Progressive Functional and Neuroretinal Affectation in Patients With Multiple Sclerosis Treated With Fingolimod.

BACKGROUND: To evaluate the effect of fingolimod in visual function and neuroretinal structures in patients with multiple sclerosis (MS) for a period of 1 year. METHODS: This longitudinal and observational cohort study included 78 eyes of 78 patients with MS treated with fingolimod. All subjects were evaluated every 3 months during 12 months and compared with 32 patients treated with interferon beta. All patients were examined for high-contrast and low-contrast (2.5% and 1.25%) visual acuity (VA), contrast sensitivity vision (CSV) (using Pelli-Robson and CSV-1000E tests), color vision (Farnsworth D-15 and L'Anthony D-15 desaturated tests), and retinal structural measurements (retinal nerve fiber layer [RNFL] and ganglion cell layer [GCL] thickness) using optical coherence tomography (OCT) technology. RESULTS: Patients with MS treated with fingolimod for a period of 1 year showed significant reduction in 100% and 1.25% contrast VA (P = 0.009 and 0.008, respectively), an alteration of contrast sensitivity and color perception (Pelli-Robson test, CSV-1000E test, Farnsworth D-15 desaturated test, and L'Anthony D-15 desaturated test; P < 0.001), GCL thickness reduction (P = 0.007), and an average macular central thickness increase of 2.6 µm (P = 0.006). Patients with MS treated with interferon beta did not show significant changes in visual function tests neither in macular thickness measurements, but they showed a significant reduction in GCL and RNFL thicknesses. The reduction in neuroretinal structures observed by OCT was significantly higher in the interferon-beta group, but patients treated with fingolimod showed a significant increase in macular central thickness and a reduction in low contrast vision (P < 0.001). CONCLUSIONS: Patients with MS treated with fingolimod and with no clinically observable macular edema show a significant change in visual function parameters and average macular central thickness increase compared with those treated with interferon beta. These findings are probably due to subclinical macular edema produced by fingolimod, which might be considered as an indicator for pharmacovigilance of sphingosine-1-phosphate inhibitors to be improved.

Early Diagnosis of Multiple Sclerosis Using Swept-Source Optical Coherence Tomography and Convolutional Neural Networks Trained with Data Augmentation.

BACKGROUND: The aim of this paper is to implement a system to facilitate the diagnosis of multiple sclerosis (MS) in its initial stages. It does so using a convolutional neural network (CNN) to classify images captured with swept-source optical coherence tomography (SS-OCT). METHODS: SS-OCT images from 48 control subjects and 48 recently diagnosed MS patients have been used. These images show the thicknesses (45 × 60 points) of the following structures: complete retina, retinal nerve fiber layer, two ganglion cell layers (GCL+, GCL++) and choroid. The Cohen distance is used to identify the structures and the regions within them with greatest discriminant capacity. The original database of OCT images is augmented by a deep convolutional generative adversarial network to expand the CNN's training set. RESULTS: The retinal structures with greatest discriminant capacity are the GCL++ (44.99% of image points), complete retina (26.71%) and GCL+ (22.93%). Thresholding these images and using them as inputs to a CNN comprising two convolution modules and one classification module obtains sensitivity = specificity = 1.0. CONCLUSIONS: Feature pre-selection and the use of a convolutional neural network may be a promising, nonharmful, low-cost, easy-to-perform and effective means of assisting the early diagnosis of MS based on SS-OCT thickness data.

VISUAL FUNCTION AND RETINAL CHANGES IN PATIENTS WITH BIPOLAR DISORDER.

PURPOSE: To evaluate visual and retinal changes in patients with bipolar disorder. To analyze the correlation between structural changes and visual function parameters. METHODS: Thirty patients with bipolar disorder and 80 healthy controls underwent visual function evaluation with Early Treatment Diabetic Retinopathy Study charts at 100%, 2.50%, and 1.25% contrast, Pelli-Robson chart, and color vision Farnsworth and Lanthony tests. Analysis of the different retinal layers was performed using Spectralis optical coherence tomography with automated segmentation software. Correlation analysis between structural and functional parameters was conducted. RESULTS: Patients with bipolar disorder presented worse color vision compared with controls (Lanthony's index, P = 0.002). Full macular thickness, the retinal nerve fiber layer (RNFL), ganglion cell layer, and inner plexiform layer were reduced in patients compared with healthy individuals (P < 0.005). The inner nuclear layer was significantly thickened in patients (P < 0.005). Peripapillary RNFL thickness was reduced in all temporal sectors (P < 0.005). Significant correlations were found between visual acuity and the RNFL thickness, the Pelli-Robson score and the inner plexiform layer, and between the Lanthony's color index and the ganglion cell layer thickness. CONCLUSION: Patients with bipolar disorder present quantifiable thinning of the macular RNFL, ganglion cell layer, and inner plexiform layer, as well as in the peripapillary RNFL thickness, and increasing thinning in the inner nuclear layer.

Retinal and Optic Nerve Degeneration in Patients with Multiple Sclerosis Followed up for 5 Years.

PURPOSE: To quantify retinal nerve fiber layer (RNFL) changes in patients with multiple sclerosis (MS) and healthy controls with a 5-year follow-up and to analyze correlations between disability progression and RNFL degeneration. DESIGN: Observational and longitudinal study. PARTICIPANTS: One hundred patients with relapsing-remitting MS and 50 healthy controls. METHODS: All participants underwent a complete ophthalmic and electrophysiologic exploration and were re-evaluated annually for 5 years. MAIN OUTCOME MEASURES: Visual acuity (Snellen chart), color vision (Ishihara pseudoisochromatic plates), visual field examination, optical coherence tomography (OCT), scanning laser polarimetry (SLP), and visual evoked potentials. Expanded Disability Status Scale (EDSS) scores, disease duration, treatments, prior optic neuritis episodes, and quality of life (QOL; based on the 54-item Multiple Sclerosis Quality of Life Scale score). RESULTS: Optical coherence tomography (OCT) revealed changes in all RNFL thicknesses in both groups. In the MS group, changes were detected in average thickness and in the mean deviation using the GDx-VCC nerve fiber analyzer (Laser Diagnostic Technologies, San Diego, CA) and in the P100 latency of visual evoked potentials; no changes were detected in visual acuity, color vision, or visual fields. Optical coherence tomography showed greater differences in the inferior and temporal RNFL thicknesses in both groups. In MS patients only, OCT revealed a moderate correlation between the increase in EDSS and temporal and superior RNFL thinning. Temporal RNFL thinning based on OCT results was correlated moderately with decreased QOL. CONCLUSIONS: Multiple sclerosis patients exhibit a progressive axonal loss in the optic nerve fiber layer. Retinal nerve fiber layer thinning based on OCT results is a useful marker for assessing MS progression and correlates with increased disability and reduced QOL.

Titanium implants coated with UV-irradiated vitamin D precursor and vitamin E: in vivo performance and coating stability.

OBJECTIVES: This study aimed at evaluating the biological response of titanium implants coated with UV-irradiated 7-dehydrocholesterol (7-DHC) and vitamin E (VitE) in vivo and analyzing the effects of aging on their stability and bioactivity in vitro. MATERIAL AND METHODS: Titanium surfaces were coated with 7-DHC and VitE, UV-irradiated and incubated for 48 h at 23°C to allow cholecalciferol synthesis. The in vivo biological response was tested using a rabbit tibia model after 8 weeks of healing by analyzing the wound fluid and the mRNA levels of several markers at the bone-implant interface (N = 8). The stability of the coating after storage up to 12 weeks was determined using HPLC analysis, and the bioactivity of the stored modified implants was studied by an in vitro study with MC3T3-E1 cells (N = 6). RESULTS: A significant increase in gene expression levels of osteocalcin was found in the bone tissue attached to implants coated with the low dose of 7-DHC and VitE, together with a higher ALP activity in the wound fluid. Implants treated with the high dose of 7-DHC and VitE showed increased tissue necrosis and inflammation. Regarding the aging effects, coated implants were stable and bioactive up to 12 weeks when stored at 4°C and avoiding oxygen, light and moisture. CONCLUSION: This study demonstrates that Ti implants coated with UV-irradiated 7-DHC and VitE promote in vivo gene expression of bone formation markers and ALP activity, while they keep their osteopromotive potential in vitro and composition when stored up to 12 weeks at 4°C.

A new role for 5-methoxytryptophol on bone cells function in vitro.

The present study investigates the direct action of 5-methoxytryptophol (5-MTX) in both MC3T3-E1 and RAW264.7 cells and compares it with melatonin (MEL), another 5-methoxyindol known to play a significant role on bone metabolism. We first screened increasing doses of both 5-MTX and MEL to determine their effect on metabolic activity and viability of preosteoblastic MC3T3-E1 cells. The optimal dose was used to determine its effect on differentiation of MC3T3-E1 cells and preosteoclastic RAW264.7 cells. Finally, we investigated the mechanism of action by adding the melatonin receptor antagonist luzindole (LUZ) and detecting the immunostaining of phospho-ERK. In MC3T3-E1 cells, most of the 5-MTX doses reduced slightly the metabolic activity of osteoblasts compared with the control, while MEL only decreased it for the highest dose (2.5 mM). As regards to cytotoxicity, low doses (0.001-0.1 mM) of both indoles showed a protective effect on osteoblasts, while the highest dose of MEL showed a higher cytotoxicity than the 5-MTX one. After 14 days of cell culture, Rankl mRNA levels were decreased, especially for 5-MTX. 5-MTX also induced a higher osteocalcin secretion and mineralization capacity than MEL. In RAW264.7 cells, 5-MTX decreased the number of osteoclast formed and its activity whereas MEL did not affect significantly the number of multinucleated TRAP-positive cells formed and showed a lower activity. Finally, MEL and 5-MTX promoted activation of the ERK1/2 pathway through the phosphorylation of ERK, while LUZ addition suppressed this effect. In conclusion, the present study demonstrates a new role of 5-MTX inhibiting osteoclastogenesis and promoting osteoblast differentiation.

One year outcome of hemi-Descemet membrane endothelial keratoplasty.

PURPOSE: To evaluate the 1-year clinical outcome after semi-circular Descemet membrane endothelial keratoplasty (hemi-DMEK) in a first case series. METHODS: In three eyes of three patients with Fuchs endothelial dystrophy, best corrected visual acuity (BCVA), endothelial cell density (ECD), pachymetry, and intra- and postoperative complications were evaluated after transplantation of a semi-circular ~12 mm diameter Descemet graft (hemi-DMEK graft). RESULTS: All corneas cleared within 6 months and showed a stable pachymetry thereafter (527, 535, and 490 µm, respectively). Compared to preoperative measurements, average central ECDs dropped by 51 % (56, 39, and 59 %, respectively) at 3 months, 53 % (57, 38, and 63 %, respectively) at 6 months, and 59 % (60, 47, and 71 %, respectively) at 12 months. Denuded stromal areas adjacent to the hemi-DMEK graft cleared and at 12 months peripheral ECD counts ranged from 724 to 1051 cells/mm(2). At 12 months, BCVA was 20/22 (0.9), 20/40 (0.5, amblyopic eye) and 20/17 (1.2). No postoperative complications occurred throughout the study period. CONCLUSIONS: Hemi-DMEK may provide visual outcomes similar to those in standard DMEK at the 1-year postoperative mark. If also graft survival and complication rates prove to be similar, hemi-DMEK could become the next step in endothelial keratoplasty, owing to its potential to double the yield of transplants from the same donor pool (two hemi-DMEK grafts can be prepared from one donor cornea).

Retina measurements for diagnosis of Parkinson disease.

PURPOSE: To test the diagnostic ability of spectral domain optical coherence tomography for the detection of Parkinson disease using retinal nerve fiber layer and retinal thickness parameters. Retinal pigment epithelium produces levodopa. METHODS: Patients with Parkinson disease (n = 111) and healthy subjects (n = 200) were enrolled. The Spectralis optical coherence tomography was used to obtain retinal nerve fiber layer thickness and retinal measurements. Two linear discriminant functions (LDFs) were developed, one using retinal nerve fiber layer parameters and another using retinal thickness. A validating set was used to test the performance of both LDFs. Receiver operating characteristic curves were plotted and compared with the standard parameters provided by optical coherence tomography for both LDFs. Sensitivity and specificity were used to evaluate diagnostic performance. RESULTS: The Retinal LDF combines only retinal thickness parameters and provided the best performance: 31.173 + 0.026 × temporal outer - 0.267 × superior outer + 0.159 × nasal outer - 0.197 × inferior outer - 0.060 × superior inner + 0.049 × foveal thickness. The largest areas under the receiver operating characteristic curve were 0.902 for Retinal LDF. The Retinal LDF yielded the highest sensitivity values. CONCLUSION: Measurements of retinal thickness differentiate between subjects who are healthy and those with advanced Parkinson disease.

UV-irradiated 7-dehydrocholesterol coating on polystyrene surfaces is converted to active vitamin D by osteoblastic MC3T3-E1 cells.

The aim of the present study was to determine the effects of UV irradiation on the conversion of 7-dehydrocholesterol (7-DHC), which has been coated onto a polystyrene surface, to cholecalciferol (D3), and the resulting effect on the formation of vitamin D (1,25-D3) by MC3T3-E1 cells. The changes in gene expression of the enzymes regulating its hydroxylation, Cyp27b1 and Cyp27a1, were monitored as well as the net effect of the UV-treated 7-DHC coating on cell viability and osteoblast differentiation. MC3T3-E1 cells were found to express the enzymes required for synthesizing active 1,25-D3, and we found a dose-dependent increase in the production of both 25-D3 and 1,25-D3 levels for UV-activated 7-DHC samples unlike UV-untreated ones. Cell viability revealed no cytotoxic effect for any of the treatments, but only for the highest dose of 7-DHC (20 nmol per well) that was UV-irradiated. Furthermore, osteoblast differentiation was increased in cells treated with some of the higher doses of 7-DHC when UV-irradiated, as shown by collagen-I, osterix and osteocalcin relative mRNA levels. The conversion of 7-DHC to preD3 exogenously by UV irradiation and later to 25-D3 by MC3T3-E1 cells was determined for the optimum 7-DHC dose (0.2 nmol per well), i.e. 8.6 ± 0.7% of UV-activated 7-DHC was converted to preD3 and 6.7 ± 2.8% of preD3 was finally converted to 25-D3 under the conditions studied. In conclusion, we demonstrate that an exogenous coating of 7-DHC, when UV-irradiated, can be used to endogenously produce active vitamin D. We hereby provide the scientific basis for UV-activated 7-DHC coating as a feasible approach for implant therapeutics focused on bone regeneration.

Ability of Swept-source OCT and OCT-angiography to detect neuroretinal and vasculature changes in patients with Parkinson disease and essential tremor.

BACKGROUND/OBJECTIVES: To evaluate the ability of swept-source optical coherence tomography (SS-OCT) implemented with angiography analysis (SS-OCTA) to detect neuro-retinal and vasculature changes in patients with Parkinson's disease (PD) and essential tremor (ET), and to distinguish between both pathologies. SUBJECTS/METHODS: A total 42 PD and 26 ET patients and 146 controls underwent retinal evaluation using SS-OCT plus OCT-Angio™. The macular (m) and peripapillary (p) retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), and macular vasculature were assessed. A Linear discriminant function (LDF) was calculated to evaluate the diagnostic ability of SS-OCTA in both PD and ET. RESULTS: PD patients presented a reduction in mRNFL (p < 0.005), mGCL (all sectors, p < 0.05) and pRNFL (p < 0.005) vs healthy controls, and in mRNFL and pRNFL vs ET patients (p < 0.001). ET patients showed a significant reduction in mGCL vs controls (p < 0.001). No differences were observed in the macular vasculature between groups. Predictive diagnostic variables were significant only for PD and a LDF was obtained with an area under the ROC curve of 0.796. CONCLUSIONS: Neuro-retinal thinning is present in both diseases, being greater in PD. While SS-OCT could be useful in diagnosing ET and PD, the diagnostic potential for SS-OCTA based on an LDF applies only to PD, not ET.

Evaluation of multiple sclerosis severity using a new OCT tool.

PURPOSE: To assess the ability of a new posterior pole protocol to detect areas with significant differences in retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness in patients with multiple sclerosis versus healthy control subjects; in addition, to assess the correlation between RNFL and GCL thickness, disease duration, and the Expanded Disability Status Scale (EDSS). METHODS: We analyzed 66 eyes of healthy control subjects and 100 eyes of remitting-relapsing multiple sclerosis (RR-MS) patients. Double analysis based on first clinical symptom onset (CSO) and conversion to clinically definite MS (CDMS) was performed. The RR-MS group was divided into subgroups by CSO and CDMS year: CSO-1 (≤ 5 years) and CSO-2 (≥ 6 years), and CDMS-1 (≤ 5 years) and CDMS-2 (≥ 6 years). RESULTS: Significant differences in RNFL and GCL thickness were found between the RR-MS group and the healthy controls and between the CSO and CDMS subgroups and in both layers. Moderate to strong correlations were found between RNFL and GCL thickness and CSO and CDMS. Furthermore, we observed a strong correlation with EDSS 1 year after the OCT examination. CONCLUSIONS: The posterior pole protocol is a useful tool for assessing MS and can reveal differences even in early stages of the disease. RNFL thickness shows a strong correlation with disability status, while GCL thickness correlates better with disease duration.

Ability and reproducibility of Fourier-domain optical coherence tomography to detect retinal nerve fiber layer atrophy in Parkinson's disease.

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.

Diagnostic ability of a linear discriminant function for spectral-domain optical coherence tomography in patients with multiple sclerosis.

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.

Evaluation of Progressive Retinal Degeneration in Bipolar Disorder Patients over a Period of 5 Years.

PURPOSE: To quantify visual and retinal changes in patients with bipolar disorder (BD) over 5 years, compared with controls. METHODS: Thirty-eight patients with BD and 122 healthy subjects underwent visual acuity (VA) evaluation, contrast sensitivity vision testing (CSV) with the Pelli Robson and CSV 1000E tests, and retinal thicknesses measurement [ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL)] using Spectralis Optical Coherence Tomography (OCT). All subjects were re-evaluated after 5 years. The relationship between progressive structural changes and disease duration was analyzed. RESULTS: Visual function parameters in BD patients remained unchanged during the follow-up period. A progressive decrease affecting macular and peripapillary RNFL thickness (p < 0.050) was observed in patients. Progressive changes in BD were more pronounced when compared with healthy controls (p < 0.050). A significant correlation between GCL thickness changes and disease duration was found (GCL outer temporal, r = -0.680, p = 0.016; GCL central, r = -0.540, p = 0.038). CONCLUSIONS: Progressive axonal loss was detected in BD patients. Visual function parameters were not affected after the 5-year follow-up. Despite observed changes in the neuroretina of patients with BD, axonal degeneration in these patients seemed to be mild and might be slowed down by other factors, such as BD treatments.

Diagnostic Ability and Capacity of Optical Coherence Tomography-Angiography to Detect Retinal and Vascular Changes in Patients with Fibromyalgia.

Background: To evaluate the neuroretina and retinal vasculature of fibromyalgia (FM) patients and calculate a linear discriminant function (LDF) to improve retinal parameters' contribution to FM diagnosis. Methods: Fifty FM patients and 232 healthy controls underwent retinal evaluation using swept-source optical coherence tomography (SS-OCT) angiography (Triton plus; Topcon) and spectral domain OCT (SD-OCT) (Spectralis; Heidelberg). The macular (m) and peripapillary (p) retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) were assessed, as was the macular vascular density. A logistic regression analysis was performed, and an LDF was calculated to evaluate OCT's contribution to FM diagnosis. Results: With Triton OCT, the patients presented pRNFL thinning in the temporal sector (p=0.006). Spectralis OCT measurements showed decreased pRNFL in patients in the following sectors: superonasal, p=0.001; nasal, p=0.001; inferonasal, p=0.006; temporal, p=0.001; and inferotemporal, p=0.001. No significant differences were observed in the macular vascular plexus between patients and controls. However, vascular density in the superior sector showed a strong inverse correlation with disease duration (r = -0.978, p=0.022). The LDF calculated for Spectralis OCT yielded an area under the ROC curve of 0.968. Conclusions: FM patients present RNFL thinning observable using SS- and SD-OCT. However, these patients show similar vascular density in the macular area to healthy controls. The LDF that combines several RNFL parameters obtained using Spectralis OCT gives this device a powerful ability to differentiate between healthy individuals and individuals with FM.

Objective Diagnosis of Fibromyalgia Using Neuroretinal Evaluation and Artificial Intelligence.

Background/Objective: This study aims to identify objective biomarkers of fibromyalgia (FM) by applying artificial intelligence algorithms to structural data on the neuroretina obtained using swept-source optical coherence tomography (SS-OCT). Method: The study cohort comprised 29 FM patients and 32 control subjects. The thicknesses of complete retina, 3 retinal layers [ganglion cell layer (GCL+), GCL++ (between the inner limiting membrane and the inner nuclear layer boundaries) and retinal nerve fiber layer (RNFL)] and choroid in 9 areas around the macula were obtained using SS-OCT. Discriminant capacity was evaluated using the area under the curve (AUC) and the Relief algorithm. A diagnostic aid system with an automatic classifier was implemented. Results: No significant difference (p ≥ .660) was found anywhere in the choroid. In the RNFL, a significant difference was found in the inner inferior region (p = .010). In the GCL+, GCL++ layers and complete retina, a significant difference was found in the 4 regions defining the inner ring: temporal, superior, nasal and inferior. Applying an ensemble RUSBoosted tree classifier to the features with greatest discriminant capacity achieved accuracy = .82 and AUC = .82. Conclusions: This study identifies a potential novel objective and non-invasive biomarker of FM based on retina analysis using SS-OCT.

Antecedentes/Objetivo: Identificar biomarcadores objetivos de fibromialgia (FM) aplicando inteligencia artificial a datos estructurales de retina obtenidos mediante tomografía de coherencia óptica Swept Source (TCO-SS). Método: Se evaluó una cohorte de 29 pacientes con FM y otra de 32 sujetos control, registrando los espesores de la retina completa, de varias capas de la retina [capa de células ganglionares (CCG+), CCG ampliada (CCG++, entre la membrana limitante interna y los límites de la capa nuclear interna) y capa de fibras nerviosas (CFNR)] y de la coroides, mediante TCO-SS. La capacidad discriminante se evaluó mediante el área bajo la curva ROC (AROC) y el algoritmo Relief. Se implementó un sistema de ayuda al diagnóstico con clasificador automático. Resultados: No se observó diferencia significativa (p ≥ .660) en la coroides, pero sí en el sector inferior del anillo interno de la CFNR (p = .010) y en los cuatro sectores del anillo interno en las capas CCG+, CCG++ y retina completa. Utilizando un árbol de decisión ensemble RUSBoosted como clasificador de las características con mayor capacidad discriminante, se obtuvo una predicción alta (AROC=.820). Conclusiones: Se identifica un potencial biomarcador objetivo y no invasivo para el diagnóstico de FM basado en el análisis de la neurorretina mediante TCO-SS.

Automatic Diagnosis of Bipolar Disorder Using Optical Coherence Tomography Data and Artificial Intelligence.

BACKGROUND: The aim of this study is to explore an objective approach that aids the diagnosis of bipolar disorder (BD), based on optical coherence tomography (OCT) data which are analyzed using artificial intelligence. METHODS: Structural analyses of nine layers of the retina were analyzed in 17 type I BD patients and 42 controls, according to the areas defined by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The most discriminating variables made up the feature vector of several automatic classifiers: Gaussian Naive Bayes, K-nearest neighbors and support vector machines. RESULTS: BD patients presented retinal thinning affecting most layers, compared to controls. The retinal thickness of the parafoveolar area showed a high capacity to discriminate BD subjects from healthy individuals, specifically for the ganglion cell (area under the curve (AUC) = 0.82) and internal plexiform (AUC = 0.83) layers. The best classifier showed an accuracy of 0.95 for classifying BD versus controls, using as variables of the feature vector the IPL (inner nasal region) and the INL (outer nasal and inner inferior regions) thickness. CONCLUSIONS: Our patients with BD present structural alterations in the retina, and artificial intelligence seem to be a useful tool in BD diagnosis, but larger studies are needed to confirm our findings.

Ganglion Cell and Retinal Nerve Fiver Layers Correlated with Time Disease of Bipolar Disorder Using 64 Cell Grid OCT Tool.

MATERIALS AND METHODS: Twenty-five eyes of 25 patients with bipolar disorder and 74 eyes of 74 healthy controls underwent retinal measurements of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness. Measurements were obtained using the Spectralis-OCT device with the new Posterior Pole protocol which assesses the macular area by analyzing retinal thickness in a grid of 64 (8*8) cells. RESULTS: Significant differences (p < 0.05) in RNFL and GCL thickness were found between BD patients and healthy controls, in parafoveal and perifoveal cells respectively. Significant inverse correlations were found between RNFL and GCL thinning at their thickest location and the duration of bipolar disorder. Several predictive variables were observed with a binary logistic regression for the presence/absence of BD: cell 1.3 RNFL (p = 0.028) and GCL in cells 7.8 (p = 0.012), 2.7 (p = 0.043) and 1.3 (p = 0.047). CONCLUSION: Posterior Pole OCT protocol is a useful tool to assess changes in the inner retinal layers in bipolar disorder. These observed changes, especially those affecting the GCL, may be associated with disease evolution and may be predictive of the presence of the disease. OCT data could potentially be a useful tool for clinicians to diagnose and monitor BD patients.

Membrane of Plasma Rich in Growth Factors in Primary Pterygium Surgery Compared to Amniotic Membrane Transplantation and Conjunctival Autograft.

This prospective and comparative study aimed to compare the use of a conjunctival autograft (CAG), plasma rich in growth factors fibrin membrane (mPRGF) or amniotic membrane transplantation (AMT) in primary pterygium surgery. Patients were assigned for surgery with CAG (group A), mPRGF (group B), or AMT (group C). Pterygium recurrence, Best Corrected Visual Acuity (BCVA), graft size (measured with anterior segment optical coherence tomography (AS-OCT)), and ocular surface symptoms (visual analogue scale (VAS) and ocular surface disease index (OSDI)) were evaluated. Thirteen eyes in group A, 26 in group B, and 10 in group C were evaluated. No changes in BCVA (p > 0.05) were found. Recurrence cases for groups A, B, and C were none, two, and two, respectively, and three cases of pyogenic granulomas in group A. The horizontal/vertical graft size was lower in group B vs group A (p < 0.05) from months 1 to 12. The improvement in VAS frequency for groups A, B, and C was: 35.5%, 86.2%, and 39.1%, respectively. The OSDI scale reduction for groups A, B, and C was: 12.7%, 39.0%, and 84.1%. The use of the three surgical techniques as a graft for primary pterygium surgery was safe and effective, showing similar results. The mPRGF graft represents an autologous novel approach for pterygium surgery.

Ability of Swept source OCT technology to detect neurodegeneration in patients with type 2 diabetes mellitus without diabetic retinopathy.

PURPOSE: To evaluate neurodegeneration in patients with type 2 Diabetes Mellitus (DM2) without diabetic retinopathy, and to assess the possible role of chronic systemic ischaemia and disease duration in retinal changes. STUDY DESIGN: Observational cross sectional study. METHODS: Sixty eyes of 60 patients with DM2 without signs of diabetic retinopathy (DR), and 60 eyes of 60 healthy controls underwent retinal (ganglion cell layer (GCL), and retinal nerve fiber layer (RNFL) and choroidal evaluation using Swept source Optical coherence tomography, which allows high quality analysis of the different retinal layers and the choroidal plexus. Comparison between patients with presence/absence of systemic vascular complications and different disease duration time was performed. RESULTS: Macular GCL and RNFL were reduced in patients compared to controls (p < 0.001). In the peripapillary area, a reduction of the RNFL (p < 0.001) was observed in patients with DM2. There were no significant changes observed in the choroidal plexus of these patients. Patients with systemic ischaemia presented significant thinning of the choroid and further reduction of the temporal RNFL (p = 0.014) and GCL (p = 0.016) thickness. The GCL and the choroid were also thinner in patients with longer disease duration. CONCLUSIONS: Patients with early DM2 present retinal neurodegeneration prior to the appearance of clinically observable vascular retinal changes. In these patients chronic systemic ischaemia caused reduction of the choroidal plexus and further damage to the retinal layers, adding new information on systemic chronic ischaemia and retinal neurodegeneration in patients with DM2 without DR.