitreal (IVT) needles using multiple approaches covering culturing, 16S rRNA gene sequencing, fluorescent in situ hybridisation (FISH) and scanning electron microscopy (SEM). METHODS: IVT needles were obtained immediately after injection from patients undergoing treatment for predominantly age-related macular degeneration. Eighteen needles were analysed by culturing on chocolate blood agar. In addition, 40 needles were analysed by extracting DNA and paired-end sequencing of the 16S rRNA gene. Sequences were quality filtered (USEARCH), taxonomically classified (SILVA) and contaminant filtered (DECONTAM). Nine needles were analysed by either FISH using the bacterial probe EUB338 or SEM. RESULTS: Using culturing, three bacteria were identified from 5 of 18 needles (28%) - Kocuria kristinae, Staphylococcus hominis and Sphingomonas paucimobilis. The negative control needles showed no growth. Following rigorous data filtering, bacterial community analysis using 16S rRNA gene sequencing showed the presence of predominantly Corynebacterium but also Pseudomonas, Acinetobacter, Sphingomonas, Staphylococcus and Bacillus on the needles. Cocci-shaped cells in a tetrad formation were observed using FISH, while SEM images showed cocci-shaped bacteria in pairs and irregular tetrads. CONCLUSIONS: The study showed evidence for a large diversity of bacteria on IVT needles and visually confirmed their adherence. The diversity was similar to that found on the ocular surface and in conjunctival tissue. This suggests the risk of exogenous endophthalmitis remains even with sterilization of the conjunctival surface.
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Microbiota , Agujas , Humanos , Micrococcaceae , ARN Ribosómico 16S/genética , SphingomonasRESUMEN
Aim: The ocular surface is continually exposed to bacteria from the environment and traditional culture-based microbiological studies have isolated a low diversity of microorganisms from this region. The use of culture-independent methods to define the ocular microbiome, primarily involving 16S ribosomal RNA gene sequencing studies, have shown that the microbial communities present on the ocular surface have a greater diversity than previously reported. Method: A review of the literature on ocular microbiome research in health and disease. Results: Molecular techniques have been used to investigate the effect of contact lens wear and disease on the microbiota of the ocular surface and eyelids and the immunoregulatory role of the ocular surface microbiota. Studies have shown that compositional changes in the microbiota occur in ocular surface disorders such as blepharitis, trachoma and dry eye and also suggest a role of the ocular and non-ocular microbiome in retinal disease including age-related macular degeneration, glaucoma, uveitis and diabetic retinopathy. However, ocular microbiome studies need to recognise the potential for contamination to impact findings and carefully control each stage of the experimental procedure and to utilise statistical methods to identify contamination signals. Conclusion: The healthy ocular surface is characterised by a relatively stable, comparatively low diversity microbiome with recent findings that the bacteria of the ocular surface appear to have a role in maintaining homeostasis by modulating immune function.
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Bacterias/aislamiento & purificación , Conjuntiva/microbiología , Párpados/microbiología , Genoma Bacteriano/genética , Microbiota/genética , ARN Ribosómico 16S/genética , Humanos , MetagenómicaRESUMEN
PURPOSE: The human eye is composed of numerous microhabitats. The aim of this study was to understand the communality and differences in the microbiomes of various regions of the eye. METHODS: Four ocular sites from different subject groups were assessed including the eyelid margin tissue from patients with lid abnormalities (nâ¯=â¯20), fornix and limbus conjunctival tissue from patients with pterygia (nâ¯=â¯23), ocular (conjunctival) surface swabs (nâ¯=â¯45) and facial skin swabs (nâ¯=â¯16). Microbial communities were analysed by extracting total DNA from samples and sequencing the 16S ribosomal(r)RNA gene using the Illumina MiSeq platform. Sequences were quality filtered, clustered into unique sequences (zOTUs) using the UNOISE pipeline in USEARCH and taxonomically classified using SILVA. RESULTS: A difference in bacterial richness and diversity was found between sites (Pâ¯<â¯0.001) and for age (Pâ¯<â¯0.035) but not for sex (Pâ¯>â¯0.05). There was a difference in bacterial community structure and composition between sites (Pâ¯<â¯0.001). Bacterial distribution could be broadly classified into three groups - zOTUs resident on the skin and lid margin but with low abundances at other sites (Corynebacterium, Staphylococcus), zOTUs found mainly on the ocular surface (Acinetobacter, Aeribacillus) and zOTUs mostly present in the conjunctiva and lid margin (Pseudomonas). CONCLUSION: The microhabitats of the human eye (ocular surface, conjunctiva, lid margin and skin) have a distinct bacterial biogeography with some bacteria shared between multiple regions while other bacteria occupy a more confined niche.
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Bacterias/genética , ADN Bacteriano/análisis , Infecciones Bacterianas del Ojo/microbiología , Microbiota , Conjuntiva/microbiología , Párpados/microbiología , Femenino , Humanos , MasculinoRESUMEN
AIM: A series of proof-of-principle extended wear (EW) contact lens studies were conducted to assess what effect different interventions had on adverse events (AEs). Comparative analysis of AEs across studies was conducted to determine whether some interventions were more effective at reducing inflammatory AEs. METHOD: Multiple logistic regression analysis of AEs from 30-day EW studies each with a different intervention including (1) nightly replacement (NR) of lenses, (2) morning replacement (MR) of lenses, (3) instillation of prophylactic antibiotic drops (AB) each morning/evening, (4) daily lens cleaning (LC) each morning. All studies conducted at the same site using same lens type (lotrafilcon A) and EW schedule. RESULTS: Comparison of the different interventions to the individual control groups showed no difference in significant corneal infiltrative event (CIE) or mechanical events. Replacing lenses nightly, during an EW schedule, had the highest incidence of significant CIEs (4.9% [NR] vs. 2.5% [MR] vs. 1.8% [AB] vs. 0% [LC]); however, adjusted logistic regression analysis of the combined control data compared with the individual interventions showed no difference in significant CIEs (P=0.086) or mechanical AEs (P=0.140). CONCLUSIONS: Replacing lenses each night seemed to be inferior compared with the other interventions of replacing lenses each morning, daily lens cleaning, and daily antibiotic drop instillation during EW. The results of the collective studies and additional analysis suggest that overnight wear of contact lenses seems to create an adverse environment that remains, despite the various interventions intended to improve this adverse environment.
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Antibacterianos/administración & dosificación , Lentes de Contacto de Uso Prolongado/efectos adversos , Infecciones Bacterianas del Ojo/prevención & control , Equipos Desechables , Infecciones Bacterianas del Ojo/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Soluciones Oftálmicas , Estudios Prospectivos , Adulto JovenRESUMEN
Purpose: Knowledge of whether microorganisms reside in protected niches of the conjunctiva is potentially significant in terms of minimizing risks of contact lens inflammation/infection and endophthalmitis. We define if and how microbial communities from limbal and forniceal conjunctival tissue differ from those on the conjunctival surface. Methods: Human limbal and forniceal conjunctival tissue was obtained from 23 patients undergoing pterygium surgery and analyzed with data from a recent study of conjunctival surface swabs (n = 45). Microbial communities were analyzed by extracting total DNA from tissue samples and surface swabs and sequencing the 16S rRNA gene using the Illumina MiSeq platform. Sequences were quality filtered, clustered into operational taxonomic units (OTUs) at 97% similarity. OTUs associated with blank extraction and sampling negative controls were removed before analysis. Fluorescent in situ hybridization (FISH) was performed on cyrosections of limbal and forniceal conjunctival tissue. Results: There was a significant difference in bacterial community structure between the conjunctival surface and fornix (P = 0.001) and limbus (P = 0.001) tissue. No difference was found in bacterial communities between the limbus and fornix (P = 0.764). Fornix and limbal samples were dominated by OTUs classified to the genus Pseudomonas (relative abundance 79.9%), which were found only in low relative abundances on conjunctival surfaces (6.3%). Application of FISH showed the presence of Pseudomonas in the forniceal tissue sample. Conclusions: There is a discrete tissue-associated microbiome in freshly-collected human limbal and fornix tissue, which is different from the microbial community structure and composition of the ocular surface microbiome.
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Bacterias/aislamiento & purificación , Conjuntiva/microbiología , Limbo de la Córnea/microbiología , Microbiota , Adulto , Anciano , Femenino , Humanos , Hibridación Fluorescente in Situ , Masculino , Persona de Mediana Edad , ARN Bacteriano/análisis , ARN Ribosómico 16S/análisisRESUMEN
OBJECTIVES: To investigate whether adaptation of accommodative responses occurred in non-presbyopic myopes fitted with four multifocal contact lens (MFCL) designs. METHODS: Prospective, subject-masked clinical investigation comprising 40 experienced myopic lens wearers (18-25 years) fitted bilaterally with single-vision (SV) control lens (Air Optix Aqua [Alcon, Fort Worth, TX]) and randomized to two of four test MFCL (Proclear MFCL [Distance and Near] [CooperVision, Pleasanton, CA], Air Optix Aqua MFCL, Purevision MFCL [Bausch & Lomb, Rochester, NY]). Lenses were dispensed on a daily wear basis and worn for a minimum of 8 (maximum 14) days over three assessment visits, with a 1-week wash out between stages. Paraxial curvature matched spherical equivalent (M) was measured with lenses on eye using the BHVI-EyeMapper with an internal movable fixation target positioned at target vergences of +1.00 diopter (D) (fogging) and -2.00 to -5.00 in 1.00 D steps (accommodative stimuli). Accommodative facility was assessed by several flips of ±2.00 D/min (cycles/min) at 33 cm and horizontal phoria with a Howell phoria card at distance (3 m) and near (33 cm). RESULTS: For center-distance MFCL (Proclear D), the spherical equivalent (M) at all near vergences became significantly more negative at the follow-up visits compared with the dispensing visit (P<0.029). For all center-near MFCLs and SV lens, M remained invariant during the adaptation period, however (P≥0.267). At distance, M became significantly less minus with Air Optix Aqua MFCL over time (P=0.049). Accommodative facility increased over the three assessment visits for participants wearing Air Optix Aqua SV, Air Optix Aqua MFCL, and PureVision MFCL (P=0.003). Distance and near horizontal phoria remained stable over the three assessment visits for all lens types (P≥0.181). CONCLUSIONS: Adaptation differences were not consistently found for static accommodative measures gauged by M, as measured with lenses on eye, and phoria but were found in dynamic measures (facility), perhaps indicating some learning effects. Accommodative adaptation seems unlikely to occur with long-term MFCL in non-presbyopes.
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Acomodación Ocular/fisiología , Lentes de Contacto Hidrofílicos , Miopía/rehabilitación , Adulto , Estudios Cruzados , Femenino , Humanos , Masculino , Miopía/fisiopatología , Estudios Prospectivos , Agudeza Visual/fisiología , Adulto JovenRESUMEN
To determine if there is a core ocular surface microbiome and whether there are microbial community changes over time, the conjunctiva of 45 healthy subjects were sampled at three time points over three months and processed using culture-dependent and -independent methods. Contaminant taxa were removed using a linear regression model using taxa abundances in negative controls as predictor of taxa abundances in subject samples. Both cultured cell counts and sequencing indicated low microbial biomass on the ocular surface. No cultured species was found in all subjects at all times or in all subjects at any one time. After removal of contaminant taxa identified in negative controls using a statistical model, the most commonly detected taxon was Corynebacterium (11.1%). No taxa were found in all subjects at all times or in all subjects in any one time, but there were 26 taxa present in at least one or more subjects at all times including Corynebacterium and Streptococcus. The ocular surface contains a low diversity of microorganisms. Using culture dependent and independent methods, the ocular surface does not appear to support a substantial core microbiome. However, consistently present taxa could be observed within individuals suggesting the possibility of individual-specific core microbiomes.
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Conjuntiva/microbiología , Párpados/microbiología , Microbiota , Adulto , Femenino , Humanos , Masculino , Metagenoma , Metagenómica/métodos , Persona de Mediana Edad , ARN Ribosómico 16SRESUMEN
PURPOSE: The purpose of the study was to assess what effect daily cleaning of contact lenses with a multipurpose disinfection solution (MPDS), during 30 nights extended wear, would have on contact lens-related adverse events. METHODS: This was a prospective, open-label, randomized, controlled, parallel-group, 3-month clinical study in which 193 participants were dispensed with lotrafilcon A silicone hydrogel lenses for a 30-day extended-wear schedule and with lenses replaced monthly. Participants were randomized to a control or test group. Test subjects were required to remove lenses daily after waking, clean them with the MPDS, and reinsert the lenses. Control subjects wore lenses without removal for 30 days extended wear. Handling-related lens contamination was assessed at the baseline visit. RESULTS: There was no significant difference between the test and control groups for the incidence of significant corneal infiltrative events (1.3 vs. 4.9%, p = 0.368), total corneal infiltrative events (2.6 vs. 4.9%, p = 0.682), or mechanical events (1.3 vs. 2.5%, p = 1.00). The test group had greater corneal staining (p < 0.047) and fewer mucin balls (p = 0.033). Handling-related lens contamination (unworn lenses) resulted in isolation of Gram-positive bacteria from 92.5% of test lenses compared with 87.5% of control lenses (p = 0.712). Gram-negative bacteria were isolated from 5% of test subjects compared with 2.5% of control subjects (p = 1.00). Fungus was isolated from 2.5% of subjects in both the test and control groups (p = 1.00). CONCLUSIONS: The intervention of daily morning cleaning of the lens surface with an MPDS during extended wear did not significantly influence the incidence of adverse events.
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Soluciones para Lentes de Contacto/uso terapéutico , Lentes de Contacto de Uso Prolongado/efectos adversos , Lentes de Contacto de Uso Prolongado/microbiología , Infecciones Bacterianas del Ojo/etiología , Hongos/aislamiento & purificación , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/aislamiento & purificación , Adolescente , Recuento de Colonia Microbiana , Femenino , Desinfección de las Manos , Humanos , Hidrogeles , Incidencia , Masculino , Estudios Prospectivos , SiliconasRESUMEN
PURPOSE: Covalent immobilization of antimicrobial peptide melimine onto contact lenses can produce broad-spectrum antimicrobial lenses. The purpose of this study was to investigate the performance of melimine-coated contact lenses in an animal model and human clinical trial. METHODS: Melimine was covalently attached onto the surface of contact lenses via EDC (1-ethyl-3-[3-dimethylaminopropyl] carbodiimide hydrochloride) coupling. A rabbit model of daily contralateral wear of lenses for 22 days was conducted to assess the lens safety. A prospective, randomized, double-masked, one-day human clinical trial was used to evaluate subjective responses and ocular physiology during contralateral wear of melimine-coated (test) and uncoated (control) lenses. Delayed reactions were monitored during follow-up visits after 1 and 4 weeks. Ex vivo retention of antimicrobial activity of worn lenses was assessed by reduction in numbers of viable Pseudomonas aeruginosa and Staphylococcus aureus. RESULTS: Melimine-coated lenses produced no ocular signs or symptoms that would indicate cytotoxicity during the lens wear of rabbits. No histological changes were found in rabbit corneas. During the human trial, no differences were observed in wettability, surface deposition, lens-fitting centration, movement, tightness, and corneal coverage between test and control lenses (p > 0.05). There were no significant differences in bulbar, limbal, or palpebral redness or conjunctival staining (p > 0.05). Mean corneal (extent, depth, and type) staining was higher for test lenses compared with that for control lenses (p < 0.05). There was no significant difference in subjective responses for lens comfort, dryness, and awareness (p > 0.05). No delayed reactions were associated with the test lenses. Worn test lenses retained more than 1.5 log inhibition against both bacterial types. CONCLUSIONS: Melimine-coated contact lenses were worn safely by humans. However, they were associated with higher corneal staining. The melimine-coated lenses retained high antibacterial activity after wear.
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Antiinfecciosos/uso terapéutico , Péptidos Catiónicos Antimicrobianos/uso terapéutico , Materiales Biocompatibles Revestidos/uso terapéutico , Lentes de Contacto Hidrofílicos , Modelos Animales de Enfermedad , Adulto , Animales , Antiinfecciosos/efectos adversos , Péptidos Catiónicos Antimicrobianos/efectos adversos , Materiales Biocompatibles Revestidos/efectos adversos , Recuento de Colonia Microbiana , Córnea/fisiología , Método Doble Ciego , Femenino , Humanos , Masculino , Ensayo de Materiales , Metacrilatos , Estudios Prospectivos , Ajuste de Prótesis , Pseudomonas aeruginosa/efectos de los fármacos , Conejos , Staphylococcus aureus/efectos de los fármacos , HumectabilidadRESUMEN
PURPOSE: Overnight lens wear is associated with increased lens contamination and risk of developing a corneal infiltrate or infectious event. Antibacterial lenses have been proposed as a potential strategy for reducing lens contamination. A proof-of-principle study was conducted to investigate what effect control of potential pathogens, through the use of antibiotic eye drops, would have on the incidence of corneal infiltrative events (CIEs) and on the ocular microbiota and lens contamination. METHODS: This is a prospective, open-label, controlled, parallel-group, 1-month clinical study in which 241 subjects were dispensed with lotrafilcon A silicone hydrogel lenses for 30 days of continuous wear. Subjects were randomized into either test (moxifloxacin 0.5%) or control (rewetting solution) group. One drop was instilled into each eye on waking and before sleeping, while lenses were on-eye. Follow-ups were conducted after one night and 1 month. Lid margin swabs were taken at baseline and at 1 month and worn lenses were aseptically collected at 1 month. RESULTS: The incidence of CIEs was not significantly different between the test (2.6%) and control (3.9%) groups (p = 0.72). Microorganism levels from the test group swabs were significantly lower than those from the control group (p = 0.001). Gram-positive bacteria were less frequently recovered from lower lid swabs from the test group (39.6% vs. 66.0% [p < 0.001], test vs. control, respectively) or from contact lens samples (1.9% vs. 10.5% [p = 0.015], test vs. control, respectively), but there was no difference in gram-negative bacteria (GNB). Corneal infiltrative events were associated with higher levels of lens contamination (p = 0.014) and contamination of lenses with GNB (CIE: 7.3% vs. 0.6% [p = 0.029], GNB contamination vs. no GNB contamination, respectively). DISCUSSION: Twice-daily antibiotic instillation during continuous wear of lenses did not significantly influence the rate of inflammatory events. Corneal infiltrative events were associated with higher levels of lens contamination in general and with contamination by GNB specifically.