Advances in the mechanisms of keratoconus secondary to vernal keratoconjunctivitis / 国际眼科杂志(Guoji Yanke Zazhi)

Vernal keratoconjunctivitis is an allergic ocular surface disease mostly present with recurrent chronic inflammation, which usually affects children and adolescents and possibly results in corneal complications such as keratoconus. Keratoconus is a corneal disease characterized by a local cone-like corneal deformation. Previous studies have respectively put forward pathological mechanisms of vernal keratoconjunctivitis and keratoconus and the progressive risk factors, among which we find there's mutual mechanisms as well as cytokines' expression, including type I and IV hypersensitivity, inflammatory reaction, enzymatic changes, oxidative stress and mechanical injury. This review aims at summarizing the possible intrinsic mechanisms and cytokines exacerbating vernal keratoconjunctivitis patients corneas to keratoconus, so as to provide reference for the prevention and management in keratoconus caused by vernal keratoconjunctivitis.

Daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation followed by daratumumab and lenalidomide maintenance therapy for primary plasma cell leukemia: report of one case and review of literature / 白血病·淋巴瘤

Objective:To observe the therapeutic efficacy and prognosis of daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) followed by daratumumab and lenalidomide maintenance treatment for primary plasma cell leukemia (PCL).Methods:The clinical data of a patient with primary PCL admitted to the First People's Hospital of Yunnan Province in January 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:The patient was diagnosed with primary PCL and treated with daratumumab combined with BD (bortezomib + dexamethasone) for 1 course and BCDD (bortezomib + cyclophosphamide + liposomaldoxorubicin + dexamethasone) for two courses. The patient was treated with daratumumab combined with allo-HSCT after complete remission. The donor cells were successfully implanted and the chimerism rate of donor cells was 94.36% without acute graft-versus-host disease reaction. And then the patient received intermittent maintenance therapy of daratumumab combined with low dose lenalidomide after transplantation, and the current remission period after transplantation reached 4 months.Conclusions:Daratumumab combined with chemotherapy bridging to allo-HSCT followed by daratumumab and lenalidomide may improve the prognosis of primary PCL and prolong survival time.

Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves the antiangiogenic efficacy for advanced stage mouse corneal neovascularization.

PURPOSE: Pericytes, which are recruited to vessels via platelet-derived growth factor (PDGF), are linked to vessel formation and stabilization during pathological corneal neovascularization. In advanced stage, maturated vessels are restricted to anti-VEGF therapy. This study was undertaken to investigate the potential anti-angiogenesis effect of PDGF receptor inhibitor and the therapeutic effect of simultaneously targeting VEGF/PDGF signaling in advanced stage mouse corneal neovascularization. METHOD: Corneal neovascularization was induced in wild-type BALB/C mice by removal of the corneal and limbal epithelia. To study the effects of anti-angiogenic inhibitor on new vessel growth prevention, mice were treated with VEGF receptor tyrosin kinase inhibitor II(anti-VEGF/VEGFR group) for 10 days immediately following injury at day 0 (D0). To study the effects of anti-angiogenic inhibitors on vessel regression, mice were treated with VEGF receptor tyrosin kinase inhibitor II or PDGF receptor inhibitor AG 1296 (anti-PDGF/PDGFR group) or both (combined group) for 10 days starting at day 10 (D10) post-injury. Corneas were harvested and immunostained with CD31 for endothelial cells and Ng2 for pericytes. Threshold analysis was used to calculate the area of corneal new vessels. Corneal flatmounts were studied under fluorescence microscope and confocal microscope. RESULTS: Mice treated with the VEGF receptor tyrosin kinase inhibitor II from D0 showed an inhibition of corneal neovascularization of 15.4% compared with untreated animals (P < 0.01). But the same amount of VEGF receptor tyrosin kinase inhibitor II had no significant anti-angiogenic effect when used at D10 (P > 0.05). Mice treated with either AG1296 or AG1296 plus VEGF receptor tyrosin kinase inhibitor II at D10 showed an inhibition of corneal neovascularization of 12.59% (P < 0.05) and 20.85% (P < 0.01) respectively. Decreased pericyte coverage and vessel density was observed in AG1296 group. Compared to the anti-VEGF/VEGFR group, only the combined therapy group showed a significant anti-angiogenesis effect (P < 0.01). CONCLUSION: Inhibition of the PDGF signal pathway results in loss of pericytes and a reduction in vessel density in advanced stage mouse corneal neovascularization. Furthermore, pericyte attenuation caused by blockade PDGF signaling can enhance the anti-angiogenesis efficacy of VEGF receptor inhibitor. Combined treatment against both endothelial cells and pericytes is required for advanced stage corneal new vessels.