Diabetic retinopathy and diabetic macula oedema: The effects of dietary polyphenols
I will be using materials from a paper by Fanaro et al. New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy. Antioxidants (Basel) 2023 Jun; 12(6): 1237. Ciulla et al. Diabetic Retinopathy and Diabetic Macular Edema. Pathophysiology, screening, and novel therapies. Diabetes Care 26:2653–2664, 2003.
Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM) and the leading cause of blindness, affecting approximately 95 per cent of patients with type 1 DM and more than 60 per cnt of patients with type 2 DM. DR is a public health and socioeconomic burden that could be prevented or reduced by implementing interventions, such as glycemic control, healthy lifestyle behaviours, and dietary modification.
According to data from the International Diabetes Federation (IDF), 537 million people aged 20 to 79 years were diagnosed with diabetes worldwide in 2021, an increase of 16 per cent over the previous two years, and projections for 2030 point to 643 million cases. The alarming global evolution of DM and the increasing development and progression of DR suggest early diagnosis and more effective, accessible, and cost-effective prophylactic and therapeutic measures.
Diabetic Retinopathy-Risk Factors
Poor glycemic (and hyperglycaemia) and blood pressure control and duration of diabetes are significant risk factors for developing DR, and rigorous control of these parameters promotes long-term benefits in delaying or preventing DR. Pregnancy and puberty, kidney disease], and a high body mass index (BMI) are also risk factors for DR. Even when these risk factors are under control, some patients still develop diabetic macular edema (DME), the major vision-threatening late complication of DR.
Despite remarkable progress in understanding the molecular and pathophysiological mechanisms of DR, some gaps remain, including those related to the early stages of DR. Currently, therapeutic strategies, including glycemic and blood pressure control, laser photocoagulation, intravitreal injections of anti-inflammatory or vascular endothelial growth factor (VEGF) neutralising agents, and vitreoretinal surgery are limited to late stages of the disease, reducing the chances of preventing vision loss. In addition, not all patients respond satisfactorily to current clinical therapies, suggesting that developing effective strategies for the prevention and treatment of DR is critical.
The increasing number of individuals with diabetes worldwide suggests that DR and DME will continue to be major contributors to vision loss and associated functional impairment for years to come. Early detection of retinopathy in individuals with diabetes is critical in preventing visual loss, but current methods of screening fail to identify a sizable number of high-risk patients. The control of diabetes-associated metabolic abnormalities (i.e., hyperglycemia, hyperlipidemia, and hypertension) is also important in preserving visual function because these conditions have been identified as risk factors for both the development and progression of DR/DME. The currently available interventions for DR/DME, laser photocoagulation and vitrectomy, only target advanced stages of disease.
Diabetic Retinopathy- A multifactorial condition
DR is a multifactorial pathology that results from a dysfunction in a variety of retinal cells, including Müller glia, ganglion cells, endothelial cells, and photoreceptors, as well as optic nerve damage and, later, retinal neuronal cell death and vascular lesions. Neural retina/optic nerve changes occur before vascular alterations in both human and animal models. DR is a chronic microvascular disease characterized by vasculopathy, hyperpermeability, hypoperfusion, and neo angiogenesis of slow progression, accompanied by vitreous hemorrhage, retinal detachment, diabetic macular edema process (DME), and/or macular ischemia, resulting in neural abnormalities and retinal deficits. Although DME and macular ischemia can occur at any stage of the disease, they are more common in the later stages of DR.
Chronic hyperglycemia promotes the thickening of the retinal capillary basement membrane, impairs adherence of tight junctions between endothelial cells, and makes blood vessels more permeable. These events define the process known as the blood–retinal barrier (BRB) breakdown.
Stages of Diabetic Retinopathy
DR is classified based on pathophysiological characteristics and vascular manifestations during the clinical course, the initial phase, known as non-proliferative DR (NPDR), and the advanced phase, known as proliferative DR (PDR). The presence of new blood vessels characterizes the PDR stage.
Oxidative stress
The retina is susceptible to oxidative stress due to its rapid oxygen and glucose uptake. Another critical element in the pathophysiology of DR is inflammation. The oxidative stress induces reactive oxygen species (ROS) production, the root cause of neuropathy and retinopathy. The nature of DR requires early screening of persons with diabetes. Some experts have suggested screening for persons with very high risk for diabetes.
Advanced stages of Diabetic Retinopathy
Advanced stages of DR are characterised by the growth of abnormal retinal blood vessels secondary to ischaemia. These blood vessels grow to supply oxygenated blood to the hypoxic retina. At any time during the progression of DR, patients with diabetes can also develop DME, which involves retinal thickening in the macular area. DME occurs after breakdown of the blood-retinal barrier because of leakage of dilated hyperpermeable capillaries and microaneurysms. The current management strategy for DR/ DME requires early detection and optimal glycaemic control to slow the progression of disease. Adherence to these recommendations is hampered by the fact that the condition is generally asymptomatic at early stages. Current treatments for DR/DME, such as laser photocoagulation, only target advanced stages of disease.
Early detection of retinal abnormalities is essential in preventing DR/DME and loss of vision. Treatments, such as photocoagulation, can decrease vision loss. However, it is generally not possible to restore visual acuity (VA) once it has deteriorated. Because DR can progress to irreversible stages with relatively few symptoms, the optimal time for treatment is before VA is impaired. Studies have confirmed that the clinical outcome is better if patients are screened and treated early. The benefits of early management, such as intensive diabetes control, persist for years.
Prevention
Control of the metabolic abnormalities of diabetes has a major effect on the development of diabetic microvascular complications. The Diabetes Control and Complications Trial and the U.K. Prospective Diabetes Study showed that optimal metabolic control could reduce the incidence and progression of DR. The benefits of intensive glycemic control persisted over an extended follow-up. Thus, optimal metabolic control should be an important treatment goal and should be implemented early and maintained for as long as it is safely possible. All efforts must be made to control blood glucose, blood pressure, blood cholesterol and the body mass index.
Polyphenols
Polyphenol-rich foods noted for their antioxidant, antiatherogenic, blood-glucose lowering, blood pressure lowering and lipid lowering properties should be made integral part of the preventive strategies against DR/DME. Cocoa is an excellent source of polyphenols.
DR. EDWARD O. AMPORFUL
CHIEF PHARMACIST
COCOA CLINIC
BY DR. EDWARD O. AMPORFUL