EFFICACY OF INTRAVITREAL AFLIBERCEPT IN MACULAR TELANGIECTASIA TYPE 1 IS LINKED TO THE OCULAR ANGIOGENIC PROFILE.

To evaluate intravitreal aflibercept in macular telangiectasia Type 1 (MacTel 1) patients and measure their ocular angiogenic profile. Eight subjects with MacTel 1 refractory to bevacizumab, ranibizumab, or laser therapy and switched to aflibercept were included. Best-corrected visual acuity, central macular thickness, and cystic areas quantified on optical coherence tomography B-scans were assessed during 12 months. Perifoveal capillary densities were measured on optical coherence tomography angiography. Aqueous humor was sampled from six patients and eight control subjects undergoing cataract extraction. Growth factors were quantified using a multiarray immunoassay. Over 12 months, patients received 6.6 ± 1.4 (range, 5-8) intravitreal aflibercept injections. Twelve months after switching to aflibercept, best-corrected visual acuity increased by ≥5 letters in 5 of 8 patients, compared with preaflibercept levels. Mean best-corrected visual acuity improved from 79.6 (∼20/50) to 88.0 (∼20/35) Early Treatment Diabetic Retinopathy Study letters (P = 0.042), and central macular thickness decreased from 434 ± 98 μm to 293 ± 59 μm (P = 0.014). Compared with control subjects, the profile of angiogenic factors in MacTel 1 eyes revealed no difference in vascular endothelial growth factor-A levels but significantly higher levels of placental growth factor (P = 0.029), soluble vascular endothelial growth factor receptor-1 (sFlt-1; P = 0.013), vascular endothelial growth factor-D (P = 0.050), and Tie-2 (P = 0.019). Placental growth factor levels inversely correlated with both superficial and deep capillary plexus densities on optical coherence tomography angiography (P = 0.03). The clinical response to aflibercept coupled to the angiogenic profile of MacTel 1 eyes support the implication of the placental growth factor/Flt-1 pathway in MacTel 1

Retinal Vascular Analysis in a Fully Automated Method for the Segmentation of DRT Edemas Using OCT Images

[Abstract] Optical Coherence Tomography (OCT) is a well-established medical imaging technique that allows a complete analysis and evaluation of the main retinal structures and their histopathology properties. Diabetic Macular Edema (DME) implies the accumulation of intraretinal fluid within the macular region. Diffuse Retinal Thickening (DRT) edemas are considered a relevant case of DME disease, where the pathological regions are characterized by a “sponge-like” appearance and a reduced intraretinal reflectivity, being visible in OCT images. Additionally, the presence of other structures may alter the OCT image characteristics, confusing the pathological identification process. This is the case of the retinal vessels over all the eye fundus, whose presence produce shadow projections over the retinal layers that may hide the “sponge-like” appearance of the DRT edemas. Thus, in this paper, we present a proposal for the automatic extraction of DRT edemas, also using as reference the information provided by the automatic identifications of the retinal vessels in the OCT images. To do that, firstly, the system delimits three retinal regions of interest. These retinal regions facilitate the posterior identification of the vessel structures and the segmentation of the DRT regions. For the identification of the vessels structures, the method combined the localization of the upper bright vascular profiles with the presence of their corresponding lower dark vascular shadows. Finally, a learning strategy is implemented for the segmentation of the DRT edemas. Satisfactory results were obtained, reaching values of 0.8346 and 0.9051 of Jaccard index and Dice coefficient, respectively, for the extraction of the existing DRT edemas.Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-047This work is supported by the Instituto de Salud Carlos III, Government of Spain and FEDER funds of the European Union through the DTS18/00136 research projects and by the Ministerio de Economía y Competitividad, Government of Spain through the DPI2015-69948-R research project. Also, this work has received financial support from the European Union (European Regional Development Fund - ERDF) and the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016-2019, Ref. ED431G/01; and Grupos de Referencia Competitiva, Ref. ED431C 2016-047

Caracterización del Edema Macular Diabético mediante análisis automático de Tomografías de Coherencia Óptica

Programa Oficial de Doctorado en Computación. 5009V01[Abstract] Diabetic Macular Edema (DME) is one of the most important complications of diabetes and a leading cause of preventable blindness in the developed countries. Among the di erent image modalities, Optical Coherence Tomography (OCT) is a non-invasive, cross-sectional and high-resolution imaging technique that is commonly used for the analysis and interpretation of many retinal structures and ocular disorders. In this way, the development of Computer-Aided Diagnosis (CAD) systems has become relevant over the recent years, facilitating and simplifying the work of the clinical specialists in many relevant diagnostic processes, replacing manual procedures that are tedious and highly time-consuming. This thesis proposes a complete methodology for the identi cation and characterization of DMEs using OCT images. To do so, the system combines and exploits di erent clinical knowledge with image processing and machine learning strategies. This automatic system is able to identify and characterize the main retinal structures and several pathological conditions that are associated with the DME disease, following the clinical classi cation of reference in the ophthalmological eld. Despite the complexity and heterogeneity of this relevant ocular pathology, the proposed system achieved satisfactory results, proving to be robust enough to be used in the daily clinical practice, helping the clinicians to produce a more accurate diagnosis and indicate adequate treatments[Resumen] El Edema Macular Diabético (EMD) es una de las complicaciones más importantes de la diabetes y una de las principales causas de ceguera prevenible en los países desarrollados. Entre las diferentes modalidades de imagen, la Tomografía de Coherencia Óptica (TCO) es una técnica de imagen no invasiva, transversal y de alta resolución que se usa comúnmente para el análisis e interpretación de múltiples estructuras retinianas y trastornos oculares. De esta manera, el desarrollo de los sistemas de Diagnóstico Asistido por Ordenador (DAO) se ha vuelto relevante en los últimos años, facilitando y simplificando el trabajo de los especialistas clínicos en muchos procesos diagnósticos relevantes, reemplazando procedimientos manuales que son tediosos y requieren mucho tiempo. Esta tesis propone una metodología completa para la identificación y caracterización de EMDs utilizando imágenes TCO. Para ello, el sistema desarrollado combina y explota diferentes conocimientos clínicos con estrategias de procesamiento de imágenes y aprendizaje automático. Este sistema automático es capaz de identificar y caracterizar las principales estructuras retinianas y diferentes afecciones patológicas asociadas con el EMD, siguiendo la clasificación clínica de referencia en el campo oftalmológico. A pesar de la complejidad de esta relevante patología ocular, el sistema propuesto logró resultados satisfactorios, demostrando ser lo sufi cientemente robusto como para ser usado en la práctica clínica diaria, ayudando a los médicos a producir diagnósticos más precisos y tratamientos más adecuados.[Resumo] O Edema Macular Diabético ( EMD) é unha das complicacións máis importantes da diabetes e unha das principais causas de cegueira prevenible nos países desenvoltos. Entre as diferentes modalidades de imaxe, a Tomografía de Coherencia Óptica ( TCO) é unha técnica de imaxe non invasiva, transversal e de alta resolución que se usa comunmente para a análise e interpretación de múltiples estruturas retinianas e trastornos oculares. Desta maneira, o desenvolvemento dos sistemas de Diagnóstico Asistido por Computador ( DAO) volveuse relevante nos últimos anos, facilitando e simplificando o traballo dos especialistas clínicos en moitos procesos diagnósticos relevantes, substituíndo procedementos manuais que son tediosos e requiren moito tempo. Esta tese propón unha metodoloxía completa para a identificación e caracterización de EMDs utilizando imaxes TCO. Para iso, o sistema desenvolto combina e explota diferentes coñecementos clínicos con estratexias de procesamento de imaxes e aprendizaxe automático. Este sistema automático é capaz de identificar e caracterizar as principais estruturas retinianas e diferentes afeccións patolóxicas asociadas co EMD, seguindo a clasificación clínica de referencia no campo oftalmolóxico. A pesar da complexidade desta relevante patoloxía ocular, o sistema proposto logrou resultados satisfactorios, demostrando ser o sufi cientemente robusto como para ser usado na práctica clínica diaria, axudando aos médicos para producir diagnósticos máis precisos e tratamentos máis adecuados

Foveal avascular zone segmentation in optical coherence tomography angiography images using a deep learning approach

The purpose of this study was to introduce a new deep learning (DL) model for segmentation of the fovea avascular zone (FAZ) in en face optical coherence tomography angiography (OCTA) and compare the results with those of the device�s built-in software and manual measurements in healthy subjects and diabetic patients. In this retrospective study, FAZ borders were delineated in the inner retinal slab of 3 � 3 enface OCTA images of 131 eyes of 88 diabetic patients and 32 eyes of 18 healthy subjects. To train a deep convolutional neural network (CNN) model, 126 enface OCTA images (104 eyes with diabetic retinopathy and 22 normal eyes) were used as training/validation dataset. Then, the accuracy of the model was evaluated using a dataset consisting of OCTA images of 10 normal eyes and 27 eyes with diabetic retinopathy. The CNN model was based on Detectron2, an open-source modular object detection library. In addition, automated FAZ measurements were conducted using the device�s built-in commercial software, and manual FAZ delineation was performed using ImageJ software. Bland�Altman analysis was used to show 95 limit of agreement (95 LoA) between different methods. The mean dice similarity coefficient of the DL model was 0.94 ± 0.04 in the testing dataset. There was excellent agreement between automated, DL model and manual measurements of FAZ in healthy subjects (95 LoA of � 0.005 to 0.026 mm2 between automated and manual measurement and 0.000 to 0.009 mm2 between DL and manual FAZ area). In diabetic eyes, the agreement between DL and manual measurements was excellent (95 LoA of � 0.063 to 0.095), however, there was a poor agreement between the automated and manual method (95 LoA of � 0.186 to 0.331). The presence of diabetic macular edema and intraretinal cysts at the fovea were associated with erroneous FAZ measurements by the device�s built-in software. In conclusion, the DL model showed an excellent accuracy in detection of FAZ border in enfaces OCTA images of both diabetic patients and healthy subjects. The DL and manual measurements outperformed the automated measurements of the built-in software. © 2021, The Author(s)

Diabetic Macular Edema Characterization and Visualization Using Optical Coherence Tomography Images

[Abstract] Diabetic Retinopathy and Diabetic Macular Edema (DME) represent one of the main causes of blindness in developed countries. They are characterized by fluid deposits in the retinal layers, causing a progressive vision loss over the time. The clinical literature defines three DME types according to the texture and disposition of the fluid accumulations: Cystoid Macular Edema (CME), Diffuse Retinal Thickening (DRT) and Serous Retinal Detachment (SRD). Detecting each one is essential as, depending on their presence, the expert will decide on the adequate treatment of the pathology. In this work, we propose a robust detection and visualization methodology based on the analysis of independent image regions. We study a complete and heterogeneous library of 375 texture and intensity features in a dataset of 356 labeled images from two of the most used capture devices in the clinical domain: a CIRRUSTM HD-OCT 500 Carl Zeiss Meditec and 179 OCT images from a modular HRA + OCT SPECTRALIS® from Heidelberg Engineering, Inc. We extracted 33,810 samples for each type of DME for the feature analysis and incremental training of four different classifier paradigms. This way, we achieved an 84.04% average accuracy for CME, 78.44% average accuracy for DRT and 95.40% average accuracy for SRD. These models are used to generate an intuitive visualization of the fluid regions. We use an image sampling and voting strategy, resulting in a system capable of detecting and characterizing the three types of DME presenting them in an intuitive and repeatable way.Xunta de Galicia; ED431G 2019/01This research was funded by Instituto de Salud Carlos III, Government of Spain, DTS18/00136 research project; Ministerio de Ciencia, Innovación y Universidades, Government of Spain, RTI2018-095894-B-I00 research project, Ayudas para la formación de profesorado universitario (FPU), grant ref. FPU18/02271; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)

Automatic macular edema identification and characterization using OCT images

© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. This version of the article: Samagaio, G., Estévez, A., Moura, J. de, Novo, J., Fernández, M. I., & Ortega, M. (2018). “Automatic macular edema identification and characterization using OCT images” has been accepted for publication in Computer Methods and Programs in Biomedicine, 163, 47–63. The Version of Record is available online at: https://doi.org/10.1016/j.cmpb.2018.05.033.[Abstract]: Background and objective: The detection and characterization of the intraretinal fluid accumulation constitutes a crucial ophthalmological issue as it provides useful information for the identification and diagnosis of the different types of Macular Edema (ME). These types are clinically defined, according to the clinical guidelines, as: Serous Retinal Detachment (SRD), Diffuse Retinal Thickening (DRT) and Cystoid Macular Edema (CME). Their accurate identification and characterization facilitate the diagnostic process, determining the disease severity and, therefore, allowing the clinicians to achieve more precise analysis and suitable treatments. Methods: This paper proposes a new fully automatic system for the identification and characterization of the three types of ME using Optical Coherence Tomography (OCT) images. In the case of SRD and CME edemas, multilevel image thresholding approaches were designed and combined with the application of ad-hoc clinical restrictions. The case of DRT edemas, given their complexity and fuzzy regional appearance, was approached by a learning strategy that exploits intensity, texture and clinical-based information to identify their presence. Results: The system provided satisfactory results with F-Measures of 87.54% and 91.99% for the DRT and CME detections, respectively. In the case of SRD edemas, the system correctly detected all the cases that were included in the designed dataset. Conclusions: The proposed methodology offered an accurate performance for the individual identification and characterization of the three different types of ME in OCT images. In fact, the method is capable to handle the ME analysis even in cases of significant severity with the simultaneous existence of the three ME types that appear merged inside the retinal layers.This work is supported by the Instituto de Salud Carlos III, Government of Spain and FEDER funds of the European Union through the PI14/02161 and the DTS15/00153 research projects and by the Ministerio de Economía y Competitividad, Government of Spain through the DPI2015-69948-R research project. Also, this work has received financial support from the European Union (European Regional Development Fund - ERDF) and the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019, Ref. ED431G/01; and Grupos de Referencia Competitiva, Ref. ED431C 2016-047.Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-04