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Acute annular outer retinopathy associated with human immunodeficiency virus
Retinopatía anular externa aguda asociada al virus de la inmunodeficiencia humana
Servicio de Oftalmología, Sección de Retina, Fundación Jiménez Díaz, Madrid, Spain
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(a) Retinography: clinical appearance of mushroom-shaped melanoma (red arrow). (b) Ultrasound of mushroom-shaped melanoma: Bruch's membrane rupture and fungiform appearance of MM (red arrow), retinal detachment (blue arrow). (c) T2 MRI coronal plane: mushroom-shaped melanoma (red arrow).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. García Tirado, M. Asencio Durán, J. Peralta Calvo, A. Berjón, E. Ruiz Bravo-Burguillos" "autores" => array:5 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "García Tirado" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Asencio Durán" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Peralta Calvo" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Berjón" ] 4 => array:2 [ "nombre" => "E." 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García-Torre, R. Castro-Flórez" "autores" => array:2 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "García-Torre" "email" => array:1 [ 0 => "mergato@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "R." "apellidos" => "Castro-Flórez" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Oftalmología, Sección de Retina, Fundación Jiménez Díaz, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Retinopatía anular externa aguda asociada al virus de la inmunodeficiencia humana" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2574 "Ancho" => 3333 "Tamanyo" => 566002 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">(a) Retinographs: one month after diagnostic the ring has disappeared and 3 years later it exhibits a patched alteration of the peripapillary RPE. (b) Autofluorescence: without alterations one month after diagnostic and with areas of patched hyper- and hypofluorescence 3 years after diagnostic in the peripapillary zone outside of the arches. (c) Fluorescein angiography: slight hyperfluorescence in the zones comprised within the ring. (d) OCT with loss of outer layers, respecting the macular area and mfERG with persistence of electroretinographic alterations. (e) VF: generalized sensitivity loss respecting the macula.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute annular outer retinopathy (AAOR) was first described by Gass and Stern<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> in 1995 as a variant of acute zonal occult outer retinopathy [AZOOR]). This is a rare pathology of unknown etiology. Classic presentation is characterized by the presence of photopsia, scotoma and electroretinographic alterations, all of which are accompanied by a characteristic retinal whitish ring concentric to the papilla and located in the deep layers of the retina. Typically it affects young adults, more frequently females, and presents unilaterally. It is rarely associated to systemic symptoms.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A case of AAOR is presented in which, in the course of the study, positive result for the human immunodeficiency virus (HIV) was found. It is the first case describing association between both entities.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Clinic case report</span><p id="par0015" class="elsevierStylePara elsevierViewall">Male patient, 41, who visited the Emergency Dept. with a history of central scotoma with photopsia in the left eye (LE) with 15 days evolution. Relevant personal history included secondary syphilis treated 5 years earlier. No familial or personal history of self-immune disease. Ophthalmological examination with slit lamp and ocular fundus (OF) gave normal results, with a visual acuity (VA) of 1.0 in both eyes (BE).</p><p id="par0020" class="elsevierStylePara elsevierViewall">The patient was examined at the Retina practice 5 days later. VA was still 1.0 in BE although the left OF showed a white-grayish ring located in the deep retina centered around the papilla. The retina within the ring exhibited a whitish color. Vitritis was not observed.</p><p id="par0025" class="elsevierStylePara elsevierViewall">LE fluorescein angiography evidenced a discrete window defect in the inner ring area, while autofluorescence showed a slight diffuse hyperautofluorescence in the same area. Optical coherence tomography (OCT) showed perimacular loss of external retinal layers respecting the fovea in the LE (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">The visual field (VF) showed parapapillary absolute scotoma while multifocal electroretinogram (mfERG) showed depressed macular function (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">On the basis of the above results, the acute annular outer retinopathy (AAOR) diagnostic was concluded.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Laboratory tests evidenced the positive results for HIV, which was previously unknown, and the patient was referred to Internal Medicine and defined as HIV stage A1 with 580 CD4 lymphocytes but with a viral load of 104,511 copies/ml. Said high viral load prompted the decision to begin triple therapy with epivlera (emtricitabine plus rilpivirine and tenofovir).</p><p id="par0050" class="elsevierStylePara elsevierViewall">The ophthalmological examination carried out 1 month later showed that the whitish ring had disappeared completely. OCT showed persistence of external retinal layer loss in the perimacular area. VF showed generalized loss of sensitivity with relative macular respect, while mfERG showed the persistence of the left macular depression.</p><p id="par0055" class="elsevierStylePara elsevierViewall">The above-mentioned alterations persist to this date. In the latest examination 3 years after the diagnostic, said alterations remained with the presence of a new patchy alteration of the retinal pigment epithelium (RPE) in the internal ring zone, respecting the posterior pole (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0060" class="elsevierStylePara elsevierViewall">In many aspects, AAOR has a very similar presentation to that of AZOOR. Many authors consider the former as a variant of the latter. The difference between both entities is that, at diagnostic, AAOR exhibits a peripapillary white-grayish ring whereas AZOOR does not exhibit any funduscopy changes.</p><p id="par0065" class="elsevierStylePara elsevierViewall">The etiology of AAOR is unknown, although viral infection<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> or a self-immune process have been suggested as triggering factors. This hypothesis is supported by the presence of antibodies against retinal antigens<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">2,3</span></a> and antinuclear antibodies<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">4</span></a> in the serum of some patients.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The present case is relevant due to positive HIV, as these patients do not usually include associated systemic pathology. This is the first described case of an association between both entities. The authors do not know the role that HIV infection or secondary immunosuppression could have played in the development of AAOR. Several studies have observed that immunodepression stabilizes the disease,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> although this immunosuppression could facilitate opportunistic infections that might trigger AAOR clinic.</p><p id="par0075" class="elsevierStylePara elsevierViewall">AAOR is unilateral in 60% of cases, although the appearance of symptoms in the opposite eye could appear up to 2 years later, and presentation in these patients is usually asymmetrical.</p><p id="par0080" class="elsevierStylePara elsevierViewall">The visual acuity of said patients is highly variable: from 1 to hands movement.</p><p id="par0085" class="elsevierStylePara elsevierViewall">According to Gass and Stern,<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> the intraretinal ring could correspond to an immunological ring. Fekrat et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> suggest that the causing agent of AAOR arrives at the retina from the central nervous system and the optic nerve, which would explain the concentric arrangement of the immunological ring around the papilla.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Due to the short life of the intraretinal ring, which disappears in 3–4 weeks, it is likely that some AAOR cases are diagnosed as AZOOR.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In most cases, campimetric alterations consist in scotoma that make contact with the blind spots.</p><p id="par0100" class="elsevierStylePara elsevierViewall">The atrophy of the paramacular outer retina observed in OCT, the absence of alterations in the blood-retina barrier and the severe functional retinal compromise point toward a primary compromise of the outer retina.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Gass and Stern<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> propose that, if photoreceptors recover their function, the condition would not leave sequels but otherwise the outer retina would exhibit progressive degeneration and pigment epithelium atrophy, which was the case of the present patient.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Mjeren et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> described a triple zone pattern in the imaging tests of said chronic patients. Retinal autofluorescence that remains externally to the ring is normal as is corresponds to a healthy retinal area. The dotted hyperautofluorescence zone located at the edge of the lesion is due to the onset of choroidal atrophy, while the central hypoautofluorescence zone corresponds to an established choroidal atrophy area. Retinographies and indocyanine green angiography also showed said triple pattern. The images of the present patient 3 years after diagnostic showed a healthy area of the retina and the patched hyperfluorescence zone. A longer evolution time may be needed to see hypofluorescent changes in the choroidal atrophy zone (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><p id="par0115" class="elsevierStylePara elsevierViewall">In order to reach the AAOR diagnostic, a differential diagnostic must be made with other entities: white spot syndromes, lymphomas, optic neuropathies, paraneoplastic syndromes, self-immune retinopathies and chorioretinal infectious diseases among others. The absence of vitritis and chorioretinal scars, the presence of the white-grayish ring between the compromised and healthy retina and the triple zone pattern described above, as well as the compromise of the mfERG and the selective loss of outer retinal layers, facilitate the AAOR diagnostic.</p><p id="par0120" class="elsevierStylePara elsevierViewall">At this point in time efficient treatments have not been developed for AAOR. Luckie et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> published an AAOR case treated with intravenous acyclovir with positive response. Fekrat et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">5</span></a> described 2 cases that responded to the administration of corticoids. Tang et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> obtained positive response with plasmapheresis followed by cyclophosphamide. However, at this point in time said treatments have demonstrated limited usefulness.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Greater experience is necessary to make progress in the knowledge of the etiology, the clinic characteristics and therapeutic options for AAOR.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Conflict of interests</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors declare the absence of any commercial interest or the receipt of any financial support for this study.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1184806" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1104917" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1184807" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1104916" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Clinic case report" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Conflict of interests" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-04-09" "fechaAceptado" => "2018-10-05" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1104917" "palabras" => array:5 [ 0 => "AAOR" 1 => "Acute zonal occult outer retinopathy" 2 => "HIV" 3 => "Retinal disease" 4 => "Autoimmune disease" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1104916" "palabras" => array:5 [ 0 => "AOOR" 1 => "AZOOR" 2 => "VIH" 3 => "Enfermedad retiniana" 4 => "Enfermedad autoinmune" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A case of acute annular outer retinopathy (AAOR) is presented in a patient that was later proved to be positive for the human immunodeficiency virus (HIV).</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The etiology of AAOR remains unknown, although a viral infection or an autoimmune mechanism has been suggested. The case presented here is noteworthy because it is the first case described in a patient with HIV positive serology. Even so, the precise role played by HIV infection or secondary immunosuppression in the development of the AAOR is not known.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Presentamos un caso de retinopatía anular externa aguda (<span class="elsevierStyleItalic">acute annular outer retinopathy</span> [AAOR]) en un paciente en el que se demostró positividad para el virus de la inmunodeficiencia humana (VIH).</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La etiología de la AAOR es desconocida, aunque se han sugerido como desencadenantes la infección viral o un mecanismo autoinmune. Nuestro caso es relevante por ser el primero descrito en un paciente con serología positiva para VIH. Aun así, desconocemos el papel que ha jugado la infección por VIH o la inmunosupresión secundaria en el desarrollo de la AAOR.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: García-Torre M, Castro-Flórez R. Retinopatía anular externa aguda asociada al virus de la inmunodeficiencia humana. Arch Soc Esp Oftalmol. 2019;94:232–236.</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" => 1972 "Ancho" => 3083 "Tamanyo" => 525464 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">(a) Patient retinography at diagnostic showing the white-grayish ring concentric to the papilla. (b) Autofluorescence with slight hyperautofluorescence in the ring zone. (c) Fluorescing angiography with discrete hyperfluorescence.</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" => 1578 "Ancho" => 2917 "Tamanyo" => 421809 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tests at diagnostic. (a) VF of LE with increased blind spot. (b) OCT of LE with atrophy of the perimacular outer layers. (c) mfERG of LE with macular function depression.</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" => 2574 "Ancho" => 3333 "Tamanyo" => 566002 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">(a) Retinographs: one month after diagnostic the ring has disappeared and 3 years later it exhibits a patched alteration of the peripapillary RPE. (b) Autofluorescence: without alterations one month after diagnostic and with areas of patched hyper- and hypofluorescence 3 years after diagnostic in the peripapillary zone outside of the arches. (c) Fluorescein angiography: slight hyperfluorescence in the zones comprised within the ring. (d) OCT with loss of outer layers, respecting the macular area and mfERG with persistence of electroretinographic alterations. 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