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Analysis and follow-up of type 1 choroidal neovascularisation with optical coherence tomography–angiography after antiangiogenic treatment
Análisis y seguimiento con angiografía por tomografía de coherencia óptica de neovascularización coroidea tipo 1 en degeneración macular tras tratamiento antiangiogénico
R. Torrecillas-Picazo
Corresponding author
raultorrecillas@gmail.com

Corresponding author.
, M. Cerdà-Ibáñez, I. Almor Palacios, J.M. Hervás Hernandis, R. Ramón-Cosín, N. Ruiz del Rio, A. Duch-Samper
Servicio de Oftalmología, Hospital Clínico Universitario de Valencia, Valencia, 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">Since the 60s&#44; the visualization of the retinal and choroidal vascular network was based on 2 main techniques&#58; Fluorescein angiography &#40;FAG&#41; and indocyanine green angiography &#40;ICG&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">1</span></a> Both techniques allow the observer to watch vessels filling up in real-time and to determine contrast leak and the time when it occurs&#46; Fluorescein patterns in ARMD have enabled the characterization of neovascular proliferative lesions and facilitated the understanding of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">2&#44;3</span></a> As described by Gass&#44;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">4</span></a> classic CNV &#40;CNV type 2&#41; is characterized by well-defined hyperfluorescence in early FAG stages with extravasation in late stages that masks lesion edges&#46; Hidden CNV &#40;CNV type 1&#41; is defined by a regular elevation of the retina pigment epithelium &#40;RPE&#41; with dotted hyperfluorescence occurring 1&#8211;2<span class="elsevierStyleHsp" style=""></span>min after fluorescein injection and diffuse extravasation in the final phase&#46; For this reason&#44; the distortion of the image that produces contrast extravasation&#44; particularly in late stages&#44; makes it difficult to adequately characterize these structures&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">With the appearance of spectral domain optical coherence tomography &#40;SD-OCT&#41;&#44; the activity or quiescence of neovascular membranes type 1 has been calculated on the basis of indirect parameters such as RPE smoothness&#44; reflectiveness of the space underlying the RPE and the presence of subretinal hypo-reflective material corresponding to subretinal fluid &#40;SRF&#41; exudation which&#44; together with the presence of intraretinal liquid&#44; has traditionally determined the decision to treat&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">5</span></a> Unfortunately&#44; this technique is unable to discriminate an active neovascular network from other adjacent tissue as well as fibrotic scars or drusenoid RPE detachments&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">1&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">OCT angiography &#40;A-OCT&#41; is a novel diagnostic imaging technique that&#44; without being invasive&#44; enables the characterization of retinal blood flow and visualization of the vascular network&#46; To this end&#44; it applies phase or amplitude decorrelation technology that is able to detect the movement of erythrocytes that occurs between successive B-scan sections generated by OCT&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#8211;9</span></a> The majority of the algorithms applied by A-OCT are based on amplitude decorrelation as it does not require complex phase correction methods and exhibits an improved signal-noise ratio&#46; The most widely used algorithm is split spectrum amplitude decorrelation angiography &#40;SSADA&#41;&#46; The end results are high resolution 3-D images enabling a volumetric angiographic analysis of retinal layers in combination with the structural analysis provided by OCT&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of this study is to describe the vascular network of neovascular lesions&#44; inferring the response to treatment on the basis of quantitative parameters and to sequentially quantify A-OCT changes after treatment with anti-VEGF&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects&#44; material and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A prospective observational study that included 6 eyes of 6 patients with na&#239;ve CNV&#46; The patients were selected between February and April 2016 at the Clinic Hospital of Valencia &#40;Valencia&#44; Comunitat Valenciana&#44; Spain&#41;&#46; The study had the approval of the ethical committee of the hospital and all participants signed an informed consent prior to the study&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Selected subjects underwent a basic ophthalmological examination that included anamnesis and clinical history&#44; best corrected visual acuity &#40;BCVA&#41;&#44; anterior and posterior pole evaluation with slit lamp and intraocular pressure measurements with applanation tonometry&#46; The study excluded patients with a history of retinal alterations other than ARMD&#44; but had received previous treatments such as photodynamic therapy&#44; laser photocoagulation&#44; anti-VEGF injections or vitreoretinal surgery and refractive defects beyond the range of &#8722;6D to &#43;6D&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The A-OCT and OCT images were taken with AngioPlex Cirrus HD-OCT model 5000 &#40;Carl Zeiss Meditec&#44; Inc&#46;&#44; Dublin&#44; USA&#41; and DRI OCT Triton SS-OCT Angio &#40;Topcon&#44; Medical Systems&#44; Inc&#46;&#44; Oakland&#44; NJ&#44; USA&#41;&#46; In all cases&#44; a scanner centered in the fovea having 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm and 6<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>mm was utilized&#46; The scan is a selected for the follow-up period in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1&#8211;3</a> correspond to A-OCT DRI OCT Triton due to better image quality&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">AngioPlex applies the optical microangiography algorithm &#40;OMAG&#41;&#44; with a scanning speed of 68&#44;000<span class="elsevierStyleHsp" style=""></span>scans&#47;s and a source of light with a wavelength centered at 840<span class="elsevierStyleHsp" style=""></span>nm&#46; The resulting 3D cube comprises 245 B-scans&#44; each made up by 245 A-scans&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">12</span></a> DRI OCT Triton SS-OCT Angio is based on the OCTARA algorithm and has a scanning speed of 100&#44;000<span class="elsevierStyleHsp" style=""></span>scans&#47;s and a wavelength centered at 1050<span class="elsevierStyleHsp" style=""></span>nm&#46; The final resolution of the 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm cube reaches 320<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>320 A-scans&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> Both devices generate an automatic segmentation of retinal layers&#44; that was manually adjusted for enhancing the display of the choriocapillary plexus&#46; The membrane areas were measured manually with the software provided by the devices&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">During the follow-up period&#44; patients were treated with a total of 3 injections of an anti-VEGF medicaments&#44; comprising ranibizumab &#40;Lucentis&#59; Novartis Pharma AG&#44; Basel&#44; Switzerland&#41; as well as aflibercept &#40;Eylea&#59; Bayer&#44; Basel&#44; Switzerland&#41;&#44; separated by a 30-day period&#46; A-OCT was taken before each injection&#44; 24<span class="elsevierStyleHsp" style=""></span>h thereafter &#40;only in the first cycle&#41; and at 7 days&#46; BCVA was assessed at baseline and one month after each injection&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">According to the classification proposed by Freund et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">14</span></a> all the cases included in the study were diagnosed as CNV type 1 through OCT as they exhibited lesions indicating neovascularisation in a space limited below by the hyper-reflective monolayer corresponding to Bruch&#39;s membrane &#40;BM&#41; and above by the hyper reflective RPE strip&#46; Exudation took place predominantly in the subretinal space&#46; In contrast&#44; CNV type II is defined by the lesions that penetrate through the RPE&#47;BM complex and proliferate over the RPE and below the external photoreceptor layer&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The evaluation of the activity rate of CMV was based on the criteria developed by Coscas et al&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">15</span></a> for A-OCT that establishes a 5 relevant parameters&#58; shape&#44; ramification pattern&#44; anastomosis&#44; configuration of vessel ends and presence of perilesional hypointense halo&#46; To characterize the form of the neovascular membranes&#44; the description proposed by Kuehlewein et al&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> was followed&#46; This description distinguishes 2 main morphological types&#44; one with a central nutritional vessel and ramification from the center of the lesion &#40;medusa pattern&#41; and another where over 90&#37; of the neovascular network emerges from a lateral nutritional vessel &#40;sea fan pattern&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">The study included 4 males and 2 females&#44; all being Caucasian&#46; The age range was comprised between 62 and 86 years&#44; with a mean of 74 years&#46; Baseline BCVA ranged between 0&#46;15 and 0&#46;6 &#40;decimal scale&#44; Snellen test&#41;&#44; with a mean of 0&#46;31&#46; Four subjects were given ranibizumab charge doses and 2 were given aflibercept&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Case 1 is a 76-year-old male with diminished VA with 2 months evolution and metamorphopsia&#46; Baseline BCVA was 0&#46;3&#46; Posterior pole photography &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>a&#41; evidenced perifoveolar hard to drusen and an area temporal to the fovea with a slightly grayish appearance &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>b&#41;&#46; The cross-section in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the segmentation lines between RPE and BM&#44; corresponding to the location of the analyzed <span class="elsevierStyleItalic">in face</span> angiograms&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>c shows a neovascular membrane with well defined edges and the typical wheel form&#46; The ramification pattern features numerous thin capillaries with multiple anastomotic loops and vessels ending in a highly populated peripheral arch&#46; The last activity parameter defined by the presence of hypointense perilesional halo was not fulfilled&#46; Overall&#44; for out of the 5 activity items proposed by Coscas et al&#46; appear in this CNV and predict positive response to treatment&#46; According to the Kuehlewein classification&#44; case one CNV is compatible with the sea fan pattern&#46; The area of the lesion prior to treatment &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>f&#41; was 1549<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Twenty-four hours after the first anti-VEGF injection&#44; the anastomosis is diminished&#44; terminal vessels receded and capillaries disappeared&#46; Swept-source OCT &#40;SS-OCT&#41; reveals an incipient SRF reduction &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>a&#41;&#46; The CNV area diminished 18&#46;2&#37; &#40;down to 1267<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&#41;&#46; Seven days later&#44; the biggest area reduction can be seen &#40;overall reduction of 46&#37; down to 837<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&#41;&#46; Rarefaction of anastomosis and fragmentation of capillaries increases &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>b&#41;&#46; The lateral nutritional vessel maintains the baseline appearance&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">One month after the first injection the area remained stable &#40;826<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&#41; although the first signs of re-proliferation can be seen such as increased density of superior vascular endings and of the thickness of vessels depending from the nutritional vessel &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>c&#41;&#46; Seven days after the second anti-VEGF injection the changes observed in the first cycle are repeated and the re-proliferation processes is halted&#46; The area is of 528<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> and overall reduction reaches 58&#46;3&#37; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>d&#41;&#46; One month after the 2nd injection a significant sharpening of the vessels takes place together with nearly complete attenuation of the initial anastomosis &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>e&#41;&#46; The last A-OCT corresponding to the week after the last treatment showed an interactive neovascular lesion&#46; The only identifiable structure compared to baseline was the nutritional vessel&#46; The final area was 255<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> and the overall reduction of 83&#46;5&#37; when compared to the original area &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>f&#41;&#46; SS-OCT reveals complete SRF reabsorption and persistence of uneven RPE&#46; BCVA improved from 0&#46;3 to 0&#46;6&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Case 2 presents a 62-year-old male with progressive VA reduction and none exudative ARMD diagnostic in the contralateral eye&#46; Baseline BCVA was 0&#46;6&#46; SS-OCT centered in the macula revealed findings compatible with MNV type 1 &#40;hyper-reflective material underlying irregular RPE&#41;&#44; with very little SRF &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>a&#41;&#46; In this case&#44; the neovascular network through A-OCT exhibited a lengthened shape &#40;in sea fan pattern&#41; with large&#44; mature looking of vessels&#46; The initial area was 408<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&#46; A very low number of thin capillaries can be observed and no anastomotic loops could be found&#46; Vascular endings exhibited a shop and appearance and no perilesional hypointense halo could be found&#46; The activity criteria described above suggested quiescent CNV and predicted poor response to treatment&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Twenty-four after the first anti-VEGF injection&#44; the area remained stable without substantial morphological changes &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>b&#41;&#46; During the rest of the follow-up&#44; no new CNV exudation was observed&#46; The main nutritional vessel and the rest of the described network remained unaltered during successive checkups&#46; The angiogram of the week after the 3rd treatment revealed the absence of changes&#46; The final area was 346<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span> &#40;a vessel that seemed more attenuated was excluded from the measurement&#41; with total reduction of only 15&#46;2&#37; vis-&#224;-vis the baseline area &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>c and d&#41;&#46; BCVA remained at 0&#46;6&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Of the 4 remaining cases&#44; to did not complete the follow-up due to exhibiting CNV eccentric to the fovea and the impossibility of centering the angiogram on the desire to macular area&#46; In these cases&#44; the images obtained did not enable an adequate evaluation of the lesions&#46; The remaining 2 cases exhibited characteristics similar to case 2&#46; The results are summarized in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">A-OCT is a novel technique that is being used increasingly in hospitals all over the world due to the possibility of noninvasively characterizing neovascular complexes in pathologies such as exudative ARMD&#46; Applying the SSADA algorithm&#44; Jia et al&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> demonstrated the relationship between the flow index in CNV and the density of the neovascular network&#44; and characterized the first membranes with a definition of lesion edges superior to techniques such as FAG&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In a series of cases&#44; Palejwala et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">17</span></a> identified 2 patients with CNV type I that was &#8220;non-exudative&#8221;&#44; i&#46;e&#46;&#44; without late losses in FAG or SRF in SD-OCT&#41; and emphasized the value of the screening technique for high risk patients before visual deterioration&#46; Other authors also reported good sensitivity and specificity rates in the detection of quiescent type I neovascular membranes&#44; as well as type II and angiomatous proliferations&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">18</span></a> A high percentage of quiescent CNV lacks a central&#44; thick nutritious vessel&#44; which could indicate protection against more aggressive forms of the disease&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The present study enabled monitoring the evolution of several type I CNV cases during a cycle of 3 anti-VEGF injections spanning 3 months&#46; The activity criteria proposed by Coscas et al&#46; have demonstrated to be a useful tool that is able to predict the response to treatment&#46; Case 1 is a good example of the role that A-OCT plays in the follow-up of these patients&#46; The regression pattern and the cyclic re-proliferation of CMV follows time frames that are consistent with other studies such as that by Lumbroso et al&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">19</span></a> who carried out a follow-up in CNV type 2 and determined that the duration of the complete cycle is approximately 45&#8211;60 days&#46; The early effect of the medicament &#40;24<span class="elsevierStyleHsp" style=""></span>h&#41; is surprising&#44; showing attenuation of capillaries and anastomosis&#46; The maximum activation of the neovascular network seems to occur between day 7 and 28&#44; and the first signs of re-proliferation appear in A-OCT taken one month after treatment&#46; After each of the 3 treatments&#44; the same vessels tend to reappear with diminished flow and lower capillary density&#46; In the present case&#44; no neovascularization areas were found&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The fact that throughout the entire process the main nutritious vessel remains unaltered is significant&#46; This peculiarity was described by Spaide<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">20</span></a> and is replicated in other cases&#46; It has been suggested that&#44; in contrast with the rest of the neovascular network&#44; the endothelial cells comprising the main vessel are coated with pericytes&#46; This makes the nutritional vessel more resistant to the action of anti-VEGF medicaments and explains its persistence despite continued treatment&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The main limitation of the study is its small sample size and the short follow-up period&#46; The study protocol did not include comparison with FAG&#47;ICG&#44; with the CNV diagnostic being obtained exclusively through OCT&#46; The limitations of said technique also had a bearing on the results&#46; The algorithms applied in A-OCT depend on blood flow detection&#44; which means that small movements by the patient produced considerable artifacts&#46; The time utilized by the majority of available devices is higher than the time required by standard OCT&#44; and therefore it is a challenge to acquire quality images of patients with fixation alterations&#46; Present device software includes manual application measurement tools on <span class="elsevierStyleItalic">in face</span> sections&#44; which influences the reliability of results&#46; For this reason&#44; the authors consider that at present the technique can contribute more to the qualitative and descriptive aspect of clinic work&#46; At this time&#44; there are no 3-D volumetric measurement tools&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">21</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Despite the above&#44; A-OCT emerges as a promising imaging mode that can supplement the use of other techniques&#46; The possibility of visualizing CNV in ARMD opens an unexplored research field&#46; The detection of quiescent neovascular membranes enables the identification of patients who require close follow-up&#46; By way of conclusion&#44; it can be stated that the diverse activity criteria related to lesion morphology could assist in planning the time to treat&#44; particularly in <span class="elsevierStyleItalic">pro re nata</span> protocols&#44; as well as facilitating the qualitative and quantitative follow-up of said pathology&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">No conflict of interests was declared by the authors&#46;</p></span></span>"
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            0 => "Choroidal neovascularisation"
            1 => "Optical coherence tomography angiography"
            2 => "Age-related macular degeneration"
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            0 => "Neovascularizaci&#243;n coroidea"
            1 => "Angiograf&#237;a por tomograf&#237;a de coherencia &#243;ptica"
            2 => "Degeneraci&#243;n macular asociada a la edad"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aim</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe the characteristics of type 1 choroidal neovascularisation &#40;CNV&#41; in age-related macular degeneration &#40;ARMD&#41; using two different optical coherence tomography angiography &#40;OCT-A&#41; devices sequentially during a standard protocol of three intravitreal injections of an anti-vascular endothelial growth factor &#40;anti-VEGF&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The study included 6 eyes with na&#239;ve neovascular ARMD&#46; Macular OCT-A images were acquired using AngioPlex Cirrus HD-OCT 5000 &#40;Carl Zeiss Meditec&#44; Inc&#46;&#44; Dublin&#44; USA&#41; and DRI OCT Triton SS-OCT Angio &#40;Topcon&#44; Medical Systems&#44; Inc&#46;&#44; Oakland&#44; NJ&#44; USA&#41;&#46; The macular OCT-A scan covered an area of 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm&#46; Distinct morphological patterns and quantifiable features of the neovascular membranes were studied on <span class="elsevierStyleItalic">en face</span> projection images&#44; which were taken at different stages of the follow-up&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Treatment response could be estimated using the OCT-A criteria of CNV activity&#46; Higher activity scores before treatment resulted in a greater decrease in the membrane area&#46; The estimated net decline in area ranged from 83&#46;5&#37; to 1&#46;4&#37;&#46; The OCT-A performed one-week after treatment revealed the greatest area reductions&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">OCT-A provides new possibilities for the non-invasive assessment of features of neovascular networks and CNV structural morphology&#46; Newly described activity criteria can also guide therapeutic decisions&#44; and help in evaluating responses&#46; Quantitative and qualitative information can be provided with this technique&#46; However&#44; further software development and future investigation are essential to define the role of this tool on a daily basis&#46;</p></span>"
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          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Aim"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir las caracter&#237;sticas de la neovascularizaci&#243;n coroidea &#40;NVC&#41; tipo 1 en pacientes con degeneraci&#243;n macular asociada a la edad &#40;DMAE&#41;&#44; utilizando la angiograf&#237;a por tomograf&#237;a de coherencia &#243;ptica &#40;A-OCT&#41; secuencialmente durante el transcurso de un protocolo est&#225;ndar de 3 inyecciones intrav&#237;treas de f&#225;rmaco anti-VEGF&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Seis ojos con DMAE neovascular no tratados previamente fueron incluidos&#46; Se obtuvieron im&#225;genes por A-OCT empleando AngioPlex Cirrus HD-OCT 5000 &#40;Carl Zeiss Meditec&#44; Inc&#46;&#44; Dublin&#44; EE&#46; UU&#46;&#41; y DRI OCT Triton SS-OCT Angio &#40;Topcon&#44; Medical Systems&#44; Inc&#46; Oakland&#44; NJ&#44; EE&#46; UU&#46;&#41;&#46; El &#225;rea estudiada comprende un esc&#225;ner macular de 3<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm&#46; Diferentes patrones morfol&#243;gicos y aspectos cuantificables de las membranas neovasculares han sido evaluados con im&#225;genes en proyecci&#243;n <span class="elsevierStyleItalic">en face</span>&#44; que fueron tomadas en distintos tiempos del seguimiento de los pacientes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El grado de respuesta al tratamiento fue estimado empleando criterios de actividad de NVC para A-OCT&#46; Puntuaciones m&#225;s altas en los &#237;tems de actividad antes del tratamiento resultaron en mayores reducciones del &#225;rea de las membranas&#46; Los resultados finales de reducci&#243;n de &#225;rea oscilaron entre el 83&#44;5 y el 1&#44;4&#37;&#46; Las A-OCT realizadas a la semana de tratamiento revelaron los mayores porcentajes de reducci&#243;n&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La A-OCT ofrece la posibilidad de analizar en profundidad las caracter&#237;sticas morfol&#243;gicas y estructurales en NVC de tipo 1&#46; Los criterios de actividad permiten guiar decisiones terap&#233;uticas y evaluar la respuesta al tratamiento&#46; Con esta t&#233;cnica puede obtenerse informaci&#243;n &#250;til tanto cualitativa como cuantitativa&#46; Sin embargo&#44; son necesarios avances en el desarrollo del software y en investigaci&#243;n para poder definir el papel de esta herramienta en la pr&#225;ctica diaria&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Torrecillas-Picazo R&#44; Cerd&#224;-Ib&#225;&#241;ez M&#44; Almor Palacios I&#44; Herv&#225;s Hernandis JM&#44; Ram&#243;n-Cos&#237;n R&#44; Ruiz del Rio N&#44; et al&#46; An&#225;lisis y seguimiento con angiograf&#237;a por tomograf&#237;a de coherencia &#243;ptica de neovascularizaci&#243;n coroidea tipo 1 en degeneraci&#243;n macular tras tratamiento antiangiog&#233;nico&#46; Arch Soc Esp Oftalmol&#46; 2017&#59;92&#58;265&#8211;272&#46;</p>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1375
            "Ancho" => 1800
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Structural OCT of the macular area&#44; indicated in b&#46; Segmentation lines under RPE and over BM&#44; with associated subretinal fluid&#46; &#40;b&#41; Posterior pole photography with macular cube indicating the scanned 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm area&#46; &#40;c&#41; <span class="elsevierStyleItalic">In face</span> projection angiogram&#44; 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm&#44; centered in the fovea of the sea fan neovascular complex &#40;d&#41; equivalent angiogram with manually defined area through device software&#46; &#40;e&#41; Color reconstruction of the different retinal vascular plexi &#40;CNV in blue&#41;&#46; &#40;f&#41; Wide SS-OCT of the macular area with the above-mentioned findings&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Wide angiogram and SS-OCT 24<span class="elsevierStyleHsp" style=""></span>h after the first anti-VEGF injection&#46; &#40;b&#41; Wide angiogram and SS-OCT 7 days after the first injection&#46; &#40;c&#41; Wide angiogram and SS-OCT one month after the first injection&#46; &#40;d&#41; Wide angiogram and SS-OCT 7 days after the 2nd injection&#46; &#40;e&#41; Wide angiogram and SS-OCT one month after the 2nd injection&#46; &#40;f&#41; Wide angiogram and SS-OCT one week after the last injection&#46; The structural OCT shows complete SRF reabsorption with uneven RPE&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1675
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">&#40;a&#41; Structural OCT of the macula showing RPE over elevation and unevenness&#44; with very little SRF&#46; &#40;b&#41; <span class="elsevierStyleItalic">In face</span> projection angiogram&#44; 3<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleHsp" style=""></span>&#215;<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm&#44; of the foveal area showing CNV in sea fan pattern with prominent lateral nutritional vessel&#46; Color reconstruction&#46; Definition of the CNV area&#46; &#40;c&#41; Angiogram 24<span class="elsevierStyleHsp" style=""></span>h the first anti-VEGF injection&#46; &#40;d&#41; Angiogram taken one week after the last injection&#46; &#40;e&#41; Structural OCT one week after the last injection&#44; showing RPE alteration persistence and SRF absorption&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:1 [
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            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="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Case&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Eye&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Initial VA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Final VA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Initial area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Final area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#37; reduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;549<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">255<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">83&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">408<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">346<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">512<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">505<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">OI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">409<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">375<span class="elsevierStyleHsp" style=""></span>&#956;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1427463.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Demographic and ophthalmological characteristics of patients before and after the study&#46;</p>"
        ]
      ]
      4 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
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        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
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              "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="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Standard deviation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&#44; years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initial VA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Final VA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initial area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">719&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">555&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Final area&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">370&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">103&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#37; Of area reduction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Article information
ISSN: 21735794
Original language: English
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