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array:24 [ "pii" => "S2173579421000761" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.11.006" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1891" "copyright" => "Sociedad Española de Oftalmología" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2021;96 Supl 1:60-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0365669121000071" "issn" => "03656691" "doi" => "10.1016/j.oftal.2020.11.025" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1891" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2021;96 Supl 1:60-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Revisión</span>" "titulo" => "Alteraciones maculares en aniridia congénita" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "67" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Macular involvement in congenital aniridia" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figura 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2597 "Ancho" => 1508 "Tamanyo" => 700332 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Propuesta de subclasificación de estructuras morfológicas afectadas por OCT en hipoplasia foveal grado 3 y 4 junto con la presumible correlación en capas histológicas. (Arriba) CFH diferenciada, con un mayor número y longitud de axones de fotorreceptores, retina externa más gruesa. (Centro) CFH irregular, difusa, axones de fotorreceptores más cortos y menos numerosos. (Abajo) CFH indistinguible, retina externa más delgada. Esquema de subclasificación basado en los hallazgos de Katagiri et al.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> y Pedersen et al.<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a>. CC: cilios conectores; CFH: capa de fibras de Henle; CFNR: capa de fibras nerviosas de la retina; CGG: capa de células ganglionares; CNE: capa nuclear externa; CPE: capa plexiforme externa; CPI: capa plexiforme interna; EPR: epitelio pigmentario de la retina; MLE: membrana limitante externa; SE: capa segmentos externos; SI: capa segmentos internos; ZI: zona de interdigitación.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "P. 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OD: right eye; OS: left eye.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. Vásquez Quintero, P. Pérez-Merino, A.I. Fernández García, H. De Smet" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "Vásquez Quintero" ] 1 => array:2 [ "nombre" => "P." "apellidos" => "Pérez-Merino" ] 2 => array:2 [ "nombre" => "A.I." "apellidos" => "Fernández García" ] 3 => array:2 [ "nombre" => "H." "apellidos" => "De Smet" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669121000290" "doi" => "10.1016/j.oftal.2021.01.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669121000290?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421000785?idApp=UINPBA00004N" "url" => "/21735794/00000096000000S1/v1_202111240624/S2173579421000785/v1_202111240624/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173579421001377" "issn" => "21735794" "doi" => "10.1016/j.oftale.2020.11.011" "estado" => "S300" "fechaPublicacion" => "2021-11-01" "aid" => "1908" "copyright" => "Sociedad Española de Oftalmología" "documento" => "article" "crossmark" => 1 "subdocumento" => "rev" "cita" => "Arch Soc Esp Oftalmol. 2021;96 Supl 1:52-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Aniridic glaucoma: An update" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "52" "paginaFinal" => "59" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Actualización en glaucoma anirídico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 808 "Ancho" => 1207 "Tamanyo" => 137632 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Patient in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> after penetrating keratoplasty and repositioning of the valve tube.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "F.J. Muñoz-Negrete, M.A. Teus, J. García-Feijoó, M.I. Canut, G. Rebolleda" "autores" => array:5 [ 0 => array:2 [ "nombre" => "F.J." "apellidos" => "Muñoz-Negrete" ] 1 => array:2 [ "nombre" => "M.A." "apellidos" => "Teus" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "García-Feijoó" ] 3 => array:2 [ "nombre" => "M.I." "apellidos" => "Canut" ] 4 => array:2 [ "nombre" => "G." "apellidos" => "Rebolleda" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0365669120304287" "doi" => "10.1016/j.oftal.2020.11.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0365669120304287?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173579421001377?idApp=UINPBA00004N" "url" => "/21735794/00000096000000S1/v1_202111240624/S2173579421001377/v1_202111240624/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Review</span>" "titulo" => "Macular involvement in congenital aniridia" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "60" "paginaFinal" => "67" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P. Casas-Llera, D. Ruiz-Casas, J.L. Alió" "autores" => array:3 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Casas-Llera" "email" => array:1 [ 0 => "casasdellerapilar@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "D." "apellidos" => "Ruiz-Casas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "J.L." "apellidos" => "Alió" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Unidad de Glaucoma, Vissum Mirasierra, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Glaucoma, Fernández Casas Oftalmólogos, Torrelavega, Cantabria, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Departamento de Oftalmología, Hospital Ramón y Cajal, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Unidad de Córnea, Cataratas y Cirugía Refractiva de Vissum (Grupo Miranza), Alicante, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Departamento de Oftalmología, Patología y Cirugía, Universidad Miguel Hernández, Alicante, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Alteraciones maculares en aniridia congénita" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2597 "Ancho" => 1508 "Tamanyo" => 651424 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Proposed subclassification of morphological structures affected by OCT in grades 3 and 4 foveal hypoplasia together with the presumed correlation in histological layers. (Top) Differentiated HFL, with increased number and length of photoreceptor axons, thicker outer retina. (Centre) Irregular, diffuse HFL, shorter and fewer photoreceptor axons. (Bottom) HFL indistinguishable, thinner outer retina. Subclassification scheme based on the findings of Katagiri et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and Pedersen et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> CC: connecting cilia; HFL: Henle’s fibre layer; RNFL: retinal nerve fibre layer; GCL: ganglion cell layer; ENL: outer nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; RPE: retinal pigment epithelium; OLM: outer limiting membrane; OS: outer segments layer; IS: inner segments layer; IZ: interdigitation zone.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Congenital aniridia is a complex disease that affects not only the iris but also the cornea, iridotrabecular angle, lens, retina and optic nerve.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> This pathology is caused by heterozygous mutations of the PAX6 gene or associated regulatory regions that cause an insufficiency of the functional PAX6 protein.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Among other effects, this insufficiency produces an alteration in ocular development that will lead to a variety of anterior and posterior segment ocular malformations, the main signs of which are iris defects, nystagmus and foveal hypoplasia.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> While the absence of the iris is considered the hallmark of this pathology, foveal hypoplasia is present in 94.7%−84% of patients<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–7</span></a> and is seen even in cases with very subtle iris hypoplasia.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,4,8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Foveal hypoplasia clinic comprises a loss of foveal reflex, hypopigmentation and incursion of retinal vessels into the expected foveal avascular zone (FAZ). It is usually associated with nystagmus and low vision, and is the main cause of visual limitation in people with congenital aniridia early in life. The development of cataracts, glaucoma and corneal opacification will be responsible for progressive visual loss later in life.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Optical coherence tomography (OCT) is useful for objectively confirming the presence of foveal hypoplasia.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In addition, OCT allows stratification of hypoplasia according to the time at which foveal development has stopped, which has been shown to be a good indicator of visual function in patients with congenital aniridia.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> Macular morphological assessment in patients with congenital aniridia is highly useful, both diagnostically and prognostically for visual potential, and is of interest before indicating surgery or proposing visual rehabilitation treatment.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The aim of this review is to update knowledge on the morphological assessment of foveal hypoplasia in congenital aniridia and to summarise the macular genotype-phenotype correlations known to date. To this end, an extensive search of the automated MEDLINE database was carried out. The keywords used were: <span class="elsevierStyleItalic">aniridia, PAX6, foveal hypoplasia, optical coherence tomography</span> and <span class="elsevierStyleItalic">genotype-phenotype correlations</span>. The reference lists of retrieved articles were also manually reviewed to include additional articles that were not captured by the automated search. No restriction by publication date was used. Articles produced by this search included those published in English and Spanish.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">How does foveal arrest occur?</span><p id="par0025" class="elsevierStylePara elsevierViewall">Normal foveal development proceeds through two fundamental milestones: centrifugal displacement of inner retinal neurons and centripetal conglutination of cones and Müller glia.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,13</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The incipient fovea can be identified from gestational week 11<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> by its characteristic lamination. Macular pigment appears around gestational week 17 and is thought to direct the formation of the FAZ. The FAZ is defined by the combined effect of gradients of EphA6 and RPE-derived factor (PEDF) expression: a gradient of EphA6 that regulates the rate of astrocyte migration and a gradient of PEDF expression that has a negative control of endothelial cell proliferation in the foveal region.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">At week 25, the fovea begins to differentiate at the site of the foveal avascular zone (FAZ)<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and does so by centrifugal displacement of the inner layers, which is completed between the first and second year of life.</p><p id="par0040" class="elsevierStylePara elsevierViewall">However, the outer retina is extremely immature at birth, especially at the foveal level. The foveal cones change little in late gestation, but in the first year of life they develop into elongated cells with inner segments (IS), outer segments (OS) and long axons, becoming the longest IS and OS of the retina by four to six years of age. This sequence explains the early absence of the outer retinal bands equivalent to the photoreceptor inner ellipsoid segment band and the photoreceptor outer segment band. At about five years of age, the IS and OS segments are adult both histologically and in OCT, and the multiple outer retinal bands can be seen on OCT<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">At the same time, the cones are compressed in the fovea to a density of 10×.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,16</span></a> After birth there is a gradual thickening of the foveal band corresponding to the outer nuclear layer (ONL) and Henle’s fibre layer (HFL), attributable to central cone compression, which increases the thickness of the foveal ONL from a single layer to 10–12 times greater by six to eight years of age and adds axons to the HFL.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,15</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Role of PAX 6 in foveal development</span><p id="par0050" class="elsevierStylePara elsevierViewall">PAX6 is absolutely essential for the generation of all retinal cell types, having a specific role in maintaining the pluripotency of retinal progenitor cells.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">PAX6 mutations may affect the expression of axon guidance factors and anti-angiogenic factors in the developing foveal region.</p><p id="par0060" class="elsevierStylePara elsevierViewall">A functional insufficiency of the PAX6 protein causes abnormal development of ganglion cells. These cells, in addition to the retinal pigment epithelium (RPE), are largely responsible for expressing PEDF in the developing retina. Considering the known anti-angiogenic properties of PEDF, it is reasonable to think that the absence of this factor may play a key role in the absence of a defined FAZ.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,18</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In addition, this alteration of ganglion cell development would affect EphA6 expression. The gradient of EphA6 expression in the macula repels astrocytes, slowing their rate of migration towards the fovea and causing delayed formation of retinal vessels in the macula. The lack of this gradient would favour this migration and the absence of FAZ.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Two EphA6 ligands, ephrin A1 and A4, are expressed by astrocytes immunoreactive to PAX2 in the optic nerve and the retina.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Macular thickness in congenital aniridia</span><p id="par0070" class="elsevierStylePara elsevierViewall">Central macular thickness is greater in patients with congenital aniridia compared to healthy controls.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11,21,22</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In a study with time domain OCT, Holmstrom et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> reported in congenital aniridia an abnormally thick macula that was associated with a normal retinal profile outside this area, producing an overall flat retinal profile. This was in contrast to the findings in foveal hypoplasia in albinism where an abnormally thick macula was associated with an abnormally thin retina outside this area, giving a domed posterior pole profile. However, other authors<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,21,23</span></a> identified a domed profile also in congenital aniridia, so this retinal profile in foveal hypoplasia is not exclusive to albinism.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Subsequently, OCT automated retinal layer segmentation analysis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> showed that the nasal and temporal parafoveal and perifoveal retinal thickness is thinner than that of the central fovea at the expense of thinner inner (retinal nerve fibre layer [RNF] + ganglion cell layer [GCL] + inner plexiform layer [IPL]) and outer (ENL + IS + photoreceptor OS + RPE) layers.</p><p id="par0085" class="elsevierStylePara elsevierViewall">No association between best corrected visual acuity (BCVA) and central macular thickness has been found.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,11</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Foveal hypoplasia classification system</span><p id="par0090" class="elsevierStylePara elsevierViewall">Thomas et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> described a classification system for foveal hypoplasia based on the presence or absence of foveal depression, elongation of the photoreceptor SEs and cupulisation of the ENL at the foveal level (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). In a population of 69 patients with foveal hypoplasia said author found a statistically significant difference between best corrected visual acuity and degrees of foveal hypoplasia (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">In our own study<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> we classified foveal hypoplasia in 19 patients (31 eyes) with congenital aniridia based on the previously described classification and correlated it with best-corrected visual acuity. We were able to verify that the degree of foveal hypoplasia does indeed correlate with visual acuity, but we also found that the presence of photoreceptor OS elongation at the foveal level is a determining factor in predicting visual function (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0100" class="elsevierStylePara elsevierViewall">Gregory-Evans et al.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> also found in two patients with congenital aniridia that the thickening of the ENL at the foveal level could not be identified. These two patients can be classified as grade 4 foveal hypoplasia. The best corrected visual acuity in these patients was 0.70/0.80 and 1/1 LogMAR, congruent with the degree of foveal immaturity.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Not surprisingly, Wilk et al.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> reported that patients with albinism and more differentiated degrees of foveal hypoplasia tend to have higher maximum cone densities than patients with less developed fovea.</p><p id="par0110" class="elsevierStylePara elsevierViewall">However, the absence of foveal depression does not necessarily have a major impact on visual function.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a> Many individuals who lack foveal depression and FAZ have structures in the central outer retina compatible with normal compressed cone density and may have normal visual acuity. There are varying degrees of cone specialisation and foveal morphologies, from the presence of a domed profile to flat foveal depressions, supporting the idea that central cone specialisation can occur without the presence of a foveal depression.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">In fact, some authors<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,26</span></a> consider that the qualitative classification of isolated foveal hypoplasia may be insufficient to fully characterise foveal formation in aniridia and its relationship to visual potential in these individuals.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Katagiri et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> studied a cohort of 23 patients with foveal hypoplasia, 14 with congenital aniridia. Because all their patients had severe foveal immaturity, as they were concentrated in advanced stages of foveal hypoplasia (grades 3 and 4), they advocated that one should look for some feature between these two stages to try to further individualise this classification. To this end, they classified the eyes into three types depending on the appearance of the HFL on OCT images of the predicted fovea: those with a differentiated HFL, with almost the same appearance as normal subjects; those with a blurred, irregular HFL appearance; and those with an HFL indistinguishable from the outer nuclear layer (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Their results show that best corrected visual acuity was worse in eyes with diffuse HFL or indistinguishable HFL than in eyes with differentiated HFL and that the outer retinal thickness (OPL + HFL + ENL) was thinner in eyes without HFL than in those with differentiated HFL. However, it should be noted that, in OCT evaluation of the outer retina, it is difficult to differentiate FHC from ENL. The HFL is hyporeflective on OCT and is not clearly distinguishable from the ENL, there must necessarily be optical contrast for this layer to be visualised. This optical contrast can be achieved by directing the entrance angle of the OCT beam, which alters the reflectivity of this layer relative to ENL<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,27</span></a> (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">Pedersen et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> agree with Katagiri et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> in that the thickness of the outer retinal layers is significantly thinner in aniridia, particularly in the centre of the fovea compared to healthy controls. Furthermore, they found a strong negative correlation between the thickness of the outer retinal layers at the foveal level and high-contrast logMAR visual acuity, being the strongest predictor of high-contrast logMAR visual acuity in patients with aniridia-associated keratopathy grade 2 or lower. When assessing outer retinal thickness in aniridia, they considered HFL-ENL as a single layer. In addition, in some patients they found it difficult to distinguish the reflectivity of the bands corresponding to the zone of interdigitation of photoreceptor OS-RPE and/or the outer limiting membrane, no doubt because the appearance of multiple bands in the outer retina is closely related to the morphological development of the photoreceptors and, in particular, to the elongation of the IS and OS of the foveal cones.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,15</span></a> Therefore, they used a combined measurement of ENL, IS and OS of photoreceptors and RPE to provide a more robust measure of the outer retinal layers.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Analysis of foveal morphology by OCT is therefore a valuable tool to include in the diagnostic and therapeutic management of a person with congenital aniridia. It provides very useful information to be taken into account before considering corneal or cataract surgery or proposing visual rehabilitation treatment for patients of susceptible ages.</p><p id="par0135" class="elsevierStylePara elsevierViewall">However, the fact that maturation of the outer retina is not complete until five to six years of age<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,15</span></a> should prompt us to use these classifications and make visual prognoses with caution in children under six years of age.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Genotype-phenotype correlation</span><p id="par0140" class="elsevierStylePara elsevierViewall">85%–95% of patients with congenital aniridia carry mutations affecting the coding region of PAX6, either heterozygous point mutations (50%) or microdeletions (30%) which may be of the entire PAX6 gene or of PAX6 together with contiguous genes.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Heterozygous point mutations PAX6</span><p id="par0145" class="elsevierStylePara elsevierViewall">Most heterozygous PAX6 mutations are truncated variants, which introduce a premature stop codon (PTC), resulting in haploinsufficiency due to nonsense-mediated decay <span class="elsevierStyleItalic">of</span> messenger RNA. A single allele is not sufficient to produce the biologically active protein and causes a severe phenotype. Indeed, grades 3 and 4 foveal hypoplasias have been identified in patients with mutations introducing PTC.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">Other heterozygous point mutations introduce c-terminal extensions (CTE): they change the c-terminal stop codon and result in an abnormally extended protein. They have been associated with complete foveal hypoplasia, thinning of the outer layers and short axial length, with profound visual impairment.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> In addition, these types of mutations have also been associated with high myopia and macular chorioretinal atrophy.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,28</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Finally, the third type of point mutations are missense variants, which change one amino acid for another, producing abnormal proteins that can fold and function abnormally. These mutations are particularly difficult to predict as it will depend on the function of the mutant protein. In more than 50% they give rise to atypical phenotypes ranging from mild iridian defects to more severe phenotypes, including optic nerve malformations.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> In a cohort of 43 patients with PAX6 mutations, foveal hypoplasia was present in 84% of patients with congenital aniridia. However, foveal hypoplasia was identified in only 33% of patients with congenital aniridia and missense mutations.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Microdeletions affecting PAX6</span><p id="par0160" class="elsevierStylePara elsevierViewall">Microdeletions on 11p13 affecting the PAX6 gene may do so exclusively or together with adjacent genes. Deletions including PAX6 and other neighbouring genes do not change the clinical expression of the disease in relation to the mutation limited to PAX6. Such deletions are associated with a severe phenotype.</p><p id="par0165" class="elsevierStylePara elsevierViewall">However, cases of large PAX6 deletions where the retina-specific enhancer has been removed from the regulatory region have been associated with milder foveal hypoplasias.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Mutations in non-coding regions</span><p id="par0170" class="elsevierStylePara elsevierViewall">Approximately 5%–15% of patients with aniridia, however, will carry mutations in non-coding regions, either point mutations in non-coding regions or microdeletions on 11p13 affecting only cis-regulatory elements (preserving the PAX6 coding sequence).<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,6</span></a> The quantitative and spatial-temporal expression of PAX6 must be finely controlled during embyogenesis. It is mediated by a cis-regulatory domain comprising a large number of tissue-specific regulators, most of them distributed over hundreds of kilobases between the neighbouring genes RCN1 and ELP4.</p><p id="par0175" class="elsevierStylePara elsevierViewall">The best developed retinas have been associated<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> with mutations upstream of the translational start codon (PAX6 5′ UTR), deletions that exclusively include the 3′ regulatory region (ELP4-DCDC1) and large deletions of PAX6 where the retina-specific enhancer has been removed from the regulatory region.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Other macular disorders in congenital aniridia</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Myopic macular chorioretinal atrophy</span><p id="par0180" class="elsevierStylePara elsevierViewall">In several genotype-phenotype correlation studies in families with congenital aniridia, families with a high frequency of high myopia or extreme myopia have been reported, including cases of chorioretinal atrophy consistent with degenerative myopia.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,6,28</span></a> Interestingly, the families had CTE mutations.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,28</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Regarding the role of PAX6 in the development of myopia unrelated to congenital aniridia, other studies, including a meta-analysis of association studies, indicated that PAX6 is a susceptibility gene for high and/or extreme myopia; however, its effect is small as myopia is a complex disease resulting from the interaction of multiple genetic and environmental factors, and usually develops after birth.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Coats-like exudative retinopathy</span><p id="par0190" class="elsevierStylePara elsevierViewall">Hingorani et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> described two patients with congenital aniridia and unilateral exudative retinopathy. Both patients had CTE mutations. The frequency of this pathology in patients with aniridia and whether it is limited to patients with CTE mutations is not known at this time. It is possible that it has been underdetected because it may develop when retinal visualisation is compromised by other complications such as corneal abnormalities or cataracts.</p><p id="par0195" class="elsevierStylePara elsevierViewall">Proteins derived by CTE mutations would have an effect on the expression of the transcription factor PAX2 that directs astrocyte network migration and consequently alter retinal angiogenesis.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,20</span></a></p></span></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0200" class="elsevierStylePara elsevierViewall">The analysis of foveal morphology by OCT is a very useful prognostic tool for the visual potential of a person with aniridia. It provides valuable information before surgery is indicated or optical visual rehabilitation is proposed. A foveal morphology in which outer retinal structures can be identified, with elongation of the photoreceptor outer segments and increased retinal thickness, is associated with a better visual prognosis, whether or not a foveal depression is identified. This analysis can be performed once the outer retina has been able to complete its development, from the age of six years onwards.</p><p id="par0205" class="elsevierStylePara elsevierViewall">Mutations introducing a PTC, CTE or deletions involving PAX6 have been associated with reduced foveal differentiation. Better developed foveae have been associated with mutations in non-coding regions of PAX6.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Funding</span><p id="par0210" class="elsevierStylePara elsevierViewall">This study has been partly funded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Thematic Network for Cooperative Health Research</span> “OFTARED” — Reference: RD16/0008/0012. Funded by the <span class="elsevierStyleGrantSponsor" id="gs0010">Instituto de Salud Carlos III</span>/<span class="elsevierStyleGrantSponsor" id="gs0015">National Research Agency</span> and by the <span class="elsevierStyleGrantSponsor" id="gs0020">European Regional Development Fund</span> (ERDF) “A way of doing Europe”.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflict of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">No conflict of interest was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1614996" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1443672" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1614995" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1443671" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:9 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "How does foveal arrest occur?" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Role of PAX 6 in foveal development" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Macular thickness in congenital aniridia" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Foveal hypoplasia classification system" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Genotype-phenotype correlation" ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Heterozygous point mutations PAX6" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Microdeletions affecting PAX6" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Mutations in non-coding regions" ] 8 => array:3 [ "identificador" => "sec0050" "titulo" => "Other macular disorders in congenital aniridia" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Myopic macular chorioretinal atrophy" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Coats-like exudative retinopathy" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0065" "titulo" => "Conclusion" ] 6 => array:2 [ "identificador" => "sec0070" "titulo" => "Funding" ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-10-27" "fechaAceptado" => "2020-11-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1443672" "palabras" => array:5 [ 0 => "Congenital aniridia" 1 => "PAX6" 2 => "Optical coherence tomography" 3 => "Foveal hypoplasia" 4 => "Genotype-phenotype correlations" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1443671" "palabras" => array:5 [ 0 => "Aniridia congénita" 1 => "PAX6" 2 => "Tomografía de coherencia óptica" 3 => "Hipoplasia foveal" 4 => "Correlación genotipo-fenotipo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">This review updates the knowledge about the morphological assessment of the foveal hypoplasia in congenital aniridia and resumes the reported genotype-phenotype correlations known to date.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Congenital aniridia is a pan ocular disease. Although iris absence is considered the hallmark of this entity, foveal hypoplasia is present in 94.7%–84% of patients. A foveal morphology assessed by optical coherence tomography in which external retina structures can be identified, with presence of the lengthening of photoreceptors outer segment and a greater external retinal thickness, is associated with a better visual outcome, regardless a foveal pit is identified or not. This analysis can be performed once the external retina has completed its differentiation, by 6 years old.</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PAX6 mutations that introduce premature termination codon, C terminal extension or PAX6 involving deletions have been related to lesser foveal differentiation. Better foveal differentiation has been associated to non-coding PAX6 mutations.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">En esta revisión se realiza una actualización de los conocimientos sobre la evaluación morfológica de la hipoplasia foveal en aniridia congénita y una síntesis de las correlaciones genotipo-fenotipo macular conocidas hasta el momento.</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La aniridia congénita es una enfermedad panocular en la que, aunque la ausencia del iris se considere el sello distintivo, se identifica una la hipoplasia foveal en el 94,7–84% de los casos. Una morfología foveal analizada mediante tomografía de coherencia óptica en la que puedan identificarse las estructuras de la retina externa, con elongamiento de los segmentos externos de los fotorreceptores y con un mayor grosor de la misma, está asociada a un mejor pronóstico visual, independientemente de que se identifique o no una depresión foveal. Este análisis puede ser realizado una vez la retina externa ha podido completar su desarrollo, a partir de los seis años de edad.</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Las mutaciones que introducen un codón de parada prematuro, extensión C terminal o deleciones que comprometen al PAX6 se han asociado a una menor diferenciación foveal. Las fóveas mejor desarrolladas han sido asociadas a mutaciones en regiones no codificantes del PAX6.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Casas-Llera P, Ruiz-Casas D, Alió JL. Alteraciones maculares en aniridia congénita. Arch Soc Esp Oftalmol. 2021;96(S1):60–67.</p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 663 "Ancho" => 2341 "Tamanyo" => 183078 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Schematic of morphological structures identified by optical coherence tomography in the normal fovea. CC: connecting cilia; RNFL: retinal nerve fibre layer; GCL: ganglion cell layer; ENL: outer nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; RPE: retinal pigment epithelium; OLM: outer limiting membrane; OS: outer segment layer; IS: inner segment layer; IZ: interdigitation zone.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1915 "Ancho" => 2508 "Tamanyo" => 557353 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Diagram of foveal morphological structures identified by optical coherence tomography according to the classification system for foveal hypoplasia described by Thomas et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> ENL: outer nuclear layer; OS: outer segments.</p>" ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2597 "Ancho" => 1508 "Tamanyo" => 651424 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Proposed subclassification of morphological structures affected by OCT in grades 3 and 4 foveal hypoplasia together with the presumed correlation in histological layers. (Top) Differentiated HFL, with increased number and length of photoreceptor axons, thicker outer retina. (Centre) Irregular, diffuse HFL, shorter and fewer photoreceptor axons. (Bottom) HFL indistinguishable, thinner outer retina. Subclassification scheme based on the findings of Katagiri et al.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and Pedersen et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> CC: connecting cilia; HFL: Henle’s fibre layer; RNFL: retinal nerve fibre layer; GCL: ganglion cell layer; ENL: outer nuclear layer; OPL: outer plexiform layer; IPL: inner plexiform layer; RPE: retinal pigment epithelium; OLM: outer limiting membrane; OS: outer segments layer; IS: inner segments layer; IZ: interdigitation zone.</p>" ] ] 3 => array:8 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2590 "Ancho" => 2508 "Tamanyo" => 879507 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">OCT image of grades 2, 3 and 4 foveal hypoplasia in congenital aniridia. (Upper) Grade 2 hypoplasia. Absence of excavation of inner layers and absence of foveal depression but presence of residual elongation of photoreceptor outer segments and cupulisation of ENL. (Middle) Foveal hypoplasia grade 3. Absence of extrusion of inner layers, absence of foveal depression and elongation of photoreceptor OS, only presence of INL cupulisation. (Lower) Foveal hypoplasia grade 4, none of the foveal morphological findings occur. (Authors’ figure, previously published in Casas-Llera et al.,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> reproduced with express permission of SAGE Publishing).</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">RNFL: retinal nerve fibre layer; GCL: ganglion cell layer; IPL: inner plexiform layer; INL: inner nuclear layer; OPL: outer plexiform layer; INL: inner nuclear layer; OLM: outer limiting membrane; IS: inner segment layer; CC: connecting cilia; OS: outer segment layer; RPE: retinal pigment epithelium.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0025" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "fx1.jpeg" "imagenAlto" => 1683 "imagenAncho" => 2508 "imagenTamanyo" => 289663 ] ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Central macular thickness values and degree of correlation between foveal hypoplasia and best corrected visual acuity reported in patients with congenital aniridia.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ocular and nonocular findings in patients with aniridia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. 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