A protocol for the treatment of retinopathy of prematurity in Spain | Archivos de la Sociedad Española de Oftalmología (English Edition)

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"apellidos" => "Garcia Campos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "r" "identificador" => "aff0090" ] ] ] ] "afiliaciones" => array:18 [ 0 => array:3 [ "entidad" => "Servicio de Oftamología, Hospital Infantil, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital de Cruces, Bilbao, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Vall d’Hebron, Barcelona, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Hospital Sant Joan de Déu, Barcelona, Spain" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Hospital Universitario La Fe, Valencia, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Hospital Virgen de las Nieves, Granada, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Hospital Universitario San Cecilio, Granada, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Hospital Carlos Haya, Málaga, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Hospitales Universitarios Virgen del Rocío, Sevilla, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "Hospital Universitario Reina Sofía, Córdoba, Spain" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas, Gran Canaria, Spain" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "p" "identificador" => "aff0080" ] 16 => array:3 [ "entidad" => "Complejo Hospitalario de Navarra, Pamplona, Spain" "etiqueta" => "q" "identificador" => "aff0085" ] 17 => array:3 [ "entidad" => "Complejo Hospitalario Universitario, Santiago de Compostela, A Coruña, Spain" "etiqueta" => "r" "identificador" => "aff0090" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Protocolo de tratamiento de la retinopatía del prematuro en España" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1130 "Ancho" => 2243 "Tamanyo" => 163614 ] ] "descripcion" => array:1 [ "en" => "Retinopathy of prematurity classification." ] ] ] "textoCompleto" => "IntroductionRetinopathy of prematurity (ROP) is a peripheral proliferative vitreoretinopathy that expresses in immature premature infants of as yet unknown etiopathogeny. Premature babies are born with an immature retina in what concerns vascularization. Through a mechanism which to date is unknown even though there is an increasing amount of information, a number of metabolic events occur at the limits of the mature–immature retina which restricts the normal growth and development of vessels and causes the secondary appearance of neovessels and fibrovascular tissue that could evolve toward traction with retina detachment.ROP has a very important social and economic impact. About 5% of survivors weighing less than 1000g are legally blind. A higher percentage exhibits significant visual alterations. Severe ROP is directly associated to severe neurological development disorders and, in the presence of visual problems, the functional evolution of these patients is worse, as 77% are unable to take care of themselves. The severity of ROP is taken as a long-term neurological dysfunction marker<a class="elsevierStyleCrossRef" href="#bib0005">1</a> and currently it is considered an important health problem.It is essential to have a diagnostic and follow-up protocol in order to ensure adequate management of ROP.Classification of retinopathy of prematurityIn order to establish a treatment protocol for ROP it is essential to determine its classification. In 1984 the International ROP Classification was published and modified in 1997 to include the classification of DR, cicatricial changes and sequels. In 2005 it was reviewed to include standards for each parameter by means of photographs<a class="elsevierStyleCrossRef" href="#bib0010">2</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Each ROP case is defined according to 3 areas.LocalizationThe retina is divided in 3 concentric zones:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Zone I is the innermost area centered in the papilla from which the vessels progress. Its radius is twice the distance between the papilla and the macula.</li><li class="elsevierStyleListItem" id="lsti0010">-Zone II is concentric to zone I and its diameter reaches the nasal ora serrata. Recent studies have differentiated and anterior and posterior zone II because the involvement in posterior zone I or zone II is more severe. Accordingly, the ROP developed in this “posterior zone” (posterior zone I+zone II) is defined as posterior ROP. Clinically, the limit of said posterior zone is established when looking through the lens of 2.2 or 25D, with the papilla being at the opposite limit of the lens.</li><li class="elsevierStyleListItem" id="lsti0015">-Zone III is the temporal half moon which goes from zone II to the limits of the temporal ora serrata.</li></ul>Circumferential/clock extensionThe involvement must be specified in circumferential clock hours.Evolutionary stageFive stages have been differentiated:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">-Stage 1 corresponds to the line separating the vascular and avascular retina.</li><li class="elsevierStyleListItem" id="lsti0025">-Stage 2 corresponds to the monticular crest, with thickened separation line which becomes prominent. Possibility of arteriovenous shunts and thickening of vessels posteriorly to the crest.</li><li class="elsevierStyleListItem" id="lsti0030">-Stage 3 corresponds to extra-retinal vascularization, with crest reddening and posterior growth of continuous or discontinuous anomalous vessels. This neovascularization is derived from the posterior edge of the crest and is usually accompanied by glyal proliferation.</li><li class="elsevierStyleListItem" id="lsti0035">-Stage 4 corresponds to subtotal, exudative or tractional retina detachment without or with involvement of the fovea (4a, 4b respectively).</li><li class="elsevierStyleListItem" id="lsti0040">-Stage 5 corresponds to total RD, subdivided in open or closed anterior and posterior tunnel.</li></ul>In addition, the classification establishes the “plus disease”, a sign of severity which may appear at any stage. It indicates a high flow vascular short-circuit due to active arteriovenous shunts and is characterized by tortuosity and dilatation of the posterior pole vessels in at least 2 quadrants, and/or pupil rigidity. The presence of disease plus is indicated adding a plus sign to the stage.There are additional concepts which must be known in ROP, such as the “pre-threshold disease” and the “threshold disease”, which appeared with the development of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity<a class="elsevierStyleCrossRefs" href="#bib0015">3–5</a> and the ETROP Study<a class="elsevierStyleCrossRef" href="#bib0030">6</a> (Early Treatment for ROP Randomized Trial). The “type I prethreshold disease” is defined as: zone I, any stage with disease plus; zone I, stage 3 without disease plus and zone II, stage 2+ and 3+, and “prethreshold disease type 2” as: zone I, stage 1 or 2 without disease plus, and zone II, stage 3 without disease plus. “Threshold disease” is defined as the presence in zone I or II of stage 3+ in 5 consecutive hours or 8 overall hours.Finally, “posterior ROP” is defined as any degree of retinopathy in the posterior zone (posterior zone I and zone II) in the presence of plus signs.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a>Retinopathy of prematurity treatmentTreatment criteriaTreatment is considered to be necessary in the presence of:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045">1.Threshold disease: 5 consecutive hours or 8 overall hours in stage 3 plus.</li><li class="elsevierStyleListItem" id="lsti0050">2.Prethreshold disease type 1:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055">-Zone I, any stage with disease plus.</li><li class="elsevierStyleListItem" id="lsti0060">-Zone I, stage 3 without disease plus.</li><li class="elsevierStyleListItem" id="lsti0065">-Zone II, stage 2+ and 3+.</li></ul></li></ul>Treatment methodologyDiode laser photocoagulationAt this time, diode laser photocoagulation is the treatment of choice. In what concerns methodology, the following is applicable.Pre-treatment guidelines<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0070">1.The treatment must be applied within 48–72hours after diagnosis.</li><li class="elsevierStyleListItem" id="lsti0075">2.The ophthalmologist and the anesthetist must present an informed consent to the parents or legal custodians.</li><li class="elsevierStyleListItem" id="lsti0080">3.Pre-surgery midriasis must be achieved applying the minimum dosage to avoid the side effects of midriatics,<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> achieving at the same time efficient and lasting midriasis enabling the application of laser. Ideally, parasympathetic blockers should be associated (1% tropicamide or 0.5 or 1% cyclopentolate) with sympathomimetics (phenylephrine at 2.5 or 1%). Guidelines for midriasis may be established in each center on the basis of studies demonstrating efficacy and safety.</li></ul>Treatment guidelines<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0085">-Anesthesia can be topical, sedation with gases, IV sedation, general anesthesia with intubation or laryngeal mask according to the criteria of each center on the basis of its experience and results.<a class="elsevierStyleCrossRef" href="#bib0055">11</a></li><li class="elsevierStyleListItem" id="lsti0090">-Anesthesia can be applied in the neonatal unit or operating theater at the choice of each hospital.</li><li class="elsevierStyleListItem" id="lsti0095">-It is recommended to maintain adequate environmental temperature and apply thermal protection to the infant.</li><li class="elsevierStyleListItem" id="lsti0100">-It can be applied through indirect ophthalmoscopy, the most widely used method, or transscleral by means of a retinopexy probe. In the case of indirect ophthalmoscopy, it is essential to be extremely careful to avoid accidental application on the macular area.</li><li class="elsevierStyleListItem" id="lsti0105">-The initial energy is of about 350mW (depending on the equipment and the time of use: with longer time more powerful energies are required), with an application time of 200ms and repetition time of 400ms, which enables focusing on the different zones maintaining the foot on the pedal. A whitish-creamy lesion must be obtained and it should be applied in nearly confluent manner throughout the avascular retina.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> The final scars are broader than the impacts and this must be taken into account in posterior retinopathy to avoid scars close to the paramacular zone. The entire avascular retina must be treated in a single session. Partial treatment is not recommended.</li><li class="elsevierStyleListItem" id="lsti0110">-The 360° of avascular retina must be treated, although the meridians of II and IX may be left untreated.</li></ul>Post-treatment guidelines<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0115">-Topical anti-inflammatories can be prescribed after treatment.</li><li class="elsevierStyleListItem" id="lsti0120">-After the treatment, the patient must be checked within 7–10 days from the first application. If signs of activity and untreated areas persist, these must be completed.</li></ul>CryotherapyAt present, cryotherapy is not the first choice of treatment and is applied in the following circumstances:<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0125">-Poor midriasis or opacities making laser application impossible.</li><li class="elsevierStyleListItem" id="lsti0130">-As coadjuvant to laser treatment in case of persistent neovascularizations that could benefit from application of cryotherapy. These cases involve high risk of bleeding and therefore application must be carried out with extreme caution.</li><li class="elsevierStyleListItem" id="lsti0135">-Urgent cases of aggressive ROP requiring urgent treatment and laser is not available.</li></ul>Pretreatment guidelinesThese are the same as the diode laser application guidelines. An informed consent must be given to parents and pre-surgery midriasis must follow said indications.Treatment guidelines<ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0140">-Treatment must be carried out in the operating room.</li><li class="elsevierStyleListItem" id="lsti0145">-It is recommended to maintain adequate temperature in the environment and apply thermal protection to the premature.</li><li class="elsevierStyleListItem" id="lsti0150">-Pediatric probes must be used. The use of adult probes is contraindicated.</li><li class="elsevierStyleListItem" id="lsti0155">-General anesthesia is recommended as this is a more painful treatment and causes more cardiorespiratory instability conditions in the patient.</li><li class="elsevierStyleListItem" id="lsti0160">-It is applied with ophthalmoscopy coagulation control.</li><li class="elsevierStyleListItem" id="lsti0165">-The probe is maintained until a whitish scar is obtained.</li><li class="elsevierStyleListItem" id="lsti0170">-Defreezing must be awaited before separating the probe with great care because the sclera of prematures is very fragile.</li><li class="elsevierStyleListItem" id="lsti0175">-Care must be taken to avoid very anterior applications which could damage the ciliary body, with the risk of phthisis bulbi.</li><li class="elsevierStyleListItem" id="lsti0180">-A palpebral opening could be necessary in extremely posterior applications.</li><li class="elsevierStyleListItem" id="lsti0185">-Action on extraocular muscles must be avoided.</li><li class="elsevierStyleListItem" id="lsti0190">-Intra-surgery general anti-inflammatories can be applied to diminish inflammatory reactions.</li></ul>Post-treatment guidelines<ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0195">1.Post-surgery chemosis is practically the rule in the case of cryotherapy and therefore topical treatment with anti-inflammatories must be prescribed. General anti-inflammatories can also be utilized according to the criterion of the ophthalmologist.</li><li class="elsevierStyleListItem" id="lsti0200">2.Due to increased conjunctival manipulation, it is recommended to utilize post-surgery topical antibiotic therapy as well.</li><li class="elsevierStyleListItem" id="lsti0205">3.The first examination is recommended to be carried out at 24–48hours to assess the degree of inflammation and the presence of possible complications such as vitreous hemorrhage, conjunctival tears, hypotony, cataracts, etc. and prescribe the corresponding treatment. Subsequently, the ocular fundus must be examined within 7–10 days.</li></ul>Treatment in advanced stages of the diseaseIf conventional laser photocoagulation treatment fails and the disease progresses to stage IV or more, the patient must be referred to the national reference Center for treating the advanced stages of the disease.At present, treatment alternatives comprise:<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0210">-Cerclage for stage 4.</li><li class="elsevierStyleListItem" id="lsti0215">-Vitrectomy with lens preservation for stage 4.</li><li class="elsevierStyleListItem" id="lsti0220">-Vitrectomy+lensectomy via pars plana.</li><li class="elsevierStyleListItem" id="lsti0225">-Open vitrectomy.</li></ul>Use of anti-vascular endothelial growth factorThe use of anti-VEGF is justified in ROP for the following reasons:<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0230">-VEGF is directly involved in the pathogeny of ROP.<a class="elsevierStyleCrossRefs" href="#bib0065">13–15</a></li><li class="elsevierStyleListItem" id="lsti0235">-Anti-VEGF has demonstrated its efficacy in ophthalmological pathologies involving neovascularization in adults with a similar physiopathological basis (ARMD with neovascular proliferation, ischemic retinal venous thrombosis, etc.).<a class="elsevierStyleCrossRefs" href="#bib0080">16,17</a></li><li class="elsevierStyleListItem" id="lsti0240">-In contrast with ARMD or diabetic retinopathy where the production stimuli is sustained in time, in ROP there is a single VEGF release pulsation.</li><li class="elsevierStyleListItem" id="lsti0245">-The eye is an immunologically and anatomically privileged area for the application of these therapies.<a class="elsevierStyleCrossRef" href="#bib0090">18</a></li><li class="elsevierStyleListItem" id="lsti0250">-Reports have been published on animal experiments.<a class="elsevierStyleCrossRef" href="#bib0095">19</a></li><li class="elsevierStyleListItem" id="lsti0255">-Reports have been published on isolated cases.<a class="elsevierStyleCrossRefs" href="#bib0100">20–28</a></li><li class="elsevierStyleListItem" id="lsti0260">-Clinical trials are in progress for use in prematures.<a class="elsevierStyleCrossRefs" href="#bib0145">29–31</a></li></ul>Indications for useTreatment with anti-VEGF is indicated in the following cases:<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0265">-ROP laser treated over 360° with risk of progression and threatening loss of vision, if no fibrous membranes are marked.</li><li class="elsevierStyleListItem" id="lsti0270">-ROP in which laser treatments cannot be performed as first choice due to poor midriasis, opacity of media or other causes.</li><li class="elsevierStyleListItem" id="lsti0275">-ROP requiring vitrectomy due to association.</li></ul>As anti-VEGF is an off-label treatment, the appearance of new indications could be evaluated in due course, provided there is sufficient clinical experience and positive references.<a class="elsevierStyleCrossRef" href="#bib0160">32</a>Drug and dosageEven though several anti-VEGF agents have been approved (pegaptanib [Macugen®, Pfizer], partial VEGF blocker; ranibizumab [Lucentis®, Novartis], total blocker with monoclonal antibody fraction, and bevacizumab [Avastin®, Roche], total blocker with full monoclonal antibody), bevacizumab is the most widely used and experienced drug in prematures. As this is an off-label treatment, special consent must be obtained for its use together with bibliographic support.The dosage can vary between 0.65 and 0.70mg in 0.03ml.Methodology<ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0280">-It can be applied in the operating room or in the neonatology unit, in the latter case taking extreme care in what concerns sterilization.</li><li class="elsevierStyleListItem" id="lsti0285">-It can be applied with anesthetic sedation or general anesthesia.</li><li class="elsevierStyleListItem" id="lsti0290">-Prior to surgery, betadine eyedrops must be applied in 3 administrations at 10min intervals, antibiotic eye drops (latest generation quinolone) and 0.5% thimolole eyedrops, as well as periocular and eyelid skin cleaning with betadine solution.</li><li class="elsevierStyleListItem" id="lsti0295">-The injection must be applied at 2–3mm of the sclerocorneal limbus in the inferior temporal or nasal quadrant toward the location of the optic nerve. After applying the injection, antibiotic eye drops must be administered.</li><li class="elsevierStyleListItem" id="lsti0300">-Antibiotic and mydriatic eyedrops shall be prescribed for the post surgery period.</li><li class="elsevierStyleListItem" id="lsti0305">-24hours after the treatment the patient must be examined for early identification of complications, with special attention to the possibility of endophthalmitis.</li><li class="elsevierStyleListItem" id="lsti0310">-The ocular fundus must be examined within 7–10 days from the treatment. If laser photocoagulation is not available and the visualization conditions improve laser can be applied in the avascular zone.</li></ul>Conflict of interestsNo conflict of interests has been declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:2 [ "identificador" => "xres273620" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Material and method" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec255623" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres273621" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Material y método" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec255624" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Classification of retinopathy of prematurity" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Localization" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Circumferential/clock extension" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Evolutionary stage" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Retinopathy of prematurity treatment" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Treatment criteria" ] 1 => array:3 [ "identificador" => "sec0040" "titulo" => "Treatment methodology" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0045" "titulo" => "Diode laser photocoagulation" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Pre-treatment guidelines" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Treatment guidelines" ] ] ] ] ] 2 => array:3 [ "identificador" => "sec0060" "titulo" => "Post-treatment guidelines" "secciones" => array:3 [ 0 => array:3 [ "identificador" => "sec0065" "titulo" => "Cryotherapy" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Pretreatment guidelines" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Treatment guidelines" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Post-treatment guidelines" ] ] ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Treatment in advanced stages of the disease" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Use of anti-vascular endothelial growth factor" ] ] ] 3 => array:3 [ "identificador" => "sec0095" "titulo" => "Indications for use" "secciones" => array:1 [ 0 => array:3 [ "identificador" => "sec0100" "titulo" => "Drug and dosage" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Methodology" ] ] ] ] ] ] ] 7 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-07-20" "fechaAceptado" => "2012-07-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec255623" "palabras" => array:3 [ 0 => "Retinopathy of prematurity" 1 => "Protocol" 2 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec255624" "palabras" => array:3 [ 0 => "Retinopatía del prematuro" 1 => "Protocolo" 2 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo prepare a protocol for the treatment of retinopathy of prematurity (ROP) agreed by the majority of Spanish ophthalmologists dedicated to this topic. Material and methodA draft of the protocol was produced taking into account the experience of the participants and up to date publications. This draft was corrected by all the ophthalmologists participating in the project, and the final document was agreed by all of them. ResultsWe present general guidelines as an aid for the treatment of ROP, including treatment criteria, treatment methods, a calendar of action, and follow-up. ConclusionsIt is important to have a common working protocol for the treatment of ROP to improve care and to avoid mistakes. Although individual Hospitals may adapt the protocol to their daily activity, it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "ObjetivoRealizar un protocolo de tratamiento de la retinopatía del prematuro (ROP) consensuado por la mayor parte de oftalmólogos españoles dedicados al tema. Material y métodoSe realizó un borrador del protocolo según la experiencia de los participantes y las publicaciones actualizadas. Este borrador fue corregido por los participantes en el protocolo y se llegó al documento final consensuado por todos los participantes. ResultadosSe presentan las directrices generales para realizar el tratamiento de la ROP, incluyendo criterios de tratamiento, metodología de actuación, calendario de actuación y seguimiento. ConclusionesEs importante disponer de un protocolo de actuación común en el tratamiento de la ROP para mejorar la actuación y evitar errores. Aunque cada centro hospitalario deba adaptar el protocolo a su actividad clínica, es recomendable que existan un mínimo de procedimientos consensuados por todos los oftalmólogos dedicados a la ROP." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ferrer Novella C, et al. Protocolo de tratamiento de la retinopatía del prematuro en España. Arch Soc Esp Oftalmol. 2013;88:231–6." ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1130 "Ancho" => 2243 "Tamanyo" => 163614 ] ] "descripcion" => array:1 [ "en" => "Retinopathy of prematurity classification." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:32 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severity of retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. 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A protocol for the treatment of retinopathy of prematurity in Spain

Protocolo de tratamiento de la retinopatía del prematuro en España

C. Ferrer Novellaa, I. González Viejoa,

Corresponding author

igonzalezv@salud.aragon.es

Corresponding author.

, V. Pueyo Royoa, R. Martínez Fernándezb, M. Galdós Iztuetab, J. Peralta Calvoc, J. Abelairas Gómezc, P. Tejada Palaciosd, N. Martín Beguée, Ch. Wolley-Dode, S. Alarcón Portabellae, A. Serra Castaneraf, M. Morales Ballúsf, M.A. Harto Castañog, R. Martinez-Costa Perezg, F.J. Rodriguez-Hurtadoh, J.L. García Serranoi, J. Escudero Gómezj, C. Morales Guillénk, M.T. Pastor Ramosk..., A. Galván Ledesmak, B. Balboa Huguetk, E. García Roblesk, J.M. Gallardo Galeral, B. Cabrera Marrerm, J. Castellano Solanesm, L. Cordovés Dortan, P. Vals Quintanan, M.A. Gil Hernandezo, S. Perez-Torresp, L. Cortazar Galarzap, M.A. Ardanaz Aldaveq, M. Bové Guriq, M.J. Blanco Teijeiror, P. Mera Yañezr, J. Garcia CamposrVer más

a Servicio de Oftamología, Hospital Infantil, Hospital Universitario Miguel Servet, Zaragoza, Spain

b Hospital de Cruces, Bilbao, Spain

c Hospital Universitario La Paz, Madrid, Spain

d Hospital Universitario 12 de Octubre, Madrid, Spain

e Hospital Vall d’Hebron, Barcelona, Spain

f Hospital Sant Joan de Déu, Barcelona, Spain

g Hospital Universitario La Fe, Valencia, Spain

h Hospital Virgen de las Nieves, Granada, Spain

i Hospital Universitario San Cecilio, Granada, Spain

j Hospital Carlos Haya, Málaga, Spain

k Hospitales Universitarios Virgen del Rocío, Sevilla, Spain

l Hospital Universitario Reina Sofía, Córdoba, Spain

m Complejo Hospitalario Universitario Insular-Materno Infantil, Las Palmas, Gran Canaria, Spain

n Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain

o Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

p Hospital Donostia, San Sebastián, Guipúzcoa, Spain

q Complejo Hospitalario de Navarra, Pamplona, Spain

r Complejo Hospitalario Universitario, Santiago de Compostela, A Coruña, Spain

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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Retinopathy of prematurity classification&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Retinopathy of prematurity &#40;ROP&#41; is a peripheral proliferative vitreoretinopathy that expresses in immature premature infants of as yet unknown etiopathogeny&#46; Premature babies are born with an immature retina in what concerns vascularization&#46; Through a mechanism which to date is unknown even though there is an increasing amount of information&#44; a number of metabolic events occur at the limits of the mature&#8211;immature retina which restricts the normal growth and development of vessels and causes the secondary appearance of neovessels and fibrovascular tissue that could evolve toward traction with retina detachment&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">ROP has a very important social and economic impact&#46; About 5&#37; of survivors weighing less than 1000<span class="elsevierStyleHsp" style=""></span>g are legally blind&#46; A higher percentage exhibits significant visual alterations&#46; Severe ROP is directly associated to severe neurological development disorders and&#44; in the presence of visual problems&#44; the functional evolution of these patients is worse&#44; as 77&#37; are unable to take care of themselves&#46; The severity of ROP is taken as a long-term neurological dysfunction marker<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and currently it is considered an important health problem&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">It is essential to have a diagnostic and follow-up protocol in order to ensure adequate management of ROP&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Classification of retinopathy of prematurity</span><p id="par0020" class="elsevierStylePara elsevierViewall">In order to establish a treatment protocol for ROP it is essential to determine its classification&#46; In 1984 the International ROP Classification was published and modified in 1997 to include the classification of DR&#44; cicatricial changes and sequels&#46; In 2005 it was reviewed to include standards for each parameter by means of photographs<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Each ROP case is defined according to 3 areas&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Localization</span><p id="par0030" class="elsevierStylePara elsevierViewall">The retina is divided in 3 concentric zones&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0035" class="elsevierStylePara elsevierViewall">Zone I is the innermost area centered in the papilla from which the vessels progress&#46; Its radius is twice the distance between the papilla and the macula&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0040" class="elsevierStylePara elsevierViewall">Zone II is concentric to zone I and its diameter reaches the nasal <span class="elsevierStyleItalic">ora serrata</span>&#46; Recent studies have differentiated and anterior and posterior zone II because the involvement in posterior zone I or zone II is more severe&#46; Accordingly&#44; the ROP developed in this &#8220;posterior zone&#8221; &#40;posterior zone I<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>zone II&#41; is defined as posterior ROP&#46; Clinically&#44; the limit of said posterior zone is established when looking through the lens of 2&#46;2 or 25D&#44; with the papilla being at the opposite limit of the lens&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Zone III is the temporal half moon which goes from zone II to the limits of the temporal <span class="elsevierStyleItalic">ora serrata</span>&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Circumferential&#47;clock extension</span><p id="par0050" class="elsevierStylePara elsevierViewall">The involvement must be specified in circumferential clock hours&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Evolutionary stage</span><p id="par0055" class="elsevierStylePara elsevierViewall">Five stages have been differentiated&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Stage 1 corresponds to the line separating the vascular and avascular retina&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">Stage 2 corresponds to the monticular crest&#44; with thickened separation line which becomes prominent&#46; Possibility of arteriovenous shunts and thickening of vessels posteriorly to the crest&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Stage 3 corresponds to extra-retinal vascularization&#44; with crest reddening and posterior growth of continuous or discontinuous anomalous vessels&#46; This neovascularization is derived from the posterior edge of the crest and is usually accompanied by glyal proliferation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Stage 4 corresponds to subtotal&#44; exudative or tractional retina detachment without or with involvement of the fovea &#40;4a&#44; 4b respectively&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Stage 5 corresponds to total RD&#44; subdivided in open or closed anterior and posterior tunnel&#46;</p></li></ul></p><p id="par0085" class="elsevierStylePara elsevierViewall">In addition&#44; the classification establishes the &#8220;plus disease&#8221;&#44; a sign of severity which may appear at any stage&#46; It indicates a high flow vascular short-circuit due to active arteriovenous shunts and is characterized by tortuosity and dilatation of the posterior pole vessels in at least 2 quadrants&#44; and&#47;or pupil rigidity&#46; The presence of disease plus is indicated adding a plus sign to the stage&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">There are additional concepts which must be known in ROP&#44; such as the &#8220;pre-threshold disease&#8221; and the &#8220;threshold disease&#8221;&#44; which appeared with the development of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> and the ETROP Study<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> &#40;<span class="elsevierStyleItalic">Early Treatment for ROP Randomized Trial</span>&#41;&#46; The &#8220;type I prethreshold disease&#8221; is defined as&#58; zone I&#44; any stage with disease plus&#59; zone I&#44; stage 3 without disease plus and zone II&#44; stage 2&#43; and 3&#43;&#44; and &#8220;prethreshold disease type 2&#8221; as&#58; zone I&#44; stage 1 or 2 without disease plus&#44; and zone II&#44; stage 3 without disease plus&#46; &#8220;Threshold disease&#8221; is defined as the presence in zone I or II of stage 3&#43; in 5 consecutive hours or 8 overall hours&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Finally&#44; &#8220;posterior ROP&#8221; is defined as any degree of retinopathy in the posterior zone &#40;posterior zone I and zone II&#41; in the presence of plus signs&#46;<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7&#44;8</span></a></p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Retinopathy of prematurity treatment</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Treatment criteria</span><p id="par0100" class="elsevierStylePara elsevierViewall">Treatment is considered to be necessary in the presence of&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">1&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Threshold disease&#58; 5 consecutive hours or 8 overall hours in stage 3 plus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">2&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Prethreshold disease type 1&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0115" class="elsevierStylePara elsevierViewall">Zone I&#44; any stage with disease plus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0120" class="elsevierStylePara elsevierViewall">Zone I&#44; stage 3 without disease plus&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">Zone II&#44; stage 2&#43; and 3&#43;&#46;</p></li></ul></p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Treatment methodology</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Diode laser photocoagulation</span><p id="par0130" class="elsevierStylePara elsevierViewall">At this time&#44; diode laser photocoagulation is the treatment of choice&#46; In what concerns methodology&#44; the following is applicable&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Pre-treatment guidelines</span><p id="par0135" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">1&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">The treatment must be applied within 48&#8211;72<span class="elsevierStyleHsp" style=""></span>hours after diagnosis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">2&#46;</span><p id="par0145" class="elsevierStylePara elsevierViewall">The ophthalmologist and the anesthetist must present an informed consent to the parents or legal custodians&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">3&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Pre-surgery midriasis must be achieved applying the minimum dosage to avoid the side effects of midriatics&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> achieving at the same time efficient and lasting midriasis enabling the application of laser&#46; Ideally&#44; parasympathetic blockers should be associated &#40;1&#37; tropicamide or 0&#46;5 or 1&#37; cyclopentolate&#41; with sympathomimetics &#40;phenylephrine at 2&#46;5 or 1&#37;&#41;&#46; Guidelines for midriasis may be established in each center on the basis of studies demonstrating efficacy and safety&#46;</p></li></ul></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Treatment guidelines</span><p id="par0155" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">Anesthesia can be topical&#44; sedation with gases&#44; IV sedation&#44; general anesthesia with intubation or laryngeal mask according to the criteria of each center on the basis of its experience and results&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">Anesthesia can be applied in the neonatal unit or operating theater at the choice of each hospital&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0170" class="elsevierStylePara elsevierViewall">It is recommended to maintain adequate environmental temperature and apply thermal protection to the infant&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0175" class="elsevierStylePara elsevierViewall">It can be applied through indirect ophthalmoscopy&#44; the most widely used method&#44; or transscleral by means of a retinopexy probe&#46; In the case of indirect ophthalmoscopy&#44; it is essential to be extremely careful to avoid accidental application on the macular area&#46;</p></li><li class="elsevierStyleListItem" id="lsti0105"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">The initial energy is of about 350<span class="elsevierStyleHsp" style=""></span>mW &#40;depending on the equipment and the time of use&#58; with longer time more powerful energies are required&#41;&#44; with an application time of 200<span class="elsevierStyleHsp" style=""></span>ms and repetition time of 400<span class="elsevierStyleHsp" style=""></span>ms&#44; which enables focusing on the different zones maintaining the foot on the pedal&#46; A whitish-creamy lesion must be obtained and it should be applied in nearly confluent manner throughout the avascular retina&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The final scars are broader than the impacts and this must be taken into account in posterior retinopathy to avoid scars close to the paramacular zone&#46; The entire avascular retina must be treated in a single session&#46; Partial treatment is not recommended&#46;</p></li><li class="elsevierStyleListItem" id="lsti0110"><span class="elsevierStyleLabel">-</span><p id="par0185" class="elsevierStylePara elsevierViewall">The 360&#176; of avascular retina must be treated&#44; although the meridians of II and IX may be left untreated&#46;</p></li></ul></p></span></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Post-treatment guidelines</span><p id="par0190" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0115"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">Topical anti-inflammatories can be prescribed after treatment&#46;</p></li><li class="elsevierStyleListItem" id="lsti0120"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">After the treatment&#44; the patient must be checked within 7&#8211;10 days from the first application&#46; If signs of activity and untreated areas persist&#44; these must be completed&#46;</p></li></ul></p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Cryotherapy</span><p id="par0205" class="elsevierStylePara elsevierViewall">At present&#44; cryotherapy is not the first choice of treatment and is applied in the following circumstances&#58;<ul class="elsevierStyleList" id="lis0040"><li class="elsevierStyleListItem" id="lsti0125"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">Poor midriasis or opacities making laser application impossible&#46;</p></li><li class="elsevierStyleListItem" id="lsti0130"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">As coadjuvant to laser treatment in case of persistent neovascularizations that could benefit from application of cryotherapy&#46; These cases involve high risk of bleeding and therefore application must be carried out with extreme caution&#46;</p></li><li class="elsevierStyleListItem" id="lsti0135"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Urgent cases of aggressive ROP requiring urgent treatment and laser is not available&#46;</p></li></ul></p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Pretreatment guidelines</span><p id="par0225" class="elsevierStylePara elsevierViewall">These are the same as the diode laser application guidelines&#46; An informed consent must be given to parents and pre-surgery midriasis must follow said indications&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Treatment guidelines</span><p id="par0230" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0045"><li class="elsevierStyleListItem" id="lsti0140"><span class="elsevierStyleLabel">-</span><p id="par0235" class="elsevierStylePara elsevierViewall">Treatment must be carried out in the operating room&#46;</p></li><li class="elsevierStyleListItem" id="lsti0145"><span class="elsevierStyleLabel">-</span><p id="par0240" class="elsevierStylePara elsevierViewall">It is recommended to maintain adequate temperature in the environment and apply thermal protection to the premature&#46;</p></li><li class="elsevierStyleListItem" id="lsti0150"><span class="elsevierStyleLabel">-</span><p id="par0245" class="elsevierStylePara elsevierViewall">Pediatric probes must be used&#46; The use of adult probes is contraindicated&#46;</p></li><li class="elsevierStyleListItem" id="lsti0155"><span class="elsevierStyleLabel">-</span><p id="par0250" class="elsevierStylePara elsevierViewall">General anesthesia is recommended as this is a more painful treatment and causes more cardiorespiratory instability conditions in the patient&#46;</p></li><li class="elsevierStyleListItem" id="lsti0160"><span class="elsevierStyleLabel">-</span><p id="par0255" class="elsevierStylePara elsevierViewall">It is applied with ophthalmoscopy coagulation control&#46;</p></li><li class="elsevierStyleListItem" id="lsti0165"><span class="elsevierStyleLabel">-</span><p id="par0260" class="elsevierStylePara elsevierViewall">The probe is maintained until a whitish scar is obtained&#46;</p></li><li class="elsevierStyleListItem" id="lsti0170"><span class="elsevierStyleLabel">-</span><p id="par0265" class="elsevierStylePara elsevierViewall">Defreezing must be awaited before separating the probe with great care because the sclera of prematures is very fragile&#46;</p></li><li class="elsevierStyleListItem" id="lsti0175"><span class="elsevierStyleLabel">-</span><p id="par0270" class="elsevierStylePara elsevierViewall">Care must be taken to avoid very anterior applications which could damage the ciliary body&#44; with the risk of phthisis bulbi&#46;</p></li><li class="elsevierStyleListItem" id="lsti0180"><span class="elsevierStyleLabel">-</span><p id="par0275" class="elsevierStylePara elsevierViewall">A palpebral opening could be necessary in extremely posterior applications&#46;</p></li><li class="elsevierStyleListItem" id="lsti0185"><span class="elsevierStyleLabel">-</span><p id="par0280" class="elsevierStylePara elsevierViewall">Action on extraocular muscles must be avoided&#46;</p></li><li class="elsevierStyleListItem" id="lsti0190"><span class="elsevierStyleLabel">-</span><p id="par0285" class="elsevierStylePara elsevierViewall">Intra-surgery general anti-inflammatories can be applied to diminish inflammatory reactions&#46;</p></li></ul></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Post-treatment guidelines</span><p id="par0290" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0050"><li class="elsevierStyleListItem" id="lsti0195"><span class="elsevierStyleLabel">1&#46;</span><p id="par0295" class="elsevierStylePara elsevierViewall">Post-surgery chemosis is practically the rule in the case of cryotherapy and therefore topical treatment with anti-inflammatories must be prescribed&#46; General anti-inflammatories can also be utilized according to the criterion of the ophthalmologist&#46;</p></li><li class="elsevierStyleListItem" id="lsti0200"><span class="elsevierStyleLabel">2&#46;</span><p id="par0300" class="elsevierStylePara elsevierViewall">Due to increased conjunctival manipulation&#44; it is recommended to utilize post-surgery topical antibiotic therapy as well&#46;</p></li><li class="elsevierStyleListItem" id="lsti0205"><span class="elsevierStyleLabel">3&#46;</span><p id="par0305" class="elsevierStylePara elsevierViewall">The first examination is recommended to be carried out at 24&#8211;48<span class="elsevierStyleHsp" style=""></span>hours to assess the degree of inflammation and the presence of possible complications such as vitreous hemorrhage&#44; conjunctival tears&#44; hypotony&#44; cataracts&#44; etc&#46; and prescribe the corresponding treatment&#46; Subsequently&#44; the ocular fundus must be examined within 7&#8211;10 days&#46;</p></li></ul></p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Treatment in advanced stages of the disease</span><p id="par0310" class="elsevierStylePara elsevierViewall">If conventional laser photocoagulation treatment fails and the disease progresses to stage IV or more&#44; the patient must be referred to the national reference Center for treating the advanced stages of the disease&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">At present&#44; treatment alternatives comprise&#58;<ul class="elsevierStyleList" id="lis0055"><li class="elsevierStyleListItem" id="lsti0210"><span class="elsevierStyleLabel">-</span><p id="par0320" class="elsevierStylePara elsevierViewall">Cerclage for stage 4&#46;</p></li><li class="elsevierStyleListItem" id="lsti0215"><span class="elsevierStyleLabel">-</span><p id="par0325" class="elsevierStylePara elsevierViewall">Vitrectomy with lens preservation for stage 4&#46;</p></li><li class="elsevierStyleListItem" id="lsti0220"><span class="elsevierStyleLabel">-</span><p id="par0330" class="elsevierStylePara elsevierViewall">Vitrectomy<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>lensectomy via pars plana&#46;</p></li><li class="elsevierStyleListItem" id="lsti0225"><span class="elsevierStyleLabel">-</span><p id="par0335" class="elsevierStylePara elsevierViewall">Open vitrectomy&#46;</p></li></ul></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Use of anti-vascular endothelial growth factor</span><p id="par0340" class="elsevierStylePara elsevierViewall">The use of anti-VEGF is justified in ROP for the following reasons&#58;<ul class="elsevierStyleList" id="lis0060"><li class="elsevierStyleListItem" id="lsti0230"><span class="elsevierStyleLabel">-</span><p id="par0345" class="elsevierStylePara elsevierViewall">VEGF is directly involved in the pathogeny of ROP&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;15</span></a></p></li><li class="elsevierStyleListItem" id="lsti0235"><span class="elsevierStyleLabel">-</span><p id="par0350" class="elsevierStylePara elsevierViewall">Anti-VEGF has demonstrated its efficacy in ophthalmological pathologies involving neovascularization in adults with a similar physiopathological basis &#40;ARMD with neovascular proliferation&#44; ischemic retinal venous thrombosis&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#44;17</span></a></p></li><li class="elsevierStyleListItem" id="lsti0240"><span class="elsevierStyleLabel">-</span><p id="par0355" class="elsevierStylePara elsevierViewall">In contrast with ARMD or diabetic retinopathy where the production stimuli is sustained in time&#44; in ROP there is a single VEGF release pulsation&#46;</p></li><li class="elsevierStyleListItem" id="lsti0245"><span class="elsevierStyleLabel">-</span><p id="par0360" class="elsevierStylePara elsevierViewall">The eye is an immunologically and anatomically privileged area for the application of these therapies&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p></li><li class="elsevierStyleListItem" id="lsti0250"><span class="elsevierStyleLabel">-</span><p id="par0365" class="elsevierStylePara elsevierViewall">Reports have been published on animal experiments&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p></li><li class="elsevierStyleListItem" id="lsti0255"><span class="elsevierStyleLabel">-</span><p id="par0370" class="elsevierStylePara elsevierViewall">Reports have been published on isolated cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;28</span></a></p></li><li class="elsevierStyleListItem" id="lsti0260"><span class="elsevierStyleLabel">-</span><p id="par0375" class="elsevierStylePara elsevierViewall">Clinical trials are in progress for use in prematures&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;31</span></a></p></li></ul></p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Indications for use</span><p id="par0380" class="elsevierStylePara elsevierViewall">Treatment with anti-VEGF is indicated in the following cases&#58;<ul class="elsevierStyleList" id="lis0065"><li class="elsevierStyleListItem" id="lsti0265"><span class="elsevierStyleLabel">-</span><p id="par0385" class="elsevierStylePara elsevierViewall">ROP laser treated over 360&#176; with risk of progression and threatening loss of vision&#44; if no fibrous membranes are marked&#46;</p></li><li class="elsevierStyleListItem" id="lsti0270"><span class="elsevierStyleLabel">-</span><p id="par0390" class="elsevierStylePara elsevierViewall">ROP in which laser treatments cannot be performed as first choice due to poor midriasis&#44; opacity of media or other causes&#46;</p></li><li class="elsevierStyleListItem" id="lsti0275"><span class="elsevierStyleLabel">-</span><p id="par0395" class="elsevierStylePara elsevierViewall">ROP requiring vitrectomy due to association&#46;</p></li></ul></p><p id="par0400" class="elsevierStylePara elsevierViewall">As anti-VEGF is an off-label treatment&#44; the appearance of new indications could be evaluated in due course&#44; provided there is sufficient clinical experience and positive references&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a></p><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Drug and dosage</span><p id="par0405" class="elsevierStylePara elsevierViewall">Even though several anti-VEGF agents have been approved &#40;pegaptanib &#91;Macugen<span class="elsevierStyleSup">&#174;</span>&#44; Pfizer&#93;&#44; partial VEGF blocker&#59; ranibizumab &#91;Lucentis<span class="elsevierStyleSup">&#174;</span>&#44; Novartis&#93;&#44; total blocker with monoclonal antibody fraction&#44; and bevacizumab &#91;Avastin<span class="elsevierStyleSup">&#174;</span>&#44; Roche&#93;&#44; total blocker with full monoclonal antibody&#41;&#44; bevacizumab is the most widely used and experienced drug in prematures&#46; As this is an off-label treatment&#44; special consent must be obtained for its use together with bibliographic support&#46;</p><p id="par0410" class="elsevierStylePara elsevierViewall">The dosage can vary between 0&#46;65 and 0&#46;70<span class="elsevierStyleHsp" style=""></span>mg in 0&#46;03<span class="elsevierStyleHsp" style=""></span>ml&#46;</p><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Methodology</span><p id="par0415" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0070"><li class="elsevierStyleListItem" id="lsti0280"><span class="elsevierStyleLabel">-</span><p id="par0420" class="elsevierStylePara elsevierViewall">It can be applied in the operating room or in the neonatology unit&#44; in the latter case taking extreme care in what concerns sterilization&#46;</p></li><li class="elsevierStyleListItem" id="lsti0285"><span class="elsevierStyleLabel">-</span><p id="par0425" class="elsevierStylePara elsevierViewall">It can be applied with anesthetic sedation or general anesthesia&#46;</p></li><li class="elsevierStyleListItem" id="lsti0290"><span class="elsevierStyleLabel">-</span><p id="par0430" class="elsevierStylePara elsevierViewall">Prior to surgery&#44; betadine eyedrops must be applied in 3 administrations at 10<span class="elsevierStyleHsp" style=""></span>min intervals&#44; antibiotic eye drops &#40;latest generation quinolone&#41; and 0&#46;5&#37; thimolole eyedrops&#44; as well as periocular and eyelid skin cleaning with betadine solution&#46;</p></li><li class="elsevierStyleListItem" id="lsti0295"><span class="elsevierStyleLabel">-</span><p id="par0435" class="elsevierStylePara elsevierViewall">The injection must be applied at 2&#8211;3<span class="elsevierStyleHsp" style=""></span>mm of the sclerocorneal limbus in the inferior temporal or nasal quadrant toward the location of the optic nerve&#46; After applying the injection&#44; antibiotic eye drops must be administered&#46;</p></li><li class="elsevierStyleListItem" id="lsti0300"><span class="elsevierStyleLabel">-</span><p id="par0440" class="elsevierStylePara elsevierViewall">Antibiotic and mydriatic eyedrops shall be prescribed for the post surgery period&#46;</p></li><li class="elsevierStyleListItem" id="lsti0305"><span class="elsevierStyleLabel">-</span><p id="par0445" class="elsevierStylePara elsevierViewall">24<span class="elsevierStyleHsp" style=""></span>hours after the treatment the patient must be examined for early identification of complications&#44; with special attention to the possibility of endophthalmitis&#46;</p></li><li class="elsevierStyleListItem" id="lsti0310"><span class="elsevierStyleLabel">-</span><p id="par0450" class="elsevierStylePara elsevierViewall">The ocular fundus must be examined within 7&#8211;10 days from the treatment&#46; If laser photocoagulation is not available and the visualization conditions improve laser can be applied in the avascular zone&#46;</p></li></ul></p></span></span></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conflict of interests</span><p id="par0455" class="elsevierStylePara elsevierViewall">No conflict of interests has been declared by the authors&#46;</p></span></span>"
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          "titulo" => "Classification of retinopathy of prematurity"
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          "titulo" => "Retinopathy of prematurity treatment"
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                  "titulo" => "Treatment in advanced stages of the disease"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To prepare a protocol for the treatment of retinopathy of prematurity &#40;ROP&#41; agreed by the majority of Spanish ophthalmologists dedicated to this topic&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A draft of the protocol was produced taking into account the experience of the participants and up to date publications&#46; This draft was corrected by all the ophthalmologists participating in the project&#44; and the final document was agreed by all of them&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We present general guidelines as an aid for the treatment of ROP&#44; including treatment criteria&#44; treatment methods&#44; a calendar of action&#44; and follow-up&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">It is important to have a common working protocol for the treatment of ROP to improve care and to avoid mistakes&#46; Although individual Hospitals may adapt the protocol to their daily activity&#44; it is recommended that there is a minimal working protocol agreed by most of professionals dedicated to pediatric ophthalmology in Spain&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Realizar un protocolo de tratamiento de la retinopat&#237;a del prematuro &#40;ROP&#41; consensuado por la mayor parte de oftalm&#243;logos espa&#241;oles dedicados al tema&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; un borrador del protocolo seg&#250;n la experiencia de los participantes y las publicaciones actualizadas&#46; Este borrador fue corregido por los participantes en el protocolo y se lleg&#243; al documento final consensuado por todos los participantes&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se presentan las directrices generales para realizar el tratamiento de la ROP&#44; incluyendo criterios de tratamiento&#44; metodolog&#237;a de actuaci&#243;n&#44; calendario de actuaci&#243;n y seguimiento&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Es importante disponer de un protocolo de actuaci&#243;n com&#250;n en el tratamiento de la ROP para mejorar la actuaci&#243;n y evitar errores&#46; Aunque cada centro hospitalario deba adaptar el protocolo a su actividad cl&#237;nica&#44; es recomendable que existan un m&#237;nimo de procedimientos consensuados por todos los oftalm&#243;logos dedicados a la ROP&#46;</p>"
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                0 => array:2 [
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                        0 => array:2 [
                          "etal" => false
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                            0 => "T&#46;N&#46; Fleming"
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2012.07.011

The statistics are updated each day

Year/Month	Html	Pdf	Total

2018 February	51	3	54
2018 January	32	0	32
2017 December	49	2	51
2017 November	45	3	48
2017 October	44	1	45
2017 September	42	6	48
2017 August	48	5	53
2017 July	44	3	47
2017 June	67	13	80
2017 May	100	2	102
2017 April	60	39	99
2017 March	66	12	78
2017 February	126	4	130
2017 January	52	2	54
2016 December	54	9	63
2016 November	83	9	92
2016 October	78	12	90
2016 September	76	10	86
2016 August	66	1	67
2016 July	42	2	44
2016 June	52	7	59
2016 May	61	16	77
2016 April	46	13	59
2016 March	47	9	56
2016 February	33	10	43
2016 January	35	13	48
2015 December	51	9	60
2015 November	44	4	48
2015 October	41	8	49
2015 September	27	5	32
2015 August	42	7	49
2015 July	25	2	27
2015 June	15	1	16
2015 May	21	5	26
2015 April	22	13	35
2015 March	23	9	32
2015 February	17	5	22
2015 January	30	5	35
2014 December	53	12	65
2014 November	27	6	33
2014 October	60	8	68
2014 September	58	11	69
2014 August	52	7	59
2014 July	50	6	56
2014 June	26	1	27
2014 May	44	7	51
2014 April	26	6	32
2014 March	44	5	49
2014 February	34	8	42
2014 January	34	2	36
2013 December	43	6	49
2013 November	1	3	4

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