Analysis of the Asymmetry between Both Eyes in Early Diagnosis of Glaucoma Combining Features Extracted from Retinal Images and OCTs into Classification Models.

This study aims to analyze the asymmetry between both eyes of the same patient for the early diagnosis of glaucoma. Two imaging modalities, retinal fundus images and optical coherence tomographies (OCTs), have been considered in order to compare their different capabilities for glaucoma detection. From retinal fundus images, the difference between cup/disc ratio and the width of the optic rim has been extracted. Analogously, the thickness of the retinal nerve fiber layer has been measured in spectral-domain optical coherence tomographies. These measurements have been considered as asymmetry characteristics between eyes in the modeling of decision trees and support vector machines for the classification of healthy and glaucoma patients. The main contribution of this work is indeed the use of different classification models with both imaging modalities to jointly exploit the strengths of each of these modalities for the same diagnostic purpose based on the asymmetry characteristics between the eyes of the patient. The results show that the optimized classification models provide better performance with OCT asymmetry features between both eyes (sensitivity 80.9%, specificity 88.2%, precision 66.7%, accuracy 86.5%) than with those extracted from retinographies, although a linear relationship has been found between certain asymmetry features extracted from both imaging modalities. Therefore, the resulting performance of the models based on asymmetry features proves their ability to differentiate healthy from glaucoma patients using those metrics. Models trained from fundus characteristics are a useful option as a glaucoma screening method in the healthy population, although with lower performance than those trained from the thickness of the peripapillary retinal nerve fiber layer. In both imaging modalities, the asymmetry of morphological characteristics can be used as a glaucoma indicator, as detailed in this work.

Decision Trees for Glaucoma Screening Based on the Asymmetry of the Retinal Nerve Fiber Layer in Optical Coherence Tomography.

Purpose: The aim of this study was to analyze the relevance of asymmetry features between both eyes of the same patient for glaucoma screening using optical coherence tomography. Methods: Spectral-domain optical coherence tomography was used to estimate the thickness of the peripapillary retinal nerve fiber layer in both eyes of the patients in the study. These measurements were collected in a dataset from healthy and glaucoma patients. Several metrics for asymmetry in the retinal nerve fiber layer thickness between the two eyes were then proposed. These metrics were evaluated using the dataset by performing a statistical analysis to assess their significance as relevant features in the diagnosis of glaucoma. Finally, the usefulness of these asymmetry features was demonstrated by designing supervised machine learning models that can be used for the early diagnosis of glaucoma. Results: Machine learning models were designed and optimized, specifically decision trees, based on the values of proposed asymmetry metrics. The use of these models on the dataset provided good classification of the patients (accuracy 88%, sensitivity 70%, specificity 93% and precision 75%). Conclusions: The obtained machine learning models based on retinal nerve fiber layer asymmetry are simple but effective methods which offer a good trade-off in classification of patients and simplicity. The fast binary classification relies on a few asymmetry values of the retinal nerve fiber layer thickness, allowing their use in the daily clinical practice for glaucoma screening.

B-SCAN ULTRASONOGRAPHY OF VITREOUS DYNAMICS DURING INTRAVITREAL ADMINISTRATION OF ANTIANGIOGENICS.

PURPOSE: To study the distribution of angiogenesis inhibitors (anti-Vascular Endothelial Growth Factor) injected into the vitreous cavity by means of simultaneous ultrasonography. METHODS: Three hundred and thirty-two B-scan ultrasound sequences of 121 eyes from 95 patients were recorded simultaneously to the intravitreal anti-Vascular Endothelial Growth Factor administration. The dynamics of the injected substance and the presence of reflux were studied, associating them with the presence/absence of total posterior vitreous detachment. RESULTS: Three well-defined patterns were distinguished. Pattern A: the medication penetrates the vitreous in a linear manner until reaching the retina (3.6%, n = 12). Pattern B: the medication adopts a globular shape and then moves down reaching the retrohyaloid space (37%, n = 123). Pattern C: the medication remains in a globular form (54%, n = 180). The pattern was not identified in 17 (5.1%) injections. Pattern A was only observed in vitrectomized eyes. The reflux (7.8%) was exclusive in eyes showing a C pattern. A relationship (P < 0.001) was observed between the presence/absence of total posterior vitreous detachment, the patterns, and the presence of reflux. CONCLUSION: This study document for the first time the behavior of antiangiogenic medication injected into the vitreous cavity and how its distribution and the presence of reflux is conditioned by the previous state of the vitreous body.

Automatic Segmentation of the Retinal Nerve Fiber Layer by Means of Mathematical Morphology and Deformable Models in 2D Optical Coherence Tomography Imaging.

Glaucoma is a neurodegenerative disease process that leads to progressive damage of the optic nerve to produce visual impairment and blindness. Spectral-domain OCT technology enables peripapillary circular scans of the retina and the measurement of the thickness of the retinal nerve fiber layer (RNFL) for the assessment of the disease status or progression in glaucoma patients. This paper describes a new approach to segment and measure the retinal nerve fiber layer in peripapillary OCT images. The proposed method consists of two stages. In the first one, morphological operators robustly detect the coarse location of the layer boundaries, despite the speckle noise and diverse artifacts in the OCT image. In the second stage, deformable models are initialized with the results of the previous stage to perform a fine segmentation of the boundaries, providing an accurate measurement of the entire RNFL. The results of the RNFL segmentation were qualitatively assessed by ophthalmologists, and the measurements of the thickness of the RNFL were quantitatively compared with those provided by the OCT inbuilt software as well as the state-of-the-art methods.

Oxidative Stress Mediates Epigenetic Modifications and the Expression of miRNAs and Genes Related to Apoptosis in Diabetic Retinopathy Patients.

Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.

PAPILA: Dataset with fundus images and clinical data of both eyes of the same patient for glaucoma assessment.

Glaucoma is one of the ophthalmological diseases that frequently causes loss of vision in today's society. Previous studies assess which anatomical parameters of the optic nerve can be predictive of glaucomatous damage, but to date there is no test that by itself has sufficient sensitivity and specificity to diagnose this disease. This work provides a public dataset with medical data and fundus images of both eyes of the same patient. Segmentations of the cup and optic disc, as well as the labeling of the patients based on the evaluation of clinical data are also provided. The dataset has been tested with a neural network to classify healthy and glaucoma patients. Specifically, the ResNet-50 has been used as the basis to classify patients using information from each eye independently as well as using the joint information from both eyes of each patient. Results provide the baseline metrics, with the aim of promoting research in the early detection of glaucoma based on the joint analysis of both eyes of the same patient.

Inactivation of intracellular Rho to stimulate axon growth and regeneration.

Our studies indicate that the small GTPase Rho is an important intracellular target for promoting axon regrowth after injury. In tissue culture, inactivation of the Rho signaling pathway is effective in promoting neurite growth on growth inhibitory CNS substrates by two different methods: inactivation of Rho with C3 transferase, and inactivation by dominant negative mutation of Rho. In vivo, we have documented the regeneration of transfected axons after treatment with C3 in two different animals models, microcrush lesion of the adult rat optic nerve, and over-hemisection of adult mouse spinal cord. Mice treated with C3 after SCI showed impressive functional recovery, notwithstanding the fact that mice differ from rats in their response to spinal cord injury, especially in the extent of cavitation at the lesion site (Steward et al., 1999). It remains to be determined to what extent the regeneration of specific descending and ascending spinal axons contribute to the recovery, and whether inactivation of Rho enhances the spontaneous plasticity of axonal and dendritic remodeling after SCI. Inactivation of Rho with C3 to promote regeneration and functional recovery after SCI is simple, and our studies reveal the potential for a new, straightforward technique to promote axon regeneration.