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Choroidal neovascularisation associated with optic nerve head drusen: Case report and review of literature
Neovascularización coroidea asociada a drusas del nervio óptico: caso clínico y revisión de la literatura
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Castro-Rebollo, J. González Martin-Moro, I. Lozano Escobar" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Castro-Rebollo" "email" => array:1 [ 0 => "mariarebollo@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "González Martin-Moro" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Lozano Escobar" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Hospital Universitario del Henares, Coslada, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad Francisco de Vitoria, Pozuelo de Alarcón, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Neovascularización coroidea asociada a drusas del nervio óptico: caso clínico y revisión de la literatura" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1723 "Ancho" => 1305 "Tamanyo" => 183514 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) RE OCT showing active CNV (age 21). (B) RE fundus showing CNV (age 21).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Optic nerve head drusen (ONHD) are acellular deposits with intra-and extra-cellular location. ONHD were first described by Müller in 1858. Their size varies between 5 and 1000<span class="elsevierStyleHsp" style=""></span>μm diameter and are located in front of the <span class="elsevierStyleItalic">cribrosa plate</span>. They contain amino acids, nucleic acids, iron and calcium and their prevalence is of 0.5–2.4% in adults. The pathogenesis of ONHD is unknown although 3 theories have been proposed to explain their formation: as a consequence of alteration in axonal metabolism with diminished axoplasmic flow; optic nerve dysplasia with a tendency to the formation of drusen, or the presence of a small scleral channel that physically compresses axons, causing the death of ganglion cells with extrusion and calcification of the mitochondria. ONHD are generally bilateral and asymmetric with a preference for the female sex. Their origin is mainly idiopathic although some have a dominant inheritance pattern.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Patients with ONHD exhibit a higher incidence of ocular vascular anomalies such as the presence of cilioretinal arteries, acute tortuosity, abnormal bifurcations, retina choroidal collaterals, hemorrhages, peripapillary neovascularisation, anterior ischemic optic neuropathy and occlusive vascular venous and arterial disease.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> A clinic case is presented evidencing that the nature of ONHD is not always benign and can be associated to vascular complications.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinic case</span><p id="par0010" class="elsevierStylePara elsevierViewall">Male patient in follow-up in the authors’ Dept. since age 16 for ONHD. History comprised non-artheritic anterior ischemic optic neuropathy (NAAION) in both eyes (BE) since age 12, followed up in another center. Snellen visual acuity (VA) was 0.4 in BE and intraocular pressure (IOP) was 14<span class="elsevierStyleHsp" style=""></span>mmHg in BE. Biomicroscopy (BMC) was normal and ocular fundus (OF) exhibited raised and asymmetrical papilla with rounded and yellowish lumps (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Visual field (<span class="elsevierStyleSmallCaps">VF</span>) 24–2 Humphrey showed deeper defects in BE (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B) and optic nerve optical coherence tomography (OCT) revealed drusen. In a routine checkup at age 21 it was observed that the VA was 0.3 in BE, BMC was normal and OF temporal to the papilla under the papillomacular bundle of the right eye (RE) exhibited a grayish lesion of 1 papilla diameter, confirmed as choroidal neovascularisation (CNV) with OCT (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>A and B) and fluorescein angiography. The patient was treated with one dose of intravitreal ranibizumab (0.5<span class="elsevierStyleHsp" style=""></span>mg/0.05<span class="elsevierStyleHsp" style=""></span>ml, Lucentis<span class="elsevierStyleSup">®</span>) and one dose of intravitreal bevacizumab (1.25<span class="elsevierStyleHsp" style=""></span>mg/0.05<span class="elsevierStyleHsp" style=""></span>ml, Avastin<span class="elsevierStyleSup">®</span>) at a 2-month interval. Six months after the second injection, MNV fibrosis was confirmed with OCT, having a VA of 0.15 in the RE and 0.3 in the LE. The rest of the examination did not produce changes (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>A–C). Three years after said intravitreal treatment, the patient remains stable. VA has not changed and ONHD exhibits a similar appearance, with fibrosis in the area occupied by CNV.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0015" class="elsevierStylePara elsevierViewall">In the majority of cases, ONHD are a casual finding in OF examinations without patients exhibiting clinic related to that disease. In children, ONHD is a frequent cause of pseudo-papiledema that requires adequate differential diagnostic with other central nervous system diseases such as tumors or intracranial hypertension to avoid exposing patients to unnecessary tests.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> During childhood, drusen are usually buried but with the passage of time their size increases, becoming more superficial and calcified. For this reason they are extruded and become visible enabling easy diagnostic with autofluorescence or echography.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The most frequent defect in the VF is diminished sensitivity in the inferior nasal quadrants although blind spot increases have also been described as well as concentric constriction or arc-shaped defects that can simulate chronic glaucoma.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> The present patient exhibited bilateral inferior arc-shaped lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B) due to the NAAION that occurred a few years before. It has been described that VA is rarely affected by ONHD, which did not occur in the present patient who exhibited several described complications associated to AION.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> These complications include scotoma in VF, hemorrhages, NAAION, vascular occlusions and CNV. Classically, choroidal neovascularisation has been regarded as an infrequent complication. However, a recently published retrospective series found this complication in 24 out of 98 eyes with ONHD.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The incidence of CNV in patients with ONHD is unknown but it is believed that it is more frequent in children.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Typically it is located in the peripapillary region and courses with good VA. However, in some occasions (as in the present patient) neovascularisation or subretinal fluid could extend to the macula and impair VA.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The pathogeny of neovascularisation is not yet fully understood. It has been proposed that, in their growth, ONHD could erode vessels or produce venous congestion in the ciliary retinal venous communicating vessels. It could also be explained due to the release of growth factors secondary to ischemia produced by the increased size thereof.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">It is difficult to determine the best technique for diagnosing ONHD in children. Ocular echography continues to be the technique of choice due to low cost and high sensitivity to detect calcifications, with the drawback that in children these are not visible because in many cases they are not yet calcified.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> ONHD also exhibits autofluorescence, although this diagnostic method comprises an important limitation in that it can only evidence extruded ONHDs. Accordingly, both techniques have limited usefulness in children because in many cases their ONHDs are not yet extruded or calcified.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In case of doubt or to discard a genuine papilla edema secondary to a cerebral process, it could be indicated to request computerized axial tomography (CAT) of the brain, although this technique is more expensive and involves the use of ionizing radiation. OCT could also be useful because with this technique ONHDs are displayed as a hypo-reflective mass posterior to the plexiform and outer nuclear layers with absence of bonds to the photoreceptor inner-outer segments. Improved resolution and penetration capacity of OCT has produced an increased sensitivity to detect ONHD. Some authors have demonstrated that the <span class="elsevierStyleItalic">Enhanced Depth Imaging</span> (EDI) technology is more sensitive than echography to identify ONHD. In addition, it enables their visualization and size assessment. With this technology, ONHD appeared as hypo-reflective oval-shaped structures surrounded by a hypo-reflective margin, in front of the cribrosa Plate.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">According to Noval et al, when analyzing the retinal nerve fiber layer (RNFL), thickness increase is bigger in the nasal quadrant, which is consistent with the more frequent VF defect and, as with other optic neuropathies, macular ganglion cell analysis would show early thinning in the case of buried ONHD.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">4</span></a> In what concerns treatment of MNVSR associated to ONHD, several methods have been applied in the past including laser photocoagulation, photodynamic therapy or macular surgery.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">6–9</span></a> Since 2012, anti-VEGF therapy is successfully applied. In the present patient, the membrane exhibited fibrosis after administering only 2 doses of anti-VEGF. Due to the infrequent nature of this entity and the absence of randomized clinical trials, it is impossible to determine whether the injection of said medicaments actually improved the prognosis of this form of choroidal neovascularisation, or if said membranes demonstrated spontaneous evolution toward cicatrization.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conclusion</span><p id="par0050" class="elsevierStylePara elsevierViewall">CNV associated to ONHD is an infrequent complication although recently the literature seems to indicate that it is more common than we thought.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Prognostic is better than in other forms of subretinal neovascularisation. Response to the intravitreal administration of anti-VEGF drugs is good. In the majority of cases it is possible to achieve CNV deactivation with one or 2 doses, as reported by published cases.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">2,3,8</span></a> However, additional studies are needed to demonstrate that said medicaments actually modify the final prognosis.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conflict of interests</span><p id="par0055" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1157264" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1084480" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1157265" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1084481" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-04-20" "fechaAceptado" => "2018-07-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1084480" "palabras" => array:4 [ 0 => "Choroidal neovascularisation" 1 => "Optic nerve drusen" 2 => "Bevacizumab" 3 => "Ranibizumab" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1084481" "palabras" => array:4 [ 0 => "Neovascularización coroidea" 1 => "Drusas del nervio óptico" 2 => "Bevacizumab" 3 => "Ranibizumab" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A 21-year-old man was seen for follow-up of optic nerve head drusen (ONHD) in the ophthalmology department. Funduscopy revealed the presence of choroidal neovascularisation (CNV) in the papillomacular bundle of his right eye (RE). The patient was successfully treated with two intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF). Peri-papillary choroidal neovascularisation in papillomacular bundle is a rare complication in patients with ONHD. These forms of CNV show a good response to anti-VEGF treatment.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Varón de 21 años en seguimiento en el servicio de oftalmología por drusas del nervio óptico (DNO). En una revisión rutinaria se evidenció la presencia de neovascularización coroidea (NVC) bajo el haz papilomacular en el ojo derecho (OD). El paciente fue tratado con 2 inyecciones intravítreas de anti-vascular <span class="elsevierStyleItalic">endothelial growth factor</span> (anti-VEGF, por sus siglas en inglés) con buena respuesta. La aparición de NVC en el haz papilomacular es una complicación infrecuente en los pacientes con DNO. Estas NVC presentan una buena respuesta al tratamiento con inyecciones intravítreas de anti-VEGF.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Castro-Rebollo M, González Martin-Moro J, Lozano Escobar I. Neovascularización coroidea asociada a drusas del nervio óptico: caso clínico y revisión de la literatura. Arch Soc Esp Oftalmol. 2019;94:149–152.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1493 "Ancho" => 2086 "Tamanyo" => 231146 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">(A) Ocular fundus at the first exploration in the authors’ center (age 16) showing extruded ONHD in BE. (B) RE visual field with concentric defect. LE exhibited inferior arc-shaped defect.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1723 "Ancho" => 1305 "Tamanyo" => 183514 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">(A) RE OCT showing active CNV (age 21). (B) RE fundus showing CNV (age 21).</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 373 "Ancho" => 1505 "Tamanyo" => 74661 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">(A) RE OCT showing CNV 6 months post-treatment. 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