First Author: J.Henriques PORTUGAL
Co Author(s): J. Figueira J. Nascimento L. Goncalves P. Caldeira Rosa M. Dutra Medeiros R. Silva
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DME is a complex and a multifactorial disease. Considering its pathophysiology, different targets can be sought to treat DME. While VEGF levels increase, as disease progresses tend to become chronic and mainly inflammatory with cytokines (others than the VEGF family) dramatically high. For focal DME, laser treatment is usually responsive. However, for diffuse DME it is often needed a combined therapy to fight DME. A disease segmentation and a personalized treatment can be a more effective treatment.
The authors present an updated algorithm to treat DME in an individualized regimen; this update was accomplished by GER (Portuguese Retina Study Group).
In our review, we analyzed different DME randomized clinical trials (RCT) such as early treatment diabetic retinopathy Study (ETDRS), Protocol T and I from DRCRnet, RISE and RIDE, RESOLVE, RESTORE, VIVID and VISTA, MEAD and FAME studies. The aim of this review was to propose a new and updated algorithm for the treatment of DME, based on the staging of the disease.
According to the DME stage: focal or diffuse, with or without involvement of the centre of the macula and in presence of epiretinal membrane, an individualized treatment regimen was defined in 3 different therapeutical arms: (1) No involvement of the centre of the macula, (2) With the involvement of the centre of the macula; (3) Epiretinal membrane. If (1) treat accordingly with ETDRS protocol. If (2) perform a fluorescein angiography to classify into focal, diffuse or ischaemic. If focal with exudation points further away than 500 microns of the fovea, the first line of treatment is laser. Otherwise or if Diffuse, consider anti-VEGFs as first line and corticosteroids as second-line therapy. Consider steroids as first-line if patient is pregnant or breastfeeding, or myocardial infarction or stroke occurred less than 6 months. Dexamethasone if patient is pseudophakic and, or vitrectomized. Fluocinolone Acetonide in case of chronic DME (more than 18 months), inadequate response to previous therapies, phakic, aphakic, pseudophakic and, or vitrectomized patients. In ischaemic cases, consider intravitreal treatment. If patient presents macular traction and/or epiretinal membrane, surgery should be considered. In a presence of insufficient response to previous treatments a rescue with laser can be proposed.
There are several methods to treat DME, including laser photocoagulation, vitrectomy, corticosteroids and VEGF antagonists. VEGF inhibitors, consist of recombinant humanized monoclonal antibodies that interfere with VEGF binding to VEGF receptors (VEGF-A, VEGF-B, and PIGF receptors) and has showed to be an important therapy against diffuse DME, combined or monotherapy. Corticosteroids improved pathological processes associated with DME via inhibition of leukostasis and by decreasing the expression of VEGF and inflammatory cytokines, resulting in functional and structural improvements and should be considered an alternative as monotherapy or in combination treatment with anti-VEGF, laser or vitrectomy. Laser treatment has been associated in mostly clinical trials as rescue therapy (mainly in the bevacizumab arms) showing how crucial is this non-drug therapy. Here we present in our best understanding the algorithm to treat DME in an individualized regimen, taking advantage of the combination therapy.