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Smart contact lens: A promising therapeutic tool in aniridia
Lente de contacto inteligente: una prometedora herramienta terapéutica en aniridia
A. Vásquez Quinteroa,
Corresponding author
andres.vasquez@ugent.be

Corresponding author.
, P. Pérez-Merinob,c, A.I. Fernández Garcíad, H. De Smeta
a Ghent University/IMEC, Zwijnaarde, Belgium
b Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain
c Medical Engineering Development and Innovation Center, Universidad Autónoma de Madrid, Madrid, Spain
d Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Aniridia is a congenital and rare global disorder of the eye&#44; of which iris hypoplasia is the most obvious clinical sign&#46; The disease affects all ocular structures including the cornea&#44; iris&#44; ciliary body&#44; lens&#44; retina and optic nerve&#44; and is clinically characterised by the development of different ocular pathologies such as keratopathy&#44; cataract&#44; glaucoma and nystagmus&#46; Aniridia is a congenital and hereditary disease mainly caused by deletion of the PAX6 gene on chromosome 11-p13&#44; which leads to altered development of the ocular globe&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Aniridia can also occur in an acquired form as a result of traumatic or iatrogenic injury following surgery&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Congenital aniridia is a bilateral disease with an incidence between 1&#58;65&#44;000&#8211;95&#44;000&#44; which affects both sexes equally and is not more prevalent according to race&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Symptoms in these patients can range from intense photophobia&#44; glare and low visual acuity to severe dry eye&#44; with frequent symptoms of irritation and itching&#46; The second most compromised ocular structure is the cornea&#44; representing the most frequent cause of congenital limbal deficiency&#46; In patients with aniridia&#44; the corneal epithelium does not regenerate optimally and causes keratopathies of varying degrees&#44; with conjunctival epithelialisation over the peripheral cornea&#44; peripheral superficial vascularisation&#44; appearance of fibrocellular nodular lesions under the conjunctival epithelium and opacities in the corneal stroma being the main clinical findings observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;7</span></a> In addition&#44; patients with aniridia present with dry eye due to tear deficiency&#44; tear film instability and dysfunction of the meibomian glands&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;8&#44;9</span></a> With age&#44; limbic insufficiency progresses and dry eye also worsens&#44; both factors being related to the progression of keratopathy&#46; These patients also often develop glaucoma and cataracts in the first two decades of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#8211;12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">At present there is no effective treatment for aniridia&#44; so each symptom must be treated individually&#46; Traditionally&#44; both filters and fixed aperture artificial iris diaphragms have been incorporated into spectacles&#44; contact lenses and intraocular lenses to improve visual quality and diminish photophobia&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#8211;17</span></a> However&#44; the use of contact lenses is not widespread among these patients due to the associated discomfort caused by the dryness of their eyes&#46; In addition&#44; if they use soft contact lenses&#44; these are <span class="elsevierStyleItalic">per se</span> a disruptive element of the physiology of the ocular surface due to the involvement of the limbal area&#46; In this respect&#44; the recent appearance on the market of different designs of scleral support contact lenses could represent a major therapeutic advance in aniridia&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Scleral contact lenses range in diameter from 12&#46;5 to 20&#160;mm&#44; and the design can be customised for each eye based on the dome that best fits over the ocular surface to provide the best visual quality and comfort&#46; Scleral support preserves the limbal area and creates a smooth&#44; even fluid space between the corneal surface and the contact lens&#44; preserving the integrity of the ocular surface and partially alleviating the symptoms associated with dry eye pathology&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a> In this way&#44; the scleral lens would also serve to bandage&#44; protect and hydrate the cornea and limbus&#46; Specifically&#44; several studies have been published on patients with Sj&#246;gren&#39;s syndrome&#44; Stevens&#8211;Johnson syndrome or epithelial defects who improved visual quality and reduced dry eye symptoms with the use of scleral platform contact lenses&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#8211;23</span></a> In addition&#44; promising results in pediatric patients with dry eye triggering disease&#44; both in visual quality and corneal surface integrity&#44; have also been reported with the scleral contact lens&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Lastly&#44; the scleral design presents an ideal platform for encapsulating electronic components in a contact lens to control the aperture of an artificial iris according to environmental conditions&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#8211;28</span></a> This fact would allow us to seek a physiological solution in aniridia with the development of a smart contact lens&#44; as it has the advantages of &#40;i&#41; an active iris with variable aperture that would automatically modulate the illuminance on the retina and &#40;ii&#41; a choice of pupillary centre that minimises corneal aberrations&#44; overcoming the disadvantages of passive and irreversible intraocular implants with fixed aperture&#44; and the associated surgical complications&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;15&#44;16</span></a> For the application of artificial iris in smart contact lenses&#44; liquid crystal cells are effective as an active electro-optic component&#44; as they can produce rapid and automatic changes in pupil size depending on the orientation of the liquid crystal&#44; filtering the amount of light entering the eye and&#44; consequently&#44; significantly reducing photophobia&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">This paper discusses preclinical tests especially of optical simulation of a scleral lens with a platform inserted into it&#44; replicating the experimentally obtained contrast of liquid crystal cells&#46; In addition&#44; the simulations are performed with real data from eyes with congenital aniridia&#44; properly represented in optical models&#46; These tests are the prelude to the clinical trials that are currently underway at the University Hospital of Ghent University &#40;Belgium&#41; with healthy volunteers&#46; The results of these tests&#44; in combination with biocompatibility tests &#40;ISO 10993&#41;&#44; will be used to design and implement clinical trials with active devices and aniridia patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Smart contact lens manufacturing process</span><p id="par0035" class="elsevierStylePara elsevierViewall">The smart contact lens is composed of two main parts &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#58; &#40;i&#41; ultra-thin gold-based circuit and &#40;ii&#41; <span class="elsevierStyleItalic">Guest-Host Liquid Crystal</span> Cell &#40;GH-LCD&#41;&#46; On the one hand&#44; the circuit is made with photolithography and chemical etching processes in order to achieve thin layers of gold and fabricate the interconnects and the antenna&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> On the other hand&#44; the GH-LCD cell consists of a flexible&#44; transparent substrate and transparent PEDOT&#58;PSS electrodes on each side&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> The cell combines liquid crystals with a dichroic dye that has the property of absorbing segments of the visible spectrum depending on its orientation&#46; This orientation can be graduated through an electric field applied directly by the transparent electrodes&#46; The system is designed with concentric GH-LCD rings that can be activated in a controlled and consecutive manner in order to mimic the function of a healthy iris&#46; Additionally&#44; the internal silicon chip measures the amount of light in the environment &#40;via photodiodes&#41; and automatically acts on the respective number of rings to control the effective size of the artificial pupil&#46; Finally&#44; the circuit connected to the GH-LCD cell is thermoformed and integrated directly into a scleral contact lens with its conventional design to optimise vision and patient comfort&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Transmittance of the smart contact lens</span><p id="par0040" class="elsevierStylePara elsevierViewall">The main advantage of the smart contact lens with artificial iris function is that it will reduce the amount of light entering the eye in a programmed manner with the ambient illumination&#44; resulting in a reduction of retinal illuminance adapted to the visual needs of the patient&#46; <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> shows that the transmittance in the visible part of the electromagnetic spectrum decreases from 98&#46;8 to 65&#37; in the off state &#40;GH-LCD OFF&#41;&#44; since the liquid crystal configuration itself produces a filtering effect on the perceived image&#44; and drops to 32&#37; when the liquid crystal configuration has the artificial iris function active &#40;GH-LCD ON&#41;&#44; attenuating the illuminance levels 1&#58;2&#46;03&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Visual quality of the smart contact lens</span><p id="par0045" class="elsevierStylePara elsevierViewall">Scleral contact lenses can correct both astigmatism and corneal aberrations in patients with aniridia&#44; as the optical system formed by the contact lens and the cornea becomes more regular in shape&#46; The irregularities of the corneal surface are compensated by the lacrimal meniscus between the inner surface of the lens and the anterior surface of the cornea&#44; leaving the anterior surface of the scleral contact lens &#40;with a regular surface&#41; as the outer part of the optical system&#46; However&#44; a conventional scleral design of spherical geometry is not able to compensate for all ocular aberrations&#44; as can be seen by comparing <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#40;a&#41; and &#40;b&#41;&#44; since a pupil diameter of 8&#160;mm presents spherical aberration of large magnitude&#46; This magnitude of spherical aberration would be partly compensated by an aspheric geometry design&#44; <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#40;c&#41;&#46; However&#44; as we see in <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#40;d&#41;&#44; the impact of the aberrations would be almost entirely compensated with the same design by decreasing the pupil diameter&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#40;d&#41;&#44; we also see the attenuation of light intensity produced by the liquid crystal configuration&#46; The inherent fact of having a filter in the smart contact lens itself would allow us to programmatically control safe retinal illumination levels&#44; reduce glare&#44; and perhaps delay lens opacification and the onset of cataracts in adolescence&#46; <a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows an OCT image of an aniridia patient &#40;data used in the optical models&#41;&#44; showing a pattern of lens opacification in the posterior and peripheral part of the lens&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The concept presented in this article is being clinically validated using passive &#40;i&#46;e&#46;&#44; without electronics&#41; scleral prototypes with light filters to replicate pupil and iris function&#46; This testing would allow compliance with medical regulations and biocompatibility testing before using active prototypes with patients&#46; The validation is part of clinical trials currently being evaluated with 10 healthy volunteers &#40;using drops to dilate the pupil and mimic the condition of aniridia with pupils of 8&#46;5&#160;mm in diameter&#41; at the University Hospital of Ghent University&#46; The tests focus on comparing contrast sensitivity and visual acuity &#40;as primary objectives&#41;&#44; as well as comfort and oxygen transparency &#40;as secondary objectives&#41;&#46; After this validation&#44; tests with active devices including liquid crystal cells and electronics will be clinically evaluated with healthy volunteers and aniridia patients&#46; Such devices will be more advantageous than current devices due to their automatic adaptability and high discretion&#46; The results of tests with passive and active scleral prototypes will be presented in a future article&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0060" class="elsevierStylePara elsevierViewall">Due to the possibility offered by integrated microelectronics and photonics&#44; allowing us to generate and control optical signals within a circuit&#44; and the current ability to implement electronic chips&#44; wireless circuits&#44; batteries and miniaturised sensors in optical solutions&#44; we are at a stage where we can encapsulate active elements in a passive element&#44; a contact lens&#44; and explore with precision and in real time optical and physiological responses that cannot be achieved with traditional methods&#44; and thus cover part of the visual needs of patients with aniridia&#46; The ability to implement light-adaptive transmission and focus expansion with flexible electronic circuits and the inclusion of programmable liquid crystals in the scleral contact lens configuration with the potential to preserve the integrity of the ocular surface&#44; in particular the limbal zone&#44; in this pathology is very promising in this respect&#46; This article demonstrates by means of optical simulations the concept of a small pupil integrated into a scleral contact lens for patients with aniridia&#46; It also paves the way for clinical trials with healthy volunteers &#40;induced large pupils&#41; and aniridia patients&#46; The results demonstrate reduced retinal illumination and higher visual quality&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0065" class="elsevierStylePara elsevierViewall">This study has been funded in part by the <span class="elsevierStyleGrantSponsor" id="gs0005">VLAIO IM</span> project number&#58; <span class="elsevierStyleGrantNumber" refid="gs0005">H8C&#46;2018&#46;0170</span> and in part by the Thematic Network for Cooperative Health Research &#34;OFTARED&#34; &#8211; Reference&#58; RD16&#47;0008&#47;0012&#46; Funded by the <span class="elsevierStyleGrantSponsor" id="gs0010">Instituto de Salud Carlos III&#47;State Research Agency</span> and by the <span class="elsevierStyleGrantSponsor" id="gs0015">European Regional Development Fund &#40;ERDF&#41;</span>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interest</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "titulo" => "Methods"
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              "identificador" => "sec0015"
              "titulo" => "Smart contact lens manufacturing process"
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              "titulo" => "Transmittance of the smart contact lens"
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    "fechaRecibido" => "2020-12-01"
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            0 => "Aniridia"
            1 => "Scleral contact lenses"
            2 => "Liquid crystal cells"
            3 => "Optical simulations"
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            0 => "Aniridia"
            1 => "Lentes de contacto esclerales"
            2 => "Celdas de cristal l&#237;quido"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The perform pre-clinical testing using optical design tools to simulate the optical quality of a smart artificial iris platform encapsulated in a scleral contact lens&#46; These tools allow us to generate aniridia eye models and evaluate different metrics of visual quality and retinal illumination based on the aperture of the artificial iris based on liquid crystals&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">The OCT imaging technique was used to measure the geometry of the anterior segment in a patient with aniridia and&#44; from these data&#44; the eye model was generated with the Zemax optical design program and specific programs developed in Matlab&#46; Ocular aberrations were calculated and the visual function of the anirida eye model was evaluated in three scenarios&#58; &#40;i&#41; without optical correction&#44; &#40;ii&#41; with correction with a commercial scleral contact lens&#44; and &#40;iii&#41; with correction with an optical lens&#46; Intelligent contact based on artificial iris&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Optical quality in patients with aniridia is limited by the magnitude of high-order aberrations&#46; Conventional scleral contact lens design accurately corrects for blur but is unable to compensate for high-order ocular aberrations&#44; especially spherical aberrations&#46; The artificial iris-based smart contact lens design enables virtually all high-order aberrations to be compensated with active control of the pupillary diameter &#40;activation of liquid crystal cells based on ambient lighting&#41;&#46; In addition to minimizing high-order aberrations&#44; reducing the pupil size would increase the depth of focus&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">This article demonstrates by means of optical simulations the concept of an intelligent artificial iris platform encapsulated in a scleral contact lens and its possible application in patients with aniridia&#46; Furthermore&#44; it allows us to anticipate possible visual results in clinical trials with healthy patients &#40;after application of mydriatic agents&#41; and in patients with aniridia&#46; The results demonstrate a better visual quality and a decrease in retinal illumination&#46;</p></span>"
        "secciones" => array:4 [
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            "identificador" => "abst0005"
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            "titulo" => "Method"
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          2 => array:2 [
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Realizar las pruebas pre-cl&#237;nicas por medio de herramientas de dise&#241;o &#243;ptico para simular la calidad &#243;ptica de una plataforma inteligente de iris artificial encapsulada en una lente de contacto escleral&#46; Estas herramientas nos permiten generar modelos de ojo de aniridia y evaluar distintas m&#233;tricas de calidad visual y de iluminaci&#243;n retiniana en funci&#243;n de la apertura del iris artificial basado en cristal l&#237;quido&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se utiliz&#243; la t&#233;cnica de imagen de OCT para medir la geometr&#237;a del segmento anterior en un paciente con aniridia y&#44; a partir de estos datos&#44; se gener&#243; el modelo de ojo con el programa de dise&#241;o &#243;ptico Zemax y programas espec&#237;ficos desarrollados en Matlab&#46; Se calcularon las aberraciones oculares y se evalu&#243; la funci&#243;n visual del modelo de ojo de anirida en tres escenarios&#58; &#40;i&#41; sin correcci&#243;n &#243;ptica&#44; &#40;ii&#41; con la correcci&#243;n con lente de contacto escleral comercial y &#40;iii&#41; con la correcci&#243;n con lente de contacto inteligente basada en iris artificial&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">La calidad &#243;ptica en pacientes con aniridia est&#225; limitada por la magnitud de las aberraciones de alto orden&#46; El dise&#241;o de lente de contacto escleral convencional corrige de forma precisa el desenfoque pero no es capaz de compensar las aberraciones oculares de alto orden&#44; especialmente la aberraci&#243;n esf&#233;rica&#46; El dise&#241;o de lente de contacto inteligente basada en iris artificial permite compensar pr&#225;cticamente la totalidad de las aberraciones de alto orden con un control activo del di&#225;metro pupilar &#40;activaci&#243;n de las celdas de cristal l&#237;quido en funci&#243;n de la iluminaci&#243;n ambiental&#41;&#46; Adem&#225;s de minimizar las aberraciones de alto orden&#44; al reducir el tama&#241;o de pupila se aumentar&#237;a la profundidad de foco&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Este art&#237;culo demuestra por medio de simulaciones &#243;pticas el concepto de una plataforma inteligente de iris artificial encapsulada en una lente de contacto escleral y su posible aplicaci&#243;n en pacientes con aniridia&#46; Adem&#225;s&#44; nos permite anticipar los posibles resultados visuales en las pruebas cl&#237;nicas con pacientes sanos &#40;previa aplicaci&#243;n de agentes midri&#225;ticos&#41; y en pacientes con aniridia&#46; Los resultados demuestran una mejor calidad visual y una disminuci&#243;n de la iluminaci&#243;n retiniana&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; V&#225;squez Quintero A&#44; P&#233;rez-Merino P&#44; Fern&#225;ndez Garc&#237;a AI&#44; De Smet H&#46; Lente de contacto inteligente&#58; una prometedora herramienta terap&#233;utica en aniridia&#46; Arch Soc Esp Oftalmol&#46; 2021&#59;96&#40;S1&#41;&#58;68&#8211;73&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Reference image &#40;without smart contact lens&#41;&#59; &#40;b&#41; smart contact lens&#44; with the liquid crystal configuration in the off state &#40;GH-LCD OFF&#41; and &#40;c&#41; smart contact lens&#44; with the liquid crystal configuration in the on state &#40;GH-LCD ON&#41;&#46; The right-hand side shows the attenuation of the illumination on the letter &#34;e&#34; as a function of the liquid crystal configuration encapsulated in the smart contact lens&#46; Image obtained from V&#225;squez Quintero et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46;</p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Visual simulations of the Snellen letter E and illustration of its corresponding PSF&#46; &#40;a&#41; Aniridia patient &#40;pupil diameter&#58; 8&#160;mm&#41;&#59; &#40;b&#41; aniridia patient with a conventional scleral contact lens design of spherical geometry &#40;pupil diameter&#58; 8&#160;mm&#41;&#59; &#40;c&#41; aniridia patient with custom scleral contact lens surface design &#40;pupil diameter&#58; 8&#160;mm&#41;&#59; &#40;d&#41; aniridia patient with custom scleral contact lens surface design and active artificial iris function &#40;pupil diameter&#58; 6&#160;mm&#41;&#46; Image obtained from V&#225;squez Quintero et al&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a>&#46;</p>"
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                      "titulo" => "Implication of non-coding PAX6 mutations in aniridia"
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                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Plaisanci&#233;"
                            1 => "M&#46; Tarilonte"
                            2 => "P&#46; Ramos"
                            3 => "C&#46; Jeanton-Scaramouche"
                            4 => "V&#46; Gaston"
                            5 => "H&#46; Dollfus"
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                      "doi" => "10.1007/s00439-018-1940-x"
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                        "tituloSerie" => "Hum Genet&#46;"
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                        "volumen" => "137"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30291432"
                            "web" => "Medline"
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Original language: English
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