Cerebellar functional connectivity relates to lower urinary tract function: A 7 Tesla study.

OBJECTIVES: The objective of this study is to explore the functional connectivity (FC) of the cerebellum during the storage phase of micturition, through detecting spontaneous blood-oxygen-level dependent signal between the cerebellum and different brain regions using a high-resolution 7 Tesla magnetic resonance imaging (MRI) scanner. MATERIALS AND METHODS: We recruited healthy individuals with no reported history of neurological disease or lower urinary tract (LUT) symptoms. Participants were asked to drink 500 mL of water and then empty their bladders before entering the MRI scanner. They underwent a T1-weighted anatomical scan, followed by an initial (8 min) empty bladder resting state functional MRI (rs-fMRI) acquisition. Once subjects felt the desire to void, a second rs-fMRI scan was obtained, this time with a full bladder state. We established a priori cerebellar regions of interest from the literature to perform seed-to-voxel analysis using nonparametric statistics based on the Threshold Free Cluster Enhancement method and utilized a voxel threshold of p < 0.05. RESULTS: Twenty individuals (10 male and 10 female) with a median age of 25 years (IQR [3.5]) participated in the study. We placed 31 different 4-mm spherical seeds throughout the cerebellum and assessed their FC with the remainder of the brain. Three of these (left cerebellar tonsil, right posterolateral lobe, right posterior lobe) showed significant differences in connectivity when comparing scans conducted with a full bladder to those with an empty bladder. Additionally, we observed sex differences in FC, with connectivity being higher in women during the empty bladder condition. CONCLUSION: Our initial findings reveal, for the first time, that the connectivity of the cerebellar network is modulated by bladder filling and is associated with LUT function. Unraveling the cerebellum's role in bladder function lays the foundation for a more comprehensive understanding of urinary pathologies affecting this area.

Anti-epithelial-derived cytokines for severe asthma: Systematic review and meta-analysis.

BACKGROUND: Therapies directed against epithelial-derived cytokines, often referred to as alarmins, have been studied in large randomized trials, and reports suggest possible benefit for non-type 2 as well as type 2 severe asthma. METHODS: We performed a systematic review of Medline, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process, and Web of Science databases from inception to March 2022. We performed a random-effects pairwise meta-analysis of randomized controlled trials addressing antialarmin therapy in severe asthma. Results use relative risk (RR) values and 95% confidence intervals (CIs). For continuous outcomes, we report mean difference (MD) values and 95% CIs. We define high eosinophils as ≥300 cells/µL and low eosinophils as <300 cells/µL. We used Cochrane-endorsed RoB 2.0 software to assess the risk of bias of trials, and we used the Grades of Recommendation Assessment, Development, and Evaluation (aka GRADE) framework to assess the certainty of the evidence. RESULTS: We identified 12 randomized trials including 2391 patients. Antialarmins probably reduce annualized exacerbation rates in patients with high eosinophils (RR 0.33 [95% CI 0.28 to 0.38]; moderate certainty). Antialarmins may reduce this rate in patients with low eosinophils (RR 0.59 [95% CI 0.38 to 0.90]; low certainty). Antialarmins improve FEV1 in patients with high eosinophils (MD 218.5 mL [95% CI 160.2 to 276.7]; high certainty). Antialarmin therapy probably does not improve FEV1 in patients with low eosinophils (MD 68.8 mL [95% CI 22.4 to 115.2]; moderate certainty). Antialarmins reduce blood eosinophils, total IgE, and fractional excretion of nitric oxide across studied subjects. CONCLUSION: Antialarmins are effective at improving lung function and probably reduce exacerbations in patients with severe asthma and blood eosinophils ≥300 cells/µL. The effect on patients with lower eosinophils is less certain.

A comparison of the effectiveness of biologic therapies for asthma: A systematic review and network meta-analysis.

BACKGROUND: Trials have not directly compared biologics for the treatment of asthma. OBJECTIVE: To compare the relative efficacy of biologics in asthma. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and clinicaltrials.gov from inception to May 31, 2022 for randomized trials addressing biologic therapies for asthma. Reviewers worked independently and in duplicate to screen references, extract data, and assess risk of bias. We performed a frequentist network meta-analysis and assessed the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. We present dichotomous outcomes as absolute risk differences per 1000 patients and relative risk with 95% confidence intervals (95% CI) and continuous outcomes as mean difference (MD) and 95% CI. RESULTS: We identified 64 trials, including 26,630 patients. For patients with eosinophilic asthma, tezepelumab (329 fewer exacerbations per 1000 [95% CI, 272.6-366.6 fewer]) and dupilumab (319.6 fewer exacerbations per 1000 [95% CI, 272.6-357.2 fewer]) reduce exacerbations compared with placebo (high certainty). Tezepelumab (MD, 0.24 L [95% CI, 0.16-0.32]) and dupilumab (0.25 L [95% CI, 0.21-0.29]) improve lung function compared with placebo (high certainty). Both tezepelumab (110.97 fewer hospital admissions per 1000 [95% CI, 94.53-120.56 fewer]) and dupilumab (97.27 fewer hospitalizations [4.11-124.67 fewer]) probably reduce hospital admissions compared with placebo (moderate certainty). For patients with low eosinophils, biologics probably do not improve asthma outcomes. For these patients, tezepelumab (MD, 0.1 L [95% CI, 0-0.19]) and dupilumab (MD, 0.1 L [95% CI, 0-0.20]) may improve lung function (low certainty). CONCLUSION: Tezepelumab and dupilumab are effective at reducing exacerbations. For patients with low eosinophils, however, clinicians should probably be more judicious in using biologics, including tezepelumab, because they probably do not confer substantial benefit.

Medical treatments for idiopathic pulmonary fibrosis: a systematic review and network meta-analysis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder with a poor prognosis. Our objective is to assess the comparative effectiveness of 22 approved or studied IPF drug treatments. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov from inception to 2 April 2021. We included randomised controlled trials (RCTs) for adult patients with IPF receiving one or more of 22 drug treatments. Pairs of reviewers independently identified randomised trials that compared one or more of the target medical treatments in patients with IPF. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for network meta-analysis. We calculated pooled relative risk (RR) ratios and presented direct or network estimates with 95% credibility intervals (95% CI), within the GRADE framework. RESULTS: We identified 48 (10 326 patients) eligible studies for analysis. Nintedanib [RR 0.69 (0.44 to 1.1), pirfenidone [RR 0.63 (0.37 to 1.09); direct estimate), and sildenafil [RR (0.44 (0.16 to 1.09)] probably reduce mortality (all moderate certainty). Nintedanib (2.92% (1.51 to 4.14)), nintedanib+sildenafil (157 mL (-88.35 to 411.12)), pirfenidone (2.47% (-0.1 to 5)), pamrevlumab (4.3% (0.5 to 8.1)) and pentraxin (2.74% (1 to 4.83)) probably reduce decline of overall forced vital capacity (all moderate certainty). Only sildenafil probably reduces acute exacerbation and hospitalisations (moderate certainty). Corticosteroids+azathioprine+N-acetylcysteine increased risk of serious adverse events versus placebo (high certainty). CONCLUSION AND RELEVANCE: Future guidelines should consider sildenafil for IPF and further research needs to be done on promising IPF treatments such as pamrevlumab and pentraxin as phase 3 trials are completed.

Sildenafil for idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis have a poor overall prognosis and there are few evidence-based drug therapies that reduce mortality. OBJECTIVE: We aimed to perform a systematic review and meta-analysis to assess whether sildenafil reduces mortality, disease progression and adverse side effects. METHODS: We reviewed randomized controlled studies (RCTs) from MEDLINE, Cochrane registry of clinical trials, and EMBASE. Our outcomes of interest included mortality, change in FVC, acute exacerbations and hospitalizations and adverse drug effects leading to discontinuation. We used an inverse variance fixed effects meta-analysis method to calculate pooled relative risk (RR) and mean difference (MD). RESULTS: A total of 4 studies were included in the systematic review. Sildenafil probably reduces mortality when compared to placebo or to standard care, [RR 0.73 (95% CI 0.51 to 1.04); moderate certainty]. Pooled estimates showed sildenafil may not alter the rate of change of FVC [MD 0.61% (95% CI -0.29 to 1.52)], or DLCO [MD 0.97% (95% CI 0.04 to 1.90)] (both low certainty). Pooled estimated showed sildenafil may not reduce the number of hospitalizations or acute exacerbations, [RR 1.10 (95% CI 0.61 to 1.98); low certainty]. There is probably no difference in drug discontinuation due to adverse effects when comparing sildenafil to the control group, [RR 0.79 (95% CI 0.56, 1.10); moderate certainty]. CONCLUSION: Sildenafil probably reduces all-cause mortality in IPF patients. More studies need to be done to confirm the magnitude and reliability of the point estimate.

Pathophysiology and treatment options of varicocele: An overview.

Varicocele is the most common correctable cause for male infertility, but not all men with varicocele are affected equally by this condition. The pathophysiology of varicocele-induced fertility remains ill-defined. While evidence suggests that oxidative stress remains a central factor, other mechanisms likely include scrotal hyperthermia, reflux of metabolites, hypoxia and cadmium accumulation. Microsurgical varicocelectomy remains the gold standard treatment option for infertile men with a clinically palpable varicocele and abnormal semen parameters. Newer evidence suggests a potential role for antioxidant supplementation and a meaningful role of varicocelectomy for patients destined for ART to improve pregnancy outcomes.

Assessing online price transparency of sperm cryopreservation across the United States.

Although the lack of information on the costs and pricing of healthcare services prevails throughout the medical industry, empiric observations have demonstrated that pricing information is even more obscured in the sperm cryopreservation market. Thus, the objectives of our study are to assess and compare online price transparency and the price of sperm cryopreservation across various healthcare settings in the United States. This study examined online pricing published by facilities that have an active registration to store spermatozoa with the Food and Drug Administration. Less than one-fifth of registered facilities display any pricing information online. Price transparency also varies among census regions and facility types. Nationally, the median initial bank fee and annual price of storage are $350 and $385 respectively. Although there were no differences in the initial fee by facility type and census region, the annual price of storing spermatozoa is highest in the Northeast, which could be attributed to laboratory techniques, demographic patterns or insurance coverage. Guidelines from professional societies or different legislation and regulatory requirements across different US states can increase price transparency, which can promote consumer decision-making and decrease the barrier for men seeking fertility preservation.

Prevalence and patterns of antipsychotic use in youth at the time of admission and discharge from an inpatient psychiatric facility.

The objective of this study was to examine the prevalence and patterns of antipsychotic use in children and adolescents at the time of admission and discharge from a tertiary care inpatient psychiatric facility. This retrospective analysis included all patients 18 years and younger, who were admitted and discharged from a child and adolescent tertiary care inpatient psychiatric facility between May 1, 2008 and December 31, 2009. Data for medications at admission were obtained using a province-wide network that links all pharmacies in British Columbia, Canada to a central set of data systems, whereas data for medications at discharge were obtained using the Department of Pharmacy's (British Columbia Children's Hospital, Vancouver, British Columbia, Canada) inpatient computer database. Apart from antipsychotics, overall drug use included antidepressants, mood stabilizers, benzodiazepines, anticholinergics, stimulants, and sleep medications. Referral and discharge diagnoses were also examined. During the study period, 335 patients were admitted and discharged from the tertiary care inpatient psychiatric facility. Significantly, more patients were prescribed with an antipsychotic at the time of discharge from hospital compared with that of the time when they were admitted to hospital (51.6% vs 30.7%; P < 0.0001). Antidepressants were most often coprescribed with an antipsychotic at admission and discharge (32.0% vs 42.2%, respectively) followed by attention-deficit/hyperactivity disorder medications (22.3% vs 24.9% at admission and discharge, respectively) and anticonvulsants (19.4% vs 19.1% at admission and discharge, respectively). Whether the significant increase in antipsychotic use seen from the time of admission to discharge is solely attributed to clinical worsening or other variables requires further investigation.

Home high flow nasal cannula for chronic hypercapnic respiratory failure in COPD: A systematic review and meta-analysis.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) with chronic hypercapnia is usually treated with non-invasive ventilation (NIV). High flow nasal cannula (HFNC) may be an appropriate alternative. However, the efficacy of HFNC in COPD patients with chronic hypercapnia is yet to be optimally summarized. METHODS: We conducted a systematic review and meta-analysis using random effects with inverse variance methods. Randomized controlled trials involving adult COPD patients initiated on HFNC for at least one month were included. Outcomes of interest were all-cause mortality, acute exacerbations, hospitalizations, and change in St. George Respiratory Questionnaire (SGRQ). We assessed the risk of bias using ROB 2.0 and assessed the quality of the evidence using GRADE. RESULTS: We included four randomized trials involving 440 patients. HFNC probably reduces acute exacerbations compared to standard care (RR 0.77 [95 % CI 0.66 to 0.89]; moderate certainty), suggesting 69 fewer acute exacerbations per 1000 patients. HFNC may reduce hospital admissions (RR 0.87 [95 % CI 0.69 to 1.09]; low certainty) and may lower the SGRQ score (MD 8.12 units lower [95 % CI 13.30 to 2.95 lower]; low certainty). However, HFNC may have no effect on mortality (RR 1.22 [95 % CI 0.64 to 2.35]; low certainty). CONCLUSION: HFNC probably reduces acute exacerbations and might reduce hospital admissions in COPD patients with chronic hypercapnia. However, its effect on mortality is uncertain. Future larger RCTs with longer follow-up periods are recommended to provide more robust evidence on the efficacy of HFNC in patients with COPD.

Higher- versus Lower-Dose Corticosteroids for Severe to Critical COVID-19: A Systematic Review and Dose-Response Meta-analysis.

Rationale: Corticosteroids are standard of care for patients with severe coronavirus disease (COVID-19). However, the optimal dose is uncertain. Objectives: To compare higher doses of corticosteroids with lower doses in patients with COVID-19. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, MedRxiv, and Web of Science from inception to August 1, 2022, for trials that randomized patients with severe-to-critical COVID-19 to corticosteroids, standard care, or placebo. Reviewers, working in duplicate, screened references, extracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. We performed a dose-response meta-analysis and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. We present our results both in relative risk and absolute risk difference per 1,000, with 95% confidence intervals (CIs). Results: We included 20 trials, with 10,155 patients. We show that, compared with lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (absolute risk difference, 14 fewer deaths per 1,000 [95% CI, 26 fewer to 2 fewer]; moderate certainty) and may reduce the need for mechanical ventilation (absolute risk difference, 11.6 fewer per 1,000 [95% CI, 23.2 fewer to 6.9 more]; low certainty). The effect of corticosteroids on nosocomial infections is uncertain (16.7 fewer infections per 1,000 [95% CI, 5.4 fewer to 25.0 fewer]; very low certainty). Conclusions: Relatively higher doses of corticosteroids may be beneficial in patients with severe-to-critical COVID-19 and may not increase the risk of nosocomial infections.

Medications for the treatment of pulmonary arterial hypertension: a systematic review and network meta-analysis.

BACKGROUND: There is no consensus on the most effective treatments of pulmonary arterial hypertension (PAH). Our objective was to compare effects of medications for PAH. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrials.gov from inception to December 2021. We performed a frequentist random-effects network meta-analysis on all included trials. We rated the certainty of the evidence using the Grades of Recommendation, Assessment, Development, and Evaluation approach. RESULTS: We included 53 randomised controlled trials with 10 670 patients. Combination therapy with endothelin receptor antagonist (ERA) plus phosphodiesterase-5 inhibitors (PDE5i) reduced clinical worsening (120.7 fewer events per 1000, 95% CI 136.8-93.4 fewer; high certainty) and was superior to either ERA or PDE5i alone, both of which reduced clinical worsening, as did riociguat monotherapy (all high certainty). PDE5i (24.9 fewer deaths per 1000, 95% CI 35.2 fewer to 2.1 more); intravenous/subcutaneous prostanoids (18.3 fewer deaths per 1000, 95% CI 28.6 fewer deaths to 0) and riociguat (29.1 fewer deaths per 1000, 95% CI 38.6 fewer to 8.7 more) probably reduce mortality as compared to placebo (all moderate certainty). Combination therapy with ERA+PDE5i (49.9 m, 95% CI 25.9-73.8 m) and riociguat (49.5 m, 95% CI 17.3-81.7 m) probably increase 6-min walk distance as compared to placebo (moderate certainty). CONCLUSION: Current PAH treatments improve clinically important outcomes, although the degree and certainty of benefit vary between treatments.

Inflammatory biomarkers as independent prognosticators of 28-day mortality for COVID-19 patients admitted to general medicine or ICU wards: a retrospective cohort study.

Inflammatory biomarkers may be associated with disease severity and increased mortality in COVID-19 patients but have not been studied in North American populations. We sought to determine whether a set of commonly ordered inflammatory biomarkers can predict 28-day mortality. We analyzed a multi-centered (four) COVID-19 registry cohort from March 4th to December 7th, 2020. This cohort included COVID-19-positive patients admitted to medical wards or intensive care units. Patients presenting to the emergency department for COVID-19 symptoms and then subsequently discharged were also included. We performed Cox-regression analysis to measure whether commonly used biomarkers were associated with an increased 28-day mortality. Of 336 COVID-19-positive patients, 267 required hospital admission, and 69 were seen in the emergency room and discharged. The median age was 63 years (IQR 80-50) and the female-to-male ratio was 49:51. Derivation of internally validated cut-offs suggested that C-reactive protein ≥ 78.4 mg/L, neutrophil-to-lymphocyte ratio ≥ 6.1, lymphocyte-to-white blood cell ratio < 0.127, and a modified Glasgow prognostic score equal to 2 vs. 1 or 0 were associated with the highest increased risk of 28-day mortality. We provide early estimates of cut-off values for inflammatory biomarkers and indices measured at the time of admission that may be useful to clinicians for predicting 28-day mortality in North American COVID-19 patients.

Incidence and Outcomes of Acute Kidney Injury in Patients Admitted to Hospital With COVID-19: A Retrospective Cohort Study.

BACKGROUND: The incidence of acute kidney injury (AKI) in patients with COVID-19 and its association with mortality and disease severity is understudied in the Canadian population. OBJECTIVE: To determine the incidence of AKI in a cohort of patients with COVID-19 admitted to medicine and intensive care unit (ICU) wards, its association with in-hospital mortality, and disease severity. Our aim was to stratify these outcomes by out-of-hospital AKI and in-hospital AKI. DESIGN: Retrospective cohort study from a registry of patients with COVID-19. SETTING: Three community and 3 academic hospitals. PATIENTS: A total of 815 patients admitted to hospital with COVID-19 between March 4, 2020, and April 23, 2021. MEASUREMENTS: Stage of AKI, ICU admission, mechanical ventilation, and in-hospital mortality. METHODS: We classified AKI by comparing highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We calculated the unadjusted and adjusted odds ratio for the stage of AKI and the outcomes of ICU admission, mechanical ventilation, and in-hospital mortality. RESULTS: Of the 815 patients registered, 439 (53.9%) developed AKI, 253 (57.6%) presented with AKI, and 186 (42.4%) developed AKI in-hospital. The odds of ICU admission, mechanical ventilation, and death increased as the AKI stage worsened. Stage 3 AKI that occurred during hospitalization increased the odds of death (odds ratio [OR] = 7.87 [4.35, 14.23]). Stage 3 AKI that occurred prior to hospitalization carried an increased odds of death (OR = 5.28 [2.60, 10.73]). LIMITATIONS: Observational study with small sample size limits precision of estimates. Lack of nonhospitalized patients with COVID-19 and hospitalized patients without COVID-19 as controls limits causal inferences. CONCLUSIONS: Acute kidney injury, whether it occurs prior to or after hospitalization, is associated with a high risk of poor outcomes in patients with COVID-19. Routine assessment of kidney function in patients with COVID-19 may improve risk stratification. TRIAL REGISTRATION: The study was not registered on a publicly accessible registry because it did not involve any health care intervention on human participants.

Transient parkinsonism associated with acute Legionnaires' disease.

A 44-year-old right-handed man with a 5-day history of non-productive cough associated with subjective fevers/chills and night sweats presented to the emergency department with slurred speech. Radiography and urine antigen testing confirmed the diagnosis of Legionella pneumonia The hospital course was complicated by acute hypoxic respiratory failure that required 7 days of invasive mechanical ventilation. Following extubation, the patient had dysarthria and developed new parkinsonism features. Brain imaging revealed a non-specific focal lesion in the left frontal lobe of unclear significance. Ciprofloxacin was decided as the final antibiotic of choice for its favourable central nervous system profile. Levodopa-carbidopa was initiated to help activate the basal ganglia. The patient had complete resolution of pneumonia and transient parkinsonism. He was able to regain most of his baseline functional status with intensive rehabilitation.

Sperm granuloma masquerading as a supernumerary testis.

Sperm granuloma is a common finding following vasectomy, with majority of the lesions located at the site of the vasectomy defect. Sperm granulomas are typically small and asymptomatic. We describe a case in which the nodule presented similarly to a supernumerary testis by radiographic features.

Factors Affecting Response Rates in Medical Imaging Survey Studies.

RATIONALE AND OBJECTIVE: To review response rates published in medical imaging journals, and to analyze potential factors which contributed to a low response rate. MATERIALS AND METHODS: A literature search was performed in MEDLINE and Embase to identify and assess published medical imaging survey studies. Variables assessed were response rate, incentives such as reminders and remuneration, and rationales provided for a potential low response rate. Statistical significance was calculated using unpaired t tests, ANOVA, Mann-Whitney, and Kruskal-Wallis tests. RESULTS: Three hundred and fifty-six unique surveys were included for analysis. The mean survey response rate in the current age of predominately electronic surveys was 45%. Factors which statistically significantly demonstrated a difference in response rate were survey location (European countries: 52%, Canada: 47%, United States: 42%; p < 0.05), survey topic (musculoskeletal: 69%, nuclear medicine: 64%, and education: 47%; p < 0.05), survey delivery method (telephone: 76%, email: 41%; p < 0.0001), and survey question type (short answer: 62%, multiple choice: 43%; p < 0.01). Statistically significant linear correlations were observed between the response rate compared to the number of reminders sent (r = 0.27; p < 0.01) and the number of participants (r = -0.26; p < 0.0001). CONCLUSION: The survey response rate serves as a surrogate marker for nonresponse bias. Survey response controlled for intrinsic nonadjustable characteristics offer achievable research goals. Adjustable factors to low response, including survey delivery method, question type, and number of reminders demonstrated statistical difference in response rate, and can be utilized by researchers to prospectively minimize nonresponse bias.

Staphylococcus aureus Leukocidins Target Endothelial DARC to Cause Lethality in Mice.

The pathogenesis of Staphylococcus aureus is thought to depend on the production of pore-forming leukocidins that kill leukocytes and lyse erythrocytes. Two leukocidins, Leukocidin ED (LukED) and γ-Hemolysin AB (HlgAB), are necessary and sufficient to kill mice upon infection and toxin challenge. We demonstrate that LukED and HlgAB cause vascular congestion and derangements in vascular fluid distribution that rapidly cause death in mice. The Duffy antigen receptor for chemokines (DARC) on endothelial cells, rather than leukocytes or erythrocytes, is the critical target for lethality. Consistent with this, LukED and HlgAB injure primary human endothelial cells in a DARC-dependent manner, and mice with DARC-deficient endothelial cells are resistant to toxin-mediated lethality. During bloodstream infection in mice, DARC targeting by S. aureus causes increased tissue damage, organ dysfunction, and host death. The potential for S. aureus leukocidins to manipulate vascular integrity highlights the importance of these virulence factors.

Biomechanical Changes After LASIK Flap Creation Combined With Rapid Cross-Linking Measured With Brillouin Microscopy.

PURPOSE: To evaluate the biomechanical changes occurring after LASIK flap creation and rapid corneal cross-linking (CXL) measured with Brillouin light microscopy. METHODS: Porcine eyes (n = 11) were evaluated by Brillouin light microscopy sequentially in the following order: virgin state, after LASIK flap creation, and after rapid CXL. Each eye served as its own control. Depth profile of the Brillouin frequency shift was computed to reveal the depth-dependent changes in corneal stiffness. RESULTS: There was a statistically significant reduction of Brillouin shift (reduced corneal stiffness) after LASIK flap creation compared to virgin corneas across total corneal thickness (-0.035 GHz, P = .0195) and within the anterior stromal region (-0.104 GHz, P = .0039). Changes in the central (-0.029 GHz, P = .0391) and posterior (-0.005 GHz, P = .99) stromal regions were not significant. There was a small increase in Brillouin shift after rapid cross-linking that was not statistically or clinically significant across total corneal thickness (0.006 GHz, P = .4688 for any specific stromal region; 0.002 to 0.009 GHz, P > .46 for all). CONCLUSIONS: LASIK flap creation significantly reduced Brillouin shift in the anterior third of the stroma in porcine eyes. Rapid corneal cross-linking had no significant effect on Brillouin shift after LASIK flap creation in porcine eyes. With further validation, non-contact, non-perturbative Brillouin microscopy could become a useful monitoring tool to evaluate the biomechanical impact of corneal refractive procedures and corneal cross-linking protocols. [J Refract Surg. 2017;33(6):408-414.].

Mechanical outcome of accelerated corneal crosslinking evaluated by Brillouin microscopy.

PURPOSE: To quantify corneal mechanical changes induced by corneal crosslinking (CXL) procedures of different ultraviolet-A (UVA) intensity and exposure time using Brillouin microscopy. SETTINGS: University of Maryland, College Park, Maryland, USA. DESIGN: Experimental study. METHODS: Porcine cornea samples were debrided of epithelia and soaked with riboflavin 0.1% solution. Samples were exposed to a standard 5.4 J/cm2 of UVA radiation with varying intensity and exposure time as follows: 3 mW/cm2 for 30.0 minutes, 9 mW/cm2 for 10.0 minutes, 34 mW/cm2 for 2.65 minutes, and 50 mW/cm2 for 1.80 minutes. Using Brillouin microscopy, the Brillouin modulus for each sample was computed as a function of radiation intensity/exposure time. For validation, the Young's modulus was found with the stress-strain test and compared at each irradiation condition. RESULTS: The standard 3 mW/cm2 irradiance condition produced a significantly larger increase in corneal Brillouin modulus than the 9 mW/cm2 (P ≤ .05), 34 mW/cm2 (P ≤ .01), and 50 mW/cm2 (P ≤ .01) conditions. Depth analysis showed similar anterior sections of the standard and 9 mW/cm2 conditions but significantly less stiffening in the central and posterior of the 9 mW/cm2 condition. The stiffening of the standard protocol was significantly larger in all sections of the 34 mW/cm2 and 50 mW/cm2 conditions (P ≤ .01). The overall change in Brillouin-derived Brillouin modulus correlated with the increase in Young's modulus (R2 = 0.98). CONCLUSIONS: At a constant UVA light dose, accelerating the irradiation process decreased CXL stiffening. Brillouin analysis showed that accelerated protocols were especially ineffective in the deeper portions of the cornea.