Foveal Pit Morphology Characterization: A Quantitative Analysis of the Key Methodological Steps

Disentangling the cellular anatomy that gives rise to human visual perception is one of the main challenges of ophthalmology. Of particular interest is the foveal pit, a concave depression located at the center of the retina that captures light from the gaze center. In recent years, there has been a growing interest in studying the morphology of the foveal pit by extracting geometrical features from optical coherence tomography (OCT) images. Despite this, research has devoted little attention to comparing existing approaches for two key methodological steps: the location of the foveal center and the mathematical modelling of the foveal pit. Building upon a dataset of 185 healthy subjects imaged twice, in the present paper the image alignment accuracy of four different foveal center location methods is studied in the first place. Secondly, state-of-the-art foveal pit mathematical models are compared in terms of fitting error, repeatability, and bias. The results indicate the importance of using a robust foveal center location method to align images. Moreover, we show that foveal pit models can improve the agreement between different acquisition protocols. Nevertheless, they can also introduce important biases in the parameter estimates that should be considered.This research was funded by the Department of Health of the Basque Government through the projects 2019111100 and 2020333033, Instituto de Salud Carlos III through the project PI16/00005 (Co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”) and the Basque Foundation for Health Innovation and Research (BIOEF) through the 2017 EITB Telemaratoia call (BIO17/ND/010)

Potential Tear Biomarkers for the Diagnosis of Parkinson’s Disease—A Pilot Study

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. In this study, the tear proteome profile of patients with idiopathic PD (iPD, n = 24), carriers of the E46K-SNCA mutation (n = 3) and healthy control (CT, n = 27) subjects was analyzed to identify candidate biomarkers for the diagnosis of PD. An observational, prospective and case-control pilot study was carried out, analyzing the participants tear samples by nano-liquid chromatography–mass spectrometry (nLC–MS/MS) and assessing their neurological impairment. The proteomic data obtained are available at ProteomeXchange with identifier 10.6019/PXD028811. These analyses led to the identification of 560 tear proteins, some of which were deregulated in PD patients and that have been implicated in immune responses, inflammation, apoptosis, collagen degradation, protein synthesis, defense, lipid transport and altered lysosomal function. Of these proteins, six were related to neurodegenerative processes and showed a good capacity to classify patients and controls. These findings revealed that certain proteins were upregulated in the tears of PD patients, mainly proteins involved in lysosomal function. Thus, in this study, tear proteins were identified that are implicated in neurodegeneration and that may be related to an aggressive disease phenotype in PD patients.This work was supported by MINECO-Retos Fondos Fender (RTC-2016-48231), Gobierno Vasco (PUE_2018_1_0004), ELKARTEK (KK-2019/00086), PIBA 2020-1-0026, MINECO-Retos (PID2019-111139RB-I00) and ELKARTEK (KK-2021/00023)

Spatial characterization of the effect of age and sex on macular layer thicknesses and foveal pit morphology

Characterizing the effect of age and sex on macular retinal layer thicknesses and foveal pit morphology is crucial to differentiating between natural and disease-related changes. We applied advanced image analysis techniques to optical coherence tomography (OCT) to: 1) enhance the spatial description of age and sex effects, and 2) create a detailed open database of normative retinal layer thickness maps and foveal pit shapes. The maculae of 444 healthy subjects (age range 21–88) were imaged with OCT. Using computational spatial data analysis, thickness maps were obtained for retinal layers and averaged into 400 (20 x 20) sectors. Additionally, the geometry of the foveal pit was radially analyzed by computing the central foveal thickness, rim height, rim radius, and mean slope. The effect of age and sex on these parameters was analyzed with multiple regression mixed-effects models. We observed that the overall age-related decrease of the total retinal thickness (TRT) (-1.1% per 10 years) was mainly driven by the ganglion cell-inner plexiform layer (GCIPL) (-2.4% per 10 years). Both TRT and GCIPL thinning patterns were homogeneous across the macula when using percentual measurements. Although the male retina was 4.1 μm thicker on average, the greatest differences were mainly present for the inner retinal layers in the inner macular ring (up to 4% higher TRT than in the central macula). There was an age-related decrease in the rim height (1.0% per 10 years) and males had a higher rim height, shorter rim radius, and steeper mean slope. Importantly, the radial analysis revealed that these changes are present and relatively uniform across angular directions. These findings demonstrate the capacity of advanced analysis of OCT images to enhance the description of the macula. This, together with the created dataset, could aid the development of more accurate diagnosis models for macular pathologies.This study was partially co-funded by the Instituto de Salud Carlos III (https://www.isciii.es) through the projects PI14/00679 (IG) and PI16/00005 (IG), by the Basque Foundation for Health Innovation and Research (https://www.bioef.org) through the project BIO17/ND/010 (IG), and by the Department of Health of the Basque Government (https://www.euskadi.eus/gobierno-vasco/departamento-salud) through the projects 2019111100 (IG), 2020333033(IG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Parafoveal thinning of inner retina is associated with visual dysfunction in Lewy body diseases

Background Retinal optical coherence tomography findings in Lewy body diseases and their implications for visual outcomes remain controversial. We investigated whether region-specific thickness analysis of retinal layers could improve the detection of macular atrophy and unravel its association with visual disability in Parkinson's disease. Methods Patients with idiopathic Parkinson's disease (n = 63), dementia with Lewy bodies (n = 8), and E46K mutation carriers in the alpha-synuclein gene (E46K-SNCA) (n = 4) and 34 controls underwent Spectralis optical coherence tomography macular scans and a comprehensive battery of visual function and cognition tests. We computed mean retinal layer thicknesses of both eyes within 1-, 2-, 3-, and 6-mm diameter macular discs and in concentric parafoveal (1- to 2-mm, 2- to 3-mm, 1- to 3-mm) and perifoveal (3- to 6-mm) rings. Group differences in imaging parameters and their relationship with visual outcomes were analyzed. A multivariate logistic model was developed to predict visual impairment from optical coherence tomography measurements in Parkinson's disease, and cutoff values were determined with receiver operating characteristic analysis. Results When compared with controls, patients with dementia with Lewy bodies had significant thinning of the ganglion cell-inner plexiform layer complex within the central 3-mm disc mainly because of differences in 1- to 3-mm parafoveal thickness. This parameter was strongly correlated in patients, but not in controls, with low contrast visual acuity and visual cognition outcomes (P < .05, False Discovery Rate), achieving 88% of accuracy in predicting visual impairment in Parkinson's disease. Conclusion Our findings support that parafoveal thinning of ganglion cell-inner plexiform complex is a sensitive and clinically relevant imaging biomarker for Lewy body diseases, specifically for Parkinson's disease. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.This study was partially cofunded by the Michael J. Fox Foundation (2014 Rapid Response Innovation Awards; Grant 10189), by the Carlos III Health Institute through Projects PI14/00679 and PI16/00005, and Juan Rodes Grant JR15/00008 (I.G.) (cofunded by the European Regional Development Fund/European Social Fund "Investing in Your Future"), and by the Department of Health of the Basque Government through Project 201611100

Retinal thickness predicts the risk of cognitive decline in Parkinson's disease

Objective: To analyze longitudinal changes of retinal thickness and their predictive value as biomarkers of disease progression in idiopathic Parkinson’s disease (iPD). Methods: Patients with Lewy body diseases (LBDs) were enrolled and prospectively evaluated at 3 years, including patients with iPD (n=42), dementia with Lewy bodies (DLB, n=4), E46K-SNCA mutation carriers (n=4) and controls (n=17). All participants underwent Spectralis retinal optical coherence tomography and Montreal Cognitive Assessment (MoCA), and Unified Parkinson’s Disease Rating Scale (UPDRS) score was obtained in patients. Macular ganglion-inner plexiform layer complex (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) thickness reduction rates were estimated with linear mixed models. Risk ratios were calculated to evaluate the association between baseline GCIPL and pRNFL thickness and the risk of subsequent cognitive and motor worsening, using clinically meaningful cut-offs. Results: GCIPL thickness in the parafoveal region (1- to 3-mm ring) presented the largest reduction rate. The annualized atrophy rate was 0.63 µm in iPD patients and 0.23 µm in controls (p<0.0001). iPD patients with lower parafoveal GCIPL and pRNFL thickness at baseline presented an increased risk of cognitive decline at 3 years (RR 3.49, 95% CI 1.10 – 11.1, p=0.03 and RR 3.28, 95% CI 1.03 – 10.45, p=0.045, respectively). We did not identify significant associations between retinal thickness and motor deterioration. Interpretation: Our results provide evidence of the potential use of OCT-measured parafoveal GCIPL thickness to monitor neurodegeneration and to predict the risk of cognitive worsening over time in iPD