Diabetic Macular Edema (DME) is a complication associated with RD and the main cause of vision loss in diabetic patients
Diabetic Macular Edema
Diabetic Macular Edema (DME) it is a complication associated with DR and the main cause of vision loss in diabetic patients. It represents the main cause of blindness in the active population in industrialized countries, and presents a prevalence of around 7.5% of diabetic patients (1). In Europe there are 4 million people with DME and in Spain, approximately 300,000 patients.
DME affects the macula, which is the central region of the retina where there is the highest concentration of photoreceptors and is where the central vision is generated and in greater detail.
Traditionally it has been defined as a clinical picture characterized by the existence of a thickening of the retina in the macular area (in an area of 2 papillary diameters from the center of the macula) that occurs as a result of the appearance of microvascular changes that compromise to the blood-retinal barrier, which separates the blood from the retina (2).
In most cases, the DME is a pathology that requires interventions and continued treatment. Laser, which has traditionally been considered the treatment of choice in these patients, has been replaced, in many cases, by pharmacotherapy to the point where different treatment options are available today. The key to success lies in knowing how to choose the most appropriate for each specific case.
The pathogenesis of this disease varies with time and between patients. In early stages, DME is mainly mediated by the angiogenic factor VEGF (Vascular Endothelial Growth Factor), which is induced due to the hypoxia suffered by the tissue of the retina and which favors the accelerated and abnormal growth of blood vessels of poor quality. that contribute to the filtration of plasma components in the retina and the consequent appearance of inflammation and edema. At this time it is convenient to block the action of VEGF by intravitreal anti-VEGF drugs.
But as the disease progresses and, in turn, the degree of severity of DR increases, VEGF levels remain relatively constant while the levels of other pro-inflammatory cytokines increase exponentially (3). In this phase, which can reach, with high interindividual variability, between 1 and 2 years after diagnosis, it may be necessary to treat with an anti-inflammatory drug (4), (5).
Intravitreal corticosteroids have shown in numerous studies that, in addition to blocking numerous pro-inflammatory cytokines, they also have a known anti-angiogenic effect (6). Thus, in this phase of the disease, anti-VEGF are not as suitable since they have effect only against VEGF and conversely, corticoids can do much better treatment of this multifactorial disease. Currently, there are 2 options of corticosteroid for the treatment of DME: a short-acting one that requires reinjections every 3-6 months and a long-acting one, which has shown a duration of effect of 3 years.
The diagnosis and assessment of edema should be carried out by an expert ophthalmologist and in the follow-up should always take into account: best corrected visual acuity (BCVA), biomicroscopic examination and OCT (optical coherence tomography), non-invasive test with which the thickness of the enlarged macula can be measured quantitatively, one of the signs that there is edema (thickening in the macular area) (2).
Recommendations in DME
If in diabetic retinopathy (DR), metabolic control is indisputable, in DME it is even more evident. The approach to this complication must be multidisciplinary. It is necessary to insist on the control of blood glucose, blood pressure, overweight and lipids sending the patient to the endocrine, internist, nephrologist whenever necessary given the great influence of these risk factors. There are numerous studies that point to poor metabolic control as a risk factor for the progression of DME. The recommendation is to keep HbA1c around 7-8.5%. Hypertension is also a risk factor and progression of DME and the recommended values are currently around 140/80 (2).
Diabetic retinopathy (DR) is the most frequent microvascular complication in diabetic patients, with a rate that can reach 30% of patients, and with 10% of patients at high risk of severe loss of vision (7).
It is a pathology that affects the retina, a specialized tissue highly sensitive to light that is located in the back of the eyeball and where the images that our brain interprets are projected.
The main risk factors are blood glucose concentration and duration of diabetes, but there are other factors that can contribute to the development of DR, such as high blood pressure or hyperlipidemia.
In the pathogenesis of DR, the persistent hyperglycemia that is characteristic of diabetes, seems to be responsible for the activation or alteration of multiple metabolic pathways of the body and the production of intermediate metabolites that eventually cause changes in blood vessels . The modifications result in an increase in vascular permeability and in a loss of normal blood vessel function. In an eye fundus, hemorrhages, microaneurysms (dilation of the vessels) and the presence of hard exudates (leaks of plasma components) in the retina (8) would be observed.
The production of VEGF (Vascular Endothelial Growth Factor) and inflammatory cytokines by cells of the retina and the immune system, also contributes to changes in blood vessels. In more advanced stages of DR, there is a marked obstruction of the vessels associated with severe hypoxia (lack of oxygen reaching the tissue) and neovascularization dominates. This anomalous growth of new weak vessels is dangerous since these vessels can rupture leading to hemorrhages that can severely compromise vision (8).
In addition to abnormalities in the vascular system, there is also neurodegeneration and nerve fiber alterations due to diabetes (10).
For the prevention of DR, it is essential to adequately monitor patients at risk of suffering visual loss due to diabetes before irreversible damage occurs (2). For this reason, all diabetic patients should undergo regular ophthalmological examinations, check the fundus, correctly control diabetes, blood pressure and not smoke (11).
Diabetes mellitus (DM) represents one of the greatest causes of morbidity and mortality in the world and is one of the greatest global health emergencies of the 21st century. According to the latest demographic update carried out by the International Diabetes Federation (IDF), the global impact of diabetes is 415 million people in the world and its prevalence, which ranges between 7.2% and 11.4 %, is increasing, with a forecast of 642 million in 2040. In Europe the number of diabetics amounts to 59.8 million adults and, in the case of Spain, the affected population exceeds 3.5 million. It is estimated that 1 in 11 adults have diabetes in the world, and that 1 in 2 adults with diabetes is not diagnosed.
Diabetes affects more poor societies and middle and lower income countries. The two countries with the highest number of diabetics in the world are China with 109.6 million, followed by India with 69.2 million (12).
Classification of diabetes
A diabetic person is characterized by having high blood glucose levels, either because he is not producing enough insulin, the hormone that regulates his levels, or because the body does not respond correctly to insulin. We can classify diabetes mainly in two well differentiated types:
- Type 1 Diabetes (known as insulin-dependent): It is characterized by a deficient production of insulin by beta cells in the islets of Langerhans of the pancreas. This type of diabetes requires daily administration of insulin, through injections or pump, to regulate blood glucose and for survival. Symptoms include excessive feeling of urination, thirst, constant hunger, weight loss, changes in vision and fatigue. The exact causes of type 1 diabetes still remain unknown, although it is generally accepted that there is a genetic factor. Most cases develop in childhood or adolescence.
- Type 2 Diabetes: It is usually the result of the ineffective use of insulin by the body, which is known as insulin resistance. Type 2 diabetes is related to obesity, with an increasing prevalence among all groups and all ages. It represents approximately 90% of all diabetes cases. The symptoms resemble those of type 1 diabetes, but less marked or even absent. It is for this reason that years can go by without being diagnosed. It is controlled by diet, lifestyle and with oral medications (for example, metformin) or insulin injections in advanced cases. The risk factors in this case are age, obesity, smoking, physical inactivity, ethnicity (more incident in the black race) and genetic.
- Gestational diabetes: It is a temporary condition that can occur during pregnancy. In this case, blood glucose levels are above normal, but below those of diabetes diagnosis. It poses an increased risk of complications during pregnancy and for the fetus. Risk factors include age, obesity, family history, etc. Gestational diabetes increases the risk of developing type 2 diabetes (12).
Diabetes increases the risk of serious health complications, which accelerate if there is poor metabolic control of the disease. The main complications of diabetes are cardiovascular disease, kidney disease, damage to the nervous system, diseases of the eyes, diabetic foot and also oral health problems.
One of the most prevalent complications of diabetes is diabetic retinopathy, which affects the retina, a specialized tissue very sensitive to light that is located in the back of the eyeball and where the images we see are projected.
|1.||Corcostegui B, et al. Update on diagnosis and treatment of diabetic retinopathy: a consensus guideline of the working group of ocular health (spanish society of diabetes and spanish vitreous and retina society). J Ophthalmol. 2017.|
|2.||Manejo de las complicaciones oculares de la diabetes. Retinopatía Diabética y Edema Macular.. “Guías de práctica clínica de la SERV”. Disponible en www.serv.es. Sociedad Española de Retina y Vítreo; Segunda revisión: 2015.|
|3.||Dong N, et al. Study of 27 aqueous humor cytokines in patients with type 2 diabetes with or without retinopathy. Molecular Vision. 2013;(19): p. 1734-46.|
|4.||Schmidt-Erfurth U, et al. Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology. 2014; 121(5): p. 1045-53.|
|5.||Cunha-Vaz, et al. Sustained delivery fluocinolone acetonide vitreous implant. Ophthalmology. 2014; 121(10): p. 1-12.|
|6.||Sohn HJ, et al. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Ophthalmol. 2011;(152): p. 686-694.|
|7.||Klein BE. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiology. 2007; 14: p. 179-183.|
|8.||Wong TY, et al. Diabetic retinopathy. Nat Rev Dis Primers. 2016; 2(17).|
|9.||Antonetti DA, et al. Diabetic Retinopathy: mechanisms of disease. N Engl J Med. 2012;(366): p. 1227-1239.|
|10.||Retinopatía diabética. Infográfico. Clínica Universidad de Navarra; 2014.|
|11.||International Diabetes Federation, IDF, 7th edition. [Online]. [cited 2017 Jul. Available from: http://www.diabetesatlas.org/.|
|12.||Global report on diabetes. World Health Organization; 2016.|
|13.||Wong TY, et al. Diabetic retinopathy. Nature Reviews. 2016;(16012).|