Effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer.<p>METHODS: From May 2015 to May 2018, 200 patients with corneal ulcer were selected and divided into combined group and glucocorticoid group according to different treatment methods, 100 cases each. In the combined group, cyclosporine A was given on the basis of the glucocorticoid group. C-reactive protein(CRP)and interleukin-6(IL-6)were measured to evaluate the quality of life, clinical symptoms, treatment efficiency, recurrence rate and incidence of adverse reactions.<p>RESULTS: After treatment, the levels of CRP and IL-6 in the two groups were lower than that before treatment, and the quality of life was higher than that before treatment(<i>P</i><0.05). The level of CRP and IL-6 in the combined group was lower than that in the glucocorticoid group, and the quality of life was higher than that in the glucocorticoid group(<i>P</i><0.05). The time of conjunctival hyperemia, ophthalmalgia and ulcer healing in the combined group were lower than those in the glucocorticoid group(<i>P</i><0.05). The effective rate of combined group was higher than that of glucocorticoid group, and the recurrence rate of combined group was lower than that of glucocorticoid group(<i>P</i><0.05).<p>CONCLUSION: Cyclosporine a combined with hormone is effective in the treatment of corneal ulcer, which can improve the clinical symptoms, reduce the inflammation, improve the quality of life and reduce the recurrence.

Pyroptosis and eye disease / 中华实验眼科杂志

Pyroptosis is a new programmed cell death which has been found recently.Pyroptosis features rapid plasma-membrane rupture and release of pro-inflammatory intracellular contents.Pyroptosis plays a vital role in intracellular bacterial clearance,but may also be involved in the pathological process of inflammatory and autoimmune diseases.It exists in the occurrence,development and dying of many eye diseases.The researches of pyroptosis in agerelated macular degeneration (AMD),cataract,dry eye disease,Mooren's ulcer and acute glaucoma have emerged,an in-depth research may be useful in understanding eye diseases in a deeper level.In this artile,the concept of pyroptosis and its involvement in AMD,cataract,dry eye disease,Mooren's ulcer and acute glaucoma are reviewed.

Current progress on clinical application of cyclosporine A / 国际眼科杂志(Guoji Yanke Zazhi)

@#Cyclosporine A is a new and potent immunosuppressant with high specificity and is widely used in controlling a variety of immunological rejection after organ transplantation. Research found that cyclosporine A suppresses the immune rejection in moderate to severe dry eye syndrome treatment. For mooren ulcers and autoimmune eye diseases, it has a significant effect. The application progress of Cyclosporine A in clinical ophthalmology is now reviewed.

A Two Case of 360 Degree Keratolimbal Allograft

PURPOSE: To report the clinical outcomes of 360-degree keratolimbal allograft in 2 patients. CASE SUMMARY: An 83-year-old female who had uncontrolled Mooren's ulcer invading 360 degrees of the limbus with corneal opacity received a 360-degree keratolimbal allograft (KLAL). Another 63-year-old female who had central corneal opacity and corneal neovascularization due to severe limbal cell deficiency with chemical injury received a 360-degree KLAL. During the average 17.5 months of follow-up, both eyes were tectonically maintained without severe graft rejection. CONCLUSIONS: A 360-degree KLAL may be an effective tectonic procedure for corneal opacity caused by limbal stem cell deficiency. Herein, we report 2 cases of successfully performed 360-degree KLAL with a literature review.

A Case of Autologous Tragal Perichondrium Graft in a Patient with Mooren's Ulcer

PURPOSE: To report the effectiveness of an autologous tragal perichondrium graft for an active Mooren's ulcer. CASE SUMMARY: A 49-year-old male was referred to our clinic with Mooren's ulcer in his left eye. On the first visit, the ulcer involved the entire 360 degrees of the peripheral cornea and the visual acuity was 0.04. As the ulcer did not respond to medical treatment and progressed rapidly, the authors decided on surgical treatment. First, the involved cornea and nearby conjunctiva were removed and the defect was successfully reconstructed with autologous tragal perichondrium and allogenic limbal graft. The progression of corneal ulceration ceased after surgery and the patient's symptoms remarkably improved. Additionally, the graft showed rapid vascularization and engraftment within a week. However, as the opacity evolved and progressed to the central cornea, penetrating keratoplasty (PKP) was performed 5 months after the perichondrial graft. There was no rejection and corneal translucency was kept clear with low-dose steroid eye drops until 6 months after PKP without any sign of limbal deficiency. The patient's final best corrected visual acuity was 0.125. CONCLUSIONS: The present study shows that autologous tragal perichondrium graft is an effective method of treatment for active Mooren's ulcer by defect reconstruction and results in survival of the co-transplanted graft as well as maintaining corneal functions.

Change of Th1 and Th2 cells in patients with active Mooren's ulcer / 中华实验眼科杂志

Background Mooren 's ulcer is an immune-related corneal inflammatory disease,and its pathogenesis remains below understood.Previous studies showed that the imbalance of T helper cell type 1 (Th1) and Th2 cell play important roles in the development of some autoimmune diseases.Thereby the influence of Th1/Th2 cells on the pathogenesis of Mooren's ulcer is being concerned.Objective This study was to investigate the change of Th1 and Th2 subsets in periphery blood of patients with active Mooren's ulcer.Methods Eleven consecutive patients with active Mooren's ulcer and 8 age-and gener-matched healthy controls were included in Zhongshan Ophthalmic Center,Sun Yat-sen University from January 2012 to July 2013 under the approval of Ethic Committee of this hospital and informed consent of each subject.The peripheral blood samples of all the subjects were obtained separately and periphery blood mononuclear cells (PBMCs)were isolated.The percentages of Th1 and Th2 in the PBMCs were assayed by flow cytometer.The relative expressions of T-bet mRNA,GATA-3 mRNA and signal transducer and activator of transcription 5 (Stat5) mRNA in the PBMCs were examined and compared by real-time fluorescence quantitative PCR (RT-qPCR) Results The percentage of Th1 cells in CD4+ T cells and Th1/Th2 value was 0.21％ (0.11％,0.31％) and 8.01 (4.49,12.01) respectively in the Mooren's ulcer group,which were significantly lower than 0.35％ (0.22％,0.71％)and 23.90 (22.49,33.49)in the normal control group,respectively (Z =-2.01,P =0.04 ; Z =-3.06,P =0.00).However,no significant difference was found in the percentage of Th2 between the two groups (Z=-1.98,P＞0.05).The relative expressions of T-bet mRNA and GATA-3 mRNA in PBMCs were significantly lower in the Mooren's ulcer group than those in the normal control group (Z =-3.47,-3.06,both at P=0.00) ;While the relative expression of Stat5 mRNA in PBMCs was insignificant changed between the two groups (Z =-1.05,P =0.33).Conclusions Th1 and Th2 cells are unbalanced in the active Mooren's ulcer patients.In addition,the down-expression of relevant transcription factors in peripheral blood also is seen in these patients.It is inferred that Th1 and Th2 cells may participate in the progress of Mooren's ulcer.

The Clinical Manifestations and Prognostic Factors of Autoimmune-Related Peripheral Corneal Ulcers

PURPOSE: To investigate clinical manifestations and prognostic factors of autoimmune-related peripheral corneal ulcers. METHODS: Nineteen eyes in 18 patients who were diagnosed with autoimmune-related peripheral corneal ulcer from November 1999 to August 2010 were enrolled in the present study. Clinical manifestations and treatment results were investigated retrospectively. RESULTS: The average age at presentation was 64.6 years with female (66.7%) and unilateral (94.4%) dominance. The main etiologies were Mooren's ulcer (53.6%) and rheumatoid arthritis (26.3%). The ulcer depth was greater than 75% of the corneal thickness in more than half of the cases (57.9%) and the mean extent of the ulcer was 69.5degrees. There were no significant improvements in visual acuity after treatment (p = 0.789) and no significant differences in treatment outcomes among etiologies or treatment modalities. The patients who underwent ulcer recurrence (p = 0.048) or treatment failure (p = 0.005) had poorer final visual acuity than those patients who did not. The ulcer depth correlated with treatment failure (p = 0.037). The final visual acuity showed positive correlations with visual acuity at presentation (p = 0.031) and negative correlations with the number of recurrences (p = 0.042). CONCLUSIONS: The visual acuity at presentation and ulcer depths were significant prognostic factors. These factors appeared to be helpful in the treatment of marginal keratitis depending on the depth of the ulcer.

Microtechnique of bilayer amniotic membrane transplantation for treatment of Mooren's ulcer / 中华显微外科杂志

Objective To investigate the mierotechnique of bilayer amniotic membrane transplantation for treatment of Mooren's ulcer and evaluate the efficacy. Methods Six patients (6 eyes) with Mooren's ulcer were recruited for this study. After medical treatment or lameilar keratoplasty failed to arrest progress of corneal ulcer, bilayer amniotic membrane transplantation was performed for the treatment. We investigated the integrity of corneal epithelium, the healing of corneal ulcer, the improvement of stromal edema, the atrophy of neovessels, the transformation of amniotic membrane and the occurrence of relapse. Results All patients were followed up for 24-34 months (mean 30 months). In all cases, superficial anmiotic membrane dissolved or shed on postoperative day 7-11, disconnecting now. Corneal ulcer healed within 7-15 days postoperatively. In 5 eyes, corneal stromal edema faded away within 2-3 weeks. Corneal neovessels regressed within 2-3 months. The deeper grafts were adhered into the ulcer and fused with the cornea 3 months after the operation. Corneal transparence or macula was achieved within 5-8 months. No recurrence of Moorcn's ulcer was oc-curred in 4 patients during the follow-up period, while 2 eyes relapsed for the exposure of sutures and not re-moving the stitches timely, which had been treated with lamellar keratoplasty and no recurrence again during the follow-up period. Conclusion Bilayer amniotic membrane transplantation has advantages for Mooren's ulcer treatment. Mastering the microsurgical techniques and removing the stitches timely are the key to the success of surgery. It also provides good conditions for the further conduct of keratoplasty.

The Amniotic Membrane Transplantation in Corneal Perforation due to Mooren's Ulcer

PURPOSE: To report patients with corneal perforation with Mooren's ulcer treated successfully with amniotic membrane transplantation and cryotherapy. METHODS: We performed conjunctival recession, permanent amniotic membrane transplantation, cryotherapy, amniotic membrane patch to treat corneal perforation associated with severe inflammatory Mooren's ulcer of 4 eyes in 3 patients. We investigated the interval of absence of inflammation, reepithelization over grafted amniotic membrane, and restoration of visual acuity. RESULTS: The perforated corneal lesion was sealed successfully by the amniotic membrane in 4 eyes. The complete reepithelization over grafted amniotic membrane was achieved 21+/-2.7 days and complete remission was achieved 94+/-13.0 days after surgery. There was no recurrence in 3 eyes during 21+/-2.7 months. A patient who recurred inflammatory impending corneal perforation underwent limbal transplantation with amniotic membrane re-transplantation, which resulted in remission after 13 months. All 3 eyes restored visual acuity Except one who developed cataract. CONCLUSIONS: Amniotic membrane transplantation may be useful in treating corneal perforation with active inflammation in Mooren's ulcer.

Amniotic membrane transplantation for the managenment of earlier Mooren's ulcer / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy and safety of annular conjunctival excision combined with amniotic membrane transplantation for the management of earlier Mooren's ulcer.METHODS: Thirty eyes (24 patients) with earlier Mooren's ulcer were treated with this method, followed-up for 5-30mo. The characteristic of these patients was localized periphery corneal ulcer: the ulcer involved 30-120° corneal limbus with depth of 1/3-1/2 cornealthickness and width of 2-5mm.RESULTS: After surgery, symptoms subsided remarkably and immediately in all patients,and almost disappeared after stitches were removed. Corneal melts were controlled. At postoperative 2-3mo, the corneal thickness of the ulcer area became almost stable, which in some patients recovered normal and in others were still thinner than normal, and the average increase was about 1/3 of the corneal thickness. Corneal transparence and vision were improved. During follow-up, no severe complications or recurrence were noted.CONCLUSION: Conjunctival peritomy combined with amniotic membrane transplantation is an effective and safe method for the treatment of earlier Mooren's ulcer.

The Involvement of Multipotential Progenitor Cells in Mooren's Ulcer

The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and alpha-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and yen a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

Expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in Mooren's ulcer cornea / 第三军医大学学报

Objective To investigate the expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases in active Mooren's ulcer corneas.Methods An indirect immunofluorescent technique was used to visualize the presence of matrix metalloproteinase-1,2,3,9 and tissue inhibitor of metalloproteinase-1,2 in active Mooren's ulcer corneas from 6 patients and normal human corneas from 4 corpses.The results were further analyzed by an image-processing system.Results Only TIMP1,2 were detected in normal corneal epithelium while MMP-1,2,3,9,and TIMP-1,2 all were found in Mooren's ulcer corneas.MMP-2,TIMP-2 expressed in epithelium,MMP-3 expressed in stroma,MMP-1,9,and TIMP-1 expressed in both epithelium and stroma.Conclusion In active Mooren's ulcer cases,corneal lesion and corneal wound healing coexist,but the destructive reaction is greater than wound healing.Over-expression of MMP-9 and unbalanced regulation of MMPs/TIMPs may play an important role in the Mooren's ulcer of this stage.

The Clinical Manifestations of Mooren's Ulcer

PURPOSE: To investigate the clinical manifestations and treatment results of Mooren's ulcer. METHODS: Sixteen eyes in eleven patients who were diagnosed as Mooren's ulcer at Seoul National University Hospital from 1995 to 2000 were enrolled. The clinical manifestations and treatment results were investigated retrospectively. RESULTS: The average age was 44.2 years and the male to female ratio was 5:6. The average follow up period was 26 months. Five patients had bilateral involvement. Nine patients were of limited type and two of progressive type. Ocular pain was the most frequently presenting symptom(82%). Topical corticosteroid application was the main therapeutic modality (75%) and all the patients responded well to the treatment. The prognosis was better in patients with unilateral lesion or in younger patients. As complications, one case of corneal perforation and one case of herpes keratitis occurred. CONCLUSIONS: Our retrospective study on Korean Mooren's ulcer cases revealed 1) there were few cases of progressive type, 2) most of them responded well to only topical steroid application, and 3) the prognosis was poor in patients with bilateral lesions or in old patients.

Peripheral Corneal Ulcer after Simultaneous Surgery for Cataract and Pterygium: Secondary Mooren's Ulcer

PURPOSE: To report a previously unreported secondary Mooren's ulcer associated with simultaneous sur-gery for cataract and pterygium. METHODS: Case report. Five days after simultaneous surgery for cataract and pterygium, an 86-year-old woman developed severe pain and a superior and inferior peripheral corneal ulcer that had the characteristic clinical appearance of Mooren's ulcer. RESULTS: Peripheral corneal ulcer is rapidly progressive, painful, beginning at the limbus with a gray, overhanging, infiltrated edge at its central border. She had no history of collagen-vascular disease, negative serologic test result, and negative culture for pathogen. Surgical trauma may have been the inciting factor in development of the ulcer. She was treated with topical and systemic steroids. After complete control of the inflammation, the patient remained in remission.

Expression of collagen type Ⅲ, laminin and fibronectin in Mooren's ulcer / 第三军医大学学报

Objective To compare the locations and levels of collagen type Ⅲ, laminin, and fibronectin in Mooren's ulcer and normal human corneas. Methods An indirect immunofluorescent technique and immunohistochemical staining were used to determine the distribution of collagen type Ⅲ, laminin, and fibronectin. The positive results were quantitatively analyzed with an image-processing system. Results Collagen type Ⅲ was not detected in the normal cornea. However, the staining could be seen in the corneal stroma close to Mooren's ulcer focus. Laminin was expressed faintly in the basement membrane of the normal cornea and the positive expression increased in the basement membrane and Bowman's membrane of Mooren's ulcer. In the normal cornea basement membrane, fibronectin was located continuously. In Mooren's ulcer basement membrane, however, fibronectin could not be found in all sections in which one expressed in epithelium and the others in stoma close to the ulcer focus. Conclusion Epithelial basement membrane may play a potential role in the pathogenesis of Mooren's ulcer.