Effects of orbital decompression on duction, cyclotorsion and diplopia.

BACKGROUND: Orbital decompression is commonly performed to correct proptosis in patients with Graves' orbitopathy (GO). In literature, the incidence of new-onset constant diplopia after orbital decompression varies. Few studies have evaluated changes in duction and cyclodeviation after orbital decompression. We evaluated the changes in duction, cyclodeviation, eye position and degree of diplopia after orbital decompression. METHODS: We retrospectively analysed data from patients who underwent orbital decompression at our hospital between January 2016 and July 2020. Data regarding the type of decompression, eye position, duction, cyclodeviation and level of diplopia according to the Gorman score were recorded. RESULTS: Data from 281 eyes/orbits of 156 patients were analysed. Proptosis decreased from 23.8±2.5 to 20.9±2.5 mm. Horizontal and vertical duction range decreased (horizontal d=0.40 and vertical 0.30; p=0.000) after surgery; however, the change was not clinically significant (≤5°). Horizontal deviation changed towards esodeviation (d=-0.45; p=0.000), whereas vertical deviation remained stable (d=0.15; p=0.161). Preoperative cyclotorsion in the primary and downgaze positions changed towards incyclodeviation (primary: d=0.30, p=0.021; downgaze d=0.30, p=0.039). Diplopia improved in 22% (18 patients), whereas new-onset constant diplopia developed in 11% (12 patients). Elevation has an excellent predictive value of causing new-onset constant diplopia when measured preoperatively as <19°, sensitivity 88.0%, specificity 41.7% (area under the curve 0.812 (95% CI 0.660 to 0.963); p=0.000). CONCLUSION: After orbital decompression, incidence of new-onset constant diplopia was 11% and 22% of the patients had partial or complete improvement of their diplopia. The changes in duction, cyclodeviation and horizontal deviation showed a statistical but not clinical difference. Patients with GO and a preoperatively restricted elevation of <19° are at risk of developing new-onset constant diplopia. In addition, preoperative incyclodeviation may worsen after decompression surgery.

Metalloproteinases facilitate connection of wound bed vessels to pre-existing skin graft vasculature.

BACKGROUND: Despite advances in tissue engineering of human skin, the exact revascularization processes remain unclear. Therefore it was the aim of this study to investigate the vascular transformations during engraftment and to identify associated proteolytic factors. METHODS: The modified dorsal skinfold chamber with autologous skin grafting was prepared in C57BL/6J mice, and intravital microscopy was performed. The expression of proteases and vascular factors was quantified by immunohistochemistry. RESULTS: Reperfusion of the skin graft after 72hours was followed by a temporary angiogenic response of the graft vessels. Wound bed bud formation appeared after 24 to 48hours representing starting points for capillary sprouting. In the reperfused skin graft larger buds developed over several days without transformation into angiogenic sprouts; instead pruning took place. MT1-MMP was detected at sprout tips of in-growing vessels. MMP-2 expression was located at the wound bed/graft connection sites. Pericytes were found to withdraw from the angiogenic vessel in order to facilitate sprouting. CONCLUSIONS: Skin graft vasculature responded with temporary angiogenesis to reperfusion, which was pruned after several days and exhibited a different morphology than regular sprouting angiogenesis present within the wound bed. Furthermore we identified MT1-MMP as sprout-tip located protease indicating its potential role as sprout growth facilitator as well as potentially in lysing the existing graft capillaries in order to connect to them. The differences between the wound bed and skin graft angiogenesis may represent a relevant insight into the processes of vascular pruning and may help in the engineering of skin substitutes.

In vivo visualization of the origination of skin graft vasculature in a wild-type/GFP crossover model.

INTRODUCTION: Skin substitutes are increasingly produced in tissue engineering, but still the understanding of the physiological skin revascularization process is lacking. To study in vivo conditions we recently introduced a mouse model, in which we already characterized the angiogenic changes within the wound bed and the skin graft. The aim of this study was to identify the origination of the vasculature during skin graft revascularization in vivo and to track vessel development over time. METHODS: We created a crossover wild-type/GFP skin transplantation model, in which each animal carried the graft from the other strain. The preparation of the modified dorsal skin fold chamber including cross-over skin grafting was performed in male C57BL/6J wild-type mice (n=5) and C57BL/6-Tg(ACTB-EGFP)1O sb/J mice (n=5). Intravital microscopy in 12 areas of wild-type and GFP skin grafts was performed daily over a time period of 10 days. RESULTS: Graft reperfusion started after 48-72 h. After reperfusion GFP-positive structures from the wound bed were visible in the graft capillaries with the highest density in the center of the graft. Overall, we observed a replacement of existing graft capillaries with vessels from the wound bed in 68% of the vessels. Of note, vessel replacement occurred in almost 100% of graft vessels in the periphery. Additionally, vessels within the graft showed a temporary angiogenic response between days 3-8, which originated predominantly from the autochthonous graft vasculature, but also contained already grown-in vessels from the wound bed. CONCLUSIONS: These in vivo data indicate an early in-growth of angiogenic bed vessels into the existing vascular channels of the graft and subsequent centripetal replacement. Additionally we observed a temporary angiogenic response of the autochthonous capillaries of the skin graft with contribution from bed vessels. These findings further support the theory that sprouting angiogenesis from the wound bed in combination with the replacement of existing graft vessels are the key factors in skin graft taking. Thus, manufacturing of skin substitutes should be aimed at providing pre-formed vascular channels within the construct to improve vascularization.

Temporary angiogenic transformation of the skin graft vasculature after reperfusion.

BACKGROUND: In the era of tissue engineering, the physiologic process of skin graft revascularization remains unclear, preventing the successful development of skin substitutes. Therefore, the authors developed a new in vivo model with which to visualize the process of engraftment and its microvascular architecture. The aim of this study was to specifically investigate the vascular transformations within the skin graft to gain applicable knowledge on how vascular processes during engraftment occur. METHODS: Microsurgical preparation of the modified dorsal skinfold chamber including autologous skin grafting was performed in male C57BL/6J mice (n = 10). In addition, immunohistochemistry of angiogenic factors, endothelial cells, and pericytes, and corrosion casting were performed to further characterize the specific mechanisms. RESULTS: The graft exhibited capillary widening starting at day 3, resulting in the temporary formation of spherical protrusions at the graft capillary divisions starting in the center of the graft 24 to 48 hours after revascularization. Confocal microscopy showed the simultaneous expression of CD31 and desmin. Corrosion casting and evaluation by light microscopy and scanning electron microscopy showed the three-dimensional formation of capillaries in the wound bed that connected to the preexisting capillary loops of the skin graft. CONCLUSIONS: The authors were able to show for the first time a temporary angiogenic response within the capillaries of the skin graft. This most likely represents a reaction to reperfusion allowing the supply of proangiogenic factors to the hypoxic skin graft. The detection of an angiogenic response within the graft capillaries is for the first time made possible in the newly developed model and is therefore completely novel.