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1.
J Allergy Clin Immunol ; 150(3): 631-639, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35390403

RESUMEN

BACKGROUND: Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti-sialic acid-binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. OBJECTIVE: We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. METHODS: Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. RESULTS: Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (-61%; 95% CI, -75% to -48%) and Ocular Symptom Scores (-53%; 95% CI, -76% to -31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with -55% (95% CI, -78% to -31%), -50% (95% CI, -82% to -19%), and -63% (95% CI, -87% and -38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. CONCLUSIONS: Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears.


Asunto(s)
Antineoplásicos , Conjuntivitis Alérgica , Enfermedad Injerto contra Huésped , Queratoconjuntivitis , Antineoplásicos/efectos adversos , Conjuntivitis Alérgica/diagnóstico , Conjuntivitis Alérgica/tratamiento farmacológico , Ojo , Humanos , Calidad de Vida , Lágrimas
2.
Curr Opin Ophthalmol ; 31(4): 247-252, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32412958

RESUMEN

PURPOSE OF REVIEW: Autoimmune and immune-mediated diseases are considered contraindications for laser refractive surgeries according to the US Food and Drug Administration's guideline. This guideline, however, is based on limited case reports or complications reported during other intraocular procedures. There have been only a handful of new clinical studies that evaluate the efficacy and safety of refractive surgery in this specific patient population. The aim of this article is to review currently available research and offer updated recommendations for the evaluation and management of laser refractive surgery (LRS) in patients with autoimmune diseases. RECENT FINDINGS: More recent retrospective studies have reported good refractive outcomes in patients with well controlled autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, among others. No severe sight-threatening complications have been reported in these reports. Although postoperative complications occur, the risk of refractive surgery is comparable with those without autoimmune diseases. SUMMARY: With the exception of primary Sjogren's syndrome, patients with autoimmune diseases may be good candidates for LRS if diseases are well controlled and have minimal ophthalmic manifestation. Patients should be made aware of the potential surgical complications and be informed of the currently available data. More multicenter and larger prospective studies are needed to compare the refractive outcomes and surgical complications in patients with and without autoimmune diseases. This will help patients make better informed medical decisions.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Oftalmopatías/complicaciones , Procedimientos Quirúrgicos Refractivos , Humanos
3.
N Engl J Med ; 375(10): 932-43, 2016 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-27602665

RESUMEN

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo. (Funded by AbbVie; VISUAL I ClinicalTrials.gov number, NCT01138657 .).


Asunto(s)
Adalimumab/uso terapéutico , Uveítis/tratamiento farmacológico , Adalimumab/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Insuficiencia del Tratamiento , Trastornos de la Visión/prevención & control , Adulto Joven
4.
Retina ; 37(4): 662-666, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-27429380

RESUMEN

PURPOSE: To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. METHODS: Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. RESULTS: Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. CONCLUSION: Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.


Asunto(s)
Endoftalmitis , Infecciones Bacterianas del Ojo/complicaciones , Infecciones Fúngicas del Ojo/complicaciones , Queratitis , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Endoftalmitis/etiología , Endoftalmitis/microbiología , Endoftalmitis/terapia , Infecciones Bacterianas del Ojo/microbiología , Infecciones Bacterianas del Ojo/terapia , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/terapia , Femenino , Humanos , Queratitis/complicaciones , Queratitis/microbiología , Queratitis/terapia , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Oftalmológicos , Estudios Retrospectivos , Factores de Riesgo , Agudeza Visual
5.
Retina ; 36(7): 1237-43, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27243928

RESUMEN

PURPOSE: The authors aimed to analyze the causes and outcomes of golf-related ocular injuries in this retrospective meta-analysis, literature review, and original case series. METHODS: Forty-one articles identified by PubMed search resulted in 11 included studies yielding 102 subjects. Included articles described all ocular golf injuries that presented to an institution during a determined period. Eight factors were analyzed: age, sex, location and mechanism of injury, protective eyewear use, resulting open-globe injury, resulting enucleation, and visual acuity changes. RESULTS: No subjects wore adequate protective eyewear. Significantly more subjects were injured by golf balls (72%) than golf clubs (27%) or foreign body (1%) (P < 0.0001). The ratio of golf ball to club injuries was significantly higher in adults (92%) than in children (23%) (P < 0.0001). Forty-seven of 93 (51%) injuries resulted in an open globe, whereas 27/82 (33%) injuries resulted in enucleation. The mean ± SD logMAR visual acuity improved by -0.641 ± 0.745 after treatment (>6 lines of improvement; P = 0.0001). CONCLUSION: Reported ocular golf injuries occur less frequently than other ocular sports injuries, but may result in devastating outcomes. Supervision of children using golf equipment should be encouraged.


Asunto(s)
Lesiones Oculares/etiología , Golf/lesiones , Enucleación del Ojo/estadística & datos numéricos , Dispositivos de Protección de los Ojos/estadística & datos numéricos , Humanos , Factores de Riesgo , Agudeza Visual/fisiología
6.
Eye Contact Lens ; 41(4): 210-3, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25503906

RESUMEN

OBJECTIVE: To evaluate the use of topical cyclosporine A (CSA) 1% in the treatment of chronic follicular conjunctivitis (CFC). METHODS: Retrospective chart review from 2001 to 2012 identified 12 patients (22 eyes) with CFC (mean ± standard deviation [SD] age, 50.2 ± 15.4 years; 75% female; 92% white) treated with CSA. Main outcome measures included inflammation grade, visual acuity, concurrent corticosteroid (CS) therapy, effect on CS taper, and adverse effects. RESULTS: Mean ± SD follow-up time was 11.7 ± 9.7 months. Mean ± SD time from diagnosis to CSA treatment initiation was 2.4 ± 3.2 months. Mean ± SD duration of CSA treatment was 5.8 ± 2.8 months. Four patients (33%) complained of irritation (n = 2), redness (n = 1), itching (n = 1), and burning (n = 1) but none discontinued treatment. Concurrent CSs were tapered off in all patients after a mean ± SD of 5.0 ± 2.5 weeks. Mean ± SD initial vision was 0.078 ± 0.093 logMAR, whereas vision at final examination was 0.056 ± 0.081 logMAR (P = 0.02). Mean ± SD initial inflammation grade of 1.9 ± 1.0 was significantly reduced to final grade of 0.7 ± 0.9 (P = 0.0002). Mean ± SD time to initial inflammation control in 9 patients (75%) was 33.2 ± 24.5 days. Two patients (17%) switched to oral CSA because of lack of inflammation control. CONCLUSIONS: Topical CSA 1% is an effective and well-tolerated therapy that decreased chronic inflammation and tapered topical CS in patients with CFC. The use of CSA in such patients warrants further investigation.


Asunto(s)
Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Queratoconjuntivitis/tratamiento farmacológico , Soluciones Oftálmicas/uso terapéutico , Administración Tópica , Adulto , Anciano , Ciclosporina/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Agudeza Visual
7.
Eye Contact Lens ; 40(5): 283-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25083780

RESUMEN

OBJECTIVE: To evaluate the use of topical cyclosporine A (CsA) 1% emulsion in the treatment of chronic ocular surface inflammation (OSI). METHODS: We conducted a retrospective chart review of patients with various forms of OSI treated with topical CsA 1% from 2001 to 2012. RESULTS: Twenty-nine patients (52 eyes) with various forms of OSI, including epidemic keratoconjunctivitis (n=14), chronic follicular conjunctivitis (n=12), Thygeson superficial punctate keratopathy (n=2), and vernal keratoconjunctivitis (n=1), were included. Twenty-seven patients had inflammation refractory to prior therapies. Twenty-four patients received concurrent medications with CsA 1%. Twenty-three of 24 patients on concurrent corticosteroids (CS) were able to taper their use while receiving CsA 1%. Thirteen patients experienced ocular discomfort with CsA 1%; one patient discontinued therapy all together as a result of these side effects; another switched to CsA 0.5% with improvement of adverse symptoms. Inflammation was controlled in 22 (92%) of the 24 patients who received CsA 1% for at least 2 months in duration. CONCLUSION: Topical CsA 1% helps to control inflammation and spares CS use in patients with chronic OSI.


Asunto(s)
Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Queratoconjuntivitis/tratamiento farmacológico , Administración Tópica , Adolescente , Adulto , Anciano , Niño , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas/uso terapéutico , Estudios Retrospectivos , Adulto Joven
8.
Indian J Ophthalmol ; 72(Suppl 2): S248-S253, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38146973

RESUMEN

PURPOSE: To study the long-term clinical outcome and treatment strategies of recurrent and chronic non-infectious anterior uveitis. METHODS: Multicenter study of anterior uveitis patients from 2001 to 2022. Outcome measures included ocular complications, medical and surgical therapies, and visual acuity measured at the beginning of follow-up and at 1, 2, and 5 years thereafter. RESULTS: In total, 76 patients were included, with a mean follow-up of 6.8 years. Idiopathic anterior uveitis was the most common etiology (56%). Immunomodulatory agents (IMAs) were used in almost half of the cohort. Early initiation of IMAs was associated with a lower risk of developing glaucoma ( P = 0.019). Mean best corrected visual acuity (BCVA) improved after 5 years in both groups. Early use of immunomodulation was correlated with a better visual outcome at 2 years ( P = 0.024). CONCLUSION: Chronic and recurrent anterior uveitis were associated with greater risk than expected for ocular complications, surgeries, and vision impairment. Early initiation of immunomodulation should be strongly considered to improve clinical course and outcome.


Asunto(s)
Glaucoma , Uveítis Anterior , Uveítis , Humanos , Estudios de Seguimiento , Estudios Retrospectivos , Uveítis Anterior/diagnóstico , Uveítis Anterior/terapia , Enfermedad Crónica , Glaucoma/complicaciones , Uveítis/complicaciones , Resultado del Tratamiento
9.
JAMA Ophthalmol ; 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39023880

RESUMEN

Importance: Noninfectious uveitis is a leading cause of visual impairment with an unmet need for additional treatment options. Objective: To assess the efficacy and safety of filgotinib, a Janus kinase 1 (JAK1) preferential inhibitor, for the treatment of noninfectious uveitis. Design, Setting, and Participants: The HUMBOLDT trial was a double-masked, placebo-controlled, phase 2, randomized clinical trial conducted from July 2017 to April 2021 at 26 centers in 7 countries. Eligible participants (aged ≥18 years) had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite at least 2 weeks of treatment with oral prednisone (10-60 mg per day). Interventions: Participants were randomly assigned 1:1 to receive filgotinib, 200 mg, or placebo orally once daily for up to 52 weeks. Main Outcomes and Measures: The primary end point was the proportion of participants experiencing treatment failure by week 24. Treatment failure was a composite end point represented by assessment of the presence of chorioretinal and/or retinal vascular lesions, best-corrected visual acuity, and anterior chamber cell and vitreous haze grades. Safety was assessed in participants who received at least 1 dose of study drug or placebo. Results: Between July 26, 2017, and April 22, 2021, 116 participants were screened, and 74 (mean [SD] age, 46 [16] years; 43 female [59.7%] of 72 participants, as 2 participants did not receive treatment doses) were randomly assigned to receive filgotinib (n = 38) or placebo (n = 36). Despite early termination of the trial for business reasons ahead of meeting enrollment targets, a significantly reduced proportion of participants who received filgotinib experienced treatment failure by week 24 vs placebo (12 of 32 participants [37.5%] vs 23 of 34 participants [67.6%]; difference vs placebo -30.1%; 95% CI, -56.2% to -4.1%; P = .006). Business reasons were unrelated to efficacy or safety. Adverse events were reported in 30 of 37 participants (81.1%) who received filgotinib and in 24 of 35 participants (68.6%) who received placebo. Serious adverse events were reported in 5 of 37 participants (13.5%) in the filgotinib group and in 2 of 35 participants (5.7%) in the placebo group. No deaths were reported during the trial. Conclusions and Relevance: Results of this randomized clinical trial show that filgotinib lowered the risk of treatment failure in participants with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis vs placebo. Although the HUMBOLDT trial provided evidence supporting the efficacy of filgotinib in patients with active noninfectious uveitis, the premature termination of the trial prevented collection of additional safety or efficacy information of this JAK1 preferential inhibitor. Trial Registration: ClinicalTrials.gov Identifier: NCT03207815.

10.
Acc Chem Res ; 45(7): 1089-99, 2012 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-22242774

RESUMEN

Therapeutic gene delivery can alter protein function either through the replacement of nonfunctional genes to restore cellular health or through RNA interference (RNAi) to mask mutated and harmful genes. Researchers have investigated a range of nucleic acid-based therapeutics as potential treatments for hereditary, acquired, and infectious diseases. Candidate drugs include plasmids that induce gene expression and small, interfering RNAs (siRNAs) that silence target genes. Because of their self-assembly with nucleic acids into virus-sized nanoparticles and high transfection efficiency in vitro, cationic polymers have been extensively studied for nucleic acid delivery applications, but toxicity and particle stability have limited the clinical applications of these systems. The advent of living free radical polymerization has improved the quality, control, and reproducibility of these synthesized materials. This process yields well-defined, narrowly disperse materials with designed architectures and molecular weights. As a result, researchers can study the effects of polymer architecture and molecular weight on transfection efficiency and cytotoxicity, which will improve the design of next-generation vectors. In this Account, we review findings from structure-function studies that have elucidated key design motifs necessary for the development of effective nucleic acid vectors. Researchers have used robust methods such as atom transfer radical polymerization (ATRP), reverse addition-fragmentation chain transfer polymerization (RAFT), and ring-opening metastasis polymerization (ROMP) to engineer materials that enhance extracellular stability and cellular specificity and decrease toxicity. In addition, we discuss polymers that are biodegradable, form supramolecular structures, target specific cells, or facilitate endosomal release. Finally, we describe promising materials with a range of in vivo applications from pulmonary gene delivery to DNA vaccines.


Asunto(s)
Radicales Libres/química , Ácidos Nucleicos/metabolismo , Polímeros/química , Animales , Ratones , Ácidos Nucleicos/genética , Plásmidos/genética , Plásmidos/metabolismo , Polimerizacion , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transfección
11.
Eye Contact Lens ; 39(2): 186-7, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21912259

RESUMEN

OBJECTIVE: To describe a case of Haemophilus influenza endophthalmitis after pterygium surgery. METHOD: Retrospective case report. RESULTS: A 50-year-old Hispanic male underwent a pterygium excision with amniotic membrane graft (AMG) and 0.02% MMC. He presented 3.5 months later with severe pain, yellow-white discharge, and decreased visual acuity for several days, and conjunctival injection for 3 months. Repair of perforation with a corneal graft was performed. Intravitreal antibiotics were administered. Many ß-lactamase negative H. influenza organisms were cultured from the vitreous aspirate. The vitritis significantly improved and hypopyon resolved over the next week. The patient underwent surgery for a combined tractional and rhegmatogenous RD 9 days later. The endophthalmitis resolved; however, he developed proliferative vitreoretinopathy (PVR) with redetached retina 21 days after the initial RD repair. He underwent subsequent surgery. Six months later, AMG was performed for recurrent corneal erosion with a large epithelial defect. At last follow-up, the vision remains at hand motions, the retina is flat, there is mild corneal decompensation, the eye is soft to palpation, and there are signs of early phthisis. CONCLUSIONS: A prospective study to identify the optimal concentration and period of application for MMC, as well as patient characteristics resulting in the highest clinical benefit-to-risk ratio may be warranted.


Asunto(s)
Endoftalmitis/microbiología , Infecciones Bacterianas del Ojo/microbiología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/aislamiento & purificación , Complicaciones Posoperatorias/microbiología , Pterigion/cirugía , Humanos , Masculino , Persona de Mediana Edad
12.
Eye Contact Lens ; 39(3): e7-11, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-22683916

RESUMEN

PURPOSE: To report the clinical use of ProKera (Bio-Tissue, Inc., Miami, FL) under topical anesthesia in an outpatient for the management of ocular manifestations of acute Stevens-Johnson syndrome (SJS). METHODS: Interventional case report. RESULTS: A 19-year-old woman developed acute SJS with ocular involvement after ingestion of oral antibiotics. Slit-lamp examination performed 2 weeks later showed severe inflammation and areas of ulceration along all 4 lids and complete, bilateral sloughing of bulbar and palpebral conjunctivae, including the limbus. ProKera was placed under topical anesthesia without sedation in both eyes instead of an amniotic membrane due to excess risk of general anesthesia. Three weeks after placement, slit-lamp examination showed complete re-epithelialization of both corneas and conjunctivae, with only trace conjunctival injection and minor limbal epithelial irregularities. Three months postprocedure, there were no signs of clinically significant scarring, and the visual acuity (VA) was 20/20 bilaterally. Fourteen months postprocedure, VA remained stable, and the patient did not have dry eye, photophobia, clinically significant scarring, or symblepharon. CONCLUSIONS: ProKera placement performed under topical anesthesia may be appropriate for the treatment of ocular surface manifestations of acute SJS particularly in those patients followed in an outpatient setting with milder forms of disease and/or with contraindications to general anesthesia.


Asunto(s)
Amnios/trasplante , Enfermedades de la Conjuntiva/cirugía , Enfermedades de la Córnea/cirugía , Síndrome de Stevens-Johnson/complicaciones , Enfermedad Aguda , Enfermedades de la Conjuntiva/etiología , Enfermedades de la Córnea/etiología , Femenino , Humanos , Resultado del Tratamiento , Adulto Joven
13.
IDCases ; 33: e01839, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37645532

RESUMEN

Pseudomonas aeruginosa is one of the common gram-negative organisms that cause severe invasive infections in different organ systems. P. aeruginosa has unique intrinsic mechanisms to develop antimicrobial resistance quickly, making it extremely difficult to treat. We report a case of extensively drug-resistant (XDR) P. aeruginosa panophthalmitis due to contaminated artificial tears. This report investigates the role of systemic and intravitreal antimicrobials, summarizes the resistance mechanisms of P. aeruginosa, and provides an overview on cefiderocol, a novel antimicrobial that targets multidrug-resistant (MDR) and XDR Gram-negative pathogens.

14.
J Am Chem Soc ; 134(40): 16554-7, 2012 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-23013485

RESUMEN

Adaptation of in vitro optimized polymeric gene delivery systems for in vivo use remains a significant challenge. Most in vivo applications require particles that are sterically stabilized, which significantly compromises transfection efficiency of materials shown to be effective in vitro. We present a multifunctional well-defined block copolymer that forms particles useful for cell targeting, reversible shielding, endosomal release, and DNA condensation. We show that targeted and stabilized particles retain transfection efficiencies comparable to the nonstabilized formulations. A novel, double-head agent that combines a reversible addition-fragmentation chain transfer agent and an atom transfer radical polymerization initiator through a disulfide linkage is used to synthesize a well-defined cationic block copolymer containing a hydrophilic oligoethyleneglycol and a tetraethylenepentamine-grafted polycation. This material effectively condenses plasmid DNA into salt-stable particles that deshield under intracellular reducing conditions. In vitro transfection studies show that the reversibly shielded polyplexes afford up to 10-fold higher transfection efficiencies than the analogous stably shielded polymer in four different mammalian cell lines. To compensate for reduced cell uptake caused by the hydrophilic particle shell, a neuron-targeting peptide is further conjugated to the terminus of the block copolymer. Transfection of neuron-like, differentiated PC-12 cells demonstrates that combining both targeting and deshielding in stabilized particles yields formulations that are suitable for in vivo delivery without compromising in vitro transfection efficiency and are thus promising carriers for in vivo gene delivery applications.


Asunto(s)
ADN/administración & dosificación , Etilenodiaminas/química , Neuronas/metabolismo , Plásmidos/administración & dosificación , Polietilenglicoles/química , Transfección , Animales , Línea Celular , ADN/farmacocinética , Endocitosis , Humanos , Neuronas/citología , Péptidos/química , Péptidos/metabolismo , Plásmidos/farmacocinética , Poliaminas/química , Polielectrolitos , Polimerizacion , Ratas
15.
J Curr Glaucoma Pract ; 16(3): 205-207, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36793260

RESUMEN

Aim: To report a case of uveitis-glaucoma-hyphema (UGH) syndrome secondary to a tilted toric intraocular lens (IOL). Background: Over the past few decades, upgrades in lens design, surgical techniques, and posterior chamber IOLs have drastically decreased the incidence of UGH syndrome. We present a rare case of UGH syndrome developing 2 years after a seemingly uneventful cataract surgery and its subsequent management. Case description: A 69-year-old female presented with episodes of sudden visual disturbance in her right eye 2 years after a seemingly uneventful cataract surgery with placement of a toric IOL. Workup included ultrasound biomicroscopy (UBM), which revealed a tilted IOL and confirmed haptic-induced iris transillumination defects consistent with the diagnosis of UGH syndrome. The patient underwent surgical repositioning of the IOL, which led to the resolution of UGH. Conclusion: Uuveitis-glaucoma-hyphema developed from a tilted toric IOL inducing posterior iris chaffing. Careful examination and UBM revealed the IOL and haptic out of the bag position, which was critical in determining the underlying UGH mechanism. The surgical intervention led to the resolution of UGH syndrome. Clinical significance: In patients with a history of uneventful cataract surgery who develop UGH-like symptoms, continued examination of implant orientation and haptic position is critical in preventing the need for future procedures. How to cite this article: Zhou B, Bekerman VP, Chu DS, et al. Late Onset Uveitis-glaucoma-hyphema Syndrome with Out-the-bag Placement of Intraocular Lens. J Curr Glaucoma Pract 2022;16(3):205-207.

16.
Cornea ; 41(1): 45-51, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34050065

RESUMEN

PURPOSE: The purpose of this study was to report the clinical course and outcome of patients with refractory ocular mucous membrane pemphigoid (MMP) treated by repository corticotropin injection (RCI). METHODS: Patients with biopsy-proven ocular MMP treated with RCI from 3 tertiary medical centers were evaluated. Medical records between January 2013 and January 2021 were reviewed and deidentified to retrieve relevant disease-related data. Primary outcome measures included conjunctival inflammatory activity, change in Foster clinical conjunctival scarring staging after RCI treatment, and the development of ocular and systemic complications. RESULTS: Included were 15 patients (10 women and 5 men; 36-95 yrs of age) with a mean follow-up of 4.5 years. Most of the patients (80%) had Foster stage 3 at presentation, and all patients had active MMP. Each patient had failed to respond to at least 1 immunomodulatory drug during the follow-up, and 9 (60%) patients had treatment failure of at least 2 other agents before the use of RCI. The mean duration of RCI treatment was 21 months (range, 3-54 mo). Foster stage did not change in any of the 15 patients at the last follow-up. Nine patients continued RCI therapy at the last follow-up, and in all of them, the disease activity of MMP was well controlled. No serious adverse events because of RCI were documented during the follow-up in any treated patient. CONCLUSIONS: RCI may serve as an alternative or an adjunctive treatment in patients with severe and refractory ocular MMP. Treatment with RCI seems to be safe and well-tolerated.


Asunto(s)
Hormona Adrenocorticotrópica/administración & dosificación , Conjuntiva/patología , Penfigoide Benigno de la Membrana Mucosa/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Hormonas/administración & dosificación , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Penfigoide Benigno de la Membrana Mucosa/diagnóstico , Estudios Retrospectivos , Microscopía con Lámpara de Hendidura , Resultado del Tratamiento
17.
Ocul Surf ; 19: 38-42, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33264685

RESUMEN

PURPOSE: To report occurrence of cicatrizing conjunctivitis as an extraglandular ocular manifestation of primary Sjögren's syndrome (SS). METHODS: Medical charts of all patients with SS evaluated at two tertiary ophthalmological referral centers were reviewed. Patients who demonstrated clinical findings of cicatrizing conjunctivitis were included in this review. Patient and disease-related data including ocular complications, therapies and outcomes were collected. RESULTS: Eight patients with a diagnosisis of SS were noted to have cicatrizing conjunctivitis findings over a period of 11 years (between 2009 and 2020). Mean age of patients was 79. All patients had a negative immunoreactant deposition in conjunctival biopsy. Mean follow-up time was 6 years (range, 18-197 months). Three patients had progression of conjunctival scarring. Worsening of vision occurred in 4 patients due to corneal complications, including ulceration, perforation and scarring. CONCLUSIONS: SS is an under-recognized etiology of severe progressive cicatrizing conjunctivitis that can lead to ocular morbidity and loss of vision without appropriate management.


Asunto(s)
Enfermedades de la Conjuntiva , Conjuntivitis , Síndrome de Sjögren , Cicatriz/complicaciones , Cicatriz/patología , Conjuntiva/patología , Conjuntivitis/diagnóstico , Conjuntivitis/etiología , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico
18.
Cornea ; 40(12): 1639-1643, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34173369

RESUMEN

PURPOSE: Proctored surgical instruction has traditionally been taught through in-person interactions in either the operating room or an improvised wet lab. Because of the COVID-19 pandemic, live in-person instruction was not feasible owing to social distancing protocols, so a virtual wet lab (VWL) was proposed and implemented. The purpose of this article is to describe our experience with a VWL as a Descemet membrane endothelial keratoplasty (DMEK) skills-transfer course. This is the first time that a VWL environment has been described for the instruction of ophthalmic surgery. METHODS: Thirteen participant surgeons took part in VWLs designed for DMEK skills transfer in September and October 2020. A smartphone camera adapter and a video conference software platform were the unique media for the VWL. After a didactic session, participants were divided into breakout rooms where their surgical scope view was broadcast live, allowing instructors to virtually proctor their participants in real time. Participants were surveyed to assess their satisfaction with the course. RESULTS: All (100%) participants successfully injected and unfolded their DMEK grafts. Ten of the 13 participants completed the survey. Respondents rated the experience highly favorably. CONCLUSIONS: With the use of readily available technology, VWLs can be successfully implemented in lieu of in-person skills-transfer courses. Further development catering to the needs of the participant might allow VWLs to serve as a viable option of surgical education, currently limited by geographical and social distancing boundaries.


Asunto(s)
Queratoplastia Endotelial de la Lámina Limitante Posterior/educación , Fotograbar/instrumentación , SARS-CoV-2 , Teléfono Inteligente/instrumentación , Cirugía Asistida por Video/educación , Comunicación por Videoconferencia/instrumentación , COVID-19/epidemiología , Sistemas de Computación , Humanos , Oftalmólogos/educación , Programas Informáticos , Encuestas y Cuestionarios , Interfaz Usuario-Computador
19.
Acta Ophthalmol ; 99(6): 669-678, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33751822

RESUMEN

PURPOSE: Diagnosis and management of non-infectious uveitis (NIU), a major cause of blindness worldwide, are challenging. Corticosteroids, the cornerstone of therapy, are not appropriate for long-term use, and while non-biologic and biologic immunomodulators may be used for some patients, data on their efficacy and safety in this population are limited. Repository corticotropin injection (RCI), believed to affect uveitis by multiple mechanisms, has received regulatory approval for treatment of ophthalmic diseases including posterior uveitis, but is not widely used or discussed in guidelines for the management of uveitis and ocular inflammatory diseases. METHODS: The index study employed a modified Delphi process with a panel of 14 US-based ophthalmologists. Consensus recommendations were developed through a series of three questionnaires. Panellists rated statements on a Likert scale from -5 (strongly disagree) to +5 (strongly agree). RESULTS: The Delphi panel provided consensus recommendations on examinations and testing needed for diagnosis, treatment goals, and the use of corticosteroids, as well as the use of non-biologic and biologic immunomodulators. The panel reached consensus that RCI may be considered for posterior and pan-uveitis, and dosing should be individualized for each patient. Dose reduction/discontinuation should be considered for excessive RCI-related toxicity, hyperglycaemia and/or diabetic complications, excessive costs, or remission ≥ 2 years. Patients should be weaned from RCI if uveitis is stable and well controlled. Adverse events during RCI therapy can be managed by appropriate interventions, with dose reduction/discontinuation considered if events are severe or recurrent. CONCLUSIONS: Expert consensus suggests RCI may be an appropriate treatment option for some patients with uveitis when other therapies are ineffective or intolerable.


Asunto(s)
Hormona Adrenocorticotrópica/administración & dosificación , Consenso , Técnica Delphi , Manejo de la Enfermedad , Uveítis/tratamiento farmacológico , Adolescente , Adulto , Niño , Femenino , Hormonas/administración & dosificación , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Oftalmólogos , Uveítis/diagnóstico , Adulto Joven
20.
Eye Contact Lens ; 36(4): 190-4, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20626114

RESUMEN

OBJECTIVES: To examine seven cases of contact lens-related Fusarium keratitis that resulted in therapeutic penetrating keratoplasty, to investigate which factors were associated with favorable versus poor graft outcome in this population. METHODS: Seven patients who underwent corneal transplant after contact lens-related, culture-proven Fusarium keratitis were identified through a retrospective chart review. The cases occurred between September 2005 and January 2006 at the University of Medicine and Dentistry of New Jersey and Wills Eye Hospital. All seven patients had used Bausch and Lomb's ReNu with MoistureLoc. The outcomes studied were graft status, infection recurrence, and 6-month postoperative visual acuity. RESULTS: The rejection rate was 57.1% and the recurrence rate was 28.6% in this study. No eyes were lost to fungal endophthalmitis. In this population, larger ulcer size and a greater total number of medical agents used before and after penetrating keratoplasty were significantly associated with poor outcomes, namely graft rejection and poor visual acuity. In addition, it was noted that the patients who suffered recurrence of infection had both a larger median graft size and a longer median duration of postoperative antifungal use although these results did not reach statistical significance. CONCLUSIONS: Larger ulcer size, larger graft size, a greater number of medical agents used, and a longer duration of postoperative antifungal therapy may be useful parameters in predicting surgical outcomes in patients with fungal keratitis. Further research is needed to validate our results and to elucidate the mechanisms behind graft rejection in the setting of fungal keratitis.


Asunto(s)
Lentes de Contacto/efectos adversos , Infecciones Fúngicas del Ojo/cirugía , Fusarium/aislamiento & purificación , Queratitis/cirugía , Queratoplastia Penetrante/métodos , Adulto , Lentes de Contacto/microbiología , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Femenino , Estudios de Seguimiento , Humanos , Queratitis/diagnóstico , Queratitis/microbiología , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento , Agudeza Visual
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