Dataset Information

The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

ABSTRACT: The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant defense genes was increased soon after the onset of DM. In addition, ischemia/oxidative stress caused less death in the retinal vasculature of DM versus non-DM mice. Further investigation with T1D mice revealed that protection was transient; it waned as the duration of DM was prolonged. Finally, a loss of protection was associated with the manifestation of both neural and vascular abnormalities that are diagnostic of DR in mice. These observations demonstrate that DM can transiently activate protection from oxidative stress, which is a plausible explanation for the delay in the development of DR from the onset of DM.

SUBMITTER: Li Y

PROVIDER: S-EPMC10341443 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

Li Yanliang Y Baccouche Basma B Del-Risco Norma N Park Jason J Song Amy A McAnany J Jason JJ Kazlauskas Andrius A

International journal of molecular sciences 20230629 13

The purpose of this study was to investigate the reason that diabetic retinopathy (DR) is delayed from the onset of diabetes (DM) in diabetic mice. To this end, we tested the hypothesis that the deleterious effects of DM are initially tolerated because endogenous antioxidative defense is elevated and thereby confers resistance to oxidative stress-induced death. We found that this was indeed the case in both type 1 DM (T1D) and type 2 DM (T2D) mouse models. The retinal expression of antioxidant d ...[more]

PMID: 37446043

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Project description:ImportanceMachine learning (ML) algorithms have the potential to identify eyes with early diabetic retinopathy (DR) at increased risk for disease progression.ObjectiveTo create and validate automated ML models (autoML) for DR progression from ultra-widefield (UWF) retinal images.Design, setting and participantsDeidentified UWF images with mild or moderate nonproliferative DR (NPDR) with 3 years of longitudinal follow-up retinal imaging or evidence of progression within 3 years were used to develop automated ML models for predicting DR progression in UWF images. All images were collected from a tertiary diabetes-specific medical center retinal image dataset. Data were collected from July to September 2022.ExposureAutomated ML models were generated from baseline on-axis 200° UWF retinal images. Baseline retinal images were labeled for progression based on centralized reading center evaluation of baseline and follow-up images according to the clinical Early Treatment Diabetic Retinopathy Study severity scale. Images for model development were split 8-1-1 for training, optimization, and testing to detect 1 or more steps of DR progression. Validation was performed using a 328-image set from the same patient population not used in model development.Main outcomes and measuresArea under the precision-recall curve (AUPRC), sensitivity, specificity, and accuracy.ResultsA total of 1179 deidentified UWF images with mild (380 [32.2%]) or moderate (799 [67.8%]) NPDR were included. DR progression was present in half of the training set (590 of 1179 [50.0%]). The model's AUPRC was 0.717 for baseline mild NPDR and 0.863 for moderate NPDR. On the validation set for eyes with mild NPDR, sensitivity was 0.72 (95% CI, 0.57-0.83), specificity was 0.63 (95% CI, 0.57-0.69), prevalence was 0.15 (95% CI, 0.12-0.20), and accuracy was 64.3%; for eyes with moderate NPDR, sensitivity was 0.80 (95% CI, 0.70-0.87), specificity was 0.72 (95% CI, 0.66-0.76), prevalence was 0.22 (95% CI, 0.19-0.27), and accuracy was 73.8%. In the validation set, 6 of 9 eyes (75%) with mild NPDR and 35 of 41 eyes (85%) with moderate NPDR progressed 2 steps or more were identified. All 4 eyes with mild NPDR that progressed within 6 months and 1 year were identified, and 8 of 9 (89%) and 17 of 20 (85%) with moderate NPDR that progressed within 6 months and 1 year, respectively, were identified.Conclusions and relevanceThis study demonstrates the accuracy and feasibility of automated ML models for identifying DR progression developed using UWF images, especially for prediction of 2-step or greater DR progression within 1 year. Potentially, the use of ML algorithms may refine the risk of disease progression and identify those at highest short-term risk, thus reducing costs and improving vision-related outcomes.

Project description:PurposeTo evaluate the relationship between diabetic retinal neurodegeneration (DRN), as quantified by optical coherence tomography (OCT), to the development of diabetic retinopathy (DR), progression of DR, and development of proliferative DR (PDR).MethodsThis was a prospective cohort study, including 385 eyes with no DR or nonproliferative DR at baseline. The thicknesses of the macular ganglion cell-inner plexiform layer (m-GCIPL), macular retinal nerve fiber layer, and peripapillary RNFL (p-RNFL) were measured using Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA). DR outcomes were determined from macula- and optic disc-centered fundus photographs, following the modified Airlie House classification system. Cox proportional hazards models were used to estimate hazard ratio (HR) adjusting for age, mean arterial blood pressure, diabetes mellitus duration, HbA1c, diabetic kidney disease, axial length, OCT signal strength, and disc area (for p-RNFL only).ResultsAfter a median follow-up of 6.2 years (range 5.0-7.7 years), 79 eyes developed DR, 99 eyes developed DR progression, and 38 eyes developed PDR. Thinner mean and sectorial m-GCIPL thicknesses were significantly associated with higher risk of DR development, with HRs ≥ 1.373 (1.023-1.843), except for the superonasal and superotemporal sectors. Similar to DR development, thinner m-GCIPL thicknesses were significantly associated with DR progression and PDR development, with HRs ranging from 1.306 (1.094-1.559) to 2.331 (1.524-3.566). Additionally, the inclusion of inferior m-GCIPL thickness significantly improved the predictive discrimination for DR development (C statistics: 0.661 vs. 0.705, P < 0.001), and DR progression (C statistics: 0.704 vs. 0.729, P < 0.001), as well as inferotemporal m-GCIPL for PDR development (C statistic: 0.917 vs. 0.930, P < 0.001) beyond established risk factors.ConclusionsOCT measurements that elucidate DRN may enhance prognostic identification and predictive discrimination of DR development, DR progression, and PDR development beyond established risk factors.

Project description:PurposeThe purpose of this study was to explore the succession of the central and peripheral neurovascular and microstructural impairments in patients with full-course diabetic retinopathy (DR), consisting of preclinical DR, nonproliferative DR (NPDR), and proliferative DR (PDR).MethodsOur analysis included 81 participants (including 23 healthy controls, 23 with preclinical DR [diabetes without retinopathy], 13 with NPDR, and 22 with PDR) from the Guangdong Diabetic Retinopathy Multiple Omics Study. Retinal structure and function were evaluated and quantified using ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA), electroretinography (ERG), and adaptive optics scanning laser ophthalmoscopy (AOSLO). Correlation analysis was conducted to explore the relationship between structural parameters and functional parameters.ResultsIn the preclinical DR group, decreased amplitude in the DR assessment protocol were observed (P = 0.003), with no changes in structure and photoreceptor cells (all P > 0.05). In the NPDR group, photoreceptor cells were impaired (all P < 0.05) with delayed implicit time in the International Society for Clinical Electrophysiology of Vision (ISCEV) Photopic flicker protocol, increased macular and inner nuclear layer thickness, and decreased vessel density and perfusion area of the deep capillary plexus (all P < 0.05). In the PDR group, delayed implicit time and decreased amplitude in the ISCEV Photopic flicker and photopic negative response (PhNR) protocol, and neurovascular impairments were observed (all P < 0.05). Correlation analysis demonstrated a significant correlation between functional parameters and various structural indicators (all P < 0.05).ConclusionsThe cone pathway function began to decline in preclinical DR and distinct photoreceptor cell disorders were observed in NPDR. Notably, instruments with a wider field of view or more detailed microscopic techniques will provide enhanced neurovascular imaging, offering fresh insights into full-course DR.

Dataset Information

The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

Publications

The Slow Progression of Diabetic Retinopathy Is Associated with Transient Protection of Retinal Vessels from Death.

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