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"apellidos" => "Ziakas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "2<span class="elsevierStyleSup">nd</span> Departamento de Oftalmología, Universidad Aristóteles de Tesalónica, Facultad de Medicina, Hospital General Papageorgiou, Tesalónica, Greece" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "St Paul’s Eye Unit, Royal Liverpool University Hospital, Liverpool, United Kingdom" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto Oftalmológico de Tracia, Universidad Demócrito de Tracia, Alexandroupoli, Greece" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "<span class="elsevierStyleItalic">Corresponding author</span>." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efecto de la acetazolamida en la vasculatura retiniana y coroidea de la mácula y el disco óptico mediante angiografía OCT" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2076 "Ancho" => 3341 "Tamanyo" => 1131608 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">OCTA parameters studied at the optic disc region.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acetazolamide (AZ) is a reversible systemic inhibitor of carbonic anhydrase enzyme that catalyses the reaction of carbon dioxide and water to dissociated ions of carbonic acid. Carbonic anhydrase forms a family of enzymes in almost all human body tissues. In the eye, it is found in the retina, choroid, vessels, cornea, lens and ciliary body<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a>. AZ is commonly used for its ocular hypotensive effect mediated mainly through inhibiting aqueous inflow<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a>. However, it has also been postulated to increase retinal blood circulation and has been used in treating retinal artery occlusion<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>. In the central nervous system (CNS), it reduces the production of cerebrospinal fluid and intracranial pressure<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>. Studies in cerebral circulation have shown that it can lead to vessel dilatation through an increase in the partial pressure of carbon dioxide and pH reduction in extracellular fluid<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a>.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathophysiological mechanisms and hemodynamic effects of acetazolamide in different vascular beds have been assessed in several studies using clinical and laboratory techniques, providing relative blood flow measurements. Each technique calculates different vascular parameters of the ocular circulation, with blood flow velocity most frequently measured<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>. However, OCTA uses red blood cells as a contrast agent to form three-dimensional images of the retinal and choroidal microvasculature<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a>. By comparing changes in reflectance signals between consecutive B-scans, OCTA can detect in detail blood flow and delineate blood vessels without requiring any dye injection. Quantitative analysis of these images can provide metrics, such as vessel density (VD), defined as the percentage of the area occupied by flowing blood vessels over the total measured area<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>.</p><p id="par0015" class="elsevierStylePara elsevierViewall">In the present study, OCTA imaging was used to evaluate the effects of AZ on the vasculature of the retinal capillaries and the choriocapillaris in the macular area, as well as the radial peripapillary capillaries (RPC) in the optic disc in normal-tension healthy volunteers.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This observational cross-sectional study was conducted at the 2nd Ophthalmology Clinic, Aristotle University of Thessaloniki, between February and October 2021. The study followed the tenets of the Declaration of Helsinki and was approved by the local Biomedical Ethics Committee. Written informed consent was obtained from all participants after a detailed explanation of the protocol before entering the study.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Patients scheduled for cataract surgery in our clinic were enrolled in the study. A complete ophthalmic and systematic history and their topical and systemic medication were recorded. All patients underwent a comprehensive ophthalmic examination, including refraction, best-corrected visual acuity, slit-lamp examination, tonometry and fundoscopy 3–5 days before surgery. To be included in the study, all participants had to be between 18–90 years old, with visual acuity better than 20/30 and clear media in the study (non-operated) eye, refraction within six diopters of spherical equivalent and three diopters of astigmatism, with no prior history of high myopia and a history of uneventful phacoemulsification at least three months before the study measurement. Exclusion criteria were the presence of macular or optic nerve pathology in the study eye as well as retinal or choroidal vascular disease, uncontrolled systemic vascular disease, renal disease, obstructive sleep apnea, lens or corneal disease that would limit the quality of imaging and increased intraocular pressure (IOP<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>21<span class="elsevierStyleHsp" style=""></span>mmHg).</p><p id="par0030" class="elsevierStylePara elsevierViewall">On the day of surgery, patients underwent cataract surgery in one eye under topical anaesthesia with alcaine drops (proparacaine hydrochloride 0.5%). An hour post-surgery, patients underwent IOP measurement using a Goldmann applanation tonometer in the study (non-operated) eye and systemic blood pressure (BP) measurement using the automatic digital blood pressure meter Edan M3A Vital Signs Monitor (Edan instruments Inc, Shenzhen, P.R.China) by the same physician under the same examining conditions. BP was measured in the sitting position on the patient’s right upper arm. The mean of three consecutive measurements was recorded. Patients were asked to refrain from coffee consumption and nicotine use until the completion of the study procedures. OCTA imaging was performed using the Optovue Avanti with Angiovue OCT-Angiography Imaging system (Optovue, Inc., Fremont, California, USA). The high definition (HD) Angio-retina 6<span class="elsevierStyleHsp" style=""></span>mm scan protocol for the macula and the HD optic nerve 4.5<span class="elsevierStyleHsp" style=""></span>mm for the optic nerve head were acquired in all patients. Each patient then received 250<span class="elsevierStyleHsp" style=""></span>mg AZ per os. AZ was given as part of the standard postoperative protocol for all patients undergoing phacoemulsification. After a resting period of 60 minutes, the macular and optic nerve head OCTA scans and IOP and BP measurements were repeated.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Each OCTA scan was acquired twice, and the better-quality image was used for analysis. Scans with motion artefacts (e.g. eye blinks and movements) and/or projection artefacts and/or poor quality, with Signal Strength Index (SSI) values <45, were not analysed<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">OCTA parameters</span><p id="par0040" class="elsevierStylePara elsevierViewall">Macular microvascular parameters were calculated based on volumetric OCTA scans of the central 6<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>mm area (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The instrument’s built-in software (version 2017.1.0.151) was used. The main parameters were VD in the superficial capillary plexus (SCP VD), deep capillary plexus (DCP VD) and choriocapillaris (CC). The slab used for SCP VD extended between the internal limiting membrane and 10<span class="elsevierStyleHsp" style=""></span>μm below the inner plexiform layer (IPL). The slab used for DCP analysis was between 10<span class="elsevierStyleHsp" style=""></span>μm below IPL and 10<span class="elsevierStyleHsp" style=""></span>μm above the outer plexiform layer, whereas the CC slab was set between 30 and 60<span class="elsevierStyleHsp" style=""></span>μm below the retinal pigment epithelium. VDs were recorded in the foveal (central ring with a diameter of 1<span class="elsevierStyleHsp" style=""></span>mm), parafoveal (between the 1<span class="elsevierStyleHsp" style=""></span>mm and 3<span class="elsevierStyleHsp" style=""></span>mm diameter ring) and perifoveal area (between the 3<span class="elsevierStyleHsp" style=""></span>mm and 6<span class="elsevierStyleHsp" style=""></span>mm diameter ring). In the optic nerve region, RPC VD was measured for the entire scanned area, the area inside the optic disc and the peripapillary area (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The RPC WI VD is calculated based on the 4.5<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4.5<span class="elsevierStyleHsp" style=""></span>mm area centred on the optic disc, whereas the RPC Inside Disc (ID) refers to the area within the optic disc boundaries. The RPC peripapillary VD was calculated from an 0.75<span class="elsevierStyleHsp" style=""></span>mm-wide elliptical annulus extending outwards from the optic disc margin. Total retinal thickness and retinal nerve fiber layer (RNFL) thickness were also automatically measured by the instrument’s built-in software at baseline and after AZ intake.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">All statistical analyses were performed using Statistical Package for Social Sciences software (SPSS, version 25.0; IBM SPSS, Inc., Chicago, IL, USA). The distribution of continuous variables was tested for normality using a Shapiro-Wilk test. Descriptive statistics are presented as mean and standard deviation (SD) since the data were normally distributed. The Student’s paired <span class="elsevierStyleItalic">t</span>-test was used to compare the baseline measurements and those after AZ. Correlation analyses were conducted with the Pearson correlation coefficient. A <span class="elsevierStyleItalic">P</span>-value <.05 was considered significant.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">Forty-five patients (23 male, 22 female) with a mean age of 73.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.9 years (range 55–84 years) were enrolled in this study. Thirty-five (35/45, 77.78%) were under treatment for systematic hypertension, and eight patients (8/45, 17.78%) had well-controlled diabetes, whereas no other systemic therapy was recorded.</p><p id="par0055" class="elsevierStylePara elsevierViewall">All study participants well tolerated orally administered AZ without any adverse effects. Mean IOP was decreased by 10.72%, from 13.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.0<span class="elsevierStyleHsp" style=""></span>mmHg to 11.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.2<span class="elsevierStyleHsp" style=""></span>mmHg (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001). AZ also had a small but significant lowering effect on arterial blood pressure. Specifically, systolic blood pressure was reduced by 4.90% (from 144.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21.8 to 137.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.0, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.021) and diastolic blood pressure by 4.72% (from 80.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.7 to 76.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.7, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.030).</p><p id="par0060" class="elsevierStylePara elsevierViewall">There was no significant change in SCP and DCP VD before and after AZ intake. CC VD also remained unchanged, and RPC VD was similar after AZ, compared to baseline (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">OCT mean retinal thickness measurements showed a slight increase from 248.98 (±23.89) to 250.33 (±23.74) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and from 311.62 (±16.53) to 311.98 (±16.38) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.046) in the central fovea and the parafovea respectively. In contrast, no significant difference was noted in the retinal thickness of the perifovea (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.171). No significant difference was found in the NFL thickness (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.780) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">We also analysed the data for possible associations between VD and patients’ characteristics (gender, age, hypertension, diabetes). VD change showed no correlation with systematic hypertension or diabetes (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.3) or the patient’s age and gender (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.5, for all parameters). There was also no correlation between the parameters of age, IOP, SBP and DBP and the measured parameters of OCT or OCTA (thickness and SCP, DCP, CC or RPC VD) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.5, for all parameters).</p><p id="par0075" class="elsevierStylePara elsevierViewall">Interestingly, a positive correlation was found between foveal thickness and foveal SCP VD (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.636, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and DCP VD (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.640, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001), whereas no similar correlation was observed with parafoveal and perifoveal thickness. NFL thickness was also positively correlated with peripapillary RPC VD (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.665, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and RPC VD WI (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.679, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001).</p><p id="par0080" class="elsevierStylePara elsevierViewall">Finally, SSI in the fovea was positively correlated with SCP VD both in the parafoveal (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.607, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and perifoveal area (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.614, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001) and DCP VD in the perifoveal area (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.635, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001). SSI in the disc was also correlated with both SCP and DCP VD in the parafoveal (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.474 <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.001 and r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.346 <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.020 respectively) and the perifoveal area (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.390 <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.008 and r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.526 <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001 respectively). There was no significant difference when comparing the SSI before and after AZ in the macular or optic disc images (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.720 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.603, respectively).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">This study used OCTA imaging to evaluate changes in the ocular microvasculature after AZ treatment. We did not observe any significant vasodilating effect in different ocular vascular beds after administering 250<span class="elsevierStyleHsp" style=""></span>mg AZ orally. Most of the OCTA parameters indicated a slight increase in VD, whereas few revealed a decrease, with all these changes not reaching statistical significance. Our findings are in accordance with an earlier report of Grunwald et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a>, who examined retinal circulation in the macular area 3<span class="elsevierStyleHsp" style=""></span>h after AZ administration using the blue light entoptoscope technique that measures the number and mean velocity of white blood cells. Their study demonstrated a slow rise of macular blood flow after 500<span class="elsevierStyleHsp" style=""></span>mg oral AZ, which was not significant. Harris et al.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> also failed to detect changes in ophthalmic and central retinal artery 3<span class="elsevierStyleHsp" style=""></span>h after 1000<span class="elsevierStyleHsp" style=""></span>mg AZ was given orally, using the Color Doppler Imaging technique.</p><p id="par0090" class="elsevierStylePara elsevierViewall">There are studies in the literature, however, that have reported an increase in ocular blood flow when AZ is given intravenously (iv). Rassam et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> studied the effect of 500<span class="elsevierStyleHsp" style=""></span>mg of iv AZ on retinal circulation using the Doppler technique. They showed an increase in the flow and velocity of retinal red blood cells 30 and 60<span class="elsevierStyleHsp" style=""></span>min after administration. Dallinger et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> used an intravenous injection of a larger dose of AZ (1000<span class="elsevierStyleHsp" style=""></span>mg) and documented increased choroidal blood flow with the laser interferometry. Haustein et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> also used 1000<span class="elsevierStyleHsp" style=""></span>mg AZ and measured retinal vessel diameters with the Retina Vessel Analyzer and blood flow in the disc rim and the parapapillary retina with the use of Laser Doppler Flowmetry. They reported retinal dilatation, increased flow in the optic nerve head and a concurrent decrease in the parapapillary retinal blood flow.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Conversely, Kerty et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> studied 15 healthy individuals using transcranial Doppler Ultrasonography and found a significant decrease in ophthalmic artery flow velocity and pulsatile ocular volume after a single 1000<span class="elsevierStyleHsp" style=""></span>mg AZ iv dose. In our study, OCTA imaging depicted no significant effects of AZ on the retinal and choroidal microcirculation in the macular area and the optic disc. The dose and type of AZ administration, the imaging modality for vascular diameter and blood flow assessment and the vascular bed being examined may account for the differences in the findings of each study.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Several studies have also focused on the effects of topical CAI and the ways these drugs could affect ocular microcirculation, excluding the possible systemic action of AZ in the vasculature. Lester et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> investigated the effect of topical 1% brinzolamide twice-daily for one month with the Heidelberg Retina Flowmeter. They documented improvement in retinal blood flow, which was present in the temporal and nasal areas, while no difference was observed in the inferior and superior sectors. In the studies by Grunwald et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and Tamaki et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> no change was found in ocular hemodynamic parameters examined after dorzolamide using Laser Speckle Flowgraphy.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Another interesting finding in our study was that foveal thickness was positively correlated with both foveal SCP VD and DCP VD. In contrast, no association between thickness and VD was found in the parafoveal and perifoveal regions. This agrees with Falavarjani et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> results, who studied retinal characteristics and correlations using OCTA in healthy subjects. Foveal thickness also increased by 0.55% after AZ administration. Parafoveal thickness was also raised, and perifoveal thickness showed no significant change. Interestingly, AZ has been used in attempting macular thickness reduction<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> in the macular oedema setting. Given that the change observed in the present study was small, it is unclear if it bears any clinical significance in normal eyes.</p><p id="par0110" class="elsevierStylePara elsevierViewall">IOP demonstrated an average decrease of 10.7%, whereas systolic and diastolic BP were also affected, indicating an average reduction of 4.9% and 4.7%. The ocular hypotonic action of AZ is well established. AZ can reduce IOP by 10%–37%, depending on the baseline IOP, and its action is more pronounced when delivered intravenously<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,12,13</span></a>. There are conflicting results in the literature, with some studies pointing to a decrease in systemic blood pressure with AZ, while others have not shown any effect. Dallinger et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> and Haustein et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> used 1000<span class="elsevierStyleHsp" style=""></span>mg of intravenous AZ in healthy subjects, and they did not report any significant change in blood pressure or heart rate.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nevertheless, other studies in the literature support a hypotensive action of AZ in both systolic and diastolic blood pressure in agreement with our results<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20–23</span></a>. Wettrell et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> demonstrated a significant decrease in standing systolic BP and a small reduction in pulse rate after 250<span class="elsevierStyleHsp" style=""></span>mg AZ administration b.i.d. The pathophysiology behind this effect is not clear. Carbonic anhydrase inhibitors may cause tissue hypercapnia and changes in nitric oxide metabolism, which are both factors that can contribute to a vasodilatory response and BP lowering<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24–26</span></a>.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Certain limitations need to be taken into account while interpreting the results of a study with a cross-sectional design. This study used the oral administration of 250<span class="elsevierStyleHsp" style=""></span>mg AZ, while others used intravenous injection and/or higher drug dosages and different blood flow assessment methods. An increased drug dose is associated with a more pronounced IOP-lowering effect and a more remarkable change in ocular perfusion pressure. However, the scope of our study was not to document the effects of large doses of AZ but rather to investigate the effects of commonly prescribed doses of the drug on the ocular microvasculature in clinical settings. It is known that OCT angiography does not provide blood flow information, but it depicts volumetric angiographic information<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>. In this study, VD was used quantitively to characterise the microvasculature in different vascular beds. However, OCTA has certain limitations, such as depicting flow within a specific range<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>. Additionally, our results regarding optic disc microvasculature changes should be interpreted with caution given the challenging image segmentation within the optic disc and the low measurement repeatability of the optic disc scans compared to the macular ones<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>. Given that all examinations in our study started 1<span class="elsevierStyleHsp" style=""></span>h after the surgery, an effect of postoperative stress on the cardiovascular system cannot be ruled out<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a>. This may, at least partly, explain the small but significant BP drop that was noticed in our study. Finally, the presence of well-controlled systemic hypertension and diabetes in several participants also needs to be considered. However, all measurements were performed within a strict timeframe after AZ intake in a large group of participants that may be regarded as representative of the patients often encountered in the clinic.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, one hour after its administration, acetazolamide was not found to have any significant vasodilatory effect on the retinal and choroidal microvasculature of the macula and the radial peripapillary capillaries with OCTA imaging. Despite many reports using other methods, to the best of our knowledge, this is the first study that evaluated the effect of acetazolamide in ocular microcirculation using OCTA technology. It remains unclear if AZ can affect glaucoma patients' microvasculature. Future studies should be conducted to assess the effect of oral AZ on ocular microvasculature two or more hours after its administration.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Funding sources</span><p id="par0130" class="elsevierStylePara elsevierViewall">This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interest statement</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statement of ethics</span><p id="par0140" class="elsevierStylePara elsevierViewall">Study approval statement: This study protocol was reviewed by the ethics committee of the 2nd Department of Ophthalmology of Papageorgiou University Hospital, Thessaloniki, Greece. Ethics approval was not required. Consent to participate statement: A written informed consent was obtained from all participants after detailed explanation of the protocol before entering the study. The study followed the tenets of the Declaration of Helsinki.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Data availability statement</span><p id="par0145" class="elsevierStylePara elsevierViewall">All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Author contributions/statement</span><p id="par0150" class="elsevierStylePara elsevierViewall">Dr. Asimina Mataftsi devised the project and the main conceptual ideas. Patients’ examination, diagnosis and material preparation were performed by Dr. Asterios Diafas, Dr. Maria Samouilidou and Dr. Argyrios Tzamalis. Dr. Anna Dastiridou contributed to data collection and presentation. Dr. Ioannis Tsinopoulos contributed to the statistical analysis of the results. The original draft of the manuscript was written by Dr. Asterios Diafas and all authors commented on final version of the manuscript. Dr. Vassilios Kozobolis and Dr. Nikolaos Ziakas supervised research activity planning and execution. All authors read and approved the final manuscript.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1856511" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1614318" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1856510" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1614319" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "OCTA parameters" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Funding sources" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest statement" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Statement of ethics" ] 11 => array:2 [ "identificador" => "sec0050" "titulo" => "Data availability statement" ] 12 => array:2 [ "identificador" => "sec0055" "titulo" => "Author contributions/statement" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2022-09-16" "fechaAceptado" => "2022-11-30" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1614318" "palabras" => array:5 [ 0 => "Acetazolamide" 1 => "Optical coherence tomography angiography" 2 => "Vessel density" 3 => "Ocular blood flow" 4 => "Intraocular pressure" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1614319" "palabras" => array:5 [ 0 => "Acetazolamida" 1 => "Angiografía por tomografía de coherencia óptica" 2 => "Densidad de vasos" 3 => "Flujo sanguíneo ocular" 4 => "Presión intraocular" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objectives</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">To investigate the effect of acetazolamide (AZ) on the retinal and choroidal ocular microvasculature in the macula and radial peripapillary capillaries (RPC) of the optic disc with OCT Angiography (OCTA).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Nine-month observational cross-sectional study. Forty-five eyes from 45 healthy participants who underwent cataract surgery were recruited. Macular retina and choriocapillaris vessel density (VD) and RPC VD in the optic disc area were compared before and 60<span class="elsevierStyleHsp" style=""></span>min after 250<span class="elsevierStyleHsp" style=""></span>mg acetazolamide per os. Intraocular pressure (IOP) and systemic blood pressure (BP) were also measured before each scan.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Mean age was 73.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.9 years. VDs in the superficial (SCP) and deep (DCP) capillary plexus of the retina and the choriocapillaris (CC) in the macular area showed no significant change (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.5, for all parameters). VD in the RPC showed no significant change with AZ (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.5, for all parameters). Foveal and parafoveal thickness increased from 248.98 (±23.89) to 250.33 (±23.74) and from 311.62 (±16.53) to 311.98 (±16.38) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.046), respectively. IOP decreased from 13.2 (±3.0) mmHg to 11.8 (±3.2) mmHg (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.001), while systolic and diastolic BP decreased from 144.8 (±21.8) to 137.7 (±19.0) and from 80.0 (±12.7) to 76.2 (±11.7) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.021 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.030), respectively.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">OCTA imaging did not reveal any significant changes in the VD of the optic disc or the retinal and choroidal VD in the macula with oral AZ one hour after its administration in otherwise healthy participants who underwent cataract surgery.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and 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">Introducción y objetivos</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Investigar el efecto de la acetazolamida (AZ) sobre la microvasculatura ocular retiniana y coroidea en la mácula y los capilares peripapilares radiales (CPR) del disco óptico con Angiografía-OCT (OCTA).</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y métodos</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Estudio transversal observacional de nueve meses de duración. Se reclutaron 45 ojos de 45 participantes sanos que se sometieron a cirugía de cataratas. Se comparó la densidad de vasos (DV) de la retina macular y la coriocapilar y la DV de la CPR en la zona del disco óptico antes y 60 minutos después de administrar 250<span class="elsevierStyleHsp" style=""></span>mg de acetazolamida por vía oral También se midieron la presión intraocular (PIO) y la presión arterial (PA) sistémica antes de cada exploración.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">La edad media era de 73,1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6,9 años. La densidad de vasos (DV) en el plexo capilar superficial (PCS) y profundo (PCP) de la retina y la coriocapilar (CC) en el área macular no mostraron cambios significativos (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>,5, para todos los parámetros). La DV en los CPR no mostró cambios significativos con la AZ (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>,5, para todos los parámetros). El grosor foveal y parafoveal aumentó de 248,98 (±23,89) a 250,33 (±23,74) y de 311,62 (±16,53) a 311,98 (±16,38) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>,001 y <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>,046), respectivamente. La PIO disminuyó de 13,2 (±3,0) mmHg a 11,8 (±3,2) mmHg (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>,001), mientras que la PA sistólica y diastólica disminuyó de 144,8 (±21,8) a 137,7 (±19,0) y de 80,0 (±12,7) a 76,2 (±11,7) (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>,021 y <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>,030), respectivamente.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Las imágenes de OCTA no revelaron cambios significativos en el VD del disco óptico ni en el VD de la retina y la coroides en la mácula con AZ oral una hora después de su administración en participantes por lo demás sanos que se sometieron a cirugía de cataratas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Materiales y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2076 "Ancho" => 3341 "Tamanyo" => 1062428 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">OCTA parameters studied at the fovea.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2076 "Ancho" => 3341 "Tamanyo" => 1131608 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0045" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">OCTA parameters studied at the optic disc region.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0050" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">P</span> values for the paired <span class="elsevierStyleItalic">t</span>-test are presented.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">VD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Vessel Density, SCP<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Superficial Capillary Plexus, DCP<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Deep Capillary Plexus, CC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Choroidal Capillaries, WI<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Whole Image, RPC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Radial Peripapillary Capillaries.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After Acetazolamide \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Difference % \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foveal SCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">17.76<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18.04<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.58% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.626 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parafoveal SCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.62<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.77% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.715 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perifoveal SCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44.68<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44.77<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.20% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.873 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foveal DCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.78<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.06<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.85% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.758 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parafoveal DCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.36<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51.87<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.99% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.852 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perifoveal DCP VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44.87<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">45.16<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.65% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.788 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CC WI VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71.20<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71.33<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.17% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.777 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RPC ID VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.34<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48.84<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.01% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.512 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RPC Peripapillary VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.48<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.44% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.531 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RPC WI VD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.67<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.57<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.21% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.743 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">OCT-A parameters before and after acetazolamide administration.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0055" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">P</span> values for the paired <span class="elsevierStyleItalic">t</span>-test are presented.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">RNFL<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>Retinal Nerve Fiber Layer.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Parameters \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">After Acetazolamide \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Difference % \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Foveal Thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">248.98<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>23.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">250.33<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>23.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.55% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">< .001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parafoveal Thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">311.62<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">311.98<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>16.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.12% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.046 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perifoveal Thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">268.64<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">268.91<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.10% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.204 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RNFL Thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.47<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">102.38<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.09% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.780 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Choroidal Thickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">244.11<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>60.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">243.91<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>58.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−0.08% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">.925 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">OCT parameters before and after acetazolamide administration.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Carbonic anhydrase isoenzymes CA I and CA II in the human eye" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P.J. 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