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Fibrin glue as agent for sealing corneal and conjunctival wound leaks
Abstract
PurposeTo describe a novel use of fibrin glue in managing leaking blebs and leaking wounds following trauma or surgery.Methods
Interventional case series.ResultsWe report eight patients, including three where intra-operative or immediate post-penetrating keratoplasty recalcitrant leaks from the graft-host junction and/or openings created by the needle pass, were noted. All three had thin recipient beds in the sector of leak. This was managed by intra-cameral injection of fibrin glue in the affected quadrant. This stopped the leak and allowed the defect to heal. One patient of Descemets-stripping-endothelial-keratoplasty had leak from the surgical wound, which was also sealed with fibrin glue. Two patients with leaking glaucoma-surgery-related blebs were treated with intra-bleb injection of fibrin glue to stop the leak. One patient with a penetrating corneal injury with a metal wire had a brisk leak upon removal of the wire. This was sealed with fibrin glue. Another patient of chemical burn with spontaneous leaks was managed by glue injection in the perforations. Transient rise of intraocular pressure in one patient with a leaking bleb was the only adverse event recorded.Conclusion
This novel adaptation of the application of fibrin glue can help to deal with persistent intra-operative, post-operative and traumatic aqueous and air leaks.Eye advance online publication, 27 October 2017; doi:10.1038/eye.2017.227.
... Fibrin is approved by the FDA as a glue for use in surgery and products currently on the market (e.g. Evicel and Tisseel) have demonstrated records of safety in the eye and brain after several decades of clinical use [26][27][28]. Previously, we generated fibrin gels with appropriate geometry, suitable mechanical properties, and degradation kinetics for use in RPE transplantation [24]. ...
... Fibrin has a long history of safe use for a variety of applications in the clinic [25,32]. This includes ocular use for corneal and conjunctival leaks, sclerotomy closure, and retinal breaks [27,28,32]. Our implant uses the same formulation as the fibrin glue currently used in the clinic. ...
Retinal pigment epithelium (RPE) transplantation for the treatment of macular degeneration has been studied for over 30 years. Human clinical trials have demonstrated that RPE monolayers exhibit improved cellular engraftment and survival compared to single cell suspensions. The use of a scaffold facilitates implantation of a flat, wrinkle-free, precisely placed monolayer. Scaffolds currently being investigated in human clinical trials are non-degradable which results in the introduction of a chronic foreign body. To improve RPE transplant technology, a degradable scaffold would be desirable. Using human fibrin, we have generated scaffolds that support the growth of an RPE monolayer in vitro. To determine whether these scaffolds are degraded in vivo, we developed a surgical approach that delivers a fibrin hydrogel implant to the sub-retinal space of the pig eye and determined whether and how fast they degraded. Using standard ophthalmic imaging techniques, the fibrin scaffolds were completely degraded by postoperative week 8 in 5 of 6 animals. Postmortem histologic analysis confirmed the absence of the scaffold from the subretinal space at 8 weeks, and demonstrated the reattachment of the neurosensory retina and a normal RPE–photoreceptor interface. When mechanical debridement of a region of native RPE was performed during implantation surgery degradation was accelerated and scaffolds were undetectable by 4 weeks. These data represent the first in situ demonstration of a fully biodegradable scaffold for use in the implantation of RPE and other cell types for treatment of macular degeneration and other retinal degenerative diseases.
... Hydrogels alone or together with cells as "repair patch" filling in corneal defects can be categorized into 2 classes: synthetic and naturally derived hydrogels. To name a few, cyanoacrylates, 24 polyethylene glycol, 25 collagen, 26,27 fibrin, 28 alginate, 29 chitosan, 16 gelatin, 30 and decellularized extracellular matrix (ECM) 31 have been studied for corneal repair. Synthetic hydrogels are easy to customize and preferable in meeting certain desired properties, but they may not promote tissue regeneration. ...
Purpose
The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ–forming hydrogel and study its effects on preventing corneal stromal opacity.
Methods
The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca ²⁺ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC–hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation.
Results
The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) ( P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups ( P < 0.05). The MSC–hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2’-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation.
Conclusions
The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.
... (Zmora et al., 2003;Kawamura et al., 2005) Furthermore, fibrin glue has been shown to be safe and effective as an ocular tissue sealant in ocular surface surgeries as well as in vitreoretinal surgeries. It has been used in ocular surface surgery for sealing corneal and conjunctival wound leaks, corneal stem cell transplantation, pterygium surgery, conjunctival closure after surgery, etc., (Pfister and Sommers, 2005;Srinivasan et al., 2009;Sonmez and Beden, 2011;Yang et al., 2013;Romano et al., 2016;Scalcione et al., 2018) Furthermore, isolated case reports have presented excellent results of fibrin glue as an adjunctive option in the surgical treatment of optic disc pit-associated macular detachment. (de Oliveira et al., 2017;Almeida et al., 2018) Therefore, it is theoretically feasible to apply fibrin glue to seal retinal breaks in patients with RRD based on favorable biocompatibility and sealing properties. ...
Rhegmatogenous retinal detachment (RRD) is the most common retinological emergency that can cause blindness without surgical treatment. RRD occurs when liquefied vitreous accumulates between the neurosensory retina and the retinal pigment epithelium via retinal breaks, which are caused by the separation of the vitreous from the retina with aging. Currently, the main treatment option is pars plana vitrectomy, which involves surgical removal of the vitreous and laser photocoagulation around retinal breaks to generate firm chorioretinal adhesion, as well as subsequent filling of the vitreous cavity with long-lasting substitutes (expansile gas or silocone oil) to prevent the connection between the subretinal space and the vitreous cavity via the breaks before the chorioretinal adhesion firm enough. However, the postoperative face-down position and the not very satisfactory first retinal reattachment rate place a heavy burden on patients. With the development of technology and materials engineering, researchers have developed biomaterials that can be used as a retinal patch to seal retinal breaks and prevent the connection of subretinal space and vitreous cavity via breaks, thus replacing the long-lasting vitreous substitutes and eliminating the postoperative face-down position. Preclinical studies have demonstrated that biomaterial sealants have enough biocompatibility and efficacy in the in vitro and in vivo experiments. Some sealants have been used in clinical trials on a small scale, and the results indicate promising application prospects of the biomaterial sealants as retinal patches in the repair of RRD. Herein, we review the recent advances in biomaterials as retinal patches for the repair of RRD, focusing on the biomaterial categories, methods, and procedures for sealing retinal breaks, as well as their biocompatibility and efficacy, current limitations, and development perspectives.
... Unique properties of either synthetic or natural biomaterials often provide tunability required for cornea regeneration. For instance, fibrin glue is used to restore corneal integrity after frequent intraoperative and postoperative corneal traumas and perforations [28,29]. A chemically modified UV crosslinkable material based on GelCORE gelatin has been developed which mimics the natural stiffness of the cornea and is highly adhesive, cytocompatible, and biodegradable. ...
Nowadays, tissue engineering is one of the most promising approaches for the regeneration of various tissues and organs, including the cornea. However, the inability of biomaterial scaffolds to successfully integrate into the environment of surrounding tissues is one of the main challenges that sufficiently limits the restoration of damaged corneal tissues. Thus, the modulation of molecular and cellular mechanisms is important and necessary for successful graft integration and long-term survival. The dynamics of molecular interactions affecting the site of injury will determine the corneal transplantation efficacy and the post-surgery clinical outcome. The interactions between biomaterial surfaces, cells and their microenvironment can regulate cell behavior and alter their physiology and signaling pathways. Nanotechnology is an advantageous tool for the current understanding, coordination, and directed regulation of molecular cell–transplant interactions on behalf of the healing of corneal wounds. Therefore, the use of various nanotechnological strategies will provide new solutions to the problem of corneal allograft rejection, by modulating and regulating host–graft interaction dynamics towards proper integration and long-term functionality of the transplant.
... Fibrin that has been utilized as an option to suturing for keratoplasties is created by combining fibrinogen and thrombin. Fibrin uses to close corneal wounds and leaks after surgery due to damage caused by trauma [77]. Fibrin has been used for corneal development in conjunction with agarose [78,79]. ...
Corneal transplantation from donor tissue is one of the primary healing of cornea diseases. However, the scarcity of donor tissue is a serious problem. Tissue engineering approaches offer an alternative recourse for corneal regeneration. Corneal tissue engineering (CTE) can provide tissue substitute to preserve and enhance corneal functions combining cells, bioactive molecules, and three-dimensional scaffolds for native cornea transplantation. 3D printing is a novel and rising process for constructing layer-by-layer fabrication of these materials in clinical applications. Among the different materials, gel-based inks are remarkable materials to use as ink in the 3D printing. In view of the printability feature of the inks, the processing abilities of the gel-ink formulation is an important parameter to consider. Furthermore, to produce gel-ink with transparency, non-toxicity, and mechanical properties almost identical to the human cornea have a vital role in replacing corneal tissues. Herein, the desired properties for selecting gel-inks and combination and characterization of inks for 3D printing in CTE are presented in detail.
... polymerization [12]. By contrast, the transparency, biocompatibility and biodegradability of fibrin-based adhesives make them appealing choices for application in the cornea [13]. Fibrin adhesives have been used in various ocular surgeries to treat corneal perforations, ocular surface disorders and glaucoma [10,[14][15][16]. ...
Keratoplasty is the gold standard treatment for visual impairment caused by corneal damage. The use of suturing as the bonding method is the source of many complications following keratoplasty. Currently available corneal adhesives do not have both adequate adhesive strength and acceptable biocompatibility. Herein, we developed a photocurable bioadhesive hydrogel which was composed of gelatin methacryloyl and oxidized dextran for sutureless keratoplasty. The bioadhesive hydrogel exhibited high light transmittance, resistance to enzymatic degradation and excellent biocompatibility. It also had higher adhesive strength than commercial adhesives (fibrin glue). In a rabbit model of lamellar keratoplasty, donor corneal grafts could be closely bonded to the recipient corneal bed and remained attached for 56 days by using of this in situ photopolymerized bioadhesive hydrogel. The operated cornea maintained transparent and noninflamed. Sutureless keratoplasty using bioadhesive hydrogel allowed rapid graft re-epithelialization, typically within 7 days. In vivo confocal microscopic and histological evaluation of the operated cornea did not show any apparent abnormalities in terms of corneal cells and ultrastructure. Thus, this bioadhesive hydrogel is exhibited to be an appealing alternative to sutures for keratoplasty and other corneal surgeries.
... 130 Scalcione et al reported successful use of fibrin glue in a case of DSAEK. 131 Fredell and Hamill retrospectively analysed 48 cases of DMEK closed with PEG and reported a rebubbling rate of 12.5%. 132 Although limited in number, these studies demonstrate the effectiveness of tissue adhesives in maintaining AC tamponade. ...
Graft detachment is the most common complication of endothelial keratoplasty. With the ongoing advancements in the field of endothelial keratoplasty, our understanding of risk factors of graft detachments and its management has been evolving. Various prevention measures have been described in literature including presoaking the donor graft, anterior chamber tamponade, venting incisions, sutures to prevent dislocation of graft. Management of a detached graft involves secondary interventions such as rebubbling, suturing and regrafts. In this review, we discuss graft detachment in different types of endothelial keratoplasty techniques including Descemet stripping endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty and Descemet’s membrane endothelial keratoplasty; with emphasis on incidence, risk factors, preventive measures and their management.
... В настоящее время фибриновый гель активно используется в клинике для гемостатических целей, закрытия раневой поверхности и в качестве герметика. В ТИ ведутся поиски в области создания фибриновых матриксов в офтальмологии (восстановление склеры [4] и хрусталика [5]), в неврологии (восстановление нервных сплетений и периферических нервов [6]), в травматологии и ортопедии (восстановление хряща [7]), при создании искусственной кожи [8] и т. д. Будучи натуральным физиологическим каркасом, он поддерживает ангиогенез и репарацию тканей [9]. ...
This review looks at the use of fibrin in vascular tissue engineering (VTE). Autologous fibrin is one of the most affordable biopolymers because it can be obtained from peripheral blood by simple techniques. A description and comparative analysis of the methods and approaches for producing fibrin gel is provided. The ability of fibrin to promote cell attachment and migration, survival and angiogenesis, to accumulate growth factors and release them in a controlled manner, are unique and extremely useful in VTE. Fibrin gels can serve as a three-dimensional matrix molded in different sizes and shapes to be applied in a variety of ways, including as a scaffold, coating, or impregnation material. Fibrin’s high porosity and biodegradability allows controllable release of growth factors, yet fibrinolysis must be tightly regulated to avoid side effects. We discuss the main methods of regulating the rate of fibrinolysis, as well as possible side effects of such exposure. Low mechanical strength is the main limitation in using fibrin as a scaffold for vascular tissue engineering. Possible options for increasing the strength properties of fibrin matrix and evaluating their effectiveness are presented. We propose that unique biocompatibility and ideal biodegradation profile of fibrin justify its use as a scaffold material for developing an ideal fully autologous small-diameter tissue-engineered vascular graft.
... When applied to a corneal perforation, this hemostatic plug forms an effective sealant, and when used for defects up to 2 mm is as effective as cyanoacrylate. [30,31] However, for defects between 2-3 mm, cyanoacrylate appears to be superior. [32] Due to its role in the coagulation pathway, fibrin plays an integral role in wound healing. ...
Corneal perforation is a potentially devastating complication that can result from numerous conditions that precipitate corneal melting. It is associated with significant morbidity and prompt intervention is necessary to prevent further complications. Causes include microbial keratitis, ocular surface disease, and autoimmune disorders and trauma. Various management options have been described in the literature to facilitate visual rehabilitation. This rview discusses the treatment options that range from temporising measures such as corneal gluing through to corneal transplantation, with decision making guided by the location, size, and underlying aetiology of the perforation.
... [132][133][134] These were also applied for effective healing of neurological surgical sites, corneal or conjunctival wound leaks. 135,136 Similarly, albumin/glutaraldehyde adhesives are also approved for use in wound healing. [137][138][139][140] Other types of adhesives are also effectively used for wound healing. ...
Bioadhesives and glues are widely used as an adjunct to conventional methods employed in healing the post‐surgical injuries and restoration of normal tissue functions. Protein‐based bioadhesives have been used for a long time, and they are a more biocompatible alternative compared with synthetic adhesives. They offer advantages such as ease of application, reduction in surgery time, improved quality and strength of the seal, and effective sealing. Also, bioadhesives are being exploited in different fields like controlled and site‐specific drug delivery systems, and in tissue engineering and regeneration. There are various marketed protein‐based glues that are available in different forms. Thus, all in all, it is a patient compliant system, thereby increasing its recent popularity. This article provides insight into different types and sources of protein‐based bioadhesives, their history of use, mechanism of adhesion. and various products that have been approved by the regulatory authorities for clinical use. It also includes information regarding the products in clinical trials and potential applications.
Corneal diseases are the fourth reason for blindness around the world which can be treated with corneal transplantation as a gold standard approach. However, alternative strategies get more valuable to peruse due to the challenges of donor shortage and failing the corneal transplantation procedure. This study aims to find the trend of biological products introduced to the market for corneal regeneration.
Biological products introduced by different companies were evaluated in this review. The available and underevaluation products introduced to market are reported in this review. This search was done by keywords related to corneal/product, corneal/biological scaffold, corneal/biological product, corneal/allograft, corneal/xenograft, eye drops, biological eye drops, and amniotic membrane/cornea.
Decellularized products of xenogeneic or allogeneic cornea and amniotic membrane matrixes were mostly employed as corneal scaffold. In addition, biological eye drops, gels, and (platelet-rich plasma) PRP are used in several reports as bioactive ingredients.
Herein, the most important issue about biological products that researchers are involved in is preserving the most active ingredients after decellularization or extraction process with minimum modification along with reasonable final cost.
Although at first glance cornea appears as simple avascular collagenous tissue, corneal diseases are the fourth leading cause of blindness according to the WHO reports. Currently, corneal transplantation has been chosen as a gold standard treatment. In recent years, the rising growth of smart biomaterials can be considered as a turning point in modern medicine by using smart scaffolds, a hydrogel with self-healing properties that could be potentially loaded with a drug, autologous cells, or stem cells. Here, we review available and under evaluation products introduced to the market to some extent overcome the cornea transplantation side effects.
Ocular injuries and their complications represent the most common causes of visual impairment. For ocular surgery, there is an unmet need for highly transparent bioadhesives with superior adhesion, biocompatibility, and regenerative properties. Herein, a novel high‐transparent bioadhesive hydrogel composed of gelatin methacryloyl (GelMA) and dopamine methacrylamide (DMA) is developed by in situ oxidative free‐radical polymerization. This bioadhesive hydrogel overcomes the fundamental weakness of mussel‐inspired adhesive copolymers in clinical practice by combining multiple favorable properties, including high light transmission, mechanical strength, adhesive strength, and biocompatibility. DMA significantly enhances corneal epithelial cells adhesion, proliferation, and migration on GelMA, and prevents the accumulation of reactive oxygen species (ROS) in corneal epithelial cells. In rabbit models of corneal and conjunctiva transplantation, the bioadhesive is able to decrease the inflammatory response and fibrosis formation induced by suture surgical trauma. In addition, the rabbit corneal stromal defect model reveals that the Gel/DMA bioadhesive could effectively seal corneal defects, accelerates corneal re‐epithelialization, and promotes wound healing. Thus, given the advantages of high bioactivity and simple preparation, the Gel/DMA bioadhesive represents a promising strategy for suture‐free ocular repair.
Severe corneal injury can lead to a decrease in light transmission and even blindness. Currently, corneal transplantation has been applied as the primary treatment for corneal blindness; however, the worldwide shortage of suitable corneal donor tissue means that a large proportion of patients have no access to corneal transplants. This situation has contributed to the rapid development of various corneal substitutes. The development and optimization of novel hydrogels that aim to replace partial or full-thickness pathological corneas have advanced in the last decade. Meanwhile, with the help of 3D bioprinting technology, hydrogel materials can be molded to a refined and controllable shape, attracting many scientists to the field of corneal reconstruction research. Although hydrogels are not yet available as a substitute for traditional clinical methods of corneal diseases, their rapid development makes us confident that they will be in the near future. We summarize the application of hydrogel materials for various types of corneal injuries frequently encountered in clinical practice, especially focusing on animal experiments and preclinical studies. Finally, we discuss the development and achievements of 3D bioprinting in the treatment of corneal injury.
Cornea as the outermost layer of the eye is at risk of various genetic and environmental diseases that can damage the cornea and impair vision. Corneal trans-plantation is among the most applicable surgical procedures for repairing the defected tissue. However, the scarcity of healthy tissue donations as well as transplantation failure has remained as the biggest challenges in confront of corneal grafting. Therefore, alternative approaches based on stem-cell transplantation and classic regenerative medicine have been developed for corneal regeneration. In this review, the application and limitation of the recently-used advanced approaches for regeneration of cornea are discussed. Additionally, other emerging powerful techniques such as 5D printing as a new branch of scaffold-based technologies for construction of tissues other than the cornea are highlighted and suggested as alternatives for corneal reconstruction. The introduced novel techniques may have great potential for clinical applications in corneal repair including disease modeling, 3D pattern scheming, and personalized medicine. K E Y W O R D S
Corneal perforations are emergencies that require prompt diagnosis and treatment. Perforations may be traumatic or non-traumatic; non-traumatic perforations may be further subdivided into infectious and non-infectious causes. A thorough clinical history, physical examination, and workup should be performed to determine the cause of the perforation. Management should be directed at both treating the underlying cause as well as sealing the full-thickness corneal defect quickly. Depending on the characteristics of the perforation, treatment may involve just aqueous suppressants and a bandage contact lens, or prompt surgical intervention with glue, amniotic membranes, and/or keratoplasty.
The increasing demands for the management of hemostasis and tissue sealing drive the development of novel bioadhesives, which can overcome the disadvantages of conventional sutures such as additional tissue damage, increased infection probability, and body fluid/air leakage. Bioadhesives can form a protective layer with seamless adhesion between the injured tissues, thereby quickly closing the wound and creating appropriate microenvironments for wound healing. In this review, the recent advancement in bioadhesives made of natural macromolecules (polysaccharides and proteins, etc.) and synthetic macromolecules (cyanoacrylate, polyethylene glycol, polyurethane, etc.) have been summarized. The gelation and adhesion mechanisms that determine the bioadhesive properties and sealing functions are highlighted, and the current clinical applications of bioadhesives are also discussed. Based on these findings, a brief outlook on the future of bioadhesive is explored.
The successful management of infectious keratitis is usually achieved with a combination of tools for accurate diagnosis and targeted timely antimicrobial therapy. An armamentarium of surgical interventions is available in the acute stage which can be resorted to in a step wise manner or in combination guided by the response to treatment. Simple surgical modalities can facilitate accurate diagnosis e.g. corneal biopsy and alcohol delamination. Surgery to promote epithelial healing can vary from tarsorrhaphy, amniotic membrane transplantation or conjunctival flaps depending on the extent of infection, visual prognosis, availability of tissue and surgeon's experience. Collagen crosslinking has been increasingly utilized with successful results to strengthen the cornea and reduce the infective load consequently the need for further elaborate surgical interventions. It has shown encouraging results specially in superficial bacterial and fungal keratitis but for deeper infections, viral and acanthamoeba keratitis, its use remains questionable. When globe integrity is compromised, corneal gluing is the most commonly used procedure to seal small perforations. In larger perforations/fulminant infections a tectonic/therapeutic graft is advisable. Partial thickness grafts are increasingly popular to treat superficial infection or internally tamponade perforations. Peripheral therapeutic grafts face challenges with potential requirement for a manually fashioned graft, and increased risk of rejection due to proximity to the limbal vessels. Late stage visual rehabilitation is likely to require further surgical interventions after complete resolution of infection and inflammation. A preliminary assessment of corneal sensation and integrity of the ocular surface are key for any successful surgical intervention to restore vision.
Three-dimensional (3D) bioprinting, consisting of computer-controlled deposition of scaffolds and cells into designed patterns, is an innovative and promising biofabrication strategy for creating artificial tissues and organs. Bioprinted skin has the potential for clinical transplantation, drug testing, cosmetic assaying as well as fundamental researches. Remarkable advancements have been done over the past decades in the improvement of engineered substitutes that mimic skin by applying the advances in polymer engineering, bioengineering, and nanomedicine. Prior to the printing stage, the pre-design of the process, selection of cell, and biofunctional inks are significant steps for the successful fabrication of 3D bioprinted skin constructs. It is crucial to seek and decide on an appropriate source of biofunctional ink capable of stimulating and supporting printed cells for tissue development. Based on this perspective, this chapter deals with the skin and wound structure, skin tissue engineering, the performance and properties of a broad range of biofunctional inks available for 3D bioprinting technologies to produce skin structures. Besides, the current challenges and advances in designing and developing biofunctional inks with desired properties are overviewed.
Corneal blindness is one of the most common causes of vision loss worldwide, affecting millions of people. To treat these patients, researchers have been examining different approaches to engineer corneal scaffolds suitable for transplantation. Scaffolds have been developed to replace part or all of the cornea depending on the patient requirements. Both acellular and cell‐seeded scaffolds have been tested in animal models. Materials that have been under investigation for manufacturing scaffolds include collagen, silk fibroin, amniotic membrane, decellularized cornea, fibrin, chitosan, gelatin, agarose, alginate, and hyaluronic acid in addition to several synthetic polymers. Different combinations of materials, fiber crosslinking techniques, and incorporation of bioactive molecules have also been examined. Factors such as the physical properties, cytocompatibility, degradation behavior, and optical characteristics have to be considered when selecting a suitable scaffold material. Recent advancements in materials fabrication techniques such as bioprinting, electrospinning, and different collagen alignment techniques, allow scaffolds to be generated that more accurately mimic the structure of the corneal stroma. A number of scaffolds have commenced clinical trials to determine their suitability for corneal regeneration. This review examines different design parameters, biomaterials, and fabrication processes used to develop scaffolds for corneal tissue engineering. Different state‐of‐the‐art approaches for generating scaffolds to replace the different layers of the cornea are discussed, and the advantages and limitations of different biomaterials and manufacturing techniques are highlighted.
Ocular hypotony is an infrequent, yet potentially vision-threatening, entity. The list of differential causes is extensive, involving any condition that may compromise aqueous humor dynamics or the integrity of the globe and sometimes following medical treatments or procedures. Depending on the cause and the clinical impact, treatment options aim to correct the underlying pathology and to reestablish anatomical integrity, as well as visual function. We review the pathophysiology, clinical presentation, different causes, and associated therapeutic options of ocular hypotony.
Introduction
Pterygium is a non-cancerous growth of the conjunctival tissue over the cornea that may lead to visual impairment in advanced stages, restriction of ocular motility, chronic inflammation and cosmetic concerns. Surgical removal is the treatment of choice, but recurrence of pterygium is a frequent problem. It has been previously shown that fibrin glue may result in less recurrence and may take less time than sutures for fixing the conjunctival graft in place during pterygium surgery. However, fibrin glue is a biological material and it carries the risk of transmitting infectious agents from pooled and single-donor blood donors and anaphylaxis in susceptible individuals. Cauterisation is another surgical option, and it would be advantageous to know whether cauterisation may be superior surgical option compared with fibrin glue. This protocol describes the rationale and design of the randomised controlled trial (RCT) in which we will compare cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery.
Methods and analyses
This will be a parallel group RCT comparing cauterisation versus fibrin glue for conjunctival autografting in primary pterygium surgery. Computer-generated randomisation will be used, and allocation concealment will be conducted using sequentially numbered opaque sealed envelopes. Surgeons will not be blinded to the procedures, but participants, other investigators and outcome assessors will be blinded. Adult participants with primary pterygium operated in a tertiary hospital in Split, Croatia, will be included. Primary outcome will be recurrence of pterygium, defined as any regrowth of tissue from the area of excision across the limbus onto the cornea after 180 days.
Ethics and dissemination
The trial was approved by the ethics review board of the University Hospital Split (500-03/17-01/68). Results will be disseminated at conferences and through peer-reviewed publications.
Trial registration number
NCT03321201; Pre-results.
Tube exposure is a known complication of Ahmed glaucoma valve (AGV) implantation. Repair of the exposed tube is not easy. A 42-year-old monocular aphakic male had undergone retinal detachment repair with placement of an episcleral-encircling band followed by implantation of AGV. He presented to the clinic on routine review with exposure of the shunt tube. The complication was managed by placing scleral and conjunctival grafts over the exposed tube using a fibrin adhesive (Tisseel kit; Baxter AG, Vienna, Austria). The novel use of the fibrin sealant in the repair of AGV tube exposure was for better graft-integration.
To evaluate the outcomes and safety of lamellar keratoplasty (LK) assisted by fibrin glue in corneal perforations.
Six eyes of 6 patients affected by different corneal pathologies (2 posttraumatic corneal scar and 3 bacterial keratitis) underwent LK procedures by using fibrin glue. The mean corneal perforation diameter was 1.35±0.64mm (range, 0.7-2.5mm), and the greatest diameter of the ulcerative stromal defect was 2.47±0.77mm in average (range, 1.5-3.5mm). The donor corneal lamella diameters were 0.20-mm larger and thicker than the recipient to restore a physiologic corneal thickness and shape: mean donor diameter was 8.34±0.28mm (range, 8.2-8.7mm) and mean thickness was 352±40.27mm (range, 220-400mm). Mean follow-up was 7.33±1.97 months (range, 6-11 months). Postoperatively, the graft status, graft clarity, anterior chamber response, the visual prognosis, intraocular pressures, and postoperative complications were recorded.
All the corneal perforations were successfully healed after the procedure. The best-corrected visual acuity (BCVA) ranged from 20/1 000 to 20/50 in their initial presentation, and from 20/100 to 20/20 in their last visit, showed increase in all the patients. No major complications such as graft dislocation and graft failure were noted. Neovascularization developed in the superficial stroma of donor graft in 1 case. High intraocular pressure developed on day 2 after surgery, while was remained in normal range after application of anti-glaucomatous eyedrops for 1 week in 1 case.
Fibrin glue-assisted sutureless LK is valuable for maintaining the ocular integrity in the treatment of corneal perforations.
Fibrin glue consists of two main components: fibrinogen and thrombin. Aprotinin is added to fibrin glue to delay the fibrinolytic action of plasmin [1,2,3]. We applauded the insightful editorial of I.H.Atrah for his concern about critical surgical emergency conditions where fibrin glue often plays a crucial role.Here we discussed about our concern on anaphylactic potential of aprotinin when used as additive to fibrin glue. Aprotinin is an antifibrinolytic agent commonly used in fibrin glue. It acts by inhibiting kallikrein and trypsin [4] while preserving platelet function. It helps in hemostasis and therefore, very often used during major surgical interventions to reduce the total quantity of blood transfusion required otherwise.
During trabeculectomy, tight suturing of the scleral flap to avoid overfiltration may pose a risk of increased intraocular pressure (IOP) and a flat non-functioning bleb. Furthermore, the nylon sutures usually used to reattach the conjunctiva to the limbus may tear out of the conjunctiva and induce an inflammatory reaction. To overcome these problems, investigators have suggested the use of laser suture lysis1 or releasable sutures2 or other types of closure methods, such as staples, tapes and adhesives.3
Quixil (Omrix Biopharmaceuticals, Ramat Gan, Israel) is a human fibrin sealant consisting of two biological components that form a clot within 30 s of placement on the tissue surface. The clot promotes collagen crosslinking and, consequently, wound healing, and is absorbed after a few days. The aim of this study was to determine whether our good preliminary results with Quixil in an animal model could be extrapolated to human eyes.
The study group consisted of five …
PurposeFibrin glue has been used successfully in numerous ophthalmic surgical procedures. Recently, fibrin glue has been used in limbal stem cell transplantation to reduce both operative time and to negate the need for sutures. The aim of this study was to determine the effects of fibrin glue on epithelial cell migration in vitro.Methods
Corneoscleral rims were split to retain the epithelial layer, Bowman's layer, and anterior stroma. Rims were cut into eight equal-sized pieces and were placed directly on culture plates or affixed with fibrin glue. Rims were maintained in culture for 25 days and epithelial cell growth was monitored. Cells were photographed to measure area or growth and immunofluorescence staining of explants for fibrin was performed.ResultsExplants that were glued demonstrated significantly delayed epithelial cell growth and migration as compared with explants without glue. By day 16, all fibrin glue had dissolved and coincided with onset of cell growth from glued explants. Cell growth commenced between days 3 and 4 for control explants without glue and around days 14-16 for explants with fibrin glue.Conclusions
Fibrin glue delays epithelial cell migration by acting as a physical barrier and can potentially interfere with explant-derived limbal epithelial cell migration on to the corneal surface. We propose that glue should be used to attach the conjunctival frill of the limbal explant but care should be taken to ensure that the glue does not wrap around the explant if used to secure the explant as well. Strategic use of glue, to attach the recessed conjunctiva, can be advantageous in delaying conjunctival cell migration and reducing the need for sequential sector conjunctival epitheliectomy.Eye advance online publication, 1 July 2016; doi:10.1038/eye.2016.127.
Background
Careful surgical management of traumatic wounds is important in open globe injury repair. This study examines the clinical outcomes following repair of open globe injuries with particular focus on wound-related issues.DesignRetrospective, cohort study of consecutive open globe injuries presenting to a tertiary referral eye hospital from 1 January 2009 to 31 December 2011.Participants267 eyes of 263 patients, mainly male (82.5%) with a mean age of 44.8 (range:4–97) years. Average follow up was 6.9 months.Methods
All cases classified according to Ocular Trauma Classification Group.Main Outcome MeasuresVisual outcomes, risk factors for, and rates of post-operative complications and endophthalmitis.ResultsThere were 83 globe ruptures, 182 penetrating and 2 perforating eye injuries, of which 43 cases had intraocular foreign body. Factors contributing to final VA <6/60 were poor presenting VA (Odds Ratio [OR]=16.0,95%CI:4.81–53.1), globe rupture (OR=4.64,[1.99–10.8]), retinal detachment (OR=3.40,[1.19–9.74]) and age ≥50 (OR=2.45,[1.05–5.74]). Wound leak occurred in 44 eyes (16%). Of these, 18 (41%) proceeded to re-suturing. Factors contributing to wound leak were stellate-shaped wound (OR=3.28,[1.39–7.73]) and delayed presentation (OR=2.80,[1.02–7.71]). Ten eyes (3.7%) developed endophthalmitis. Factors associated with endophthalmitis were delayed presentation (OR=8.91,[1.71–46.6]), microbial keratitis (OR=12.5,[1.85–85.0]) and lens capsule breach (OR=12.4,[1.85–83.1]).Conclusions
Wound leak is an important post-operative complication of open globe injury repair. Delayed presentation is an important risk factor for post-operative wound leak and endophthalmitis. Prompt and meticulous wound management of open globe injury may reduce these complications.
A 61-year-old woman presented with a paracentral buttonhole flap defect associated with a linear tear, extensive epithelial ingrowth, and macrostriae in the right eye. A laser in situ keratomileusis enhancement had been performed 3 weeks earlier. The epithelial ingrowth was removed after careful lifting of the flap, and tissue adhesive was used postoperatively as a barrier to further ingrowth. Six months postoperatively, the patient's corrected distance visual acuity had improved to 20/20 and the slitlamp examination showed no evidence of recurrent epithelial ingrowth. This case presents a novel approach to the management of a buttonhole defect.
Financial Disclosure
Neither author has a financial or proprietary interest in any material or method mentioned.
Purpose: To assess the safety and efficacy of a fibrin tissue adhesive (Tissucol Duo®) used to close the conjunctiva in trabeculectomy.
Methods: A nonrandomized prospective study including 57 patients with chronic simple glaucoma who underwent trabeculectomy surgery. All the trabeculectomies were conducted by the same surgeon using the same surgical technique with the exception that conjunctival closure was achieved by either running Nylon 10/0 suture (n = 29) or using the fibrin glue (n = 28). Preoperative and postoperative data were obtained on intraocular pressure (IOP), number of hypotensive medications used, self-reported discomfort and complications arising during and after surgery.
Results: No differences were detected between the two patient groups regarding the intraocular pressure reduction achieved during follow-up. In the first 2 weeks of follow-up, reported discomfort assessed using a visual analogue scale was significantly lower in the Tissucol Duo® group. Two patients in the Tissucol Duo® group suffered conjunctival dehiscence and suturing was required at 24 hours postsurgery. Remaining complications were similar in the two groups.
Conclusion: The use of Tissucol Duo® seems to be a safe and efficient option for conjunctival closure in trabeculectomy that simplifies the surgical procedure and reduces patient discomfort in the immediate postoperative period.
To report a technique of intracameral injection of Tisseel fibrin sealant as an adjunct in the performance of tectonic deep anterior lamellar keratoplasty in cases with preexisting or intraoperative macroperforation.
Patients with corneal perforations up to 4 mm in greatest dimension first had the defect sealed externally with cyanoacrylate adhesive or fibrin sealant. An air bubble was injected into the anterior chamber (AC), followed by intracameral Tisseel fibrin sealant. This was injected via a 21-G cannula or needle, introduced into the AC from the limbus, with the tip positioned just under the perforation. Fibrin sealant was injected to completely cover the perforation site. Deep anterior lamellar keratoplasty then proceeded with a manual technique without chamber loss. Postoperatively, slit-lamp examination to assess resolution of fibrin sealant and graft status was performed, and visual acuities and intraocular pressures were recorded.
Two patients with preexisting corneal perforations and 1 patient with an intraoperative perforation were included. In all patients, lamellar dissection proceeded uneventfully after intracameral fibrin injection. Fibrin sealant in the AC spontaneously resorbed by the second postoperative week. There were no postoperative intraocular pressure spikes and no cases of severe anterior uveitis. All grafts were clear at last follow-up with no evidence of endothelial decompensation.
Intracameral fibrin sealant injection seems to be a safe adjunct to allow completion of deep anterior lamellar keratoplasty in cases with corneal perforation with the aim of avoiding higher risk penetrating keratoplasty. Cases were characterized by a lack of complications postoperatively, and no cases of persistent double AC were encountered.
To treat chronic hypotony with decreased vision after filtration surgery.
After observation from 3 1/2 to 13 months with no spontaneous improvement, eyes were treated with the experimental therapy and followed up closely to determine the results.
Four eyes with chronic hypotony, selected from a series of 125 eyes receiving trabeculectomy augmented by intraoperative mitomycin. All eyes had posterior chamber pseudophakia. All eyes had postoperative laser cutting of sutures holding the scleral flap of the trabeculectomy.
After administration of topical prophylactic 0.3% ciprofloxacin hydrochloride and topical anesthetic, the bleb was inflated with whole autologous blood through a 27-gauge needle passed subconjunctivally into the bleb.
Change in intraocular pressure, change in vision, change in choroidal detachment, any type of complication.
Average intraocular pressure increased from 5.5 to 8.2 mm Hg. Average vision improved from 20/148 to 20/33. In two eyes with choroidal detachment, the detachment absorbed in one eye and decreased in the other. No complications occurred.
Intrableb injection of autologous blood deserves further study as a possible treatment for hypotony following filtration.
A minireview: aprotinin in fibrin glue-a major concern!
- J Pramanik
- T Pramanik
- L Juntang
- G Zhikun
Pramanik J, Pramanik T, Juntang L, Zhikun G. A minireview: aprotinin in fibrin glue-a major concern!. BMJ 1994;
308: 933.