An adequate blood supply is important for the success of skin flap or free skin grafts in plastic reconstructive surgery, and oculoplastic surgeons must, therefore, have considerable knowledge on the perfusion in the periorbital area. However, the clinical rules of thumb concerning the design of flaps are mostly based on empirical observations and beliefs, rather than actual knowledge of blood perfusion. Several imaging techniques have been developed during the past decades offering high-resolution images of the structure and function of tissue. Peroperative monitoring can improve our understanding of how blood perfusion is affected by surgical interventions and will hopefully allow surgical techniques to be improved, resulting in better clinical outcome. Despite the significant interest in blood perfusion among surgeons, knowledge regarding blood perfusion during and after reconstructive surgery in the periocular area is still limited. This article presents a comprehensive review of modern techniques for perfusion monitoring and the current state of knowledge regarding the effects on blood perfusion in the periocular area during and after reconstructive surgery.
Knowledge of the arterial supply to the periocular area is essential when anticipating the effects of reconstructive surgery on blood perfusion. The vascular anatomy of the eyelids is illustrated in Fig. 1. The eyelids are mainly supplied by the internal carotid artery via the ophthalmic artery and secondarily by the external carotid artery, through the branches of the infraorbital, facial, and superficial temporal arteries. Branches of the lacrimal artery, i.e., the lateral superior and inferior palpebral arteries, run in the lateral to medial direction in the upper and lower eyelids. Together with the medial palpebral arteries, they create an anastomosis, forming the superior and inferior arterial arch of the eyelids.1 The anatomy of the periocular vascular system has mostly been investigated by the dissection of human cadavers.2 Novel perfusion and oxygenation monitoring techniques provide the opportunity to learn more about the physiology of blood perfusion in the periocular area in vivo.
TECHNIQUES FOR MONITORING BLOOD PERFUSION AND OXYGENATION
The assessment of the viability of tissue during and after surgery is of outermost importance, especially in complex surgical procedures. Clinical examination allows the surgeon to examine the status of perfusion using traditional methods such as observations of skin temperature, turgor, color, smell, and capillary refill time.3 Other techniques for the clinical evaluation of perfusion include bleeding following a pinprick test to assess the color (bright red vs. cyanotic) and speed of flow (brisk vs. slow).4 The observation of clinical signs is a highly subjective means of assessing perfusion and depends on the experience of the surgeon. There has thus been a need to develop techniques to monitor perfusion objectively. Brief descriptions of these techniques are given below.
Various pharmacological agents were employed in early studies on blood perfusion. For instance, in 1948, Hynes demonstrated a technique for estimating blood flow in pedicle skin flaps and tubes using the vasodilator activity of atropine.5 Conway et al. used the cutaneous histamine reaction to evaluate the perfusion of tubed pedicles and flaps, as histamine is known to be a powerful vasodilator.6 However, these methods are invasive, they lack objectivity, and there is a risk of systemic reactions, making them less suitable.
Fluorescein angiography has been a popular method due to its low cost and availability for intraoperative use. Sodium fluorescein is injected intravenously and diffuses across capillary walls into the extracellular fluid compartment. The tissue is illumined with ultraviolet light (e.g., with a Wood’s lamp), and the distribution of the fluorescent dye is observed. Fluorescent angiography has been a frequently used technique to facilitate tracing of the vasculature and has been used in in many studies to monitor the blood perfusion in tissue.7–12 Apart from being an invasive method, the dye discolors the tissue for up to 18 hours after injection, meaning that measurements cannot be repeated within 24 hours. There is also the risk of an allergic reaction to the dye, although this is relatively low. This technique has been further developed by the implementation of computer-aided digital morphometry to measure skin fluorescence. In 1996, Issing and Naumann reported that this technique gave a more reliable prediction of flap survival than pH and temperature monitoring.13
Indocyanine green is another type of fluorescent dye, with absorption in the near-infrared range (790–805 nm). It is widely used in ophthalmology to examine choroidal blood flow and associated pathology. It has been proposed as an alternative to sodium fluorescein, since it has more favorable pharmacokinetics due to its protein-binding properties. There is less leakage from the capillaries, and it thus remains in the vessel longer, giving a clearer image of the vessel.14 However, its use in reconstructive surgery has been limited as it still requires an intravenous injection, and repeated monitoring is time consuming and only possible after the dye from the previous injection has been cleared from the tissue.
Disulfine blue dye, or similar dyes such as isosulfan blue or patent blue, is frequently used for lymphatic mapping and sentinel node biopsy in cancer surgery.15 It is also used to map fistulas before and after surgical excision.16–18 This technique has been shown experimentally to be useful for visualizing the perfusion of flaps.19 After injection, the dye collects in well-perfused areas and is visible to the naked eye without the need for an imaging system. However, it has been reported that blue discoloration can persist for over 12 months at the site of injection in 68% of treated patients20 and that blue discoloration of the body may last for several hours.21–23 Although rare, there are also reports of anaphylactic reactions to the dye.21–23 This method is, therefore, not appropriate for use in the clinical setting.
Subcutaneous pH monitoring has been used to assess flap viability as inadequate tissue perfusion increases anaerobic metabolism, resulting in the accumulation of acidic metabolites. The use of subcutaneous or intramuscular probes has been demonstrated to be efficient in measuring pH to evaluate tissue viability, especially in muscle flaps where it is difficult to observe the color.24 However, there is a substantial delay between a change in perfusion and in the pH, and the pH does not decrease until the process of necrosis has started. This method is, therefore, not suitable for predicting flap survival.
Radioactive isotopes have been widely used to monitor myocardial perfusion25,26 and in porcine studies to study myocutaneous flap ischemia27 and the microcirculation in myocutaneous island flaps in pigs.28 This method involves the injection of a radioactive isotope tracer into a vessel, immediately followed by scans with a gamma camera to visualize the distribution of the injected radioisotope. The uptake will be high in healthy, well-perfused tissue. Several isotopes have been used in flap surgery in humans, including sodium-22 and xenon-133. Apart from the fact that the method involves the handling of radioactive materials and waste, another drawback is that measurements cannot be repeated within 24 hours due to remaining background radioactivity.29
Hydrogen Gas Clearance
Hydrogen gas clearance and radioactive isotopes are based on the same principle, but the risks associated with ionizing radiation are avoided. The subject breathes in a mixture of hydrogen and oxygen gas, and the level of hydrogen gas in the tissue is measured using implanted platinum probes. Repeated and quantitative measurements are also possible. The hydrogen is then eliminated via the lungs. This technique has not been found useful clinically since it requires a probe to be implanted in the tissue and provides only point measurements of perfusion.30
Microdialysis is used clinically in neurointensive care to monitor secondary cerebral ischemia after brain injury or intracranial hemorrhage. Microdialysis has primarily been used in preclinical animal studies but also in human studies to help understand, for example, skin inflammation and skin inflammatory disorders,31 and to monitor perfusion in the human femoral head32 and the brain.33 Catheters, with membranes connected to a pump perfused with a suspension, are implanted in the tissue of interest. The suspension is adjusted so as to create an equilibrium between the pressure in the catheter and the interstitial fluid pressure. After the diffusion of plasma products such as glucose, lactate, pyruvate, and glycerol, a sample of the suspension is collected from the catheter and analyzed. A lactate/pyruvate ratio above 25 has been proposed by Ungerstedt and Rostami to indicate ischemia.34 Hickner et al. used a microdialysis ethanol technique to determine the nutritive blood flow in skeletal muscle in a cat model and concluded that it was a simple and valid method in comparison to direct measurements.35 The microdialysis technique has undergone much development since its first use in 1972,36 but there is still a need for the implantation of a catheter, making it invasive and time-consuming. Furthermore, the temporal and spatial resolution are relatively low, and information on perfusion can only be obtained in a very limited volume.
It has been suggested that tissue temperature reflects perfusion. Skin temperature can be easily monitored using noninvasive, infrared cameras. However, skin temperature is not solely dependent on perfusion but is also affected by thermoregulating enzymes, core temperature, air temperature, humidity, light, and vasomotor responses. Although there is a delay in the change in skin temperature following a decrease in perfusion, the measurements are repeatable, and when properly performed, the sensitivity of surface-temperature monitoring using thermoelectric thermometers has been reported to be 98%, and the predictive value to be 75% when monitoring free flaps.37
The Clark Electrode
The Clark electrode is an implantable probe that has been used to monitor flap oxygenation and predict viability.38,39 It has also been used as part of a postoperative warning system for impaired flap oxygenation, leading to successful surgical interventions.40 The electrode is enclosed in a semipermeable membrane, allowing tissue oxygen to diffuse into the electrode chamber, where it is reduced by a gold polarographic cathode. This produces an electric current that is proportional to tissue oxygenation. The electrode only allows a point measurement around the electrode, making it susceptible to the detection of nonrepresentable data in tissues with heterogeneous oxygenation.
Oxygen saturation can also be assessed using spectroscopic methods, such as near-infrared spectroscopy. Tissue is exposed by light in the 690- to 1000-nm spectral range where different molecular components exhibit unique absorption features. The light that is not absorbed and is reflected by the tissue is measured, from which the absorbing species can be identified. Hemoglobin has different wavelength absorption peaks when it is oxygenated and deoxygenated, allowing the analysis of tissue oxygenation and perfusion. A small probe that both emits the light and detects the reflected light can either be implanted subcutaneously or placed on the skin surface. Techniques employing a wider spectral range (900–1700 nm) have evolved that provide comprehensive information on blood perfusion and tissue response in human skin.41,42 Spectroscopic techniques exploit the spectral information obtained from the tissue, although they lack the spatial resolution needed to identify heterogeneous tissue oxygenation.
The most common clinical implementation of spectroscopic methods is pulse oximetry. This method compares the transmittance of light of two different wavelengths in the near-infrared spectral range (660 and 940 nm) through tissue and is based on the fact that oxygenated and deoxygenated hemoglobin absorb light differently. The total amount of hemoglobin determines how much light is transmitted at both wavelengths. The volumetric changes in blood flow can also be determined continuously by measuring the transmittance several times per second. Surface-based pulse oximetry is widely used in the clinical setting to monitor oxygen saturation during anesthesia or failing vital functions over a relatively small surface area, such as the tip of a finger, a toe, or an earlobe.
Diffuse Optical Tomography
Diffuse optical tomography is an imaging modality employing near-infrared spectroscopy and is capable of providing a spatial map of oxygen saturation over a larger area. It is based on the same principle of absorption and reflection, as described above, but employs an array of probes that systematically emit and detect light from different locations, allowing a tomographic image of the sample to be constructed. The equipment is relatively compact and can be transported for bedside use. The disadvantage of diffuse optical tomography is that image stability is obtained at the expense of spatial resolution, which is limited to ≈1 cm. To overcome this obstacle, diffuse optical tomography is often combined with other imaging modalities with high spatial resolution, such as magnetic resonance imaging or ultrasound, which allows the clinician to interpret the diffuse optical tomography findings based on a more anatomically precise image.43
Hyperspectral imaging is a noninvasive technique in which the tissue is irradiated using a white incandescent light source (broad spectrum), after which the reflected light is processed to extract a map of spatially resolved reflectance spectra. Hyperspectral imaging has found use in the clinical setting in providing spatial maps of oxygen saturation of skin flaps, arms, and legs.44,45 As the technique employs white light, it could be used in the periocular area, although this has not yet been done.
Standard Commercial Red Green Blue Cameras
Standard commercial Red Green Blue cameras capture images with spectral information corresponding to the sensitivity of human vision. Although the spectral information is not as extensive as that obtained with hyperspectral imaging methods, Red Green Blue cameras can be used to qualitatively assess changes in blood flow and oxygenation. Sheikh et al. demonstrated this by monitoring vasoconstriction of the superficial vascular plexus in human forearm skin following an injection of lidocaine and epinephrine.46 Blanching of the skin led to slightly different responses in the three color channels, and the overall change in all three channels, compared to baseline values, allows monitoring of the relative changes in blood perfusion over time.
Magnetic Resonance Angiography
Magnetic resonance angiography has been found successful in monitoring arterial and venous occlusion experimentally, but its availability is so limited that it is of little practical use.
Photoacoustic imaging is regarded as one of the most promising noninvasive biomedical imaging techniques and offers molecular images with high spatial resolution.47 The benefits of spectroscopic-based specificity and ultrasound imaging depth are combined. Photons are transmitted from a laser source are absorbed in the tissue and the thermoelastic response gives rise to acoustic waves. The detection of sound, using an ultrasound probe, to determine the light absorption affords photoacoustic imaging the unique feature of high spatial resolution. If the absorption spectra is analyzed by applying spectral unmixing, it is possible to extract molecular information, including relative concentrations of oxyhemoglobin and deoxyhemoglobin.48 Using photoacoustic imaging, it is possible to map oxygen saturation at specific locations in the tissue, noninvasively.
Most of the studies in which photoacoustic imaging was used to assess the possibility of measuring oxygen saturation have so far been performed preclinically.49,50 Photoacoustic imaging was recently adapted for the examination of the temporal region in humans51 and was proven safe with regard to visual function.52 However, its future use in the periocular area is envisaged, provided that the energy levels of the laser light are closely regulated and the eyes are protected. The pigment cells of the retina absorb light in the 680- to 970-nm wavelength range, and there is thus a risk of damage when using photoacoustic imaging. However, the most important factors are the absorption power and the focusing effect of the lens and cornea, and photoacoustic imaging with low energy levels and the eyes closed should not pose a risk. However, further studies are needed on the safety of the method before it can be applied in vivo. This technique has considerable potential for translation to the clinical setting since it allows noninvasive molecular imaging at high resolution at sufficient imaging depths, with diverse endogenous and exogenous contrast. Initial studies have shown that photoacoustic imaging can map tissue oxygenation in humans.53,54 A recent study proved the feasibility of preoperative vascular mapping in human thigh flap surgery,55 and it may be a good indicator of the degree of tissue damage in patients with skin burns.55,56 Initial studies of eyelids show clear spectral differences between different anatomical structures,57 and tumors of the eyelids can be delineated to achieve a more precise excision.58 Photoacoustic imaging is a promising technique for monitoring oxygenation during reconstructive surgery, but further studies are needed.
Laser Doppler Flowmetry
The first laser was introduced in 196059 and laser-based techniques are today the most frequently used clinically to assess microcirculation. Laser Doppler flowmetry is based on the Doppler principle. The skin is illuminated by coherent laser light at infrared or near-infrared wavelengths that penetrate the surface. Light particles hitting moving red blood cells undergo a change in wavelength, a so-called Doppler shift, while light particles encountering static structures will be reflected unchanged.60 The signal is interpreted as perfusion and given in arbitrary units. Laser Doppler flowmetry allows changes in perfusion to be monitored in real time at the bedside. However, skin surface probes, or filament or needle probes, need to be inserted into the tissue and perfusion is only measured in a volume of about 1 mm3 around the probe.61,62
Laser Doppler Perfusion Imaging
Laser Doppler perfusion imaging has been developed to overcome the problems associated with small sampling areas and the variability due to the spatial heterogeneity in the microcirculation of the skin. The scattered light, from the scanning laser beam, is detected by a photodetector, in the same way as in the laser Doppler flowmetry technique. In laser Doppler perfusion imaging, the wavelength of the reflected light is also affected by the movement of red blood cells (as described above). It has been used for tissue monitoring in conjunction with reconstructive surgery, but is not used to any great extent clinically. However, attempts have been made to overcome the long acquisition time, and the technique is used at some centers for burn wound assessment.43,63,64 The greatest drawback yet to be overcome is that any tissue motion during the lengthy scan will be interpreted by the system as falsely high blood flow, in addition to compromising the accuracy of flow in the various regions.
Laser Speckle Contrast Imaging
Laser speckle contrast imaging (LSCI) is often considered the most useful, noninvasive technique for clinical perfusion monitoring in reconstructive surgery. It was introduced in 1993 by Yamamoto et al., who reported a new visual blood flow meter employing a dynamic laser speckle effect.65 The technique was initially introduced to evaluate retinal blood flow in various diseases, including glaucoma, retinopathy, and macular degeneration,66,67 and has evolved into a method with the potential to monitor perfusion during reconstructive surgery.68–70 The principle of LSCI is illustrated in Fig. 2. The area of interest is illuminated by an infrared laser at 785 nm. Interference of the light backscattered from moving particles in the illuminated area results in dark and bright areas, creating a speckled pattern. This speckled pattern is recorded in real time by a camera. The system then calculates movement in the tissue by analyzing the variations in the speckled pattern. The movement is interpreted as a measure of perfusion. The main advantage of LSCI is that it is completely noninvasive and does not require contact with the tissue. Other advantages include short acquisition times and high spatial resolution; the speckle pattern being recorded in real time at a rate of up to 100 images per second, with a high resolution of 100 μm/pixel. LSCI enables a relatively large area to be monitored, e.g., 24 × 24 cm, which makes it less sensitive to regional variations in microvasculature, generating data with less interobserver variability than the laser Doppler technique.71 However, due to the absence of contact between the tissue and sensors, environmental conditions, such as room lighting, may affect the results.72
Laser-based techniques are sensitive to tissue movement, e.g., due to breathing or other involuntary movements. Various methods of overcoming this problem have been suggested, such as shorter sampling times, careful selection of appropriate images for analysis, and simultaneous recording of the signal backscattered from an adjacent opaque surface.73 The perfusion at a given point in time is also affected by the peripheral circulation of the patient, which will vary as a result of physical activity, smoking, food intake, and temperature. In order to compare measurements made at follow-up and between different individuals, the perfusion measured in, for instance, a skin flap must be normalized to a reference point outside the flap where the basal blood perfusion should be unaffected by surgery. Furthermore, the maximum penetration depth of laser-based techniques is about 0.3 to 1 mm, depending on the vascular anatomy and the concentration of red blood cells in the upper dermis.62 This means that perfusion is monitored in the outermost layer of the skin, while the spatial resolution in the deeper layers, which are of interest, for example, in the evaluation of burn injuries, is poor. Despite these drawbacks, LSCI is today the most commonly used technique for perfusion monitoring during reconstructive surgery68–70 and for the assessment of burns71,74–76 and wound healing.77
PERFUSION AND OXYGENATION MONITORING IN OCULOPLASTIC SURGERY
The earliest records of plastic reconstructive surgery have been found in an ancient Egyptian document called the “Edwin Smith Papyrus,” probably dating from the early dynastic period around 1500 BC. This document describes a variety of surgical procedures. In 1920, Sir Harold Gillies performed groundbreaking surgery on disfigured soldiers following World War I, and many of these reconstructive surgical techniques are still used today, including skin grafts and the tubed pedicle, as presented in his textbook of plastic surgery.78 Procedures for plastic reconstructive surgery were thus developed long before techniques were available for monitoring the oxygen saturation and blood perfusion in tissue, and knowledge was mainly empirical, based on observations of the rate of flap survival. Modern techniques now allow the systematic evaluation of the effects of surgical procedures on perfusion,79 allowing improvements of existing surgical procedures and the development of new ones. The present review focuses specifically on the advances in perfusion monitoring in oculoplastic surgery.
In order to identify studies on blood perfusion and oxygen monitoring in the periocular area, a systematic Medline search was performed on PubMed. No restrictions were placed on the date of publication. Only articles published in English were included. The search terms included “reconstructive surgery,” “oculoplastic,” “periocular,” “periorbital,” “blood flow,” “blood perfusion,” “oxygen,” “monitoring,” “flap,” “skin graft,” “reperfusion,” “revascularization,” and “viability.”
Rich Vascular Supply of the Periocular Region
The first tentative attempts to monitor perfusion in the periocular area confirmed the rich vascular supply. In 1996, Mannor et al. reported in a laser Doppler perfusion imaging study that the perfusion of the eyelids was an order of magnitude higher than that in, for example, the forearm.80 Furthermore, the perfusion in pretarsal skin was twice as high as that in preseptal skin, which may be explained by the arterial supply by the tarsal arcades. In 2018, Fei et al. investigated blood perfusion using a full-field laser perfusion imager, showing the highest cutaneous perfusion in the eyelid.81 The rich vascular supply of the periorbital region makes it forgiving to reconstructive surgery. However, deeper knowledge of the perfusion in the periocular area may increase our understanding of the effects of reconstructive surgery and hopefully facilitate the improvement of existing surgical procedures and lead to the development of novel surgical approaches. A description of the effects on perfusion during and after common oculoplastic procedures is given below.
The modified Hughes tarsoconjunctival flap is one of the most commonly used techniques for reconstructing the posterior lamella of large full-thickness eyelid defects after cutaneous malignancy excision.82–84 This reconstructive technique is based on the combination of an avascular graft with a vascularized flap. It comprises a vascularized tarsoconjunctival flap from the upper eyelid to reconstruct the posterior lamella and a free skin graft to reconstruct the anterior lamella.85 The conjunctival pedicle from the upper eyelid is divided once vascularization of the reconstructed lower eyelid is deemed to be adequate, usually after 3 to 4 weeks.86 This makes the Hughes procedure a 2-stage procedure involving the occlusion of the eye during the process of vascularization, and there is thus much to gain from making the technique a 1-stage procedure, especially in older patients with impaired vision in the contralateral eye.
Surprisingly, recent perfusion monitoring studies have shown that the perfusion in the tarsoconjunctival flap is virtually nonexistent, but despite this, the free skin graft usually revascularizes and heals without necrosis. In a porcine model of tarsoconjunctival flaps, Memarzadeh et al. used laser Doppler velocimetry and a Clark electrode to show that blood perfusion and oxygenation decreased gradually during dissection and advancement of the tarsoconjunctival flap, and at the time when the flap was sutured into placed, the perfusion was negligible.39 Despite this, all the flaps survived, and there was no sign of necrosis in any of the histological samples collected.39 In a later study, Tenland et al. showed minimal perfusion in tarsoconjunctival flaps in humans using laser Doppler flowmetry and LSCI.87 In a different study, the revascularization of the overlying skin grafts was studied using LSCI, showing gradual reperfusion over 3 to 8 weeks.70
The excellent graft survival despite the lack of perfusion in the underlying flap, may be due to nourishment of the tarsus and skin graft by the vascular supply of the remaining eyelid, the tarsoconjunctival flap being a secondary, nonessential contributor. Furthermore, the tarsoconjunctival flap and the free skin grafts are soaked in tear fluid, which is known to have a high level of oxygenation and the same spectrum of nutrients as the blood.88
Others have questioned the importance of perfusion of the tarsoconjunctival flap for the survival of the overlying graft. Bartley et al. reported premature flap dehiscence 1 to 11 days postoperatively in 8 patients who underwent the modified Hughes procedure, and all the eyelids healed well.89 Hargiss suggested a 2-tubed conjunctival flap for providing satisfactory vascular support equivalent to an apron flap.90 Furthermore, Leibsohn and associates intentionally made a small optical buttonhole in the flap without affecting the healing.91 In 2 studies by McNab and colleagues, satisfactory results were achieved when the conjunctival pedicle was divided already after 2 weeks.92,93 A shorter interval before dividing the conjunctival pedicle has been suggested by others.94,95
The pedicle in the tarsoconjunctival flap offers a vertical lift by supporting the skin graft of the anterior lamella during healing. However, the disadvantage of this procedure is that the eyelids must be sewed together for several weeks. Additionally, it has been shown by Klein-Theyer et al. that the Hughes tarsoconjunctival flap may cause tear film dysfunction and damage to the corneal surface by affecting the function of the Meibomian glands.96 Based on the knowledge that the blood perfusion in tarsoconjunctival flaps is limited, a single-stage grafting procedure may be an attractive alternative, removing the need for postoperative eye occlusion.
Free Bilamellar Grafts.
Free bilamellar eyelid grafting is a single-stage procedure in which a full-thickness graft is taken from the opposing or contralateral eyelid to repair large eyelid defects. In 2020, Tenland et al. reported on 10 patients undergoing free bilamellar eyelid grafts, in which perfusion monitoring using LSCI showed rapid revascularization, being 90% after 8 weeks, and the clinical outcome was excellent.97
The use of free bilamellar grafts is supported by others. Memarzadeh et al. described a case of an upper eyelid defect that was reconstructed using a free eyelid composite graft from the lower eyelid of the ipsilateral eye. There were no complications, and the graft healed well.98 A similar outcome was described in a case of traumatic amputation of the lateral 2/3 of the upper eyelid, which was sutured in place and survived with good results even after 10 years.99 There are numerous other case reports extending farther back in time supporting these findings,100–102 as well as descriptions of the technique in textbooks.103
However, there have also been reports of partial graft necrosis in free bilamellar grafts.103 It may be that free bilamellar grafts need to be fairly small to facilitate rapid revascularization. The grafts in the study by Tenland et al. were less than 1 cm wide.97 The use of free composite grafts is well-known from other specialties, for example, the repair of a nasal wing defect using a free composite graft from the outer ear.104,105 To the best of our knowledge, the use of a composite free graft of skin and cartilage from the ear for the repair of coloboma of the nose was first published in 1946 by Brown and Cannon.106 Another factor that may be of importance for graft survival is the patient’s microvascular status. Further studies are needed to investigate the effects of factors like this on perfusion and the final surgical outcome.
Free Bilamellar Grafts With a Vascularized Component.
An alternative to free bilamellar grafts, to minimize the risk of necrosis, is to combine them with vascularized tissue. In 1978, Putterman suggested a technique for the repair of upper eyelid defects by removing the skin from the composite graft, creating a composite graft that consisted of eyelid margin, conjunctiva, and tarsus, which was covered by a skin flap to aid its revascularization.107 In 1984, Putterman described a revision of this procedure in which a composite graft was combined with a semicircular temporal skin flap.108 In 1993, Werner et al. reviewed the records of 51 patients who had undergone composite grafting (conjunctiva and tarsus) combined with a skin flap since 1983 by Putterman. The authors agreed that this was a valuable method for eyelid reconstruction that provided acceptable cosmetic results.109 It would be of great interest to monitor perfusion using this procedure, since this has yet not been done.
Hewes Flap Procedure.
The Hewes flap procedure is a single-stage procedure in which a tarsoconjunctival eyelid flap, based at the lateral canthal tendon, is raised and rotated, and stretched to repair the posterior lamella, while a free skin graft is used for the repair of the anterior lamella.110 Perfusion monitoring has been performed in a porcine model of the Hewes flap procedure, and the results showed fairly well-preserved perfusion in the flap despite rotating and stretching it to cover a defect in the opposing eyelid.69 Perfusion monitoring of this procedure has not yet been performed in humans.
Canthotomy is frequently used to mobilize extra tissue when repairing larger lower eyelid defects.111 Laser Doppler monitoring in a porcine model showed that wedge resection in combination with canthotomy reduced blood perfusion in the eyelid: the closer the canthotomy to the wedge resection, the lower the blood perfusion.112 This is probably due to the fact that the lateral palpebral arteries that give rise to the marginal and peripheral arcades supplying the eyelid are cut.113 There are well developed anastomoses to the eyelid from the anterior ciliary arteries through the conjunctiva and from branches of the external carotid artery system, and an alternative explanation could be that the canthotomy disrupts the additional blood supply from these dermal plexus anastomoses. With this in mind, it can be speculated whether an internal cantholysis without a canthotomy, i.e., a preserved anastomotic plexus, would lead to less of a decrease in the perfusion.114 It may be particularly important to consider this in cases of large eyelid defects, in which lateral canthotomy is required to alleviate tension. This is seldom a problem in cases of direct closure of an eyelid defect since perfusion is unaffected on both sides of the defect. However, if avascular grafts are required to fill the defect, such as in a composite graft97–102 or synthetic grafts, it should be considered whether it is wise to perform a canthotomy, as this would reduce the blood perfusion. Another procedure that should perhaps not be combined with canthotomy is the tarsoconjunctival flap in the modified Hughes procedure, since it has been shown that there is only minimal blood supply to the tarsus.38,87 A reconstructive procedure in which perfusion has not been studied is the use of periosteal flaps to lengthen and repair eyelids, sometimes combined with synthetic grafts. It would be interesting to monitor changes in perfusion following these procedures. In conclusion, it is necessary to consider the risk of reduced perfusion to the eyelids resulting from canthotomy, in particular, when using avascular grafts.
There may be other reasons to avoid canthotomy if it is not absolutely necessary. Thaller avoided canthotomy by closing eyelid defects under extreme tension.115 The eye bulb acted as an expander, and postoperative outcomes after 2 months were excellent, both cosmetically and functionally, especially in lower eyelids. Thaller recommended avoiding canthotomy since it counteracts the expansion of the eyelid.115–117 With careful suturing of a composite graft, i.e., firm suturing of the tarsus, closing the defect under tension to avoid canthotomy may be a better approach.
Random Pattern Skin Flaps
Skin defects are often reconstructed with a local skin flap, since they better match the color and texture of the periorbital skin, have their own blood supply, and exhibit less contraction upon healing than free skin grafts.118 Successful design of the flaps depends on understanding the vascular supply and the process of revascularization. In a random pattern skin flap, the blood supply is derived from many small unspecified vessels (i.e., diffuse perfusion in the microvascular network, without blood supply from a larger blood vessel). Recent studies indicate that the dissection of a random advancement flap will result in hypoperfusion and that oxygenation depends on different factors, such as the length and thickness of the flap,39 whether it consists of skin only or skin and orbicularis muscle,119 whether it is stretched or rotated,68 and whether its base is subjected to diathermy.120 A more detailed description of how the perfusion is affected is given below.
Clinical rules of thumb often governed the design of flaps, and the viable length of a flap is thought to depend on the width of its pedicle. In 1920, Sir Harold Gillies suggested that a flap should not be longer than the width of its base.78 This principle became foundational and continued to evolve throughout the 20th century. In 1970, Milton et al. used a porcine model to study the surviving area of rectangular, different sized flaps.121 The surviving area was found to have a constant ratio to the base of the flaps, and it was concluded that a constant area-to-base ratio was required, with the proviso that there is an upper limit on the surviving length that cannot be increased by increasing the width of the base.122 These are all anecdotal studies, and the development of perfusion monitoring techniques offers the opportunity to carry out detailed studies of how the length:width ratio influences the perfusion in advancement flaps.
Laser Doppler perfusion imaging and Clark electrode oxygenation measurements in a porcine model showed that it is not possible to predict the degree of perfusion and oxygenation of a random advancement skin flap by the length:width ratio but rather is correlated to the length of the flap.39,123 This has also been confirmed using LSCI in human skin flaps dissected in the upper eyelid during the blepharoplasty procedure, in which the medial end of the flap remained attached, to mimic a flap.68,120 It has been shown that perfusion is primarily maintained in the first 15 mm from the flap base in human cutaneous upper eyelid flaps but is very limited at greater distances.120 In a similar study, the base was made 10 mm wide, and the blood perfusion was seen to decrease in a similar manner.68 Clinically, the length of an eyelid skin flap should allow it to be moved from the donor to the recipient site, while still containing sufficient vascular elements to ensure viability of the tissue. Based on the results of the above studies, the distal part of a long flap appears to function as a free graft68,120 but with the advantage that it matches the color and texture of the recipient site. The early principle regarding the maximum area or length of a flap being dependent on the width of the base78 might have had some important degree of truth, but technical advances, such as incorporating surgical delay, have allowed the use of extended flaps beyond the acute survival length.
Perfusion monitoring has provided clear evidence that the thickness of a random pattern flap is of great importance for its perfusion and oxygenation.39 In a recent study by the authors, the perfusion was monitored using LSCI in patients undergoing blepharoplasty, in which the medial end of the flap remained attached, to mimic a frequently used flap. The results showed that blood perfusion was better preserved in myocutaneous flaps than in flaps that consisted only of cutaneous tissue.119 These results are consistent with those of a previous study on porcine flaps, using laser Doppler perfusion imaging and Clark electrode oxygenation monitoring, in which a thick flap, which was dissected all the way through the subcutaneous tissue down to the muscle fascia, had better perfusion and oxygenation than a thin flap, which was only dissected halfway through the subcutaneous tissue.39 The better perfusion in myocutaneous flaps can probably be explained by the vascular anatomy of the upper eyelid. The deeper segmental artery of the area gives off branches that run perpendicularly toward the surface of the skin, penetrating muscle layers and adipose tissue. The cutaneous microcirculation is organized into a deeper plexus at the junction between the dermis and the underlying subdermal fat and a plexus approximately superficial to the basement membrane. The more extensive vascular network in the dermal and subdermal vascular plexuses will allow higher perfusion of the myocutaneous flap. Making a thick flap, i.e., including the underlying orbicularis muscle, may be of particular importance in patients with poor microcirculation needing a long flap for reconstructive surgery.
Stretching and Rotating Flaps.
Flaps are commonly stretched and rotated to cover a defect. In advancement flaps, adjacent tissue is stretched linearly. In rotation flaps, adjacent tissue is pivoted around an axis to close a defect, essentially rotating the skin into the defect. It is often necessary to both rotate and stretch skin flaps in order to cover defects. LSCI of upper eyelid flaps in humans showed that only rotation of the flap by 90° had no significant effect on perfusion,68 which is in line with the results of previous studies on porcine and human eyelid flaps.68,124 Stretching the nonrotated flaps affected the perfusion slightly. However, the combination of stretching and rotating the flap reduced the blood perfusion markedly.68 This is consistent with the results of other studies on porcine and human eyelid flaps.123,124 A compromise must thus be found between the length of the flap and the degree to which it is stretched, especially in cases of long flaps. This may be of particular importance when using synthetic grafts, or when combining, for instance, buccal mucosa, periosteal flaps, and skin-muscle flaps.
Effects of Diathermy.
Cauterization of blood vessels is common to prevent excessive bleeding during surgical procedures in the periorbital region. Little could be found in the literature on the effects of diathermy on flap perfusion. In a study on upper eyelid skin flaps using LSCI, it was found that diathermy, especially repeated diathermy, of the base of the flap had detrimental effects on perfusion.120 Similar results were found in a Hewes tarsoconjunctival flap in a porcine model.69 The observations suggest that the use of diathermy should be carefully considered, especially in cases of long thin flaps that are poorly perfused. Repeated diathermy of the base of the flap most likely causes the flap to function more like a free skin graft than a flap.
The H-plasty procedure involves the use of bipedicle advancement flaps with a random blood supply. The procedure is commonly used to repair defects after tumor surgery in the head and neck region. LSCI during H-plasty procedures in the periorbital region showed impaired perfusion immediately after surgery. The lengths of the bipedicle flaps were 8 to 20 mm, and the median perfusion at the distal end of the flap was 54%. Reperfusion occurred rapidly, presumably due to the existing vascular network of the flap pedicle, and the flaps were fully reperfused after 1 week. The H-plasty healed well in all cases, and no tissue necrosis was seen.125 Random flaps are known to be more viable in the face than elsewhere, viability decreasing with the distance from the face.122
Repair of the medial canthal area after tumor excision can be challenging for the surgeon, and the glabellar flap is a common choice. This is a V-Y flap, based on a random blood supply, allowing the advancement of skin from the lax glabellar skin region into the medial canthal area.110 Perfusion monitoring of the glabella flap procedure has recently been performed, showing that during surgery, perfusion decreased along the length of flap, with a further slight decrease upon rotation and suturing of the flap into place, reaching a minimum 15 mm from the flap base. Reperfusion was almost completely restored already after a week, which may be explained by its connection to the vascular network via the flap pedicle. This confirms the general opinion that the glabellar flap is a good reconstructive technique, especially in the periorbital region with its rich vascular supply.126 However, there have been reports of both short- and long-term problems associated with glabellar flap reconstruction, including necrosis of the tip or edges of the flap in the early postoperative period.127
Large upper eyelid defects can be repaired by rotational full-thickness lower eyelid flaps.110 LSCI was performed in a case in which removal of a basal cell carcinoma on the upper eyelid resulted in a defect measuring 26 mm horizontally and 10 mm vertically. The defect was repaired by advancing and rotating a full-thickness flap from the lower eyelid by 180°. Perfusion of the flap decreased by 50% during surgery but was almost completely restored 5 weeks later at flap division (91%).128 In a study including 9 patients undergoing the Quickert procedure due to entropion, the tissue was dissected to mimic a full-thickness lower eyelid flap of approximate width 0.5 cm and length 2 cm.124 The results indicated that these full-thickness eyelid flaps were better perfused than random pattern skin flaps on the eyelid68,120 and could be made 15 mm long with retained perfusion.124 Similar results were obtained using laser Doppler velocimetry, LSCI, and thermography in full-thickness eyelid flaps in a porcine model.129 The fact that full-thickness eyelid flaps are so well perfused is most probably due to the fact that this is an axial flap, or arterial flap, which is a myocutaneous flap containing a direct cutaneous artery along its longitudinal axis, in this case the anastomosis of the medial and lateral palpebral arteries. A random skin flap, however, does not have a specific vessel for vascularization and is perfused by musculocutaneous microcirculation in the tissue.130
Free Skin Grafts
The tissue available for reconstructive surgery in the periocular area is often limited, and it may be difficult to ensure wound coverage. In cases where primary closure or closure using flaps is not possible, free full-thickness skin grafts are often considered. In oculoplastic surgery, a skin graft from the upper eyelid above the skin crease is often preferable, since it matches the color and texture and often heals well. If there is insufficient skin on the upper eyelid, or a local skin flap is not possible, free skin grafts from the inside of the arm, the pre- or postauricular area, or the supraclavicular fossa can be considered.110 Using a free full-thickness skin graft instead of a long flap is especially preferable when excising a tumor where the borders are difficult to define. If the primary excision is found not to be complete, it is easier to perform a secondary excision to remove the remaining tumor if the tissue is not distorted by a flap.
The authors monitored the reperfusion of free full-thickness skin grafts, taken from the upper eyelid or the upper inner arm, grafted to the periocular area, using LSCI. Reperfusion was found to be rapid and was completely restored within 7 weeks after surgery.131 Several factors are thought to influence the survival of grafts; the underlying graft bed being one of the most important. Grafts placed on well-vascularized tissue are believed to be more likely to survive than those on a less vascularized tissue.132 However, in a LSCI study on skin grafts overlying tarsoconjunctival flaps when using the modified Hughes procedure 2019, we found that the grafts overlying the tarsus were reperfused within 3 to 8 weeks, despite overlying a tarsoconjunctival flap,70 which has been reported to be avascular.87 We attributed these observations to the rich vascularization of the periocular area and the fact that the grafts had been soaked in tear fluid, which is known to have similar nutrients to those in blood.88
The process of revascularization of free skin grafts has been extensively studied in animal studies in several areas but not the periocular area.133–137 It is believed that anastomoses initially develop between graft and host vessels. A new system of blood vessels then extends into the graft from sprouting angiogenesis in the wound bed.138,139
Preexisting graft vessels have been shown to act as nonviable conduits for the ingrowth of the endothelium of new vessels.140 In 1956, Converse and Rapaport reported sluggish flow in the vessels in full-thickness skin grafts on the forearm in humans on the third day postoperatively, based on microscopic observations.133 In 1960, Ohmori and Kurata used intravenous injections of radioisotopes in a rabbit model, showing blood flow and isotope uptake in the graft 4 days postoperatively.134 Rapid reperfusion was also reported by Clemmesen and Ronhovde in 1968 who found dilated vessels connected to the original vessels of the graft in biopsies from humans 3 days after surgery.135 In 2006, Capla et al. observed vascular ingrowth in the periphery of full-thickness grafts on day 3 in a mouse model upon histological examination.136 In 2008, Lindenblatt et al. studied skin graft healing in a mouse model using repetitive intravital microscopy and saw capillary buds and sprouts on day 2 and blood in the graft capillaries on day 3. The original skin microcirculation was almost completely restored on day 5.137 This is in line with the studies of free skin grafts in the periocular area showing rapid revascularization.70,131
Local Anesthesia With Epinephrine in the Periocular Area
Epinephrine (adrenaline) is used in conjunction with local anesthetics to minimize bleeding during surgical procedures. Epinephrine has been shown to reduce bleeding (by vasoconstriction), prolong the analgesic effect,141 and reduce the systemic effects of local anesthetic agents (lidocaine).142,143 Surgeons usually wait several minutes for epinephrine to act before commencing surgery in order to minimize bleeding. The optimal delay often advocated in textbooks is 7 to 10 minutes.144 The optimal delay often advocated in textbooks is 7 to 10 minutes.144 However, in 2013, McKee et al., used oxygen spectroscopy to monitor the relative hemoglobin concentration in the skin of the arms in healthy volunteers and observed the lowest cutaneous hemoglobin level 26 minutes after injection.145 This was later confirmed in another study by the same authors, when measuring the blood loss from the skin in patients during carpal tunnel release surgery. In their later study, they observed a significant reduction in bleeding when skin incision was delayed by 30 minutes, compared to 7 minutes.146 However, these findings differ markedly from clinical experience in oculoplastic surgery. The optimal concentration of epinephrine to achieve vasoconstriction is also the subject of debate. Since epinephrine may affect systemic hemodynamics, there is a risk of disturbances such as hypertension and arrhythmia, making it important to define the lowest concentration of epinephrine that produces local vasoconstriction.147,148
In order to resolve these controversies, the effect of a local anesthetic with adrenaline on perfusion and oxygen saturation in the periocular region has been studied in detail. In a study on porcine eyelid flaps, using laser Doppler velocimetry, LSCI, and diffuse reflectance spectroscopy, maximum hypoperfusion was achieved at a dose of 10 μg epinephrine/mL. Furthermore, the time from the injection of epinephrine to the stabilization of hypoperfusion was 75 seconds.148 These findings were later confirmed in studies on human forearms.42,46 Bleeding was measured in patients undergoing upper eyelid blepharoplasty149 and in a porcine model.150 The time taken to reach maximal hemostatic effect was found to be 7 minutes. Waiting longer did not reduce bleeding further. In a recent LSCI study on a local anesthetic with epinephrine in patients undergoing blepharoplasty surgery, minimal perfusion was obtained already after approximately 2 minutes.151 Taken together, the findings above indicate that a concentration of 10 μg/mL epinephrine is adequate to ensure vasoconstriction before oculoplastic surgery and that incision need only be delayed for about 2 to 7 minutes.
Modern imaging techniques such as LSCI allow the monitoring of blood perfusion during and after reconstructive surgery, e.g., reconstructive periocular surgery using free skin grafts combined with flaps. There are several surgical procedures in which blood perfusion has not been studied using modern imaging techniques, and it would be of interest to monitor the changes in perfusion and the reperfusion in more complex reconstructive procedures and when combining flaps and free grafts.
Studies of larger groups would allow subgroup analyses, allowing factors known to affect blood perfusion and compromise the oxygenation of tissue, such as smoking, diabetes, previous surgery, and radiation therapy, to be investigated. It would also be of interest to study other factors that may promote wound healing, such as vitamin D.
The periocular area is known for its rich vascular supply, and flap survival may be higher than in other less forgiving areas of the body with lower blood perfusion. The design of flaps and free full-thickness skin grafts may be more important for the outcome and survival of tissue in other areas on the body, where flap viability, graft failure, and dehisced wounds constitute greater problems. Perfusion monitoring may be useful in such cases for the early identification of flap failure.
Further development of techniques not affected by motion artifacts, which currently limit the use of laser-based techniques, will hopefully be seen. Photoacoustic imaging is a promising laser-based technique with the potential to limit the effects of motion artifacts due to its innovative combination of laser excitation and ultrasound detection. Other optically based noninvasive techniques cannot match photoacoustic imaging regarding imaging depth, which can provide a spatial map of oxygenated and deoxygenated hemoglobin at depths down to 2 cm in the tissue. A problem associated with the use of photoacoustic imaging around the eye is that even very low photon doses can cause damage to the eye since, due to its coherence, laser light is more readily focused by the lens onto the retina. Methods employing incoherent light sources are, therefore, desirable, making hyperspectral imaging better suited to characterize the reflected light from a white light source to determine the molecular composition of tissue. Hyperspectral imaging could thus provide a functional map describing the oxygen saturation without the complications associated with laser-based methods, although this information is limited to the surface. Combining the detailed depth-resolved information provided by photoacoustic imaging with the surface-resolved information provided by hyperspectral imaging could prove to be an optimal solution for the comprehensive characterization of the molecular composition of tissue.
Modern imaging techniques allow detailed perfusion monitoring in flaps and in free skin grafts. This provides opportunities to improve current surgical procedures and thus the outcome and to better understand the healing process. Improved knowledge on perfusion and reperfusion will help surgeons in their choice of reconstructive technique and enable more tailored approaches for each patient.
We would particularly like to thank Jenny Hult and Rafi Sheikh for the figures. We are also most grateful to Elin Bohman for carefully reading the manuscript and giving valuable clinical input.
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