Treatment of cystoid macular edema after cataract surgery.

The purpose of this review was to determine the optimum pharmacologic treatment for cystoid macular edema (CME) after cataract surgery in nondiabetic and diabetic patients. The Cochrane Library, Medline, and Embase databases were searched, and all randomized controlled trials (RCTs) that compared at least 2 pharmacologic strategies for CME after cataract surgery were included. Studies were excluded if preoperative CME or other risk factors for developing CME postoperatively were present. Ten RCTs were included in the systematic review. Five trials included at least 30 participants. Three RCTs showed a greater visual acuity improvement in patients treated with topical nonsteroidal antiinflammatory drugs (NSAIDs) than with a placebo. Other studies comparing the efficacy of topical NSAIDs, topical corticosteroids, sub-Tenon corticosteroids, oral NSAIDs, and oral acetazolamide did not report significant differences between treatment groups. Therefore, large RCTs are needed to provide evidence-based recommendations for the optimum treatment of CME after cataract surgery.

Intrauterine Lipopolysaccharide-Induced Chorioamnionitis in a Sheep: Does It Affect the Auditory System?

BACKGROUND: Fetal exposure to in utero inflammation such as chorioamnionitis is related to central nervous system injury. We hypothesized that chorioamnionitis can provoke inflammatory changes in the perilymph and alter hearing outcome. METHODS: Pregnant ewes were randomized into 2 groups: intrauterine injection with lipopolysaccharide (LPS; n = 19) or saline (n = 21). In the first experiment, fetal perilymph samples were taken for cytokine analysis. In the second experiment, consecutive bone-conducted auditory brain stem responses were obtained from 1 to 7 months after birth. RESULTS: Perilymph samples showed a significant elevation in interleukin 8 in the LPS group. Auditory brain stem response analysis demonstrated higher response thresholds and a prolongation of absolute peak V and interpeak intervals I to V and III to V in the LPS group compared to sham treatment. CONCLUSION: Our study confirms the hypothesis that an intrauterine inflammation by LPS can result in a fetal perilymphatic inflammatory response and functional impaired hearing outcomes after birth in a sheep model.

Prevention of Cystoid Macular Edema After Cataract Surgery in Nondiabetic and Diabetic Patients: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the optimum medical strategy to prevent cystoid macular edema (CME) after cataract surgery. DESIGN: Systematic review and meta-analysis. METHODS: setting: Cochrane, MEDLINE, and EMBASE databases were searched to identify eligible randomized controlled trials (RCTs). STUDY POPULATION: RCTs comparing medical strategies to prevent CME after uncomplicated cataract surgery in nondiabetic and diabetic patients. OBSERVATION PROCEDURES: Data were extracted by 2 authors independently. Quality of individual RCTs was assessed using the Cochrane Collaboration's tool for assessing risk of bias and Delphi criteria. MAIN OUTCOME MEASURES: Odds of developing CME within 3 months postoperatively and foveal thickness, macular volume and corrected distance visual acuity change within 3 months postoperatively, as compared to baseline. RESULTS: Seventeen trials reported incidence rates. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) significantly reduced the odds of developing CME as compared to topical corticosteroids in nondiabetic (odds ratio [OR] 0.11; 95% confidence interval [95% CI] 0.03-0.37) and mixed populations (OR 0.05; 95% CI 0.02-0.11). A combination of topical corticosteroids and NSAIDs significantly reduced the odds of developing CME as compared to topical corticosteroids in nondiabetic (OR 0.21; 95% CI 0.10-0.44) and diabetic patients (OR 0.17; 95% CI 0.05-0.50). Intravitreal corticosteroid or anti-vascular endothelial growth factor injections did not show any additional benefit in diabetic subjects. CONCLUSIONS: Topical NSAIDs significantly reduced the odds of developing CME, as compared to topical corticosteroids, in nondiabetic and mixed populations. A combination of topical NSAIDs and corticosteroids reduced the odds of developing CME in nondiabetic and diabetic patients, as compared to topical corticosteroids.

Comparison of airway responses in sheep of different age in precision-cut lung slices (PCLS).

BACKGROUND: Animal models should display important characteristics of the human disease. Sheep have been considered particularly useful to study allergic airway responses to common natural antigens causing human asthma. A rationale of this study was to establish a model of ovine precision-cut lung slices (PCLS) for the in vitro measurement of airway responses in newborn and adult animals. We hypothesized that differences in airway reactivity in sheep are present at different ages. METHODS: Lambs were delivered spontaneously at term (147d) and adult sheep lived till 18 months. Viability of PCLS was confirmed by the MTT-test. To study airway provocations cumulative concentration-response curves were performed with different allergic response mediators and biogenic amines. In addition, electric field stimulation, passive sensitization with house dust mite (HDM) and mast cells staining were evaluated. RESULTS: PCLS from sheep were viable for at least three days. PCLS of newborn and adult sheep responded equally strong to methacholine and endothelin-1. The responses to serotonin, leukotriene D4 and U46619 differed with age. No airway contraction was evoked by histamine, except after cimetidine pretreatment. In response to EFS, airways in PCLS from adult and newborn sheep strongly contracted and these contractions were atropine sensitive. Passive sensitization with HDM evoked a weak early allergic response in PCLS from adult and newborn sheep, which notably was prolonged in airways from adult sheep. Only few mast cells were found in the lungs of non-sensitized sheep at both ages. CONCLUSION: PCLS from sheep lungs represent a useful tool to study pharmacological airway responses for at least three days. Sheep seem well suited to study mechanisms of cholinergic airway contraction. The notable differences between newborn and adult sheep demonstrate the importance of age in such studies.

Effects of intra-amniotic lipopolysaccharide exposure on the fetal lamb lung as gestation advances.

BACKGROUND: Intra-amniotic lipopolysaccharide (LPS) exposure may affect neonatal outcome by altering fetal lung and immune system development. We hypothesized that intra-amniotic LPS exposure would cause persistent fetal pulmonary responses as the lungs develop in utero. METHODS: Fetal lambs were exposed to intra-amniotic LPS at 118 or at 118 and 123 d of gestational age (GA) with delivery at 125, 133, or 140 d (term = 147 d). Immune responses, PU.1 expression, Toll-like receptor (TLR)-1,2,4,6 mRNA levels, mast cell levels, and pulmonary elastin deposition were evaluated. RESULTS: After a single dose of LPS, pulmonary inflammatory responses were observed with increases of (i) PU.1 and TLR1 at 125 d GA and (ii) monocytes, lymphocytes, TLR2, and TLR6 at 133 d GA. Repetitive LPS exposure resulted in (i) increases of neutrophils, monocytes, PU.1, and TLR1 at 125 d GA; (ii) increases of neutrophils, PU.1, and TLR2 at 133 d GA; and (iii) decreases of mast cells, elastin foci, TLR4, and TLR6 at early gestation. At 140 d GA, only PU.1 was increased after repetitive LPS exposure. CONCLUSION: The preterm fetal lung can respond to a single exposure or repeated exposures from intra-amniotic LPS in multiple ways, but the absence of inflammatory and structural changes in LPS-exposed fetuses delivered near term suggest that the fetus can resolve an inflammatory stimulus in utero with time.

Comparison of recruitment manoeuvres in ventilated sheep with acute respiratory distress syndrome.

BACKGROUND: Recruitment manoeuvres are widely used in clinical practice to open the lung and prevent lung injury by derecruitment, although the evidence is still discussed. In this study two different recruitment manoeuvres were compared to no recruitment manoeuvres (control) in ventilated sheep with acute respiratory distress syndrome (ARDS), induced by lung lavage. METHODS: We performed a prospective, randomised study in 26 ventilated sheep with ARDS, to evaluate the effect of two different recruitment manoeuvres on gas exchange, blood pressure and lung injury. The two different recruitment manoeuvres, the high pressure recruitment manoeuvre (HPRM), with high peak pressure, and the smooth and moderate recruitment manoeuvre (SMRM), with lower peak pressure, were compared to controls (no recruitment) after disconnection. Oxygenation index and ventilation efficacy index were calculated to evaluate gas exchange. Lung injury was assessed by inflammatory response in broncho-alveolar lavage fluid (BALF) and blood and histology of the lung. RESULTS: Oxygenation index improved significantly after both recruitment manoeuvres compared with controls, but no significant difference was found between the recruitment manoeuvres. Blood pressure decreased after HPRM but not after SMRM. HPRM induced a higher number of total cells and more neutrophils in the BALF. In the histology of the lung, mean alveolar size was increased in the dorsocranial region of the lung of SMRM compared to controls. CONCLUSION: Recruitment manoeuvres improved oxygenation, but SMRM was superior, with respect to hemodynamics and pulmonary inflammation, in ventilated sheep suffering from ARDS induced by lung lavage.

Neurally mediated airway constriction in human and other species: a comparative study using precision-cut lung slices (PCLS).

The peripheral airway innervation of the lower respiratory tract of mammals is not completely functionally characterized. Recently, we have shown in rats that precision-cut lung slices (PCLS) respond to electric field stimulation (EFS) and provide a useful model to study neural airway responses in distal airways. Since airway responses are known to exhibit considerable species differences, here we examined the neural responses of PCLS prepared from mice, rats, guinea pigs, sheep, marmosets and humans. Peripheral neurons were activated either by EFS or by capsaicin. Bronchoconstriction in response to identical EFS conditions varied between species in magnitude. Frequency response curves did reveal further species-dependent differences of nerve activation in PCLS. Atropine antagonized the EFS-induced bronchoconstriction in human, guinea pig, sheep, rat and marmoset PCLS, showing cholinergic responses. Capsaicin (10 µM) caused bronchoconstriction in human (4 from 7) and guinea pig lungs only, indicating excitatory non-adrenergic non-cholinergic responses (eNANC). However, this effect was notably smaller in human responder (30 ± 7.1%) than in guinea pig (79 ± 5.1%) PCLS. The transient receptor potential (TRP) channel blockers SKF96365 and ruthenium red antagonized airway contractions after exposure to EFS or capsaicin in guinea pigs. In conclusion, the different species show distinct patterns of nerve-mediated bronchoconstriction. In the most common experimental animals, i.e. in mice and rats, these responses differ considerably from those in humans. On the other hand, guinea pig and marmoset monkey mimic human responses well and may thus serve as clinically relevant models to study neural airway responses.

Sex differences in lung gas volumes after lipopolysaccharide-induced chorioamnionitis in fetal sheep.

BACKGROUND: Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival. OBJECTIVE: Given the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses. METHODS: Time-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days). We assessed inflammatory responses in bronchoalveolar lavage fluid and cord blood, lung maturation with pressure-volume curves, and lung structure. RESULTS: Lung gas volume showed differences between the sexes after 2 days LPS (male 4.6 [1.2] mL/kg, female 7.7 [4.4] mL/kg; P = 0.02) and 7 days LPS (male 20.5 [9.3] mL/kg, female 27.0 [7.0] mL/kg; P = 0.01). The control group was not different by sex (male 8.0 [3.6] mL/kg, female 8.9 [3.9] mL/kg; P > 0.05). No difference in lung structure and in pulmonary and systemic inflammatory response was evident by sex. CONCLUSION: Preterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.

Lipopolysaccharide-induced chorioamnionitis is confined to one amniotic compartment in twin pregnant sheep.

BACKGROUND: Chorioamnionitis is a major risk factor for preterm birth in multifetal pregnancies. However, there is little clinical data whether chorioamnionitis is restricted to one amniotic compartment in multifetal pregnancies. OBJECTIVE: To explore whether chorioamnionitis is confined to the exposed compartment and does not cross to the unaffected fetus in twin pregnancy. METHODS: In twin pregnant sheep, one of the twins was exposed to either 2 or 14 days of intra-amniotic lipopolysaccharide (LPS) while the co-twin was exposed to either 2 or 14 days of intra-amniotic saline (n = 3 for each exposure). Singletons were included in this study to compare the grade of inflammation with twins. All fetuses were delivered at 125 days of gestation (term = 150 days). Chorioamnionitis was confirmed by histological examination. Lung inflammation was assessed by cell count in bronchoalveolar lavage. Lung compliance was assessed at 40 cm H(2)O. Results were compared using analysis of variance (ANOVA) with a post-hoc Tukey analysis. RESULTS: Inflammation in placenta, membranes and lung of LPS-exposed twins was significantly higher after 2 and 14 days of exposure when compared to the saline-exposed co-twins. Lung compliance in LPS-exposed twins was significantly increased after 14 days when compared to saline-exposed co-twins. Intrauterine LPS exposure increased lung compliance and inflammation in the membranes, placenta and lung to the same extent in twins as in singletons. CONCLUSION: In twin pregnant sheep, inflammation of the membranes, placenta and fetal lung was strictly limited to the exposed fetus in the amniotic compartment in which the LPS was injected.

Fetal responses to lipopolysaccharide-induced chorioamnionitis alter immune and airway responses in 7-week-old sheep.

OBJECTIVE: We hypothesized that fetal innate immune responses to lipopolysaccharide-induced chorioamnionitis would alter postnatal systemic immune and airway responsiveness. STUDY DESIGN: Ewes received intraamniotic injections with saline or lipopolysaccharide at 90, 100, and 110 days of gestation. Immune status and airway responsiveness were evaluated at term and at 7 weeks of age. RESULTS: At term, lymphocytes, monocytes, and neutrophils were significantly increased (respectively, 24-fold, 127-fold, and 31,000-fold) in lungs and blood monocytes became Toll-like receptor 2 responsive after lipopolysaccharide exposures. Furthermore, CD4 and CD4/CD25 lymphocytes were increased in thymus and lymph nodes. At 7 weeks, airway reactivity decreased and concentrations of CD8 cytotoxic T lymphocytes changed in the lungs and thymus relative to controls. CONCLUSION: Early gestational lipopolysaccharide exposure increased leukocyte responsiveness at term. Decreased airway reactivity and changes in lymphocytes at 7 weeks postnatal demonstrate persistent effects of fetal exposure to LPS.