New developments in the management of persistent corneal epithelial defects.

A persistent epithelial defect (PED) is a corneal epithelial defect that failed to heal after 2weeks. It is a condition that carries much morbidity, and our understanding of PED remains poor, with current treatment methods often having unsatisfactory outcomes. With PEDs becoming more prevalent, more efforts are required to establish reliable treatment modalities. Our reviews describe the causes of PEDs and the different approaches developed to manage them, as well as their associated limitations. Emphasis is placed on understanding various advances in the development of new treatment modalities. We have also described a case of a woman with a background of graft-versus-host disease on long-term topical corticosteroids who developed complicated PED involving both eyes. The current approach to managing PEDs generally involves exclusion of an active infection, followed by treatment modalities that aim to encourage corneal epithelial healing. Success rates, however, remain far from desirable, as treatment remains challenging due to multiple underlying etiologies. In summary, advances in the development of new therapies may be able to facilitate progress in the understanding and treatment of PED.

The role of bone morphogenetic protein 4 in corneal injury repair.

PURPOSE: Corneal injury may cause neovascularization and lymphangiogenesis in cornea which have a detrimental effect to vision and even lead to blindness. Bone morphogenetic protein 4 (BMP4) regulates a variety of biological processes, which is closely relevant to the regulation of corneal epithelium and angiogenesis. Herein, we aimed to evaluate the effect of BMP4 on corneal neovascularization (CNV), corneal lymphangiogenesis (CL), corneal epithelial repair, and the role of BMP4/Smad pathway in these processes. METHODS: We used MTT assay to determine the optimal concentration of BMP4. The suture method was performed to induce rat CNV and CL. We used ink perfusion and HE staining to visualize the morphological change of CNV, and utilized RT-qPCR and ELISA to investigate the expression of angiogenic factors and lymphangiogenic factors. The effects of BMP4 and anti-VEGF antibody on migration, proliferation and adhesion of corneal epithelium were determined by scratch test, MTT assay and cell adhesion test. RESULTS: BMP4 significantly inhibited CNV and possibly CL. Topical BMP4 resulted in increased expression of endogenous BMP4, and decreased expression of angiogenic factors and lymphangiogenic factors. Compared with anti-VEGF antibody, BMP4 enhanced corneal epithelium migration, proliferation and adhesion, which facilitated corneal epithelial injury repair. Simultaneously, these processes could be regulated by BMP4/Smad pathway. CONCLUSIONS: Our results demonstrated unreported effects of BMP4 on CNV, CL, and corneal epithelial repair, suggesting that BMP4 may represent a potential therapeutic target in corneal injury repair.

Corneal Repair with Adhesive Cell Sheets of Fetal Cartilage-Derived Stem Cells.

BACKGROUND: Corneal scarring or disease may lead to severe corneal opacification and consequently, severe loss of vision due to the complete loss of corneal epithelial cells. We studied the use of epithelial cell sheets differentiated from fetal cartilage-derived stem cells (FCSC) to resurface damaged cornea. METHODS: The FCSC were isolated from the femoral head of immature cartilage tissue. The ability of the FCSCs to differentiate into corneal epithelial cells was evaluated using differentiation media at 2 days and 7 days post-seeding. A sheet fabricated of FCSCs was also used for the differentiation assay. The results of the in vitro studies were evaluated by immunocytochemistry and Western blots for corneal epithelial cell markers (CK3/12 and Pax6) and limbal epithelial stem cell markers (ABCG2 and p63). To test the material in vivo, an FCSC-sheet was applied as a treatment in a chemically burned rabbit model. The healing ability was observed histologically one week after treatment. RESULTS: The in vitro experiments showed morphological changes in the FCSCs at two and seven days of culture. The differentiated cells from the FCSCs or the FCSC-sheet expressed corneal epithelial cells markers. FCSC were create cell sheet that successfully differentiated into corneal epithelial cells and had sufficient adhesion so that it could be fused to host tissue after suture to the ocular surface with silk suture. The implanted cell sheet maintained its transparency and the cells were alive a week after implantation. CONCLUSION: These results suggest that carrier-free sheets fabricated of FCSCs have the potential to repair damaged corneal surfaces.

Meta analysis of therapeutic effects of domestic deproteinized calf blood extract eye gel on corneal epithelial repair after laser refractive surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To systemically evaluate the clinical efficacy and safety of domestic deproteinized calf blood extract eye gel for corneal epithelial repair after laser refractive surgery.METHODS:We performed a comprehensive search via Pubmed,Embase,Cochrane Library,VIP Chinese Science and Technology Journal Database,CNKI and Wan Fang Chinese periodical Database for the randomized controlled trials(RCTs) at home and abroad about effects of the domestic deproteinized calf blood extract eye gel for corneal epithelial repair after laser corneal refractive surgery with retrieval time from January 2007 to December 2016.According to the inclusion and exclusion criteria,2 medical researchers independently screened documents,extracted data and evaluated the quality.Review Manager 5.3 software was used for Meta analysis.RESULTS:Seven RCTs involving 1042 eyes,including 523 eyes in the treatment group and 519 eyes in the control group,were selected for this Meta-analysis.The results showed that the clinical efficacy in the treatment group was better than that in the control group (OR=1.81,95％CI:1.39 ～2.35;P＜0.001).And the corneal injury symptom score in the treatment group was superior to that in the control group (WMD=-0.33,95％CI:-0.45 to-0.21;P＜0.001).And the corneal healing time in the treatment group was shorter than that in the control group (WMD=-1.26,95％CI:-1.56 to-0.97;P＜0.001).CONCLUSION:The domestic deproteinized calf blood extract eye gel can relieve the patients' symptoms after laser refractive surgery,improve the corneal epithelial recovery and the efficiency of treatment.Due to the limited quality and quantity of the studies these conclusions should be further validated by more welldesigned randomized double blind controlled trials.