A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong disability.Currently,there are no FDA-approved therapies available to promote nerve regeneration.Tacrolimus accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve surgery.The authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug exposure.Tacrolimus is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 days.Size and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible byproducts.Tacrolimus released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic delivery.Given its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

Relative carcinogenicity of tacrolimus vs mycophenolate after solid organ transplantation and its implications for liver transplant care

BACKGROUND De novo malignancy is a leading cause of late morbidity and mortality in liver transplant recipients.Cumulative immunosuppression has been shown to contribute to post-transplant malignancy(PTM)risk.There is emerging evidence on the differential carcinogenic risk profile of individual immunosuppressive drugs,independent of the net effect of immunosuppression.Calcineurin inhibitors such as tacrolimus may promote tumourigenesis,whereas mycophenolic acid(MPA),the active metabolite of mycophenolate mofetil,may limit tumour progression.Liver transplantation(LT)is relatively unique among solid organ transplantation in that immunosuppression monotherapy with either tacrolimus or MPA is often achievable,which makes careful consideration of the risk-benefit profile of these immunosuppression agents particularly relevant for this cohort.However,there is limited clinical data on this subject in both LT and other solid organ transplant recipients.AIM To investigate the relative carcinogenicity of tacrolimus and MPA in solid organ transplantation.METHODS A literature search was conducted using MEDLINE and Embase databases using the key terms“solid organ transplantation”,“tacrolimus”,“mycophenolic acid”,and“carcinogenicity”,in order to identify relevant articles published in English between 1st January 2002 to 11th August 2022.Related terms,synonyms and explosion of MeSH terms,Boolean operators and truncations were also utilised in the search.Reference lists of retrieved articles were also reviewed to identify any additional articles.Excluding duplicates,abstracts from 1230 records were screened by a single reviewer,whereby 31 records were reviewed in detail.Full-text articles were assessed for eligibility based on pre-specified inclusion and exclusion criteria.RESULTS A total of 6 studies were included in this review.All studies were large population registries or cohort studies,which varied in transplant era,type of organ transplanted and immunosuppression protocol used.Overall,there was no clear difference demonstrated between tacrolimus and MPA in de novo PTM risk following solid organ transplantation.Furthermore,no study provided a direct comparison of carcinogenic risk between tacrolimus and MPA monotherapy in solid organ transplantation recipients.CONCLUSION The contrasting carcinogenic risk profiles of tacrolimus and MPA demonstrated in previous experimental studies,and its application in solid organ transplantation,is yet to be confirmed in clinical studies.Thus,the optimal choice of immunosuppression drug to use as maintenance monotherapy in LT recipients is not supported by a strong evidence base and remains unclear.

Stromal lenticule addition keratoplasty with corneal crosslinking for corneal ectasia secondary to FS-LASIK:a case series

●AIM:To explore the clinical efficacy and safety of stromal lenticule addition keratoplasty(SLAK)with corneal crosslinking(CXL)on patients with corneal ectasia secondary to femtosecond laser-assisted in situ keratomileusis(FS-LASIK).●METHODS:A series of 5 patients undertaking SLAK with CXL for the treatment of corneal ectasia secondary to FS-LASIK were followed for 4-9mo.The lenticules were collected from patients undertaking small incision lenticule extraction(SMILE)for the correction of myopia.Adding a stromal lenticule was aimed at improving the corneal thickness for the safe application of crosslinking and compensating for the thin cornea to improve its mechanical strength.●RESULTS:All surgeries were conducted successfully with no significant complications.Their best corrected visual acuity(BCVA)ranged from 0.05 to 0.8-2 before surgery.The pre-operational total corneal thickness ranged from 345-404μm and maximum keratometry(Kmax)ranged from 50.8 to 86.3.After the combination surgery,both the corneal keratometry(range 55.9 to 92.8)and total corneal thickness(range 413-482μm)significantly increased.Four out of 5 patients had improvement of corneal biomechanical parameters(reflected by stiffness parameter A1 in Corvis ST).However,3 patients showed decreased BCVA after surgery due to the development of irregular astigmatism and transient haze.Despite the onset of corneal edema right after SLAK,the corneal topography and thickness generally stabilized after 3mo.●CONCLUSION:SLAK with CXL is a potentially beneficial and safe therapy for advanced corneal ectasia.Future work needs to address the poor predictability of corneal refractometry and compare the outcomes of different surgical modes.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.

Simultaneous tectonic Descemet stripping endothelial keratoplasty and tectonic Bowman layer transplant for the management of corneal perforation

AIM:To report the outcomes of three cases of corneal perforation managed with simultaneous tectonic Descemet stripping endothelial keratoplasty(t-DSEK)and tectonic Bowman layer transplant(t-BLT)as an alternative to tectonic penetrating keratoplasty(t-PKP).METHODS:Three eyes of three patients receiving simultaneous t-DSEK and t-BLT for corneal perforation were included.The technique for DSEK was modified depending on individual requirements.The t-BLT technique was standardised using an 8 mm graft and fixated with a running suture.Success was measured by the ability of this procedure to close a corneal perforation.RESULTS:All three cases achieved tectonic eye globe restoration and remained stable during the minimum 3-month observation period.Reinterventions were relatively common:2 cases required amniotic membrane transplant for persistent epithelial defects.One case required DSEK rebubbling.One case developed angle closure glaucoma requiring surgical peripheral iridectomy.CONCLUSION:Simultaneous t-DSEK and t-BLT may be a useful strategy for the management of corneal perforation as an alternative management to t-PKP for selected cases.

Donor cornea quality used for penetrating keratoplasty vs deep anterior lamellar keratoplasty

Deep anterior lamellar keratoplasty(DALK) has recently been introduced as an alternative procedure to penetrating keratoplasty(PK) for corneal pathologies not affecting the corneal endothelium. DALK does not rely on donor endothelium and requires less rigid criteria for donor corneal tissue quality. Therefore, DALK makes it possible to use donor corneas deemed unsuitable for PK. Furthermore, lamellar keratoplasty allows acellular corneal tissue to be transplanted. As a result, long-term preservation techniques are being revisited to increase the availability of donor corneas and subsequently alleviate constraints of availability, cost, storage, and transportation in many countries. The recent alterations in corneal transplantation techniques and hence the type of donor cornea tissues used for each technique, may require corneal surgeons and eye banks to reevaluate their selection criteria. The purpose of this systematic review is to present an updated analysis on the type and quality of donor corneas used for PK and DALK, assess the influence of donor and eye bank factors on the quality of donor corneas, and determine whether any of these donor factors affect clinical outcomes, complications, and graft survivals.

Two-step strategy—conjunctival flap covering surgery combined with secondary deep anterior lamellar keratoplasty for the treatment of high-risk fungal keratitis

AIM:To investigate whether the two-step strategy[conjunctival flap covering surgery(CFCS)combined with secondary deep anterior lamellar keratoplasty(DALK)]is effective for patients with high-risk fungal keratitis(FK).METHODS:In this noncomparative,retrospective case series,10 subjects(6 males,4 females)with a mean age of 56.5±7.1(range 47-72)y with high-risk FK undergone the two-step strategy were included.Reported outcome measures were healing of the corneal ulcer,recurrence of FK,reject reaction,improvement in best corrected visual acuity(BCVA)and relevant complications.RESULTS:The average diameter of corneal infiltrates was 7.50±0.39 mm,ranging from 6.94 to 8.13 mm.The mean depth of corneal infiltrates was 422.4±77.1μm,ranging from 350 to 535μm.The mean corneal thickness was 597.4±117.3μm,ranging from 458 to 851μm.Hypopyon and endothelial plaques were presented in all patients.The period between the two steps was 3.65±0.9(ranging from 3 to 5)mo.The graft diameter was 7.75±0.39 mm.At the last follow-up(average 9.25±3.39,ranging from 5.5 to 17mo),no fungal recurrence or graft rejection appeared,and all patients showed improvement of BCVA.One patient suffered from liver function impairment due to oral voriconazole for 4wk and recovered spontaneously after 1wk of drug withdrawal.CONCLUSION:The two-step strategy is safe and effective in the treatment of high-risk FK by transforming intentional therapeutic penetrating keratoplasty during acute infection to later optical DALK.It is a practical strategy,especially in areas lacking fresh donor corneas and eye bank services.

Reversible Chronic Interstitial Nephritis Induced by Tacrolimus —Tacrolimus Chronic Interstitial Nephritis

Calcineurin inhibitors (CNI) are potent immunosuppressive agents in prophylaxis against graft rejection and autoimmune diseases including primary glomerulopathies. Previous research showed reversible;acute afferent arteriolar vasculopathy and irreversible chronic interstitial fibrosis associated with CNI nephrotoxicity. In this case report we describe a patient, with minimal change disease, that had developed chronic and progressive renal disease while receiving therapeutic dose of Tacrolimus. His serum creatinine had reached 537 umol/L and his nephrotic state worsened. Kidney biopsy showed chronic interstitial nephritis. Tacrolimus was discontinued and he was treated with 1 mg/kg prednisone in addition to Mycophenolate mofetil (MMF) 1 g twice daily. By the 2nd month;serum creatinine returned to normal and by the 3rd month serum albumin too. After 1 month of therapy;the dose of Prednisone was tapered down gradually till 5 mg daily by the end of 3rd month. Moreover, the dose of MMF was reduced to 500 mg X2 by the end of 3rd month. After 2 years of follow up;he remained stable and without relapse of NS or renal failure. In conclusion, reversible renal disease, due to chronic interstitial nephritis can be induced by CNI which is amenable to treatment with Prednisone and MMF.

Association between the early high level of serum tacrolimus and recurrence of hepatocellular carcinoma in ABO-incompatible liver transplantation

BACKGROUND Clinical factors predicting graft survival(GS)after ABO-incompatible(ABOi)liver transplantation(LT),and differences between recipients with and without hepatocellular carcinoma(HCC)are unclear.AIM To analyze the impact of serial serum tacrolimus trough concentration in recipients with or without(HCC)in ABOi living-donor liver transplantation(LDLT).METHODS We analyzed a historical cohort of 89 recipients who underwent ABOi LDLT,including 47 patients with HCC.RESULTS The 1-,3-,5-,and 10-year GS rates were 85.9%,73.3%,71.4%,and 71.4%,respectively,and there were no significant differences between HCC and non-HCC recipients.In multivariate Coxregression analyses,tacrolimus trough concentrations below 5.4 ng/mL at 24 wk post-LT,in addition to the antibody-mediated rejection(AMR)were associated with poor-graft outcomes.In HCC patients,AMR[hazard ratio(HR)=63.20,P<0.01]and HCC recurrence(HR=20.72,P=0.01)were significantly associated with poor graft outcomes.HCCs outside Milan criteria,and tacrolimus concentrations at 4 wk post-LT>7.3 ng/mL were significant predictive factors for HCC recurrence.After propensity score matching,patients with high tacrolimus concentrations at 4 wk had significantly poor recurrence-free survival.CONCLUSION Elevated tacrolimus levels at 4 wk after ABOi LDLT have been found to correlate with HCC recurrence.Therefore,careful monitoring and control of tacrolimus levels are imperative in ABOi LT recipients with HCC.

Impact of tacrolimus intra-patient variability in adverse outcomes after organ transplantation

Tacrolimus(Tac)is currently the most common calcineurin-inhibitor employed in solid organ transplantation.High intra-patient variability(IPV)of Tac(Tac IPV)has been associated with an increased risk of immune-mediated rejection and poor outcomes after kidney transplantation.Few data are available concerning the impact of high Tac IPV in non-kidney transplants.However,even in kidney transplantation,there is still a controversy whether high Tac IPV is indeed detrimental in respect to graft and/or patient survival.This may be due to different methods employed to evaluate IPV and distinct time frames adopted to assess graft and patient survival in those reports published up to now in the literature.Little is also known about the influence of high Tac IPV in the development of other untoward adverse events,update of the current knowledge regarding the impact of Tac IPV in different outcomes following kidney,liver,heart,lung,and pancreas tran-splantation to better evaluate its use in clinical practice.

Dosing strategies for de novo once-daily extended release tacrolimus in kidney transplant recipients based on CYP3A5 genotype

BACKGROUND Tacrolimus extended-release tablets have been Food and Drug Administrationapproved for use in the de novo kidney transplant population.Dosing requirements often vary for tacrolimus based on several factors including variation in metabolism based on CYP3A5 expression.Patients who express CYP3A5 often require higher dosing of immediate-release tacrolimus,but this has not been established for tacrolimus extended-release tablets in the de novo setting.AIM To obtain target trough concentrations of extended-release tacrolimus in de novo kidney transplant recipients according to CYP3A5 genotype.METHODS Single-arm,prospective,single-center,open-label,observational study(ClinicalTrials.gov:NCT037-13645).Life cycle pharma tacrolimus(LCPT)orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight.If weight is more than 120%of ideal body weight,an adjusted body weight was used.LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL.Pharmacogenetic analysis of CYP3A5 genotype was performed at study conclusion.RESULTS Mean time to therapeutic tacrolimus trough concentration was longer in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(6 d vs 13.5 d vs 4.5 d;P=0.025).Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in CYP3A5 intermediate and extensive metabolizers vs CYP3A5 non-expressers(16 mg vs 16 mg vs 12 mg;P=0.010)(0.20 mg/kg vs 0.19 mg/kg vs 0.13 mg/kg;P=0.018).CYP3A5 extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to CYP3A5 intermediate metabolizers and non-expressers(7.98 ng/mL vs 9.18 ng/mL vs 10.78 ng/mL;P=00.008).No differences were identified with regards to kidney graft function at 30-d post-transplant.Serious adverse events were reported for 13(36%)patients.CONCLUSION Expression of CYP3A5 leads to higher starting doses and incremental dosage titration of extended-release tacrolimus to achieve target trough concentrations.We suggest a higher starting dose of 0.2 mg/kg/d for CYP3A5 expressers.

Relationship Between the Efficacy of Low-Dose Glucocorticoids Combined with Tacrolimus in the Treatment of Adult Idiopathic Membranous Nephropathy and the Level of Serum Anti-PLA2R Antibodies

Objective:To further evaluate the efficacy and safety of low-dose glucocorticoids combined with tacrolimus in the treatment of adult idiopathic membranous nephropathy(IMN)in a clinical setting.Methods:We carried out a single-center prospective study of 88 patients with IMN who were admitted into the Affiliated Hospital of Hebei University from January 2019 to December 2021,and the participants were divided into two groups based on their serum anti-PLA2R antibody levels:the negative group and the positive group.46 patients were positive for anti-PLA2R antibodies and 42 were negative.Results:After 6 months of treatment,the serum albumin,cholesterol,and 24h urine protein quantification in the anti-PLA2R negative group improved more significantly compared to the positive group(P<0.05);after 6 months of treatment,the remission rate of the positive group was significantly lower than that of the negative group,and(P<0.05);Conclusion:After treatment with tacrolimus combined with low-dose glucocorticoids,patients with idiopathic membranous nephropathy who were tested positive for anti-PLA2R antibodies had a higher overall remission rate compared those who were tested negative for serum anti-PLA2R antibodies.

Indications for and techniques of keratoplasty at Vietnam National Institute of Ophthalmology

AIM： To report the indications for and techniques of corneal transplantation at Vietnam National Institute of Ophthalmology （VNIO） over a period of 12y （2002-2013）, METHODS： Records of patients who had undergone corneal transplantation at VNIO from January 1, 2002 to January 1, 2014 were reviewed to determine the indication for and type of corneal transplant performed. Patient age, gender, indication for corneal transplantation and surgical technique were recorded and analyzed. RESULTS： Corneal transplantation were underwent in 1390 eyes of 1278 patients with a mean age of 44.9±18.1y during the period under review. The most common indication was infectious corneal ulcer （n=670; 48.2%）, followed by corneal scar （n=333, 24.0% ）, corneal dystrophy （n=138, 9.9%） and failed graft （n=112, 8.1%）. Nearly all procedures performed were penetrating keratoplasty （n=1300, 93.5% ）, with a few lamellar keratoplasty procedures performed： lamellar keratoplasty （n=52, 3.7%）, Descemet＇s stripping automated endothelial keratoplasty （n =27, 1.9% ） and deep anterior lamellar keratoplasty （n =11, 0.8%）.CONCLUSION： While the most common indication for keratoplasty was infectious keratitis, nearly all indications for corneal transplantation were managed with penetrating keratoplasty, However, lamellar keratoplasty techniques, including deep anterior lamellar keratoplasty and Descemet＇s stripping automated endothelial keratoplasty, are being performed with increasing frequency for isolated stromal and endothelial disorders, respectively,

Early tacrolimus exposure does not impact long-term outcomes after liver transplantation

BACKGROUND Tacrolimus trough levels(TTL)during the first weeks after liver transplantation(LT)have been related with long-term renal function and hepatocellular carcinoma recurrence.Nevertheless,the significance of trough levels of tacrolimus during the early post-transplant period for the long-term outcome is under debate AIM To evaluate the effect of TTL during the first month on the long-term outcomes after LT.METHODS One hundred fifty-five LT recipients treated de novo with once-daily tacrolimus were retrospectively studied.Patients with repeated LT or combined transplantation were excluded as well as those who presented renal dysfunction prior to transplantation and/or those who needed induction therapy.Patients were classified into 2 groups according to their mean TTL within the first month after transplantation:≤10(n=98)and>10 ng/mL(n=57).Multivariate analyses were performed to assess risk factors for patient mortality.RESULTS Mean levels within the first month post-transplant were 7.4±1.7 and 12.6±2.2 ng/mL in the≤10 and>10 groups,respectively.Donor age was higher in the high TTL group 62.9±16.8 years vs 45.7±17.5 years(P=0.002)whilst mycophenolate-mofetil was more frequently used in the low TTL group 32.7%vs 15.8%(P=0.02).Recipient features were generally similar across groups.After a median follow-up of 52.8 mo(range 2.8-81.1),no significant differences were observed in:Mean estimated glomerular filtration rate(P=0.69),hepatocellular carcinoma recurrence(P=0.44),de novo tumors(P=0.77),new-onset diabetes(P=0.13),or biopsy-proven acute rejection rate(12.2%and 8.8%,respectively;P=0.50).Eighteen patients died during the follow-up and were evenly distributed across groups(P=0.83).Five-year patient survival was 90.5%and 84.9%,respectively(P=0.44),while 5-year graft survival was 88.2%and 80.8%,respectively(P=0.42).Early TTL was not an independent factor for patient mortality in multivariate analyses.CONCLUSION Differences in tacrolimus levels restricted to the first month after transplant did not result in significant differences in long-term outcomes of LT recipients.

Destructive effects on endothelial cells of grafts in cytomegalovirus DNA-positive patients after keratoplasty

AIM:To investigate corneal graft survival rate and endothelial cell density(ECD)loss after keratoplasty in cytomegalovirus(CMV)positive patients.METHODS:This was a retrospective cohort study.We analyzed the clinical data of patients who underwent viral DNA detection in aqueous humor/corneal tissue collected during keratoplasty from March 2015 to December 2018 at the Peking University Third Hospital,Beijing,China.To further evaluate the effect of CMV on graft survival rate and ECD loss,patients were divided into three groups:1)CMV DNA positive(CMV+)group;2)viral DNA negative(virus-)group,comprising virus-group eyes pairwise matched to eyes in the CMV+group according to ocular comorbidities;3)control group,comprising virus-group eyes without ocular comorbidities.The follow-up indicators including graft survival rate,ECD,ECD loss,and central corneal thickness(CCT),were analyzed by Tukey honestly significant difference(HSD)test.RESULTS:Each group included 29 cases.The graft survival rate in CMV+group were lowest among the three groups(P=0.000).No significant difference in donor graft ECD was found among three groups(P=0.54).ECD in the CMV+group was lower than the virus-group at 12(P=0.009),and 24mo(P=0.002)after keratoplasties.Furthermore,ECD loss was higher in the CMV+group than in the virus-group in the middle stage(6-12mo)postkeratoplasty(P=0.017),and significantly higher in the early stage(0-6mo)in the virus-group than in the control group(P=0.000).CONCLUSION:CMV reduces the graft survival rate and exerts persistent detrimental effects on the ECD after keratoplasty.The graft ECD loss associate with CMV infection mainly occurrs in the middle stage(6-12mo postoperatively),while ocular comorbidities mainly affects ECD in the early stage(0-6mo postoperatively).

Tacrolimus对糖尿病大鼠肾脏巨噬细胞Toll样受体2与4表达的影响

目的探讨Toll样受体(Toll-like receptor,TLR)2和TLR4在糖尿病大鼠肾脏巨噬细胞的表达水平及tacrolimus对其的调节作用。方法将40只Wistar大鼠随机分为对照组、模型组、tacrolimus(0.5、1.0 mg.kg-1)给药组,通过腹腔注射链脲佐菌素(STZ)诱导糖尿病模型,4周后测大鼠血糖、相对肾质量、尿白蛋白排泄率(UAER),应用免疫组化单染及双染方法检测肾组织ED-1+细胞、NF-κB-p-p65+细胞及ED-1+TLR2+细胞、ED-1+TLR4+细胞的表达。结果 ta-crolimus 1.0 mg.kg-1给药组大鼠相对肾质量明显低于模型组(P<0.05),tacrolimus(0.5、1.0 mg.kg-1)给药组大鼠UAER较模型组明显减少(P<0.05或P<0.01)。免疫组化显示:模型组大鼠肾组织ED-1+、ED-1+TLR2+、ED-1+TLR4+及NF-κB-p-p65+细胞数明显高于对照组(P<0.01),tacrolimus 0.5与1.0 mg.kg-1给药组ED-1+细胞数与模型组比较无差异,而ED-1+TLR2+、ED-1+TLR4+及NF-κB-p-p65+细胞数则明显低于模型组(P<0.05)。结论糖尿病大鼠肾脏巨噬细胞TLR2和TLR4的过度表达与巨噬细胞的活化及由此引发的炎症反应有关,tacrolimus可通过直接或间接作用下调肾脏巨噬细胞TLR2与TLR4表达,从而抑制与TLR-NF-κB信号转导及调控途径有关的炎症反应。

Changes in endothelial cell density following penetrating keratoplasty and deep anterior lamellar keratoplasty

· AIM: To compare the corneal endothelial cell density (ECD) of clear grafts after penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK). · METHODS: The study included 44 and 54 patients treated with PK and DALK, respectively, between March 2006 and April 2010. Corneal ECD was examined using specular microscopy at postoperative 1, 3, 6, 12, and 18 months, and the values were compared. · RESULTS: Corneal ECD reduction in the PK group was 7.4%, 15.2%, 23.5%, and 28.9% at 3, 6, 12 and 18 months respectively after surgery, compared with 4.2 % in the first month (P <0.01). These figures were 3.0%, 6.7%, 7.2%, and 7.7% at 3, 6, 12 and 18 months respectively, compared with 2.2 % in the first month in the DALK group (P >0.05). · CONCLUSION: Compared with DALK,PK significantly reduced ECD of the clear grafts. These results suggest that survival of endothelial cells in grafts is better after DALK than after PK. ·

Clinical results of non-Descemet stripping endothelial keratoplasty

AIM： To investigate the impact of non-Descemet stripping endothelial keratoplasty（non-DSEK） on graft rejection rate,and its overall procedural effectiveness in patients.METHODS： Non-DSEK was performed on 65 eyes of 64 patients,and the procedural outcomes,including rejection episodes,failure and dislocation of the grafts,best corrected visual acuity（BCVA）,endothelial cell density（ECD）,and other complications,were analyzed retrospectively.RESULTS： Of the 65 eyes,63 recovered from bullous keratopathy with a clear cornea.The mean follow-up time was 26.4mo（range,6-84mo）.The mean BCVA improved from 1.70 log MAR preoperatively to 0.54 log MAR at 3mo,0.46 logM AR at 6mo,and 0.37 logM AR at 1y after surgery.The postoperative donor ECD of the 25 patients who successfully underwent specular microscopic examination was 1918±534 cells/mm^2（range,637 to 3056 cells/mm^2）,and the mean endothelial cell loss was 41.9% at 24 mo postoperatively.One eye developed secondary glaucoma and required regrafting via penetrating keratoplasty（PKP）.Another eye had postoperative graft failure due to rejection at 26 mo.Postoperative graft dislocation occurred in eight eyes.All of the eight dislocated grafts were reattached using air reinjection.CONCLUSION： Immunological graft rejection of the donor graft rarely occurs in non-DSEK.Therefore,non-DSEK is a safe,concise,and effective alternative to restore corneal decompensation when the Descemet membrane is disease-free.

Indications for penetrating keratoplasty and anterior lamellar keratoplasty during 2010-2017

AIM: To review the indications of penetrating keratoplasty(PK) and anterior lamellar keratoplasty(ALK) at Qingdao Eye Hospital, Shandong Eye Institute, Qingdao, China, from 2010 to 2017. METHODS: The data of all patients undergoing PK or ALK from January 2010 to December 2017 was retrospectively reviewed, with the indications during 2010-2013 and 2014-2017 compared. RESULTS: A total of 1869 eyes were included, among which 1405 eyes(75.2%) had PK and 464 eyes(24.8%) had ALK. The leading indications were suppurative keratitis(36.8%), keratoconus(15.5%), herpes keratitis(13.1%), and regraft(10.5%). In eyes undergoing PK, the top four indications were suppurative keratitis(38.7%), herpes keratitis(15.3%), keratoconus(12.6%), and regraft(12.5%) during 2014-2017, with the proportion of suppurative keratitis and herpes keratitis decreased while regraft and keratoconus increased compared with 2010-2013. In eyes with ALK, suppurative keratitis(30.8%), keratoconus(24.1%), corneal dystrophies and degenerations(10.6%), and corneal dermoid tumor(9.7%) were the top four indications, and there was no significant difference for the proportion of each indication between 2010-2013 and 2014-2017. CONCLUSION: Suppurative keratitis is the most common indication for PK and ALK at Qingdao Eye Hospital during 2010-2017, followed by keratoconus, herpes keratitis, and regraft. In eyes treated with PK, the proportion of suppurative keratitis and herpes keratitis decrease while regraft and keratoconus increase during 2014-2017 compared with 2010-2013.