Prevention and innovative treatments for the best patient management
The diseases that can impair sight create great concern, but for people with diabetes the threat is even more critical. This is due to the fact that in case of low vision or blindness, in addition to the enormous psychological troubles created by vision loss, many problems arise because of the loss of self-management skills, which are essential for everyday activities such as the preparation of insulin injections or measurement of the levels of blood sugar and pressure.
For this reason that Diabetic Macular Edema (DME),together with Diabetic Retinopathy (RD), is the most feared ocular complication of Diabetes Mellitus, since its progression can seriously and irreversibly hinder central visual function.
DME causes and prevention
Speaking of DME inevitably means referring to what is now considered the “pandemic” of the new millennium: the exponential growth of the prevalence rates of diabetes worldwide.
According to the data provided by the International Diabetes Federation (IDF), the total number of people with diabetes worldwide attained 451 millions in 2017 (with an increase of 10 million units compared to 2015) and at the current trends the number can rise to 693 millions by 20451.
Diabetes causes a serious prejudice to quality of life of affected individuals, also due to its complications, which can involve different apparatuses: cardiovascular, renal, neuromuscular and visual one, the latest with retinopathy and macular edema.
DME is a pathology with a complex pathogenesis, whose incidence increases correspondingly with the duration and severity of the diabetic disease: in fact among patients who suffer from diabetes mellitus for more than 20 years about 30% develop DME 2.
The onset of the disease is caused by a set of factors, where the lack of an adequate glycemic control plays a primary role.
In fact, hyperglycemia can cause widespread damage to retinal capillaries. Resulting capillary occlusion and increased vascular permeability determine phenomena of lack of capillary perfusion and vascular leakage, with accumulation of intra- or sub-retinal fluid. These mechanisms underlying DME can also be associated with other factors of an inflammatory or mechanical nature, which lead to clinical conditions that are different from patient to patient.
In terms of prevention, adequate glycemic control is therefore the first goal to be pursued in case of diabetes, in association with the control of other systemic parameters such as blood pressure and blood lipid levels.
In addition, the management of the patient by a multidisciplinary medical team can bring many benefits in terms of timeliness of choices and appropriateness of interventions.
In general, the diabetic patient is constantly looked after by the general practitioner and/or a diabetologist who, within a multidisciplinary team (which includes an ophthalmologist, a nephrologist, a cardiologist and other specialists) will carry out a role of coordination and direction during the various stages of the disease progression.
For the prevention of the eye complications of diabetes, the general practitioner must recommend appropriate regular check-ups and promptly advice the patient to call on an ophthalmologist at the first signs of ocular complications, also because the visual loss due to DME progresses quite slowly and, therefore, an early diagnosis followed by the use of the most appropriate treatment can be the crucial factor in order to maintain the visual function3.
In Italy, the National Plan on the Diabetic Disease of the Ministry of Health has been enforced since 2013, according with Law no. 115 of 1987, which stated and recognized the social relevance of the diabetic disease. The National Plan has contributed to consolidate an Italian model of treatment for diabetic disease based on , as well as family physicians, a capillary network of specialist centers spread throughout the national territory, centered on multi-professional skills (diabetologist, nurse, nutritionist, at times psychologist and/or podiatrist, and according to specific needs also a cardiologist, a nephrologist, a neurologist, and an ophthalmologist). These regularly provide guidance for about 50% of people with diabetes, mainly but not exclusively, those with a more complex and/or complicated disease. In this regard, the role of diabetic care in reducing mortality in people with diabetes, should be highlighted: those who are assisted in diabetic centers show lower rates of total mortality and cardiovascular mortality than those who do not attend them4.
Treatments: from traditional therapies to innovative treatments
In case of a diagnosis of DME, in the past, the only therapeutic option which was available was focal laser photocoagulation, which could be employed in cases where the DME did not involve the center of the macula (the central portion of the retina) or when central retinal thickness at OCT (Computerized Optical Tomography) was less than 400 μm. Laser treatment for several years has represented the gold standard for DME management, but today it is used only in combination with the most innovative therapies, as it does not provide adequate chances to ensure a visual acuity recovery.
The great novelty is nowadays represented by the introduction of intravitreal therapies with anti-VEGF agents for the treatment of maculopathies, first of all DMLE, followed by studies aimed at the extention of this treatment to diabetic retinopathy and DME
Today, intravitreal administration of the vascular endothelial growth factor (VEGF) receptor antagonists is the first-line treatment in patients with DME involving the center of the macula and determining a reduction of visual acuity.
Antiangiogenic therapy is administered to patients who meet the prescribed requirements, under reimbursement, with expenses charged to the Italian National Health Service (Servizio Sanitario Nazionale).
Anti-VEGF therapy is an effective approach, that can be useful to recover the lost visual acuity, but it requires frequent administration, on average at intervals between 30 and 60 days, for a total of approximately 7-8 injections during the first year, decreasing during the second and third year of treatment.
Moreover, a certain number of patients do not meet the requirements to be treated with anti-VEGF agents, while about 40% of the treated subjects demonstrate an insufficient therapeutic response both from an anatomical and functional point of view. It is precisely in these cases that the most innovative treatments with steroid drugs administered by intravitreal injection come into play.
The active ingredients currently administered in hospital under a reimbursement regime are dexamethasone and fluocinolone acetonide. The latter, in particular, is available with an innovative micro-implant that ensures a prolonged and continuous release of the active ingredient with a single intravitreal injection, the effects of which last for 3 years.
According to the latest guidelines for treatment of DME, even though anti-VEGF represent the first therapeutic choice in most cases, steroid drugs are indicated as a first approach in pseudophakic patients (those who have already undergone cataract surgery) and with elevated cardiovascular risk5.
Patient quality of life
It is then clear that today the diabetic patient faces better perspectives both for the management of the systemic disease and the control of the complications that may affect the various apparatuses, first of all the eye.
As for the eye there are many advantages in accessing intravitreal treatments such as the last one based on fluocinolone acetonide, which allows a 3-year administration,.
To begin with we must consider the reduction of the stress and of the risk of infections due to the lower number of intravitreal injections. Then there is the reduction of the burden on the patient and his family in terms of lost working days and costs sustained in order to reach the hospital sites where the treatment is administered .
Lower costs for public health
In terms of costs, the use of long-term steroid implants in long-term management of DME can indeed be a winning choice, as already reported by studies published in other countries, including the United States and the United Kingdom.
In 2017, a study was published in Italy based on an economic model aimed at estimating the budget of the Lombardy Region over a period of three years and in which it has been reported how the use of corticosteroids is potentially linked to a lower expenditure of up to 13%, compared to that estimated with the use of anti-anti-VEGF drugs6.
Treatments that reduce the number of administrations, as in the case of the implant with fluocinolone acetonide, also entail other advantages for a health system, such as the shortening of the waiting lists in the centers where injective therapies are administered, which register continually increasing requests of assistance.
Fewer administrations also imply less time required to the ultra-specialized medical staff that performs intra-vitreous injections and provides for all the check-ups and instrumental examinations associated with repetitive treatment sessions over time.
Good news from “real life” studies
Further good news concerns the implants that release fluocinolone acetonide and comes from real-life studies, which report data from clinical practice, that compared to the controlled and randomized clinical trials has the advantage of covering variegated contexts and diversified patient populations and therefore, can provide useful information on profiles of efficacy and safety of therapeutic treatments.
The latest real life data confirms the positive results in terms of improvement in visual acuity and average reduction of edema, already reported in Literature, but the good news concerns the lower adverse event rates, thanks also to a careful selection of patients to be treated with intraocular steroids7.
Authors: Sabrina Zappia and Ada Puglisi
- IDF Diabetes Atlas. Eighth edition 2017.
- Moss SE, Klein R, Klein BE. The 14-year incidence of visual loss in a diabetic population. Ophthalmology 1998;105:998-1003.
- Diabetes Eye Health: a guide for health professionals. International Diabetes Federation and the Fred Hollows Foundation. https://www.idf.org/our-activities/care-prevention/eye-health/eye-health-guide.html
- 10thItalian Diabetes & Obesity Barometer Report 2016. Facts and Figures about type 2 diabetes & obesity in Italy. 3rdYear – April 2017 – N° 1.
- Linee-guida per lo screening, la diagnostica e il trattamento della retinopatia diabetica In Italia, Gruppo di Lavoro sulle Complicanze Oculari del Diabete, Società Italiana di Diabetologia, 2015.
- Foglia E, Ferrario L, Bandello F, et al. Diabetic macular edema, innovative technologies and economic impact: New opportunities for the Lombardy Region healthcare system? Acta Ophthalmol.2017 Dec 14.
- Loewenstein A, Chakravarthy U. 0.19 mg fluocinolone acetonide intravitreal implant: place in the management of diabetic macular edema. Minerva Oftalmol 2018;60:71-82.
Sabrina Zappia is the Founder & Director of CITYnet, an international communication, pr and branding agency promoting development opportunities across the global market, aiming towards innovative solutions and creative experiences designed for businesses, institutions and cultural enterprises who work actively in the Italian and international markets.
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