RESUMEN
Military trainees are at high risk for skin and soft-tissue infections (SSTIs). Although Staphylococcus aureus is associated with purulent SSTI, it is unclear to what degree this pathogen causes nonpurulent cellulitis. To inform effective prevention strategies and to provide novel insights into SSTI pathogenesis, we aimed to determine the etiology of SSTI in this population. We conducted a prospective observational study in US Army Infantry trainees with SSTI (cutaneous abscesses and cellulitis) from July 2012 through December 2014. We used standard microbiology, serology, and high-throughput sequencing to determine the etiology of SSTI. Furthermore, we compared purported risk factors as well as anatomic site colonization for S. aureus. Among 201 SSTI cases evaluated for SSTI risk factors, cellulitis was associated with lower extremity blisters (P = 0.01) and abscess was associated with methicillin-resistant S. aureus (MRSA) colonization (P<0.001). Among the 22 tested cellulitis cases that were part of the microbiome analysis, only 1 leading edge aspirate was culturable (Coagulase-negative Staphylococcus). Microbiome evaluation of aspirate specimens demonstrated that Rhodanobacter terrae was the most abundant species (66.8% average abundance), while abscesses were dominated by S. aureus (92.9% average abundance). Although abscesses and cellulitis share the spectrum of clinical SSTI, the bacterial etiologies as determined by current technology appear distinct. Furthermore, the presence of atypical bacteria within cellulitis aspirates may indicate novel mechanisms of cellulitis pathogenesis. CLINICAL TRIALS REGISTRATION: NCT01105767.
Asunto(s)
Absceso/microbiología , Fenómenos Fisiológicos Bacterianos , Celulitis (Flemón)/microbiología , Infecciones de los Tejidos Blandos/microbiología , Adolescente , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/metabolismo , ADN Bacteriano/química , ADN Bacteriano/aislamiento & purificación , ADN Bacteriano/metabolismo , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Staphylococcus aureus Resistente a Meticilina/fisiología , Microbiota , Personal Militar , Estudios Prospectivos , Factores de Riesgo , Análisis de Secuencia de ADN , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificación , Staphylococcus aureus/fisiología , Adulto JovenRESUMEN
Skin and soft tissue infections (SSTIs) are common in the general population, with increased prevalence among military trainees. Previous research has revealed numerous nasal microbial signatures that correlate with SSTI development and Staphylococcus aureus colonization. Thus, we hypothesized that the ecology of the inguinal, oropharynx, and perianal regions may also be altered in response to SSTI and/or S. aureus colonization. We collected body site samples from 46 military trainees with purulent abscess (SSTI group) as well as from 66 asymptomatic controls (non-SSTI group). We also collected abscess cavity samples to assess the microbial composition of these infections. Samples were analyzed by culture, and the microbial communities were characterized by high-throughput sequencing. We found that the nasal, inguinal, and perianal regions were similar in microbial composition and significantly differed from the oropharynx. We also observed differences in Anaerococcus and Streptococcus abundance between the SSTI and non-SSTI groups for the nasal and oropharyngeal regions, respectively. Furthermore, we detected community membership differences between the SSTI and non-SSTI groups for the nasal and inguinal sites. Compared to that of the other regions, the microbial compositions of the nares of S. aureus carriers and noncarriers were dramatically different; we noted an inverse correlation between the presence of Corynebacterium and the presence of Staphylococcus in the nares. This correlation was also observed for the inguinal region. Culture analysis revealed elevated methicillin-resistant S. aureus (MRSA) colonization levels for the SSTI group in the nasal and inguinal body sites. Together, these data suggest significant microbial variability in patients with SSTI as well as between S. aureus carriers and noncarriers. IMPORTANCE While it is evident that nasal colonization with S. aureus increases the likelihood of SSTI, there is a significant lack of information regarding the contribution of extranasal colonization to the overall risk of a subsequent SSTI. Furthermore, the impact of S. aureus colonization on bacterial community composition outside the nasal microbiota is unclear. Thus, this report represents the first investigation that utilized both culture and high-throughput sequencing techniques to analyze microbial dysbiosis at multiple body sites of healthy and diseased/colonized individuals. The results described here may be useful in the design of future methodologies to treat and prevent SSTIs.
RESUMEN
Cardiovascular disease (CVD) is the leading cause of death in the United States. One-third of these deaths may be preventable through healthy lifestyle choices including diet and physical activity. The Mediterranean diet is associated with reduced cardiovascular mortality, whereas the Dietary Approaches to Stop Hypertension (DASH) eating plan is associated with a reduced risk of coronary artery disease. Substituting dietary saturated fat with polyunsaturated fatty acids is associated with improved cardiovascular outcomes, although exogenous supplementation with omega-3 fatty acids does not improve cardiovascular outcomes. There is an association between increased sodium intake and cardiovascular risk, but reducing dietary sodium has not consistently shown a reduction in cardiovascular risk. Physical activity recommendations for adults are at least 150 minutes of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination. Increases in physical activity by any level are associated with reduced cardiovascular risk. Introducing muscle-strengthening activities at least twice per week in previously inactive adults is associated with improved cardiovascular outcomes. Inactive adults without known CVD can gradually increase activity to a moderate-intensity level without consulting a physician. The U.S. Preventive Services Task Force recommends behavioral counseling to promote healthy diet and physical activity in adults at high risk of CVD. Evidence of benefit for counseling patients at average risk is less established.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Dietoterapia , Ejercicio Físico , Adulto , Educación Médica Continua , Humanos , Factores de Riesgo , Estados UnidosRESUMEN
We describe the selection of reduced chlorhexidine susceptibility during chlorhexidine use in a patient with two episodes of cutaneous USA300 methicillin-resistant Staphylococcus aureus abscess. The second clinical isolate harbors a novel plasmid that encodes the QacA efflux pump. Greater use of chlorhexidine for disease prevention warrants surveillance for resistance.
Asunto(s)
Absceso/tratamiento farmacológico , Proteínas Bacterianas/genética , Desinfectantes/uso terapéutico , Farmacorresistencia Bacteriana/genética , Proteínas de Transporte de Membrana/genética , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Enfermedades Cutáneas Bacterianas/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Absceso/diagnóstico , Absceso/microbiología , Adolescente , Clorhexidina/uso terapéutico , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Personal Militar , Datos de Secuencia Molecular , Plásmidos/genética , Recurrencia , Selección Genética/efectos de los fármacos , Selección Genética/genética , Enfermedades Cutáneas Bacterianas/diagnóstico , Enfermedades Cutáneas Bacterianas/microbiología , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Encuestas y CuestionariosAsunto(s)
Antiinfecciosos Locales/uso terapéutico , Clorhexidina/uso terapéutico , Gastroenteritis/prevención & control , Desinfección de las Manos/métodos , Personal Militar , Enfermedades Cutáneas Bacterianas/prevención & control , Infecciones de los Tejidos Blandos/prevención & control , Enfermedad Aguda , Adolescente , Adulto , Georgia , Promoción de la Salud/métodos , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants (P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus (P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI.
Asunto(s)
Microbiota , Cavidad Nasal/microbiología , Mucosa Nasal/microbiología , Piel/microbiología , Infecciones de los Tejidos Blandos/microbiología , Adolescente , Adulto , Técnicas de Tipificación Bacteriana , Secuencia de Bases , Corynebacterium/aislamiento & purificación , Infecciones por Corynebacterium/inmunología , Infecciones por Corynebacterium/microbiología , Infecciones por Corynebacterium/patología , ADN Bacteriano/genética , Humanos , Masculino , Personal Militar , Proteobacteria/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Piel/inmunología , Piel/patología , Infecciones de los Tejidos Blandos/inmunología , Infecciones de los Tejidos Blandos/patología , Infecciones Cutáneas Estafilocócicas/inmunología , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/patología , Staphylococcus aureus/aislamiento & purificación , Adulto JovenRESUMEN
In a field-based trial among military trainees, personal hygiene measures, including chlorhexidine (CHG) body wash, did not prevent overall and methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTI). We conducted a secondary analysis of anterior nares cultures obtained during the trial to evaluate the impact of hygiene measures on Staphylococcus aureus colonization. A cluster-randomized trial for SSTI prevention was conducted among U.S. Army infantry trainees from May 2010 to January 2012. There were three study groups with incrementally increasing education- and hygiene-based components: standard (S), enhanced standard (ES), and CHG. Anterior nares cultures were obtained from participants to determine the prevalence of S. aureus colonization. A total of 1,706 participants (469 S, 597 ES, and 640 CHG) without SSTI were included in the colonization analysis. Of those randomized to the CHG group, 360 (56.3%) reported frequent use of body wash. Frequent use of body wash had no effect on overall S. aureus colonization (53.3% versus 56.8% among infrequent/nonusers; P=0.25). MRSA colonization prevalence was marginally lower among frequent users (2.5% versus 4.7%; P=0.07). In multivariable analysis, the odds of MRSA colonization were lower among frequent users (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.16 to 0.77). This CHG-associated reduction was not observed when comparing colonization with USA300 to that with non-USA300 types (OR, 0.59; 95% CI, 0.06 to 5.76). Frequent use of CHG body wash was associated with a reduction in MRSA nasal colonization among high-risk military trainees. Topical chlorhexidine may contribute to MRSA SSTI prevention by reducing colonization. However, further studies evaluating the pathogenesis of SSTI are needed. (This study has been registered at ClinicalTrials.gov under registration no. NCT01105767).
Asunto(s)
Antiinfecciosos Locales/uso terapéutico , Clorhexidina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Adolescente , Adulto , Femenino , Humanos , Masculino , Personal Militar/estadística & datos numéricos , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Cutáneas Estafilocócicas/prevención & control , Adulto JovenRESUMEN
OBJECTIVE: Determine the prevalence and relatedness of Staphylococcus aureus anterior nares colonization in individuals with community-associated staphylococcal skin and soft-tissue infection (SSTI). DESIGN: Observational cohort. SETTING: US Army soldiers undergoing infantry training. PARTICIPANTS: Trainees who developed SSTI from May 2010 to January 2012. METHODS: Participants underwent anterior nares culture at the time of presentation for purulent SSTI. We determined the prevalence of S. aureus nasal colonization and strain relatedness between colonizing and clinical isolates with pulsed-field gel electrophoresis (PFGE). RESULTS: We enrolled 1,203 SSTI participants, of whom 508 had culture-confirmed S. aureus SSTI. Overall, 70% (357/508) were colonized with S. aureus. Phenotypically, concordant colonization was more common with methicillin-susceptible S. aureus (MSSA; 56%; 122/218) than methicillin-resistant S. aureus (MRSA) SSTI (41%; 118/290; P < .01). With PFGE, 48% (121 of 254) of clinical-colonizing pairs were indistinguishable, and concordant colonization was more common with MRSA (53%; 92/173) than MSSA SSTI (36%; 29/81; P < .01). Restricting analysis to concomitant MRSA-MRSA or MSSA-MSSA pairs, 92% (92/100) of MRSA SSTI were indistinguishable, and 40% (29/72) MSSA SSTI were indistinguishable (P < .01). All 92 MRSA pairs were USA300. CONCLUSIONS: On the phenotypic level, concordant anterior nares colonization with incident staphylococcal SSTI is more common in MSSA than MRSA; however, the opposite is observed when accounting for molecular typing, and MRSA SSTI displays greater concordance. USA300 was responsible for strain concordance with MRSA SSTI. Studies are needed to examine the roles of nasal and extra-nasal carriage, colonization preceding infection, and increased virulence in the pathogenesis of MRSA SSTI. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01105767.
Asunto(s)
Cavidad Nasal/microbiología , Infecciones de los Tejidos Blandos/microbiología , Infecciones Cutáneas Estafilocócicas/microbiología , Adolescente , Adulto , Estudios de Cohortes , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Electroforesis en Gel de Campo Pulsado , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina , Prevalencia , Infecciones de los Tejidos Blandos/epidemiología , Infecciones Cutáneas Estafilocócicas/epidemiología , Staphylococcus aureus , Adulto JovenAsunto(s)
Antibacterianos/uso terapéutico , Impétigo/tratamiento farmacológico , Administración Tópica , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antiinfecciosos Locales/uso terapéutico , Bacitracina/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Cefalexina/uso terapéutico , Clindamicina/uso terapéutico , Cloxacilina/uso terapéutico , Dicloxacilina/uso terapéutico , Diterpenos , Eritromicina/uso terapéutico , Ácido Fusídico/uso terapéutico , Gentamicinas/uso terapéutico , Humanos , Metaanálisis como Asunto , Mupirocina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Chlorhexidine has been increasingly utilized in outpatient settings to control methicillin-resistant Staphylococcus aureus (MRSA) outbreaks and as a component of programs for MRSA decolonization and prevention of skin and soft-tissue infections (SSTIs). The objective of this study was to determine the prevalence of chlorhexidine resistance in clinical and colonizing MRSA isolates obtained in the context of a community-based cluster-randomized controlled trial for SSTI prevention, during which 10,030 soldiers were issued chlorhexidine for body washing. We obtained epidemiological data on study participants and performed molecular analysis of MRSA isolates, including PCR assays for determinants of chlorhexidine resistance and high-level mupirocin resistance and pulsed-field gel electrophoresis (PFGE). During the study period, May 2010 to January 2012, we identified 720 MRSA isolates, of which 615 (85.4%) were available for molecular analysis, i.e., 341 clinical and 274 colonizing isolates. Overall, only 10 (1.6%) of 615 isolates were chlorhexidine resistant, including three from the chlorhexidine group and seven from nonchlorhexidine groups (P > 0.99). Five (1.5%) of the 341 clinical isolates and five (1.8%) of the 274 colonizing isolates harbored chlorhexidine resistance genes, and four (40%) of the 10 possessed genetic determinants for mupirocin resistance. All chlorhexidine-resistant isolates were USA300. The overall prevalence of chlorhexidine resistance in MRSA isolates obtained from our study participants was low. We found no association between extended chlorhexidine use and the prevalence of chlorhexidine-resistant MRSA isolates; however, continued surveillance is warranted, as this agent continues to be utilized for infection control and prevention efforts.
Asunto(s)
Antiinfecciosos Locales/farmacología , Clorhexidina/farmacología , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Staphylococcus aureus Resistente a Meticilina/genética , Adolescente , Adulto , Técnicas de Tipificación Bacteriana , Electroforesis en Gel de Campo Pulsado , Desinfección de las Manos , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Personal Militar , Mupirocina/farmacología , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & controlRESUMEN
BACKGROUND: Effective measures are needed to prevent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections (SSTIs) in high-risk community settings. The study objective was to evaluate the effect of personal hygiene-based strategies on rates of overall SSTI and MRSA SSTI. METHODS: We conducted a prospective, field-based, cluster-randomized trial in US Army Infantry trainees from May 2010 through January 2012. There were 3 study groups with incrementally increased education and hygiene-based interventions: standard (S), enhanced standard (ES), and chlorhexidine (CHG). The primary endpoints were incidence of overall SSTI and MRSA SSTI. RESULTS: The study included 30 209 trainees constituting 540 platoons (168 S, 192 ES, and 180 CHG). A total of 1203 (4%) participants developed SSTI, 316 (26%) due to MRSA. The overall SSTI rate was 4.15 (95% confidence interval [CI], 3.77-4.58) per 100 person-cycles. SSTI rates by study group were 3.48 (95% CI, 2.87-4.22) for S, 4.18 (95% CI, 3.56-4.90) for ES, and 4.71 (95% CI, 4.03-5.50) for CHG. The MRSA SSTI rate per 100 person-cycles for all groups was 1.10 (95% CI, .91-1.32). MRSA SSTI rates by study group were 1.0 (95% CI, .70-1.42) for S, 1.29 (95% CI, .98-1.71) for ES, and 0.97 (95% CI, .70-1.36) for CHG. CONCLUSIONS: Personal hygiene and education measures, including once-weekly use of chlorhexidine body wash, did not prevent overall SSTI or MRSA SSTI in a high-risk population of military trainees. CLINICAL TRIALS REGISTRATION: NCT01105767.
Asunto(s)
Higiene/normas , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones de los Tejidos Blandos/microbiología , Infecciones de los Tejidos Blandos/prevención & control , Infecciones Cutáneas Estafilocócicas/microbiología , Infecciones Cutáneas Estafilocócicas/prevención & control , Adolescente , Adulto , Desinfección/métodos , Educación en Salud/métodos , Humanos , Incidencia , Masculino , Personal Militar , Estudios Prospectivos , Estados Unidos , Adulto JovenRESUMEN
We describe a cutaneous abscess caused by catalase-negative methicillin-susceptible Staphylococcus aureus subsp. aureus in a patient who was concomitantly colonized with virulent USA300 methicillin-resistant S. aureus (MRSA). Sequencing of the katA gene demonstrated a thymine insertion leading to a frameshift mutation and premature truncation of catalase to 21 amino acids.
Asunto(s)
Absceso/diagnóstico , Absceso/microbiología , Catalasa/genética , Infecciones Cutáneas Estafilocócicas/diagnóstico , Infecciones Cutáneas Estafilocócicas/microbiología , Staphylococcus aureus/enzimología , Staphylococcus aureus/aislamiento & purificación , Codón sin Sentido , Mutación del Sistema de Lectura , Humanos , Masculino , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
Orthostatic hypotension is defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with blood pressure from the sitting or supine position. It results from an inadequate physiologic response to postural changes in blood pressure. Orthostatic hypotension may be acute or chronic, as well as symptomatic or asymptomatic. Common symptoms include dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache. Less common symptoms include syncope, dyspnea, chest pain, and neck and shoulder pain. Causes include dehydration or blood loss; disorders of the neurologic, cardiovascular, or endocrine systems; and several classes of medications. Evaluation of suspected orthostatic hypotension begins by identifying reversible causes and underlying associated medical conditions. Head-up tilt-table testing can aid in confirming a diagnosis of suspected orthostatic hypotension when standard orthostatic vital signs are nondiagnostic; it also can aid in assessing treatment response in patients with an autonomic disorder. Goals of treatment involve improving hypotension without excessive supine hypertension, relieving orthostatic symptoms, and improving standing time. Treatment includes correcting reversible causes and discontinuing responsible medications, when possible. Nonpharmacologic treatment should be offered to all patients. For patients who do not respond adequately to nonpharmacologic treatment, fludrocortisone, midodrine, and pyridostigmine are pharmacologic therapies proven to be beneficial.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Terapia por Ejercicio/métodos , Hipotensión Ortostática , Síncope/complicaciones , Vasoconstrictores/uso terapéutico , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/terapia , Presión Sanguínea , Humanos , Hipotensión Ortostática/etiología , Hipotensión Ortostática/fisiopatología , Hipotensión Ortostática/terapia , Síncope/fisiopatología , Síncope/terapiaRESUMEN
Salzmann's nodular degeneration (subepithelial fibrosis) may cause symptoms of irritation and decreased vision. Removing the subepithelial fibrosis may improve symptoms and vision. In this article, a simple surgical technique to remove the subepithelial fibrosis is described.
Asunto(s)
Enfermedades de la Córnea/cirugía , Epitelio Corneal/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos , Enfermedades de la Córnea/patología , Epitelio Corneal/patología , Fibrosis , Humanos , Procedimientos Quirúrgicos Oftalmológicos/instrumentaciónRESUMEN
PURPOSE: To propose and define the "1, 2, 3" rule as a system of categorizing the severity of bacterial keratitis and to determine its value in predicting the likelihood of visual loss after healing of bacterial corneal infection. METHODS: Seventy patients were evaluated for infectious corneal ulcers by 2 cornea subspecialists (J.D.L., M.C.V.) at a tertiary facility between October 30, 2001, and November 1, 2004. Forty-one patients met the inclusion criteria. Visual acuities, ulcer characteristics, culture results, and treatment data were collected. RESULTS: The sensitivity of the "1, 2, 3" rule for detecting potentially sight-threatening (PST) ulcers that would result in 0.20 logMAR (2 Snellen lines) or greater loss in best spectacle-corrected visual acuity (BSCVA) was 100%. The specificity of the "1, 2, 3" rule in correctly labeling an ulcer that did not cause vision loss as rarely sight threatening (RST) was 57.14%. The positive predictive value of the "1, 2, 3" rule was 28.57%. The negative predictive value of the "1, 2, 3" rule was 100%. CONCLUSIONS: Corneal ulcers classified as PST are at significantly higher risk for sustaining loss of BCSVA compared with RST corneal ulcers. The "1, 2, 3" rule is sensitive and specific enough to be clinically useful in predicting which ulcers are more likely to have vision loss and which ulcers are not.