The use of optical coherence tomography in the evaluation of patients with bipolar disorder | Archivos de la Sociedad Española de Oftalmología (English Edition)

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A shows two focus of active chorioretinitis, one extensive peripapilar inferior focus and other temporal superior focus. The AF in B presents hiperautofluorescence along the edge of the hipoautofluorescent lesions. After antibiotic treatment, both lesions appear more scared (C) and both of them reveal hipoautofluorescence, indicating inactivity (D). Figure corresponding to case 3." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.P. Figueroa-Vercellino, L. Miguel, A. Moll-Udina, C. Alba-Linero, V. Llorenç, A. Adán" "autores" => array:6 [ 0 => array:2 [ "nombre" => "J.P." "apellidos" => "Figueroa-Vercellino" ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Miguel" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Moll-Udina" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Alba-Linero" ] 4 => array:2 [ "nombre" => "V." "apellidos" => "Llorenç" ] 5 => array:2 [ "nombre" => "A." 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Figure A; patients 1–5: laser pointer maculopathies. Figure B; patients 6-12: solar maculopathy. Disruption of ellipsoid layer is observed in all cases. Figure 5RE, 5LE, 10RE and to a lesser extent 9RE, 9LE show the RPE hyperreflectivity sign. Centrifugal hyperreflective lesions are distinguished in 2RE and 5RE." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Ortiz Salvador, J. Montero Hernández, V. Castro Navarro, E. Cervera Taulet, C. Navarro Palop, C. Monferrer Adsuara, L. Remolí Sargues, N. Gonzalez Girón" "autores" => array:8 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Ortiz Salvador" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Montero Hernández" ] 2 => array:2 [ "nombre" => "V." "apellidos" => "Castro Navarro" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "Cervera Taulet" ] 4 => array:2 [ "nombre" => "C." "apellidos" => "Navarro Palop" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Monferrer Adsuara" ] 6 => array:2 [ "nombre" => "L." 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Gavín, E. Garcia-Martin, J. Garcia-Campayo, E. Viladés, E. Orduna, M. Satué" "autores" => array:6 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Gavín" "email" => array:1 [ 0 => "ali_gavi@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Garcia-Martin" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J." "apellidos" => "Garcia-Campayo" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 3 => array:3 [ "nombre" => "E." 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"apellidos" => "Satué" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Grupo de Investigación e Innovación Miguel Servet Oftalmología (GIMSO), Zaragoza, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Psiquiatría, Hospital Universitario Miguel Servet, Zaragoza, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Departamento de Psicología y Sociología, Facultad de Ciencias Sociales y Humanas, Universidad de Zaragoza, Zaragoza, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Utilidad de la tomografía de coherencia óptica en la evaluación de los pacientes con trastorno bipolar" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1852 "Ancho" => 3341 "Tamanyo" => 572106 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0080" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (RNFL) taken with Spectralis spectral domain OCT in a patient with bipolar disorder. G: global; N: nasal; NI: lower nasal; NS: upper nasal; N/T: nasal/temporal index; PMB: papillomacular beam; T: temporal; TI: lower temporal; TS: upper temporal." ] ] ] "textoCompleto" => "IntroductionBipolar disorder (BD) is a mental illness characterized by periods or episodes of extreme mood swings that affect a person’s mood, thoughts, and behavior. It is defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) as a mental disorder characterized by the presence of a manic episode (BD type I)or by the presence of one or more hypomanic episodes (less severe manic episodes) and one or more episodes of major depression (BD type II).<a class="elsevierStyleCrossRefs" href="#bib0005">1,2</a>Prevalence varies between 0.6% (BD I) and 0.4% (BD II) of the population, although there are studies that give it up to 5% prevalence.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> Episodes of mania may be accompanied by psychotic symptoms that are usually manifested as hallucinations, delusions of grandeur or invulnerability, while psychotic symptoms that accompany an episode of major depression consist of delusions of guilt, illness or death. Hypomanic episodes are not accompanied by psychotic symptoms.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Most patients remit completely between episodes (euthymic), while some of them alternate states of depression with states of mania, being called rapid-cycling if they present at least 4 episodes of altered mood in 12 months.Comorbidity is very frequent in these patients. Most of them present at least one other psychiatric disorder (such as anxiety disorder or substance abuse) or another general medical illness, mainly cardiovascular disease, diabetes or dyslipidemia, and they associate a high rate of suicide, which is up to 15 times higher than in the general population.<a class="elsevierStyleCrossRefs" href="#bib0025">5,6</a>The pathogenesis of the disease is unknown, although it is known to be multifactorial (genetic, biological and environmental).<a class="elsevierStyleCrossRef" href="#bib0035">7</a> Brain alterations have been found in BD patients studied mainly by means of nuclear magnetic resonance (MRI), such as a decrease in the density of the gray matter<a class="elsevierStyleCrossRef" href="#bib0040">8</a> and alterations in the microstructure of the white substance,<a class="elsevierStyleCrossRefs" href="#bib0045">9,10</a> with an enlargement of the ventricular system at the expense of the third ventricle and the lateral ventricle. In addition, an increase in the volume of the hippocampus and the amygdala has been found in patients treated with lithium compared to those without treatment and to healthy subjects.<a class="elsevierStyleCrossRef" href="#bib0045">9</a>There is a strong genetic influence and high levels of anxiety and stress can act as a trigger for the disorder. Currently, neurological factors that can influence mood fluctuations are being studied.The diagnosis is made based on certain clinical criteria, since currently there are no definitive diagnostic tests. The diagnostic criteria of manic episode include a period of abnormally high, expansive or irritable mood, with persistent increase in activity or energy, lasting at least one week. It is severe enough to cause significant functional impairment. In addition, at least 3 of the following symptoms are present: increased self-esteem, decreased sleep, increased speech, flight of thought, distraction, increased activity or agitation, and excessive participation in activities that may have painful consequences such as unrestrained shopping or reckless investing; psychotic symptoms may be present. The hypomanic episode will be defined by the same criteria, with the difference that the minimum time to diagnose it is 4 days and it should not be serious enough to produce a significant alteration in social or work functioning or to require hospitalization. It does not associate psychotic symptoms.The most commonly used scales in our environment for the clinical assessment of the disease are the Young’s scale (YMRS), which evaluates mania according to several items, and the modified clinical global impression scale for BD (CGI-BP-M), although there are multiple scales available depending on the parameters to be evaluated in each case (comorbidities, depressive phase, functional adaptation, etc.).The diagnosis of BD is often complicated by the lack of imaging or laboratory tests, so the search for biomarkers is a priority to assist in the diagnosis, monitoring or prognosis of the disease.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> In up to 35% of patients there is a diagnostic delay of 10 years after the first consultation, usually due to the initial presentation in the form of major depression, which delays appropriate treatment. This implies an increase in the frequency of cycles and manic episodes, with a high risk of suicide.Optical coherence tomographyThe structural evaluation of the optic nerve and the layers of the retina by means of optical coherence tomography (OCT) has gained important for evaluating neurodegenerative diseases in the last years (multiple sclerosis,<a class="elsevierStyleCrossRefs" href="#bib0060">12–15</a> Parkinson,<a class="elsevierStyleCrossRefs" href="#bib0080">16–19</a> Alzheimer,<a class="elsevierStyleCrossRefs" href="#bib0100">20–24</a> and is considered to be a biomarker for diagnosis, progression and even prognosis of these diseases. The retinal ganglion cell complex (GCC) is made up of 3 different retinal layers: the retinal nerve fiber layer (RNFL), where the axons of the retinal ganglion cells that form the optic nerve are found; the ganglion cells layer (GCL), where the soma of these neurons is found and the inner plexiform layer (IPL), where their dendrites are found.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> Since the axons of these cells lack myelin, their evaluation by OCT makes it possible to study them objectively, the thickness of the RNFL being a reliable marker of axonal damage in diseases that cause neurodegeneration, such as multiple sclerosis, Parkinson's or Alzheimer’s.<a class="elsevierStyleCrossRefs" href="#bib0060">12–22,24</a>Until now, the most widely used OCT technology was the so-called “spectral domain technology” (SD). Devices based on spectral SD allow us to perform retinal scanning at a speed of 50,000 A-scans per second, using a wavelength of 840nm. Recent automatic segmentation software has also allowed individual analysis of the different layers of the retina, providing valuable information not available in older devices.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>The latest breakthrough in OCT devices is the so-called “Swept-source technology” (SS-OCT) or scanning technology in simple terms. Through deep range imaging, the SS-OCT allows us to perform a retinal scan at a speed of 100,000 A-scans per second (much higher than the SD technology described above), using a tunable laser as light source to provide a wavelength of 1050nm. This type of device allows the analysis of different areas and layers of the macular and peripapillary retina, with high reproducibility and reliability.<a class="elsevierStyleCrossRef" href="#bib0130">26</a> In addition, it allows greater penetration of the light wave, reaching deeper layers and through non-transparent media, making it ideal for the study of the choroidal plexus and for the evaluation of elderly subjects with a certain degree of opacification of the lens.<a class="elsevierStyleCrossRef" href="#bib0130">26</a>Several studies have shown a significant thinning of the total thickness of the retina in patients with Parkinson’s disease,<a class="elsevierStyleCrossRefs" href="#bib0080">16–18</a> Alzheimer’s disease<a class="elsevierStyleCrossRefs" href="#bib0100">20–22</a> and multiple sclerosis,<a class="elsevierStyleCrossRefs" href="#bib0060">12–15</a> and an OCT-observed axonal loss has been found in other diseases such as fibromyalgia<a class="elsevierStyleCrossRef" href="#bib0135">27</a> or schizophrenia (SZP).<a class="elsevierStyleCrossRef" href="#bib0140">28</a>As noted for the neurodegenerative diseases mentioned above, several studies have shown a decrease in the thickness of RNFL and CCG through OCT in patients with BD.<a class="elsevierStyleCrossRefs" href="#bib0145">29–35</a>Mehraban et al.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> compared for the first time the NPC of 60 eyes of 30 BD patients with 60 eyes of 30 healthy controls through a prospective case series. They measured the thickness of the peripapillary nerve fiber layer using a 3D OCT model OCT-1000 (Topcon Corporation, Tokyo, Japan) and found a significant decrease in the mean thickness of the RNFL and the lower, upper and nasal quadrants of the patients (p=0.001). The group of Kalenderoglu et al.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> recently conducted a case-control study with 43 BD patients and 43 healthy controls using the OCT of SD Heidelberg Engineering Spectralis (Heidelberg, Germany), and found a significant decrease in the thickness of the RNFL in the overall count (p=0.011), as well as a significant decrease in the volume of the LGC. This was the only study that also found a decrease in the overall thickness of the RNFL in those patients treated with valproic acid compared to those who did not receive it. These results were supported by Khalil et al.,<a class="elsevierStyleCrossRef" href="#bib0155">31</a> who observed, in BD patients evaluated by SD OCT, a significant decrease in RNFL in the global and temporal thickness, upper and lower quadrants and in the mean thickness of the GCC (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Joe et al.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> suggested that not only RNFL and GCL are affected in BD patients, but also the choroids due to the microvascular dysfunctions that occur in this pathology. To study this, he carried out a transversal study in 6 patients with psychosis (3 with BD and 3 with SZP) and compared them with 18 healthy controls without finding significant differences among them with respect to the choroid thickness measured by Heidelberg Spectralis OCT. Likewise, no differences were found in the choroid thickness between patients and controls in the study by Kalenderoglu et al.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> However, said author found a significant reduction of the total thickness of the retina in the central macular area, inside the 4 quadrants and upper outer in the patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Recently, the group of Bannaia et al.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> has carried out a study evaluating the outer layers of the retina. The study comprised 25 patients with psychosis (BD and SZP) and 15 controls, finding a decrease in thickness in all layers of the retina except in the outer plexiform, which was increased. The decrease in the thickness of the rest of layers was only significant in the outer nuclear layer (ONL) in the inner temporal and central sectors of the right eye (OD) and the inner and outer upper sectors of the left eye (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).The authors’ working group has recently carried out 2 studies in BD patients, one using the OCT of SD Spectralis (Heidelberg Engineering), using the Fast Macular protocol to identify and analyze separately each of the layers of the retina and the glaucoma protocol of the RNFL for the peripapillary zone<a class="elsevierStyleCrossRef" href="#bib0170">34</a> and another with the Swept Source technology using the OCT Triton (Topcon Corporation, Tokyo, Japan)<a class="elsevierStyleCrossRef" href="#bib0175">35</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), being a pioneer in the use of this technology to evaluate subjects with BD. In the first of these two studies, a group of 30 patients was compared with 80 healthy controls of similar age and sex, and a decrease in the thicknesses of various sectors and layers of the retina was observed, as well as in the total thickness of the macular area, the upper inner, nasal and temporal sectors and the upper outer sector of the Early Treatment Diabetic Retinopathy Study (ETDRS) areas; the upper sectors of the RNFL (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), the inner sector and the macular volume of the GCL and the minimum central thickness. As a distinctive finding, a significant thickening of the inner nuclear layer was observed in all outer sectors and in the upper and lower inner sectors, in addition to a significant increase in the volume of this inner nuclear layer. This finding had not been previously observed, due to the scarcity of results published using layer segmentation software in BD (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>The second study carried out by the authors’ working group compared 23 patients with a definitive diagnosis of BD against 23 healthy controls of the same age and sex, using SS-OCT technology, which gives us more information about the GCL, providing the thicknesses of the GCL+ complex (between the RNFL and the inner nuclear) and GCL++ (between the inner limiting membrane and the inner nuclear). The results showed a decrease of the total thickness of the retina in the center and the lower temporal, nasal and lower areas of the ETDRS sectors; as well as of the GCL+ and GCL++ layers in different macular sectors. Regarding the peripapillary sectors, a decrease of the full thickness and of the GCL++ was observed, affecting both temporal and nasal sectors.Visual functionIf studies on the structural involvement of the retina in BD patients are scarce, studies on visual function in this type of patient are even more difficult to find. The only one published to date was conducted by our group in 2018,<a class="elsevierStyleCrossRef" href="#bib0170">34</a> evaluating visual acuity using the ETDRS panels, color vision using the Farnsworth D15 and Lanthony D15 test, and contrast sensitivity using the Pelli Robson test. In these patients, visual acuity and contrast sensitivity showed no alteration compared to healthy controls; however, a slight protanomaly was observed in the results of the Lanthony colorimetric test. These functional results were also significantly correlated with the structural alterations found in these patients by SD OCT.The association between retinal alterations observed in BD and the parameters corresponding to the disease itself (duration, number of manic episodes, degree of severity, etc.) has shown controversial results. Of the groups previously described, Khalil et al.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> found a positive relationship between the number of manic episodes and the thickness of the lower sector of the RE RNFL (p=0.034), while in the rest of the OCT thickness variables it failed to demonstrate an association with the number of manic, depressive or mixed episodes.<a class="elsevierStyleCrossRefs" href="#bib0150">30,31</a> The age of onset of the disease or the severity of the disease have also not been found to be related to retinal alterations, although the groups of Mehraban et al.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> and Kalenderoglu et al.<a class="elsevierStyleCrossRef" href="#bib0145">29</a> found a negative correlation between the duration of the disease and the average thickness of the RNFL. The latter also found a significant association between the number of hospitalizations and the YMRS and CGI clinical assessment scales, and the volume of the GCL and the NRFC, decreasing the thicknesses of these layers by increasing one of said parameters. Bannaia et al.’s group also related the clinical evaluation scales with the OCT<a class="elsevierStyleCrossRef" href="#bib0165">33</a> findings and found a correlation between thinning of the retinal pigment epithelium with a worse score in the YMRS scale and the decrease in the thickness of the ONL with worse results in the BACS scale (scale used in SZP), besides finding a significant association between degrees of atrophy of the ONL with a worse global cognitive functioning (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Given that BD is not currently considered a neurodegenerative disease, these results observed by OCT have raised new questions about the physiopathology of the disease since they clearly point to an underlying neurodegeneration in these patients.The prevailing hypothesis so far suggests a catecholaminergic dysfunction with an increase in dopamine and the involvement of inflammatory processes in the physiopathology of the disease. In addition, the involvement of alterations in glia and microglia<a class="elsevierStyleCrossRef" href="#bib0180">36</a> is increasingly considered, which was also observed in post mortem studies.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> In addition, the increase in the inhibitory neurotransmitter GABA has been related to the presence of BD.Nuclear magnetic resonance and optical coherence tomography in bipolar disorderSome previous studies carried out by means of MRI support this neurodegenerative hypothesis,<a class="elsevierStyleCrossRef" href="#bib0190">38</a> since a relationship has been found between the time of evolution of the disease and a smaller size of the left putamen nucleus and a decrease in the grey substance. These primary changes in grey matter may reflect a decrease in the number and size of neurons and in the density of dendrites, which is associated with abnormal cell plasticity that could be related to disease progression. Benedetti and Bollettini<a class="elsevierStyleCrossRef" href="#bib0195">39</a> conducted a review in which they postulated that patients with BD have abnormal functional connectivity between different brain areas that could be a core of affective instability. The damage to the myelin sheath produces a disruption that decreases the speed of transmission through the axons, which would alter the ability of neurons to communicate with each other efficiently. It has been suggested that in BD neurodegeneration could start in the body of the ganglion cells and later extend to their axons and dendrites, which would justify the early involvement of GCL (CCG) in these patients with respect to RNFL and its strong correlation with disease parameters.It has been observed in patients with neurodegeneration due to dementia that the loss of GCL is associated with the reduction of the volume of brain grey substance, while the loss of thickness of RNFL and IPL reflects the reduction of volume of white substance; although a statistically significant association has only been found between the volume of grey substance and the thickness of IPL and GCL in the temporal and occipital lobes.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> It has also been observed in psychotic patients<a class="elsevierStyleCrossRef" href="#bib0165">33</a> that a decrease in the total thickness of the retina is associated with a lower total cerebral volume, while a decrease in the ONL in some sectors is also correlated with a lower global cerebral volume and also with a decrease in the volume of the white substance.The influence of medication<a class="elsevierStyleCrossRefs" href="#bib0180">36,41</a> on the differences in brain volumes has been significant in those patients treated with lithium, finding in these a greater total volume of the hippocampus and the amygdala with respect to those who do not take lithium and even to healthy subjects. No differences have been found regarding the use of other medications in patients with BD, although they have been found in the use of valproic acid<a class="elsevierStyleCrossRef" href="#bib0210">42</a> in epilepsy, where a decrease of the volume of the parietal lobe, of the total brain volume and of the white substance has been found in those subjects in treatment with this substance, usually used in the manic phases of patients with BD.In healthy subjects, a linear association measured by MRI has been found between the primary visual cortex (Broadman’s area 17 [BA17]) and the macular thickness in the OCT, being able to predict the volume variation of BA17 as a function of macular thickness, related to variations by age.<a class="elsevierStyleCrossRef" href="#bib0215">43</a>On the other hand, the alterations found in the retina of BD patients have not been observed in patients with isolated major depression, in whom it appears that the retinal structure measured by OCT is intact.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> This fact strengthens the hypothesis of neurodegeneration in BD and establishes one more physiopathological difference between this disorder and isolated major depression. However, at present there are too few published studies on BD to establish consistent hypotheses about a possible neurodegenerative origin of this disorder.Electroretinogram in bipolar disorderThe electroretinogram (ERG) has been the first ophthalmological tool in which alterations have been repeatedly found in patients with BD and other psychiatric diseases such as SZP or major depression. A decrease in the response of the rods in the form of a lower amplitude and an increase in the latency of the b-wave have even been observed in healthy subjects of high genetic risk (descendants of BD patients).<a class="elsevierStyleCrossRefs" href="#bib0225">45,46</a> It has been postulated that these alterations are due to the enzyme glycogen synthetase kinase-3,<a class="elsevierStyleCrossRefs" href="#bib0235">47,48</a> a molecule involved in the regulation of neurotransmitters such as dopamine and serotonin, and that it exhibits deregulation in these patients.Retinal vasculature in bipolar disorderThe ophthalmological examination is useful to evaluate patients with BD, not only because of the findings found in the OCT analysis but also because of the image of the retinal vasculature as a representation of the brain and evaluated by retinography images.It is known that patients with BD have a higher incidence of cardiovascular disease; therefore, the group of Naiberg et al.<a class="elsevierStyleCrossRef" href="#bib0245">49</a> decided to study the retinal vasculature of adolescents with BD and compare it with healthy subjects; however, they found no statistically significant differences between both groups in terms of the arteriovenous ratio and the diameters of the central retinal artery and the central retinal vein. As a limitation in their study they had a small sample size (n=30) and only adolescents were used, with a mean age of 17.97±1.86 years.Following the same theory of a higher incidence of cardiovascular events in patients with BD and schizophrena with respect to the general population, and with the evidence that these patients present a generalized microvascular dysfunction, the group led by Appaji et al. has recently published several works<a class="elsevierStyleCrossRefs" href="#bib0250">50–53</a> in which they analyze the retinal vasculature in patients with BD to compare it with that of healthy subjects and to correlate it with the rest of alterations exhibited by these patients, through the exploration of the fundus of the eye as a non-invasive approximation of the state of the cerebral vasculature. These works are based on the knowledge<a class="elsevierStyleCrossRef" href="#bib0250">50</a> that the retinal microvasculature shares embryological origin and presents common morphological and physiological characteristics. They explored the alterations in 100 patients with SZP, 100 with BD and 100 healthy volunteers, excluding all those who exhibited high blood pressure, diabetes, previous cardiovascular accident or history of eye surgery or trauma. They found a significant difference in the diameter between arterioles and venules between patients and healthy ones, the former being narrower and the latter flatter in patients, and this significant difference being between patients with SZP and BD, with greater alteration in BD.<a class="elsevierStyleCrossRef" href="#bib0250">50</a> In the same line, they suggest that both wider blood vessels and narrower arteries are associated with cognitive defects in adults with SZP and BD, as suggested also by the cerebral vasculature.<a class="elsevierStyleCrossRef" href="#bib0255">51</a>With the same groups of patients and controls, said authors analyzed the different pathways of the retinal vessels to relate them to the thickness of the RNFL, which as we have already seen is a reliable marker of brain alterations.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> They were based on the work of Yamashita et al.,<a class="elsevierStyleCrossRef" href="#bib0270">54</a> who studied the angle formed by the main infra-temporal arteries and veins with the supra-temporal ones and which related with the thickness peaks of the peripapillary RNFL, observing that this correlated with the analysis of RNFL thickness by sectors positively in some of them and negatively in others, but in a statistically significant manner. Appaji et al.<a class="elsevierStyleCrossRef" href="#bib0260">52</a> determined that patients with BD had a flatter and wider retinal artery pathway and the curve of their arms was farther away from the pitting than in healthy subjects, which is associated with a decrease in RNFL thickness. However, they found no correlation between the clinical variables of duration of the disease, age of onset, score on the clinical scales (YMRS) or treatment with antipsychotics and the pathway of arteries and veins.Vascular tortuosity in the retinal vessels of these patients has also been evaluated<a class="elsevierStyleCrossRef" href="#bib0265">53</a> as it is considered even more stable than the diameter since it is not influenced by pulse variations. The result in this case was an increase in the rate of arteriolar tortuosity in BD and SZP patients compared to healthy subjects and of BD patients compared to SZP patients, an observation they were not able to explain.In recent years the study of retinal vasculature has emerged through the use of angiography associated with OCT, which is called OCT-angiography. It is a new non-invasive method in which the vasculature can be visualized in three dimensions without the need to inject contrast. It is based on the detection of particle movement (the red blood cells within the vessels) and the acquisition of repeated OCT images in the same area, which makes it possible to locate and show the blood vessels. Its first indications have focused on the study of choroidal neovascularization and other diseases that specifically affect the retina (such as diabetic retinopathy or venous obstructions), but it is already beginning to be used in the evaluation of neurodegenerative diseases,<a class="elsevierStyleCrossRefs" href="#bib0275">55,56</a> although to date no research has been published on its application in BD.ConclusionsBD is a neurodegenerative disease that causes structural alterations in the brain. The search for biomarkers of the disease through different ophthalmological examinations (ERG, retinography, OCT) enhances the usefulness of ophthalmological examination as a way to access the brain and determines the need to find a safe, fast and reliable means such as OCT, capable of observing and quantifying these alterations.Until now, it had only been possible to assess brain damage in vivo using MRI and in postmortem studies. OCT study allows us to evaluate in a safe, non-invasive, fast and efficient way the neurodegenerative process of these patients, assessing the retinal neuronal compromise that correlates with the cerebral neuronal impairment. Longitudinal studies would be necessary to establish the possible correlation between the loss of retinal ganglion cells and the progression of the disease and to determine the possible role of retinal parameters as a diagnostic and progression biomarker in BD. This would allow an earlier diagnosis of the disease in order to apply therapies early in these patients and thus minimize the number of episodes, slow the course of the disease or improve the quality of life of patients and families. Currently, there are few results on the influence of BD treatment with lithium or antipsychotics and alterations in OCT; however, the findings found in MRI studies in which it has been seen that these drugs influence the total and grey matter volumes of the brain lead to the assumption that variations in OCT can be found depending on patient treatments, which could be favored if the use of OCT for monitoring the response to treatment were significant and would help to understand the brain changes that occur in relation to treatment.Its use versus MRI, which is commonly used for evaluation of this disease, would allow faster and less costly evaluation, so it could be used routinely allowing accurate monitoring of progression.Retinography and the recent use of OCT angiography as an evaluation of the cerebral vascular system paves the way for studying psychiatric diseases through ophthalmological examination. The correlation between these findings and those found in OCT could provide added value to all studies conducted to date.FundingThis work has been partly funded by the Juan Rodés grants JR17/00010, PI17/01726 (Instituto de Salud Carlos III).Conflict of interestNo conflict of interest was declared by the authors." "textoCompletoSecciones" => array:1 [ "secciones" => array:9 [ 0 => array:3 [ "identificador" => "xres1472802" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1341214" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1472803" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1341213" "titulo" => "Palabras clave" ] 4 => array:3 [ "identificador" => "sec0005" "titulo" => "Introduction" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Optical coherence tomography" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Visual function" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Nuclear magnetic resonance and optical coherence tomography in bipolar disorder" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Electroretinogram in bipolar disorder" ] 4 => array:2 [ "identificador" => "sec0030" "titulo" => "Retinal vasculature in bipolar disorder" ] ] ] 5 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 6 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 7 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 8 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-05-06" "fechaAceptado" => "2020-07-12" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1341214" "palabras" => array:6 [ 0 => "Bipolar disorder" 1 => "Optical coherence tomography" 2 => "Retinal nerve fibre layer" 3 => "Ganglion cell layer" 4 => "Swept-source" 5 => "Spectral domain" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1341213" "palabras" => array:6 [ 0 => "Trastorno bipolar" 1 => "Tomografía de coherencia óptica" 2 => "Capa de fibras nerviosas de la retina" 3 => "Capa de células ganglionares" 4 => "Swept-source" 5 => "Dominio espectral" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Bipolar disorder (BD) is a mental disorder characterised by episodes of extremal mood changes. In recent years, some researchers found neurodegeneration in patients with BD using Magnetic Resonance Imaging. Evaluation of the optic nerve and the retinal layers using optical coherence tomography (OCT) has proved to be a useful, non-invasive tool for diagnosis and monitoring of neurodegenerative diseases. Accordingly, a decrease in the retinal nerve fibre layer and the ganglion cell complex measured by OCT was found in patients with BD in different studies, suggesting that BD is a neurodegenerative process in addition to a psychiatric disorder. Therefore, the neuro-ophthalmological evaluation of these patients could be used as a marker for diagnosis of this disease.This work analyses literature on retinal degeneration in bipolar disorder patients, and evaluates the ability of OCT devices in the detection of neuronal degeneration affecting the different retinal layers in these patients, and its possible role in the diagnosis and monitoring of the disease." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El trastorno bipolar (TB) es una enfermedad mental caracterizada por episodios de alteraciones extremas del humor en la que existe evidencia de presencia de neurodegeneración, determinada mediante resonancia magnética nuclear. En los últimos años, la evaluación del nervio óptico y de las capas de la retina mediante tomografía de coherencia óptica (OCT) en enfermedades neurodegenerativas ha demostrado su utilidad como biomarcador no invasivo de diagnóstico y progresión. En pacientes con TB diversos estudios han encontrado disminución de la capa de fibras nerviosas de la retina y del complejo de células ganglionares objetivables mediante OCT, lo que apoyaría la hipótesis de que el TB se trata de una enfermedad neurodegenerativa además de un proceso psiquiátrico. Por ello, el estudio neuro-oftalmológico de estos pacientes podría servir como marcador diagnóstico de esta patología. Este trabajo revisa la bibliografía reciente sobre degeneración retiniana en pacientes con TB y evalúa la capacidad de los dispositivos de OCT en la detección de degeneración neuronal que afecta a las diferentes capas de la retina en estos pacientes y su posible papel en el diagnóstico y seguimiento de la enfermedad." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Gavín A, Garcia-Martin E, Garcia-Campayo J, Viladés E, Orduna E, Satué M. Utilidad de la tomografía de coherencia óptica en la evaluación de los pacientes con trastorno bipolar. Arch Soc Esp Oftalmol. 2021;96:141–151." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2403 "Ancho" => 3341 "Tamanyo" => 813131 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0075" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Optical coherence tomography (OCT) of the ganglion cells layer (A and B) and the total thickness of the retina in the macular area (C and D) of the left eye of the same patient measured by Swept-source OCT (Triton) (A and C) and by Spectralis spectral domain OCT (B and D)." ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1852 "Ancho" => 3341 "Tamanyo" => 572106 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0080" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (RNFL) taken with Spectralis spectral domain OCT in a patient with bipolar disorder. G: global; N: nasal; NI: lower nasal; NS: upper nasal; N/T: nasal/temporal index; PMB: papillomacular beam; T: temporal; TI: lower temporal; TS: upper temporal." ] ] 2 => array:8 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3089 "Ancho" => 3341 "Tamanyo" => 894228 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0085" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Optical coherence tomography (OCT) of the inner nuclear layer taken with Spectralis spectral domain OCT of a patient with bipolar disorder. ETDRS: Early Treatment Diabetic Retinopathy Study; Vol: volume." ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0090" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "RNFL: retinal nerve fiber layer; ETDRS: Early Treatment Diabetic Retinopathy Study; GCL: ganglion cell layer; INL: inner nuclear layer; IPL: inner plexiform layer; RE: right eye; LE: left eye; ONL: outer nuclear layer; OPL: outer plexiform layer." "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" style="border-bottom: 2px solid black">Group \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">Type of 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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">n \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">OCT \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">Results \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">Mehraban et al. \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">Prospective control case \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">120 eyes (60 cases 60 controls) \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">Spectral domain \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">RNFL: decrease in the middle thickness, lower, upper and nasal quadrants \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"> \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">GCL and choroidal thickness not evaluated \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">Kalenderoglu et al. \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">Control case \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">86 (43 cases, 43 controls) \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">Spectral domain \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">RNFL: overall thickness reduction \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"> \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">GCL: decrease in volume \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"> \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">No significant difference in choroidal thickness \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">Khalil et al. \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">Control case \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">80 (40 cases, 40 controls) \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">Spectral domain \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">RNFL: decrease overall thickness and temporary, upper and lower quadrants \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"> \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">GCL: average decrease and in upper sector \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"> \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">Unevaluated choroidal thickness \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">Joe et al. \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">Transversal study \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">24 (3 BD, 3 SZP, 18 controls) \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">Spectral domain \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">RNFL and GCL: not evaluated \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"> \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">Total retinal thickness: decreased central macular area, inner of the 4 quadrants and upper outer \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"> \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">No significant difference in choroidal thickness \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">Bannaia et al. \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">Transversal study \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 (5 BD, 12 SZP, 8 schizoaffective disorder, 15 controls) \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">Spectral domain \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">Total retinal thickness, RNFL, CCG, IPL, INL: no statistically significant decrease \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"> \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">OPL: increase in temporary inner sector of both eyes and of the upper inner and outer sectors of the LE \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"> \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">NPO: temporary and central inner sector of the RE and the higher inner and outer sectors of the LE \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">Garcia-Martin et al. \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">Control case \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">110 (30 patients, 80 controls) \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">Spectral domain \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">RNFL: average decrease and temporary sectors \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"> \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">GCL: decrease in volume and thickness of the 4 inner macular sectors \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"> \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">Total retinal thickness: decrease in the upper inner, nasal and lower and upper outer sectors \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"> \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">IPL: decrease of inner nasal, lower and temporal sectors of the macular area \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"> \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">INL: increase in volume and thickness in the 4 outer sectors of the macular area and the upper and lower inner sectors \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"> \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">Unevaluated choroidal thickness \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">Polo et al. \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">Control case \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">46 (23 patients, 23 controls) \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">Swept-source \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">RNFL middle, upper-temporal and upper nasal decrease of peripapillary sectors \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"> \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">GCL+: middle, superior, super-nasal, infero-nasal and inferior decrease of the ETDRS areas, middle, superior, superior-nasal, inferior-nasal and inferior decrease of the 6 macular sectors and decrease of the peripapillary nasal sector \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"> \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">GCL++: infero-temporal and infero-nasal decrease and of the macular and middle, super-temporal, super-nasal and inferotemporal sectors of the peripapillary area \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"> \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">Decrease in total retinal thickness in the middle peripapillary, upper temporal, upper nasal, nasal and lower temporal sectors and in the central, interior-temporal, interior-nasal and interior-inferior ETDRS areas \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"> \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">No significant differences in choroidal thickness in the ETRDS and peripapillary areas \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2534363.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Results of published studies on OCT and bipolar disorder." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:56 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic and statistical manual of mental disorders. 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The use of optical coherence tomography in the evaluation of patients with bipolar disorder

Utilidad de la tomografía de coherencia óptica en la evaluación de los pacientes con trastorno bipolar

A. Gavína,b,

Corresponding author

ali_gavi@hotmail.com

Corresponding author.

, E. Garcia-Martina,b, J. Garcia-Campayoc,d, E. Viladésa,b, E. Ordunaa,b, M. Satuéa,b

a Servicio de Oftalmología, Hospital Universitario Miguel Servet, Zaragoza, Spain

b Instituto de Investigación Sanitaria de Aragón (IIS Aragón), Grupo de Investigación e Innovación Miguel Servet Oftalmología (GIMSO), Zaragoza, Spain

c Servicio de Psiquiatría, Hospital Universitario Miguel Servet, Zaragoza, Spain

d Departamento de Psicología y Sociología, Facultad de Ciencias Sociales y Humanas, Universidad de Zaragoza, Zaragoza, Spain

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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Optical coherence tomography &#40;OCT&#41; of the peripapillary retinal nerve fiber layer &#40;RNFL&#41; taken with Spectralis spectral domain OCT in a patient with bipolar disorder&#46;</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">G&#58; global&#59; N&#58; nasal&#59; NI&#58; lower nasal&#59; NS&#58; upper nasal&#59; N&#47;T&#58; nasal&#47;temporal index&#59; PMB&#58; papillomacular beam&#59; T&#58; temporal&#59; TI&#58; lower temporal&#59; TS&#58; upper temporal&#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">Bipolar disorder &#40;BD&#41; is a mental illness characterized by periods or episodes of extreme mood swings that affect a person&#8217;s mood&#44; thoughts&#44; and behavior&#46; It is defined by the <span class="elsevierStyleItalic">Diagnostic and Statistical Manual of Mental Disorders</span> &#40;DSM-V&#41; as a mental disorder characterized by the presence of a manic episode &#40;BD type I<span class="elsevierStyleSmallCaps">&#41;</span>or by the presence of one or more hypomanic episodes &#40;less severe manic episodes&#41; and one or more episodes of major depression &#40;BD type II&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Prevalence varies between 0&#46;6&#37; &#40;BD I&#41; and 0&#46;4&#37; &#40;BD II&#41; of the population&#44; although there are studies that give it up to 5&#37; prevalence&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Episodes of mania may be accompanied by psychotic symptoms that are usually manifested as hallucinations&#44; delusions of grandeur or invulnerability&#44; while psychotic symptoms that accompany an episode of major depression consist of delusions of guilt&#44; illness or death&#46; Hypomanic episodes are not accompanied by psychotic symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Most patients remit completely between episodes &#40;euthymic&#41;&#44; while some of them alternate states of depression with states of mania&#44; being called rapid-cycling if they present at least 4 episodes of altered mood in 12 months&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Comorbidity is very frequent in these patients&#46; Most of them present at least one other psychiatric disorder &#40;such as anxiety disorder or substance abuse&#41; or another general medical illness&#44; mainly cardiovascular disease&#44; diabetes or dyslipidemia&#44; and they associate a high rate of suicide&#44; which is up to 15 times higher than in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The pathogenesis of the disease is unknown&#44; although it is known to be multifactorial &#40;genetic&#44; biological and environmental&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> Brain alterations have been found in BD patients studied mainly by means of nuclear magnetic resonance &#40;MRI&#41;&#44; such as a decrease in the density of the gray matter<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and alterations in the microstructure of the white substance&#44;<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9&#44;10</span></a> with an enlargement of the ventricular system at the expense of the third ventricle and the lateral ventricle&#46; In addition&#44; an increase in the volume of the hippocampus and the amygdala has been found in patients treated with lithium compared to those without treatment and to healthy subjects&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">There is a strong genetic influence and high levels of anxiety and stress can act as a trigger for the disorder&#46; Currently&#44; neurological factors that can influence mood fluctuations are being studied&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnosis is made based on certain clinical criteria&#44; since currently there are no definitive diagnostic tests&#46; The diagnostic criteria of manic episode include a period of abnormally high&#44; expansive or irritable mood&#44; with persistent increase in activity or energy&#44; lasting at least one week&#46; It is severe enough to cause significant functional impairment&#46; In addition&#44; at least 3 of the following symptoms are present&#58; increased self-esteem&#44; decreased sleep&#44; increased speech&#44; flight of thought&#44; distraction&#44; increased activity or agitation&#44; and excessive participation in activities that may have painful consequences such as unrestrained shopping or reckless investing&#59; psychotic symptoms may be present&#46; The hypomanic episode will be defined by the same criteria&#44; with the difference that the minimum time to diagnose it is 4 days and it should not be serious enough to produce a significant alteration in social or work functioning or to require hospitalization&#46; It does not associate psychotic symptoms&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The most commonly used scales in our environment for the clinical assessment of the disease are the Young&#8217;s scale &#40;YMRS&#41;&#44; which evaluates mania according to several items&#44; and the modified clinical global impression scale for BD &#40;CGI-BP-M&#41;&#44; although there are multiple scales available depending on the parameters to be evaluated in each case &#40;comorbidities&#44; depressive phase&#44; functional adaptation&#44; <span class="elsevierStyleItalic">etc&#46;</span>&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The diagnosis of BD is often complicated by the lack of imaging or laboratory tests&#44; so the search for biomarkers is a priority to assist in the diagnosis&#44; monitoring or prognosis of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In up to 35&#37; of patients there is a diagnostic delay of 10 years after the first consultation&#44; usually due to the initial presentation in the form of major depression&#44; which delays appropriate treatment&#46; This implies an increase in the frequency of cycles and manic episodes&#44; with a high risk of suicide&#46;</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Optical coherence tomography</span><p id="par0045" class="elsevierStylePara elsevierViewall">The structural evaluation of the optic nerve and the layers of the retina by means of optical coherence tomography &#40;OCT&#41; has gained important for evaluating neurodegenerative diseases in the last years &#40;multiple sclerosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;15</span></a> Parkinson&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;19</span></a> Alzheimer&#44;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;24</span></a> and is considered to be a biomarker for diagnosis&#44; progression and even prognosis of these diseases&#46; The retinal ganglion cell complex &#40;GCC&#41; is made up of 3 different retinal layers&#58; the retinal nerve fiber layer &#40;RNFL&#41;&#44; where the axons of the retinal ganglion cells that form the optic nerve are found&#59; the ganglion cells layer &#40;GCL&#41;&#44; where the soma of these neurons is found and the inner plexiform layer &#40;IPL&#41;&#44; where their dendrites are found&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Since the axons of these cells lack myelin&#44; their evaluation by OCT makes it possible to study them objectively&#44; the thickness of the RNFL being a reliable marker of axonal damage in diseases that cause neurodegeneration&#44; such as multiple sclerosis&#44; Parkinson&#39;s or Alzheimer&#8217;s&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;22&#44;24</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Until now&#44; the most widely used OCT technology was the so-called &#8220;<span class="elsevierStyleItalic">spectral domain</span> technology&#8221; &#40;SD&#41;&#46; Devices based on spectral SD allow us to perform retinal scanning at a speed of 50&#44;000 A-scans per second&#44; using a wavelength of 840<span class="elsevierStyleHsp" style=""></span>nm&#46; Recent automatic segmentation software has also allowed individual analysis of the different layers of the retina&#44; providing valuable information not available in older devices&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The latest breakthrough in OCT devices is the so-called &#8220;Swept-source technology&#8221; &#40;SS-OCT&#41; or scanning technology in simple terms&#46; Through deep range imaging&#44; the SS-OCT allows us to perform a retinal scan at a speed of 100&#44;000 A-scans per second &#40;much higher than the SD technology described above&#41;&#44; using a tunable laser as light source to provide a wavelength of 1050<span class="elsevierStyleHsp" style=""></span>nm&#46; This type of device allows the analysis of different areas and layers of the macular and peripapillary retina&#44; with high reproducibility and reliability&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> In addition&#44; it allows greater penetration of the light wave&#44; reaching deeper layers and through non-transparent media&#44; making it ideal for the study of the choroidal plexus and for the evaluation of elderly subjects with a certain degree of opacification of the lens&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Several studies have shown a significant thinning of the total thickness of the retina in patients with Parkinson&#8217;s disease&#44;<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">16&#8211;18</span></a> Alzheimer&#8217;s disease<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;22</span></a> and multiple sclerosis&#44;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#8211;15</span></a> and an OCT-observed axonal loss has been found in other diseases such as fibromyalgia<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> or schizophrenia &#40;SZP&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">As noted for the neurodegenerative diseases mentioned above&#44; several studies have shown a decrease in the thickness of RNFL and CCG through OCT in patients with BD&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#8211;35</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Mehraban et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> compared for the first time the NPC of 60 eyes of 30 BD patients with 60 eyes of 30 healthy controls through a prospective case series&#46; They measured the thickness of the peripapillary nerve fiber layer using a 3D OCT model OCT-1000 &#40;Topcon Corporation&#44; Tokyo&#44; Japan&#41; and found a significant decrease in the mean thickness of the RNFL and the lower&#44; upper and nasal quadrants of the patients &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The group of Kalenderoglu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> recently conducted a case-control study with 43 BD patients and 43 healthy controls using the OCT of SD Heidelberg Engineering Spectralis &#40;Heidelberg&#44; Germany&#41;&#44; and found a significant decrease in the thickness of the RNFL in the overall count &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;011&#41;&#44; as well as a significant decrease in the volume of the LGC&#46; This was the only study that also found a decrease in the overall thickness of the RNFL in those patients treated with valproic acid compared to those who did not receive it&#46; These results were supported by Khalil et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> who observed&#44; in BD patients evaluated by SD OCT&#44; a significant decrease in RNFL in the global and temporal thickness&#44; upper and lower quadrants and in the mean thickness of the GCC &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Joe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> suggested that not only RNFL and GCL are affected in BD patients&#44; but also the choroids due to the microvascular dysfunctions that occur in this pathology&#46; To study this&#44; he carried out a transversal study in 6 patients with psychosis &#40;3 with BD and 3 with SZP&#41; and compared them with 18 healthy controls without finding significant differences among them with respect to the choroid thickness measured by Heidelberg Spectralis OCT&#46; Likewise&#44; no differences were found in the choroid thickness between patients and controls in the study by Kalenderoglu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> However&#44; said author found a significant reduction of the total thickness of the retina in the central macular area&#44; inside the 4 quadrants and upper outer in the patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Recently&#44; the group of Bannaia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> has carried out a study evaluating the outer layers of the retina&#46; The study comprised 25 patients with psychosis &#40;BD and SZP&#41; and 15 controls&#44; finding a decrease in thickness in all layers of the retina except in the outer plexiform&#44; which was increased&#46; The decrease in the thickness of the rest of layers was only significant in the outer nuclear layer &#40;ONL&#41; in the inner temporal and central sectors of the right eye &#40;OD&#41; and the inner and outer upper sectors of the left eye &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">The authors&#8217; working group has recently carried out 2 studies in BD patients&#44; one using the OCT of SD Spectralis &#40;Heidelberg Engineering&#41;&#44; using the Fast Macular protocol to identify and analyze separately each of the layers of the retina and the glaucoma protocol of the RNFL for the peripapillary zone<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> and another with the Swept Source technology using the OCT Triton &#40;Topcon Corporation&#44; Tokyo&#44; Japan&#41;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#44; being a pioneer in the use of this technology to evaluate subjects with BD&#46; In the first of these two studies&#44; a group of 30 patients was compared with 80 healthy controls of similar age and sex&#44; and a decrease in the thicknesses of various sectors and layers of the retina was observed&#44; as well as in the total thickness of the macular area&#44; the upper inner&#44; nasal and temporal sectors and the upper outer sector of the Early Treatment Diabetic Retinopathy Study &#40;ETDRS&#41; areas&#59; the upper sectors of the RNFL &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#44; the inner sector and the macular volume of the GCL and the minimum central thickness&#46; As a distinctive finding&#44; a significant thickening of the inner nuclear layer was observed in all outer sectors and in the upper and lower inner sectors&#44; in addition to a significant increase in the volume of this inner nuclear layer&#46; This finding had not been previously observed&#44; due to the scarcity of results published using layer segmentation software in BD &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The second study carried out by the authors&#8217; working group compared 23 patients with a definitive diagnosis of BD against 23 healthy controls of the same age and sex&#44; using SS-OCT technology&#44; which gives us more information about the GCL&#44; providing the thicknesses of the GCL&#43; complex &#40;between the RNFL and the inner nuclear&#41; and GCL&#43;&#43; &#40;between the inner limiting membrane and the inner nuclear&#41;&#46; The results showed a decrease of the total thickness of the retina in the center and the lower temporal&#44; nasal and lower areas of the ETDRS sectors&#59; as well as of the GCL&#43; and GCL&#43;&#43; layers in different macular sectors&#46; Regarding the peripapillary sectors&#44; a decrease of the full thickness and of the GCL&#43;&#43; was observed&#44; affecting both temporal and nasal sectors&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Visual function</span><p id="par0095" class="elsevierStylePara elsevierViewall">If studies on the structural involvement of the retina in BD patients are scarce&#44; studies on visual function in this type of patient are even more difficult to find&#46; The only one published to date was conducted by our group in 2018&#44;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> evaluating visual acuity using the ETDRS panels&#44; color vision using the Farnsworth D15 and Lanthony D15 test&#44; and contrast sensitivity using the Pelli Robson test&#46; In these patients&#44; visual acuity and contrast sensitivity showed no alteration compared to healthy controls&#59; however&#44; a slight protanomaly was observed in the results of the Lanthony colorimetric test&#46; These functional results were also significantly correlated with the structural alterations found in these patients by SD OCT&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The association between retinal alterations observed in BD and the parameters corresponding to the disease itself &#40;duration&#44; number of manic episodes&#44; degree of severity&#44; <span class="elsevierStyleItalic">etc&#46;</span>&#41; has shown controversial results&#46; Of the groups previously described&#44; Khalil et al&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> found a positive relationship between the number of manic episodes and the thickness of the lower sector of the RE RNFL &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#41;&#44; while in the rest of the OCT thickness variables it failed to demonstrate an association with the number of manic&#44; depressive or mixed episodes&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30&#44;31</span></a> The age of onset of the disease or the severity of the disease have also not been found to be related to retinal alterations&#44; although the groups of Mehraban et al&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> and Kalenderoglu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> found a negative correlation between the duration of the disease and the average thickness of the RNFL&#46; The latter also found a significant association between the number of hospitalizations and the YMRS and CGI clinical assessment scales&#44; and the volume of the GCL and the NRFC&#44; decreasing the thicknesses of these layers by increasing one of said parameters&#46; Bannaia et al&#46;&#8217;s group also related the clinical evaluation scales with the OCT<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> findings and found a correlation between thinning of the retinal pigment epithelium with a worse score in the YMRS scale and the decrease in the thickness of the ONL with worse results in the BACS scale &#40;scale used in SZP&#41;&#44; besides finding a significant association between degrees of atrophy of the ONL with a worse global cognitive functioning &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Given that BD is not currently considered a neurodegenerative disease&#44; these results observed by OCT have raised new questions about the physiopathology of the disease since they clearly point to an underlying neurodegeneration in these patients&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The prevailing hypothesis so far suggests a catecholaminergic dysfunction with an increase in dopamine and the involvement of inflammatory processes in the physiopathology of the disease&#46; In addition&#44; the involvement of alterations in glia and microglia<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> is increasingly considered&#44; which was also observed in <span class="elsevierStyleItalic">post mortem</span> studies&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> In addition&#44; the increase in the inhibitory neurotransmitter GABA has been related to the presence of BD&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Nuclear magnetic resonance and optical coherence tomography in bipolar disorder</span><p id="par0115" class="elsevierStylePara elsevierViewall">Some previous studies carried out by means of MRI support this neurodegenerative hypothesis&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> since a relationship has been found between the time of evolution of the disease and a smaller size of the left putamen nucleus and a decrease in the grey substance&#46; These primary changes in grey matter may reflect a decrease in the number and size of neurons and in the density of dendrites&#44; which is associated with abnormal cell plasticity that could be related to disease progression&#46; Benedetti and Bollettini<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> conducted a review in which they postulated that patients with BD have abnormal functional connectivity between different brain areas that could be a core of affective instability&#46; The damage to the myelin sheath produces a disruption that decreases the speed of transmission through the axons&#44; which would alter the ability of neurons to communicate with each other efficiently&#46; It has been suggested that in BD neurodegeneration could start in the body of the ganglion cells and later extend to their axons and dendrites&#44; which would justify the early involvement of GCL &#40;CCG&#41; in these patients with respect to RNFL and its strong correlation with disease parameters&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">It has been observed in patients with neurodegeneration due to dementia that the loss of GCL is associated with the reduction of the volume of brain grey substance&#44; while the loss of thickness of RNFL and IPL reflects the reduction of volume of white substance&#59; although a statistically significant association has only been found between the volume of grey substance and the thickness of IPL and GCL in the temporal and occipital lobes&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> It has also been observed in psychotic patients<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> that a decrease in the total thickness of the retina is associated with a lower total cerebral volume&#44; while a decrease in the ONL in some sectors is also correlated with a lower global cerebral volume and also with a decrease in the volume of the white substance&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The influence of medication<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">36&#44;41</span></a> on the differences in brain volumes has been significant in those patients treated with lithium&#44; finding in these a greater total volume of the hippocampus and the amygdala with respect to those who do not take lithium and even to healthy subjects&#46; No differences have been found regarding the use of other medications in patients with BD&#44; although they have been found in the use of valproic acid<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> in epilepsy&#44; where a decrease of the volume of the parietal lobe&#44; of the total brain volume and of the white substance has been found in those subjects in treatment with this substance&#44; usually used in the manic phases of patients with BD&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">In healthy subjects&#44; a linear association measured by MRI has been found between the primary visual cortex &#40;Broadman&#8217;s area 17 &#91;BA17&#93;&#41; and the macular thickness in the OCT&#44; being able to predict the volume variation of BA17 as a function of macular thickness&#44; related to variations by age&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">On the other hand&#44; the alterations found in the retina of BD patients have not been observed in patients with isolated major depression&#44; in whom it appears that the retinal structure measured by OCT is intact&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> This fact strengthens the hypothesis of neurodegeneration in BD and establishes one more physiopathological difference between this disorder and isolated major depression&#46; However&#44; at present there are too few published studies on BD to establish consistent hypotheses about a possible neurodegenerative origin of this disorder&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Electroretinogram in bipolar disorder</span><p id="par0140" class="elsevierStylePara elsevierViewall">The electroretinogram &#40;ERG&#41; has been the first ophthalmological tool in which alterations have been repeatedly found in patients with BD and other psychiatric diseases such as SZP or major depression&#46; A decrease in the response of the rods in the form of a lower amplitude and an increase in the latency of the b-wave have even been observed in healthy subjects of high genetic risk &#40;descendants of BD patients&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">45&#44;46</span></a> It has been postulated that these alterations are due to the enzyme glycogen synthetase kinase-3&#44;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">47&#44;48</span></a> a molecule involved in the regulation of neurotransmitters such as dopamine and serotonin&#44; and that it exhibits deregulation in these patients&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Retinal vasculature in bipolar disorder</span><p id="par0145" class="elsevierStylePara elsevierViewall">The ophthalmological examination is useful to evaluate patients with BD&#44; not only because of the findings found in the OCT analysis but also because of the image of the retinal vasculature as a representation of the brain and evaluated by retinography images&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">It is known that patients with BD have a higher incidence of cardiovascular disease&#59; therefore&#44; the group of Naiberg et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> decided to study the retinal vasculature of adolescents with BD and compare it with healthy subjects&#59; however&#44; they found no statistically significant differences between both groups in terms of the arteriovenous ratio and the diameters of the central retinal artery and the central retinal vein&#46; As a limitation in their study they had a small sample size &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; and only adolescents were used&#44; with a mean age of 17&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;86 years&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Following the same theory of a higher incidence of cardiovascular events in patients with BD and schizophrena with respect to the general population&#44; and with the evidence that these patients present a generalized microvascular dysfunction&#44; the group led by Appaji et al&#46; has recently published several works<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50&#8211;53</span></a> in which they analyze the retinal vasculature in patients with BD to compare it with that of healthy subjects and to correlate it with the rest of alterations exhibited by these patients&#44; through the exploration of the fundus of the eye as a non-invasive approximation of the state of the cerebral vasculature&#46; These works are based on the knowledge<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> that the retinal microvasculature shares embryological origin and presents common morphological and physiological characteristics&#46; They explored the alterations in 100 patients with SZP&#44; 100 with BD and 100 healthy volunteers&#44; excluding all those who exhibited high blood pressure&#44; diabetes&#44; previous cardiovascular accident or history of eye surgery or trauma&#46; They found a significant difference in the diameter between arterioles and venules between patients and healthy ones&#44; the former being narrower and the latter flatter in patients&#44; and this significant difference being between patients with SZP and BD&#44; with greater alteration in BD&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">50</span></a> In the same line&#44; they suggest that both wider blood vessels and narrower arteries are associated with cognitive defects in adults with SZP and BD&#44; as suggested also by the cerebral vasculature&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">51</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">With the same groups of patients and controls&#44; said authors analyzed the different pathways of the retinal vessels to relate them to the thickness of the RNFL&#44; which as we have already seen is a reliable marker of brain alterations&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> They were based on the work of Yamashita et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> who studied the angle formed by the main infra-temporal arteries and veins with the supra-temporal ones and which related with the thickness peaks of the peripapillary RNFL&#44; observing that this correlated with the analysis of RNFL thickness by sectors positively in some of them and negatively in others&#44; but in a statistically significant manner&#46; Appaji et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">52</span></a> determined that patients with BD had a flatter and wider retinal artery pathway and the curve of their arms was farther away from the pitting than in healthy subjects&#44; which is associated with a decrease in RNFL thickness&#46; However&#44; they found no correlation between the clinical variables of duration of the disease&#44; age of onset&#44; score on the clinical scales &#40;YMRS&#41; or treatment with antipsychotics and the pathway of arteries and veins&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Vascular tortuosity in the retinal vessels of these patients has also been evaluated<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a> as it is considered even more stable than the diameter since it is not influenced by pulse variations&#46; The result in this case was an increase in the rate of arteriolar tortuosity in BD and SZP patients compared to healthy subjects and of BD patients compared to SZP patients&#44; an observation they were not able to explain&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In recent years the study of retinal vasculature has emerged through the use of angiography associated with OCT&#44; which is called OCT-angiography&#46; It is a new non-invasive method in which the vasculature can be visualized in three dimensions without the need to inject contrast&#46; It is based on the detection of particle movement &#40;the red blood cells within the vessels&#41; and the acquisition of repeated OCT images in the same area&#44; which makes it possible to locate and show the blood vessels&#46; Its first indications have focused on the study of choroidal neovascularization and other diseases that specifically affect the retina &#40;such as diabetic retinopathy or venous obstructions&#41;&#44; but it is already beginning to be used in the evaluation of neurodegenerative diseases&#44;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;56</span></a> although to date no research has been published on its application in BD&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusions</span><p id="par0175" class="elsevierStylePara elsevierViewall">BD is a neurodegenerative disease that causes structural alterations in the brain&#46; The search for biomarkers of the disease through different ophthalmological examinations &#40;ERG&#44; retinography&#44; OCT&#41; enhances the usefulness of ophthalmological examination as a way to access the brain and determines the need to find a safe&#44; fast and reliable means such as OCT&#44; capable of observing and quantifying these alterations&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Until now&#44; it had only been possible to assess brain damage <span class="elsevierStyleItalic">in vivo</span> using MRI and in <span class="elsevierStyleItalic">postmortem</span> studies&#46; OCT study allows us to evaluate in a safe&#44; non-invasive&#44; fast and efficient way the neurodegenerative process of these patients&#44; assessing the retinal neuronal compromise that correlates with the cerebral neuronal impairment&#46; Longitudinal studies would be necessary to establish the possible correlation between the loss of retinal ganglion cells and the progression of the disease and to determine the possible role of retinal parameters as a diagnostic and progression biomarker in BD&#46; This would allow an earlier diagnosis of the disease in order to apply therapies early in these patients and thus minimize the number of episodes&#44; slow the course of the disease or improve the quality of life of patients and families&#46; Currently&#44; there are few results on the influence of BD treatment with lithium or antipsychotics and alterations in OCT&#59; however&#44; the findings found in MRI studies in which it has been seen that these drugs influence the total and grey matter volumes of the brain lead to the assumption that variations in OCT can be found depending on patient treatments&#44; which could be favored if the use of OCT for monitoring the response to treatment were significant and would help to understand the brain changes that occur in relation to treatment&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">Its use versus MRI&#44; which is commonly used for evaluation of this disease&#44; would allow faster and less costly evaluation&#44; so it could be used routinely allowing accurate monitoring of progression&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Retinography and the recent use of OCT angiography as an evaluation of the cerebral vascular system paves the way for studying psychiatric diseases through ophthalmological examination&#46; The correlation between these findings and those found in OCT could provide added value to all studies conducted to date&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Funding</span><p id="par0195" class="elsevierStylePara elsevierViewall">This work has been partly funded by the <span class="elsevierStyleGrantSponsor" id="gs0005">Juan Rod&#233;s</span> grants <span class="elsevierStyleGrantNumber" refid="gs0005">JR17&#47;00010</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs0005">PI17&#47;01726</span> &#40;Instituto de Salud Carlos III&#41;&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interest</span><p id="par0200" class="elsevierStylePara elsevierViewall">No conflict of interest was declared by the authors&#46;</p></span></span>"
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              "titulo" => "Nuclear magnetic resonance and optical coherence tomography in bipolar disorder"
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              "titulo" => "Electroretinogram in bipolar disorder"
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              "titulo" => "Retinal vasculature in bipolar disorder"
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    "fechaRecibido" => "2020-05-06"
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            0 => "Bipolar disorder"
            1 => "Optical coherence tomography"
            2 => "Retinal nerve fibre layer"
            3 => "Ganglion cell layer"
            4 => "Swept-source"
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            0 => "Trastorno bipolar"
            1 => "Tomograf&#237;a de coherencia &#243;ptica"
            2 => "Capa de fibras nerviosas de la retina"
            3 => "Capa de c&#233;lulas ganglionares"
            4 => "Swept-source"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Bipolar disorder &#40;BD&#41; is a mental disorder characterised by episodes of extremal mood changes&#46; In recent years&#44; some researchers found neurodegeneration in patients with BD using Magnetic Resonance Imaging&#46; Evaluation of the optic nerve and the retinal layers using optical coherence tomography &#40;OCT&#41; has proved to be a useful&#44; non-invasive tool for diagnosis and monitoring of neurodegenerative diseases&#46; Accordingly&#44; a decrease in the retinal nerve fibre layer and the ganglion cell complex measured by OCT was found in patients with BD in different studies&#44; suggesting that BD is a neurodegenerative process in addition to a psychiatric disorder&#46; Therefore&#44; the neuro-ophthalmological evaluation of these patients could be used as a marker for diagnosis of this disease&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">This work analyses literature on retinal degeneration in bipolar disorder patients&#44; and evaluates the ability of OCT devices in the detection of neuronal degeneration affecting the different retinal layers in these patients&#44; and its possible role in the diagnosis and monitoring of the disease&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El trastorno bipolar &#40;TB&#41; es una enfermedad mental caracterizada por episodios de alteraciones extremas del humor en la que existe evidencia de presencia de neurodegeneraci&#243;n&#44; determinada mediante resonancia magn&#233;tica nuclear&#46; En los &#250;ltimos a&#241;os&#44; la evaluaci&#243;n del nervio &#243;ptico y de las capas de la retina mediante tomograf&#237;a de coherencia &#243;ptica &#40;OCT&#41; en enfermedades neurodegenerativas ha demostrado su utilidad como biomarcador no invasivo de diagn&#243;stico y progresi&#243;n&#46; En pacientes con TB diversos estudios han encontrado disminuci&#243;n de la capa de fibras nerviosas de la retina y del complejo de c&#233;lulas ganglionares objetivables mediante OCT&#44; lo que apoyar&#237;a la hip&#243;tesis de que el TB se trata de una enfermedad neurodegenerativa adem&#225;s de un proceso psiqui&#225;trico&#46; Por ello&#44; el estudio neuro-oftalmol&#243;gico de estos pacientes podr&#237;a servir como marcador diagn&#243;stico de esta patolog&#237;a&#46; Este trabajo revisa la bibliograf&#237;a reciente sobre degeneraci&#243;n retiniana en pacientes con TB y eval&#250;a la capacidad de los dispositivos de OCT en la detecci&#243;n de degeneraci&#243;n neuronal que afecta a las diferentes capas de la retina en estos pacientes y su posible papel en el diagn&#243;stico y seguimiento de la enfermedad&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gav&#237;n A&#44; Garcia-Martin E&#44; Garcia-Campayo J&#44; Vilad&#233;s E&#44; Orduna E&#44; Satu&#233; M&#46; Utilidad de la tomograf&#237;a de coherencia &#243;ptica en la evaluaci&#243;n de los pacientes con trastorno bipolar&#46; Arch Soc Esp Oftalmol&#46; 2021&#59;96&#58;141&#8211;151&#46;</p>"
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                  \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">Results&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">Mehraban et al&#46;&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">Prospective control case&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">120 eyes &#40;60 cases 60 controls&#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">Spectral domain&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">RNFL&#58; decrease in the middle thickness&#44; lower&#44; upper and nasal quadrants&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">&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">GCL and choroidal thickness not evaluated&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">Kalenderoglu et al&#46;&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">Control case&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">86 &#40;43 cases&#44; 43 controls&#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">Spectral domain&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">RNFL&#58; overall thickness reduction&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">&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">GCL&#58; decrease in volume&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">&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">No significant difference in choroidal thickness&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">Khalil et al&#46;&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">Control case&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">80 &#40;40 cases&#44; 40 controls&#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">Spectral domain&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">RNFL&#58; decrease overall thickness and temporary&#44; upper and lower quadrants&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">&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">GCL&#58; average decrease and in upper sector&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">&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">Unevaluated choroidal thickness&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">Joe et al&#46;&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">Transversal study&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">24 &#40;3 BD&#44; 3 SZP&#44; 18 controls&#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">Spectral domain&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">RNFL and GCL&#58; not evaluated&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">&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">Total retinal thickness&#58; decreased central macular area&#44; inner of the 4 quadrants and upper outer&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">&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">No significant difference in choroidal thickness&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">Bannaia et al&#46;&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">Transversal study&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 &#40;5 BD&#44; 12 SZP&#44; 8 schizoaffective disorder&#44; 15 controls&#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">Spectral domain&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">Total retinal thickness&#44; RNFL&#44; CCG&#44; IPL&#44; INL&#58; no statistically significant decrease&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">&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">OPL&#58; increase in temporary inner sector of both eyes and of the upper inner and outer sectors of the LE&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">&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">NPO&#58; temporary and central inner sector of the RE and the higher inner and outer sectors of the LE&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">Garcia-Martin et al&#46;&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">Control case&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">110 &#40;30 patients&#44; 80 controls&#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">Spectral domain&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">RNFL&#58; average decrease and temporary sectors&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">&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">GCL&#58; decrease in volume and thickness of the 4 inner macular sectors&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">&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">Total retinal thickness&#58; decrease in the upper inner&#44; nasal and lower and upper outer sectors&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">&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">IPL&#58; decrease of inner nasal&#44; lower and temporal sectors of the macular area&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">&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">INL&#58; increase in volume and thickness in the 4 outer sectors of the macular area and the upper and lower inner sectors&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">&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">Unevaluated choroidal thickness&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">Polo et al&#46;&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">Control case&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">46 &#40;23 patients&#44; 23 controls&#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">Swept-source&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">RNFL middle&#44; upper-temporal and upper nasal decrease of peripapillary sectors&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">&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">GCL&#43;&#58; middle&#44; superior&#44; super-nasal&#44; infero-nasal and inferior decrease of the ETDRS areas&#44; middle&#44; superior&#44; superior-nasal&#44; inferior-nasal and inferior decrease of the 6 macular sectors and decrease of the peripapillary nasal sector&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">&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">GCL&#43;&#43;&#58; infero-temporal and infero-nasal decrease and of the macular and middle&#44; super-temporal&#44; super-nasal and inferotemporal sectors of the peripapillary area&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">&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">Decrease in total retinal thickness in the middle peripapillary&#44; upper temporal&#44; upper nasal&#44; nasal and lower temporal sectors and in the central&#44; interior-temporal&#44; interior-nasal and interior-inferior ETDRS areas&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">&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">No significant differences in choroidal thickness in the ETRDS and peripapillary areas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2534363.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Results of published studies on OCT and bipolar disorder&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:56 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic and statistical manual of mental disorders&#46; In&#58; fifth edition &#40;DSM5&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "American Psychiatric Association"
                          ]
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                    ]
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                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2013"
                        "editorial" => "American Psychiatric Association"
                        "editorialLocalizacion" => "Arlington"
                      ]
                    ]
                  ]
                ]
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            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis and management of bipolar disorder in primary care A DSM-5 update"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C&#46;J&#46; Brenner"
                            1 => "S&#46; Shyn"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.mcna.2014.06.004"
                      "Revista" => array:5 [
                        "tituloSerie" => "Med Clin NA"
                        "fecha" => "2014"
                        "volumen" => "98"
                        "paginaInicial" => "1025"
                        "paginaFinal" => "1048"
                      ]
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                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of lifetime comorbidity in the World Health Organization world mental health surveys"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;C&#46; Kessler"
                            1 => "J&#46; Ormel"
                            2 => "M&#46; Petukhova"
                            3 => "K&#46;A&#46; McLaughlin"
                            4 => "J&#46;G&#46; Green"
                            5 => "L&#46;J&#46; Russo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/archgenpsychiatry.2010.180"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arch Gen Psychiatry"
                        "fecha" => "2011"
                        "volumen" => "68"
                        "paginaInicial" => "90"
                        "paginaFinal" => "100"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21199968"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Psychosis in bipolar disorder&#58; phenomenology and impact on morbidity and course of illness"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;E&#46; Keck Jr"
                            1 => "S&#46;L&#46; McElroy"
                            2 => "J&#46;R&#46; Havens"
                            3 => "L&#46;L&#46; Altshuler"
                            4 => "W&#46;A&#46; Nolen"
                            5 => "M&#46;A&#46; Frye"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0010-440X(03)00089-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Compr Psychiatry"
                        "fecha" => "2003"
                        "volumen" => "44"
                        "paginaInicial" => "263"
                        "paginaFinal" => "269"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12923703"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Burden of general medical conditions among individuals with bipolar disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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Article information

ISSN: 21735794
Original language: English

DOI:10.1016/j.oftale.2020.07.004

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