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Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | Larrosa J.M.,University of Zaragoza | Larrosa J.M.,Aragones Institute of Health science | And 15 more authors.
American Journal of Ophthalmology | Year: 2014

Purpose To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity. Design Observational prospective study. Methods Parkinson disease patients (n = 129) and age-matched healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to automatically segment all retinal layers in a parafoveal scan using the new segmentation application prototype. Mean thickness of each layer was calculated and compared between Parkinson disease patients and healthy subjects, and between Parkinson disease patients with disease durations of less than or at least 10 years. A correlation analysis was performed to evaluate the association between retinal layer thickness, duration of disease, and Parkinson disease severity. Logistic regression analysis was performed to determine the most sensitive layer for predicting axonal atrophy. Results Parkinson disease patients showed statistically significant reduced thickness in the retinal nerve fiber, ganglion cell, inner plexiform, and outer plexiform layers and increased thickness in the inner nuclear layer compared with healthy subjects (P <.05). The inner retinal layers were more affected in Parkinson disease patients with long disease duration. The ganglion cell layer thickness was inversely correlated with disease duration and Parkinson disease severity, and was predictive of axonal damage in Parkinson disease patients. Conclusions The segmentation application of the Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage. © 2014 BY ELSEVIER INC. ALL RIGHTS RESERVED.


Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | Polo V.,University of Zaragoza | Polo V.,Aragones Institute of Health science | And 15 more authors.
Ophthalmology | Year: 2014

Purpose To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS. Design Observational, cross-sectional study. Participants Patients with MS (n = 204) and age-matched healthy subjects (n = 138). Methods The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype. Main Outcome Measures The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS. Results All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS. Conclusions Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS. © 2014 by the American Academy of Ophthalmology Published by Elsevier Inc.


Larrosa J.M.,University of Zaragoza | Larrosa J.M.,Aragones Institute of Health science | Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | And 13 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014

Purpose. We calculated and validated a linear discriminant function (LDF) for Fourier domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in the detection of Alzheimer's disease (AD). Methods. We enrolled AD patients (n - 151) and age-matched, healthy subjects (n - 61). The Cirrus and Spectralis OCT systems were used to obtain retinal measurements and circumpapillary RNFL thickness for each participant. An LDF was calculated using all retinal and RNFL OCT measurements. Receiver operating characteristic (ROC) curves were plotted and compared among the LDF and the standard parameters provided by OCT devices. Sensitivity and specificity were used to evaluate diagnostic performance. A validating set was used in an independent population to test the performance of the LDF. Results. The optimal function was calculated using the RNFL thickness provided by Spectralis OCT, using the 768 points registered during peripapillary scan acquisition (grouped to obtain 24 uniformly divided locations): 18.325 + 0.056 3 (315°-330°) - 0.122 3 (300°-315°) - 0.041 3 (285°-300°) + 0.091 3 (255°-270°) + 0.041 3 (225°-240°) + 0.183 3 (195°-210°) - 0.108 3 (150°-165°) - 0.092 3 (75°-90°) + 0.051 3 (30°-45°). The largest area under the ROC curve was 0.967 for the LDF. At 95% fixed specificity, the LDF yielded the highest sensitivity values. Conclusions. Measurements of RNFL thickness obtained with the Spectralis OCT device differentiated between healthy and AD individuals. Based on the area under the ROC curve, the LDF was a better predictor than any single parameter. © 2014 The Association for Research in Vision and Ophthalmology, Inc.


Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | Satue M.,University of Zaragoza | Fuertes I.,University of Zaragoza | And 11 more authors.
Ophthalmology | Year: 2012

Purpose: To evaluate and compare the ability of 3 protocols of Fourier-domain optical coherence tomography (OCT) to detect retinal thinning and retinal nerve fiber layer (RNFL) atrophy in patients with Parkinson's disease (PD) compared with healthy subjects. To test the intrasession reproducibility of RNFL thickness measurements in patients with PD and healthy subjects using the Cirrus (Carl Zeiss Meditec Inc., Dublin, CA) and Spectralis (Heidelberg Engineering, Inc., Heidelberg, Germany) OCT devices. Design: Observational, cross-sectional study. Participants: Patients with PD (n = 75) and age-matched healthy subjects (n = 75) were enrolled. Methods: All subjects underwent three 360-degree circular scans centered on the optic disc by the same experienced examiner using the Cirrus OCT instrument, the classic glaucoma application, and the new Nsite Axonal Analytics of the Spectralis OCT instrument. Main Outcome Measures: Differences between the eyes of healthy subjects and the eyes of patients with PD were compared using the 3 protocols. The relationship between measurements provided by each OCT protocol was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. Results: Retinal nerve fiber layer atrophy was detected in eyes of patients with PD (P = 0.025, P=0.042, and P < 0.001) with the 3 protocols used, but the Nsite Axonal Analytics of the Spectralis OCT device was the most sensitive for detecting subclinical defects. In eyes of patients with PD, RNFL thickness measurements determined by the OCT devices were correlated, but they were significantly different between the Cirrus and Spectralis devices (P = 0.038). Reproducibility was good with all 3 protocols but better using the Glaucoma application of the Spectralis OCT device. Conclusions: Fourier-domain OCT can be considered a valid and reproducible device for detecting subclinical RNFL atrophy in patients with PD, especially the Nsite Axonal Analytics of the Spectralis device. Retinal nerve fiber layer thickness measurements differed significantly between the Cirrus and Spectralis devices despite a high correlation of the measurements between the 2 instruments. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.


Satue M.,University of Zaragoza | Satue M.,Aragones Institute of Health science | Seral M.,University of Zaragoza | Otin S.,University of Zaragoza | And 12 more authors.
British Journal of Ophthalmology | Year: 2014

Aims: To determine whether there is an association between retinal thinning and functional rating scales in patients with Parkinson's disease (PD). Materials and methods Patients with PD (n=153) and controls (n=242) underwent evaluations of the macula and retinal nerve fibre layer (RNFL) using two new-generation Fourier domain optical coherence tomography (OCT) devices (Cirrus, Carl Zeiss Meditec, Dublin, California, USA; Spectralis, Heidelberg Engineering, Heidelberg, Germany). PD severity was assessed using the Schwab-England Activities of Daily Living scale, the Unified Parkinson Disease Rating Scale, the Hoehn and Yahr (HY) scale. Retinal and RNFL thicknesses were compared between patients and controls. Correlations between structural parameters and the scores of the neurologic scales were evaluated. Results: RNFL parameters were significantly reduced in patients with PD, especially when using the Spectralis OCT device. All macular parameters, except for foveal thickness, differed significantly between controls and patients with PD ( p<0.001). HY scores were significantly and inversely correlated with all macular parameters when measured with the Spectralis OCT device (p<0.05) and with RNFL thickness when measured with the Cirrus OCT device (nasal quadrant, sectors 2 and 5). Conclusions: The neurodegeneration caused by PD can be detected using Fourier domain OCT. RNFL and macular thicknesses correlate with PD severity.


Malo S.,University of Zaragoza | Jose Rabanaque M.,University of Zaragoza | Feja C.,Aragones Institute of Health science | Jesus Lallana M.,Pharmacy Service in Primary Health Care | And 2 more authors.
Basic and Clinical Pharmacology and Toxicology | Year: 2014

Heavy antibiotic users are those individuals with the highest exposure to antibiotics. They play an important role as contributors to the increasing risk of antimicrobial resistance. We applied different methods to identify and characterize the group of heavy antibiotic users in Spain as well as their exposure to antibiotics. Data on outpatient prescribing of antimicrobials (ATC J01) in 2010 were obtained from a prescription database covering Aragón (northeastern Spain). The antimicrobial consumption at the individual level was analysed both according to the volume of DDD and the number of packages purchased per year. Heavy antibiotic users were identified according to Lorenz curves and characterized by age, gender, and their antimicrobial prescription profile. Lorenz curves demonstrated substantial differences in the individual use of antimicrobials. Heavy antibiotic users (5% of individuals with highest consumption) were responsible for 21% of the total DDD consumed and received ≥6 packages per year. Elderly adults (≥60 years) and small children (0-9 years) were those exposed to the highest volume of antibiotics and with the most frequent exposure, respectively. Heavy users received a high proportion of antibiotics not recommended as first choice in primary health care. In conclusion, heavy antibiotic users consisted mainly of children and old adults. Inappropriate overuse of antibiotics (high quantity, high frequency, and inappropriate antibiotic choice) leads to a substantial risk of the emergence and spread of resistant bacteria, and interventions to reduce overuse of antibiotics should therefore primarily be targeted children and elderly people. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).


Bambo M.P.,University of Zaragoza | Bambo M.P.,Aragones Institute of Health science | Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | And 11 more authors.
British Journal of Ophthalmology | Year: 2014

Backgrounds/aims: To evaluate the effect of uncomplicated cataract phacoemulsification on the measurements of macular and retinal nerve fibre layer (RNFL) in healthy subjects using two spectral domain (SD) optical coherence tomography (OCT) instruments - Cirrus OCT (Zeiss) and Spectralis OCT (Heidelberg) - and to assess the reliability of the measurements obtained with these two devices before and after cataract surgery. Methods: The study included 60 eyes of 60 healthy subjects (22 men and 38 women, 54-88 years of age) who underwent cataract phacoemulsification. One month before and one month after surgery, three repetitions of scans were performed using the RNFL and macular analysis protocols of the Cirrus and Spectralis OCT instruments. The differences between RNFL and macular thickness measurements obtained in the two visits were analysed. Repeatability was evaluated by calculating the coefficient of variation (COV) for each of the parameters recorded and for each visit. Results: The RNFL measurements obtained with the Cirrus and Spectralis OCT differed before and after surgery, and most of these differences were statistically significant (p<0.05). Macular thickness measurements using the Spectralis OCT were not significantly different between the two visits, whereas the differences found with the Cirrus OCT were statistically significant. The repeatability was better after surgical removal of the cataract, and the differences between COV in the two visits were significant with the Cirrus OCT. Conclusions: The presence of cataracts affects RNFL and macular measurements performed with SD-OCT. The repeatability of the images significantly improved after cataract phacoemulsification when using the Cirrus OCT.


Satue M.,University of Zaragoza | Satue M.,Aragones Institute of Health science | Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | And 12 more authors.
Eye (Basingstoke) | Year: 2013

PurposeTo demonstrate axonal loss in the retinal nerve fiber layer (RNFL) of patients with Parkinson's disease (PD) and to evaluate the ability of Fourier-domain optical coherence tomography (OCT) to detect RNFL degeneration and retinal thinning in these patients.MethodsPD patients (n=100) and healthy subjects (n=100) were included in the study and underwent visual acuity, color vision, and OCT examinations using two next-generation Fourier-domain devices (Spectralis and Cirrus). Differences in the RNFL thicknesses were compared between patients and controls.ResultsRNFL thicknesses were significantly reduced in PD patients compared with healthy subjects, especially those obtained using the Spectralis OCT, in the inferotemporal quadrant (155.6±16.5 μm in healthy eyes vs 142.1±24.9 μm in patients, P=0.040) and in the superotemporal quadrant (142.6±20.9 μm in healthy eyes vs 132.77±18.6 μm in PD patients, P=0.046). Significant differences were observed between controls and patients in relation to mean macular thickness (P=0.031), foveal thickness (P=0.030), and inferior outer thickness (P=0.019).ConclusionPD is associated with RNFL loss and retinal thinning, which is detectable by Fourier-domain OCT measurements. © 2013 Macmillan Publishers Limited All rights reserved 0950-222X/13.


Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | Pablo L.E.,University of Zaragoza | Pablo L.E.,Aragones Institute of Health science | And 11 more authors.
Ophthalmology | Year: 2012

Purpose: To calculate and validate a linear discriminant function (LDF) for spectral-domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal nerve fiber layer (RNFL) thickness parameters for the detection of multiple sclerosis (MS). Design: Observational cross-sectional study. Participants: Patients with multiple sclerosis (n = 115) and age-matched healthy subjects (n = 115) were enrolled in the study. Methods: The Spectralis OCT system (Heidelberg Engineering, Heidelberg, Germany) was used to obtain the circumpapillary RNFL thickness in both eyes of each participant. Main Outcome Measures: A validating set including 60% of the study subjects (69 healthy individuals and 69 patients with MS) was used to test the performance of the LDF in an independent population. Receiver operating characteristic (ROC) curves were plotted and compared with the RNFL parameters measured using OCT. Sensitivity and specificity were used to evaluate diagnostic performance. Results: The optimized function was 4.965 - 0.40 × (mean thickness 15-30 degrees) - 0.17 × (mean thickness 300-315 degrees) + 2.743 - 0.032 × (mean thickness 105-120 degrees) - 0.031 × (mean thickness 120-135 degrees) - 0.018 × (mean thickness 225-240 degrees). The largest area under the ROC curve was 0.834 for our LDF in the validating population. At 95% fixed specificity, the LDF yielded the highest sensitivity values. Conclusions: Measurements of RNFL thickness obtained with Spectralis OCT had good ability to differentiate between healthy individuals and individuals with MS. On the basis of the area under the ROC curve, the LDF performed better than any single parameter. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2012 American Academy of Ophthalmology.


Garcia-Martin E.,University of Zaragoza | Garcia-Martin E.,Aragones Institute of Health science | Rodriguez-Mena D.,Aragones Institute of Health science | Rodriguez-Mena D.,University of Zaragoza | And 16 more authors.
Investigative Ophthalmology and Visual Science | Year: 2014

Purpose. To evaluate correlations between visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) and the severity of Parkinson disease (PD). Methods. Forty-six PD patients and 33 age and sex-matched healthy controls were enrolled, and underwent VEP, PERG, and OCT measurements of macular and RNFL thicknesses, and evaluation of PD severity using the Hoehn and Yahr scale to measure PD symptom progression, the Schwab and England Activities of Daily Living Scale (SE-ADL) to evaluate patient quality of life (QOL), and disease duration. Logistical regression was performed to analyze which measures, if any, could predict PD symptom progression or effect on QOL. Results. Visual functional parameters (best corrected visual acuity, mean deviation of visual field, PERG positive (P) component at 50 ms -P50- and negative (N) component at 95 ms -N95- component amplitude, and PERG P50 component latency) and structural parameters (OCT measurements of RNFL and retinal thickness) were decreased in PD patients compared with healthy controls. OCT measurements were significantly negatively correlated with the Hoehn and Yahr scale, and significantly positively correlated with the SE-ADL scale. Based on logistical regression analysis, fovea thickness provided by OCT equipment predicted PD severity, and QOL and amplitude of the PERG N95 component predicted a lower SE-ADL score. Conclusions. Patients with greater damage in the RNFL tend to have lower QOL and more severe PD symptoms. Foveal thicknesses and the PERG N95 component provide good biomarkers for predicting QOL and disease severity. © 2014 The Association for Research in Vision and Ophthalmology, Inc.

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