Efectividad del moxifloxacino intracameral profiláctico para reducir la endoftalmitis posterior a cirugía de cataratas en población chilena / Effectiveness of prophylactic intracameral moxifloxacin to reduce endophthalmitis after cataract surgery

BACKGROUND: Endophthalmitis is a serious infectious complication of cataract surgery, which may lead to vision loss. Aim: To evaluate the effectiveness of intracameral moxifloxacin in reducing endophthalmitis after cataract surgery in Chilean patients. MATERIAL AND METHODS: We reviewed all phacoemulsification surgeries performed between 2012 and 2020 at a public hospital. The use of intraoperative intracameral moxifloxacin and possible surgical complications were recorded. In patients with postoperative endophthalmitis, we reviewed their risk factors and clinical characteristics. RESULTS: In the study, 22,869 phacoemulsification surgeries were registered, with an annual average of 2,541. The use of prophylactic intracameral moxifloxacin started progressively in 2014. In 2018 it was used in 88% of the surgeries. Fifteen eyes evolved with postoperative endophthalmitis, but none of these surgeries used intracameral moxifloxacin. Five and seven cases occurred in 2012 and 2013, respectively. There was a trend favoring moxifloxacin use, as a preventive measure for endophthalmitis, but the difference between groups was not significant (p = 0.56). In the group with endophthalmitis, 33.3% of the eyes were from patients with type 2 diabetes mellitus, in 13.3% there was rupture of the posterior capsule and 60% of the eyes corresponded to female patients. Since 2018 there is no record of endophthalmitis after cataract surgery performed in this center. Conclusions: Intracameral moxifloxacin showed a tendency to reduce the frequency of endophthalmitis after phacoemulsification surgery, but a longer observation period is required to reach statistical significance, due to the low frequency of this complication.

[Accuracy of artificial intelligence compared to trained medical technologists in diabetic retinopathy screening]. / Exactitud de tamizaje de retinopatía diabética: inteligencia artificial versus tecnólogos médicos entrenados.

BACKGROUND: The early detection of retinopathy among diabetics is of utmost importance. AIM: To estimate the diagnostic accuracy of two diabetic retinopathy (DR) screening strategies currently used in the Chilean public health system. MATERIAL AND METHODS: Cross-sectional observational study of 371 diabetic patients aged 61 ± 14 years (61% women) who underwent DR screening at a public Hospital between July 1 and August 31, 2019. The mydriatic retinal photographs of all participants were classified using artificial intelligence software (DART) and trained medical technologists, independently. The precision of both strategies was compared with the reference standard, namely the evaluation of the fundus by an ophthalmologist with a slit lamp. Participants with severe non-proliferative DR or worse were considered as positive cases. The ophthalmologist was blind to the results of the screening tests. RESULTS: Twenty four percent of participants had DR, including 34 (9.2%) who had sight threatening DR in at least one eye. The sensitivity and specificity of DART were 100% (95% confidence intervals (CI): 90-100%) and 55,4% (95% CI: 50-61%), respectively. Medical technologists had a sensitivity of 97,1% (95% CI: 85-100%) and a specificity of 91,7% (95% CI: 88-94%). The only case missed by medical technologists was a patient with unilateral panphotocoagulated DR. CONCLUSIONS: Both strategies had a similar sensitivity to detect cases of sight-threatening DR. However, the specificity of DART was significantly lower compared to medical technologists, which would greatly increase the burden on the health system, a very important aspect to consider in a screening strategy.

Autologous serum compared to artificial tear drops for dry eye disease. / Suero autólogo comparado con lágrimas artificiales para ojo seco.

INTRODUCTION: Dry eye is one of the most common ocular surface disorders. Although artificial tear drops therapy is the most widely used treatment, it has recently been suggested that autologous serum could be a beneficial alternative treatment for this disorder, but its use is controversial. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE/PubMed, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified six systematic reviews, including seven primary studies overall, of which all were randomized trials. We concluded that autologous serum treatment might not lead to adverse effects compared to artificial teardrops, but the certainty of the evidence is low. On the other hand, we are uncertain whether autologous serum therapy improves the quality of life, severity of the pathology, pain or the corneal epitheliopathy grade compared to artificial tear drops as the certainty of the evidence has been assessed as very low.

INTRODUCCIÓN: El ojo seco es una de las patologías oculares más frecuentes. Si bien el tratamiento más utilizado es el uso de lágrimas artificiales, se ha planteado el uso de suero autólogo como una alternativa terapéutica beneficiosa para pacientes con esta condición. Sin embargo, su uso es controvertido. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método Grading of Recommendations Assessment, Development and Evaluation, GRADE. RESULTADOS Y CONCLUSIONES: Identificamos seis revisiones sistemáticas que en conjunto incluyeron siete estudios primarios, de los cuales, todos corresponden a ensayos aleatorizados. Concluimos que el uso de suero autólogo podría no presentar efectos adversos asociados a su uso, pero la certeza de la evidencia es baja. Por otro lado, no es posible establecer con claridad si el uso de suero autólogo tiene un efecto sobre la mejora de la calidad de vida, severidad del ojo seco, dolor o grado de epiteliopatía corneal debido a que la certeza de la evidencia existente ha sido evaluada como muy baja.

Exactitud de tamizaje de retinopatía diabética: inteligencia artificial versus tecnólogos médicos entrenados / Accuracy of artificial intelligence compared to trained medical technologists in diabetic retinopathy screening

Background: The early detection of retinopathy among diabetics is of utmost importance. Aim: To estimate the diagnostic accuracy of two diabetic retinopathy (DR) screening strategies currently used in the Chilean public health system. Material and Methods: Cross-sectional observational study of 371 diabetic patients aged 61 ± 14 years (61% women) who underwent DR screening at a public Hospital between July 1 and August 31, 2019. The mydriatic retinal photographs of all participants were classified using artificial intelligence software (DART) and trained medical technologists, independently. The precision of both strategies was compared with the reference standard, namely the evaluation of the fundus by an ophthalmologist with a slit lamp. Participants with severe non-proliferative DR or worse were considered as positive cases. The ophthalmologist was blind to the results of the screening tests. Results: Twenty four percent of participants had DR, including 34 (9.2%) who had sight threatening DR in at least one eye. The sensitivity and specificity of DART were 100% (95% confidence intervals (CI): 90-100%) and 55,4% (95% CI: 50-61%), respectively. Medical technologists had a sensitivity of 97,1% (95% CI: 85-100%) and a specificity of 91,7% (95% CI: 88-94%). The only case missed by medical technologists was a patient with unilateral panphotocoagulated DR. Conclusions: Both strategies had a similar sensitivity to detect cases of sight-threatening DR. However, the specificity of DART was significantly lower compared to medical technologists, which would greatly increase the burden on the health system, a very important aspect to consider in a screening strategy.

The Role of the Back Plate in Angle Anatomy with the Boston Type I Keratoprosthesis.

PURPOSE: To quantitatively evaluate the angle anatomy in eyes with the Boston type I keratoprosthesis (B-KPro) differing in the back plate (BP) material and size using anterior segment optical coherence tomography. METHODS: B-KPro eyes with poly(methyl methacrylate) (PMMA) (7.0 and 8.5 mm) and titanium (7.0, 8.5, and 9.5 mm) BPs were imaged with anterior segment optical coherence tomography. The angle opening distance at 500 µm from the scleral spur (AOD500), trabecular iris surface area at 500 µm from the scleral spur (TISA500), and trabecular iris angle at 500 µm from the scleral spur (TIA500) were measured. Among the visible quadrants, the average, the temporal, the widest, and the narrowest angle of each eye were included in the analysis. Average time between B-KPro implantation and imaging was 7.5 ± 1.4 years for a PMMA BP and 2.4 ± 2.3 years for a titanium BP (P < 0.0001). RESULTS: We analyzed 17 B-KPro eyes with PMMA BPs and 24 B-KPro eyes with titanium BPs. The average AOD500 (394.1 ± 226.9 vs. 454.5 ± 255.6 µm, P = 0.44), average TIA500 (26.2 ± 14.2 vs. 29.8 ± 13.9 degrees, P = 0.43), and average TISA500 (0.15 ± 0.08 vs. 0.17 ± 0.10 µm, P = 0.52) were not statistically different between eyes with PMMA and titanium BPs, nor were the temporal, the narrowest, and the widest angle measurements of each eye (all P > 0.05). Similarly, no significant differences were found between the angle measurements of B-KPro eyes with a titanium BP diameter of 8.5 or 9.5 mm (all P > 0.05). CONCLUSIONS: We successfully visualized the angle anatomy in 66.1% of the imaged eyes, including all BPs studied. Neither the material nor the size of the B-KPro BP had a significant impact on the angle anatomy.

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease.

In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to those of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, as well as proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

Could single-nucleotide polymorphisms (SNPs) affecting the tumour necrosis factor promoter be considered as part of rheumatoid arthritis evolution?

Tumour necrosis factor (TNF), a cytokine mainly produced by macrophages, is associated with a broad spectrum of biological effects, mainly associated with the host defense against microbes. The TNF gene is located on chromosome six within the major histocompatibility complex (MHC). Rheumatoid arthritis (RA) is a systemic autoimmune disease where TNF plays a central role in its etiology and pathogenesis. Written medical evidence of RA can be traced at least as far back as the 17th century, while human paleopathological studies appear to show the presence of RA prior to this period. The fact that RA has experienced an increment both in severity and mortality could be explained by many causes, particularly the crucial role of the immune system. Single-nucleotide polymorphisms (SNPs) are the most common genetic variations and occur at a frequency of approximately 1 in 1000 bp throughout the genome. The -308 TNF SNP is a mutation that affects the promoter region of the TNF gene. It defines the TNF1 and TNF2 alleles, determining low and high levels of TNF expression, respectively. The presence of the TNF2 allele has also been linked to increased susceptibility to and severity in a variety of autoimmune and inflammatory disorders, including RA, systemic lupus erythematosus, and ankylosing spondylitis. Studies on the functional significance of -308 SNP have detected higher levels of TNF production by cells from TNF2-carrying individuals than cells from TNF1 individuals. This difference does not appear to be due to other genes lying within the MHC region. Since the presence of the TNF2 allele may increase the host's resistance to local infection, by increasing local production of TNF at the infection site, we may suggest that such a mutation has emerged as a selective advantage to carriers of the TNF2 allele. This hypothesis may prove itself by observing the high incidence of tuberculosis and other infectious processes in those patients treated with anti-TNF therapy. Since the human lifespan has increased, the persistence of the TNF2 allele at high frequency in the population now confers what appears to be a marked survival disadvantage. As a result of the disregulation of the immune system, the genetically-predisposed host expresses larger amounts of TNF, leading to chronic inflammatory processes and autoimmune diseases, currently more prevalent. We suggest that RA, a relatively new and increasingly frequent disease, is favored by the presence of the -308 TNF promoter polymorphism, responsible for increased TNF production.

[Emergent therapies for rheumatoid arthritis]. / Terapias emergentes en artritis reumatoide.

The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

Multiple imputation procedures allow the rescue of missing data: an application to determine serum tumor necrosis factor (TNF) concentration values during the treatment of rheumatoid arthritis patients with anti-TNF therapy.

Longitudinal studies aimed at evaluating patients clinical response to specific therapeutic treatments are frequently summarized in incomplete datasets due to missing data. Multivariate statistical procedures use only complete cases, deleting any case with missing data. MI and MIANALYZE procedures of the SAS software perform multiple imputations based on the Markov Chain Monte Carlo method to replace each missing value with a plausible value and to evaluate the efficiency of such missing data treatment. The objective of this work was to compare the evaluation of differences in the increase of serum TNF concentrations depending on the -308 TNF promoter genotype of rheumatoid arthritis (RA) patients receiving anti-TNF therapy with and without multiple imputations of missing data based on mixed models for repeated measures. Our results indicate that the relative efficiency of our multiple imputation model is greater than 98% and that the related inference was significant (p-value < 0.001). We established that under both approaches serum TNF levels in RA patients bearing the G/A -308 TNF promoter genotype displayed a significantly (p-value < 0.0001) increased ability to produce TNF over time than the G/G patient group, as they received successively doses of anti-TNF therapy.

Multiple imputation procedures allow the rescue of missing data: An application to determine serum tumor necrosis factor (TNF) concentration values during the treatment of rheumatoid arthritis patients with anti-TNF therapy

Longitudinal studies aimed at evaluating patients clinical response to specific therapeutic treatments are frequently summarized in incomplete datasets due to missing data. Multivariate statistical procedures use only complete cases, deleting any case with missing data. MI and MIANALYZE procedures of the SAS software perform multiple imputations based on the Markov Chain Monte Carlo method to replace each missing value with a plausible value and to evaluate the efficiency of such missing data treatment. The objective of this work was to compare the evaluation of differences in the increase of serum TNF concentrations depending on the ¡308 TNF promoter genotype of rheumatoid arthritis (RA) patients receiving anti-TNF therapy with and without multiple imputations of missing data based on mixed models for repeated measures. Our results indicate that the relative efficiency of our multiple imputation model is greater than 98 percent and that the related inference was significant (p-value < 0.001). We established that under both approaches serum TNF levels in RA patients bearing the G/A ¡308 TNF promoter genotype displayed a significantly (p-value < 0.0001) increased ability to produce TNF over time than the G/G patient group, as they received successively doses of anti-TNF therapy.

The -308 polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene and ex vivo lipopolysaccharide-induced TNF-alpha expression in patients with aggressive periodontitis and/or type 1 diabetes mellitus.

Several single-nucleotide polymorphisms (SNPs) have been identified in the TNF-alpha gene promoter. The transition G-->A at position -308 generates the TNF-alpha1 (G/G) and TNF-alpha2 (G/A or A/A) alleles, where the polymorphic TNF-alpha2 allele is associated with a high, in vitro TNF-alpha expression and an increased susceptibility to diverse illnesses. Here we study the association of the -308 TNF-alpha SNP with the susceptibility for developing aggressive periodontitis (AP), AP combined with type 1 diabetes mellitus (DM) and DM. We also explore the TNF-alpha capability expression and the presence of the -308 polymorphism. For this purpose we recruited 27 individuals with AP (AP+ group), 27 individuals with AP combined with DM (AP+/DM+ group), and 27 individuals with DM without signs of periodontitis upon clinical examination (DM+ group). The control group was comprised of 30 subjects. Genotyping for TNF-alpha promoter was performed by PCR-RFLP analysis. For TNF-alpha expression we used a blood culture system.

[New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies]. / Nuevas armas inmunológicas para la medicina del siglo XXI: terapia biológica basada en el uso de anticuerpos monoclonales de última generación.

The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.

[Tumor necrosis factor alpha genetic polymorphism as a risk factor in disease]. / El polimorfismo genético del factor de necrosis tumoral alfa como factor de riesgo en patología.

Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNF alpha), among other cytokines, plays a central role. TNF alpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNF alpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNF alpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNF alpha cluster will be important in understanding the role of TNF alpha regulation in specific diseases.