Fine Needle-Diathermy Regresses Pathological Corneal (Lymph)Angiogenesis and Promotes High-Risk Corneal Transplant Survival

Viet Nhat Hung Le,Felix Bock,Rebecca Scholz,Ann-Charlott Schneider,Claus Cursiefen

doi:10.1038/s41598-018-24037-3

Viet Nhat Hung Le, Felix Bock + Show 3 more

Open Access

https://doi.org/10.1038/s41598-018-24037-3

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Abstract

Pathological corneal hem- and lymphangiogenesis are prime risk factors for corneal graft rejection. Fine needle-diathermy (FND) is an option to regress corneal blood vessels; however, whether this treatment besides clinically visible blood vessels also affects invisible lymphatic vessels is so far unknown. Here we test the hypothesis that FND destroys not only blood but also lymphatic vessels, thereby promotes corneal high-risk graft survival. The effect of FND was studied in vivo using BALB/c mice and the model of suture-induced corneal neovascularization. Mice were divided into three groups: FND, ANTI (anti-inflammatory therapy) and NON (control). Five, 7, 10 and 20 days after cauterization, corneas were harvested and stained with LYVE-1, CD31 to quantify (lymph)angiogenesis. The long-term survival of allografts was compared between the three groups. FND caused significant regression of both blood and lymphatic vessels compared to the control group at all time points (p < 0.05) with the most obvious effect at day 7 (p < 0.01). Graft survival was significantly prolonged when transplants were placed into the FND pretreated group (p < 0.0001). The effect of the anti-inflammatory therapy alone was less effective compared to FND (p < 0.05). This novel lymphangioregressive effect of FND can be used clinically to precondition high-risk recipients to promote graft survival.

Highlights

Their lack of availability, high cost, inaccessibility to ophthalmologists and their complications require the need for a new simple, effective and safe alternative treatment
Quantitative analysis of the neovascularised corneal area identified by immunohistochemical staining revealed that both blood and lymphatic vessels were significantly reduced in the Fine needle diathermy (FND) group compared to the NON group at all time points (p < 0.05)
(iv) this to our knowledge is the first evidence that preconditioning of high-risk eyes by induced regression of pathologic corneal blood and lymphatic vessels in these eyes prior to transplantation promotes subsequent graft survival

Summary

Introduction

Their lack of availability, high cost, inaccessibility to ophthalmologists and their complications require the need for a new simple, effective and safe alternative treatment. Fine needle diathermy (FND) is currently one clinical choice for managing mature pathologic corneal blood vessels. CoNV was precisely occluded by using 10-0 monofilament black nylon suture and diathermy current applied to the needle being located in the stromal vessel This approach has shown potential e.g. in the context of high-risk keratoplasty patients[23].The long-term efficacy and safety of this therapy were documented and demonstrated by several further researches[24,25,26,27,28,29]. FND is widely used because of its effectiveness, safety, simple procedure, and inexpensive equipment which make it accessible to any eye unit throughout the world Whether this treatment besides clinically visible blood vessels affects lymphatic vessels is so far unknown. We test the hypothesis that fine needle diathermy destroys visible blood and invisible lymphatic vessels and thereby prolongs the survival grafts of high-risk corneal transplantation

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