Effect of autologous serum after amniotic membrane transplantation for persistent corneal ulcers

AIM:To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers.METHODS:Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears(sodium hyaluronate 0.2%,ATs group,n=20)or autologous serum eye drops(ASEDs,n=20)following treatment with amniotic membrane transplantation.Digital slit lamp images were acquired from all patients before and 30d post treatment.The area with fibrovascular tissue was calculated using Image J.Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment.Scar tissue transparency was assessed with a novel optical densitometry.RESULTS:Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group,respectively.Twenty-two male and 18 female patients were included in the study.The improvement in visual acuity was significantly greater in the ASEDs group(0.14±0.04)than the ATs(0.08±0.04;P=0.00046).Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups.There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups(P=0.082).The success rate in the two groups was similar.The difference in densitometry between the ATs and ASEDs group was statistically significant(P=0.042)with greater reduction from baseline in the ASEDS group.CONCLUSION:Autologous serum eye drops can lead to better visual acuity,more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.

Amniotic membrane transplantation: an updated clinical review for the ophthalmologist

Although amniotic membrane transplantation(AMT)has long been used as an essential surgical technique for ocular surface reconstruction,its role continues to evolve and expand.In the management of numerous ocular surface disorders,ranging from inflammatory to infectious,traumatic to neoplastic,the ability to perform AMT is a valuable addition to the skillset of any ophthalmologist.The purpose of this paper is to provide ophthalmologists with an updated,evidence-based review of the clinical indications for AMT in corneal and conjunctival reconstruction,reviewing its common and even experimental applications known to date.The methods of amniotic membrane preservation,the available commercial amniotic membrane products to date,and future directions for amniotic membrane use,including amniotic membrane extract eye drops(AMEED),are also discussed.It is paramount for ophthalmologists to stay up-to-date on the applications of AMT so as to effectively incorporate this versatile treatment modality into their practice,both in the operating room and in the clinic.By familiarizing the general ophthalmologist with its diverse applications,we hope to motivate general ophthalmologists to incorporate the use of AMT into their clinical practice,or provide guidance on how to recognize when referral to a corneal specialist for amniotic membrane application is prudent.

Clinical outcome of combined conjunctival autograft transplantation and amniotic membrane transplantation in pterygium surgery

AIM： To compare long-term outcome of primary and recurrent pterygium surgery with three different techniques： combined conjunctival autograft and overlay amniotic membrane transplantation （CAT with AMT）, conjunctival autograft transplantation （CAT） alone and amniotic membrane transplantation （AMT） alone. METHODS： In this retrospective study, 142 eyes of 142 pterygium patients （104 primary, 38 recurrent）who underwent CAT （group A）, AMT （group B） or CAT with AMT （group C） respectively following surgical excision were reviewed and compared based on the recurrences and post-operative complications. RESULTS： The number of recurrence post-surgery were 17 （9 from primary, 8 from recurrent; the same description below）, 18 （10, 8） and 2 （1, 1） in groups A, B, and C respectively; dry eyes were 22 （16, 6）, 27 （18, 9） and 7 （3, 4）; conjunctival inflammations were 30 （17, 13）, 27 （16, 11） and 11 （6, 5）. Patients in group C （either pdmary or recurrent or both） mainly showed significantly better results than those in group A or B （P〈0.05） regarding above-mentioned clinical effects. CONCLUSION： Combined CAT and overly AMT have significantly lower rates of recurrence and postoperative complications for primary and recurrent pterygium surgery than CAT or AMT alone.

Comparison of trabeculectomy and trabeculectomy with amniotic membrane transplantation in the same patient with bilateral glaucoma

AIM:To observe effects of trabeculectomy with amniotic membrane transplantation(AMT) in controlling postoperative intraocular pressure(IOP) in patients with medically uncontrolled glaucoma.·METHODS:This study included adult patients with requiring bilateral glaucoma surgery.Each patient underwent trabeculectomy(Non-AMT group) in one eye and with AMT(AMT group) in the other eye according to randomized principle.Success was defined as intraocular pressure(IOP) 【21mmHg without any anti-glaucoma medications at 24 months follow-up.The two groups were compared in terms of IOP,complications and success rate.·RESULTS:Thirty-four eyes of 17 patients were investigated in this study.There was no statistically signifcant difference in pre-operative IOP between the two groups.The mean IOP was lower in AMT group compared with Non-AMT group on follow up months 12,18,and 24.Postoperative complications were more frequent in Non-AMT group(35.3%,6/17) compared with AMT group(5.9%,1/17).The success rate of surgery was88.2%(15/17) in Non-AMT group and 100%(17/17) in AMT group.·CONCLUSION:Trabeculectomy with AMT is an effective procedure to reduce IOP and complications,thereby improving surgical success rates.

Amniotic membrane transplantation for porous sphere orbital implant exposure

Objective: This study is aimed at describing the clinical outcome of amniotic membrane transplantation for exposure of porous sphere implants. Methods: A retrospective review of consecutive cases of porous sphere orbital implant exposure was carried out. Eight cases were presented between May 2004 and Oct. 2006 (5 males, 3 females; mean age 44.5 years). Six had enucleation and two had evisceration. Exposure occurred in two primary and six secondary. Orbital implant diameter was 22 mm in seven cases and 20 mm in one case. Six patients are with hydroxyapatite and two with high-density porous polyethylene (Medpor) orbital implants. The mean time from implantation to exposure was 1.1 months (range 0.8~2 months). All patients required surgical intervention. Results: The time of follow-up ranged from 3.0 to 28.0 months (mean 16.5 months). Amniotic membrane grafting successfully closed the defect without re-exposure in all of these patients. The grafts were left bare with a mean time to conjunctiva of about 1 month (range 0.8~1.5 months). Conclusion: Exposed porous sphere implants were treated suc-cessfully with amniotic membrane graft in all of patients. The graft is easy to harvest. This technique is useful, dose not lead to prolonged socket inflammation and infection, and it is valuable application extensively.

Effects of amniotic membrane transplantation on cytokines expression in chemically burned rat corneas

AIM: To investigate the effect of amniotic membrane transplantation (AMT) on the expressions of inflammatory-related, angiogenic-related and growth-related cytokines in rat corneas after chemical injury. METHODS: Alkali wounds were inflicted on the central corneas of rats by applying a round filter paper soaked in 1mol/L NaOH for 40 seconds. One week after alkali burn, 12 rats were randomly divided into 2 groups: the AMT group and the control group, and AMT was performed on the rats in the AMT group. Corneal opacity and neovascularization were observed by slit-lamp microscopy. The protein levels of interleukin (IL)-2, interferon (IFN)-gamma, IL-10 and transforming growth factor (TGF)-beta were determined by enzyme-linked immunosorbent assay 2 weeks after AMT. The mRNA levels of matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) were evaluated by real-time quantitative PCR. RESULTS: In the AMT group, the corneal opacity was improved (P =0.011) and the area of corneal neovascularization was significantly decreased (P=0.005) compared with the control group. The amount of IL-2 and IFN-gamma secreted by Th1 cells were decreased after AMT, whereas the amount of IL-10 and TGF-beta secreted by Th2 cells were increased ( P <0.05). The level of MMP-2 was significantly down-regulated (P=0.013) at the nnRNA level in the AMT group, while the expression of EGF was significantly higher (P= 0.022) compared with the control. CONCLUSION: AMT may suppress corneal neovascularization after chemical injury by modulating the expressions of soluble factors.

Sutureless amniotic membrane transplantation following excision of ocular surface neoplasia

【正】Dear Sir,S uccess of surgical management of conjunctival neoplasias primarily depends on the complete excision of the mass and eradication of tumor cells from the ocular surface[1-3].Especially in cases that extensive resections are required,primary closure may not be feasible;so ocular surface reconstruction can be a challenging problem for the surgeons.For conjunctival tissue defects different surgical

Toxic keratopathy associated with abuse of topical anesthetics and amniotic membrane transplantation for treatment

AIMTo evaluate the clinical findings of toxic keratopathy associated with abuse of topical anesthetics and the treatment efficacy of amniotic membrane transplantation (AMT).METHODSFifteen eyes of 10 patients with abuse of topical anesthetics were included in this study. The data collected included patients' demographic information, initial best corrected visual acuity (BCVA), clinical findings, time to AMT, duration of epithelization, additional treatments, posttreatment BCVA, and the results of psychiatric examination.RESULTSAll patients were male, with the mean age of 37.9&#x000b1;5.4y. The patients had received 0.5% proparacaine hydrochloride due to pain resulting from foreign bodies, such as welding flash burns and car battery explosions, for a mean of 18.2&#x000b1;12.4d. The mean initial BCVA of the patients was 0.069&#x000b1;0.100. All patients had persistent epithelial defects, stromal infiltration, ring ulcer, and corneal edema. Initially, medical treatment was attempted in all cases. Because of severe pain, persistent epithelial defects and progressing stromal thinning did not improve with medical treatment, thus, the patients underwent AMT. The mean posttreatment BCVA of the patients was 0.33&#x000b1;0.27. All of them, except for two patients, showed improved visual acuity. One patient underwent evisceration for corneal melting and endophthalmitis in another center, and one patient underwent evisceration for severe pain of unknown origin. All 5 patients who consented to a psychiatric examination had depression, had personality disorder, and used tobacco.CONCLUSIONAMT appears to be an effective method for pain relief, rapid epithelial and stromal healing; however, visual prognosis is still poor despite medical and surgical interventions.

Amniotic membrane transplantation in a patient with impending perforated corneal ulcer caused by Streptococcus mitis: A case report and review of literature

BACKGROUND Streptococcus mitis(S.mitis)is an opportunistic pathogen that can lead to severe ocular infections.In previous reports,penetrating keratoplasty(PK)was usually adopted for the treatment of persistent corneal ulcers.This report describes an unusual case of nonhealing descemetocele caused by S.mitis treated by antibiotics plus amniotic membrane transplantation(AMT).CASE SUMMARY A 63-year-old woman presented with a right persistent corneal ulcer that she had suffered from for the past 9 mo.The culture of a corneal scraping yielded S.mitis.The right eye descemetocele decreased in diameter from 3 to 0.8 mm after the continuous administration of topical vancomycin and ceftriaxone for 2 wk.Due to the slow healing,AMT was performed.Her corneal erosion healed and gradually became clear.Her visual acuity recovered from initially counting fingers to 100/200 at the last follow-up,67 mo after AMT.CONCLUSION Antibiotics plus AMT may be an effective alternative treatment other than PK to promote epithelializationand to reduce inflammation in the corneas complicated by S. mitis keratitis.

Clinical and impression cytology findings of amniotic membrane and oral mucosal membrane transplantation for the management of socket contracture

AIM:To investigate and compare the cytopathological and clinical effects of amniotic membrane transplantation(AMT)and oral mucosal membrane transplantation(OMMT)in socket contraction.METHODS:Twelve patients who could not be fitted with ocular prosthesis due to socket contracture were included in this study.Seven patients underwent AMT and 5 patients underwent OMMT.Thirteen patients who had healthy sockets were included as control group.Depth of inferior fornix,degree of inflammation,extent of the socket contracture and socket volume were measured in the preoperative period and at sixth and twelfth weeks postoperatively.Impression cytology of conjunctival fornices and tear transforming growth factor beta-1(TGFβ1)levels were determined.RESULTS:In the AMT group,socket volume and lower fornix depth values were significantly higher(P=0.030and P=0.004 respectively)and inflammation levels and impression cytology stages(P=0.037 and P=0.022respectively)were significantly lower in postoperative period compared to preoperative period.In the OMMT group,no statistical differences were found in terms of clinical parameters,inflammation levels and impression cytology stages of preoperative versus postoperative values.Preoperative tear TGFβ1 levels were higher in AMT and OMMT groups compared to the control group(25.5 ng/mL,26.3 ng/mL and 21.7 ng/mL respectively).Decreased tear TGFβ1 levels were observed in both the AMT and OMMT groups postoperatively(median decrease value=2.1 ng/mL and 2.7 ng/mL respectively).CONCLUSION:AMT is associated with postoperative improvement in inferior fornix depth,socket volume,inflammation and impression cytology levels and may bea more proper alternative method than OMMT in the management of socket contracture.

Amniotic membrane welded to contact lens by 1470-nm diode laser:a novel method for sutureless amniotic membrane transplantation

AIM: To avoid the side effects of the suture usage by welding amniotic membrane(AM) to contact lens(CL)with laser.METHODS: AM was taken from pregnant women and cleaned from blood clots with sterile phosphate-buffered physiological saline solution which included antibiotics.Stromal side of the AM was spread inside of the CL and it was welded to CL by 1470 nm diode laser. And 600 μm diameter fiber tip of the laser was contacted with the epithelial side of the AM from 4 separate points. After welding excess amniotic membrane around the CL was cut with a scalpel.RESULTS: Stromal side of the AM was spread inside of the CL and then with laser fiber, different power levels and exposure times were applied on the epithelium of AM and 340 m W for seven seconds was found optimal.CL and AM attached with the spot welding effect in 4points by touching fiber tip. CL-AM welded complex did not separated from each other while holding AM that extend beyond the CL with the help of two forceps.CONCLUSION: As a conclusion, it was aimed in this study to achieve the success of the conventional amniotic membrane transplantation(AMT) with the easiness of applying a CL and to avoid risks and side effects of corneal or conjunctival suturing. The results showed that the application of the CL-AM complex will be as easy as the application of a CL and lasts shortly.

Efficacy of rhNGF-loaded amniotic membrane transplantation for rabbit corneal epithelial and nerve regeneration

AIM:To evaluate the efficacy of recombinant human nerve growth factor-loaded amniotic membrane(rh NGF-AM)on corneal epithelial and nerve regeneration in rabbit model.METHODS:Freshly prepared human amniotic membrane(AM)were immersed into PBS buffer containing 100 or 500μg/mL rh NGF for 15,30,and 60 min at 4℃.The in vitro release kinetics of rh NGF was measured with ELISA.For in vivo evaluation,the AM were immersed with 500μg/mL rh NGF for 30 min.Fifty-seven rabbits were selected to establish corneal epithelial defect model.In addition to the 19 rabbits in control group,38 rabbits received AM transplantation with or without rh NGF after the removal of central epithelium.Corneal epithelial defect area,sub-epithelial nerve fiber density,corneal sensitivity,rh NGF contents in resident AM and corneas were measured after the surgery.RESULTS:rh NGF was sustained release from the AM within 14 d in vitro,with the positive correlation with initial immersion concentration.The immersion of AM in 500μg/mL rh NGF for 30 min achieved the most stable release within 14 d.After transplantation in rabbit cornea,a high concentration of rh NGF in resident rh NGF-AM and cornea was maintained within 8 d.Corneal epithelial healing,nerve fiber regeneration and the recovery of corneal sensitivity were significantly accelerated after the rh NGF-AM transplantation when compared to simple AM transplantation(all P<0.05).CONCLUSION:Simple immersion of AM achieves the sustained release of rh NGF,and promotes corneal epithelial wound healing and nerve regeneration,as well as the recovery of corneal sensitivity in rabbit.

Amniotic membrane transplantation with topical interferon alfa-2b after excision of ocular surface squamous neoplasia

To evaluate the outcome of amniotic membrane transplantation（AMT） after tumor excision followed by topical interferon alfa-2 b（IFNα2 b） drops for primary ocular surface squamous neoplasia（OSSN）. Twelve eyes of 12 patients with a mean age of 66±10 y were included. The average followup was 23±10 mo. All 12 patients had limbal involvement. Smooth ocular surface and transparent cornea were achieved in all cases. No sign of inflammation, neovascularization, symblepharon or recurrence was noted at the last follow-up. We conclude that AMT with topical IFNα2 b drops restores a healthy ocular surface in OSSN without recurrence.

Resection and Cryotherapy Combined with Amniotic Membrane Transplantation for the Treatment of Vernal Keratoconjunctivitis with Giant Papillae

To evaluate the efficacy and safety of resection and cryotherapy combined with amniotic membrane transplantation （AMT） for the treatment of vernal keratoconjunctivitis （VKC） with giant papillae （GP）. Eight patients （16 eyes involved） with VKC, characterized by GP on the upper tarsal conjunctiva, underwent resection and cryotherapy in combination with AMT. The follow-up lasted for 3-22 months. The results showed that corneal shield ulcers and superficial punctuate keratitis healed during the first week after surgery and did not recur. Fourteen eyes （87.5 %） were symptom-free l month after surgery, and no GE ectropion, trichiasis and other complications were noted, but the blood vessels of upper tarsal conjunctiva could not be clearly seen and a little conjunctival scar was observed. Recurrence of GP was observed in 2 eyes （12.5 %）, with the area being less and irritation milder as compared with those before the operation. Among the two eyes, one eye was treated by cyclosporine eyedrops with improvement, but the other eye showed no improvement after the treatment, and underwent a second surgery with a cotton patch soaked in fluorouracil applied onto the supratarsal area after resection and cryotherapy. Four months after the treatment the patient presented no symptoms and GP did not recur. It is concluded that the resection and cryotherapy combined with AMT is an effective and safe treatment for VKC with GP.

Human amniotic membrane transplantation: Different modalities of its use in ophthalmology

The amniotic membrane(AM) is the inner layer of the fetal membranes and consist of 3 different layers: the epithelium, basement membrane and stroma which further consists of three contiguous but distinct layers: the inner compact layer, middle fibroblast layer and the outermost spongy layer. The AM has been shown to have anti-inflammatory, anti-fibrotic, anti-angiogenic as well as anti-microbial properties. Also because of its transparent structure, lack of immunogenicity and the ability to provide an excellent substrate for growth, migration and adhesion of epithelial corneal and conjunctival cells, it is being used increasingly for ocular surface reconstruction in a variety of ocular pathologies including corneal disorders associated with limbal stem cell deficiency, surgeries for conjunctival reconstruction, as a carrier for ex vivo expansion of limbal epithelial cells, glaucoma surgeries and sceral melts and perforations. However indiscriminate use of human AM needs to be discouraged as complications though infrequent can occur. These include risk of transmission of bacterial, viral or fungal infections to the recipient if the donors are not adequately screened for communicable diseases, if the membrane is not processed under sterile condi-tions or if storage is improper. Optimal outcomes can be achieved only with meticulous case selection. This review explores the ever expanding ophthalmological indications for the use of human AM.

Comparison of the Efficacy of Pterygium Resection Combined with Conjunctival Autograft versus Pterygium Resection Combined with Amniotic Membrane Transplantation

Purpose:To compare the efficacy of pterygium resection combined with conjunctival autograft versus pterygium resection combined with amniotic membrane transplantation in the treatment of pterygium. Methods: A total of 118 cases (133 eyes) were randomly assigned to receive pterygium resection combined with conjunctival autograft (n=81) or pterygium resection combined with amniotic membrane transplantation(n=52)..Corneal wound healing and neovascularization and the presence or absence of conjunctival proliferation and hyperemia were analyzed at 12 months post-operatively. Results: In the conjunctival autograft group, 6 eyes (7.4%) had recurrent pterygium,.while in the amniotic membrane transplantation group, 10 eyes showed recurrence (19.2%,P<0.05,.chi-square)..Patients in the conjunctival autograft group recovered significantly faster compared with those in the amniotic membrane transplantation group. Conclusion:.Patients receiving pterygium surgery combined with conjunctival autograft had lower recurrence rates and experience faster recovery compared with those undergoing pterygium resection combined with amniotic membrane transplantation.

Fresh Amniotic Membrane Transplantation for Conjunctival Surface Reconstruction

Purpose:To determine whether fresh human amniotic membrane can be used to reconstruct the conjunctiveal defect creates during symblepharon lysis.Methods:Forth-two eyes of 39 consecutive patients with eye burns and Stevens-Johnson syndrome were randomized to accept fresh or preserved human amniotic membrane transplantation(AMT) during the period of severe scarring.Impression cytology was performed in 12 eyes with normal tear secretion which received fresh AMT.Results:During a mean follow-up of 11 months (range,6 to 18 months),thirty-five patients (37 eyes)showed successful ocular surface reconstruction and resolution of motility restriction while four patients (2 eyes with fresh AMT,3 eye with preserved AMT)with minimal recurrence of symblepharon.There was no significant difference statistically between two groups(Chi-square test).Amniotic epithelial cells can survive about three months after being transplanted onto ocular surfaces with normal tear secretion.Conclusion:Both fresh and preserved human amniotic membrane can be considered an ideal alternative substrate for conjunctival surface reconstruction during removal of severe symblepharon.

Amniotic Membrane Transplantation for Conjunctival Tumor

Purpose: To evaluate the possibility of amniotic membrane transplantation (AMT) for the treatment of conjunctival tumor.Methods: Preserved AMT was performed in 26 patients (26 eyes) with conjunctival tumor, including 9 eyes (34.62%) with malignant tumor (conjunctival malignant melanoma,corneal and conjunctival squamous cell carcinoma, conjunctival lymphoma), 17 eyes(65.38%) with benign tumor(conjunctival papilloma, conjunctival dermoid tumor, conjunctival nevus, hemangioma etc.).Result: All the patients are followed up for 1 ～53 months. No acute rejection was observed after preserved AMT. Ideal healing was found in conjunctiva wound.Conclusion: Preserved AMT is a very effective method to repair wound after giant conjunctival tumor operation. Complete removal of tumor and perfect fixation are the key of ocular surface reconstruction.

Fresh Amniotic Membrane Transplantation Combined Lamellar Keratoplasty for Patients with Recurrent Mooren's Ulcer

Purpose: To investigate the possibility of amniotic membrane as an immunologicalinsulating band to reduce the recurrent frequency of Mooren's ulcer.Methods: Twelve cases(12 eyes)with recurrent Mooren's Ulcer were observed. Amongthem, 4 cases(4 eyes)were male and 8 cases(8 eyes) female, ranging in age between 26and 51 years[mean(41 ± 3)years]. Three eyes recurred once, 5 eyes twice, and 4 eyesthree before. Eleven of 12 cases (11/12 eyes)with frequently recurrent Mooren's ulcerunderwent lamellar keratoplasty combined amniotic membrane transplantation(AMT).One patient who had entire corneal ulceration accepted AMT alone.Results: Follow-up time is 12 to 29 months, [mean (23 ± 6) months]. Before AMT, therecurrent frequency of Mooren's Ulcer of all cases after corneal surgery was 1 ～ 7 months[mean(3 ± 2)months]. Nine of 12 eyes with lamellar keratoplasty combined AMT did notrecur within the observation period; 2 eyes recurred 11 months after the surgery. Threemonths postoperatively, neovascularization was observed, which made it nearly impossibleto decipher between amniotic membrane and its nearby conjunctiva, only at the junctionof the transplant can some trails be observed. One case with entire AMT alone showedgraft resolution and neovascularization in 1 month.Conclusion:AMT combined with lamellar keratoplasty and lesion excision may delayrecurrence of Mooren's Ulcer, reduce its recurrent frequency. Besides the effects ofdecreasing inflammation, it may have immunological insulating function as well. Thisconclusion should be proven by further clinical comparative study of much moresamples.

Amniotic membrane mesenchymal stromal cell-derived secretome in the treatment of acute ischemic stroke:A case report

BACKGROUND Stroke is the second and third leading cause of death and disability,respectively.To date,no definitive treatment can repair lost brain function.Recently,various preclinical studies have been reported on mesenchymal stromal cells(MSCs)and their derivatives and their potential as alternative therapies for stroke.CASE SUMMARY A 45-year-old female suffered an acute stroke,which led to paralysis in the left upper and lower limbs.The amniotic membrane MSC-derived secretome(MSCsecretome)was intravenously transplanted once a week for 4 wk.MSC-secretomeregulated regulatory T cells were investigated for the beneficial effects.The clinical improvement of this patient was accompanied by an increased frequency of regulatory T cells after transplantation.CONCLUSION Intravenous administration of MSC-secretome can potentially treat patients who suffer from acute ischemic stroke.