Damian Sendler: While diabetic macular edema and retinopathy are better treated, the lower rate of fundus examinations due to a lack of medical resources means that diabetic retinopathy is harder to diagnose and treat. It is therefore critical to implement an automated diabetic retinopathy screening program and identify biomarkers that are more specific and sensitive in order to reduce the incidences of poor vision and blindness.
Damian Jacob Sendler: A common microvascular complication of diabetes, diabetic retinopathy (DR) is a leading cause of blindness among the elderly. In the early stages of diabetic retinopathy, hyperglycemia and altered metabolic pathways cause oxidative stress and neurodegeneration1. Early signs of non-proliferative diabetic retinopathy include vascular endothelial damage, microaneurysms, and dot intraretinal hemorrhage (NPDR). The hard exudates seen under fundoscopy are caused by the breakdown of the blood–retinal barrier and the leakage of multiple inflammatory cytokines and plasma proteins. Capillary occlusions lead to torturous capillaries and retinal ischemia as the disease progresses. In this stage, “cotton wool spots” can be seen. Neovascularization, vitreous hemorrhage and retinal detachment are all possibilities in the final stages of diabetic retinopathy.
Dr. Sendler: The prevalence of diabetic eye disease in Taiwan ranged from 3.75 to 3.95 percent between 2005 and 2014, and the prevalence of poor vision and blindness ranged from 0.29 to 0.35 percent. Increase in diabetic retinopathy from 14.3% in 2006 to 15.9% in 20133 has been reported for Korea. While women with type 2 diabetes had a higher prevalence of diabetic retinopathy, men had more severe retinopathy, poor vision, and/or blindness than women. All-cause, cardiovascular, and non-cancer mortality were all predicted by the severity of diabetic retinopathy4. Diabetes retinopathy has been linked to an increased risk of life-threatening arrhythmias, according to another study.
Chronic diabetes, high blood sugar, and high blood pressure all increase the risk of developing diabetic retinopathy. The progression of diabetic retinopathy is strongly linked to an increase in HbA1c levels6, 7 and intensive glycemic control reduces the incidence and progression of retinopathy8. Glycemic variability has been linked to diabetic retinopathy in type 2 diabetes9, according to recent studies. Preventing diabetic retinopathy also necessitates controlling postprandial hyperglycemia10. Furthermore, there is strong evidence that hypertension and diabetic retinopathy are linked. Retinopathy deterioration can be slowed by controlling blood pressure. Additionally, nephropathy, dyslipidemia, smoking and a higher BMI are all modifiable risk factors for diabetic retinopathy12, 13 and 14, respectively, which can help prevent its progression.
Damian Sendler
Despite the known risk factors for diabetic retinopathy, studies have revealed wide variations in the progression and severity of the disease. As a result, locating additional biomarkers for use in risk stratification or monitoring the effectiveness of treatment for diabetic retinopathy is critical.
Diabetic retinopathy and the pathogenic process are linked through the use of systemic biomarkers such as C-reactive protein (CRP)15, homocysteine16, and advanced glycation end products (AGE)17. Plasma proteomic analysis uncovered a slew of new biomarkers. These include RBP1 (retinol-binding protein), DPP3 alpha (diphosphoinositide polyphosphohydrase 3 alpha), neuroglobin (NGB), and CD160 antigen18 (CD160) downregulation in diabetic retinopathy, while HBG2 and CD160 were upregulated. Neuroglobin plasma levels, which differ significantly between the control and diabetic retinopathy groups18, may be a potential biomarker for diabetic retinopathy among the five proteins listed above. Metabolomics, micro RNAs, and genetic biomarkers are also being studied extensively.
Samples of vitreous and tears, as well as ocular imaging, are all examples of ocular biomarkers. In diabetic retinopathy, the vitreous contained increased angiogenic factors, such as VEGF21 and PDGF22, and decreased anti-angiogenic factors, such as pigment epithelium-derived factor (PEDF)23. A higher rate of retinal microaneurysm turnover24, larger retinal vessel diameters25, and retinal neurodegeneration detected by optical coherence tomography (OCT)26 were all linked to the development of diabetic retinopathy. New biomarkers for diabetic retinopathy and its clinical outcomes have not yet been used in clinical practice and require further validation studies.
Damian Jacob Markiewicz Sendler: Preventable blindness can be prevented by screening for diabetic retinopathy, which is the leading cause of visual impairment. Macular edema (ME) or proliferative diabetic retinopathy (PDR) are the first symptoms that patients with diabetic retinopathy (DR) experience. For ME or PDR-related visual impairment, panretinal laser photocoagulation (PRP) and injection of intraocular VEGF inhibitors are both effective but are better at protecting the eyes from further decline in vision. A screening program for diabetic retinopathy could help diabetics maintain their vision if implemented early enough.
Damian Jacob Sendler
In 2018, the International Council of Ophthalmology (ICO) and the American Diabetes Association (ADA) issued new guidelines for the screening of diabetic retinopathy, stating that the timing of the first eye examination and the minimum screening examinations are necessary for appropriate referral to an ophthalmologist. First eye examinations for type 2 diabetes patients should begin as soon as the diagnosis is confirmed, but this time frame should be extended to five years after the onset of diabetes for type 1 diabetics. Eye exams and retinal exams are included in the minimal screening process, however. Human-based telemedicine or an automated computer system can be used to analyze retinal imaging29. The first automated diabetic retinopathy screening program has been approved by the FDA since April 201830, with a 96.8 percent sensitivity and 87 percent specificity for detecting referable diabetic retinopathy31. When used in conjunction with telemedicine, a smartphone retinal camera has shown great promise in the detection of diabetic retinopathy32. Diabetic retinopathy screening can be cost-effective if an individual’s risk of developing proliferative retinopathy or macular edema is taken into consideration.29, 33, 34 When compared to routine annual screening for type 1 diabetes in the US, it was estimated that it would save $1 billion over the next 20 years. Type 2 diabetes screening needs to be validated using the same individualized schedule used for type 1 diabetes.
Damien Sendler: Diabetic retinopathy can be effectively treated with medical control of blood glucose, blood pressure, and serum cholesterol levels, as well as intraocular managements27, 28. Anti-VEGF therapy, including drugs like ranibizumab, bevacizumab, and aflibercept, has changed the way diabetic macular edema (DME) patients are treated. It has become increasingly clear that all three anti-VEGF agents are effective in reducing diabetic macular edema and improving vision since 2010. Although in eyes with diabetic macular edema, aflibercept may result in better visual acuity than bevacizumab at 2 years41, this is not always the case. It is still unclear how often and how long patients should receive anti-VEGF therapy injections, despite recent advances in the field. Intravitreous anti-VEGF injections may be required in the first year of treatment for the majority of patients, but as remission is maintained, these injections become less frequent.
Panretinal laser photocoagulation, in contrast, has been shown to be effective in reducing the risk of vision loss in patients with proliferative diabetic retinopathy42, 43. Patient’s with all stages of PDR and severe NPDR are considered the preferred treatment option for PRP44. Intravitreous injection of anti-VEGF has also been shown in recent studies to be a safe alternative treatment for PDR, in addition to PRP. Eyes in the anti-VEGF (aflibercept) group attained better visual-acuity outcomes than those in the PRP group at one year of follow-up in the CLARITY study. There was no difference in visual acuity outcomes between the anti-VEGF group (ranibizumab) and the PRP group at both 2 and 5 years of follow up in the Diabetic Retinopathy Clinical Research Network study47, 48. DME and PDR treatment options are compared in Table 1 to see how each compares to the other. However, when translating the results of clinical trials into real-world clinical practice, adherence to frequent follow-up, treatment burden, and patients’ preferences must be taken into account.
Due to a lack of medical resources, the diagnosis and treatment of diabetic retinopathy were delayed due to diabetic macular edema and diabetic retinopathy treatment progress. When diabetes is detected early, the prevalence of poor vision and blindness can be reduced. This necessitates the implementation of an automated diabetic retinopathy screening program, as well as the identification of biomarkers that are more specific and sensitive.