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

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.

Supplemental Anti Vegf A-Therapy Prevents Rebound Neovascularisation After Fine Needle Diathermy Treatment to Regress Pathological Corneal (LYMPH)Angiogenesis

“…Indeed, this combination treatment could significantly regress blood and lymphatic vessesels at day 7 and day 14 in comparision with the FND monotherapy. These results are compareable to our previous study where FND was combined with corticosteroids 25 . Corticosteroids are clinically used to control inflammation and CoNV due to their anti-inflammatory and anti-angiogenic properties 34 .…”

“…(2020) 10:3908 | https://doi.org/10.1038/s41598-020-60705-z www.nature.com/scientificreports www.nature.com/scientificreports/ monotherapy could induce micro trauma causing release of proangiogenic factors and should therefore be combined with anti-inflammatory eye drops or subconjunctival injection of anti-VEGF and with corneal angiography to reduce the undesired effect of FND 19,20,23,24,26 . Indeed, we recently showed that the combination of FND and corticosteroids can regress not only mature blood vessels but also clinically invisible lymphatic vessels and thereby promote subsequent high-risk corneal graft survival 25 . Nevertheless, there was no study so far formally testing whether FND treatment alone induces release of proangiogenic factors or causes rebound neovascularisation.…”

“…Fine needle diathermy (FND) is clinically used since 2000 to regress CoNV and is currently a promising clinical choice for managing mature pathologic corneal blood vessels 19,20 . The efficacy of this technique was documented by several studies in both clinical and animal settings [20][21][22][23][24][25] . We could recently show that the combination of FND and corticosteroids can regress both blood vessels and clinically invisible lymphatic vessels 25 .…”

“…The efficacy of this technique was documented by several studies in both clinical and animal settings [20][21][22][23][24][25] . We could recently show that the combination of FND and corticosteroids can regress both blood vessels and clinically invisible lymphatic vessels 25 . Based on clinical experience, many authors assume that FND in itself can induce rebound neovascularisation and should therefore be combined with anti-inflammatory eye drops or subconjunctival injection of anti-VEGF or with corneal angiography to lessen undesired effects of FND 19,20,23,24,[26][27][28] .…”

VEGF TrapR1R2 Suspended in the Semifluorinated Alkane F6H8 Inhibits Inflammatory Corneal Hem- and Lymphangiogenesis

“…4 Thus, over the past decades, anti-hem-and lymphangiogenic treatment strategies have been developed, and the benefit of this approach has already been shown in the preclinical and clinical setting. 6,[8][9][10][11][12][13][14][15][16] The members of the vascular endothelial growth factor (VEGF) family are essential growth and survival factors involved in pathological hem-and lymphangiogenesis. 17 In particular VEGF-A is one of the most important growth factors for corneal hem-and lymphangiogenesis.…”