Update on the diagnosis and treatment of choroidal hemangioma | Archivos de la Sociedad Española de Oftalmología (English Edition)

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A. OCT B-scan showing complete closure of the macular foramen with atrophy of the outer layers. B. Colour image of posterior pole of the RE showing a closed macular hole with pigment migration to the foveal region. C. OCT angiography of the RE, showing disappearance of the small hyporeflective spaces surrounding the macular hole in the inner nuclear layer and the elongated radial hyporeflective cavities that formed a stellate pattern in the outer plexiform/Henle’s fibre layer complex. C. RE en-face image." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C.M. Rangel Gualdrón, V. Galvis Ramírez, J.D. Arias Aristizabal, M. Gómez Velasco, K. Quintero Lizcano, A. Arias Gómez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "C.M." "apellidos" => "Rangel Gualdrón" ] 1 => array:2 [ "nombre" => "V." "apellidos" => "Galvis Ramírez" ] 2 => array:2 [ "nombre" => "J.D." "apellidos" => "Arias Aristizabal" ] 3 => array:2 [ "nombre" => "M." 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García Caride, J.I. Fernández-Vigo, A. Valverde-Megías" "autores" => array:3 [ 0 => array:4 [ "nombre" => "S." "apellidos" => "García Caride" "email" => array:1 [ 0 => "garca_s@hotmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.I." "apellidos" => "Fernández-Vigo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Valverde-Megías" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Departamento de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC), Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro Internacional de Oftalmología Avanzada, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización en el diagnóstico y tratamiento del hemangioma coroideo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 914 "Ancho" => 1005 "Tamanyo" => 152792 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Autofluorescence image of a circumscribed choroidal hemangioma, wide field (Optos California, Optos, Scotland), showing the low intrinsic autofluorescence (AF) of the lesion, surrounded by area of hyperautofluorescence, corresponding to subretinal fluid." ] ] ] "textoCompleto" => "IntroductionHemangioma is the most common benign vascular choroidal tumor (hamartoma). It may present clinically as an isolated, circumscribed lesion in the posterior pole (circumscribed choroidal hemangioma, CCH) or as a diffuse tumor (diffuse choroidal hemangioma, DCH) affecting a large part of the choroid, often associated with Sturge-Weber syndrome.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>EpidemiologyBeing a benign disease, the exact incidence is unknown since only symptomatic cases or incidental findings are diagnosed. Even so, it is estimated that there is one CCH case for every 15 melanomas.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Most authors point out that although it has a congenital origin,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> the average age of CCH diagnosis is between the third and fourth decades of life.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> A slight male predominance has been reported. In a recent study involving 238 patients with CCH, 60% were male, with a higher prevalence among Caucasian patients.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>In their study involving 200 consecutive cases of CCH, Shields et al. found that 5 patients also had associated cutaneous or mucous hemangiomas.<a class="elsevierStyleCrossRef" href="#bib0030">6</a> In a later study including 458 cases, the same authors reported that 33.8% of patients with CCH had systemic hypertension.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>DCH is the main manifestation of the Sturge-Weber syndrome (50%). This syndrome, also called encephalotrigeminal angiomatosis, has an incidence of 1:50,000 newborns with no difference between males and females.<a class="elsevierStyleCrossRef" href="#bib0035">7</a>HistologyHistologically, choroidal hemangioma is defined as a congenital vascular hamartoma. From a macroscopic point of view, CCH appears as a placoid or ovoid tumor, with a dark red, spongiform appearance caused by congested choroidal vessels.<a class="elsevierStyleCrossRef" href="#bib0040">8</a>From a microscopic and histopathological perspective, CCHs have been classified into 3 patterns according to the predominant vessel type inside the tumor: capillary, cavernous and mixed. The capillary type is composed of small vessels separated by loose connective tissue, the cavernous type is made up of large vessels separated by sparse connective tissue and the mixed type presents a mixture of the 2 previous types. Mixed and cavernous types are the most frequent, whereas the capillary type is considered rare.Choroidal hemangiomas displace melanocytes and choroidal lamellae towards the sclera and choriocapillaris as well as towards the tumor periphery, which histologically means that they have clearly defined boundaries. Moreover, these tumors do not exhibit any signs of cell proliferation.<a class="elsevierStyleCrossRef" href="#bib0015">3</a>Clinical presentation and diagnosisCCH is usually asymptomatic. When it presents with symptoms, it usually involves visual disturbances such as reduced visual acuity, metamorphopsia or photopsias. The underlying causes of these symptoms are the presence of subretinal fluid (SRF), macular edema, exudative retinal detachment or the affected eye's hyperopia due to the mass effect.<a class="elsevierStyleCrossRef" href="#bib0030">6</a>On ophthalmoscopic examination or retinography, CCH is visualised as a red-orange mass with blurred margins. In most cases they are unilateral lesions with a mean diameter of 7 mm, ranging from 3 to 18 mm and an average thickness of 3 mm, ranging from 1 to 7 mm (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<a class="elsevierStyleCrossRef" href="#bib0045">9</a> They are usually retro-equatorially located, generally at the macula's posterior pole, juxtapapillary, or in arcades, and do not usually grow. They may end up producing a chronic alteration in the retinal pigment epithelium (RPE) with granular deposits or signs of fibrotic metaplasia or RPE hyperplasia. In addition, intraretinal cystic degeneration may occur at the posterior pole, overlying or adjacent to the tumor.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>DCH is characterized by diffuse thickening of the choroid, with a reddish “tomato sauce” colouring of the fundus. Like CCH, the presence of DCH is often asymptomatic and its main complication is exudative retinal detachment (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<a class="elsevierStyleCrossRef" href="#bib0045">9</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>In addition to the clinical presentation, there are a number of complementary multimodal imaging tests that help guide the diagnosis of choroidal hemangioma.Fluorescein angiographyFluorescein angiography (FAG) in CCH shows in the pre-arterial and arterial phases a marked vascular network, which will give way to progressive hyperfluorescence towards the intratumoral space and subsequently to the subretinal space, forming cystic retinal spaces above the mass. This common finding in FAG only appears in one third of cases, the rest will not show fluorescence until the arterial phase. Therefore, distinguishing them from choroidal melanoma is more complicated.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>Indocianyne green angiographyIndocyanine green angiography provides very important diagnostic information. The classic characteristical pattern is a rapid contrast uptake, starting within 30 s of the onset (choroidal flash). This is due to a network of small vessels that tend to fill in from the centre of the lesion.Within 10 min, intratumoral hyperfluorescent spots may appear, corresponding to intratumoral cavernous cavities. These spots are characterised by a faster washout than the rest of the lesion.In a late phase, around 30 min, there is a reduction in central fluorescence (washout), due to the lower resistance and rapid flow of this tumor, which empties the dye faster than the surrounding choroid and has a characteristic hypofluorescent appearance.In some cases, a hyperfluorescent ring is observed despite the central hypofluorescence, due to the dye leaking into the subretinal space. This phenomenon is observed in both CCH and DCH, although considerably less in the latter (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0015"></elsevierMultimedia>AutofluorescenceChoroidal hemangiomas show low intrinsic autofluorescence. The extrinsic autofluorescence features of CCH are more striking and reveal hyperautofluorescence if there is orange pigment and overlying SRF or hypoautofluorescence if, on the contrary, there is hyperplasia of the RPE and atrophy, after resolution of chronic SRF. DCH shows similar features, but with a broader base and is usually hypoautofluorescent (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).<a class="elsevierStyleCrossRef" href="#bib0055">11</a><elsevierMultimedia ident="fig0020"></elsevierMultimedia>UltrasoundIn mode A (amplitude) the tumor shows a high sustained internal reflectivity which is key to differentiate it from choroidal melanoma, which shows low internal reflectivity. In addition, it has a regular internal structure and no significant vascularisation is observed.B-mode (brightness) shows a solid, hyperechogenic, dome-shaped lesion with no posterior shadow. B-mode ultrasound can also confirm the presence of an exudative retinal detachment and superficial calcifications (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>).<elsevierMultimedia ident="fig0025"></elsevierMultimedia>Optical coherence tomography and optical coherence tomography angiographyOptical coherence tomography (OCT) is an essential tool for both hemangioma diagnosis and follow-up, helping to understand pathological changes occurring in the choroid and the different retinal layers, and providing in vivo sections similar to those of histopathology.CCH shows a smooth, gently sloping choroidal mass on OCT. Enhanced depth imaging (EDI-OCT) images show medium and large choroidal vessel expansion without choriocapillaris compression and an intact Bruch's membrane. Observed Retinal abnormalities include SRF, lipofuscin deposit, RPE irregularity and thinning, absence or irregularity of the ellipsoid layer, absence of the outer limiting membrane, outer nuclear and plexiform layer disruption, inner nuclear layer irregularity and structural loss or edema of the inner plexiform layer.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>A new addition to the study of choroidal hemangiomas is optical coherence tomography angiography (OCTA), which is an ideal tool for the study of choroidal hemangiomas as it allows the analysis of density, flow and vascular pattern parameters of the lesions and is a non-invasive test (<a class="elsevierStyleCrossRef" href="#fig0030">Fig. 6</a>).<elsevierMultimedia ident="fig0030"></elsevierMultimedia>Recently, in images obtained by OCTA, different vascular patterns have been observed in choroidal hemangiomas. Hence, 3 differentiated patterns have been described: worm sac, spaghetti-shaped or club-shaped. For instance, these patterns are useful when establishing lesion diagnosis, as it is sometimes difficult to identify it in the fundus due to its homogeneous colouring, similar to that of the surrounding retinal parenchyma (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Another use of OCTA pattern identification in choroidal hemangiomas is to predict their activity. Thus, it has been reported that the predominance of a club-shaped vascular pattern in deep choroidal plexus is associated with more active lesions, while empty signal areas in the same deep plexus were associated with latent lesions with no activity.<a class="elsevierStyleCrossRef" href="#bib0065">13</a>Cenamo et al. followed 7 patients treated with ruthenium-106 plaque brachytherapy for one year using OCTA. Intratumoral OCTA showed a statistically significant reduction in vascular density and flow (P = .006 and .002) as well as SRF and macular edema resolution.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> In a study by Chawla et al., CCH OCTA before and after laser photocoagulation revealed laser-induced damage to the overlying choriocapillaris, showing no changes to the medium-sized vessels of the tumor itself. Therefore, this study questions the basic rationale for the use of photocoagulation to treat hemangiomas.<a class="elsevierStyleCrossRef" href="#bib0075">15</a>Nuclear magnetic resonanceMagnetic resonance imaging may be useful in the differential diagnosis of choroidal hemangiomas. The classically described pattern for choroidal hemangiomas is as follows: relative hyperintensity in respect to the vitreous for T1 images and isointensity in respect to the vitreous for T2 images, unlike amelanotic choroidal melanoma, with which it can be confused.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> However, magnetic resonance imaging has a similar drawback to computed tomography, as only tumors higher than 3 mm are clearly visible.<a class="elsevierStyleCrossRef" href="#bib0085">17</a>Differential diagnosisDespite the wide variety of imaging tests available, choroidal hemangioma diagnosis can be sometimes difficult to make. The following conditions should be kept in mind in order to distinguish them, as they are the most common diseases that could be mistaken for CCH.Amelanotic choroidal melanoma: ophthalmoscopically, amelanotic melanoma is yellowish rather than red-orange. However, the key to differentiate them is undoubtedly indocyanine green angiography and ultrasonography. Unlike choroidal hemangioma, in choroidal melanoma hyperfluorescence on indocyanine green angiography is usually late. From an ultrasound perspective, in A-scan mode the echoes are elevated in choroidal hemangioma whereas in choroidal melanoma they are usually attenuated and show the characteristic kappa angle.Choroidal metastases: these lesions take on a yellow-white hue. However, the exception to this rule is cutaneous melanoma that metastasises into the choroid, as it does not show this coloration and is usually indistinguishable from a primary choroidal melanoma. In addition, choroidal metastases can be multifocal or bilateral, whereas CCH is always single. It is also characteristic of metastases forming diffuse, small to medium-sized nodules with central excavation, with these nodules forming rosettes. The metastases implant and grow from a central point, from where they expand, being repeated at several points; this is how they form nodules (<a class="elsevierStyleCrossRef" href="#fig0035">Fig. 7</a>).<elsevierMultimedia ident="fig0035"></elsevierMultimedia>TreatmentThe aim of choroidal hemangioma treatment is to reduce their size and neutralise the vascular hyperpermeability in order to achieve subretinal fluid reabsorption and, consequently, visual acuity improvement, although chronic defects in the RPE and neurosensory retina may sometimes persist. Therefore, treatment will only be considered in symptomatic cases.Different alternatives have been proposed to achieve this objective, including diathermy,<a class="elsevierStyleCrossRefs" href="#bib0090">18,19</a> laser photocoagulation,<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> brachytherapy,<a class="elsevierStyleCrossRef" href="#bib0110">22</a> transpupillary thermotherapy, cryotherapy<a class="elsevierStyleCrossRef" href="#bib0115">23</a> and photodynamic therapy (PDT).<a class="elsevierStyleCrossRefs" href="#bib0120">24–26</a>Treatment of circumscribed choroidal hemangiomaLaser and transpupillary thermotherapyUntil the late 1990s, treatment by laser photocoagulation (argon or xenon) was the most commonly used alternative. However and mainly due to lower local side effects, nowadays this treatment has been abandoned in favour of PDT which has positioned itself as the treatment of choice for CCH.Laser treatment was indicated for small tumors, with the aim of removing subretinal fluid rather than destroying the tumor. For this purpose, bursts of 200–500 µs spot, 0.5–1.0 s long and moderately intense energy were used to produce tumor whitening.Side effects of this treatment included pigment epithelium atrophy and subsequent scotoma, which made this treatment unsuitable for subfoveal lesions. In addition, it promoted the formation of epiretinal membranes, choroidal neovascularisation and vascular occlusions.<a class="elsevierStyleCrossRefs" href="#bib0135">27,28</a>Photodynamic therapyPDT involves the use of verteporfin, a photosensitive drug which, when exposed to light, produces toxicity in the target tissue through the action of free radicals.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> The exact mechanism of action of PDT in CCH is still unknown, but it is postulated that it induces sclerosis of the choriocapillaris. Therefore, it occludes the vessels of the tumor mass and leads to a reduction in leakage. This effect is more homogeneous than the surface effect of laser photocoagulation.<a class="elsevierStyleCrossRef" href="#bib0150">30</a>The first reference to the use of PDT in choroidal tumors dates back to 1994 by Schmidt-Erfurth et al.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>Later on, in 2000, Barbazetto and Schmidt-Erfurth published 2 cases of CCH involving the posterior pole in which PDT treatment was used with standard doses of verteporfin and doubling the irradiation energy. In both cases, SRF resolution, flattening of the previous lesion and significant improvement in visual acuity were achieved.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> These 2 cases mark the beginning of what will be a new era in the treatment of CCH.Nowadays, the standard treatment consists of intravenous infusion of a verteporfin dilution at a dose of 6 mg/m2 of body surface area, in a glucose saline to a total volume of 30 ml, over a period of 10 min. Then, 15 min after the start of the infusion, an irradiation of the entire lesion with a 689 nm diode laser at an energy density of 50 J/cm2 is performed for a period of 83 s. Treatment on the optic nerve should be avoided, respecting a safety margin of one papilla diameter. A spot is usually made to include the entire tumor diameter with the addition of a 1000 µs margin.Several studies have been published comparing different PDT application techniques. Suza et al. published a study comparing the use of a single spot with 3 overlapping spots. In the case of the single spot in this study an energy of 50 J/cm2 was used for 166 s and in the case of the 3 overlapping spots an energy of 50 J/cm2 was used for 83 s. In conclusion, the authors noted that overlapping spots are indicated in large masses and are as effective and safe as a single spot.<a class="elsevierStyleCrossRef" href="#bib0165">33</a>Another variation of the technique that has been studied is the use of double the flow and duration of the PDT application in CCH. Specifically, Süsskind et al. reported a series of 27 CCH, treated with an energy of 100 J/cm2 for 166 s. This study concluded that this technique was safe and effective in the anatomical and functional recovery of the treated patients.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>Pilotto et al. performed a prospective, randomised study on 20 patients, and compared the previously mentioned standard PDT procedure with a modified treatment consisting of an injection of a verteporfin bolus (6 mg/m2) for one minute, followed by irradiation 5 min later using 100 J/cm2 for a period of 166 s. Tumor regression and visual improvement was obtained in all cases in both groups. Although alterations in the treated area of the neurosensory retina and RPE were detected in 90% of the cases treated by bolus injection and double dose irradiation, that did not occur in the group treated by the standard procedure, which were similarly associated with a reduction in retinal sensitivity measured by microperimetry in both groups.<a class="elsevierStyleCrossRef" href="#bib0175">35</a>Other authors have preferred adjusting the photosensitiser irradiation to tumor thickness, using the standard energy of 50 J/cm2 for tumors less than 3 mm thick and irradiation of 100 J/cm2 for thicker tumors, with good anatomical and functional results.<a class="elsevierStyleCrossRef" href="#bib0180">36</a>Lee et al. compared standard PDT with double-dose verteporfin (12 mg/m2) and standard irradiation with similar results, although tumor shrinkage was greater in the double-dose verteporfin treatment.<a class="elsevierStyleCrossRef" href="#bib0185">37</a>Another treatment regimen is the one described in the study by Boixadera et al., in which they propose repeat PDT in cases in which a single session does not achieve resolution of the SRF and a marked or almost complete tumor shrinkage. In their study, a periodicity of 3–5 months between sessions is established. Therefore, in their study there were patients who required 3 sessions.<a class="elsevierStyleCrossRef" href="#bib0120">24</a>However, although PDT achieves resolution of the SRF in most patients, it should be noted that in the days following its application, a transient worsening may appear along with a decrease in visual acuity, known as exudative maculopathy associated with photodynamic therapy (<a class="elsevierStyleCrossRef" href="#fig0040">Fig. 8</a>). This phenomenon has already been similarly described; it is frequent but transient after PDT in the treatment of central serous chorioretinopathy.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Ledesma et al. postulated that the cause of this increased exudation after PDT application may be the inflammatory potential on incompetent choroidal tissue.<a class="elsevierStyleCrossRef" href="#bib0195">39</a><elsevierMultimedia ident="fig0040"></elsevierMultimedia>In summary, although it is an off-label treatment and the ideal dosage is unknown, PDT CCH treatment at standard doses or with 100 J/cm2 is effective in symptomatic CCH.In terms of recurrence found after successful treatment with PDT that have achieved RSL resolution: in short-term follow-up, around 12 months, the different studies concur and show low recurrence rates, around 5% of treated patients.<a class="elsevierStyleCrossRefs" href="#bib0200">40,41</a> However, in longer follow-ups of around 36 months, the results are more variable. While some studies report low recurrence rates,<a class="elsevierStyleCrossRef" href="#bib0210">42</a> other more recent studies report recurrence rates of 35% with standard treatment guidelines.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>BrachytherapyAmong the treatments using radiotherapy, episcleral brachytherapy has been the most usually employed. The most frequently used radioactive isotopes are iodine 125 and ruthenium 106, considering the availability in each centre and the fact that 106Ru has a lower penetrance than 125I. However, 106Ru emits β radiation in a more restricted volume.<a class="elsevierStyleCrossRefs" href="#bib0220">44,45</a>Episcleral brachytherapy has proven to be an effective and safe treatment; however, due to its greater application difficulty compared to PDT, it is reserved as the first choice for exceptional cases, such as very large CCH in which PDT spots would be insufficient, CCH in which an exudative retinal detachment prevents the use of laser or recurrent CCH after PDT treatment or other techniques.Treatment of diffuse choroidal hemangiomaVarious techniques have been used for the treatment of DCH, the most popular and effective being those based on radiotherapy application: external radiotherapy, brachytherapy and stereotactic radiotherapy.External radiotherapy is the treatment of choice in this case. It results in tumor shrinkage and SRF reabsorption. However, this treatment produces retinal fibrous metaplasia, with consequent damage to the patient's visual acuity.ConclusionsChoroidal hemangioma is a benign tumor, but it can cause a significant loss in visual acuity. Currently, there is a wide range of multimodal diagnostic imaging tests that allow identifying and monitoring this tumor to establish a correct differential diagnosis. Furthermore, in recent years there has been a change in the treatment model of these lesions, which has led to a significant improvement in the visual prognosis of patients, mainly due to the use of PDT as the treatment of choice.FundingThis research has not received specific support from public or commercial sector agencies, or non-profit organizations.Conflict of interestsNo conflicts of interest were declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1897946" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1642076" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1897947" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1642077" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Histology" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Clinical presentation and diagnosis" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Fluorescein angiography" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Indocianyne green angiography" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Autofluorescence" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Ultrasound" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Optical coherence tomography and optical coherence tomography angiography" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Nuclear magnetic resonance" ] ] ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Differential diagnosis" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Treatment" ] 10 => array:3 [ "identificador" => "sec0065" "titulo" => "Treatment of circumscribed choroidal hemangioma" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Laser and transpupillary thermotherapy" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Photodynamic therapy" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Brachytherapy" ] ] ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Treatment of diffuse choroidal hemangioma" ] 12 => array:2 [ "identificador" => "sec0090" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0095" "titulo" => "Funding" ] 14 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflict of interests" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-12-31" "fechaAceptado" => "2023-02-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1642076" "palabras" => array:4 [ 0 => "Choroidal hemangioma" 1 => "Choroidal vascular tumor" 2 => "Photodynamic therapy" 3 => "Neurosensorial detachment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1642077" "palabras" => array:4 [ 0 => "Hemangioma coroideo" 1 => "Tumor vascular coroideo benigno" 2 => "Terapia fotodinámica" 3 => "Desprendimiento neurosensorial" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Choroidal hemangioma (CH) is a benign vascular tumor dependent on the choroid. Two types of lesions are distinguished: circumscribed (CCH), the most frequent variant, and diffuse (DCH), normally associated with Sturge-Weber syndrome.HCC appears as an orange mass that can present asymptomatically, however, when it produces symptoms, the most frequent is decreased visual acuity due to neurosensory retinal detachment. Due to its benign nature, only those that produce symptoms should be eligible for treatment. Knowledge of this pathology and its correct differential diagnosis is very relevant to establish the appropriate diagnosis and treatment, avoiding unnecessary treatments. There is currently a wide variety of multimodal diagnostic imaging tests that allow us to identify and adequately monitor this tumor. In addition, in recent years, there has been a change in the paradigm of the treatment of these tumors thanks to the use of photodinamic therapy, which has led to a significant improvement in the visual prognosis of these patients. This has been due to the use of photodynamic therapy as the treatment of choice for HCC." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El hemangioma coroideo (HC) es un tumor vascular benigno dependiente de la circulación coroidea. Se distinguen dos tipos de lesiones: circunscrito (HCC), variante más frecuente y difuso (HCD), asociado normalmente al síndrome de Sturge-Weber.El HCC se presenta como una masa anaranjada que puede presentarse de manera asintomática, sin embargo, cuando produce síntomas lo más frecuente es la disminución de la agudeza visual debido a un desprendimiento de retina neurosensorial. Debido a su carácter benigno sólo deberían ser subsidiarios de tratamiento aquellos que produzcan síntomas. El conocimiento de esta patología y su correcto diagnóstico diferencial es muy relevante para establecer el diagnóstico y tratamiento adecuado, evitando tratamientos innecesarios. En la actualidad existen una gran variedad de pruebas de imagen de diagnóstico multimodal que nos permiten identificar y realizar un seguimiento adecuado de este tumor. Además, en los últimos años, gracias al empleo de la terapia fotodinámica, se ha producido un cambio en el paradigma del tratamiento de estas lesiones, lo cual ha supuesto, una mejora significativa en el pronóstico visual de estos pacientes. Esto se ha debido al empleo de la terapia fotodinámica, como tratamiento de elección para el HCC." ] ] "multimedia" => array:9 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1024 "Ancho" => 1505 "Tamanyo" => 238282 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Ultra-widefield retinography (Optos California, Optos, Scotland), showing a choroidal lesion over the inferior temporal arcade with maximum transverse and longitudinal diameter measurements." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 882 "Ancho" => 1955 "Tamanyo" => 279373 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Diffuse choroidal hemangioma, showing pre-treatment images with external radiotherapy (A–C) and post-treatment images (C–E). Note the exudative retinal detachment and SRF disappearance." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 568 "Ancho" => 1505 "Tamanyo" => 120527 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Circumscribed choroidal hemangioma, retinography (A) and indocyanine green angiography (B) late phase, on the same lesion. Note the intratumoral hyperfluorescent spots on angiography corresponding to intratumoral cavernous cavities." ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 914 "Ancho" => 1005 "Tamanyo" => 152792 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Autofluorescence image of a circumscribed choroidal hemangioma, wide field (Optos California, Optos, Scotland), showing the low intrinsic autofluorescence (AF) of the lesion, surrounded by area of hyperautofluorescence, corresponding to subretinal fluid." ] ] 4 => array:8 [ "identificador" => "fig0025" "etiqueta" => "Fig. 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1167 "Ancho" => 1503 "Tamanyo" => 197803 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "B-mode ultrasound of a circumscribed choroidal hemangioma, showing a hyperechogenic dome-shaped lesion." ] ] 5 => array:8 [ "identificador" => "fig0030" "etiqueta" => "Fig. 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 647 "Ancho" => 1955 "Tamanyo" => 425586 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0030" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "OCTA image (OCT-A Plex Elite 9000 Swept-Source (Carl Zeiss Meditec, Dublin, CA, United States) of a circumscribed choroidal hemangioma, showing the deep vascular pattern that allows lesion identification." ] ] 6 => array:8 [ "identificador" => "fig0035" "etiqueta" => "Fig. 7" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr7.jpeg" "Alto" => 1401 "Ancho" => 1955 "Tamanyo" => 527583 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0035" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Set of images of a metastatic choroidal lesion representing the differential diagnosis with choroidal hemangioma. The yellow-white hue (A) and its nodular appearance observed with OCT (D) stand out." ] ] 7 => array:8 [ "identificador" => "fig0040" "etiqueta" => "Fig. 8" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr8.jpeg" "Alto" => 1505 "Ancho" => 1505 "Tamanyo" => 320112 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "OCT image acquired using OCT-A Plex Elite 9000 Swept-Source (Carl Zeiss Meditec, Dublin, CA, USA). Depicts exudative maculopathy associated with photodynamic therapy (PDT). The lesion is shown before PDT application (A), the same lesion 72 h after treatment (B), with a clear increase in the associated neurosensory detachment and, finally, the lesion is shown one month after treatment (C), with a decrease in maximum diameter and complete resolution of the associated RSL." ] ] 8 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "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">Study \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Year \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">N eyes \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Technique \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 " colspan="2" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efficiency</th></tr><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"> \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"> \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"> \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"> \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">% patients ↑ visual acuity \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="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">↓ height (mm) \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">Suza et al.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> \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">2014 \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">8 \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">Single impact spot \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">25 \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">1.5 \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"> \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">14 \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">3 overlapping impact spots \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">64.2 \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">2.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Süsskind et al.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> \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">2018 \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">27 \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">×2 flow and duration \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">56 \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Pilotto et al.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> \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">2011 \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">10 \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">Standard \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">40 \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"> \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><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">10 \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">Verteporfin bolus \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">50 \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Lee et al.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> \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">2019 \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">7 \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">Standard \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">8<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">0.4 \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"> \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">10 \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">×2 verteporfin doses \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">2<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\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">Boixadera et al.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> \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">2009 \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">31 \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">×1 standard session (n = 26) \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">22.8<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">1.6 \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"> \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><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">×2 standard sessions (n = 4) \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">9.6<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">2.3 \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"> \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><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">×3 standard sessions (n = 1) \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">0<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">1.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3172060.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "% gain in visual acuity." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of different PDT application techniques." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "RRetina" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.J. 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Update on the diagnosis and treatment of choroidal hemangioma

Actualización en el diagnóstico y tratamiento del hemangioma coroideo

S. García Caridea,

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garca_s@hotmail.com

Corresponding author.

, J.I. Fernández-Vigoa,b, A. Valverde-Megíasa

a Departamento de Oftalmología, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria (IdISSC), Madrid, Spain

b Centro Internacional de Oftalmología Avanzada, Madrid, Spain

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          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Autofluorescence image of a circumscribed choroidal hemangioma&#44; wide field &#40;Optos California&#44; Optos&#44; Scotland&#41;&#44; showing the low intrinsic autofluorescence &#40;AF&#41; of the lesion&#44; surrounded by area of hyperautofluorescence&#44; corresponding to subretinal fluid&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hemangioma is the most common benign vascular choroidal tumor &#40;hamartoma&#41;&#46; It may present clinically as an isolated&#44; circumscribed lesion in the posterior pole &#40;circumscribed choroidal hemangioma&#44; CCH&#41; or as a diffuse tumor &#40;diffuse choroidal hemangioma&#44; DCH&#41; affecting a large part of the choroid&#44; often associated with Sturge-Weber syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Epidemiology</span><p id="par0010" class="elsevierStylePara elsevierViewall">Being a benign disease&#44; the exact incidence is unknown since only symptomatic cases or incidental findings are diagnosed&#46; Even so&#44; it is estimated that there is one CCH case for every 15 melanomas&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Most authors point out that although it has a congenital origin&#44;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> the average age of CCH diagnosis is between the third and fourth decades of life&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> A slight male predominance has been reported&#46; In a recent study involving 238 patients with CCH&#44; 60&#37; were male&#44; with a higher prevalence among Caucasian patients&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In their study involving 200 consecutive cases of CCH&#44; Shields et al&#46; found that 5 patients also had associated cutaneous or mucous hemangiomas&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> In a later study including 458 cases&#44; the same authors reported that 33&#46;8&#37; of patients with CCH had systemic hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">DCH is the main manifestation of the Sturge-Weber syndrome &#40;50&#37;&#41;&#46; This syndrome&#44; also called encephalotrigeminal angiomatosis&#44; has an incidence of 1&#58;50&#44;000 newborns with no difference between males and females&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Histology</span><p id="par0030" class="elsevierStylePara elsevierViewall">Histologically&#44; choroidal hemangioma is defined as a congenital vascular hamartoma&#46; From a macroscopic point of view&#44; CCH appears as a placoid or ovoid tumor&#44; with a dark red&#44; spongiform appearance caused by congested choroidal vessels&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">From a microscopic and histopathological perspective&#44; CCHs have been classified into 3 patterns according to the predominant vessel type inside the tumor&#58; capillary&#44; cavernous and mixed&#46; The <span class="elsevierStyleItalic">capillary</span> type is composed of small vessels separated by loose connective tissue&#44; the <span class="elsevierStyleItalic">cavernous</span> type is made up of large vessels separated by sparse connective tissue and the <span class="elsevierStyleItalic">mixed</span> type presents a mixture of the 2 previous types&#46; Mixed and cavernous types are the most frequent&#44; whereas the capillary type is considered rare&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Choroidal hemangiomas displace melanocytes and choroidal lamellae towards the sclera and choriocapillaris as well as towards the tumor periphery&#44; which histologically means that they have clearly defined boundaries&#46; Moreover&#44; these tumors do not exhibit any signs of cell proliferation&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Clinical presentation and diagnosis</span><p id="par0045" class="elsevierStylePara elsevierViewall">CCH is usually asymptomatic&#46; When it presents with symptoms&#44; it usually involves visual disturbances such as reduced visual acuity&#44; metamorphopsia or photopsias&#46; The underlying causes of these symptoms are the presence of subretinal fluid &#40;SRF&#41;&#44; macular edema&#44; exudative retinal detachment or the affected eye&#39;s hyperopia due to the mass effect&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">On ophthalmoscopic examination or retinography&#44; CCH is visualised as a red-orange mass with blurred margins&#46; In most cases they are unilateral lesions with a mean diameter of 7&#8239;mm&#44; ranging from 3 to 18&#8239;mm and an average thickness of 3&#8239;mm&#44; ranging from 1 to 7&#8239;mm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> They are usually retro-equatorially located&#44; generally at the macula&#39;s posterior pole&#44; juxtapapillary&#44; or in arcades&#44; and do not usually grow&#46; They may end up producing a chronic alteration in the retinal pigment epithelium &#40;RPE&#41; with granular deposits or signs of fibrotic metaplasia or RPE hyperplasia&#46; In addition&#44; intraretinal cystic degeneration may occur at the posterior pole&#44; overlying or adjacent to the tumor&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">DCH is characterized by diffuse thickening of the choroid&#44; with a reddish &#8220;tomato sauce&#8221; colouring of the fundus&#46; Like CCH&#44; the presence of DCH is often asymptomatic and its main complication is exudative retinal detachment &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In addition to the clinical presentation&#44; there are a number of complementary multimodal imaging tests that help guide the diagnosis of choroidal hemangioma&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Fluorescein angiography</span><p id="par0065" class="elsevierStylePara elsevierViewall">Fluorescein angiography &#40;FAG&#41; in CCH shows in the pre-arterial and arterial phases a marked vascular network&#44; which will give way to progressive hyperfluorescence towards the intratumoral space and subsequently to the subretinal space&#44; forming cystic retinal spaces above the mass&#46; This common finding in FAG only appears in one third of cases&#44; the rest will not show fluorescence until the arterial phase&#46; Therefore&#44; distinguishing them from choroidal melanoma is more complicated&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Indocianyne green angiography</span><p id="par0070" class="elsevierStylePara elsevierViewall">Indocyanine green angiography provides very important diagnostic information&#46; The classic characteristical pattern is a rapid contrast uptake&#44; starting within 30&#8239;s of the onset &#40;<span class="elsevierStyleItalic">choroidal flash</span>&#41;&#46; This is due to a network of small vessels that tend to fill in from the centre of the lesion&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Within 10&#8239;min&#44; intratumoral hyperfluorescent spots may appear&#44; corresponding to intratumoral cavernous cavities&#46; These spots are characterised by a faster washout than the rest of the lesion&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In a late phase&#44; around 30&#8239;min&#44; there is a reduction in central fluorescence &#40;<span class="elsevierStyleItalic">washout</span>&#41;&#44; due to the lower resistance and rapid flow of this tumor&#44; which empties the dye faster than the surrounding choroid and has a characteristic hypofluorescent appearance&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">In some cases&#44; a hyperfluorescent ring is observed despite the central hypofluorescence&#44; due to the dye leaking into the subretinal space&#46; This phenomenon is observed in both CCH and DCH&#44; although considerably less in the latter &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Autofluorescence</span><p id="par0090" class="elsevierStylePara elsevierViewall">Choroidal hemangiomas show low intrinsic autofluorescence&#46; The extrinsic autofluorescence features of CCH are more striking and reveal hyperautofluorescence if there is orange pigment and overlying SRF or hypoautofluorescence if&#44; on the contrary&#44; there is hyperplasia of the RPE and atrophy&#44; after resolution of chronic SRF&#46; DCH shows similar features&#44; but with a broader base and is usually hypoautofluorescent &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ultrasound</span><p id="par0095" class="elsevierStylePara elsevierViewall">In mode A &#40;amplitude&#41; the tumor shows a high sustained internal reflectivity which is key to differentiate it from choroidal melanoma&#44; which shows low internal reflectivity&#46; In addition&#44; it has a regular internal structure and no significant vascularisation is observed&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">B-mode &#40;brightness&#41; shows a solid&#44; hyperechogenic&#44; dome-shaped lesion with no posterior shadow&#46; B-mode ultrasound can also confirm the presence of an exudative retinal detachment and superficial calcifications &#40;<a class="elsevierStyleCrossRef" href="#fig0025">Fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Optical coherence tomography and optical coherence tomography angiography</span><p id="par0105" class="elsevierStylePara elsevierViewall">Optical coherence tomography &#40;OCT&#41; is an essential tool for both hemangioma diagnosis and follow-up&#44; helping to understand pathological changes occurring in the choroid and the different retinal layers&#44; and providing <span class="elsevierStyleItalic">in vivo</span> sections similar to those of histopathology&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">CCH shows a smooth&#44; gently sloping choroidal mass on OCT&#46; <span class="elsevierStyleItalic">Enhanced depth imaging</span> &#40;EDI-OCT&#41; images show medium and large choroidal vessel expansion without choriocapillaris compression and an intact Bruch&#39;s membrane&#46; Observed Retinal abnormalities include SRF&#44; lipofuscin deposit&#44; RPE irregularity and thinning&#44; absence or irregularity of the ellipsoid layer&#44; absence of the outer limiting membrane&#44; outer nuclear and plexiform layer disruption&#44; inner nuclear layer irregularity and structural loss or edema of the inner plexiform layer&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">A new addition to the study of choroidal hemangiomas is optical coherence tomography angiography &#40;OCTA&#41;&#44; which is an ideal tool for the study of choroidal hemangiomas as it allows the analysis of density&#44; flow and vascular pattern parameters of the lesions and is a non-invasive test &#40;<a class="elsevierStyleCrossRef" href="#fig0030">Fig&#46; 6</a>&#41;&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">Recently&#44; in images obtained by OCTA&#44; different vascular patterns have been observed in choroidal hemangiomas&#46; Hence&#44; 3 differentiated patterns have been described&#58; worm sac&#44; spaghetti-shaped or club-shaped&#46; For instance&#44; these patterns are useful when establishing lesion diagnosis&#44; as it is sometimes difficult to identify it in the fundus due to its homogeneous colouring&#44; similar to that of the surrounding retinal parenchyma &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Another use of OCTA pattern identification in choroidal hemangiomas is to predict their activity&#46; Thus&#44; it has been reported that the predominance of a club-shaped vascular pattern in deep choroidal plexus is associated with more active lesions&#44; while empty signal areas in the same deep plexus were associated with latent lesions with no activity&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Cenamo et al&#46; followed 7 patients treated with ruthenium-106 plaque brachytherapy for one year using OCTA&#46; Intratumoral OCTA showed a statistically significant reduction in vascular density and flow &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;006 and &#46;002&#41; as well as SRF and macular edema resolution&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> In a study by Chawla et al&#46;&#44; CCH OCTA before and after laser photocoagulation revealed laser-induced damage to the overlying choriocapillaris&#44; showing no changes to the medium-sized vessels of the tumor itself&#46; Therefore&#44; this study questions the basic rationale for the use of photocoagulation to treat hemangiomas&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Nuclear magnetic resonance</span><p id="par0135" class="elsevierStylePara elsevierViewall">Magnetic resonance imaging may be useful in the differential diagnosis of choroidal hemangiomas&#46; The classically described pattern for choroidal hemangiomas is as follows&#58; relative hyperintensity in respect to the vitreous for T1 images and isointensity in respect to the vitreous for T2 images&#44; unlike amelanotic choroidal melanoma&#44; with which it can be confused&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> However&#44; magnetic resonance imaging has a similar drawback to computed tomography&#44; as only tumors higher than 3&#8239;mm are clearly visible&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Differential diagnosis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Despite the wide variety of imaging tests available&#44; choroidal hemangioma diagnosis can be sometimes difficult to make&#46; The following conditions should be kept in mind in order to distinguish them&#44; as they are the most common diseases that could be mistaken for CCH&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Amelanotic choroidal melanoma&#58;</span> ophthalmoscopically&#44; amelanotic melanoma is yellowish rather than red-orange&#46; However&#44; the key to differentiate them is undoubtedly indocyanine green angiography and ultrasonography&#46; Unlike choroidal hemangioma&#44; in choroidal melanoma hyperfluorescence on indocyanine green angiography is usually late&#46; From an ultrasound perspective&#44; in A-scan mode the echoes are elevated in choroidal hemangioma whereas in choroidal melanoma they are usually attenuated and show the characteristic kappa angle&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Choroidal metastases&#58;</span> these lesions take on a yellow-white hue&#46; However&#44; the exception to this rule is cutaneous melanoma that metastasises into the choroid&#44; as it does not show this coloration and is usually indistinguishable from a primary choroidal melanoma&#46; In addition&#44; choroidal metastases can be multifocal or bilateral&#44; whereas CCH is always single&#46; It is also characteristic of metastases forming diffuse&#44; small to medium-sized nodules with central excavation&#44; with these nodules forming rosettes&#46; The metastases implant and grow from a central point&#44; from where they expand&#44; being repeated at several points&#59; this is how they form nodules &#40;<a class="elsevierStyleCrossRef" href="#fig0035">Fig&#46; 7</a>&#41;&#46;</p><elsevierMultimedia ident="fig0035"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Treatment</span><p id="par0155" class="elsevierStylePara elsevierViewall">The aim of choroidal hemangioma treatment is to reduce their size and neutralise the vascular hyperpermeability in order to achieve subretinal fluid reabsorption and&#44; consequently&#44; visual acuity improvement&#44; although chronic defects in the RPE and neurosensory retina may sometimes persist&#46; Therefore&#44; treatment will only be considered in symptomatic cases&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Different alternatives have been proposed to achieve this objective&#44; including diathermy&#44;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#44;19</span></a> laser photocoagulation&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> brachytherapy&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> transpupillary thermotherapy&#44; cryotherapy<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and photodynamic therapy &#40;PDT&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#8211;26</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Treatment of circumscribed choroidal hemangioma</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Laser and transpupillary thermotherapy</span><p id="par0165" class="elsevierStylePara elsevierViewall">Until the late 1990s&#44; treatment by laser photocoagulation &#40;argon or xenon&#41; was the most commonly used alternative&#46; However and mainly due to lower local side effects&#44; nowadays this treatment has been abandoned in favour of PDT which has positioned itself as the treatment of choice for CCH&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Laser treatment was indicated for small tumors&#44; with the aim of removing subretinal fluid rather than destroying the tumor&#46; For this purpose&#44; bursts of 200&#8211;500&#8239;&#181;s <span class="elsevierStyleItalic">spot</span>&#44; 0&#46;5&#8211;1&#46;0&#8239;s long and moderately intense energy were used to produce tumor whitening&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Side effects of this treatment included pigment epithelium atrophy and subsequent scotoma&#44; which made this treatment unsuitable for subfoveal lesions&#46; In addition&#44; it promoted the formation of epiretinal membranes&#44; choroidal neovascularisation and vascular occlusions&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27&#44;28</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Photodynamic therapy</span><p id="par0180" class="elsevierStylePara elsevierViewall">PDT involves the use of verteporfin&#44; a photosensitive drug which&#44; when exposed to light&#44; produces toxicity in the target tissue through the action of free radicals&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> The exact mechanism of action of PDT in CCH is still unknown&#44; but it is postulated that it induces sclerosis of the choriocapillaris&#46; Therefore&#44; it occludes the vessels of the tumor mass and leads to a reduction in leakage&#46; This effect is more homogeneous than the surface effect of laser photocoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The first reference to the use of PDT in choroidal tumors dates back to 1994 by Schmidt-Erfurth et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Later on&#44; in 2000&#44; Barbazetto and Schmidt-Erfurth published 2 cases of CCH involving the posterior pole in which PDT treatment was used with standard doses of verteporfin and doubling the irradiation energy&#46; In both cases&#44; SRF resolution&#44; flattening of the previous lesion and significant improvement in visual acuity were achieved&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> These 2 cases mark the beginning of what will be a new era in the treatment of CCH&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Nowadays&#44; the standard treatment consists of intravenous infusion of a verteporfin dilution at a dose of 6&#8239;mg&#47;m<span class="elsevierStyleSup">2</span> of body surface area&#44; in a glucose saline to a total volume of 30&#8239;ml&#44; over a period of 10&#8239;min&#46; Then&#44; 15&#8239;min after the start of the infusion&#44; an irradiation of the entire lesion with a 689&#8239;nm diode laser at an energy density of 50&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> is performed for a period of 83&#8239;s&#46; Treatment on the optic nerve should be avoided&#44; respecting a safety margin of one papilla diameter&#46; A <span class="elsevierStyleItalic">spot</span> is usually made to include the entire tumor diameter with the addition of a 1000&#8239;&#181;s margin&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">Several studies have been published comparing different PDT application techniques&#46; Suza et al&#46; published a study comparing the use of a single <span class="elsevierStyleItalic">spot</span> with 3 overlapping <span class="elsevierStyleItalic">spots</span>&#46; In the case of the single <span class="elsevierStyleItalic">spot</span> in this study an energy of 50&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> was used for 166&#8239;s and in the case of the 3 overlapping spots an energy of 50&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> was used for 83&#8239;s&#46; In conclusion&#44; the authors noted that overlapping <span class="elsevierStyleItalic">spots</span> are indicated in large masses and are as effective and safe as a single spot&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">Another variation of the technique that has been studied is the use of double the flow and duration of the PDT application in CCH&#46; Specifically&#44; S&#252;sskind et al&#46; reported a series of 27 CCH&#44; treated with an energy of 100&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> for 166&#8239;s&#46; This study concluded that this technique was safe and effective in the anatomical and functional recovery of the treated patients&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">Pilotto et al&#46; performed a prospective&#44; randomised study on 20 patients&#44; and compared the previously mentioned standard PDT procedure with a modified treatment consisting of an injection of a verteporfin bolus &#40;6&#8239;mg&#47;m<span class="elsevierStyleSup">2</span>&#41; for one minute&#44; followed by irradiation 5&#8239;min later using 100&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> for a period of 166&#8239;s&#46; Tumor regression and visual improvement was obtained in all cases in both groups&#46; Although alterations in the treated area of the neurosensory retina and RPE were detected in 90&#37; of the cases treated by bolus injection and double dose irradiation&#44; that did not occur in the group treated by the standard procedure&#44; which were similarly associated with a reduction in retinal sensitivity measured by microperimetry in both groups&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Other authors have preferred adjusting the photosensitiser irradiation to tumor thickness&#44; using the standard energy of 50&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> for tumors less than 3&#8239;mm thick and irradiation of 100&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> for thicker tumors&#44; with good anatomical and functional results&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Lee et al&#46; compared standard PDT with double-dose verteporfin &#40;12&#8239;mg&#47;m<span class="elsevierStyleSup">2</span>&#41; and standard irradiation with similar results&#44; although tumor shrinkage was greater in the double-dose verteporfin treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Another treatment regimen is the one described in the study by Boixadera et al&#46;&#44; in which they propose repeat PDT in cases in which a single session does not achieve resolution of the SRF and a marked or almost complete tumor shrinkage&#46; In their study&#44; a periodicity of 3&#8211;5 months between sessions is established&#46; Therefore&#44; in their study there were patients who required 3 sessions&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">However&#44; although PDT achieves resolution of the SRF in most patients&#44; it should be noted that in the days following its application&#44; a transient worsening may appear along with a decrease in visual acuity&#44; known as exudative maculopathy associated with photodynamic therapy &#40;<a class="elsevierStyleCrossRef" href="#fig0040">Fig&#46; 8</a>&#41;&#46; This phenomenon has already been similarly described&#59; it is frequent but transient after PDT in the treatment of central serous chorioretinopathy&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Ledesma et al&#46; postulated that the cause of this increased exudation after PDT application may be the inflammatory potential on incompetent choroidal tissue&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a></p><elsevierMultimedia ident="fig0040"></elsevierMultimedia><p id="par0235" class="elsevierStylePara elsevierViewall">In summary&#44; although it is an off-label treatment and the ideal dosage is unknown&#44; PDT CCH treatment at standard doses or with 100&#8239;J&#47;cm<span class="elsevierStyleSup">2</span> is effective in symptomatic CCH&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">In terms of recurrence found after successful treatment with PDT that have achieved RSL resolution&#58; in short-term follow-up&#44; around 12 months&#44; the different studies concur and show low recurrence rates&#44; around 5&#37; of treated patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">40&#44;41</span></a> However&#44; in longer follow-ups of around 36 months&#44; the results are more variable&#46; While some studies report low recurrence rates&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> other more recent studies report recurrence rates of 35&#37; with standard treatment guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Brachytherapy</span><p id="par0245" class="elsevierStylePara elsevierViewall">Among the treatments using radiotherapy&#44; episcleral brachytherapy has been the most usually employed&#46; The most frequently used radioactive isotopes are iodine 125 and ruthenium 106&#44; considering the availability in each centre and the fact that 106Ru has a lower penetrance than 125I&#46; However&#44; 106Ru emits &#946; radiation in a more restricted volume&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44&#44;45</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Episcleral brachytherapy has proven to be an effective and safe treatment&#59; however&#44; due to its greater application difficulty compared to PDT&#44; it is reserved as the first choice for exceptional cases&#44; such as very large CCH in which PDT spots would be insufficient&#44; CCH in which an exudative retinal detachment prevents the use of laser or recurrent CCH after PDT treatment or other techniques&#46;</p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Treatment of diffuse choroidal hemangioma</span><p id="par0255" class="elsevierStylePara elsevierViewall">Various techniques have been used for the treatment of DCH&#44; the most popular and effective being those based on radiotherapy application&#58; external radiotherapy&#44; brachytherapy and stereotactic radiotherapy&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">External radiotherapy is the treatment of choice in this case&#46; It results in tumor shrinkage and SRF reabsorption&#46; However&#44; this treatment produces retinal fibrous metaplasia&#44; with consequent damage to the patient&#39;s visual acuity&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conclusions</span><p id="par0265" class="elsevierStylePara elsevierViewall">Choroidal hemangioma is a benign tumor&#44; but it can cause a significant loss in visual acuity&#46; Currently&#44; there is a wide range of multimodal diagnostic imaging tests that allow identifying and monitoring this tumor to establish a correct differential diagnosis&#46; Furthermore&#44; in recent years there has been a change in the treatment model of these lesions&#44; which has led to a significant improvement in the visual prognosis of patients&#44; mainly due to the use of PDT as the treatment of choice&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Funding</span><p id="par0270" class="elsevierStylePara elsevierViewall">This research has not received specific support from public or commercial sector agencies&#44; or non-profit organizations&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0275" class="elsevierStylePara elsevierViewall">No conflicts of interest were declared by the authors&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Choroidal hemangioma &#40;CH&#41; is a benign vascular tumor dependent on the choroid&#46; Two types of lesions are distinguished&#58; circumscribed &#40;CCH&#41;&#44; the most frequent variant&#44; and diffuse &#40;DCH&#41;&#44; normally associated with Sturge-Weber syndrome&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">HCC appears as an orange mass that can present asymptomatically&#44; however&#44; when it produces symptoms&#44; the most frequent is decreased visual acuity due to neurosensory retinal detachment&#46; Due to its benign nature&#44; only those that produce symptoms should be eligible for treatment&#46; Knowledge of this pathology and its correct differential diagnosis is very relevant to establish the appropriate diagnosis and treatment&#44; avoiding unnecessary treatments&#46; There is currently a wide variety of multimodal diagnostic imaging tests that allow us to identify and adequately monitor this tumor&#46; In addition&#44; in recent years&#44; there has been a change in the paradigm of the treatment of these tumors thanks to the use of photodinamic therapy&#44; which has led to a significant improvement in the visual prognosis of these patients&#46; This has been due to the use of photodynamic therapy as the treatment of choice for HCC&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">El hemangioma coroideo &#40;HC&#41; es un tumor vascular benigno dependiente de la circulaci&#243;n coroidea&#46; Se distinguen dos tipos de lesiones&#58; circunscrito &#40;HCC&#41;&#44; variante m&#225;s frecuente y difuso &#40;HCD&#41;&#44; asociado normalmente al s&#237;ndrome de Sturge-Weber&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">El HCC se presenta como una masa anaranjada que puede presentarse de manera asintom&#225;tica&#44; sin embargo&#44; cuando produce s&#237;ntomas lo m&#225;s frecuente es la disminuci&#243;n de la agudeza visual debido a un desprendimiento de retina neurosensorial&#46; Debido a su car&#225;cter benigno s&#243;lo deber&#237;an ser subsidiarios de tratamiento aquellos que produzcan s&#237;ntomas&#46; El conocimiento de esta patolog&#237;a y su correcto diagn&#243;stico diferencial es muy relevante para establecer el diagn&#243;stico y tratamiento adecuado&#44; evitando tratamientos innecesarios&#46; En la actualidad existen una gran variedad de pruebas de imagen de diagn&#243;stico multimodal que nos permiten identificar y realizar un seguimiento adecuado de este tumor&#46; Adem&#225;s&#44; en los &#250;ltimos a&#241;os&#44; gracias al empleo de la terapia fotodina&#769;mica&#44; se ha producido un cambio en el paradigma del tratamiento de estas lesiones&#44; lo cual ha supuesto&#44; una mejora significativa en el pron&#243;stico visual de estos pacientes&#46; Esto se ha debido al empleo de la terapia fotodin&#225;mica&#44; como tratamiento de elecci&#243;n para el HCC&#46;</p></span>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Year&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">N eyes&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Technique&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  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efficiency</th></tr><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">&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">&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">&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">&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#37; patients &#8593; visual acuity&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="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&#8595; height &#40;mm&#41;&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">Suza et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a>&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">2014&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">8&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">Single impact spot&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">25&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">1&#46;5&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">&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">14&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">3 overlapping impact spots&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">64&#46;2&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">2&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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">S&#252;sskind et al&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a>&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">2018&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">27&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">&#215;2 flow and duration&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">56&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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">Pilotto et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a>&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">2011&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">10&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">Standard&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">40&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">&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><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">10&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">Verteporfin bolus&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">50&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" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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">Lee et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a>&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">2019&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">7&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">Standard&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">8<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&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">0&#46;4&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">&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">10&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">&#215;2 verteporfin doses&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">2<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&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">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="6" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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">Boixadera et al&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&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">2009&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">31&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">&#215;1 standard session &#40;n&#8239;&#61;&#8239;26&#41;&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">22&#46;8<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&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">1&#46;6&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">&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><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">&#215;2 standard sessions &#40;n&#8239;&#61;&#8239;4&#41;&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">9&#46;6<a class="elsevierStyleCrossRef" href="#tblfn0005">&#42;</a>&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">2&#46;3&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">&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
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2023.04.006

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