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The role of corneal endothelium in macular corneal dystrophy development and recurrence

Science China(Life Sciences) 2024年第2期67卷 332-344页

作者： Bi-Ning Zhang Benxiang Qi Chunxiao Dong Bin Zhang Jun Cheng Xin Wang Suxia Li Xiaoyun Zhuang Shijiu Chen Haoyun Duan Dewei Li Sujie Zhu Guoyun Li Yihai Cao Qingjun Zhou Lixin Xie Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071China School of Ophthalmology Shandong First Medical UniversityQingdao 250021China Department of Medicine Qingdao UniversityQingdao 266071China Eye Institute of Shandong First Medical University Eye Hospital of Shandong First Medical University(Shandong Eye Hospital)Jinan 250021China Department of Ophthalmology School of Clinical MedicineWeifang Medical UniversityWeifang 261072China Institute of Translational Medicine College of MedicineQingdao UniversityQingdao 266071China Key Laboratory of Marine Drugs of Ministry of Education Shandong Provincial Key Laboratory of Glycoscience and GlycotechnologySchool of Medicine and PharmacyOcean University of ChinaQingdao 266071China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266071China Department of Microbiology Tumor and Cell BiologyBiomedicumKarolinska InstitutetStockholm 17177Sweden

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD patients.Unfortunately,postoperative recurrence remains a significant challenge.We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence.Our experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium.Selective knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients.Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial abnormalities.Intracameral injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant mice.Overall,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

关键词： macular corneal dystrophy recurrence corneal endothelium keratan sulfate penetrating keratoplasty

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Long-term comparison of full-bed deep anterior lamellar keratoplasty and penetrating keratoplasty in treating keratoconus

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第5期14卷 438-450页

作者： Yong-ming ZHANG Shuang-qing WU Yu-feng YAO Department of Ophthalmology Sir Run Run Shaw HospitalSchool of MedicineZhejiang University Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University

Objective: To compare postoperative outcomes of full-bed deep anterior lamellar keratoplasty (DALK) with penetrating keratoplasty (PK) in treating keratoconus. Methods: Seventy-five eyes of 64 patients who received full-bed DALK and 52 eyes of 51 patients who received PK between June 2000 and August 2010 were included in this retrospective study. Full-bed DALK was performed using Yao's hooking-detaching technique. PK was performed using a standard technique. Intraoperative and postoperative complications, visual acuity, rejection, graft survival, endothelial cell density, corneal sensation recovery, and re-innervation were compared between the two groups. Results: A best correct visual acuity of 0.5 or better was achieved in 90.7% of eyes after full-bed DALK and in 92.3% of eyes after PK (P=0.75). By the fifth postoperative year, graft endothelial cell loss reached 34.6% in the PK group vs. 13.9% in the full-bed DALK group (P0.05). Intraoperative microperforation occurred in seven out of 75 (9.3%) eyes with a temporally postoperative double anterior chamber in two eyes in the full-bed DALK group. Postoperative complications in the PK vs. the full-bed DALK groups respectively were: rejection (7.7% vs. 0%, P=0.015), high intraocular pressure (IOP) (46.2% vs. 1.3%, P<0.001), secondary glaucoma (9.6% vs. 0%, P=0.006), complicated cataract (19.2% vs. 0%, P<0.001), and wound dehiscence (9.6% vs. 0%, P=0.006). Conclusions: Both full-bed DALK and PK can offer long-term satisfactory visual outcomes for keratoconus. Graft rejection, secondary glaucoma, complicated cataracts, and constant endothelial cell loss were observed in eyes only after PK.

关键词： Full-bed deep anterior lamellar keratoplasty penetrating keratoplasty Keratoconus Forceps hooking Viscoelastic detaching

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Effects of Cataract Surgery on Endothelium in Transplanted Corneal Grafts： Comparison of Extracapsular Cataract Extraction and Phacoemulsification for Complicated Cataract after penetrating keratoplasty

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Chinese Medical Journal 2016年第17期129卷 2096-2101页

作者： Hong-Wei Zhou Li-Xin Xie Department of Ophthalmology Renmin Hospital of Wuhan University Wuhan Hubei 430060 China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute Shandong Academy of Medical Sciences Qingdao Shandong 266071 China

Background： The endothelium should be carefully evaluated when choosing a surgical technique for cataract removal. Therefore, we aimed to study the effects of different cataract surgery techniques on endothelial cell loss in transplanted corneal grafts. Methods： A total of 54 patients who received complicated cataract surgery in post-penetrating keratoplasty （PKP） eyes at the Shandong Eye Institute between February 2001 and June 2014 were included, and clinical records were reviewed. Baseline demographic details, clinical characteristics, endothelial cell density （ECD）, and best-corrected visual acuity （BCVA） were recorded. Wilcoxon rank-sum test and Wilcoxon signed-rank test were used to test the equality of medians. A regression model was constructed to compare the reduced rate of ECD. Results： Of the 54 eyes included in this study, extracapsular cataract extraction （ECCE） was performed in 34 eyes of 33 patients （ECCE group） whereas phacoemulsification was performed in 20 eyes of 20 patients （phacoemulsification group）. There was no signifcant difference in the median age （P = 0.081） or preoperative ECD （P = 0.585） between the two groups. At 6 months after cataract surgery, ECD in ECCE group was significantly higher than that in phacoemulsification group （P = 0.043）. In addition, the endothelial cell loss rate in ECCE group was significantly lower than that in phacoemulsification group at 2 months （P = 0.018）, 4 months （P 〈 0.001）, and 6 months （P 〈 0.001） after cataract surgery. Endothelial cell loss rate after cataract surgery increased over the 6-month study duration in both ECCE group （P 〈 0.001） and phacoemulsification group （P 〈 0.001）, but phacoemulsification resulted in a greater reduction in ECD than that of ECCE in transplanted corneal grafts （P 〈 0.001）. There was no signifcant difference in postoperative BCVA between the two groups （P = 0.065）. Conclusion： ECCE is more suitable than phacoemulsification in cataract surgery in complicated cataract after PKP.

关键词： Complicated Cataract Corneal Endothelial Cell Extracapsular Cataract Extraction penetrating keratoplasty Phacoemulsification

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Changing trends in penetrating keratoplasty indications at a tertiary eye care center in Budapest,Hungary between 2006 and 2017

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International Journal of Ophthalmology(English edition) 2020年第11期13卷 1814-1819页

作者： Milan Tamas Pluzsik Gabor Toth Jeannette Toth Andrds Matolcsy Achim Langenbucher Agnes Kerenyi Zoltdn Zsolt Nagy Nora Szentmary Department of Ophthalmology Semmelweis UniversityBudapest 1085Hungary Department of Ophthalmology Bajcsy-Zsilinszky HospitalBudapest 1106.Hungary 2^(nd)Department of Pathology Semmelweis UniversityBudapest 1091Hungary 1^(st)Department of Pathology and Experimental Cancer Research Semmelweis UniversityBudapest 1085Hungary Experimental Ophthalmology Saarland UniversityHomburg/Saar 66421Germany Dr.Rolf M.Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research Saarland University Homburg/Saar 66424Germany

AIM:To analyze the changing trends in penetrating keratoplasty(PKP)indications.METHODS:This retrospective study included all patients with PKP between 2006 and 2017.Patients were classified using histological diagnoses.Our groups were as the following:pseudophakic or aphakic bullous keratopathy,regraft,acute necrotizing and ulcerative keratitis,keratoconus,Fuchs'dystrophy,corneal dystrophy other than Fuchs',corneal scar,other diagnoses and failed endothelial keratoplasty graft.Additionally,two different time-periods(2006-2012 and 2013-2017)were analysed.RESULTS:Totally 1721 histological analyses of 1214 patients were available for review.The diagnoses were pseudophakic or aphakic bullous keratopathy in 487(28.3%),regraft in 443(25.7%),acute necrotizing and ulcerative keratitis in 313(18.2%),corneal scar in 153(8.9%),keratoconus in 140(8.1%).Fuchs'dystrophy in 61(3.5%),corneal dystrophy other than Fuchs'in 46(2.7%),other diagnoses in 44(2.6%)and failed endothelial keratoplasty graft in 34(2.0%)cases.From the first to the second analysed time-period,incidence of acute necrotizing and ulcerative keratitis,corneal scar,Fuchs'dystrophy increased(P<0.032 for all)and incidence of keratoconus significantly decreased(P=0.015).CONCLUSION:Pseudophakic or aphakic bullous keratopathy is the leading indication for PKP,followed by regraft and acute necrotizing and ulcerative keratitis.

关键词： penetrating keratoplasty indications histology

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Effects of immunosuppressants after penetrating keratoplasty:meta-analysis of randomized controlled trials

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International Journal of Ophthalmology(English edition) 2011年第5期4卷 529-536页

作者： Xin Wei Xiao-Ming Chen Lin Wang Jin-Ping Song and Yin-Ping Deng Department of Ophthalmology & Ophthalmic Laboratories West China Hospital Sichuan University Chengdu 610041 Sichuan Province China

AIM: To assess the effectiveness of immunosuppressants in the prophylaxis of corneal allograft rejection after high-risk keratoplasty and normal-risk keratoplasty. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CNKI, VIP and reference lists of articles. Date of most recent search: 18 June, 2011. All randomised controlled trials (RCTs) assessing the use of immunosupressants in the prevention of graft rejection, irrespective of publication language. Two authors assessed trial quality and extracted data independently. Only dichotomous outcomes (clear graft survival, ratio of immune reactions and side effects) were available and were expressed as relative risk (RR) and 95% confidence intervals (CI). RESULTS: Seven studies were included in this review. In the comparing of mycophenolate mofetil (MMF) with placebo, the results showed MMF could significantly reduce immune reactions compared with placebo (RR 1.08 95% Cl 0.95 to 1.21), but no effect on clear graft survival (RR 1.11 95% Cl 0.90 to 1.35). In clear graft survival and immune reactions, MMF and cyclosporine A (CsA) showed similar effect (RR 1.11 95% Cl 0.90 to 1.35, and RR 1.48, 95% Cl 0.56 to 3.93, respectively). Tacrolimus (FK506) and steroid showed similar effects on clear graft survival and immune reactions (RR 0.32, 95% CI 0.02 to 6.21, and RR 1.00, 95%CI 0.88 to 1.14, respectively). No drug relative side effect has been found. CONCLUSION: MMF may reduce immune reactions in both normal-risk and high-risk rejection of penetrating keratoplasty. CsA and FK506 showed similar effects as MMF. However, due to the lack of large clinical trials, the evidence remain weak, the quality of evidences were rated as very low to moderate. Large, properly randomised, placebo-controlled, double masked trials are needed to evaluate the effect of immunosuppressants.

关键词： immunosuppressants penetrating keratoplasty meta-analysis

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Surgical management of spontaneous,lateonset Descemet membrane detachment after penetrating keratoplasty for keratoconus:a case report

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Eye and Vision 2017年第1期4卷 66-69页

作者： Myrsini Petrelli Konstantinos Oikonomakis Konstantinos Andreanos Andreas Mouchtouris Ilias Georgalas George Kymionis Department of Ophthalmology University of AthensAthensGreece

Background:To report a surgical method for treating corneal oedema in a case of late-onset Descemet membrane detachment after penetrating keratoplasty.Case presentation:A 55-year old patient presented with sudden visual loss in his left eye 28 years after penetrating keratoplasty for keratoconus.Slit-lamp biomicroscopy revealed a distortion of the corneal graft anatomy with protrusion of the graft and peripheral thinning and steepening in the residual host tissue,accompanied by corneal graft oedema.Anterior segment optical coherence tomography revealed detachment of Descemet membrane localized to the area of the graft oedema.We proceeded with a full-thickness,partially circumferential incision in the graft-host junction,followed by repositioning and re-suturing of the graft in place,and intracameral air injection in order to achieve reattachment of Descemet membrane.Conclusions:Corneal graft repositioning in combination with re-bubbling may represent an effective therapeutic option in keratoconic patients with peripheral thinning in the residual host corneal tissue and subsequent Descemet membrane detachment.

关键词： Keratoconus penetrating keratoplasty Spontaneous Descemet membrane detachment

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Midterm outcomes of penetrating keratoplasty following allogeneic cultivated limbal epithelial transplantation in patients with bilateral limbal stem cell deficiency

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International Journal of Ophthalmology(English edition) 2021年第11期14卷 1690-1699页

作者： Jun-Fa Xue Dong-Fang Li Ya-Ni Wang Chen Chen Ru-Fei Yang Qing-Jun Zhou Ting Liu Li-Xin Xie Yan-Ling Dong School of Medicine and Life Sciences Shandong First Medical UniversityJinan 271016Shandong ProvinceChina State Key Laboratory Cultivation Base Shandong Province Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071Shandong ProvinceChina Medical College Qingdao UniversityQingdao 266071Shandong ProvinceChina Department of Ophthalmology Shandong UniversityJinan 250100Shandong ProvinceChina Qingdao Eye Hospital of Shandong First Medical University Qingdao 266071Shandong ProvinceChina

AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 eyes)with bilateral LSCD were enrolled in this prospective noncomparative case series study.Each participant underwent PK approximately 6 mo after a CLET.Topical tacrolimus,topical and systemic steroids,and oral ciclosporin were administered postoperatively.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),ocular surface grading scores(OSS),corneal graft epithelial rehabilitation,persistent epithelial defect(PED),immunological rejection,and graft survival rate were assessed.RESULTS:The time interval between PK and allogeneic CLET was 6.90±1.29(6-10)mo.BCVA improved from 2.46±0.32 log MAR preoperatively to 0.77±0.55 log MAR post-PK(P<0.001).Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100%at 12 and 24 mo and 80.0%at 36 mo.PEDs appeared in 5 eyes at different periods post-PK,and graft rejection occurred in 4 eyes.The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK.CONCLUSION:A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate.

关键词： limbal stem cell deficiency allogeneic cultured limbal epithelial transplantation penetrating keratoplasty graft rejection

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General anesthesia versus local anesthesia for penetrating keratoplasty: a prospective study

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International Journal of Ophthalmology(English edition) 2014年第2期7卷 278-282页

作者： Xu Wang Guang-Fu Dang Ying-Mei Li Wei-Fan Li Xin-Yi Wu Department of Ophthalmology Qianfoshan HospitalMedical School of Shandong University Department of Ophthalmology Jinan No.2 Hospital Department of Anesthesiology Jinan No.2 Hospital Department of Ophthalmology Qilu Hospital Medical School of Shandong University

AIM:To examine which anesthesia general or local is more effective for penetrating keratoplasty(PKP).METHODS:Patients with indications for PKP(n=141)were enrolled in a prospective study and randomly divided into general anesthesia group(group A,70 eyes)and local anesthesia group(group B,71 eyes).Patients received optical PKP(group A1,30 eyes;group B1,30eyes)or therapeutic PKP(group A2,40 eyes;group B2,41 eyes).Measurement of anterior chamber treatment time(T)for PKP patients and the ratio(R)of the area of the pupils to that of recipient graft region.T and R values,as well as perioperative and postoperative complications,were compared between groups A and B using t-test orχ2test.RESULTS:Patients were followed for 2wk after PKP.T was(13.45±8.64)min for group A and(7.36±5.24)min for group B,a statistically significant difference(P<0.001).The R value for group A was stable during the operation,while for PKP patients in group B the value initially increased then gradually decreased to normal after suturing.In group B,extrusion of intraocular contents occurred in 5 eyes,and iridal prolapse occured in 11cases;no perioperative complications occurred in group A.Relapse rate for fungal keratitis was 13.04%in group B and 0%in group A.CONCLUSION:Under general anesthesia,pupils remaine stable during PKP and perioperative complications are averted.General anesthesia gives more time to treat pathological changes in the anterior chamber and treatment success rate is higher.

关键词： penetrating keratoplasty general anesthesia local anesthesia

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Trends in the indications for penetrating keratoplasty in Shandong,2005-2010

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International Journal of Ophthalmology(English edition) 2011年第5期4卷 492-497页

作者： Jun-Yi Wang, Jing Zhao Department of Ophthalmology Renmin Hospital of Wuhan University Wuhan 430060 Hubei Province China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of Ophthalmology Shandong Eye Institute Shandong Academy of Medical Sciences Qingdao 266071 Shandong Province China

AIM: To identify the current indications and the trend shifts for penetrating keraboplasty (PKP) in Shandong. METHODS: The medical charts of all patients who underwent PKP at Shandong Eye Institute from June 1, 2005 to May 31, 2010 were analysed retrospectively. RESULTS: A total of 875 patients (875 eyes) received PKP in this 5-year period, accounting for 61.6% of all corneal transplantation surgeries. The leading indications for PKP were infectious keratitis (37.1%), HSK (19.1%), keratoconus (11.2%), bullous keratopathy (8.5%), regrafting (6.7%) and corneal scarring (4.8%). The percentage of PKP for keratoconus declined year by year, whereas the percentage of bullous keratopathy had a mild annual increase. Fungal infections accounted for 65.2% of the infectious keratitis cases, remaining the leading cause of corneal infection. In addition, 54.1% of bullous keratopathy cases were associated with cataract surgery. The leading initial diagnoses associated with regrafting were infectious keratitis (38.9%), HSK (18.6%) and corneal burn (16.9%). The major causes of regrafting included graft endothelial dysfunction (39.0%), graft ulcer (28.8%) and primary disease recurrence (15.3%). CONCLUSION: Infectious keratitis remained the leading indication for PKP in Shandong, and fungal infections were still the major cause of corneal infections. There was an increasing trend in the percentage of PKP cases indicated for bullous keratopathy but a decline in the same for keratoconus. Even with a decline in the overall proportion among all corneal transplantation surgeries, PKP is still the major corneal transplant choice in Shandong.

关键词： penetrating keratoplasty indication infectious keratitis

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Black diaphragm intraocular lens implantation and penetrating keratoplasty in aphakic eyes with traumatic aniridia

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International Journal of Ophthalmology(English edition) 2013年第2期6卷 183-186页

作者： Jun Li Xiao-Guang Dong Qingdao University Medical College Shandong Eye Institute Shandong Academy of Medical Sciences

AIM:To evaluate the long-term outcome of implantation of black diaphragm intraocular (BDI) lens combined with penetrating keratoplasty (PKP) for managing aphakic eyes with traumatic aniridia and corneal damage. METHODS: Six aphakic eyes of six patients with traumatic aniridia and corneal damage had BDI lens implantation at Qingdao Eye Hospital, Shandong Eye Institute from June 2008 to November 2011. Medical records of the patients were reviewed. Three patients received PKP and after 12-18months were implanted with BDI lens. The other three patients completed PKP and BDI lens implantation at the same time. The corrected visual acuity, intraocular pressure and number of corneal endothelial cells were monitored. RESULTS: The patients were followed up for an average of 24.3 ±12.1months (range 14-48 months). All BDI lenses were located well. The best corrected visual acuity got improved in 5 patients (0.1-1.0) and decreased in 1 patient from 0.4 to 0.2. Three patients had normal intraocular pressure (IOP) after implantation. Two patients required antiglaucoma medications to control IOP within the normal range and 1 patient implanted Ahmed glaucoma valve to control IOP. The corneal grafts kept transparent in all eyes and the corneal endothelial counting >1 000/mm2 , although two patients experienced acute graft rejection and loss more than 30% corneal endothelial cells.CONCLUSION: Implantation of BDI lens combined with PKP is an effective option for managing aphakic eyes with traumatic aniridia and corneal damage. Although the results in our study are encouraging, additional studies of the long -term safety and efficacy are required. Alarger study population and longer follow-up may be beneficial.

关键词： black diaphragm intraocular lens penetrating keratoplasty aniridia trauma

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