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Arranz-Marquez, M.Á. Teus" "autores" => array:2 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Arranz-Marquez" "email" => array:1 [ 0 => "esther.arranz@hospitalreyjuancarlos.es" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.Á." "apellidos" => "Teus" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Hospital Universitario Rey Juan Carlos, Móstoles, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Clínica Novovision, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Universidad de Alcalá, Alcalá de Henares, Madrid, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análogos de prostaglandinas en el tratamiento del glaucoma: del fármaco «milagroso» de los años 90 a la realidad del siglo XXI" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">At the end of the 20th century, the appearance of a prostaglandin analogue (PGA), latanoprost, revolutionised the treatment of glaucoma, just as timolol maleate did in the 1970s.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Prior to the launch of latanoprost, Phase III clinical trials proclaimed the excellent hypotensive efficacy of this drug, which managed to reduce IOP by an average of 6.7 mmHg, thus surpassing in efficacy the <span class="elsevierStyleItalic">gold standard of</span> the time: timolol (4.9 mmHg). In addition, as side effects they only highlighted a slight ocular hyperemia, “modest and in most cases of little clinical significance”, and an increase in iris pigmentation, described as infrequent (6.7% of patients) and of mild intensity.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Therefore, in view of the results of these first studies on efficacy and safety and with the wide dissemination of this information, it was clear that this new pharmacological group had the superiority to prevail in the glaucoma pharmaceutical market.</p><p id="par0020" class="elsevierStylePara elsevierViewall">PGAs also had a novel mechanism of action: the potentiation of aqueous outflow through the uveoscleral pathway, mediated by stimulation of FP2alpha receptors, which heralded a good hypotensive synergy with the classic beta-blockers. As an added advantage, their dosage was more convenient, since a single application per day was able to reduce IOP effectively, both day and night. On top of this, the absence of systemic adverse effects gave it a distinct advantage over the feared cardiac and bronchial effects of the hitherto ubiquitous timolol.</p><p id="par0025" class="elsevierStylePara elsevierViewall">It is not surprising, therefore, that it soon went from being a promising drug to a treatment of first choice in the management of glaucoma, thus displacing topical beta-blockers<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in practice.</p><p id="par0030" class="elsevierStylePara elsevierViewall">However, taking into account that these drugs have been among the last to arrive in the arsenal of medical treatments for glaucoma, it was to be expected that knowledge of their positive actions, but also of their harmful ones, would increase with experience. Thus, due to the efforts of individual researchers (always outside the pharmaceutical industry), it has been possible to refine the hypotensive behavior of PGAs, and to detail their side effects, both those initially known and those described after their launch.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Given the diversity of physiological and pathological effects in which natural prostaglandins are involved, it was surprising that their topical analogues had the almost supernatural ability to act exclusively on the therapeutic target of most interest to clinicians, ie., the uveoscleral pathway. Thus, we learned that some side effects such as macular edema and uveitis, which were expected and feared because we knew they were mediated by natural prostaglandins, turned out not to be as frequent with PGAs. On the other hand, we began to observe that they were capable of triggering adverse effects never described before, and quite surprising (some of these even innocently appreciated by patients as “mascara”).</p><p id="par0040" class="elsevierStylePara elsevierViewall">We discovered that secondary darkening of the iris is not as uncommon as originally announced, and to our astonishment we found that this hyperpigmentation reached significant numbers (around 69% of treated eyes)<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> and, to the astonishment of others, that it was accompanied by some histological changes in the iris rather than simply increased melanin in the melanocytes.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">It later turned out that the hyperpigmentation derived from the use of prostaglandin analogues was not limited to the iris, but also spread to everything they came into contact with, such as the periocular skin. And beyond that, because surprisingly and extraordinarily, they also proved to be able to trigger periorbital lipodystrophy, probably due to the effect of prostaglandins on orbital adipogenesis. But, even here, the most positive minds managed to turn a side effect around and look for a possible clinical utility, namely in thyroid orbitopathy.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">And, of course, if it is accepted that the main mechanism of hypotensive action of PGAs is to remodel the extracellular matrix of the main aqueous humor drainage elements, it would be strange if they were not capable of remodeling the collagen present in other ocular structures, especially those in direct contact with the active substance. Thus, although histopathological changes in the cornea, anterior chamber angle and even the ciliary body were initially ruled out, numerous subsequent independent studies have been able to demonstrate the presence of remodeling in the connective tissue of all these structures. In fact, corneal exposure to chronic APG treatment is associated with a measurable change in the biomechanical behavior of the cornea.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> That is, taking into account that PGAs are able to remodel the corneal stroma and that changes in the biomechanical characteristics of the cornea can be very powerful artifacts for Goldmann applanation tonometry (GAT), it is not unreasonable to think that at least part of the hypotensive effect recorded after chronic use of these drugs could actually be attributable to the artifact in the measuring instruments and not to a real decrease in IOP. Thus, it has been seen that, in the same population, while using GAT, IOP seems to decrease by 7.4 mmHg due to treatment with APG, if the Corvis ®ST tonometer is used, the decrease is only 4.6 mmHg.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In view of the above, we are left to ponder whether the hypotensive efficacy of PGAs is not really as high as we thought, and considering that the side effects are more frequent than initially described, perhaps it is time to reevaluate their generalized use as the drug of first choice in most patients.</p><p id="par0060" class="elsevierStylePara elsevierViewall">And, as Prof. Tuulonen pointed out in a noteworthy article, “a good clinician should be able to distinguish scientific evidence from pharmaceutical <span class="elsevierStyleItalic">marketing</span>, since research sponsored by pharmaceutical companies tends to yield more favourable results for their own products”.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest in any aspect of the article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => 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: Arranz-Marquez E, Teus MÁ. Análogos de prostaglandinas en el tratamiento del glaucoma: del fármaco «milagroso» de los años 90 a la realidad del siglo XXI. Arch Soc Esp Oftalmol. 2022;97:1–2.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Latanoprost as a new horizon in the medical management of glaucoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J. Stjernschantz" 1 => "A. 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Vol. 97. Issue 1.
Pages 1-2 (January 2022)
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Vol. 97. Issue 1.
Pages 1-2 (January 2022)
Editorial
Prostaglandin analogues for the treatment of glaucoma: From the “wonder” drug of the ‘90s to the reality of the 21st century
Análogos de prostaglandinas en el tratamiento del glaucoma: del fármaco «milagroso» de los años 90 a la realidad del siglo XXI
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