Diabetic Macular Oedema
Diabetic Macular Oedema (DMO) is a complication associated with diabetic retinopathy and the leading cause of vision loss in diabetic patients. It is the leading cause of blindness in the working-age population in industrialised countries, with a prevalence of around 7.5% among diabetic patients (1). In Europe, there are 4 million people with DMO and in Spain, approximately 300,000 patients.
DME affects the macula, which is the central region of the retina where the highest concentration of photoreceptors is found and where central vision and the highest level of detail are generated.
It has traditionally been defined as a clinical condition characterised by thickening of the retina in the macular area (within an area of 2 papillary diameters from the centre of the macula), which occurs as a result of microvascular changes that compromise the blood-retinal barrier, which separates the blood from the retina (2).
In most cases, DMO is a condition that requires ongoing intervention and treatment. Laser treatment, which has traditionally been considered the treatment of choice for these patients, has in many cases been replaced by drug therapy, to the extent that various treatment options are now available. The key to success lies in knowing how to choose the most appropriate option for each specific case.
The pathogenesis of this disease varies over time and between patients. In the early stages, DMO is primarily mediated by the angiogenic factor VEGF (Vascular Endothelial Growth Factor), which is induced by hypoxia in the retinal tissue and promotes the accelerated and abnormal growth of poor-quality blood vessels. These contribute to the leakage of plasma components into the retina and the consequent development of inflammation and oedema. At this stage, it is advisable to block the action of VEGF using intravitreal anti-VEGF drugs.
However, as the disease progresses and the severity of DR increases, VEGF levels remain relatively constant, whilst levels of other pro-inflammatory cytokines rise exponentially (3). At this stage, which may occur between 1 and 2 years after diagnosis (with considerable inter-individual variability), treatment with an anti-inflammatory drug may be necessary (4), (5).
Intravitreal corticosteroids have been shown in numerous studies to not only block numerous pro-inflammatory cytokines but also to have a known anti-angiogenic effect (6). Thus, at this stage of the disease, anti-VEGF agents are not as suitable as they act solely against VEGF; conversely, corticosteroids are much better suited to treating this multifactorial disease. There are currently two corticosteroid options for the treatment of DMO: a short-acting one that requires repeat injections every 3–6 months, and a long-acting one, which has been shown to provide relief for up to three years.
The diagnosis and assessment of oedema must be carried out by an expert ophthalmologist, and follow-up should always take into account: best corrected visual acuity (BCVA), biomicroscopic examination and OCT (Optical Coherence Tomography), a non-invasive test that can quantitatively measure increased macular thickness, one of the signs of oedema (thickening in the macular area) (2).
Diabetic Macular Oedema (DMO) is a complication associated with diabetic retinopathy and the leading cause of vision loss in diabetic patients.
Recommendations for DMO
Whilst metabolic control is essential in diabetic retinopathy (DR), it is even more crucial in DMO. The approach to this complication must be multidisciplinary. It is essential to emphasise the control of blood glucose, blood pressure, weight and lipids by referring the patient to an endocrinologist, general practitioner or nephrologist whenever necessary, given the significant influence of these risk factors. Numerous studies point to poor metabolic control as a risk factor for the progression of DMO. The recommendation is to maintain HbA1c at around 7–8.5%. High blood pressure is also a risk factor for the development and progression of DMO, and the current recommended blood pressure levels are around 140/80 (2).
Diabetic Retinopathy
Diabetic Retinopathy (DR) is the most common microvascular complication in diabetic patients, affecting up to 30% of patients, with 10% at high risk of severe vision loss (7).
It is a condition affecting the retina, a specialised tissue highly sensitive to light located at the back of the eyeball, where the images our brain interprets are projected.
The main risk factors are blood glucose levels and the duration of diabetes, but other factors may contribute to the development of DR, such as high blood pressure or hyperlipidaemia.
In the pathogenesis of DR, persistent hyperglycaemia, which is characteristic of diabetes, appears to be responsible for the activation or disruption of multiple metabolic pathways in the body and for the production of intermediate metabolites that, in the long term, ultimately cause changes in the blood vessels. These changes result in increased vascular permeability and a loss of normal blood vessel function. An eye fundus examination would reveal haemorrhages, microaneurysms (dilated blood vessels) and the presence of hard exudates (leakage of plasma components) in the retina (8).
The production of VEGF (Vascular Endothelial Growth Factor) and inflammatory cytokines by retinal and immune system cells also contributes to changes in the blood vessels. In more advanced stages of DR, there is marked vascular obstruction associated with severe hypoxia (lack of oxygen supply to the tissue) and neovascularisation predominates. This abnormal growth of new, fragile blood vessels is dangerous as these vessels can rupture, leading to haemorrhages that can seriously compromise vision (8).
In addition to abnormalities in the vascular system, there is also neurodegeneration and damage to nerve fibres caused by diabetes (10).
To prevent DR, it is essential to monitor patients at risk of vision loss due to diabetes closely before irreversible damage occurs (2). Therefore, all diabetic patients should undergo regular eye examinations, have their fundus checked, manage their diabetes and blood pressure properly, and avoid smoking (11).
Diabetes
Diabetes mellitus (DM) is one of the leading causes of morbidity and mortality worldwide and represents one of the greatest global health emergencies of the 21st century. According to the latest demographic update by the International Diabetes Federation (IDF), diabetes affects 415 million people worldwide, and its prevalence, which ranges from 7.2% to 11.4%, is on the rise, with a projected figure of 642 million by 2040. In Europe, the number of people with diabetes stands at 59.8 million adults, and in Spain, the affected population exceeds 3.5 million. It is estimated that 1 in 11 adults worldwide has diabetes, and that 1 in 2 adults with diabetes remains undiagnosed.
Diabetes affects poorer societies and low- and middle-income countries the most. The two countries with the highest number of people with diabetes in the world are China, with 109.6 million, followed by India, with 69.2 million (12).
Classification of diabetes
A person with diabetes is characterised by high blood glucose levels, either because they are not producing enough insulin, the hormone that regulates these levels, or because the body does not respond correctly to insulin. Diabetes can be classified mainly into two distinct types:
- Type 1 diabetes (also known as insulin-dependent diabetes): It is characterised by insufficient insulin production by the beta cells in the islets of Langerhans in the pancreas. This type of diabetes requires daily insulin administration, via injections or a pump, to regulate blood glucose levels and ensure survival. Symptoms include an excessive urge to urinate, thirst, constant hunger, weight loss, changes in vision, and fatigue. The exact causes of type 1 diabetes remain unknown, although it is generally accepted that there is a genetic component. Most cases develop during childhood or adolescence.
- Type 2 diabetes: This is usually the result of the body’s ineffective use of insulin, known as insulin resistance. Type 2 diabetes is linked to obesity, with a rising prevalence across all groups and age ranges. It accounts for approximately 90% of all cases of diabetes. The symptoms are similar to those of type 1 diabetes, but less pronounced or even absent. This is why it can go undiagnosed for years. It is managed through diet, lifestyle changes and oral medicinal products (e.g., metformin) or insulin injections in advanced cases. Risk factors in this case include age, obesity, smoking, physical inactivity, ethnicity (more common in black people) and genetics.
- Type 2 diabetes: This is usually the result of the body’s ineffective use of insulin, known as insulin resistance. Type 2 diabetes is linked to obesity, with a rising prevalence across all groups and age ranges. It accounts for approximately 90% of all cases of diabetes. The symptoms are similar to those of type 1 diabetes, but less pronounced or even absent. This is why it can go undiagnosed for years. It is managed through diet, lifestyle changes and oral medicinal products (e.g., metformin) or insulin injections in advanced cases. Risk factors in this case include age, obesity, smoking, physical inactivity, ethnicity (more common in black people) and genetics.
Diabetes increases the risk of serious health complications, which are accelerated if the condition is poorly controlled. The main complications of diabetes are cardiovascular disease, kidney disease, nerve damage, eye diseases, diabetic foot, and oral health problems.
One of the most common complications of diabetes is diabetic retinopathy, which affects the retina, a specialised tissue highly sensitive to light located at the back of the eyeball, 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”. Available on www.serv.es. Spanish Retina and Vitreous Society; Second revision: 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. University of Navarre Clinic; 2014.
11. International Diabetes Federation, IDF, 7th edition. [Online]. [cited 2017 Jul. Available from: https://diabetesatlas.org/.
12. Global report on diabetes. World Health Organization; 2016.
13. Wong TY, et al. Diabetic retinopathy. Nature Reviews. 2016;(16012).