Amniotic membrane, clinical applications and tissue engineering. Review of its ophthalmic use | Archivos de la Sociedad Española de Oftalmología (English Edition)

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Revisión de su uso oftalmológico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 639 "Ancho" => 855 "Tamanyo" => 51954 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Amniotic membrane stained with Masson's trichrome." ] ] ] "textoCompleto" => "Historical introductionAmniotic membrane (AM) transplant was first described in 1910, by Davis(AM)<a class="elsevierStyleCrossRef" href="#bib0005">1</a> for skin diseases. Its use was extended to other specialties like traumatology, plastic surgery, sports medicine, neurology, gynaecology, odontology.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> In 1940. AM was utilized for the first time in ophthalmology by De Rotth<a class="elsevierStyleCrossRef" href="#bib0015">3</a> for reconstructing a conjunctival surface after unsuccessful treatment of symblepharon on the basis of similar characteristics between the conjunctiva, the AM, (transparency, thickness, consistency).<a class="elsevierStyleCrossRef" href="#bib0020">4</a> In 1946. Sorsby utilized AM for covering chemical ocular abrasions but, despite positive results, the technique was forgotten. Said author was the first to state that AM had excellent mechanical as well as biological properties. Almost 50 years later, Batlle and Perdomo<a class="elsevierStyleCrossRef" href="#bib0025">5</a> used AM in conjunctival defects and Kim and Tseng for treating ocular surface pathologies, both in 1992.<a class="elsevierStyleCrossRefs" href="#bib0020">4,6–9</a>Materials and methodsA review of papers was carried out after searching the terms «amniotic membrane» and «eye» in Pubmed in the past 5years. Said search initially included «review» and was later expanded to include some articles of the References cited in the selected papers.Amniotic membrane characteristicsAM is derived from the innermost layer of the foetal membrane. Its thickness ranges between 0.2 and 0.5mm.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a> Several authors have demonstrated that AM thickness in humans varies between individuals.<a class="elsevierStyleCrossRefs" href="#bib0050">10–12</a> It consists in an epithelial layer, a thick basal membrane and an avascular stroma (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0065">13,14</a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Epithelial layer. A monolayer of cuboidal cells with microvilli on the apical surface<a class="elsevierStyleCrossRef" href="#bib0075">15</a> that are in direct contact with amniotic fluids. The AM is anchored to the basal membrane through hemidesmosomes.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Said cells secrete numerous substances that are vital for the function of AM.</li><li class="elsevierStyleListItem" id="lsti0010">•Basal membrane. This membrane consists in connective tissue linked by means of collagen bundles that maintain the mechanical stability of the membrane</li><li class="elsevierStyleListItem" id="lsti0015">•Avascular stroma. The thickest layer of fibroblasts adjacent to the chorion.<a class="elsevierStyleCrossRefs" href="#bib0030">6,12</a> This layer is divided in 3, i.e., the compact layer (in contact with the basal membrane, providing resistance to traction), the fibroblast layer (comprising of fibroblasts and Hofbauer cells) and the sponge-like layer (the outermost layer).<a class="elsevierStyleCrossRefs" href="#bib0070">14,15</a></li></ul><elsevierMultimedia ident="fig0005"></elsevierMultimedia>Said tissue comprises a number of characteristics that make it very useful for treating ocular pathologies and for tissue engineering.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Said characteristics are:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">-promoting tissue proliferation through epidermic growth factors (EGF), keratinocytic growth factors (KGF) and basic fibroblast growth factors (BFGF).</li><li class="elsevierStyleListItem" id="lsti0025">-Facilitating cell migration through lumican, a specific glycoprotein, and hyaluronic acid which also has anti-inflammatory and immunosuppressant effects<a class="elsevierStyleCrossRefs" href="#bib0060">12,17</a>).</li><li class="elsevierStyleListItem" id="lsti0030">-Promoting specific migration of keratinocytes through the serine protease inhibitor (serpin 1) and dipeptidyl peptidase IV (DPP-IV).</li><li class="elsevierStyleListItem" id="lsti0035">-Inhibiting cicatrization by suppressing the tumor growth factor Beta (TGF-β).</li><li class="elsevierStyleListItem" id="lsti0040">-Downwardly regulating the expression of cell surface markers such as CD80, CD86 and class 2 histocompatibility antigen (immune response modulators).</li><li class="elsevierStyleListItem" id="lsti0045">-inhibiting inflammation and neovascularization due to the secretion of metalloproteinase tissue inhibitors (TIMP) and cytokins (interleukin-10, anti-inflammatory interleukin and interleukin-1 receptor antagonists).</li><li class="elsevierStyleListItem" id="lsti0050">-It hardly exhibits any immunogenicity because it does not express human leukocyte antigens (HLA) A, B, C, D and DR, although it does express HLA-G (involved in the induction of immune tolerance by acting as macrophage ligand and natural killer) and Fas ligand<a class="elsevierStyleCrossRefs" href="#bib0010">2,7,8,12</a>,<a class="elsevierStyleCrossRefs" href="#bib0080">16–21</a> (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0055">-It exhibits a tectonic effect (acting as a scaffolding in structural defects).</li><li class="elsevierStyleListItem" id="lsti0060">-It also exhibits antimicrobial properties (it can also act as antimicrobial barrier).</li><li class="elsevierStyleListItem" id="lsti0065">-It functions as an in vitro and in vivo cell culture medium<a class="elsevierStyleCrossRefs" href="#bib0110">22,23</a> and for this reason could have high potential in tissue engineering.</li></ul>The sum of the above mechanisms is what enables adequate cicatrization and regeneration of wounds.Resch et al.<a class="elsevierStyleCrossRefs" href="#bib0120">24,25</a> observed that AM can integrate with corneal tissue in 4 different manners, i.e., intra-epithelial, sub-epithelial, intrastromal integration and over the corneal surface. Said authors carried out AM transplants in patients who subsequently required keratoplasty, thus enabling in-depth histological analysis. Integration according to one pattern or another depended on the surgical technique as well as on the ocular disease being treated. This raises the possibility that the knowledge of these integration patterns could help us to select the most adequate technique for the pathology to be treated.Types of amniotic membrane according to the preparation processAM is obtained from placenta donated by seronegative females who underwent elective C-section. Donor serology must exclude hepatitis B virus (HBV) andC(HCV), human immunodeficiency virus (HIV), toxoplasma and syphilis during pregnancy. Serology is repeated 3−6months after labor to discard any infection that could have been in the window period during the initial screening.<a class="elsevierStyleCrossRef" href="#bib0100">20</a>Several methods are utilized to preserve amniotic membrane, i.e. the wet method (hypothermic storage), the dried method (lyophilized) and cryopreservation.<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0070">•Fresh AM is separated from the placenta under sterile conditions and irrigated with sterile saline solution.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> It is kept in a saline solution with 50,000UI of penicillin and 1g of streptomycin for every 400ml of saline solution at 4°C.<a class="elsevierStyleCrossRefs" href="#bib0100">20,27</a> In the authors’ country it is not generally utilized due to the risk of disease transmission in the window period (HBV, HIV, etc.) and due to its low availability (it must be utilized within a timeframe).<a class="elsevierStyleCrossRef" href="#bib0140">28</a> However, AM is widely applied in developing countries in which preservation techniques are not fully implemented.<a class="elsevierStyleCrossRef" href="#bib0095">19</a></li><li class="elsevierStyleListItem" id="lsti0075">•Dried or lyophilized AM is dried under vacuum at low temperature and rehydrated prior to use. One of the advantages of lyophilization compared to cryopreservation is the possibility of storing it at room temperature. This characteristic facilitates transport as well as use in developing countries and military campaigns. In addition, dried AM is irradiated to ensure sterilization.<a class="elsevierStyleCrossRefs" href="#bib0035">7,19,20,29</a> However, dried AM exhibits lower concentration of proteins/growth factors.<a class="elsevierStyleCrossRefs" href="#bib0150">30,31</a></li><li class="elsevierStyleListItem" id="lsti0080">•Cryopreservation. This is the original method described by Kim and Tseng,<a class="elsevierStyleCrossRef" href="#bib0045">9</a> consisting in washing the membrane under a laminar flow bell and subsequently separating the amnion from the chorion. The stromal (adhesive) part of the amnion is placed on nitrocellulose paper<a class="elsevierStyleCrossRef" href="#bib0075">15</a> and subsequently washed with tamponating saline solution containing 1000U/ml of penicillin, 20mg/ml streptomycin and 2.5mg/ml amphotericinB. finally, it is stored in 100 % glycerin at 4°C. These fragments are kept in a cryoprotective substance at −80°C which enables its use up to 5years later (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). At present, said method has been modified by Lee et al.<a class="elsevierStyleCrossRefs" href="#bib0100">20,32</a> One of the disadvantages of this process is that some properties could be lost. Even so, at present it is the method of choice for processing AM in developed countries.<a class="elsevierStyleCrossRefs" href="#bib0035">7,19,20,29</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li></ul>In recent years, a medical device has appeared in the market under the trademark Prokera® (Bio-Tissue, Inc., Miami, FL, USA) that enables the utilization of AM without sutures. This has several advantages including lower inflammation, shorter surgical times and less checkup visits for removing sutures. Said device is a ring with a diameter of 15mm for pediatric patients or 16mm for adults that contains cryopreserved AM and can be easily placed with topical anesthesia. It functions as a “biological compressive bandage” with the epithelial side over the defect and is eliminated in approximately 3 days. This device is useful to prevent the formation of symblepharon in severe cases.<a class="elsevierStyleCrossRefs" href="#bib0100">20,33–35</a> Another device with a similar design is AmnioClip®<a class="elsevierStyleCrossRef" href="#bib0180">36</a> (KET Kunststoff- und Elasttechnik GmbH, Liegau-Augustusbad, Germany), comprising AM between 2 rings that can be placed as a large contact lens (similar to Prokera®).Surgical technique. Graft or patchThe surgical technique is important when using AM because, depending on the ocular pathology, it can be applied as a graft (inlay) or a patch (onlay).<a class="elsevierStyleCrossRefs" href="#bib0035">7,8,14,31</a> During the intra-surgery management of AM the surgeon is able to discern the epithelial from the stromal layer because the latter is adhesive but the former is not.When used as a graft, AM acts as an basal membrane for the development of corneal epithelium and becomes part of the treated cornea or conjunctiva. The stromal (adhesive) of AM is placed over the ocular defect without extending beyond its edges. Prior to placing the graft, necrotic remains must be debridled (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<a class="elsevierStyleCrossRefs" href="#bib0035">7,8,14</a> In this way, the adhesive surface will integrate with the defect and the perilesional epithelium will grow over the AM. The fixation of AM can be done with sutures as well as with glue (after drying the area). In order to avoid graft detachments, a therapeutic contact lens can be used or lateral tarsorraphy can be carried out. According to the etiology and the severity of the lesion, AM can be used as a single or multiple layer.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>The above technique comprises the following variations:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0085">•A lamellar sac can be made surrounding the defect using a «crescent» blade<a class="elsevierStyleCrossRef" href="#bib0185">37</a> in which the AM can be inserted.</li><li class="elsevierStyleListItem" id="lsti0090">•The «Filling technique», useful for repairing the deep ulcers. It consists in the introduction of several layers of AM cut with a punch to fill in the defect and subsequently place an upper AM with the epithelial edge facing downwards.<a class="elsevierStyleCrossRef" href="#bib0185">37</a></li><li class="elsevierStyleListItem" id="lsti0095">•The «Roll filling technique»,<a class="elsevierStyleCrossRef" href="#bib0190">38</a> in which an AM roll is introduced in the defect (specifically described for perforations) and placing 2 layers of AM with the stromal face over said roll, suturing at the edge of the defect. Perfluoropropane is subsequently introduced in the anterior chamber (AC) to avoid the roll entering the AC, placing thereafter a larger AM over the entire cornea with the stromal surface downwards.</li></ul>Indications for the use of AM as a graft described in the medical literature include epithelial defects with ulcers,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> corneal thinning,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> descematocele and corneal micro-perforations,<a class="elsevierStyleCrossRef" href="#bib0195">39</a> escision of tumors and scars,<a class="elsevierStyleCrossRef" href="#bib0200">40</a> band keratopathy,<a class="elsevierStyleCrossRef" href="#bib0205">41</a> bullous keratopathy<a class="elsevierStyleCrossRef" href="#bib0210">42</a> and limbar stem cell deficit (LSCD).<a class="elsevierStyleCrossRefs" href="#bib0115">23,43</a>The use of AM as a patch consists in the placement of the epithelial, non-adhesive side of AM in contact with the ocular defect, going over its edges (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<a class="elsevierStyleCrossRefs" href="#bib0035">7,14</a> Said side is rich in immunomodulator cytokins and epithelial growth factors and facilitates inflammation reduction, improves cicatrization and operates as a “compressive bandage/protective covering”.<a class="elsevierStyleCrossRefs" href="#bib0020">4,5,15</a> The various indications described for this technique include epithelial defects without ulceration, acute Stevens-Johnson syndrome,<a class="elsevierStyleCrossRefs" href="#bib0220">44–48</a> acute chemical burns<a class="elsevierStyleCrossRef" href="#bib0245">49</a> and high risk of corneal transplant.<a class="elsevierStyleCrossRef" href="#bib0250">50</a><elsevierMultimedia ident="fig0020"></elsevierMultimedia>It must be emphasized that the application of one technique instead of another is not linked to the pathology. In the analyzed references the authors found studies describing the use of AM as a graft for certain pathologies and other studies recommending its use as a patch for the same pathologies. In essence, the indications for AM and the techniques to be applied are not clear.Use of amniotic membrane in ocular pathology. Overview and tissue engineeringThe use of AM is described for multiple ocular pathologies including corneal abrasions,<a class="elsevierStyleCrossRefs" href="#bib0100">20,21,51–54</a> repair of filtrating blebs, trabeculectomy, persistent neurotrophic or herpetic ulcers, descematocele, perforations,<a class="elsevierStyleCrossRef" href="#bib0105">21</a> pterygium, numular keratitis, limbar insufficiencies (including limbar cell culture and subsequent transplant thereof),<a class="elsevierStyleCrossRef" href="#bib0080">16</a> band keratopathy, conjunctival reconstruction, symblepharon, etc.<a class="elsevierStyleCrossRefs" href="#bib0030">6,7,29,33</a> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The main contraindications for AM are severe dry eye, lagophthalmos and severe necrosis caused by ischemia. It is not recommended as an independent treatment for severe gradeIV abrasions (Roper-Hall classification). Despite a certain controversy in this regard, it is highly likely that AM implanted in a patient will not supply live and functional stem cells but a large number of molecules and factors which, added to the biomechanical scaffolding, enable and stimulate the differentiation of local cells. Accordingly, even though AM provides a positive microclimate, in advanced grades AM does not facilitate improvement when used as exclusive treatment.<a class="elsevierStyleCrossRefs" href="#bib0090">18,20</a>In recent years, the increasing influence of tissue engineering has facilitated the appearance of new applications for AM. One is sclerocorneal limbus cell culture that enables less aggressive surgery for treating limbar cell deficit by means of the application of intact or de-epithelized AM. It is yet to be seen which form of AM is the best although some studies<a class="elsevierStyleCrossRef" href="#bib0275">55</a> suggest that the use of intact AM is preferred. However, other studies consider it necessary to carry out more studies before reaching this conclusion.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> in vitro experiments indicate that intact AM culture supports the expansion of cells with a partially non-differentiated limbar phenotype. Culture of de-epithelized AM could induce greater differentiation although this effect would diminish with the addition of 3T3 cells.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>An additional factor that was analyzed was the stability of AM for culture. The use of various cross-linking agents began to be studied in AM as well as the use of different collagen gels, fibrin and fibronectin-fibrin gels for culture, in addition to the utilization of contact lenses.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> The aim of this analysis was to increase the stability of AM grafts in order to avoid postoperative detachments.<a class="elsevierStyleCrossRef" href="#bib0080">16</a>Despite the large number of studies related to AM in ophthalmology, its actual usefulness is not yet clear in our country.Other recent applications of AM or its derivates include AM extract, with properties similar to cryo-preserved AM, and AM extract in drops which can be combined with umbilical cord blood to be used as a variant of the solution derived from AM. Research is also being conducted on the utilization of amniotic fluid, which is a dynamic medium that changes its composition according to the stage of pregnancy as it contains a number of growth factors, electrolytes, proteins, enzymes and hormones that promote cicatrization.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>In what concerns the preparation of AM extract, due to the absence of standardized protocols several methods have been developed that endow different properties to the product. This circumstance, together with a range of problems for the adequate preservation of the extract and its short life cycle, constitute its main disadvantages. It is important to emphasize that the product does not provide the tectonic properties of AM transplants. The main advantage of its use is that, as it is prepared as an eye drop, it can be applied by the patient thus avoiding surgery and to a large extent preventing postoperative infections as well as patient discomfort, in addition to reducing health expenditure.Several in vivo and in vitro studies have demonstrated the beneficial effect of said AM extract product because it allows improved tissue regeneration. However, the authors have not found any study comparing its use compared to blood-derived autologous serum. Therefore it cannot be said that these products are superior, equal or inferior.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Many companies are marketing said products despite the absence of approval by the US Food and Drug Administration (FDA). The best-known products are Regenesol™ by Biotissue/Tissue Tech Inc. (Miami, FL, USA), amniotic cytokins extract Genesis (ACE)™, by Ocular Science Inc. (Manhattan Beach, AC, USA) and Regener-Eyes™ (Palm Beach, FL, USA).The use of said product is recommended for dry eye, chemical burns, corneal ulcers, corneal transplants and after laser-assisted subepithelial keratomileusis [LASEK]).<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Uses of amniotic membrane for specific ocular pathologiesCorneal pathologyRefractory ulcers and ocular perforationsThese pathologies are the main beneficiaries of AM. In most cases, AM is reserved for ulcers that are refractory to even preventive medical treatment in the presence of imminent perforations, preceded by descematocele or otherwise. The mechanical and biological properties of AM enable fast recovery and less fibrosis.AM is applied to ulcers that do not respond to medical treatment. Its usefulness is specially demonstrated in neurotrophic ulcers requiring reinforced treatment, although the application of AM is usually limited to ulcers in advanced stages but it can also be applied in previous stages. Several papers<a class="elsevierStyleCrossRefs" href="#bib0155">31,57,58</a> have demonstrated the efficiency of AM in ulcers resistant to treatment with lubrication, contact lenses or tarsorraphy, with many cases requiring adjuvant treatment. In what concerns infectious ulcers, in addition to the above described effects, AM acts as a reservoir enabling longer duration of antibiotics.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> Recent studies such as Mohan et al.<a class="elsevierStyleCrossRef" href="#bib0300">60</a> reported a success rate of 82.1 % in resistant bacteria and corneal ulcers. Studies based on the surgical specialties demonstrated that AM improved control over bacterian populations.<a class="elsevierStyleCrossRef" href="#bib0305">61</a>In the case of perforations, the definitive treatment is generally keratoplasty.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> The difficulty of finding adequate corneas at short notice requires the assessment of other approaches including AM, the utilization of which has been demonstrated in numerous studies<a class="elsevierStyleCrossRefs" href="#bib0190">38,63,64</a> but not for all cases. Rodríguez-Ares et al.<a class="elsevierStyleCrossRef" href="#bib0320">64</a> described the safe use of AM only in perforations under 1.5cm, in which they found high success rates. However, other papers<a class="elsevierStyleCrossRef" href="#bib0105">21</a> observed that the exclusive use of AM in ocular perforations fails in the majority of cases and recommend the search of co-adjuvant treatments when utilizing AM during surgery. This option is being researched by other authors (corneal patches, umbilical cord patches, equine pericardium, TachoSil®, fibrin glue, intra-chamber fibrin, etc.).<a class="elsevierStyleCrossRefs" href="#bib0325">65–72</a>Bullous keratopathyOngoing friction of nerves produced by edematized corneal stroma and the formation of bullas are the main cause of pain in this pathology. The utilization of AM in these patients provides relief of symptoms although limited to the duration of AM.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Pires et al.<a class="elsevierStyleCrossRef" href="#bib0365">73</a> described that 90 % of patients with bullous keratopathy and intense pain responded positively to treatment and reported relief from pain.<a class="elsevierStyleCrossRef" href="#bib0095">19</a>Chemical corneal abrasionsThe use of AM in acute abrasions is controversial because, despite its beneficial properties, its ability to inhibit vascularization restricts the recovery of limbar cells (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<a class="elsevierStyleCrossRef" href="#bib0370">74</a> Normally its use is reserved for severe acute abrasions, although there is no consensus on this. As discussed earlier, treating this pathology only with AM is not recommended and it is generally applied as adjuvant for other treatments such as tetracycline, artificial tears, vitamin C and therapeutic lenses among others.<a class="elsevierStyleCrossRef" href="#bib0100">20</a> In what concerns symptom relief and re-epithelization time, improvements have been reported. Patients with abrasions of gradeII-III (Roper-Hall classification) exhibit improved visual acuity recovery when compared to those with gradeIV abrasions.<a class="elsevierStyleCrossRef" href="#bib0100">20</a><elsevierMultimedia ident="fig0025"></elsevierMultimedia>An interesting non-surgical alternative is the use of umbilical cord serum, which has demonstrated to be superior in some parameters (longer breakup time and higher post-treatment Schirmer test values),<a class="elsevierStyleCrossRef" href="#bib0245">49</a> although it is not available in the majority of hospitals. Tamhane et al.<a class="elsevierStyleCrossRef" href="#bib0375">75</a> found that AM improves epithelization and pain relief without diminishing the risk of limbar cell deficit or improving visual acuity when compared with a control group. Recent studies<a class="elsevierStyleCrossRef" href="#bib0370">74</a> report that medical treatment in addition to AM transplant versus medical treatment on its own does not improve re-epithelization nor improve visual acuity in severe abrasions.Conjunctival pathologyPterygiumAM is a good alternative to conjunctival autograft (CAG) (gold standard) when the patient underwent numerous previous conjunctival surgeries or when the conjunctiva must be preserved for possible glaucoma surgeries in the future.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> A Cochrane systematic study<a class="elsevierStyleCrossRef" href="#bib0380">76</a> compared the effectiveness and risks of CAG versus AM, finding a relapse percentage of 3.3–16.7 % utilizing CAG compared to 6.4–42.3 % with AM. Said meta-analysis demonstrate that eyes treated with CAG had 47 % lower relapse risk at 6 months compared to those treated with AM. Another meta-analysis by Li et al.<a class="elsevierStyleCrossRef" href="#bib0385">77</a> also supported these results.Symblepharon, toxic epidermal necrolysis, stevens-johnson syndromeThe use of AM in these diseases aims at preventing the formation of symblepharon and avoiding multiple complications associated to toxic epidermal necrolysis (TEN) and to the Stevens-Johnson syndrome (SJS). The application of intense lubrication, aggressive topical corticoids and AM transplant is necessary to prevent the possibility of complications in the future, recommending AM transplant in acute TEN and SJS during the first week<a class="elsevierStyleCrossRefs" href="#bib0235">47,78,79</a>. Hsu et al.<a class="elsevierStyleCrossRef" href="#bib0400">80</a> carried out a case and control study in acute TEN and SJS and observed that the early use of AM avoided severe visual acuity loss in said patients with moderate or severe inflammation.The main signs that should call for the use of AM would be compromise of the free palpebral edge, the formation of pseudo-membranes and membranes, conjunctival and tarsal fornix defects.<a class="elsevierStyleCrossRefs" href="#bib0235">47,78</a> In these diseases, authors do not agree on the use of suture of fibrin to avoid postoperative complications.<a class="elsevierStyleCrossRefs" href="#bib0395">79,81</a>In many cases the main problem for AM transplants is that patients are significantly unstable or in the ICU and are not eligible for surgery. In these situations, as described above several devices can be used including Prokera®, AmnioClip®, etc., that can be placed under topical anesthesia and without a microscope.<a class="elsevierStyleCrossRefs" href="#bib0235">47,78</a> It should be emphasized that the use of these devices is highly recommended for preventing symblepharon, as discussed above.<a class="elsevierStyleCrossRefs" href="#bib0100">20,33–35</a>ConclusionsThis review has described numerous techniques and listed pathologies for which the application of AM is probably beneficial.It can be stated that AM features multiple positive qualities when applied to different pathologies in ophthalmology as well as in other surgical medical specialties. However, the limitations exhibited by some studies and the lack of large case and control series do not allow us to state that the use of AM is better than other biomaterials for all the described pathologies or even that the utilization of a surgical technique can be associated to the treatment of a specific pathology. Nevertheless, it is confirmed that in some diseases such as relapsing pterygium AM is not the first option for treatment and that in other diseases (ulcers and perforations, among others) it produces very positive results as an adjuvant.Notwithstanding the above, the majority of studies to date indicate that AM facilitates regeneration and more satisfactory results. The considerable development of tissue engineering and tissue preservation forecasts very good results in the near future. Accordingly, larger studies should be carried out comparing the use of AM with other biological as well as artificial tissues.Conflict of interestsNo conflict of interests has been declared by the author." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres1285907" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1188491" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1285906" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1188492" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Historical introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Amniotic membrane characteristics" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Types of amniotic membrane according to the preparation process" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Surgical technique. Graft or patch" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Use of amniotic membrane in ocular pathology. Overview and tissue engineering" ] 10 => array:3 [ "identificador" => "sec0035" "titulo" => "Uses of amniotic membrane for specific ocular pathologies" "secciones" => array:2 [ 0 => array:3 [ "identificador" => "sec0040" "titulo" => "Corneal pathology" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Refractory ulcers and ocular perforations" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Bullous keratopathy" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Chemical corneal abrasions" ] ] ] 1 => array:3 [ "identificador" => "sec0060" "titulo" => "Conjunctival pathology" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Pterygium" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Symblepharon, toxic epidermal necrolysis, stevens-johnson syndrome" ] ] ] ] ] 11 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions" ] 12 => array:2 [ "identificador" => "sec0080" "titulo" => "Conflict of interests" ] 13 => array:2 [ "identificador" => "xack441958" "titulo" => "Acknowledgment" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-07-09" "fechaAceptado" => "2019-09-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1188491" "palabras" => array:4 [ 0 => "Amniotic membrane" 1 => "Tissue engineering" 2 => "Cornea" 3 => "Ocular surface" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1188492" "palabras" => array:4 [ 0 => "Membrana amniótica" 1 => "Ingeniería tisular" 2 => "Córnea" 3 => "Superficie ocular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The use of amniotic membrane (AM) in ophthalmology has been increasing in recent years due to its multiple biological and tectonic properties, improvement in the process of obtaining, ease of use, and advancement in tissue engineering. The AM has become one of the main adjuvant treatments, in ophthalmic surgery as well as in other medical-surgical specialties. The development of tissue engineering has allowed it to be used, not only in its classic form, but also by the use of drops and other presentations. The different steps prior to its use (preparation and conservation), the different surgical techniques, and their main clinical applications are described throughout the article." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La utilización de la membrana amniótica (MA) en la oftalmología está en alza en los últimos años debido a sus múltiples propiedades biológicas y tectónicas, la mejora en el proceso de obtención, la facilidad de uso y el avance en la ingeniería tisular. La MA se ha convertido en uno de los principales tratamientos coadyuvantes, tanto en la cirugía oftalmológica como en otras especialidades médico-quirúrgicas. El desarrollo de la ingeniería tisular ha permitido su utilización no solo en su forma clásica sino también mediante gotas y otras presentaciones. A lo largo del articulo hemos realizado un resumen de los distintos pasos previo a su uso (preparación y conservación), las distintas técnicas quirúrgicas y sus principales aplicaciones clínicas." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Lacorzana J. Membrana amniótica, aplicaciones clínicas e ingeniería tisular. Revisión de su uso oftalmológico. Arch Soc Esp Oftalmol. 2020;95:15–23." ] ] "multimedia" => array:7 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 639 "Ancho" => 855 "Tamanyo" => 51954 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Amniotic membrane stained with Masson's trichrome." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 758 "Ancho" => 2508 "Tamanyo" => 196345 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0060" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A)Separation of amniotic membrane in the tissue biological bank. B)Placement on nitrocellulose paper. C)Cryo-preserved amniotic membrane, ready for transport." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 749 "Ancho" => 1525 "Tamanyo" => 52137 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0065" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Amniotic membrane as graft." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 828 "Ancho" => 1541 "Tamanyo" => 56432 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0070" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Amniotic membrane as patch." ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1950 "Ancho" => 2500 "Tamanyo" => 478997 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0075" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "A)Corneal abrasion due to caustic soda. De-epithelization of the central and lower 120° of the cornea. Intense ocular inflammation with amputation of limbar vessels between 4 and 6 o’clock. B)Amniotic membrane cover (graft). C)Placement of therapeutic contact lens on transplant to improve fixation. D,E)Applied graft 4 days later. F,G)Graft after 6 days. Graft rupture can be seen in the upper part although the lower part is adequately covered. H)Graft after 10 days, fully reabsorbed and exhibiting significant improvement. I)Graft after 20 days, showing positive postoperative result with corneal transparency and limbar vascular recovery." ] ] 5 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0080" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Property \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Molecule \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cell proliferation induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">EGFEGF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">KGF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BFGF \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neovascularization reduction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TIMPTIMP \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">XVIII collagen \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">IL 10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-scarring action \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TGF-β suppression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Low or null immunogenicity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No expression of HLA A, B, C, D and DRexpression of HLA G and Fas ligand \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cell migration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LumicanLumican \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hyaluronic acid \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Specific keratinocyte migration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Serpin-1Serpin-1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DPP-IV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corneal regeneration pool \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Collagen type I, III, IV and V \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2202802.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Main amniotic membrane properties." ] ] 6 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0085" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corneal pathology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conjunctival pathology \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-infectious ulcers due to bacteria or virus herpes zoster \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conjunctival reconstruction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Post-trauma ulcers and due to some or all chemical burns \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Conjunctivochalasis<a class="elsevierStyleCrossRef" href="#bib0280">56</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neurotrophic ulcers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Muco-synechial diseases: pemphigoid, Stevens-Johnson \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Descematocele \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Symblepharon \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Corneal perforations \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recurring pterygium and surgeries associated to pterygium \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Band keratopathies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Neoplasias \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Degenerative pathologies, dystrophy, recurring erosions \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scleral pathology \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other indications \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Necrotizing limbitis-scleritis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Filtration bleb defects in glaucomatous surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scleromalacia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Glaucomatous valve covering \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Scleral perforation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Xerosis: primary and secondary Sjögren’s syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Marfan syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prevention of postoperative opacity after photokeratectomy (PRK, PTK, in experimentation) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2202803.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Most frequent uses of amniotic membrane in ocular pathology." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:81 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skin transplantation with a review of 550 cases at the Johns Hopkins hospital" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.W. D" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Johns Hopkins Med J." "fecha" => "1910" "volumen" => "15" "paginaInicial" => "307" "paginaFinal" => "396" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Amniotic membrane extract and eye drops: a review of literature and clinical application" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.S. Murri" 1 => "M. Moshirfar" 2 => "O.C. Birdsong" 3 => "Y. Ronquillo" 4 => "Y. Ding" 5 => "P.C. Hoopes" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Clin Ophthalmol [Internet]" "fecha" => "2018" "volumen" => "12" "paginaInicial" => "1105" "paginaFinal" => "1112" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plastic repair of conjunctival defects with fetal membranes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. De Rotth" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Ophthalmol [Internet]" "fecha" => "1940" "volumen" => "23" "numero" => "3" "paginaInicial" => "522" "paginaFinal" => "525" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human amniotic membrane transplantation: past, present, and future" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "T. 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"fecha" => "1993" "volumen" => "100" "paginaInicial" => "A107" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Usos de la membrana amniótica humana en oftalmología" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Alemañy González" 1 => "F. Camacho Ruaigip" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Cuba Oftalmol." "fecha" => "2006" "volumen" => "19" "numero" => "1" "paginaInicial" => "1" "paginaFinal" => "7" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "La membrana amniótica en oftalmología: del recubrimiento-injerto a la ingeniería tisular. Artículo de revisión. Rev española Investig oftalmológicas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.M. Ortega-molina" 1 => "H.S. Agustin" 2 => "A.D.E. Revisión" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Rev Esp Inv Oftal" "fecha" => "2014" "volumen" => "IV" "numero" => "2" "paginaInicial" => "117" "paginaFinal" => "122" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sabater AL, Perez VL. Amniotic membrane use for management of corneal limbal stem cell deficiency. [cited 2018 Jun 3]; Available from: https://insights.ovid.com/pubmed?pmid=28426442." ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Transplantation of preserved human amniotic membrane for surface reconstruction in severely damaged rabbit corneas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.C. Kim" 1 => "S.C. 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Amniotic membrane, clinical applications and tissue engineering. Review of its ophthalmic use

Membrana amniótica, aplicaciones clínicas e ingeniería tisular. Revisión de su uso oftalmológico

J. Lacorzanaa,b,c

a Departamento de Oftalmología, Hospital Universitario Virgen de las Nieves, Granada, Spain

b Escuela de Doctorado y Posgrado, Universidad de Granada, Granada, Spain

c Master en Ingeniería Tisular, Universidad de Granada, Granada, Spain

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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Amniotic membrane stained with Masson&#39;s trichrome&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Historical introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Amniotic membrane &#40;AM&#41; transplant was first described in 1910&#44; by Davis&#40;AM&#41;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> for skin diseases&#46; Its use was extended to other specialties like traumatology&#44; plastic surgery&#44; sports medicine&#44; neurology&#44; gynaecology&#44; odontology&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> In 1940&#46; AM was utilized for the first time in ophthalmology by De Rotth<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> for reconstructing a conjunctival surface after unsuccessful treatment of symblepharon on the basis of similar characteristics between the conjunctiva&#44; the AM&#44; &#40;transparency&#44; thickness&#44; consistency&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In 1946&#46; Sorsby utilized AM for covering chemical ocular abrasions but&#44; despite positive results&#44; the technique was forgotten&#46; Said author was the first to state that AM had excellent mechanical as well as biological properties&#46; Almost 50 years later&#44; Batlle and Perdomo<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> used AM in conjunctival defects and Kim and Tseng for treating ocular surface pathologies&#44; both in 1992&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;6&#8211;9</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Materials and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">A review of papers was carried out after searching the terms <span class="elsevierStyleItalic">&#171;amniotic membrane&#187;</span> and <span class="elsevierStyleItalic">&#171;eye&#187;</span> in Pubmed in the past 5<span class="elsevierStyleHsp" style=""></span>years&#46; Said search initially included <span class="elsevierStyleItalic">&#171;review&#187;</span> and was later expanded to include some articles of the References cited in the selected papers&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Amniotic membrane characteristics</span><p id="par0015" class="elsevierStylePara elsevierViewall">AM is derived from the innermost layer of the foetal membrane&#46; Its thickness ranges between 0&#46;2 and 0&#46;5<span class="elsevierStyleHsp" style=""></span>mm&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a> Several authors have demonstrated that AM thickness in humans varies between individuals&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a> It consists in an epithelial layer&#44; a thick basal membrane and an avascular stroma &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Epithelial layer&#46;</span> A monolayer of cuboidal cells with microvilli on the apical surface<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> that are in direct contact with amniotic fluids&#46; The AM is anchored to the basal membrane through hemidesmosomes&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Said cells secrete numerous substances that are vital for the function of AM&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Basal membrane&#46;</span> This membrane consists in connective tissue linked by means of collagen bundles that maintain the mechanical stability of the membrane</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0030" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Avascular stroma&#46;</span> The thickest layer of fibroblasts adjacent to the chorion&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;12</span></a> This layer is divided in 3&#44; i&#46;e&#46;&#44; the <span class="elsevierStyleItalic">compact</span> layer &#40;in contact with the basal membrane&#44; providing resistance to traction&#41;&#44; the <span class="elsevierStyleItalic">fibroblast</span> layer &#40;comprising of fibroblasts and Hofbauer cells&#41; and the <span class="elsevierStyleItalic">sponge-like</span> layer &#40;the outermost layer&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14&#44;15</span></a></p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Said tissue comprises a number of characteristics that make it very useful for treating ocular pathologies and for tissue engineering&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Said characteristics are&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">promoting tissue proliferation through epidermic growth factors &#40;EGF&#41;&#44; keratinocytic growth factors &#40;KGF&#41; and basic fibroblast growth factors &#40;BFGF&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Facilitating cell migration through lumican&#44; a specific glycoprotein&#44; and hyaluronic acid which also has anti-inflammatory and immunosuppressant effects<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;17</span></a>&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Promoting specific migration of keratinocytes through the serine protease inhibitor &#40;serpin 1&#41; and dipeptidyl peptidase IV &#40;DPP-IV&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Inhibiting cicatrization by suppressing the tumor growth factor Beta &#40;TGF-&#946;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Downwardly regulating the expression of cell surface markers such as CD80&#44; CD86 and class 2 histocompatibility antigen &#40;immune response modulators&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">inhibiting inflammation and neovascularization due to the secretion of metalloproteinase tissue inhibitors &#40;TIMP&#41; and cytokins &#40;interleukin-10&#44; anti-inflammatory interleukin and interleukin-1 receptor antagonists&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">It hardly exhibits any immunogenicity because it does not express human leukocyte antigens &#40;HLA&#41; A&#44; B&#44; C&#44; D and DR&#44; although it does express HLA-G &#40;involved in the induction of immune tolerance by acting as macrophage ligand and <span class="elsevierStyleItalic">natural killer</span>&#41; and Fas ligand<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;7&#44;8&#44;12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;21</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">It exhibits a tectonic effect &#40;acting as a scaffolding in structural defects&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">It also exhibits antimicrobial properties &#40;it can also act as antimicrobial barrier&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">It functions as an in vitro and in vivo cell culture medium<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;23</span></a> and for this reason could have high potential in tissue engineering&#46;</p></li></ul></p><p id="par0090" class="elsevierStylePara elsevierViewall">The sum of the above mechanisms is what enables adequate cicatrization and regeneration of wounds&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Resch et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> observed that AM can integrate with corneal tissue in 4 different manners&#44; i&#46;e&#46;&#44; intra-epithelial&#44; sub-epithelial&#44; intrastromal integration and over the corneal surface&#46; Said authors carried out AM transplants in patients who subsequently required keratoplasty&#44; thus enabling in-depth histological analysis&#46; Integration according to one pattern or another depended on the surgical technique as well as on the ocular disease being treated&#46; This raises the possibility that the knowledge of these integration patterns could help us to select the most adequate technique for the pathology to be treated&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Types of amniotic membrane according to the preparation process</span><p id="par0100" class="elsevierStylePara elsevierViewall">AM is obtained from placenta donated by seronegative females who underwent elective C-section&#46; Donor serology must exclude hepatitis B virus &#40;HBV&#41; and<span class="elsevierStyleHsp" style=""></span>C<span class="elsevierStyleHsp" style=""></span>&#40;HCV&#41;&#44; human immunodeficiency virus &#40;HIV&#41;&#44; toxoplasma and syphilis during pregnancy&#46; Serology is repeated 3&#8722;6<span class="elsevierStyleHsp" style=""></span>months after labor to discard any infection that could have been in the window period during the initial screening&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Several methods are utilized to preserve amniotic membrane&#44; i&#46;e&#46; the wet method &#40;hypothermic storage&#41;&#44; the dried method &#40;lyophilized&#41; and cryopreservation&#46;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">&#8226;</span><p id="par0110" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Fresh</span> AM is separated from the placenta under sterile conditions and irrigated with sterile saline solution&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> It is kept in a saline solution with 50&#44;000<span class="elsevierStyleHsp" style=""></span>UI of penicillin and 1<span class="elsevierStyleHsp" style=""></span>g of streptomycin for every 400<span class="elsevierStyleHsp" style=""></span>ml of saline solution at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;27</span></a> In the authors&#8217; country it is not generally utilized due to the risk of disease transmission in the window period &#40;HBV&#44; HIV&#44; etc&#46;&#41; and due to its low availability &#40;it must be utilized within a timeframe&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> However&#44; AM is widely applied in developing countries in which preservation techniques are not fully implemented&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0115" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Dried</span> or lyophilized AM is dried under vacuum at low temperature and rehydrated prior to use&#46; One of the advantages of lyophilization compared to cryopreservation is the possibility of storing it at room temperature&#46; This characteristic facilitates transport as well as use in developing countries and military campaigns&#46; In addition&#44; dried AM is irradiated to ensure sterilization&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;19&#44;20&#44;29</span></a> However&#44; dried AM exhibits lower concentration of proteins&#47;growth factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a></p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Cryopreservation&#46;</span> This is the original method described by Kim and Tseng&#44;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> consisting in washing the membrane under a laminar flow bell and subsequently separating the amnion from the chorion&#46; The stromal &#40;adhesive&#41; part of the amnion is placed on nitrocellulose paper<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> and subsequently washed with tamponating saline solution containing 1000<span class="elsevierStyleHsp" style=""></span>U&#47;ml of penicillin&#44; 20<span class="elsevierStyleHsp" style=""></span>mg&#47;ml streptomycin and 2&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;ml amphotericin<span class="elsevierStyleHsp" style=""></span>B&#46; finally&#44; it is stored in 100 &#37; glycerin at 4<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; These fragments are kept in a cryoprotective substance at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C which enables its use up to 5<span class="elsevierStyleHsp" style=""></span>years later &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; At present&#44; said method has been modified by Lee et al&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;32</span></a> One of the disadvantages of this process is that some properties could be lost&#46; Even so&#44; at present it is the method of choice for processing AM in developed countries&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;19&#44;20&#44;29</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></li></ul></p><p id="par0125" class="elsevierStylePara elsevierViewall">In recent years&#44; a medical device has appeared in the market under the trademark Prokera&#174; &#40;Bio-Tissue&#44; Inc&#46;&#44; Miami&#44; FL&#44; USA&#41; that enables the utilization of AM without sutures&#46; This has several advantages including lower inflammation&#44; shorter surgical times and less checkup visits for removing sutures&#46; Said device is a ring with a diameter of 15<span class="elsevierStyleHsp" style=""></span>mm for pediatric patients or 16<span class="elsevierStyleHsp" style=""></span>mm for adults that contains cryopreserved AM and can be easily placed with topical anesthesia&#46; It functions as a &#8220;biological compressive bandage&#8221; with the epithelial side over the defect and is eliminated in approximately 3 days&#46; This device is useful to prevent the formation of symblepharon in severe cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;33&#8211;35</span></a> Another device with a similar design is AmnioClip&#174;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> &#40;KET Kunststoff- und Elasttechnik GmbH&#44; Liegau-Augustusbad&#44; Germany&#41;&#44; comprising AM between 2 rings that can be placed as a large contact lens &#40;similar to Prokera&#174;&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Surgical technique&#46; Graft or patch</span><p id="par0130" class="elsevierStylePara elsevierViewall">The surgical technique is important when using AM because&#44; depending on the ocular pathology&#44; it can be applied as a graft <span class="elsevierStyleItalic">&#40;inlay&#41;</span> or a patch <span class="elsevierStyleItalic">&#40;onlay&#41;</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8&#44;14&#44;31</span></a> During the intra-surgery management of AM the surgeon is able to discern the epithelial from the stromal layer because the latter is adhesive but the former is not&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">When used as a graft&#44; AM acts as an basal membrane for the development of corneal epithelium and becomes part of the treated cornea or conjunctiva&#46; The stromal &#40;adhesive&#41; of AM is placed over the ocular defect without extending beyond its edges&#46; Prior to placing the graft&#44; necrotic remains must be debridled &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8&#44;14</span></a> In this way&#44; the adhesive surface will integrate with the defect and the perilesional epithelium will grow over the AM&#46; The fixation of AM can be done with sutures as well as with glue &#40;after drying the area&#41;&#46; In order to avoid graft detachments&#44; a therapeutic contact lens can be used or lateral tarsorraphy can be carried out&#46; According to the etiology and the severity of the lesion&#44; AM can be used as a single or multiple layer&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0140" class="elsevierStylePara elsevierViewall">The above technique comprises the following variations&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">A lamellar sac can be made surrounding the defect using a &#171;crescent&#187; blade<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> in which the AM can be inserted&#46;</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">The &#171;Filling technique&#187;&#44; useful for repairing the deep ulcers&#46; It consists in the introduction of several layers of AM cut with a punch to fill in the defect and subsequently place an upper AM with the epithelial edge facing downwards&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">&#8226;</span><p id="par0155" class="elsevierStylePara elsevierViewall">The &#171;Roll filling technique&#187;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> in which an AM roll is introduced in the defect &#40;specifically described for perforations&#41; and placing 2 layers of AM with the stromal face over said roll&#44; suturing at the edge of the defect&#46; Perfluoropropane is subsequently introduced in the anterior chamber &#40;AC&#41; to avoid the roll entering the AC&#44; placing thereafter a larger AM over the entire cornea with the stromal surface downwards&#46;</p></li></ul></p><p id="par0160" class="elsevierStylePara elsevierViewall">Indications for the use of AM as a graft described in the medical literature include epithelial defects with ulcers&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> corneal thinning&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> descematocele and corneal micro-perforations&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> escision of tumors and scars&#44;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> band keratopathy&#44;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> bullous keratopathy<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> and limbar stem cell deficit &#40;LSCD&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">23&#44;43</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">The use of AM as a <span class="elsevierStyleItalic">patch</span> consists in the placement of the epithelial&#44; non-adhesive side of AM in contact with the ocular defect&#44; going over its edges &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;14</span></a> Said side is rich in immunomodulator cytokins and epithelial growth factors and facilitates inflammation reduction&#44; improves cicatrization and operates as a &#8220;compressive bandage&#47;protective covering&#8221;&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5&#44;15</span></a> The various indications described for this technique include epithelial defects without ulceration&#44; acute Stevens-Johnson syndrome&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#8211;48</span></a> acute chemical burns<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> and high risk of corneal transplant&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0170" class="elsevierStylePara elsevierViewall">It must be emphasized that the application of one technique instead of another is not linked to the pathology&#46; In the analyzed references the authors found studies describing the use of AM as a graft for certain pathologies and other studies recommending its use as a patch for the same pathologies&#46; In essence&#44; the indications for AM and the techniques to be applied are not clear&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Use of amniotic membrane in ocular pathology&#46; Overview and tissue engineering</span><p id="par0175" class="elsevierStylePara elsevierViewall">The use of AM is described for multiple ocular pathologies including corneal abrasions&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21&#44;51&#8211;54</span></a> repair of filtrating blebs&#44; trabeculectomy&#44; persistent neurotrophic or herpetic ulcers&#44; descematocele&#44; perforations&#44;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> pterygium&#44; numular keratitis&#44; limbar insufficiencies &#40;including limbar cell culture and subsequent transplant thereof&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> band keratopathy&#44; conjunctival reconstruction&#44; symblepharon&#44; etc&#46;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7&#44;29&#44;33</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0180" class="elsevierStylePara elsevierViewall">The main contraindications for AM are severe dry eye&#44; lagophthalmos and severe necrosis caused by ischemia&#46; It is not recommended as an independent treatment for severe grade<span class="elsevierStyleHsp" style=""></span>IV abrasions &#40;Roper-Hall classification&#41;&#46; Despite a certain controversy in this regard&#44; it is highly likely that AM implanted in a patient will not supply live and functional stem cells but a large number of molecules and factors which&#44; added to the biomechanical scaffolding&#44; enable and stimulate the differentiation of local cells&#46; Accordingly&#44; even though AM provides a positive microclimate&#44; in advanced grades AM does not facilitate improvement when used as exclusive treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;20</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">In recent years&#44; the increasing influence of tissue engineering has facilitated the appearance of new applications for AM&#46; One is sclerocorneal limbus cell culture that enables less aggressive surgery for treating limbar cell deficit by means of the application of intact or de-epithelized AM&#46; It is yet to be seen which form of AM is the best although some studies<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> suggest that the use of intact AM is preferred&#46; However&#44; other studies consider it necessary to carry out more studies before reaching this conclusion&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> in vitro experiments indicate that intact AM culture supports the expansion of cells with a partially non-differentiated limbar phenotype&#46; Culture of de-epithelized AM could induce greater differentiation although this effect would diminish with the addition of 3T3 cells&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">An additional factor that was analyzed was the stability of AM for culture&#46; The use of various cross-linking agents began to be studied in AM as well as the use of different collagen gels&#44; fibrin and fibronectin-fibrin gels for culture&#44; in addition to the utilization of contact lenses&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> The aim of this analysis was to increase the stability of AM grafts in order to avoid postoperative detachments&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Despite the large number of studies related to AM in ophthalmology&#44; its actual usefulness is not yet clear in our country&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Other recent applications of AM or its derivates include AM extract&#44; with properties similar to cryo-preserved AM&#44; and AM extract in drops which can be combined with umbilical cord blood to be used as a variant of the solution derived from AM&#46; Research is also being conducted on the utilization of amniotic fluid&#44; which is a dynamic medium that changes its composition according to the stage of pregnancy as it contains a number of growth factors&#44; electrolytes&#44; proteins&#44; enzymes and hormones that promote cicatrization&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In what concerns the preparation of AM extract&#44; due to the absence of standardized protocols several methods have been developed that endow different properties to the product&#46; This circumstance&#44; together with a range of problems for the adequate preservation of the extract and its short life cycle&#44; constitute its main disadvantages&#46; It is important to emphasize that the product does not provide the tectonic properties of AM transplants&#46; The main advantage of its use is that&#44; as it is prepared as an eye drop&#44; it can be applied by the patient thus avoiding surgery and to a large extent preventing postoperative infections as well as patient discomfort&#44; in addition to reducing health expenditure&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Several in vivo and in vitro studies have demonstrated the beneficial effect of said AM extract product because it allows improved tissue regeneration&#46; However&#44; the authors have not found any study comparing its use compared to blood-derived autologous serum&#46; Therefore it cannot be said that these products are superior&#44; equal or inferior&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Many companies are marketing said products despite the absence of approval by the US Food and Drug Administration &#40;FDA&#41;&#46; The best-known products are Regenesol&#8482; by Biotissue&#47;Tissue Tech Inc&#46; &#40;Miami&#44; FL&#44; USA&#41;&#44; amniotic cytokins extract Genesis &#40;ACE&#41;&#8482;&#44; by Ocular Science Inc&#46; &#40;Manhattan Beach&#44; AC&#44; USA&#41; and Regener-Eyes&#8482; &#40;Palm Beach&#44; FL&#44; USA&#41;&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">The use of said product is recommended for dry eye&#44; chemical burns&#44; corneal ulcers&#44; corneal transplants and after laser-assisted subepithelial keratomileusis &#91;LASEK&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Uses of amniotic membrane for specific ocular pathologies</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Corneal pathology</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Refractory ulcers and ocular perforations</span><p id="par0225" class="elsevierStylePara elsevierViewall">These pathologies are the main beneficiaries of AM&#46; In most cases&#44; AM is reserved for ulcers that are refractory to even preventive medical treatment in the presence of imminent perforations&#44; preceded by descematocele or otherwise&#46; The mechanical and biological properties of AM enable fast recovery and less fibrosis&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">AM is applied to ulcers that do not respond to medical treatment&#46; Its usefulness is specially demonstrated in neurotrophic ulcers requiring reinforced treatment&#44; although the application of AM is usually limited to ulcers in advanced stages but it can also be applied in previous stages&#46; Several papers<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">31&#44;57&#44;58</span></a> have demonstrated the efficiency of AM in ulcers resistant to treatment with lubrication&#44; contact lenses or tarsorraphy&#44; with many cases requiring adjuvant treatment&#46; In what concerns infectious ulcers&#44; in addition to the above described effects&#44; AM acts as a reservoir enabling longer duration of antibiotics&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> Recent studies such as Mohan et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a> reported a success rate of 82&#46;1 &#37; in resistant bacteria and corneal ulcers&#46; Studies based on the surgical specialties demonstrated that AM improved control over bacterian populations&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">In the case of perforations&#44; the definitive treatment is generally keratoplasty&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> The difficulty of finding adequate corneas at short notice requires the assessment of other approaches including AM&#44; the utilization of which has been demonstrated in numerous studies<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">38&#44;63&#44;64</span></a> but not for all cases&#46; Rodr&#237;guez-Ares et al&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> described the safe use of AM only in perforations under 1&#46;5<span class="elsevierStyleHsp" style=""></span>cm&#44; in which they found high success rates&#46; However&#44; other papers<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> observed that the exclusive use of AM in ocular perforations fails in the majority of cases and recommend the search of co-adjuvant treatments when utilizing AM during surgery&#46; This option is being researched by other authors &#40;corneal patches&#44; umbilical cord patches&#44; equine pericardium&#44; TachoSil&#174;&#44; fibrin glue&#44; intra-chamber fibrin&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">65&#8211;72</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Bullous keratopathy</span><p id="par0240" class="elsevierStylePara elsevierViewall">Ongoing friction of nerves produced by edematized corneal stroma and the formation of bullas are the main cause of pain in this pathology&#46; The utilization of AM in these patients provides relief of symptoms although limited to the duration of AM&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Pires et al&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a> described that 90 &#37; of patients with bullous keratopathy and intense pain responded positively to treatment and reported relief from pain&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Chemical corneal abrasions</span><p id="par0245" class="elsevierStylePara elsevierViewall">The use of AM in acute abrasions is controversial because&#44; despite its beneficial properties&#44; its ability to inhibit vascularization restricts the recovery of limbar cells &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> Normally its use is reserved for severe acute abrasions&#44; although there is no consensus on this&#46; As discussed earlier&#44; treating this pathology only with AM is not recommended and it is generally applied as adjuvant for other treatments such as tetracycline&#44; artificial tears&#44; vitamin C and therapeutic lenses among others&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In what concerns symptom relief and re-epithelization time&#44; improvements have been reported&#46; Patients with abrasions of grade<span class="elsevierStyleHsp" style=""></span>II-III &#40;Roper-Hall classification&#41; exhibit improved visual acuity recovery when compared to those with grade<span class="elsevierStyleHsp" style=""></span>IV abrasions&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><elsevierMultimedia ident="fig0025"></elsevierMultimedia><p id="par0250" class="elsevierStylePara elsevierViewall">An interesting non-surgical alternative is the use of umbilical cord serum&#44; which has demonstrated to be superior in some parameters &#40;longer breakup time and higher post-treatment Schirmer test values&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> although it is not available in the majority of hospitals&#46; Tamhane et al&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a> found that AM improves epithelization and pain relief without diminishing the risk of limbar cell deficit or improving visual acuity when compared with a control group&#46; Recent studies<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> report that medical treatment in addition to AM transplant versus medical treatment on its own does not improve re-epithelization nor improve visual acuity in severe abrasions&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conjunctival pathology</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Pterygium</span><p id="par0255" class="elsevierStylePara elsevierViewall">AM is a good alternative to conjunctival autograft &#40;CAG&#41; <span class="elsevierStyleItalic">&#40;</span>gold standard<span class="elsevierStyleItalic">&#41;</span> when the patient underwent numerous previous conjunctival surgeries or when the conjunctiva must be preserved for possible glaucoma surgeries in the future&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> A Cochrane systematic study<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a> compared the effectiveness and risks of CAG versus AM&#44; finding a relapse percentage of 3&#46;3&#8211;16&#46;7 &#37; utilizing CAG compared to 6&#46;4&#8211;42&#46;3 &#37; with AM&#46; Said meta-analysis demonstrate that eyes treated with CAG had 47 &#37; lower relapse risk at 6 months compared to those treated with AM&#46; Another meta-analysis by Li et al&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a> also supported these results&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Symblepharon&#44; toxic epidermal necrolysis&#44; stevens-johnson syndrome</span><p id="par0260" class="elsevierStylePara elsevierViewall">The use of AM in these diseases aims at preventing the formation of symblepharon and avoiding multiple complications associated to toxic epidermal necrolysis &#40;TEN&#41; and to the Stevens-Johnson syndrome &#40;SJS&#41;&#46; The application of intense lubrication&#44; aggressive topical corticoids and AM transplant is necessary to prevent the possibility of complications in the future&#44; recommending AM transplant in acute TEN and SJS during the first week<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;78&#44;79</span></a>&#46; Hsu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">80</span></a> carried out a case and control study in acute TEN and SJS and observed that the early use of AM avoided severe visual acuity loss in said patients with moderate or severe inflammation&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">The main signs that should call for the use of AM would be compromise of the free palpebral edge&#44; the formation of pseudo-membranes and membranes&#44; conjunctival and tarsal fornix defects&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;78</span></a> In these diseases&#44; authors do not agree on the use of suture of fibrin to avoid postoperative complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">79&#44;81</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">In many cases the main problem for AM transplants is that patients are significantly unstable or in the ICU and are not eligible for surgery&#46; In these situations&#44; as described above several devices can be used including Prokera&#174;&#44; AmnioClip&#174;&#44; etc&#46;&#44; that can be placed under topical anesthesia and without a microscope&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;78</span></a> It should be emphasized that the use of these devices is highly recommended for preventing symblepharon&#44; as discussed above&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;33&#8211;35</span></a></p></span></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0275" class="elsevierStylePara elsevierViewall">This review has described numerous techniques and listed pathologies for which the application of AM is probably beneficial&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">It can be stated that AM features multiple positive qualities when applied to different pathologies in ophthalmology as well as in other surgical medical specialties&#46; However&#44; the limitations exhibited by some studies and the lack of large case and control series do not allow us to state that the use of AM is better than other biomaterials for all the described pathologies or even that the utilization of a surgical technique can be associated to the treatment of a specific pathology&#46; Nevertheless&#44; it is confirmed that in some diseases such as relapsing pterygium AM is not the first option for treatment and that in other diseases &#40;ulcers and perforations&#44; among others&#41; it produces very positive results as an adjuvant&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Notwithstanding the above&#44; the majority of studies to date indicate that AM facilitates regeneration and more satisfactory results&#46; The considerable development of tissue engineering and tissue preservation forecasts very good results in the near future&#46; Accordingly&#44; larger studies should be carried out comparing the use of AM with other biological as well as artificial tissues&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0290" class="elsevierStylePara elsevierViewall">No conflict of interests has been declared by the author&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">The use of amniotic membrane &#40;AM&#41; in ophthalmology has been increasing in recent years due to its multiple biological and tectonic properties&#44; improvement in the process of obtaining&#44; ease of use&#44; and advancement in tissue engineering&#46; The AM has become one of the main adjuvant treatments&#44; in ophthalmic surgery as well as in other medical-surgical specialties&#46; The development of tissue engineering has allowed it to be used&#44; not only in its classic form&#44; but also by the use of drops and other presentations&#46; The different steps prior to its use &#40;preparation and conservation&#41;&#44; the different surgical techniques&#44; and their main clinical applications are described throughout the article&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La utilizaci&#243;n de la membrana amni&#243;tica &#40;MA&#41; en la oftalmolog&#237;a est&#225; en alza en los &#250;ltimos a&#241;os debido a sus m&#250;ltiples propiedades biol&#243;gicas y tect&#243;nicas&#44; la mejora en el proceso de obtenci&#243;n&#44; la facilidad de uso y el avance en la ingenier&#237;a tisular&#46; La MA se ha convertido en uno de los principales tratamientos coadyuvantes&#44; tanto en la cirug&#237;a oftalmol&#243;gica como en otras especialidades m&#233;dico-quir&#250;rgicas&#46; El desarrollo de la ingenier&#237;a tisular ha permitido su utilizaci&#243;n no solo en su forma cl&#225;sica sino tambi&#233;n mediante gotas y otras presentaciones&#46; A lo largo del articulo hemos realizado un resumen de los distintos pasos previo a su uso &#40;preparaci&#243;n y conservaci&#243;n&#41;&#44; las distintas t&#233;cnicas quir&#250;rgicas y sus principales aplicaciones cl&#237;nicas&#46;</p></span>"
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            "identificador" => "at0065"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Amniotic membrane as graft&#46;</p>"
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        "etiqueta" => "Fig&#46; 4"
        "tipo" => "MULTIMEDIAFIGURA"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A&#41;<span class="elsevierStyleHsp" style=""></span>Corneal abrasion due to caustic soda&#46; De-epithelization of the central and lower 120&#176; of the cornea&#46; Intense ocular inflammation with amputation of limbar vessels between 4 and 6 o&#8217;clock&#46; B&#41;<span class="elsevierStyleHsp" style=""></span>Amniotic membrane cover &#40;graft&#41;&#46; C&#41;<span class="elsevierStyleHsp" style=""></span>Placement of therapeutic contact lens on transplant to improve fixation&#46; D&#44;E&#41;<span class="elsevierStyleHsp" style=""></span>Applied graft 4 days later&#46; F&#44;G&#41;<span class="elsevierStyleHsp" style=""></span>Graft after 6 days&#46; Graft rupture can be seen in the upper part although the lower part is adequately covered&#46; H&#41;<span class="elsevierStyleHsp" style=""></span>Graft after 10 days&#44; fully reabsorbed and exhibiting significant improvement&#46; I&#41;<span class="elsevierStyleHsp" style=""></span>Graft after 20 days&#44; showing positive postoperative result with corneal transparency and limbar vascular recovery&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Property&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Molecule&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cell proliferation induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EGFEGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BFGF&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Neovascularization reduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TIMPTIMP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">XVIII collagen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL 10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-scarring action&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TGF-&#946; suppression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low or null immunogenicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No expression of HLA A&#44; B&#44; C&#44; D and DRexpression of HLA G and Fas ligand&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Cell migration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LumicanLumican&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hyaluronic acid&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specific keratinocyte migration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Serpin-1Serpin-1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DPP-IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Corneal regeneration pool&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Collagen type I&#44; III&#44; IV and V&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Corneal pathology</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Conjunctival pathology</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-infectious ulcers due to bacteria or virus herpes zoster&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Conjunctival reconstruction&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Post-trauma ulcers and due to some or all chemical burns&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Conjunctivochalasis<a class="elsevierStyleCrossRef" href="#bib0280">56</a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neurotrophic ulcers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Muco-synechial diseases&#58; pemphigoid&#44; Stevens-Johnson&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Descematocele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Symblepharon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Corneal perforations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Recurring pterygium and surgeries associated to pterygium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Band keratopathies&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Neoplasias&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Degenerative pathologies&#44; dystrophy&#44; recurring erosions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Scleral pathology</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Other indications</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Necrotizing limbitis-scleritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Filtration bleb defects in glaucomatous surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Scleromalacia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Glaucomatous valve covering&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Scleral perforation&nbsp;\t\t\t\t\t\t\n
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