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Hypersomnia spectrum disorders are underdiagnosed and poorly treated due to their heterogeneity and absence of biomarkers. The electroretinography has been proposed as a proxy of central dysfunction and has proved to be valuable to differentiate certain psychiatric disorders. Hypersomnolence is a shared core feature in central hypersomnia and psychiatric disorders. We therefore aimed to identify biomarkers by studying the electroretinography profile in patients with narcolepsy type 1, idiopathic hypersomnia and in controls. Cone, rod and retinal ganglion cells electrical activity were recorded with flash-electroretinography in non-dilated eye of 31 patients with idiopathic hypersomnia (women 84%, 26.6 ± 5.9 years), 19 patients with narcolepsy type 1 (women 63%, 36.6 ± 12.7 years) and 43 controls (women 58%, 30.6â ± 9.3 years). Reduced cone a-wave amplitude (p = 0.039) and prolonged cone (p = 0.022) and rod b-wave (p = 0.009) latencies were observed in patients with narcolepsy type 1 as compared with controls, while prolonged photopic negative response-wave latency (retinal ganglion cells activity) was observed in patients with idiopathic hypersomnia as compared with controls (p = 0.033). The rod and cone b-wave latency clearly distinguished narcolepsy type 1 from idiopathic hypersomnia and controls (area under the curve > 0.70), and the photopic negative response-wave latency distinguished idiopathic hypersomnia and narcolepsy type 1 from controls with an area under the curve > 0.68. This first original study shows electroretinography anomalies observed in patients with hypersomnia. Narcolepsy type 1 is associated with impaired cone and rod responses, whereas idiopathic hypersomnia is associated with impaired retinal ganglion cells response, suggesting different phototransduction alterations in both hypersomnias. Although these results need to be confirmed with a larger sample size, the electroretinography may be a promising tool for clinicians to differentiate hypersomnia subtypes.
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BACKGROUND: Our objective is twofold: determining if simulation allows residents to reach proficient surgeons' performance concerning fundamental technical skills of endovascular surgery (FEVS) while investigating effects of the program on surgeons' stress. METHODS: Using a FEVS training simulator, 8 endovascular FEVS were performed by vascular surgery residents (simulator-naive or simulator-experienced residents [SER]) and seniors. Total time needed to complete the 8 tasks, called total completion time (TCT), was the main evaluation criterion. Analgesia Nociception Index (ANI) was monitored during simulation. Likert scale questionnaire was filled out after each simulation. RESULTS: For each task, TCT was significantly lower for SER and seniors than simulator-naive residents (P = 0.0163). After only 5 simulations, SER were able to reach and even exceed the seniors' level in terms of TCT, with a median time of 10.8 min for SER and 11.9 min for seniors, and wire's movements with a median distance during cannulation of 4.44 m for SER and 4.17 m for seniors. Seniors remained better than SER in terms of precise wire manipulation (wire movement after cannulation), 4.17 m against 4.44 m (3.72-5.96), respectively. Based on the Likert scale stress analysis, seniors felt less stressed than both residents' groups (P = 0.0618). Seniors' initial ANI and mean ANI over the session were significantly lower than those of the residents, P = 0.0358 and P = 0.0250, respectively. CONCLUSIONS: We showed that 5 simulation sessions allowed residents to reach experienced surgeons' capacities on FEVS concerning TCT. Subjectively, seniors felt less stressed than residents, contrary to the results of our objective measures of stress.
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PURPOSE: To compare two drainage techniques in macula-off retinal detachment (RD) surgery: perfluorocarbon liquid (PFCL)-assisted drainage and partial subretinal fluid (SRF) drainage without PFCL. We investigated morphological and functional outcomes, focusing on metamorphopsia quantification. METHODS: Eighty eyes with macula-off RD were retrospectively included. All underwent a 25-gauge pars plana vitrectomy. In the PFCL group, SRF drainage was performed using PFCL. In the partial SRF drainage (SRFD) group, SRF was partially drained through a pre-existing retinal break without PFCL. A follow-up at 3 and 6 months evaluated anatomical outcomes using optical coherence tomography (OCT), best corrected visual acuity (BCVA) and metamorphopsia quantified with M-charts. RESULTS: Reattachment rates were comparable in the PFCL group (97.5%) and the SRFD group (95%) (p > 0.05). Mean BCVA (LogMAR) was 0.23 ± 0.32 (PFCL group) and 0.15 ± 0.13 (SRFD group) (p = 0.206). Metamorphopsia were reported by 19 patients (47.5%) in the PFCL group and by 12 patients (30%) in the SRFD group (p = 0.332). The mean metamorphopsia score was similar in both groups (0.27 ± 0.12 in the PFCL group and 0.28 ± 0.11 in the SRFD group, p = 0.866). Morphological OCT findings were comparable in both groups. CONCLUSION: Morphological and functional outcomes were similar in PFCL and SRFD groups. Metamorphopsia quantification scores did not improve with PFCL. While both of these techniques might be effective and could be recommended for primary macula-off RD management, potential PFCL toxicity should be kept in mind and its use dedicated to selected cases.
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BACKGROUND: To assess the long-term incidence and risk factors for post-keratoplasty infectious keratitis (IK), associated ocular pathogens, and antibiotic resistance profiles. METHODS: Cohort study including 2553 consecutive penetrating, endothelial, and anterior lamellar keratoplasties performed between 1992 and 2020. Medical and microbiological records of patients clinically diagnosed with IK were retrospectively reviewed. MAIN OUTCOME MEASURES: cumulative incidence of IK, infectious agent species, and antibiotics resistance profiles. RESULTS: The average follow-up time after transplantation was 112 ± 96 months. Eighty-nine IK episodes were recorded; microbiological tests were positive in 55/89 (62%). The cumulated incidence of postoperative IK was 5.50%/10.25% at 10/20 years. The occurrence of at least one episode of IK after transplantation was associated with lower graft survival in the long term (p < 0.0001). Rejection risk (adjusted Hazard Ratio, 2.29) and postoperative epithelial complications (HR, 3.44) were significantly and independently associated with a higher incidence of postoperative IK. Infectious agents included 41 bacteria, 10 HSV, 6 fungi, and 1 Acanthamoeba. The rate of antibiotic resistance was 0% for vancomycin, 13% for fluoroquinolones, 20% for rifamycin, 59% for aminoglycosides, and 73% for ticarcillin. In 41% of cases, patients were under prophylactic topical antibiotics before the infectious episode. Topical antibiotics were significantly associated with increased resistance to penicillin, carbapenems, and aminoglycosides. CONCLUSION: IK (mainly bacterial) is a frequent complication of corneal transplantation in the long term. Vancomycin and fluoroquinolones can be considered as first-line treatments. Prolonged postoperative antibiotic preventive treatment is not advisable as it may increase antibiotic resistance.
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Transplante de Córnea , Infecções Oculares Bacterianas , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/microbiologia , Infecções Oculares Bacterianas/etiologia , Incidência , Fatores de Risco , Seguimentos , Adulto , Transplante de Córnea/efeitos adversos , Úlcera da Córnea/microbiologia , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/tratamento farmacológico , Antibacterianos/uso terapêutico , Sobrevivência de Enxerto , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/etiologia , Idoso , Complicações Pós-Operatórias/epidemiologia , Ceratite/epidemiologia , Ceratite/etiologia , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ceratite/diagnóstico , Bactérias/isolamento & purificaçãoRESUMO
PURPOSE: We aimed to identify ocular comorbidities and reasons of blindness in monocular patients and to compare visual outcomes of cataract surgery between monocular and binocular patients. METHODS: A single-center case-control study was conducted between November 2011 and May 2019 to compare consecutive series of patients needing cataract surgery in Strasbourg University Hospitals, France. Cases were patients with permanent monocular vision loss. Controls were binocularly sighted patients. All patients underwent cataract surgery using phacoemulsification technique. Chart analysis included demographic data, medical history, and surgical determinants data. Student's t tests and Fisher's exact tests were the main methods used for statistical analysis. RESULTS: Each group included 80 patients. The mean age at the time of surgery was significantly higher in monocular than binocular patients (77 vs. 71 years, p < 0.001). Thirty-two monocular patients (40%) had ocular comorbidities, compared to only 19 (23%) in the control group (p < 0.05). The leading cause of monocular status was amblyopia caused by strabismus (22 patients, 27.5%). Age-related macular degeneration, open-angle glaucoma, and diabetic retinopathy were the three main ocular comorbidities that were observed in the monocular group. Monocular patients had significantly lower visual acuity than the control group (p < 0.01) before and after cataract surgery. Conversely, improvement in visual acuity after surgery was not statistically different between groups (p = 0.054). There was no statistically significant difference in the rate of surgical complications between groups (p = 0.622). CONCLUSIONS: This study illustrates that cataract surgery in monocular patients is not more complicated than in binocular patients, but that it is significantly delayed.
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Extração de Catarata , Catarata , Glaucoma de Ângulo Aberto , Facoemulsificação , Humanos , Estudos de Casos e Controles , Catarata/complicações , Glaucoma de Ângulo Aberto/complicações , Resultado do Tratamento , Cegueira , Visão BinocularRESUMO
PURPOSE: To assess the current diagnostic and therapeutic practice patterns in early management of bacterial keratitis over five continents. METHODS: Between March and August 2019, we distributed an online survey including two clinical scenarios of bacterial keratitis, namely, a mild case and severe case, to 2936 ophthalmologists from 144 countries around the world. The survey consisted of 29 questions. We performed descriptive statistics and a comparative analysis of the answers according to the participants' continent of practice, practice setting, seniority, and subspecialty. RESULTS: We received 237 surveys from 54 countries (8% response rate). The proportion of respondents performing microbiological investigations was higher in North America, Asia, Europe, and Oceania than Africa and South America (p < 0.05). This ratio was also higher among ocular surface specialists than for other ophthalmologists (p < 0.001). For mild cases, fluoroquinolone monotherapy and a combination of two or more antibiotics were prescribed by 46% and 41% respondents, respectively. For severe cases, fluoroquinolone monotherapy and a combination of antibiotics were prescribed by 20% and 78% respondents, respectively. Fluoroquinolone monotherapy was the most commonly prescribed treatment in South America, Africa, and Oceania. A combination of two antibiotics was preferentially prescribed in the rest of the world. Topical steroids were prescribed in both circumstances, respectively, in 72% and 75% of cases. CONCLUSION: Our results highlight essential geographical disparities in the current management of bacterial keratitis over five continents.
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Infecções Oculares Bacterianas , Ceratite , Humanos , Ceratite/diagnóstico , Ceratite/tratamento farmacológico , Ceratite/epidemiologia , Inquéritos e Questionários , Antibacterianos/uso terapêutico , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/epidemiologia , Fluoroquinolonas/uso terapêuticoRESUMO
PURPOSE: To determine the long-term microvascular alterations associated with macular cystic changes after retinal detachment surgery with silicone oil tamponade. METHODS: The results of two optical coherence tomography angiographies performed at 11 months and 38 months after silicone removal were retrospectively analyzed for 30 eyes. The data were compared between both measurements and between eyes with macular cysts (MC+) and without macular cysts (MC-). Two patterns of cysts were identified and compared: cysts exclusively involving the inner nuclear layer (INLc) and cysts present in all retinal layers. RESULTS: At both end points, 20 eyes (67%) presented with macular cysts, 12 of them (40%) had INLc. At the first end point, vascular density of superficial capillary plexus was higher and superficial foveal avascular zone was smaller in MC+ eyes than in MC- eyes (P = 0.04 and P = 0.017, respectively). At the second end point, vascular density of superficial capillary plexus significantly decreased in MC+ eyes as compared with the first end point (P < 0.001) and superficial foveal avascular zone enlarged (P < 0.001). Macular central thickness decreased between follow-ups only in eyes with INLc (P < 0.01). The final best-corrected visual acuity was better in eyes with INLc than in eyes with cysts present in all retinal layers (P < 0.01). There was no difference between the final best-corrected visual acuity in eyes with INLc and MC- eyes. CONCLUSION: Macular cysts are a common finding long after silicon removal. Vascular remodeling seems characterized by an initial increase of the vascular density of superficial capillary plexus in eyes with cysts, which is followed by its progressive decrease. The INLc is the most common pattern of cysts. They are associated with a progressive decrease of the central macular thickness without visual impairment.
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Cistos , Macula Lutea , Descolamento Retiniano , Humanos , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Angiofluoresceinografia/métodos , Estudos Retrospectivos , Macula Lutea/irrigação sanguínea , Tomografia de Coerência Óptica/métodos , Vasos Retinianos/diagnóstico por imagemRESUMO
BACKGROUND: Topical mast cell stabilizers were previously shown to treat the signs and symptoms of seasonal and perennial allergic conjunctivitis safely and effectively in active and placebo-controlled trials. However, mast cell stabilizers have not been compared to topical corticosteroids for efficacy. We tested the non-inferiority of a topical mast cell stabilizer, N-acetyl aspartyl glutamic acid (4.9%, NAAGA), compared to fluorometholone (0.1%, FM) during controlled exposures to the airborne birch pollen allergen, Bet v 1, in an environmental exposure chamber (EEC). METHODS: This randomized, cross-over, investigator-blinded study included 24 patients with a history of birch pollen allergic conjunctivitis. Patients were randomized to 5 days of treatment with NAAGA, then FM (n = 12) or FM, then NAAGA (n = 12). After each treatment, patients were exposed to a fixed airborne concentration of Bet v 1 in ALYATEC EEC. The primary endpoint was the amount of allergen required to trigger a conjunctival response (Abelson score ≥5). Groups were compared with a linear model for cross-over studies. Non-inferiority was assumed, when the lower bound of the risk ratio confidence interval (CI) was >0.5. RESULTS: At screening, the mean time-to-conjunctival response was 72.5 ± 35.9 min. NAAGA and FM extended the response time to 114.8 ± 55.0 and 116.6 ± 51.5 min respectively. The mean amounts of allergen required to trigger a conjunctival response were 1.165 ng after NAAGA and 1.193 ng after FM treatment. The risk ratio for the conjunctival response was 0.977 (95% CI: 0.812; 1.174), which indicated non-inferiority. Adverse events occurred less frequently with NAAGA (29.2%) than with FM (58.3%). CONCLUSION: In patients with allergic conjunctivitis to birch pollen, NAAGA was non-inferior to FM in exposures to airborne Bet v 1. The EEC was a good model for simulating real-life airborne allergen exposure and for demonstrating the efficacy and safety of eye drops for treating allergic conjunctivitis. TRIAL REGISTRATION: Not registered.
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Conjuntivite Alérgica , Alérgenos , Conjuntivite Alérgica/diagnóstico , Conjuntivite Alérgica/tratamento farmacológico , Estudos Cross-Over , Dipeptídeos , Exposição Ambiental , Fluormetolona/uso terapêutico , Ácido Glutâmico/uso terapêutico , Humanos , Estabilizadores de MastócitosRESUMO
PURPOSE: To assess the frequency of macular cysts (MCs) in retinal detachment treated with silicone oil and evaluate their impact on visual acuity and macular vascularization using optical coherence tomography-angiography. METHODS: Forty-three eyes of 41 patients treated with silicone oil for retinal detachment were retrospectively studied. Best-corrected visual acuity and 6- × 6-mm optical coherence tomography-angiography examination at least 3 months after silicone oil removal were reviewed. In eyes with MCs, cyst area was measured on the en face optical coherence tomography-angiography image using ImageJ. Density of superficial capillary plexus and area of superficial foveal avascular zone were generated by the optical coherence tomography-angiography. Density of deep capillary plexus and deep foveal avascular zone area were measured using ImageJ. RESULTS: Twenty-five eyes (58%) presented with MCs. Cysts were exclusively located in the inner nuclear layer in 60% of cases. Mean best-corrected visual acuity in the MC group was lower than that of the non-MC group (P = 0.012). Macular cyst area negatively correlated with best-corrected visual acuity (P = 0.0201). Density of superficial capillary plexus was higher in the MC group (P < 0.0001), whereas area of superficial foveal avascular zone was lower (P < 0.0001). Macular cyst area negatively correlated with density of deep capillary plexus (P < 0.001). CONCLUSION: The incidence of INL-MCs after silicone oil removal is high. These are associated with impaired vision and macular vascular remodeling. We highlight their similarity with the "retrograde maculopathy" phenomenon.
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Tamponamento Interno/métodos , Macula Lutea/patologia , Descolamento Retiniano/diagnóstico , Vasos Retinianos/patologia , Óleos de Silicone/farmacologia , Remodelação Vascular , Baixa Visão/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Angiofluoresceinografia/métodos , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Descolamento Retiniano/fisiopatologia , Descolamento Retiniano/cirurgia , Vasos Retinianos/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Tomografia de Coerência Óptica/métodos , Baixa Visão/fisiopatologia , Acuidade Visual , Adulto JovemRESUMO
PURPOSE: Although the Cochet-Bonnet esthesiometer (CBE) measures corneal sensitivity, it has heretofore only been tested on the index pulp. Tactile skin sensitivity thresholds are measured with Semmes-Weinstein monofilaments (SWM). This study measured skin sensitivity thresholds in healthy individuals using CBE and SWM, and compared both instruments in territories involved in corneal neurotization. METHODS: Overall, 27 healthy individuals were tested by a single examiner at 9 territories on the face, neck, forearm, and leg, using 20-thread SWM and CBE with a diameter of 0.12 mm. Both sides were tested. Thresholds were compared for both instruments and between the different territories using Bayesian methods. RESULTS: Mean sensitivity levels for SWM ranged from 0.010 to 1.128 g, while mean sensitivity levels for CBE ranged from 0.006 to 0.122 g. Thresholds measured with SWM were significantly higher than with CBE. Both instruments demonstrated higher thresholds in the leg territory than the forearm. However, the forearm presented higher thresholds than the head territories. No significant differences were found between the head territories themselves. Overall, right-side territories exhibited lower thresholds than left-side territories. CONCLUSIONS: We have reported the first mapping of skin sensitivity thresholds using CBE. Thresholds measured with CBE and SWM were coherent. The use of CBE on the skin is particularly relevant to the field of corneal neurotization.
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Transferência de Nervo , Teorema de Bayes , Córnea , Humanos , Limiar Sensorial , PeleRESUMO
Despite the advantages that robot-assisted surgery can offer to patient care, its use in ophthalmic surgery has not yet progressed to the extent seen in other fields. As such, its use remains limited to research environments, both basic and clinical. The technical specifications for such ophthalmic surgical robots are highly challenging, but rapid progress has been made in recent years, and recent developments in this field ensure that the use of this technology in operating theatres will soon be a real possibility. Fully automated ocular microsurgery, carried out by a robot under the supervision of a surgeon, is likely to become our new reality. This review discusses the use of robot-assisted ophthalmic surgery, the recent progress in the field, and the necessary future developments which must occur before its use in operating theatres becomes routine.
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Procedimentos Cirúrgicos Robóticos , Robótica , HumanosRESUMO
A growing number of receptors, often associated with the innate immune response, are being identified as targets for bacterial toxins of the beta-stranded pore-forming family. These findings raise the new question of whether the receptors are activated or merely used as docking points facilitating the formation of a pore. To elucidate whether the Staphylococcus aureusâ Panton-Valentine leukocidin and the leukotoxin HlgC/HlgB act through the C5a receptor (C5aR) as agonists, antagonists or differ from the C5a complement-derived peptide, their activity is explored on C5aR-expressing cells. Both leukotoxins equally bound C5aR in neutrophils and in stable transfected U937 cells and initiated mobilization of intracellular Ca(2+) . HlgC/HlgB requires the presence of robust intracellular acidic Ca(2+) stores in order to evoke a rise in free [Ca(2+) ]i , while the LukS-PV/LukF-PV directly altered reticular Ca(2+) stores. Intracellular target specificity is conferred by the F-subunit associated to the S-subunit binding the receptor. Furthermore, internalization of the two leukotoxin components (S- and F-subunits) associated to C5aR is required for the initiation of [Ca(2+) ]i mobilization. Electrophysiological recordings on living cells demonstrated that LukS-PV/LukF-PV does not alter the membrane resistance of C5aR-expressing cells. The present observations suggest that part of the pore-forming process occurs in distinct intracellular compartments rather than at the plasma membrane.
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Toxinas Bacterianas/metabolismo , Cálcio/metabolismo , Exotoxinas/metabolismo , Leucocidinas/metabolismo , Neutrófilos/microbiologia , Neutrófilos/fisiologia , Receptor da Anafilatoxina C5a/metabolismo , Staphylococcus aureus/imunologia , Células Cultivadas , Fenômenos Eletrofisiológicos , Interações Hospedeiro-Patógeno , Humanos , Monócitos/microbiologia , Monócitos/fisiologia , Ligação ProteicaRESUMO
BACKGROUND: Congenital cataract is of particular interest because of the variability of etiologies and the inflammatory reaction that are often observed. The aim of the study was to describe intraocular levels of various inflammation-related cytokines of patients with congenital cataract and to study their correlations with clinical determinants. METHODS: We followed a cohort of 18 patients (18 eyes) with congenital cataract from a University hospital and measured levels of various inflammation-related cytokines in the aqueous humor of patients with congenital cataract, and compared these levels to those observed in a control group (patients with senile cataract) using multiplex immunoassay. Correlation analysis was used to study the possible correlation between intraocular levels of cytokines and clinical determinants. RESULTS: Compared with the control group, the group with congenital cataract showed clear and significantly elevated concentrations of inflammatory markers (IL-1ß, IL-15, IFN-γ, IL-12, IL-6, IL-5, IL-9, MIP-1α, MCP-1 and IP-10). Postoperative intraocular inflammation and opacification of the posterior capsule seemed to be correlated with preoperative IL-1ß, TNF-α and IL-6 levels. CONCLUSIONS: An inflammatory condition may occur in eyes with congenital cataract. The cytokine profiles are really different than those observed in senile cataract. Moreover, cytokines levels may be of interest to predict posterior capsule opacification and to complete the etiological workup.
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Humor Aquoso/metabolismo , Opacificação da Cápsula/metabolismo , Catarata/congênito , Catarata/metabolismo , Citocinas/metabolismo , Idoso , Feminino , Humanos , Imunoensaio , Lactente , Masculino , Cápsula Posterior do Cristalino/metabolismoRESUMO
PURPOSE: The most feared complication of contact lens (CL) wear is microbial keratitis (MK), even though its incidence remains low. This study aimed to identify the risk factors of CL-related MK in a large, prospective, multicenter case-control study. METHODS: A multicenter case-control study was designed. The CL-related MK subpopulation (Case) was compared with healthy CL wearers (Control) using a 52-item anonymous questionnaire designed to determine subject demographics and lens wear history. Univariate and multivariate logistic regression analyses were performed to compare both groups. RESULTS: The study enrolled 499 cases and 508 controls. The risk factors associated with the greatest increased odds of CL-related MK were as follows: using disinfecting solution more than 3 months (odds ratio [OR]=1.94), cosmetic CL wear and use of multipurpose disinfection solution (1.37 each), overnight wear, and soft lens use (OR=1.24 each). The protective factors associated with the greatest reduction in OR were fitting by an ophthalmologist (OR=0.73) and hyperopia versus myopia (OR=0.75). CONCLUSIONS: The infectious determinants were linked to the type of lenses, hygiene routine, CL handling, disinfecting solution, and storage case. This study aimed to highlight the increasingly CL-related MK, which likely occurs because of lack of patient information regarding basic rules of hygiene and CL care and handling.
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Lentes de Contato/efeitos adversos , Úlcera da Córnea/epidemiologia , Infecções Oculares Bacterianas/epidemiologia , Adulto , Estudos de Casos e Controles , Soluções para Lentes de Contato , Lentes de Contato/classificação , Úlcera da Córnea/microbiologia , Desinfecção/métodos , Equipamentos Descartáveis , Infecções Oculares Bacterianas/microbiologia , Feminino , França/epidemiologia , Humanos , Higiene , Incidência , Masculino , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Ocular inflammation is one of the consequences of infection with the protozoan parasite Toxoplasma gondii. Even if lesions are self-healing in immunocompetent persons, they pose a lifetime risk of reactivation and are a serious threat to vision. As there are virtually no immunological data on reactivating ocular toxoplasmosis, we established a model of direct intravitreal injection of parasites in previously infected mice with a homologous type II strain. Two different mouse strains with variable ability to control retinal infection were studied in order to describe protective and deleterious reaction patterns. In Swiss-Webster mice, which are already relatively resistant to primary infection, no peak of parasite load was observed upon reinfection. In contrast, the susceptible inbred strain C57BL/6 showed high parasite loads after 7 days, as well as marked deterioration of retinal architecture. Both parameters were back to normal on day 21. C57BL/6 mice also reacted with a strong local production of inflammatory and Th1-type cytokines, like interleukin-6 (IL-6), IL-17A, and gamma interferon (IFN-γ), while Swiss-Webster mice showed only moderate expression of the Th2 cytokine IL-31. Interestingly, rapid intraocular production of anti-Toxoplasma antibodies was observed in Swiss-Webster but not in C57BL/6 mice. We then localized the cellular source of different immune mediators within the retina by immunofluorescence. Finally, neutralization experiments of IFN-γ or IL-6 demonstrated the respective protective and deleterious roles of these cytokines for parasite control and retinal integrity during reinfection. In conclusion, we developed and immunologically characterized a promising mouse model of reactivating ocular toxoplasmosis.
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Interleucina-6/imunologia , Retina/patologia , Toxoplasma/imunologia , Toxoplasmose Ocular/imunologia , Toxoplasmose Ocular/patologia , Animais , Modelos Animais de Doenças , Feminino , Interferon gama/metabolismo , Interleucina-17/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Carga Parasitária , Fatores de Tempo , Toxoplasmose Ocular/parasitologiaRESUMO
PVL (Panton-Valentine leukocidin) and other Staphylococcus aureus ß-stranded pore-forming toxins are important virulence factors involved in various pathologies that are often necrotizing. The present study characterized leukotoxin inhibition by selected SCns (p-sulfonato-calix[n]arenes): SC4, SC6 and SC8. These chemicals have no toxic effects on human erythrocytes or neutrophils, and some are able to inhibit both the activity of and the cell lysis by leukotoxins in a dose-dependent manner. Depending on the type of leukotoxins and SCns, flow cytometry revealed IC50 values of 6-22 µM for Ca2+ activation and of 2-50 µM for cell lysis. SCns were observed to affect membrane binding of class S proteins responsible for cell specificity. Electrospray MS and surface plasmon resonance established supramolecular interactions (1:1 stoichiometry) between SCns and class S proteins in solution, but not class F proteins. The membrane-binding affinity of S proteins was Kd=0.07-6.2 nM. The binding ability was completely abolished by SCns at different concentrations according to the number of benzenes (30-300 µM; SC8>SC6â«SC4). The inhibitory properties of SCns were also observed in vivo in a rabbit model of PVL-induced endophthalmitis. These calixarenes may represent new therapeutic avenues aimed at minimizing inflammatory reactions and necrosis due to certain virulence factors.
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Calixarenos/farmacologia , Exotoxinas/antagonistas & inibidores , Exotoxinas/metabolismo , Staphylococcus aureus/metabolismo , Animais , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/metabolismo , Calixarenos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/metabolismo , Humanos , Substâncias Macromoleculares/metabolismo , Modelos Biológicos , Fenóis/metabolismo , Fenóis/farmacologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Coelhos , Esfingomielina Fosfodiesterase/antagonistas & inibidores , Esfingomielina Fosfodiesterase/metabolismo , Staphylococcus aureus/patogenicidade , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/metabolismoRESUMO
Panton-Valentine leukocidin (PVL) is a pore-forming toxin associated with current outbreaks of community-associated methicillin-resistant strains and implicated directly in the pathophysiology of Staphylococcus aureus-related diseases. Humanized heavy chain-only antibodies (HCAb) were generated against S. aureus PVL from immunized transgenic mice to neutralize toxin activity. The active form of PVL consists of the two components, LukS-PV and LukF-PV, which induce osmotic lysis following pore formation in host defense cells. One anti-LukS-PV HCAb, three anti-LukF-PV HCAbs with affinities in the nanomolar range, and one engineered tetravalent bispecific HCAb were tested in vitro and in vivo, and all prevented toxin binding and pore formation. Anti-LukS-PV HCAb also binds to γ-hemolysin C (HlgC) and inhibits HlgC/HlgB pore formation. Experiments in vivo in a toxin-induced rabbit endophthalmitis model showed that these HCAbs inhibit inflammatory reactions and tissue destruction, with the tetravalent bispecific HCAb performing best. Our findings show the therapeutic potential of HCAbs, and in particular, bispecific antibodies.
Assuntos
Anticorpos Biespecíficos/imunologia , Anticorpos Neutralizantes/imunologia , Exotoxinas/imunologia , Cadeias Pesadas de Imunoglobulinas/imunologia , Staphylococcus aureus/metabolismo , Sequência de Aminoácidos , Animais , Anticorpos Biespecíficos/química , Anticorpos Neutralizantes/química , Afinidade de Anticorpos , Especificidade de Anticorpos , Ensaio de Imunoadsorção Enzimática , Humanos , Cadeias Pesadas de Imunoglobulinas/química , Dados de Sequência Molecular , Coelhos , Homologia de Sequência de AminoácidosRESUMO
OBJECTIVE: To evaluate the macular microvascular changes using optical coherence tomographic angiography (OCT-A) in children with unilateral amblyopia and their reversibility during treatment. METHODS: Patients with unilateral strabismic or anisometropic amblyopia or residual amblyopia from early congenital cataract surgery, examined between October 2019 and March 2021, were included. Vessel density and perfusion density in the superficial capillary plexus and area, perimeter and circularity of the foveal avascular zone (FAZ) were analysed using OCT-A in amblyopic eyes, contralateral eyes and control group healthy eyes. Correlation analyses between the microvascular parameters and the visual acuity were performed. In a pilot study on a few patients from the amblyopic cohort, longitudinal follow-up during treatment was also performed. RESULTS: A total of 128 eyes of 64 patients were included: 32 amblyopic eyes compared with 32 contralateral eyes and 64 control eyes. Vessel density and perfusion density in the superficial capillary plexus were significantly lower in amblyopic eyes compared to control eyes in 6 × 6â mm (p < 0.02) and 3 × 3â mm (p < 0.01) scans. Correlation analyses showed a linear decrease in vessel density and perfusion density with decreasing visual acuity. The microvascular changes observed were reversible with the occlusion treatment of amblyopia (p < 0.001). CONCLUSIONS: The study found a decrease in vessel density and perfusion density in the macula of children with unilateral functional amblyopia. These microvascular changes were correlated with visual acuity and appeared to be reversible with treatment of amblyopia. On the whole, OCT-A appears to be a relevant complementary examination when it comes to diagnosing and monitoring functional amblyopia.
Assuntos
Ambliopia , Macula Lutea , Criança , Humanos , Ambliopia/diagnóstico , Ambliopia/terapia , Fóvea Central/irrigação sanguínea , Vasos Retinianos , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia/métodos , Seguimentos , Projetos Piloto , Estudos TransversaisRESUMO
Purpose: To report the effect of internal limiting membrane (ILM) peeling prior to Voretigen Neparvovec-ryzl (VN) subretinal injection on focal chorioretinal atrophy development in patients presenting with RPE65-mediated Leber congenital amaurosis (LCA). Design: Retrospective case series. Methods: Three patients who underwent bilateral subretinal VN injection for RPE65-mediated LCA were followed up for 18-24 months. ILM peeling was performed unilaterally in patients 1 and 2 and bilaterally in patient 3. Chorioretinal atrophy was identified on fundus biomicroscopy, non-mydriatic retinography and/or ultrawide field fundus imaging. Best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), visual fields, full-field stimulus threshold (FST) and visual functioning questionnaire score (NEI-VFQ-25) were reported. Outcome measures were changes in BCVA, visual fields, FST, NEI-VFQ-25, and chorioretinal atrophy location. Results: Chorioretinal atrophy at the injection site exclusively developed in eyes which did not undergo prior ILM peeling. In patient 3, bilateral pre-operative nummular chorioretinal alterations progressed toward epithelial atrophic patches in the mid and extreme retinal periphery 18 months after VN injection. BCVA and visual fields improved bilaterally. NEI_VFQ 25 remained stable in patient 1 and improved in patient 2 and 3. FST test improved bilaterally in patient 3. Conclusions: ILM peeling prior to VN injection seems to be a smoother and safer technique to administer VN treatment and may prevent secondary focal atrophy development at the injection site. However, another type of more extended chorioretinal atrophy might exist and could be related to LCA evolution or to incompletely understood adverse effect of VN product.