Effective Fundus Image Decomposition for the Detection of Red Lesions and Hard Exudates to Aid in the Diagnosis of Diabetic Retinopathy.

Diabetic retinopathy (DR) is characterized by the presence of red lesions (RLs), such as microaneurysms and hemorrhages, and bright lesions, such as exudates (EXs). Early DR diagnosis is paramount to prevent serious sight damage. Computer-assisted diagnostic systems are based on the detection of those lesions through the analysis of fundus images. In this paper, a novel method is proposed for the automatic detection of RLs and EXs. As the main contribution, the fundus image was decomposed into various layers, including the lesion candidates, the reflective features of the retina, and the choroidal vasculature visible in tigroid retinas. We used a proprietary database containing 564 images, randomly divided into a training set and a test set, and the public database DiaretDB1 to verify the robustness of the algorithm. Lesion detection results were computed per pixel and per image. Using the proprietary database, 88.34% per-image accuracy (ACCi), 91.07% per-pixel positive predictive value (PPVp), and 85.25% per-pixel sensitivity (SEp) were reached for the detection of RLs. Using the public database, 90.16% ACCi, 96.26% PPV_p, and 84.79% SEp were obtained. As for the detection of EXs, 95.41% ACCi, 96.01% PPV_p, and 89.42% SE_p were reached with the proprietary database. Using the public database, 91.80% ACCi, 98.59% PPVp, and 91.65% SEp were obtained. The proposed method could be useful to aid in the diagnosis of DR, reducing the workload of specialists and improving the attention to diabetic patients.

Clinical and Molecular-Genetic Insights into the Role of Oxidative Stress in Diabetic Retinopathy: Antioxidant Strategies and Future Avenues.

Reactive oxygen species (ROS) overproduction and ROS-signaling pathways activation attack the eyes. We evaluated the oxidative stress (OS) and the effects of a daily, core nutritional supplement regimen containing antioxidants and omega 3 fatty acids (A/ω3) in type 2 diabetics (T2DM). A case-control study was carried out in 480 participants [287 T2DM patients with (+)/without (-) diabetic retinopathy (DR) and 193 healthy controls (CG)], randomly assigned to a daily pill of A/ω3. Periodic evaluation through 38 months allowed to outline patient characteristics, DR features, and classic/OS blood parameters. Statistics were performed by the SPSS 24.0 program. Diabetics displayed significantly higher circulating pro-oxidants (p = 0.001) and lower antioxidants (p = 0.0001) than the controls. Significantly higher plasma malondialdehyde/thiobarbituric acid reactive substances (MDA/TBARS; p = 0.006) and lower plasma total antioxidant capacity (TAC; p = 0.042) and vitamin C (0.020) was found in T2DM + DR versus T2DM-DR. The differential expression profile of solute carrier family 23 member 2 (SLC23A2) gene was seen in diabetics versus the CG (p = 0.001), and in T2DM + DR versus T2DM - DR (p < 0.05). The A/ω3 regime significantly reduced the pro-oxidants (p < 0.05) and augmented the antioxidants (p < 0.05). This follow-up study supports that a regular A/ω3 supplementation reduces the oxidative load and may serve as a dietary prophylaxis/adjunctive intervention for patients at risk of diabetic blindness.

Management and Systemic Implications of Diabetic Neovascular Glaucoma.

OBJECTIVES: To study the efficacy and safety of different treatments for diabetic neovascular glaucoma (NVG). We additionally attempt to determine if the presence of NVG could be a predictor of cardiovascular disease or death. METHOD: This is a retrospective, observational cohort study including patients diagnosed with diabetic NVG from 2006 to 2016 at the Hospital Clínico Universitario de Valladolid (Spain). Extracted data included clinical characteristics of the patients, glycated haemoglobin levels, and ocular treatment. Visual acuity (VA), intraocular pressure (IOP), cardiovascular events, and deaths were registered. RESULTS: 30 eyes from 23 patients were followed for a mean of 4.48 years (SD = 2.82 years). The IOP-lowering intervention groups were: Ahmed implant (11 eyes), laser cyclo-photocoagulation (CPC; 6 eyes), both (4 eyes), or none (9 eyes). IOP success was achieved in 100% of the eyes with Ahmed and/or laser CPC and in 44.4% of the eyes with no IOP-lowering procedure (p= 0.002). Most eyes with Ahmed implant (with or without CPC) maintained or improved their VA (100 and 63.6%, respectively). 33.3% of the eyes with laser CPC and 25% of those with no IOP-lowering intervention maintained or improved their VA (p = 0.028). Hypotony was the only adverse effect (after laser CPC). No statistically significant difference could be established between low VA (finger count or worse), poor IOP control, or bad metabolic control and mortality or cardiovascular event (p > 0.05), however, the four patients who died had poor VA at the time of NVG diagnosis. CONCLUSIONS: Ahmed implant surgery is a safe and effective treatment option for diabetic NVG. Medical treatment alone is not the best option for most cases. Advanced NVG could be an indicator of higher mortality risk in diabetic patients.

Management of diabetic macular edema patients in clinical practice in Spain.

PURPOSE: Diabetic macular edema is the main cause of blindness in diabetic patients. Vascular endothelial growth factor is involved in diabetic macular edema pathogenesis. Vascular endothelial growth factor inhibitors are an important option in diabetic macular edema therapy. This survey investigates actual clinical practice in diabetic macular edema in Spain. METHODS: An expert advisory panel of 17 Spanish ophthalmologists developed a 30-item anonymous questionnaire about diagnosis, treatment, and follow-up in diabetic macular edema. A total of 137 ophthalmologists from 10 Spanish regions completed the questionnaire online. RESULTS: Almost all of the respondents (99.3%) record the measured visual acuity and perform biomicroscopic anterior (94.9%) and posterior (91.2%) segment examinations. Similarly, 100% of responding ophthalmologists always/almost always or frequently perform optical coherence tomography. Most respondents (65%) always/almost always or frequently perform a retinography. More than 50% rarely perform fluorescein angiography. Nearly, all (96.4%) of the specialists responded that, in center-involved diabetic macular edema, the first treatment is an anti-vascular endothelial growth factor drug. For corticosteroids, the first choice of most respondents (91.2%) was the dexamethasone implant. In the follow-up, almost all (96.4%) specialists record the measured visual acuity and most also perform biomicroscopic anterior (82.5%) and posterior (83.2%) segment examination. CONCLUSION: This survey shows the actual clinical practice in diabetic macular edema in Spain, finding that anti-vascular endothelial growth factor therapy is frequently used, and that diagnosis, treatments, and follow-up examinations used by specialists are homogeneous and according to diabetic macular edema guidelines.

Combination of Global Features for the Automatic Quality Assessment of Retinal Images.

Diabetic retinopathy (DR) is one of the most common causes of visual loss in developed countries. Computer-aided diagnosis systems aimed at detecting DR can reduce the workload of ophthalmologists in screening programs. Nevertheless, a large number of retinal images cannot be analyzed by physicians and automatic methods due to poor quality. Automatic retinal image quality assessment (RIQA) is needed before image analysis. The purpose of this study was to combine novel generic quality features to develop a RIQA method. Several features were calculated from retinal images to achieve this goal. Features derived from the spatial and spectral entropy-based quality (SSEQ) and the natural images quality evaluator (NIQE) methods were extracted. They were combined with novel sharpness and luminosity measures based on the continuous wavelet transform (CWT) and the hue saturation value (HSV) color model, respectively. A subset of non-redundant features was selected using the fast correlation-based filter (FCBF) method. Subsequently, a multilayer perceptron (MLP) neural network was used to obtain the quality of images from the selected features. Classification results achieved 91.46% accuracy, 92.04% sensitivity, and 87.92% specificity. Results suggest that the proposed RIQA method could be applied in a more general computer-aided diagnosis system aimed at detecting a variety of retinal pathologies such as DR and age-related macular degeneration.

Entropy Rate Superpixel Classification for Automatic Red Lesion Detection in Fundus Images.

Diabetic retinopathy (DR) is the main cause of blindness in the working-age population in developed countries. Digital color fundus images can be analyzed to detect lesions for large-scale screening. Thereby, automated systems can be helpful in the diagnosis of this disease. The aim of this study was to develop a method to automatically detect red lesions (RLs) in retinal images, including hemorrhages and microaneurysms. These signs are the earliest indicators of DR. Firstly, we performed a novel preprocessing stage to normalize the inter-image and intra-image appearance and enhance the retinal structures. Secondly, the Entropy Rate Superpixel method was used to segment the potential RL candidates. Then, we reduced superpixel candidates by combining inaccurately fragmented regions within structures. Finally, we classified the superpixels using a multilayer perceptron neural network. The used database contained 564 fundus images. The DB was randomly divided into a training set and a test set. Results on the test set were measured using two different criteria. With a pixel-based criterion, we obtained a sensitivity of 81.43% and a positive predictive value of 86.59%. Using an image-based criterion, we reached 84.04% sensitivity, 85.00% specificity and 84.45% accuracy. The algorithm was also evaluated on the DiaretDB1 database. The proposed method could help specialists in the detection of RLs in diabetic patients.

Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD.

Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF) therapy in the treatment of neovascular age-related macular degeneration (nAMD) and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

Automated detection of diabetic retinopathy in retinal images.

Diabetic retinopathy (DR) is a disease with an increasing prevalence and the main cause of blindness among working-age population. The risk of severe vision loss can be significantly reduced by timely diagnosis and treatment. Systematic screening for DR has been identified as a cost-effective way to save health services resources. Automatic retinal image analysis is emerging as an important screening tool for early DR detection, which can reduce the workload associated to manual grading as well as save diagnosis costs and time. Many research efforts in the last years have been devoted to developing automatic tools to help in the detection and evaluation of DR lesions. However, there is a large variability in the databases and evaluation criteria used in the literature, which hampers a direct comparison of the different studies. This work is aimed at summarizing the results of the available algorithms for the detection and classification of DR pathology. A detailed literature search was conducted using PubMed. Selected relevant studies in the last 10 years were scrutinized and included in the review. Furthermore, we will try to give an overview of the available commercial software for automatic retinal image analysis.

Enhanced Oxidative Stress and Other Potential Biomarkers for Retinopathy in Type 2 Diabetics: Beneficial Effects of the Nutraceutic Supplements.

We have studied the global risk of retinopathy in a Mediterranean population of type 2 diabetes mellitus (T2DM) patients, according to clinical, biochemical, and lifestyle biomarkers. The effects of the oral supplementation containing antioxidants/omega 3 fatty acids (A/ω3) were also evaluated. Suitable participants were distributed into two main groups: (1) T2DMG (with retinopathy (+DR) or without retinopathy (-DR)) and (2) controls (CG). Participants were randomly assigned (+A/ω3) or not (-A/ω3) to the oral supplementation with a daily pill of Nutrof Omega (R) for 18 months. Data collected including demographics, anthropometrics, characteristics/lifestyle, ophthalmic examination (best corrected visual acuity, ocular fundus photographs, and retinal thickness as assessed by optical coherence tomography), and blood parameters (glucose, glycosylated hemoglobin, triglycerides, malondialdehyde, and total antioxidant capacity) were registered, integrated, and statistically processed by the SPSS 15.0 program. Finally, 208 participants (130 diabetics (68 +DR/62 -DR) and 78 controls) completed the follow-up. Blood analyses confirmed that the T2DMG+DR patients had significantly higher oxidative stress (p < 0.05), inflammatory (p < 0.05), and vascular (p < 0.001) risk markers than the T2DMG-DR and the CG. Furthermore, the A/ω3 oral supplementation positively changed the baseline parameters, presumptively by inducing metabolic activation and ameliorating the ocular health after 18 months of supplementation.