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PURPOSE: To evaluate the association between intraoperative complications of cataract surgery and postoperative mortality. METHODS: A retrospective review of patients who underwent cataract surgery at our institution from 2014 to 2020 was conducted. Intraoperative complications included choroidal hemorrhage, posterior capsule rupture, vitreous loss, retained lens, and/or severe zonular dialysis in either eye. All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Hazard ratios (HRs) from Cox proportional hazard models were used to estimate survival following cataract surgery. RESULTS: Among 8,054 patients, the mean follow-up time was 4.4 (SD = 2.3) years and the mortality rate was 15% (n = 1,175). The overall complication rate was 2.2% (n = 181), and the rate of retained lens was 0.7% (n = 58). In univariate analysis, retained lens (HR: 1.86, 95% CI: 1.08-3.21, p = 0.026), severe zonular dialysis (HR: 2.00, 95% CI: 1.29-3.12, p = 0.002), and any intraoperative complication (HR: 1.51, 95% CI: 1.09-2.11, p = 0.015) were associated with higher hazard of mortality. When adjusted for demographic factors, comorbid medical conditions, and pre-operative visual acuity, intraoperative complications were not associated with mortality. CONCLUSION: Intraoperative cataract surgery complications were associated with mortality in univariate analysis. However, this association was not significant in the multivariable analysis as it is confounded by other factors such as pre-operative visual acuity.
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Introduction: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD. Methods: We examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers. Results: There were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group. Discussion: These findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.
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PURPOSE: To quantify and compare the different prevalence rates of specific retinal imaging biomarkers in patients with intermediate AMD (iAMD) and advanced non-neovascular AMD (nnAMD). METHODS: Cross-sectional study of patients with iAMD and advanced nnAMD. Imaging studies were reviewed for qualitative imaging biomarkers. Choroidal thickness measurements were obtained subfoveally and in 1000â um and 2000â um intervals away from the fovea. The Chi-squared test and Fisher's exact test were used to compare rates of imaging biomarkers among the two cohorts. P-value of <0.05 was considered significant. RESULTS: 376 eyes of 197 patients with iAMD and 187 eyes of 97 patients with advanced nnAMD were recruited. There were significantly lower rates of the following imaging biomarkers in the iAMD compared with the advanced nnAMD cohorts: soft drusen (66.0% vs. 84.2%, p = 0.001), calcified drusen (4.3% vs. 40.0%, p < 0.0001), RPD (26.2% vs. 53.3%, p < 0.0001), ORT (0.5% vs. 46.9%, p < 0.0001), RP (1.1% vs. 46.3%, p < 0.0001), pigment migration (53.2% vs. 100%, p < 0.0001), and iRORA (17.9% vs. 80.2%, p < 0.0001). In the iAMD cohort, choroidal thickness was significantly greater at 188â µm (SD: 60) and 194â µm (SD: 69), compared to the advanced nnAMD with measurements of 153â µm (SD: 68), and 161â µm (SD: 76). This difference was statistically significant (p < 0.0001 and p = 0.0002). CONCLUSIONS: Our results highlight significant differences in imaging biomarkers between both cohorts. Key biomarkers, such as iRORA, RPD, pigment migration, and thinner choroidal thickness, were associated with advanced nnAMD. Identifying these biomarkers early may help target patients who could benefit from new treatments, potentially delaying vision loss.
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PURPOSE: The goal of this study is to describe characteristics of cataract surgery patients who previously underwent laser in situ keratomileusis/photorefractive keratectomy (LASIK/PRK) in comparison to non-LASIK/PRK cataract surgery patients including psychiatric comorbidities, as well as describe refractive prediction error after cataract surgery while accounting for axial length (AL) using the Barrett True-K and Barrett Universal II formulas. METHODS: This was a retrospective study of patients from the University of Colorado Cataract Outcomes Registry. The primary outcomes were refraction prediction error (RPE), mean absolute RPE, and median absolute RPE. Outcomes were stratified by five axial length groups. Univariate and multivariate models for RPE were stratified by the AL group. RESULTS: Two hundred eighty-one eyes with prior LASIK/PRK and 3101 eyes without are included in the study. Patients with prior LASIK/PRK were significantly younger: 67.0 vs 69.9 years, p < 0.0001. The LASIK/PRK group had significantly better mean pre-operative BCVA in comparison to the non-LASIK group, logMAR 0.204 vs logMAR 0.288, p = 0.003. The LASIK/PRK group had significantly lower rates of cardiovascular disease (18.5% vs 29.3%, p < 0.001), hypertension (49.1% vs 59.3%, p < 0.012), and type 2 diabetes (10.7% vs 26.0%, p < 0.001), and no significant difference in psychiatric disease. The absolute RPE was higher for the LASIK group for all ALs, but only significantly higher for eyes with AL less than 25 mm. CONCLUSION: Patient eyes with prior LASIK/PRK surgery undergoing cataract surgery were significantly younger, had significantly less comorbidities, and a significantly better pre-operative BCVA. Using the Barrett formulas, absolute prediction error for eyes with longer ALs was not significantly worse for LASIK/PRK eyes than those without and the difference was smaller for eyes with longer AL.
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PURPOSE: Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD). DESIGN: Prospective cohort study. METHODS: One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated. RESULTS: Average GA growth rate was 1.430 mm2/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate. CONCLUSIONS: Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.
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Biomarcadores , Angiografía con Fluoresceína , Atrofia Geográfica , Imagen Multimodal , Tomografía de Coherencia Óptica , Humanos , Atrofia Geográfica/diagnóstico , Femenino , Masculino , Estudios Prospectivos , Tomografía de Coherencia Óptica/métodos , Anciano , Angiografía con Fluoresceína/métodos , Anciano de 80 o más Años , Agudeza Visual/fisiología , Estudios de Seguimiento , Progresión de la Enfermedad , Persona de Mediana Edad , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/diagnóstico por imagen , Fondo de Ojo , Sistema de RegistrosRESUMEN
OBJECTIVE: Determine the association between severe hypertensive disease of pregnancy (HDP) with moderate-severe bronchopulmonary dysplasia (BPD) in preterm infants (< 31 weeks' gestation). STUDY DESIGN: Preterm birth cohort study of 693 mother-infant dyads. Severe HDP was defined as severe preeclampsia, HELLP syndrome or eclampsia. The outcome was moderate-severe BPD classified at 36 weeks corrected gestational age, per the NICHD Consensus statement. RESULTS: 225 (32%) mothers developed severe HDP and 234 (34%) infants had moderate-severe BPD. There was an interaction between severe HDP and gestational age (p = 0.03). Infants born at < 25 weeks gestation to mothers with HDP had increased odds for moderate-severe BPD compared to infants of normotensive mothers delivering at the same gestational age. Infants born > 28 weeks to mothers with severe HDP had decreased odds for the outcome, though not statistically significant. CONCLUSIONS: Severe HDP has a differential effect on the development of moderate-severe BPD based on gestational age.
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Displasia Broncopulmonar , Edad Gestacional , Hipertensión Inducida en el Embarazo , Recien Nacido Prematuro , Humanos , Displasia Broncopulmonar/complicaciones , Femenino , Embarazo , Recién Nacido , Adulto , Índice de Severidad de la Enfermedad , Factores de Riesgo , Preeclampsia , Masculino , Estudios de Cohortes , Modelos LogísticosRESUMEN
Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies1. Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal lung samples. Epithelial cells comprised diverse normal and cancer cell states, and diversity among cancer cells was strongly linked to LUAD-specific oncogenic drivers. KRAS mutant cancer cells showed distinct transcriptional features, reduced differentiation and low levels of aneuploidy. Non-malignant areas surrounding human LUAD samples were enriched with alveolar intermediate cells that displayed elevated KRT8 expression (termed KRT8+ alveolar intermediate cells (KACs) here), reduced differentiation, increased plasticity and driver KRAS mutations. Expression profiles of KACs were enriched in lung precancer cells and in LUAD cells and signified poor survival. In mice exposed to tobacco carcinogen, KACs emerged before lung tumours and persisted for months after cessation of carcinogen exposure. Moreover, they acquired Kras mutations and conveyed sensitivity to targeted KRAS inhibition in KAC-enriched organoids derived from alveolar type 2 (AT2) cells. Last, lineage-labelling of AT2 cells or KRT8+ cells following carcinogen exposure showed that KACs are possible intermediates in AT2-to-tumour cell transformation. This study provides new insights into epithelial cell states at the root of LUAD development, and such states could harbour potential targets for prevention or intervention.
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Adenocarcinoma del Pulmón , Diferenciación Celular , Células Epiteliales , Neoplasias Pulmonares , Animales , Humanos , Ratones , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Aneuploidia , Carcinógenos/toxicidad , Células Epiteliales/clasificación , Células Epiteliales/metabolismo , Células Epiteliales/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Organoides/efectos de los fármacos , Organoides/metabolismo , Lesiones Precancerosas/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Tasa de Supervivencia , Productos de Tabaco/efectos adversos , Productos de Tabaco/toxicidadAsunto(s)
Catarata , Etnicidad , Humanos , Colorado/epidemiología , Prevalencia , Factores de Riesgo , Catarata/epidemiologíaRESUMEN
AIM: To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract surgery. METHODS: This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of Medicine. Data collected included the patient's health history, ocular comorbidities, operative and post-operative complications, and the post-operative best corrected visual acuity (BCVA). The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the study. RESULTS: A total of 11 977 eyes from 7253 patients were included in the study. Ocular comorbidities differed by sex, with males having significantly higher percentages of traumatic cataracts (males 0.7% vs females 0.1%), prior ocular surgery (6.7% vs 5.5%), and mature cataracts (2.8% vs 1.9%). Conversely, females had significantly higher rates of pseudoexfoliation (2.0% vs 3.2%). In unadjusted analysis, males had higher rates of posterior capsular rupture (0.8% vs 0.4%) and vitreous loss (1.0% vs 0.6%), but this difference was not significant after adjustment for confounders. Males had a significantly increased risk of post-operative retinal detachment, but in multivariable analysis this was no longer significant. Males were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet (Nd:YAG) laser capsulotomy for posterior capsule opacification (OR=0.8, 95%CI=0.7-0.9, P=0.0005). The BCVA was slightly worse for males pre-operatively; but post-operatively, both sexes exhibited similar visual acuity of Snellen equivalent 20/25. CONCLUSION: The study finds that in a cohort of patients presenting for cataract surgery, sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for males. However, observed surgical complication rates exhibit almost no difference by sex after adjusting for pre-operative differences and post-operative BCVA is similar between sexes.
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Purpose: To evaluate the reliability and reproducibility of visual function assessments for patients with macula-off rhegmatogenous retinal detachment (RRD). Methods: This prospective study included patients with unilateral macula-off RRD of <10-day duration successfully treated with a single, uncomplicated surgery at least 1 year following repair. Visual function assessments were performed at time of enrollment and 1 month later. Testing included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-contrast visual acuity (VA) 2.5% and 5%, contrast sensitivity assessment with Mars and Gabor patches, reading speed (acuity, speed, and critical print size), color vision testing (protan, deutan, and tritan), and microperimetry. Spectral-domain ocular coherence tomography (SD-OCT) was performed. Paired t-statistics were used to compare values between visits and between the study and fellow eyes. Results: Fourteen patients (9 male, 5 female) with a mean age of 69 years at time of surgery were evaluated. Correlation coefficients across the two visits were highest for ETDRS BCVA (0.97), tritan color vision testing (0.96), and low-contrast VA 5% (0.96), while the average t-statistic was largest for low-luminance deficit (4.2), ETDRS BCVA (4.1), and reading speed critical print size (3.7). ETDRS BCVA did not correlate with SD-OCT findings. Conclusions: ETDRS BCVA can be considered a highly reliable and reproducible outcome measure. LLVA, protan color discrimination, contrast sensitivity, and reading speed may be useful secondary outcome measures. Translational Relevance: This study provides guidance on the selection of visual function outcome measures for clinical trials of patients with macula-off RRD.
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Retinopatía Diabética , Mácula Lútea , Desprendimiento de Retina , Humanos , Femenino , Masculino , Anciano , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Reproducibilidad de los Resultados , Estudios Prospectivos , Pruebas de Visión , Mácula Lútea/diagnóstico por imagen , Mácula Lútea/cirugíaRESUMEN
PURPOSE: To characterize cataract surgery in people with dementia (PWD) using a cataract surgery outcomes database. METHODS: Demographics, medical and ocular history, surgical characteristics, and postoperative measures were analyzed for differences between PWD and non-PWD cohorts. Patient-level data were analyzed with Fisher's Exact Test, and eye-level data were analyzed with logistic regression using generalized estimating equations to account for correlation of eyes from the same individual. RESULTS: 507 eyes from 296 PWD were identified using appropriate ICD codes and cross-referenced to a cataract surgery outcomes database containing 12,949 eyes from 7,853 patients who underwent cataract phacoemulsification at a single center between January 2014 and October 2019. PWD were older (p < .001), had shorter duration cataract surgeries (p = .006), and were more likely to have mature cataract (p = .017). The rate of general anesthesia was higher in PWD (p = .005). There were no differences in complication rates between PWD and non-PWD cohorts. Both preoperative best corrected LogMAR distance visual acuity (CDVA) (p < .001) and postoperative CDVA (p < .001) were worse in PWD. CDVA significantly improved in both groups (p < .001); however, the average magnitude of improvement in CDVA was not significantly different between groups (p = .169). CONCLUSIONS: PWD present for cataract surgery at a later age and were more likely to have mature cataracts and general anesthesia, but did not have higher rates of complication, and showed significant improvement in CDVA following surgery. These findings should be encouraging to PWD undergoing counseling for cataract surgery, and for the potential for improved function in PWD.
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Purpose: To identify risk factors and evaluate outcomes of patients with delayed presentation and advanced diabetic retinopathy in our safety-net county hospital population. Methods: A retrospective study was performed on 562 patients who presented with a new diagnosis of diabetic retinopathy (DR). Delayed presentation was defined as moderate or severe nonproliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) at the initial visit. Comparisons between patient groups were performed with chi-square or Fisher's exact test for categorical variables and multinomial logistic regression for multivariable analysis. Linear and logistic regression modeling with general estimating equations to account for patients having two eyes was used to compare eye-level outcomes. Results: Lack of a primary care provider (PCP) was highest in patients who presented initially with PDR (28.8%), compared to 14.3% in moderate/severe NPDR, 12.4% in mild NPDR, and 7.6% in no DR groups (P < 0.001). Only 69.4% of patients with a PCP had an ophthalmology screening referral. Highest lack of referral (47.2%) was seen in the PDR group (P = 0.002). Patients with PDR were more likely to be uninsured (19.2%) compared to no and mild DR groups, with rates of 7.6% and 9.0%, respectively (P = 0.001). The PDR group had worse initial and final visual acuities (P < 0.001). Conclusions: Several risk factors were noted for delayed DR presentation, including lack of PCP, lack of screening referral, and uninsured/underinsured status. Patients with advanced DR at presentation had worse final visual outcomes despite aggressive treatment. Translational Relevance: Screening programs targeting populations with identified risk factors are essential for improving outcomes.
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Diabetes Mellitus , Retinopatía Diabética , Enfermedades de la Retina , Humanos , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Hospitales de Condado , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Purpose: Chronic local inflammation underlies the pathogenesis of age-related macular degeneration (AMD) causing damage to the neurosensory retina. However, there is minimal research on systemic cell-mediated inflammation in AMD. Interleukin-4 (IL-4) is an immunoregulatory cytokine with an important role in modulating inflammation in chronic immune mediated disease. The purpose of this study was to: (1) investigate the role of systemic IL-4 in patients with intermediate AMD (iAMD) and in geographic atrophy (GA), an advanced form of AMD, compared to controls without AMD, and (2) determine if IL-4 levels are moderated by sex. Methods: We examined plasma levels of IL-4 in patients with iAMD, GA, and controls without AMD included in the University of Colorado AMD registry (August 2014 to June 2021). Cases and controls were defined by multimodal imaging. IL-4 was measured by multiplex immunoassay. Data were analyzed using a nonparametric rank based linear regression model fit to IL-4. Results: There were 199 patients with iAMD, 97 patients with GA, and 139 controls, with a percentage of female patients 61%, 55%, and 66%, respectively. We demonstrated significantly higher median IL-4 levels in GA (35.3; interquartile range [IQR] = 22.8-50.5) compared to iAMD (6.1; IQR = 2.2-11.3, P < 0.01) and controls (10.7; IQR = 5.0-16.8, P < 0.01). There were no significant differences in levels of IL-4 for cases and controls when stratified by sex. Conclusions: These findings demonstrate a systemic immunological difference between iAMD and GA, indicating IL-4 may be a systemic biomarker for GA development. Translational Relevance: The plasma biomarker IL-4 is significantly elevated in patients with GA.
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Atrofia Geográfica , Degeneración Macular , Humanos , Femenino , Interleucina-4 , Angiografía con Fluoresceína/métodos , Degeneración Macular/diagnóstico , Biomarcadores , InflamaciónRESUMEN
OBJECTIVE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and mortality in patients with various stages of age-related macular degeneration (AMD). DESIGN: Observational cohort study. PARTICIPANTS: Patients with AMD enrolled in the University of Colorado AMD Registry between July 9, 2014 and December 31, 2021 were included. METHODS: Age-related macular degeneration cases were classified into early AMD, intermediate AMD, geographic atrophy, neovascular AMD, or both advanced types of AMD (neovasuclar and geographic atrophy both present) using multimodal imaging and the Beckman and Classification of Atrophy Meetings criteria. Visual Function Questionnaire -25 composite and subscale scores at the time of study enrollment were calculated. Cox proportional hazards modeling was used to assess time to event for mortality utilizing univariate and multivariable models, which adjusted for all variables significantly associated with mortality. The measures of association were hazard ratios (HRs) and 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: All-cause mortality statistics were obtained through a collaborative agreement with the Colorado Department of Public Health and Environment. Death rates through October 19, 2022 were compared by demographics and potential confounders. RESULTS: Analysis was completed on a cohort of 876 patients, of which 180 (20.6%) died during the follow-up period. Average follow-up time for this cohort was 52.5 (standard deviation: 26.6) months. In univariate analysis, composite VFQ-25 score and all subscale scores aside from ocular pain were significantly associated with time to mortality. Additionally, age, AMD category, marital status, history of smoking, and multiple chronic comorbid conditions were significantly associated with time to mortality. In multivariable analysis, for each 10-point increase in a patient's VFQ-25 scores for general health and driving, the risk of death decreased with HR of 0.85 (95% CI: 0.80, 0.91; P < 0.0001) and 0.92 (95% CI: 0.87, 0.97; P = 0.005), respectively. Composite and other subscale scores were not significantly associated with mortality after adjusting for confounding variables. CONCLUSIONS: This cohort of AMD patients had a 20% rate of death in the 52.5-month average follow-up time. Better general health and ability to drive, as measured by the VFQ-25, were each separately associated with significantly lower risk of death among individuals with AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Atrofia Geográfica , Degeneración Macular Húmeda , Humanos , Colorado/epidemiología , Inhibidores de la Angiogénesis , Agudeza Visual , Factor A de Crecimiento Endotelial VascularRESUMEN
With the construction of the International Space Station, humans have been continuously living and working in space for 22 years. Microbial studies in space and other extreme environments on Earth have shown the ability for bacteria and fungi to adapt and change compared to "normal" conditions. Some of these changes, like biofilm formation, can impact astronaut health and spacecraft integrity in a negative way, while others, such as a propensity for plastic degradation, can promote self-sufficiency and sustainability in space. With the next era of space exploration upon us, which will see crewed missions to the Moon and Mars in the next 10 years, incorporating microbiology research into planning, decision-making, and mission design will be paramount to ensuring success of these long-duration missions. These can include astronaut microbiome studies to protect against infections, immune system dysfunction and bone deterioration, or biological in situ resource utilization (bISRU) studies that incorporate microbes to act as radiation shields, create electricity and establish robust plant habitats for fresh food and recycling of waste. In this review, information will be presented on the beneficial use of microbes in bioregenerative life support systems, their applicability to bISRU, and their capability to be genetically engineered for biotechnological space applications. In addition, we discuss the negative effect microbes and microbial communities may have on long-duration space travel and provide mitigation strategies to reduce their impact. Utilizing the benefits of microbes, while understanding their limitations, will help us explore deeper into space and develop sustainable human habitats on the Moon, Mars and beyond.
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BACKGROUND: Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP. METHODS: Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer thickness (GC + IPL) were serially evaluated by OCT. In addition, patient-reported outcomes (PROs) for changes in fatigue, mood, visual function, depression, and quality of life (QOL) were measured, and high and low contrast visual acuity were recorded. RESULTS: Thirty-seven subjects were enrolled (19 RCI; 18 IVMP); the average time from symptom to treatment was 8.8 days. At 6 months, there was no difference in the primary outcome: loss of average pRNFL thickness in the affected eye (RCI vs IVMP: -13.1 vs -11.7 µm, P = 0.88) 6 months after randomization. Additional outcomes also showed no difference between treatment groups: 6-month attenuation of GC + IPL thickness (RCI vs IVMP: -13.8 vs -12.0 µm, P = 0.58) and frequency of pRNFL swelling at 1 month (RCI vs IVMP: 63% vs 72%, P = 0.73) and 3 months (RCI vs IVMP: 26% vs 31%, P = 0.99). Both treatments resulted in improvement in visual function and PROs. CONCLUSIONS: Treatment of acute optic neuritis with RCI or IVMP produced no clinically meaningful differences in optic nerve structure or visual function.