Browsing by Subject "diabetic retinopathy"
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Item Automated Computer-Based Enumeration of Acellular Capillaries for Assessment of Diabetic Retinopathy(SPIE, 2020-02) Tuceryan, Mihran; Hemmady, Anish N.; Schebler, Craig; Alex, Alpha; Bhatwadekar, Ashay D.; Computer and Information Science, School of ScienceDiabetic retinopathy (DR) is the most common complications of diabetes; if untreated the DR can lead to a vision loss. The treatment options for DR are limited and the development of newer therapies are of considerable interest. Drug screening for the retinopathy treatment is undertaken using animal models in which the quantification of acellular capillaries (capillary without any cells) is used as a marker to assess the severity of retinopathy and the treatment response. The traditional approach to quantitate acellular capillaries is through manual counting. The purpose of this investigation was to develop an automated technique for the quantitation of acellular capillaries using computer-based image processing algorithms. We developed a custom procedure using the Python, the medial axis transform (MAT) and the connected component algorithm. The program was tested on the retinas of wild-type and diabetic mice and the results were compared to single blind manual counts by two independent investigators. The program successfully identified and enumerated acellular capillaries. The acellular capillary counts were comparable to the traditional manual counting. In conclusion, we developed an automated computer-based program, which can be effectively used for future pharmacological development of treatments for DR. This algorithm will enhance consistency in retinopathy assessment and reduce the time for analysis, thus, contributing substantially towards the development of future pharmacological agents for the treatment of DR.Item Clinical Features Distinguishing Diabetic Retinopathy Severity Using Artificial Intelligence(2022-07-29) Happe, Michael; Gill, Hunter; Salem, Doaa Hassan; Janga, Sarath Chandra; Hajrasouliha, AmirBACKGROUND AND HYPOTHESIS: 1 in 29 American diabetics suffer from diabetic retinopathy (DR), the weakening of blood vessels in the retina. DR goes undetected in nearly 50% of diabetics, allowing DR to steal the vision of many Americans. We hypothesize that increasing the rate and ease of diagnosing DR by introducing artificial intelligence-based methods in primary medical clinics will increase the long-term preservation of ocular health in diabetic patients. PROJECT METHODS: This retrospective cohort study was conducted under approval from the Institutional Review Board of Indiana University School of Medicine. Images were deidentified and no consent was taken due to the nature of this retrospective study. We categorized 676 patient files based upon HbA1c, severity of non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Retinal images were annotated to identify common features of DR: microaneurysms, hemorrhages, cotton wool spots, exudates, and neovascularization. The VGG Image Annotator application used for annotations allowed us to save structure coordinates into a separate database for future training of the artificial intelligence system. RESULTS: 228 (33.7%) of patients were diagnosed with diabetes, and 143 (62.7%) of those were diagnosed with DR. Two-sample t tests found significant differences between the HbA1c values of all diabetics compared to diabetics without retinopathy (p<0.007) and between all severities of DR versus diabetics without retinopathy (p<0.002). 283 eyes were diagnosed with a form of DR in this study: 37 mild NPDR, 42 moderate NPDR, 56 severe NPDR, and 148 PDR eyes. POTENTIAL IMPACT: With the dataset of coordinates and HbA1c values from this experiment, we aim to train an artificial intelligence system to diagnose DR through retinal imaging. The goal of this system is to be conveniently used in primary medical clinics to increase the detection rate of DR to preserve the ocular health of millions of future Americans.Item Comparisons of diabetic retinopathy events associated with glucose‐lowering drugs in patients with type 2 diabetes mellitus: A network meta‐analysis(Wiley, 2018) Tang, Huilin; Li, Guangyao; Zhao, Ying; Wang, Fei; Gower, Emily W.; Shi, Luwen; Wang, Tiansheng; Epidemiology, School of Public HealthAim To assess the comparative effects of glucose‐lowering drugs (GLDs) on the risk of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods We systematically searched Cochrane Central Register of Controlled Trials, PUBMED and EMBASE from inception to January 17, 2017 to identify randomized controlled trials (RCTs) that reported DR events among T2DM patients receiving any GLD. Random‐effects pairwise and network meta‐analyses were performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 37 independent RCTs with 1806 DR events among 100 928 patients with T2DM were included. The mean duration of diabetes was 8.7 years and mean baseline HbA1c was 8.2% (SD, 0.5%). Our network meta‐analysis found that DPP‐4i (OR, 1.20; 95% CI, 0.87‐1.65), GLP‐1RA (OR, 1.19; 95% CI, 0.94‐1.52) and SGLT2 inhibitors (OR, 0.79; 95% CI, 0.49‐1.28) were not associated with a higher risk of DR than placebo; however, a significantly increased risk of DR was associated with DPP‐4i in the pairwise meta‐analysis (OR, 1.27; 95% CI, 1.05‐1.53). Sulfonylureas, on the other hand, were associated with a significantly increased risk of DR compared to placebo (OR, 1.67; 95% CI, 1.01‐2.76). Conclusions Current evidence indicates that the association between DPP‐4i, GLP‐1RA or SGLT2 inhibitors and risk of DR remains uncertain in patients with T2DM. Some evidence suggests that sulfonylureas may be associated with increased risk of DR. However, given that DR events were not systematically assessed, these effects should be explored further in large‐scale, well‐designed studies.Item Hematopoietic stem/progenitor involvement in retinal microvascular repair during diabetes: Implications for bone marrow rejuvenation(Elsevier, 2017-10) Bhatwadekar, Ashay D.; Duan, Yaqian; Korah, Maria; Thinschmidt, Jeffrey S.; Hu, Ping; Leley, Sameer P.; Caballero, Sergio; Shaw, Lynn; Busik, Julia; Grant, Maria B.; Ophthalmology, School of MedicineThe widespread nature of diabetes affects all organ systems of an individual including the bone marrow. Long-term damage to the cellular and extracellular components of the bone marrow leads to a rapid decline in the bone marrow-hematopoietic stem/progenitor cells (HS/PCs) compartment. This review will highlight the importance of bone marrow microenvironment in maintaining bone marrow HS/PC populations and the contribution of these key populations in microvascular repair during the natural history of diabetes. The autonomic nervous system can initiate and propagate bone marrow dysfunction in diabetes. Systemic pharmacological strategies designed to protect the bone marrow-HS/PC population from diabetes induced-oxidative stress and advanced glycation end product accumulation represent a new approach to target diabetic retinopathy progression. Protecting HS/PCs ensures their participation in vascular repair and reduces the risk of vasogdegeneration occurring in the retina.Item Impaired Autophagy Diurnal Rhythmicity in Rodent Diabetic Retinopathy(Office of the Vice Chancellor for Research, 2015-04-17) Qi, Xiaoping; Mitter, Sayak; Yan, Yuanqing; Dunn, William; Busik, Juliet; Grant, Maria; Boulton, MichelePurpose: Retinal homeostasis is under both diurnal and circadian regulation. However, diurnal changes in retinal autophagy have not been hitherto explored. We sought to investigate the diurnal expression of autophagy proteins/genes in normal rodent retina to determine if this is impaired in diabetic retinopathy. Methods: Eyes from C57BL/6 mice and BBZ rats maintained under a 12h/12h; 6am/6pm light/dark cycle were enucleated every 2 or 3 hours over a 24 hour period. Eyes were also collected from C57BL/6 induced STZ for 2 or 9 month as type 1 and BBZDR/wor type 2 diabetic rats for 4 months. Immunohistochemistry, Western-blot and real-time PCR were performed for Atg7, Atg9, LC3 and Beclin. Retina vessel pathology and superoxide were assessed by enzyme digestion and a spectrofluorometer. Results: Autophagy proteins (Atgs) were abundantly expressed in neural retina and endothelia cells in both mice and rats with differential staining pattern across the retinas and demonstrated a distinctive diurnal rhythmicity. All Atgs showed localization to retinal blood vessels with Atg7 being the most highly expressed. Analysis of the immunostaining demonstrated distinctive diurnal rhythmicity of which Atg9 and LC3 shared a biphasic expression cycle with the highest level at 8:15 am and 8:15 pm. By contrast, Beclin revealed a 24-hour cycle with the highest level observed at midnight. Atg7 was also on a 24-hour cycle with peak expression at 8:15am, coinciding with the first peak expression of Atg9 and LC3. In diabetic animals, immunohistochemistry showed dramatic reduction in all four Atgs and this was further confirmed by Western Blot, especially a decrease in LC3II/LC3I ratio (a measure of autophagy flux). Furthermore, the distinctive diurnal rhythmicity of these autophagy proteins was significantly impaired and phase shifted in diabetic animals. Conclusions: Autophagy proteins show both spatial and diurnal-dependent expression in normal rodent retinas and this is severely impaired and phase shifted in both type 1 and type 2 diabetic animals. Decreased autophagy in diabetic animals may in part explain the increased generation of reactive oxygen species in diabetic retinopathy. Therefore, restoration of diurnal rhythmicity and facilitating autophagy pathway expression may provide new treatment strategies for diabetic retinopathy.Item The Mechanism of Diabetic Retinopathy Pathogenesis Unifying Key Lipid Regulators, Sirtuin 1 and Liver X Receptor(Elsevier, 2017-08) Hammer, Sandra S.; Beli, Eleni; Kady, Nermin; Wang, Qi; Wood, Kiana; Lydic, Todd A.; Malek, Goldis; Saban, Daniel R.; Wang, Xiaoxin X.; Hazra, Sugata; Levi, Moshe; Busik, Julia V.; Grant, Maria B.; Department of Ophthalmology, School of MedicineDiabetic retinopathy (DR) is a complication secondary to diabetes and is the number one cause of blindness among working age individuals worldwide. Despite recent therapeutic breakthroughs using pharmacotherapy, a cure for DR has yet to be realized. Several clinical trials have highlighted the vital role dyslipidemia plays in the progression of DR. Additionally, it has recently been shown that activation of Liver X receptor (LXRα/LXRβ) prevents DR in diabetic animal models. LXRs are nuclear receptors that play key roles in regulating cholesterol metabolism, fatty acid metabolism and inflammation. In this manuscript, we show insight into DR pathogenesis by demonstrating an innovative signaling axis that unifies key metabolic regulators, Sirtuin 1 and LXR, in modulating retinal cholesterol metabolism and inflammation in the diabetic retina. Expression of both regulators, Sirtuin 1 and LXR, are significantly decreased in diabetic human retinal samples and in a type 2 diabetic animal model. Additionally, activation of LXR restores reverse cholesterol transport, prevents inflammation, reduces pro-inflammatory macrophages activity and prevents the formation of diabetes-induced acellular capillaries. Taken together, the work presented in this manuscript highlights the important role lipid dysregulation plays in DR progression and offers a novel potential therapeutic target for the treatment of DR.Item Ranibizumab For Diabetic Macular Edema Refractory To Multiple Prior Treatments(Lippincott Williams & Wilkins, 2016-07) Ciulla, Thomas A.; Hussain, Rehan M.; Ciulla, Lauren; Sink, Bethany; Harris, Alon; Department of Ophthalmology, IU School of MedicinePurpose: Diabetic macular edema can be refractory to multiple treatment modalities. Although there have been anecdotal reports of ranibizumab showing efficacy when other modalities provided limited benefit, little has been published on treatment for refractory diabetic macular edema. This study sought to investigate this observation further. Methods: Retrospective chart review. Results: Thirty-three eyes of 22 patients with refractory diabetic macular edema were treated with 0.3 mg intravitreal ranibizumab. This group of eyes received an average of 5.1 prior treatments (macular laser, intravitreal bevacizumab, triamcinolone acetonide, or dexamethasone implant). The mean best corrected visual acuity before the initial ranibizumab injection was 20/110 and the mean central subfield thickness was 384 μm. After 7 visits over an average of 48 weeks, during which an average of 6 ranibizumab injections were administered, the mean visual acuity improved to 20/90 and the mean central subfield thickness improved to 335 μm. Both central subfield thickness and best corrected visual acuity improved with number of days of follow-up in a statistically significant fashion (P < 0.01). Similarly, both central subfield thickness and visual acuity improved with number of ranibizumab injections in a linear fashion, but this was not statistically significant. Conclusion: Ranibizumab can improve diabetic macular edema refractory to prior treatments of laser photocoagulation, intravitreal triamcinolone acetonide, and bevacizumab.Item Role of inflammatory cells in pathophysiology and management of diabetic retinopathy(Elsevier, 2022-11) Kovoor, Elias; Chauhan, Sunil K.; Hajrasouliha, Amir; Ophthalmology, School of MedicineDiabetic retinopathy (DR) is a sight-threatening complication of diabetes mellitus. Several inflammatory cells and proteins, including macrophages and microglia, cytokines, and vascular endothelial growth factors, are found to play a significant role in the development and progression of DR. Inflammatory cells play a significant role in the earliest changes seen in DR including the breakdown of the blood retinal barrier leading to leakage of blood into the retina. They also have an important role in the pathogenesis of more advanced stage of proliferative diabetic retinopathy, leading to neovascularization, vitreous hemorrhage, and tractional retinal detachment. In this review, we examine the function of numerous inflammatory cells involved in the pathogenesis, progression, and role as a potential therapeutic target in DR. Additionally, we explore the role of inflammation following treatment of DR.