Preincubation of donor tissue with a VEGF cytokine trap promotes subsequent high-risk corneal transplant survival

AimsPathological neovascularisation of the host bed and the transplant itself is the main risk factor for graft rejection after corneal transplantation. This study aims to prevent this process by preincubation of the corneal donor tissue ex vivo with an antivascular endothelial growth factor (VEGF) cytokine trap blocking additional postsurgical hemangiogenesis and lymphangiogenesis to promote high-risk graft survival.MethodsThe donor tissue was preincubated with a VEGFR1R2 cytokine trap for 24 hours prior to murine high-risk corneal transplantation (human IgG Fc was used as the control). The distribution of VEGFR1R2 Trap in the cornea was investigated by immunohistochemistry. Corneas were excised to quantify the blood vessels (BVs) and lymphatic vessels (LVs) and draining lymph nodes (dLNs) were harvested to analyse the phenotype of dendritic cells (DCs) and T cells at week 1, 2 and 8 post-transplantation. Graft survival was compared between preincubation with VEGFR1R2 Trap and human IgG Fc in high-risk recipients.ResultsVEGFR1R2 Trap was present in the graft for at least 2 weeks after surgery and additionally diffused into the corneal recipient. BVs, LVs and macrophages in the whole cornea were significantly decreased 1-week and 2-week post-transplantation (p<0.05). In dLNs the frequency of CD11c+DCs was significantly reduced, whereas CD200R+ regulatory DCs were significantly increased after keratoplasty (p<0.05). Furthermore, long-term high-risk graft survival was significantly improved (p<0.01).ConclusionsPreincubation of corneal donor tissue with a VEGFR1R2 cytokine trap can significantly promote subsequent high-risk corneal transplant survival and thereby opens new treatment avenues for high-risk corneal transplantation.

Pseudophakic corneal donor tissue in Descemet membrane endothelial keratoplasty (DMEK): implications for cornea banks and surgeons

ObjectiveIncreasingly, cornea banks are recovering donor tissue from pseudophakic donors. Little is known about their suitability for Descemet membrane endothelial keratoplasty (DMEK) surgery in terms of endothelial cell density (ECD) and preparation failure.Methods and AnalysisWe explored ECD during donor tissue preparation in 2076 grafts. Preparation failure was analysed in 1028 grafts used in DMEK surgery at our clinic. To monitor ECD and functional results, we matched 86 DMEK patients who received pseudophakic donor grafts with similar recipients of phakic donor grafts and followed them up for 36 months.ResultsAt recovery, mean ECD in pseudophakic donor grafts was 2193 cells/mm2 (SD 28.7) and 2364 cells/mm2 (SD 15.7) in phakic donor grafts (p<0.001). After cultivation, the difference increased as pseudophakic donor grafts lost 14% of ECD while phakic lost only 6% (p<0.001). At transplantation, mean ECD in pseudophakic donor grafts was 2272 cells/mm2 (SD 250) and 2370 cells/mm2 (SD 204) in phakic donor grafts (p<0.001). After transplantation, the difference in ECD increased as pseudophakic donor grafts lost 27.7% of ECD while phakic donor grafts lost only 13.3% (p<0.001). The risk of preparation failure in pseudophakic donor grafts was higher than in phakic donor grafts (OR 4.75, 95% CI 1.78 to 12.67, p=0.02). Visual acuity increased in both groups similarly.ConclusionsPseudophakic donor grafts have a lower ECD, are more prone to endothelial cell loss during recovery and surgery and are associated with a higher risk of preparation failure. Cornea banks and surgeons should consider this in the planning of graft preparation and transplantation.

The rationale application of donor material: original ten years experience, possible ways of development and literature data

Lately, layer-wise keratoplasty became the first operation of choice in case of pathology of cornea. In view of satisfying results of endothelial surgery similar operations are implemented at earlier stages that increases need in donor tissue. With increasing of life span of population, also increases number of patients in need of transplantation of cornea. The number of intact cadaver cornea decreases because of stable increase of surgical interventions on front segment of eye. The present article presents original ten years experience concerning optimization of application of donor tissue and indicate on possibilities of further increasing of number of applied keratoplasties. From 2009 to 2015 in the Helmholtz Moscow research institute of eyes diseases 652 transplantations of cornea were implemented in various modifications: straight-through keratoplasty, transplantation of Descemet's membrane with endothelium (DMEK), deep front layer-wise keratoplasty, endokeratoplasty (DSEK) with various modes of transplant formation and 23 frontal layer-wise keratoplasties. In transplantation were also used eyes of donors with radial keratotomy, after laser keratomileusis and with artificial intra-ocular lens. To implement 652 operations 528 cadaver eyes with average age 41 ± 32,5 years (varying from 21 to 87 years) were required. The number of transplantations increased approximately on 50% at potential up to 75%. The lamellar surgery permits using corneal donor tissue with altered frontal surface and to increase number of transplantations of cornea. The renunciation of application of corneal donor tissue with altered frontal surface is inexpedient.