Normative Data and Minimally Detectable Change for Inner Retinal Layer Thicknesses Using a Semi-automated OCT Image Segmentation Pipeline

Neurodegenerative and neuroinflammatory diseases regularly cause optic nerve and retinal damage. Evaluating retinal changes using optical coherence tomography (OCT) in diseases like multiple sclerosis has thus become increasingly relevant. However, intraretinal segmentation, a necessary step for interpreting retinal changes in the context of these diseases, is not standardized and often requires manual correction. Here we present a semi-automatic intraretinal layer segmentation pipeline and establish normative values for retinal layer thicknesses at the macula, including dependencies on age, sex, and refractive error. Spectral domain OCT macular 3D volume scans were obtained from healthy participants using a Heidelberg Engineering Spectralis OCT. A semi-automated segmentation tool (SAMIRIX) based on an interchangeable third-party segmentation algorithm was developed and employed for segmentation, correction, and thickness computation of intraretinal layers. Normative data is reported froma 6mmEarly Treatment Diabetic Retinopathy Study (ETDRS) circle around the fovea. An interactive toolbox for the normative database allows surveying for additional normative data. We cross-sectionally evaluated data from218 healthy volunteers (144 females/74males, age 36.5 ± 12.3 years, range 18–69 years). Average macular thickness (MT) was 313.70 ± 12.02 μm, macular retinal nerve fiber layer thickness (mRNFL) 39.53 ± 3.57 μm, ganglion cell and inner plexiform layer thickness (GCIPL) 70.81 ± 4.87 μm, and inner nuclear layer thickness (INL) 35.93 ± 2.34 μm. All retinal layer thicknesses decreased with age. MT and GCIPL were associated with sex, with males showing higher thicknesses. Layer thicknesses were also positively associated with each other. Repeated-measurement reliability for the manual correction of automatic intraretinal segmentation results was excellent, with an intra-class correlation coefficient >0.99 for all layers. The SAMIRIX toolbox can simplify intraretinal segmentation in research applications, and the normative data application may serve as an expandable reference for studies, in which normative data cannot be otherwise obtained

Progression of Retinal Pigment Epithelial Atrophy in Antiangiogenic Therapy of Neovascular Age-Related Macular Degeneration

PurposeTo monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT).DesignProspective interventional case series.Methodssetting: Clinical practice. study population: Thirty patients (31 eyes) with treatment-naïve neovascular AMD. observation procedures: Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. main outcome measures: RPE response, geographic atrophy (GA) progression.ResultsAtrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm2 at 12 months to 1.10 mm2 (standard deviation = 1.09 mm2) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased.ConclusionsProgressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes

Fractal-based analysis of optical coherence tomography data to quantify retinal tissue damage

BACKGROUND: The sensitivity of Optical Coherence Tomography (OCT) images to identify retinal tissue morphology characterized by early neural loss from normal healthy eyes is tested by calculating structural information and fractal dimension. OCT data from 74 healthy eyes and 43 eyes with type 1 diabetes mellitus with mild diabetic retinopathy (MDR) on biomicroscopy was analyzed using a custom-built algorithm (OCTRIMA) to measure locally the intraretinal layer thickness. A power spectrum method was used to calculate the fractal dimension in intraretinal regions of interest identified in the images. ANOVA followed by Newman-Keuls post-hoc analyses were used to test for differences between pathological and normal groups. A modified p value of <0.001 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to describe the ability of each parameter to discriminate between eyes of pathological patients and normal healthy eyes. RESULTS: Fractal dimension was higher for all the layers (except the GCL + IPL and INL) in MDR eyes compared to normal healthy eyes. When comparing MDR with normal healthy eyes, the highest AUROC values estimated for the fractal dimension were observed for GCL + IPL and INL. The maximum discrimination value for fractal dimension of 0.96 (standard error =0.025) for the GCL + IPL complex was obtained at a FD <= 1.66 (cut off point, asymptotic 95% Confidence Interval: lower-upper bound = 0.905-1.002). Moreover, the highest AUROC values estimated for the thickness measurements were observed for the OPL, GCL + IPL and OS. Particularly, when comparing MDR eyes with control healthy eyes, we found that the fractal dimension of the GCL + IPL complex was significantly better at diagnosing early DR, compared to the standard thickness measurement. CONCLUSIONS: Our results suggest that the GCL + IPL complex, OPL and OS are more susceptible to initial damage when comparing MDR with control healthy eyes. Fractal analysis provided a better sensitivity, offering a potential diagnostic predictor for detecting early neurodegeneration in the retina

Optical Coherence Tomographic Angiography Imaging in Age-Related Macular Degeneration.

Optical coherence tomographic angiography (OCTA) is emerging as a rapid, noninvasive imaging modality that can provide detailed structural and flow information on retinal and choroidal vasculature. This review contains an introduction of OCTA and summarizes the studies to date on OCTA imaging in age-related macular degeneration

Distinctive Mechanisms and Patterns of Exudative Versus Tractional Intraretinal Cystoid Spaces as Seen With Multimodal Imaging.

PurposeTo determine clear-cut distinctions between tractional and exudative intraretinal cystoid spaces subtypes.DesignRetrospective, multicenter, observational case series.MethodsA cohort of patients diagnosed with intraretinal cystoid spaces and imaged with optical coherence tomography (OCT), fluorescein angiography (FA), blue fundus autofluorescence (BFAF), en face OCT, and OCT angiography (OCT-A) was included in the study. All images were qualitatively and quantitatively evaluated.ResultsIn this study were included 72 eyes of 69 patients. Exudative intraretinal cystoid spaces (36/72 eyes, 50%) displayed a "petaloid" morphology as seen with en face OCT, FA, and BFAF. Tractional intraretinal cystoid spaces (24/72 eyes, 33.3%), displayed a radial "spoke-wheel" en face OCT pattern. There was no leakage with FA and BFAF did not reveal specific patterns. Eyes with full-thickness macular hole (FTMH, 12/72 eyes, 16.7%) displayed a "sunflower" en face OCT appearance. FTMH showed OCT, OCT-A, and BFAF features of both exudative and tractional cystoid spaces, but without any FA leakage. Inner nuclear layer (INL) thickness was significantly lower in tractional cystoid spaces (P &lt; .001). There were a greater number of INL cystoid spaces in both the exudative and FTMH subgroups (P = .001). The surface area of INL cystoid spaces was significantly lower in the tractional subgroup (P &lt; .001). There was a significant reduction of the microvascular density in eyes with exudative vs tractional (P = .002) and FTMH (P &lt; .001) subgroups.ConclusionsExudative and tractional intraretinal cystoid spaces displayed characteristic multimodal imaging features and they may represent 2 different pathologic conditions with equally different clinical implications

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

Automatic Detection and Characterization of Pathological Fluid Regions in Optical Coherence Tomography Images

Programa Oficial de Doutoramento en Computación. 5009V01[Abstract] Intraretinal fluid accumulation is both the common symptom and culprit of the main causes of blindness in developed countries: Age-related Macular Degeneration and Diabetic Macular Edema. For its diagnosis, experts of the domain employ Optical Coherence Tomography images (OCT), providing non-invasive cross-sectional representations of the retinal structures. However, like any medical imaging modality, OCT is influenced by multiple factors that impact its quality and subsequent interpretation. Coupled with the subjectiveness of the human experts, these factors can significantly affect the diagnostic process, treatment and quality of life for the affected individuals (particularly in these pathologies where early detection is crucial). To address these challenges, Computer-Aided Diagnosis (CAD) methodologies are developed, offering a layer of abstraction of the information present in the images. Still, in the particular scenario of these pathological fluid accumulations, the development of these methodologies is specially difficult due to their diffuse nature without defined boundaries. In this thesis, we proposed different CAD methodologies with the objective of helping expert clinicians to better detect and understand these pathologies. Furthermore, we expand the developed methodologies to other medical imaging modalities and conditions, such as macular neovascularizations in OCT Angiographies and COVID-19 diagnosis through the analysis of lung chest radiographs.[Resumen] La acumulación de líquido intrarretiniano es tanto síntoma común como culpable de las principales causas de ceguera en los países desarrollados: la degeneración macular asociada a la edad y el edema macular diabético. Para su diagnóstico, los expertos en el campo emplean imágenes de Tomografía de Coherencia Óptica (OCT), que proporcionan representaciones transversales no invasivas de las estructuras retinianas. Sin embargo, al igual que cualquier modalidad de imagen médica, OCT se ve influenciado por múltiples factores que afectan a su calidad y posterior interpretación. Junto con la subjetividad de los expertos humanos, estos factores pueden afectar significativamente el proceso diagnóstico, tratamiento y calidad de vida de las personas afectadas (particularmente en estas patologías donde una detección temprana es crucial). Para abordar estos desafíos, se desarrollan metodologías de diagnóstico asistido por ordenador (CAD), que ofrecen una capa de abstracción de la información presente en las imágenes. Sin embargo, en el escenario particular de estas acumulaciones patológicas de fluido, el desarrollo de estas metodologías es especialmente difícil debido a su naturaleza difusa, sin bordes definidos. En esta tesis doctoral proponemos diferentes metodologías CAD con el objetivo de ayudar a las personas expertas del dominio a detectar y comprender mejor estas patologías. Además, expandimos las metodologías desarrolladas a otras modalidades de imagen médica y afecciones, como al análisis de neovascularizaciones maculares en Angiografía OCT y al diagnóstico de COVID-19 mediante radiografías torácicas.[Resumo] A acumulación de líquido intrarretiniano é tanto o síntoma común como culpable das principais causas de cegueira nos países desenvolvidos: a dexeneración macular asociada á idade e o edema macular diabético. Para o seu diagnóstico, os expertos no campo empregan imaxes de tomografía de coherencia óptica (OCT), que proporcionan representacións transversais non invasivas das estruturas retinianas. Non obstante, ao igual que calquera modalidade de imaxe médica, a OCT vese influenciada por múltiples factores que afectan a s´ua calidade e a súa posterior interpretación. Xunto coa subxectividade dos expertos humanos, estes factores poden afectar significativamente ao proceso diagn´ostico, ao tratamento e á calidade de vida das persoas afectadas (particularmente nestas patoloxías onde unha detección precoz é crucial). Para abordar estes desafíos, desenvólvense metodoloxías de diagnóstico asistido por ordenador (CAD), que ofrecen unha capa de abstracción da información presente nas imaxes. Non obstante, no escenario particular das acumulacións patolóxicas de líquido, o desenvolvemento destas metodoloxías é especialmente difícil debido a súa natureza difusa, sen bordes definidos. Nesta tese de doutoramento propoñemos diferentes metodoloxías de CAD co obxectivo de axudar ás persoas expertas do campo a detectar e comprender mellor estas patoloxías. Ademais, expandimos as metodoloxías desenvoltas a outras modalidades de imaxe médica e patoloxías, como a an´alise de neovascularizacións maculares en Anxiografía OCT e ao diagnóstico da COVID-19 mediante a análise de radiografías torácicas

The Effect of Axial Length on the Thickness of Intraretinal Layers of the Macula.

PURPOSE: The aim of this study was to evaluate the effect of axial length (AL) on the thickness of intraretinal layers in the macula using optical coherence tomography (OCT) image analysis. METHODS: Fifty three randomly selected eyes of 53 healthy subjects were recruited for this study. The median age of the participants was 29 years (range: 6 to 67 years). AL was measured for each eye using a Lenstar LS 900 device. OCT imaging of the macula was also performed by Stratus OCT. OCTRIMA software was used to process the raw OCT scans and to determine the weighted mean thickness of 6 intraretinal layers and the total retina. Partial correlation test was performed to assess the correlation between the AL and the thickness values. RESULTS: Total retinal thickness showed moderate negative correlation with AL (r = -0.378, p = 0.0007), while no correlation was observed between the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCC), retinal pigment epithelium (RPE) and AL. Moderate negative correlation was observed also between the thickness of the ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and AL which were more pronounced in the peripheral ring (r = -0.402, p = 0.004; r = -0.429, p = 0.002; r = -0.360, p = 0.01; r = -0.448, p = 0.001). CONCLUSIONS: Our results have shown that the thickness of the nuclear layers and the total retina is correlated with AL. The reason underlying this could be the lateral stretching capability of these layers; however, further research is warranted to prove this theory. Our results suggest that the effect of AL on retinal layers should be taken into account in future studies