Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome

Objective To investigate the clinical efficacy of dexamethasone vitreous cavity implants(Ozurdex)for the treatment of macular edema(Irvine-Gass Syndrome)after cataract surgery.Method Eight patients(eight eyes)with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex.The patients included six men(six eyes)and two women(two eyes)with a mean age of 67.12±11.92 years.Changes in the patients best-corrected visual acuity(BCVA),central macular thickness(CMT),and intraocular pressure were compared before and after treatment.Result The mean visual acuity BCVA of the patients was 0.81±0.26 before implantation,which improved to 0.20±0.12,0.13±0.09,and 0.15±0.13 at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).The patient’s mean CMT before implantation was 703.00±148.88μm,and it reduced to 258.87±37.40μm,236.25±28.74μm,and 278.00±76.82μm at 2 weeks,1 month,and 3 months after implantation,respectively(P<0.001).Conclusion The dexamethasone vitreous cavity implant(Ozurdex)is a safe and effective treatment,which can effectively improve patient’s visual acuity and reduce macular edema associated with cataract surgery.

Dexamethasone potentiates the insulin-induced Srebp-1c expression in primary rat hepatocytes

The impacts of dexamethasone(Dex)and thyroid hormone T3 on the insulin-stimulated Srebp-1c expression were studied in primary rat hepatocytes. Primary hepatocytes from Sprague-Dawley rats were isolated, cultured and treated with insulin in the presence or absence of the indicated reagents over time. The mRNA levels of indicated genes were determined using real-time PCR. Insulin treatment induced the Srebp-1c expression and suppressed the Pck1 expression in a time-dependent manner. Dex treatment alone reduced the Srebp-1c expression, whereas potentiated the insulin-induced its expression, which reached to a level that was higher than the insulin alone group. On the other hand, insulin treatment completely suppressed the Dex-induced Pck1 expression in the same cells. T3 treatment did not affect the expressions of Srebp-1c and Pck1 alone or in the presence of absence of insulin or Dex. Interestingly, insulin treatment induced the Rxrg m RNA expression level in the absence or presence of T0901317, a specific agonist for the liver X receptor. Dex and insulin mutually affect each other's ability to regulate the expression levels of hepatic genes involved in glucose and fatty acid metabolism. Insulin induced Rxrg expression in primary hepatocytes, which may contribute to the induction of Srebp-1c expression in the same cells.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

Combination of cataract surgery with intravitreal injection of dexamethasone intravitreal implant(Ozurdex)for uveitis-induced cataract

AIM:To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone(DEX)intravitreal implant(Ozurdex).METHODS:The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),anterior chamber reaction,central macular thickness(CMT),intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively.RESULTS:A successful surgery was performed in all patients.The average follow-up period was 12mo.The female/male ratio was 13/13.Mean age was 45.65±3.83y(range 26 to 65y).Etiologically,rheumatic arthritis occurred in 6 patients(18.75%),ankylosing spondylitis in 4(12.50%),HLA-B27 associated uveitis in 3(9.38%),Vogt-KoyanagiHarada-associated uveitis in 4(12.50%),Behcet’s disease in 2(6.25%),and 7(21.88%)suffered from unknown diseases.All 32 eyes had varying degrees of improvement at 12mo after surgery,with 2 eyes showing BCVA of 0.1 or below(6.25%),6 having 0.1-0.5(18.75%),18 of 0.5-1.0(56.25%),and 6 of 1.0 or above(18.75%).No cases with increased IOP were observed.The values of mean CMT was increased at day 1,decreased at 1,3mo after surgery and increased at 6,12mo after surgery.No severe uveitis reactions,such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL,were observed after surgery.CONCLUSION:The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

The Effect of Dexamethasone versus Methylprednisolone in the Treatment of COVID-19 Patients in Jordan

Background: Previous studies focused on the treatment effect of steroids versus no steroids in treating severe COVID-19 patients, a few studies evaluated outcomes for treating those patients with either dexamethasone or methylprednisolone. Currently, we evaluate the difference in mortality associated with treating COVID-19 patients with dexamethasone versus methylprednisolone. Methods: With a retrospective multicenter study, records were reviewed for the admitted patients with severe COVID-19 during the peak of the severe COVID-19 pandemic. All admitted patients on dexamethasone or methylprednisolone were included. Patients were analyzed as all populations and propensity scores matched patients. Propensity scores were calculated for several confounders by the generalized linear model, and a “greedy” near-neighbor matching algorithm was used. Continuous variables with nonnormal distribution were analyzed by Wilcoxon signed rank test. Chi-squared and Fischer exact test analyzed categorical variables. P-values were adjusted by the Bonferroni method for both data cohorts. Body mass index was in categories. Radiological findings were divided into five categories. The outcomes: mortality, the need for home oxygen therapy, recovery, and residual symptoms on discharge were analyzed by an independent two-sample test for equality of proportions (with Yates correction), and logistic regression analysis. Results: Among the 1128 reviewed records, patients on dexamethasone or methylprednisolone were 1071, and the propensity score-matched patients were 784: dexamethasone 393 and methylprednisolone 391. There was no significant difference in the characteristics of patients between the two steroids (p-value and adjusted p-value > 0.05) for most variables. PSM adjusted a few discrepant variables before analysis. The outcome of the unmatched patients demonstrated dexamethasone benefit in the need for home oxygen therapy ( 0.05). However, matched patients demonstrated significantly lower mortality associated with dexamethasone treatment (difference -2.68%, 95%CI, -1.0, -0.004, p = 0.03, and OR 1.7, p = 0.017), and no difference for the other outcomes, including the need for home oxygen therapy (p-value > 0.05). Conclusion: Dexamethasone treatment caused significantly less mortality than methylprednisolone in treating our COVID-19 patients, but no significant difference in recovery, the need for home oxygen therapy, and residual symptoms on discharge.

Tissue microarrays in pathological examination of apoptotic acinar cells induced by dexamethasone in the pancreas of rats with severe acute pancreatitis

BACKGROUND: The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the influence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was significantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was significantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response. to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue microarrays in pathological examination of the pancreas include saving of time and energy, efficiency and highly representative.

Dexamethasone inhibits hypoxia-induced epithelial-mesenchymal transition in colon cancer

AIM:To elucidate the effects of dexamethasone on hypoxia-induced epithelial-to-mesenchymal transition(EMT) in colon cancer.METHODS:Human colon cancer HCT116 and HT29 cells were exposed to normoxic(21%) and hypoxic(1%) conditions. First,the effect of dexamethasone on cell viability was examined by MTT cell proliferation assay. In order to measure the expression levels of EMT markers(Snail,Slug,Twist,E-cadherin,and integrin αVβ6) and hypoxia-related genes [Hypoxia-inducible factor-1α(HIF-1α) and vascular endothelial growth factor(VEGF)] by dexamethasone,quantitative real-time polymerase chain reaction and western blot analysis were performed. Furthermore,the morphological changes of colon cancer cells and the expression pattern of E-cadherin by dexamethasone were detected through immunocytochemistry. Finally,the effects of dexamethasone on the invasiveness and migration of colon cancer cells were elucidated using matrigel invasion,migration,and wound healing migration assays.RESULTS:Under hypoxia,dexamethasone treatment inhibited HIF-1α protein level and its downstream gene,VEGF m RNA level in the colon cancer cell lines,HCT116 and HT29. In addition,the presence of dexamethasone down-regulated the m RNA levels of hypoxia-induced Snail,Slug,and Twist,all transcriptional factors of EMT,as well as hypoxia-induced integrin αVβ6 protein level,a well-known EMT marker for colon cancer cells. Furthermore,reduced E-cadherin in hypoxic condition was found to be recoverable by treating with dexamethasone in both colon cancer cell lines. Similarly,under hypoxic conditions,dexamethasone restored the growth pattern and morphological phenotype reminiscent of colon cancer cells grown under normoxic conditions; dexamethasone blocked the migration and invasion of both colorectal cancer cell lines in hypoxia.CONCLUSION:Our study suggested that dexamethasone has inhibitory effects on cell migration and invasion by suppressing EMT of colon cancer cell lines in hypoxic condition.

Effect of Dexamethasone and Aquaporin-1 Antisense Oligonucleotides on the Aquaporin-1 Expression in Cultured Human Trabecular Meshwork Cells

The changes in the expression of aquaporin-1 （AQP1） mRNA and protein in cultured human trabecular meshwork （HTM） cells treated with dexamethasone and transfected with antisense oligonucleotides （AS-ODN） were studied, and the implication of AQP1 regulation in corticosteroid-glaucoma and the possibility of AS-ODN inhibiting the AQP1 expression were evaluated. The cultured HTM cells in vitro were treated with different concentrations of dexamethasone and transfected with oligonucleotides for 5 days respectively. Then, total RNA and protein of HTM cells were extracted. The changes of AQP1 mRNA and protein were demonstrated qualitatively and quantitatively by RT-PCR and Western blot. Band intensities were detected by imaging analysis. There was a parallel relationship between the results of RT-PCR and those of Western blot. The expression levels of AQP1 mRNA and protein in dexamethasone-treated groups were increased initially and decreased later as dexamethasone concentration was stepped up. In the 0.04 μg/mL and 0.4 μg/mL groups, the levels of AQP1 were higher than in control group （0 μg/mL）. In the 4 μg/ mL and 40 μg/mL groups, the AQP1 expression levels were lower than in control group. AS-ODN could down-regulate the expression of AQP1 mRNA and protein in a dose-dependent manner. At 5 μg/mL, down-regulation efficiency reached the maximum. There was no statistically significant difference in the expression of AQP1 mRNA and protein between all sense oligonucleotides groups and control group. It was suggested that dexamethasone may induce the changes of the AQP1 expression in HTM cells to be involved in the occurrence of corticosteroid-glaucoma. AS-ODN can down-regulate the AQP1 expression in HTM cells to some extent.

Comparison of the anti-inflammatory effects of fluorometholone 0.1% combined with levofloxacin 0.5% and tobramycin/dexamethasone eye drops after cataract surgery

AIM： To compare the combination of fluorometholone0.1% and levofloxacin 0.5% to tobramycin/dexamethasone eye drops in controlling inflammation and preventing infection after phacoemulsification with an intraocular lens implantation.METHODS： Sixty eyes from 60 patients undergoing cataract phacoemulsification were randomized into two groups; half of the patients were treated with fluorometholone（6 times/d） combined with levofloxacin（4 times/d）, while the other half were treated with tobramycin/dexamethasone（4 times/d） eye drops for one week. Preoperative and postoperative intraocular pressure, aqueous flare, corneal thickness, and signs and symptoms were recorded before the operation and1 wk following treatments. RESULTS： There were no statistically significant differences between the two groups in corneal thickness（P ≥0.629）, aqueous flare（P ≥0.398）, and signs and symptoms scores（P ≥0.350） at each time point. Ocular hypertension was only observed in two eyes in the tobramycin/dexamethasone group. CONCLUSION： Fluorometholone combined with levofloxacin treatment shows comparable efficacy but without the tendency to increase intraocular pressure;thus, it might be a better regimen for postoperative use.

Glucocorticoid Receptor Agonist Dexamethasone Attenuates Renal Ischemia/Reperfusion Injury by Up-regulating eNOS/iNOS

The aim of this study was to determine the effect of dexamethasone（DEX） on renal ischemia/reperfusion injury（IRI）. C57BL/6 mice were randomly divided into Sham group, IRI group and DEX group. The mice in IRI and DEX groups subjected to renal ischemia for 60 min, were treated with saline or DEX（4 mg/kg, i.p.） 60 min prior to I/R. After 24 h of reperfusion, the renal function, renal pathological changes, activation of extracellular signal-regulated kinase（ERK） and glucocorticoid receptor（GR）, and the levels of iNOS and eNOS were detected. The results showed DEX significantly decreased the damage to renal function and pathological changes after renal IRI. Pre-treatment with DEX reduced ERK activation and down-regulated the level of iNOS, whereas up-regulated the level of eNOS after renal IRI. DEX could further promote the activation of GR. These findings indicated GR activation confers preconditioning-like protection against acute IRI partially by up-regulating the ratio of eNOS/iNOS.

Protein profiling identified mitochondrial dysfunction and synaptic abnormalities after dexamethasone intervention in rats with traumatic brain injury

Dexamethasone has been widely used after various neurosurgical procedures due to its anti-inflammatory property and the abilities to restore vascular permeability,inhibit free radicals,and reduce cerebrospinal fluid production.According to the latest guidelines for the treatment of traumatic brain injury in the United States,high-dose glucocorticoids cause neurological damage.To investigate the reason why high-dose glucocorticoids after traumatic brain injury exhibit harmful effect,rat controlled cortical impact models of traumatic brain injury were established.At 1 hour and 2 days after surgery,rat models were intraperitoneally administered dexamethasone 10 mg/kg.The results revealed that 31 proteins were significantly upregulated and 12 proteins were significantly downregulated in rat models of traumatic brain injury after dexamethasone treatment.The Ingenuity Pathway Analysis results showed that differentially expressed proteins were enriched in the mitochondrial dysfunction pathway and synaptogenesis signaling pathway.Western blot analysis and immunohistochemistry results showed that Ndufv2,Maob and Gria3 expression and positive cell count in the dexamethasone-treated group were significantly greater than those in the model group.These findings suggest that dexamethasone may promote a compensatory increase in complex I subunits(Ndufs2 and Ndufv2),increase the expression of mitochondrial enzyme Maob,and upregulate synaptic-transmission-related protein Gria3.These changes may be caused by nerve injury after traumatic brain injury treatment by dexamethasone.The study was approved by Institutional Ethics Committee of Beijing Neurosurgical Institute(approval No.201802001)on June 6,2018.

An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

AIM： To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema（DME） resistant to anti-vascular endothelial growth factor（VEGF） therapy.METHODS： Thirty-two DME patients were enrolled.A700 microgram slow release Intravitreal Dexamethasone Implant（Ozurdex~） was placed in the vitreous cavity.All patients were followed for 18 mo.Best-corrected visual acuity（BCVA） measured with Early Treatment Diabetic Retinopathy Study（ETDRS） and central macular thickness（CMT） exams were carried out at baseline（T0）and after 1（T1）,3（T3）,4（T4）,6（T6）,9（T9）,12（T12）,15（T15）,and 18mo（T18） post injection. RESULTS： Repeated measures ANOVA showed an effect of treatment on ETDRS（P〈0.0001）.Post hoc analyses revealed that ETDRS values were significantly increased at T1,T3,T4,T9,and T15（P 〈0.001） as compared to baseline value（T0）.At T6,T12,and T18,ETDRS values were still statistically higher than baseline（P〈0.001 vs T0）.However,at these time points,we observed a trend to return to baseline conditions.ANOVA also showed an effect of treatment（P 〈0.0001）.CMT decreased significantly at T1,T3,T4,T9,and T15（P〈0.001）.At T6（P〈0.01）,T12 and T18（P〈0.001） CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed.CONCLUSION： Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improveBCVA and CMT in DME patients resistant to anti-VEGF therapy.Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects.

Dexamethasone suppresses DU145 cell proliferation and cell cycle through inhibition of the extracellular signal-regulated kinase 1 /2 pathway and cyclin D1 expression

Aim： To determine the mechanisms of glucocorticoids in inhibiting advanced prostate cancer growth. Methods： The cell proliferation and cell cycle of prostate cancer DU145 cells following dexamethasone treatment were determined by proliferation assay and fluorescence-activated cell sorter. Western blot analysis was carried out to evaluate the effects of dexamethasone on phosphorylation of extracellular signal-regulated kinase （ERK）1/2 and expression of cyclin D1 in DU145 cells with or without glucocorticoid receptor （GR） antagonist RU486. Reverse transcription- polymerase chain reaction verified the expression of GR mRNA in DU145 cells. Results： Dexamethasone significantly inhibited DU 145 cell proliferation at the G0/G1 phase. Westem blot analysis showed a dramatic reduction of ERK1/2 activity and cyclin D1 expression in dexamethasone-treated cells. The decreased phosphorylation of ERK1/2 in dexamethasone-treated cells was attenuated by GR blockade. Additionally, the effects of dexamethasone in inhibiting cyclin D1 expression were altered by GR blockade. Conclusion： Dexamethasone suppresses DU145 cell proliferation and cell cycle, and the underlying mechanisms are through the inhibition of phosphorylation of ERK1/2 and cyclin D1 expression. The inhibition of ERK1/2 phosphorylation and cyclin D1 expression is attenuated by GR blockade, suggesting that GR regulates ERK1/2 and cyclin D1 pathways. These observations suggest that dexamethasone has a potential clinical application in prostate cancer therapy.

Hyperglycemic Effects of a Periocular Dexamethasone Injection in Diabetic Patients after Vitreoretinal Surgery

Objective To examine the hyperglycemic effects of periocular dexamethasone injection in type 2 diabetic patients after vitreoretinal surgery （VRS）. Methods This was a retrospective non-randomized controlled trial. Twenty consecutive hospitalized patients with type 2 diabetes and ocular inflammatory reaction after VRS were enrolled in this study. Ten patients received 2.5 mg dexamethasone and 10 patients received 5 mg dexamethasone. Fourteen consecutive type 2 diabetic patients without ocular inflammatory reaction after VRS were used as control group. We measured fasting blood glucose （FBG） and at 2 h after each meal （post prandial glucose, PBG; 09：00, 13：00, and 19：00 h） after periocular dexamethasone injection. Differences among three groups were determined by q tests. Results The PBG levels in both dexamethasone-treated groups started to increase within 5 h after injection （i.e., PBG at 13：00 h）, and were significantly increased at 29：00 h after injection （P〈0.05）. BG levels were almost 2-fold higher than at baseline and compared with the control group. The BG values declined gradually by 24 h to 48 h after injection. There were no differences in BG levels between the two dexamethasone-treated groups （P〉0.05）, except for PBG at 19：00 h on day 2 after injection （P〈0.05）. Conclusion Periocular dexamethasone injection can cause transient hyperglycemia in diabetic patients after VRS. BG monitoring should be performed following such injection.

Intratympanic dexamethasone injection for sudden sensorineural hearing loss in pregnancy

BACKGROUND As sudden sensorineural hearing loss(SSNHL)rarely occurs in pregnant women,there is a lack of knowledge and relevant research on its management.AIM To investigate the effect of intratympanic dexamethasone injection in the treatment of pregnant patients with SSNHL.METHODS A retrospective chart review was made for the period between June 2017 and August 2019 at our Department of Otorhinolaryngology-Head and Neck Surgery.Pregnant women who met the criteria for SSNHL were included and grouped based on the therapeutic modalities.The treatment group received intratympanic dexamethasone(2.5 mg)q.o.d.for a total of four times,while the control group received no medication other than bed rest and medical observations.All the patients were under close care of obstetricians.Pure-tone audiograms were performed before and after treatment.RESULTS Eleven patients who met the inclusion criteria were assigned to the treatment group(n=7)and the control group(n=4).The mean age of patients was 31.2±3.8 years;the right ear was affected in seven(63.64%)cases.Two patients(18.2%)suffered from vertigo,10(90.9%)suffered from tinnitus and 6(54.5%)suffered from aural fullness.The time from onset to clinic visit was relatively short,with a mean time of 1.3±0.9 d.All the women were within the second or third trimester;the average gestation period was 26.0±6.2 wk.The pure-tone averages at onset between the two groups were similar.After one wk of therapy,the treatment group had a curative rate of 57.1%and a significantly better hearing threshold and greater improvement compared to the control group(all P<0.05).Some patients experienced transient discomfort from intratympanic injections that disappeared after getting rest,while none had permanent complications.All patients delivered healthy full-term neonates with an average Apgar score of 9.7±0.5.CONCLUSION Intratympanic dexamethasone injections can be used as a first-line therapy in pregnant women with SSNHL.

Place of intravitreal dexamethasone implant in the treatment armamentarium of diabetic macular edema

Diabetic macular edema(DME)is a very important and well-known cause of visual loss in diabetics.Blood-retina barrier disruption and consequent intraretinal fluid accumulation may lead to retinal thickening at the posterior pole namely DME.Even though it is not clearly understood,current evidence suggests that chronic low-grade inflammation characterized with various cytokines has a major role in the occurrence of DME.Clinical trials are continuously shaping our treatment approaches for the eyes with DME.Today,vascular endothelial growth factor(VEGF)inhibitor and steroid administrations are the main alternatives in DME treatment.Dexamethasone(DEX)implant(Ozurdex®;Allergan,Inc.,Irvine,CA,United States)was approved by the United States Food&Drug Administration in 2014 for DME treatment.The implant is made up of a biodegradable solid copolymer that is broken down by releasing its active ingredient into the vitreous cavity over time.Biphasic release feature of this sustained-release drug delivery system ensures its efficacy for up to 6 mo with an acceptable and manageable safety profile.DEX implant provides a favorable anatomical and functional outcome in DME as shown in several randomized-controlled studies but has a relatively higher ocular side-effect profile such as increased risk of cataract formation and raised intraocular pressure when compared to the gold standard anti-VEGF agents.Thus,DEX implant becomes the second-line treatment option demonstrating inadequate clinical response to anti-VEGF therapy.However,it can be preferred as the first-line treatment in vitrectomized and pseudophakic eyes.Even in some selected conditions DEX implant is favored over anti-VEGF agents where the use of VEGF-inhibitors is either inappropriate or contraindicated such as the patients with a recent history of a major cardiovascular or cerebrovascular event,pregnancy and noncompliant to frequent visits.This mini-review briefly overviews the efficacy,safety profile and complications of DEX implant and summarizes the outcome of DEX implant administration in major clinical studies on DME treatment.

Chronic model of tympanic perforation in rats with mitomycin C and dexamethasone

A rat model of chronic tympanic membrane perforation was developed to be used in the search of new materials for the sealing of these perforations. A longitudinal study was carried out in rats subjected to incisional myr-ingotomy followed by the application of mitomycin C alone or with dexamethasone. Rats were checked at days 3, 7,1 0,1 4 and weekly thereafter until perforation closure, for up to 6 months. The addition of dexamethasone is a key component in order to obtain a chronic opening. Myringotomies treated w ith saline had a mean healing time of 8.5 days. At 8 weeks, between 62.5% and 77.7% of tympanic membranes treated w ith mitomycin C and dexamethasone remained perforated and at 6 months this number fell to 21.4%. This technique is able to maintain most tympanic membrane perforations patent for at least 8 weeks. This rat model is adequate for its use in preclinical or translational research.

Pathological changes in the retina and growth associated protein-43 expression following treatment of intracanalicular optic nerve injury via optic canal decompression,dexamethasone or their combination

BACKGROUND： The main clinical treatments for optic nerve injury are optic canal decompression and systemic administration of hormones, but both treatments have disadvantages. OBJECTIVE： To observe the pathological changes in the retina and growth associated protein-43 （GAP-43） expression, to compare the treatment of optic canal decompression, hormones, and their combination with the intracanalicular optic nerve injury.DESIGN, TIME AND SETTING： A randomized, controlled animal study was performed at the Department of Anatomy, Weifang Medical University, China, from September 2007 to November 2008.MATERIALS： Dexamethasone （Shandong Huaxin Pharmaceutical, China） and rabbit anti-GAP-43 polyclonal antibody （Boster, China） were used.METHODS： All 36 healthy adult rabbits were randomly assigned to control group （n = 4）, simple injury group （n = 20）, and treatment group （n = 12）. Intracanalicular optic nerve injury models were established using the metal cylinder free-fall impact method. The control group was left intact. The treatment group （four rabbits in each subgroup） was treated by optic nerve decompression, dexamethasone treatment （1 mg/kg daily via two intravenous infusions, 1/5 total dose reduction every 3 days, for 14 days）, and simultaneously giving surgery and hormone treatment.MAIN OUTCOME MEASURES： Pathological changes in the retina were determined using hematoxylin-eosin staining. GAP-43 expression was detected using immunohistochemistry in the retina.RESULTS： Retina injury induced obvious pathological changes in the retina. With prolonged time after optic nerve injury, the number of retinal ganglion cells was gradually decreased, and reached the minimum on day 14 （P〈0.01）. All three treatments increased the number of retinal ganglion cells （P〈0.01）, but surgery ＋ hormone treatment was most effective. No GAP-43 cells were present in the normal retinal, but they appeared 3 days after injury, peaked 7 days after injury, and then began to decline.CONCLUSION： Intracanalicular optic nerve injury induced obvious pathological changes in the retina, including increased GAP-43 expression. Optic canal decompression and hormones improved nerve repair after injury, and their combination produced better outcomes.

Single dose dexamethasone prophylaxis of postembolisation syndrome after chemoembolisation in hepatocellular carcinoma patient:A randomised,double-blind,placebo-controlled study

BACKGROUND Even in the immuno-oncology era,transcatheter arterial chemoembolisation(TACE)is the most effective way to treat intermediate stage hepatocellular carcinoma(HCC).Postembolisation syndrome(PES)is the most common side effect from TACE and there is still no standard prevention guideline.AIM To evaluate the efficacy of single dose intravenous dexamethasone regimen to prevent PES after TACE among patients with HCC.METHODS This study enrolled patients with HCC who had eligible indication for TACE without macrovascular invasion/extrahepatic metastasis.Patients were randomly assigned to either an intravenous single dose of dexamethasone 8 mg or placebo one hour before TACE.The primary outcome was a negative result of PES at 48 h after TACE,which was defined as score<2 of Southwest Oncology Group toxicity coding criteria using fever,nausea,vomiting and pain to calculated.And the secondary end point was duration of admission between two groups.RESULTS One hundred patients were randomly assigned 1:1.Under intention-to-treat analysis,49 patients were randomly assigned to the dexamethasone and 51 to the placebo groups.Both groups were similar for baseline characteristics.The negative PES rate was significantly higher in the dexamethasone group than in the placebo group(63.3%vs 29.4%;P=0.005).Mean Southwest Oncology Group toxicity coding PES was 2.14(95%CI:1.41-2.8)vs 3.71(95%CI:2.97-4.45)between the dexamethasone and placebo groups,respectively.Cumulative incidence of fever was significantly lower in dexamethasone group with P<0.001,pain,nausea and vomiting were also lower in the dexamethasone group compared with the placebo group(P=0.16,P=0.11,and P=0.49).The dexamethasone regimen was generally well tolerated by patients with HCC patients including those with hepatitis B virus infection and well-controlled diabetes mellitus.CONCLUSION Single dose dexamethasone was effective at preventing PES among patients with HCC treated with TACE.The study showed no adverse events of special interest related to dexamethasone.

Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome

AIM: To compare safety and efficacy of intravitreal dexamethasone(IVD) implant with topical nepafenac(TN) 0.1% in previously untreated Irvine-Gass syndrome(IGS) in clinical practice. METHODS: This was a retrospective study of 62 eyes with IGS after phacoemulsification with posterior chamber intraocular lens(IOL) implantation. None of the patients used treatment before IVD or TN. Best-corrected visual acuity(BCVA) with Early Treatment Diabetic Retinopathy Study chart(ETDRS), slit-lamp, intraocular pressure(IOP) measurement, fundus examination, spectral-domain optical coherence tomography(OCT) and fundus florescein angiography were performed to all subjects at baseline, 1, 3 and 6 mo. RESULTS: The mean BCVA of the IVD group was 49.3±6.8, and the mean BCVA of the TN group was 32.9±7.3 ETDRS letters in post-treatment month 6. The mean central macular thickness(CRT) of IVD group was 266.6±53.5 μm and the mean CRT of TN group was 364.9±56.3 μm in posttreatment month 6. Baseline BCVA has correlation with final BCVA in TN group however there was no correlation between baseline BCVA and final BCVA in IVD group. CONCLUSION: IVD is found to be better than TN in controlling pseudophakic macular edema and improving visual acuity. IVD group also has significantly lower CRT however IOP is not significantly different between two groups in post-treatment month 6.