Editorial
The promise of OCT as a marker of neurodegenerative pathology: A critical look
La promesa de la OCT como marcador de patología neurodegenerativa: una mirada crítica
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Busquet-Duran, J. Vidal-Alaball, S. Martínez-Somolinos, E. Pedemonte-Sarrias" "autores" => array:4 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Busquet-Duran" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Vidal-Alaball" ] 2 => array:2 [ "nombre" => "S." "apellidos" => "Martínez-Somolinos" ] 3 => array:2 [ "nombre" => "E." 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González Martín-Moro" "autores" => array:1 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "González Martín-Moro" "email" => array:2 [ 0 => "juliogmm@yahoo.es" 1 => "juliogazpeitia@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Oftalmología, Hospital Universitario del Henares, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Facultad de Medicina, Universidad Francisco de Vitoria, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La promesa de la OCT como marcador de patología neurodegenerativa: una mirada crítica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">It is a well-known fact that the medical literature tends to extol the virtues of technology while dismissing its limitations. It is difficult to find a better example than the literature published in recent years regarding the ability of optical coherence tomography (OCT) to predict neurodegenerative pathology.</p><p id="par0010" class="elsevierStylePara elsevierViewall">A biomarker is a clinical sign that can be measured with high accuracy and reproducibility.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It may have diagnostic or prognostic utility or be useful for following the progression of a disease. These signs are presumed to have a high predictive value. Several organisations consider the development of biomarkers a priority and have launched biomarker development initiatives such as the <span class="elsevierStyleItalic">Transformation Initiative</span> and the <span class="elsevierStyleItalic">Health Biomarkers Consortium</span>.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It is regarded as essential to assess the usefulness of these tools in terms of sensitivity, specificity and predictive value.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In recent years, a growing literature considers that OCT may become the marker of neurodegeneration. In the case of multiple sclerosis there is no doubt of its value, but in the case of Parkinson's, Alzheimer's and other neurodegenerative diseases its usefulness is highly questionable. However, most of the literature is very enthusiastic about the technology, giving little attention to its significant limitations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A major problem is that, in original articles, differences between healthy and sick people are usually expressed only in terms of their statistical significance, without calculating the predictive value of certain cut-off points, or taking into account the biological relevance of the differences detected or the impact of dispersion. Surprisingly, even reviews usually fail to point out these limitations. For example, a recent meta-analysis that concluded positively on the usefulness of total retinal and peripapillary nerve fibre layer thicknesses for Parkinson's disease found a mean thickness difference of 2.70 microns in the central retina between Parkinson's patients and healthy controls.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The central retina has a thickness of about 260 microns, and the dispersion of the studies included in the review was between 20 and 30 microns. This means that if we do the classic exercise of drawing the distribution curves of patients and controls, assuming normality, given the small difference and high dispersion, the result would be two curves that would completely overlap and it would be impossible to find any cut-off point that would allow us to differentiate between healthy and sick individuals. It is surprising that a 1% difference (2.7 microns in a structure that has 260 microns) could be useful to discriminate something. Should we accept that the hemoglobin level is a good parameter to differentiate healthy and sick individuals with a hematological disease because healthy people had a hemoglobin level of 10.1 and sick people had a hemoglobin level of 10? In this same meta-analysis, the calculated differences in the ganglion cell layer were somewhat larger, of the order of 3 microns in a structure that is about 80 microns thick and with a standard deviation in the order of 10. Although the magnitude of the difference is larger, again the dispersion completely negates the validity of this parameter as a useful method to differentiate healthy and diseased individuals. It seems that authors and reviewers have been dazzled by the modernity of technology and have lost the common sense to consider first and foremost the magnitude of biological differences.</p><p id="par0025" class="elsevierStylePara elsevierViewall">These studies usually compare patients affected by these degenerative diseases with healthy controls, and therefore the problem is even more accentuated in real life, where the technique should be able to differentiate between subjects with a given disease within a pool containing healthy subjects and also others affected by various diseases that also modify retinal thicknesses.</p><p id="par0030" class="elsevierStylePara elsevierViewall">A very quick search shows that in recent years some articles have been published linking retinal thicknesses to diseases as diverse as fibromyalgia,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> obesity<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> and metabolic syndrome,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> renal failure<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> and to various conditions such as low weight at birth and prematurity,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> environmental pollution,<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> antihypertensive medication, maternal hypertension during pregnancy,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> use of oral contraceptives<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> or vitamin D deficiency,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> or even passive tobacco smoke inhalation.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> If retinal thicknesses have so many determining factors, the question that immediately arises is what predictive value these measurements can have for diagnosing a particular disease.</p><p id="par0035" class="elsevierStylePara elsevierViewall">At this point, the quantification of retinal thicknesses with OCT has become an all-and-nothing marker. Unfortunately, every time a new paper is published correlating retinal thicknesses with a new disease, this technology loses value as a tool for predicting everything we previously thought it predicted. It seems increasingly clear that retinal thickness is not a specific marker of ocular health status or neurodegeneration but, in a broader sense, of an individual's general health status. It is possible that retinal thinning may be as non-specific as anemia associated with chronic process. It cannot be ruled out that the association with neurodegenerative diseases is indirect and is largely mediated by the impact that any chronic disease has on general health status.</p><p id="par0040" class="elsevierStylePara elsevierViewall">In summary, the measurement of retinal thicknesses only partially meets the definition of a biomarker. It is true that these thicknesses can be accurately and reproducibly quantified, but the changes described in neurodegenerative diseases (excluding multiple sclerosis) probably have neither the magnitude nor the specificity necessary to consider these parameters as biomarkers of neurodegeneration.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0045" class="elsevierStylePara elsevierViewall">None.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0050" class="elsevierStylePara elsevierViewall">None.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: González Martín-Moro J. 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