Safety and Efficacy of Dexamethasone Intravitreal Implant Given Either First-Line or Second-Line in Diabetic Macular Edema

Abstract

Diabetic macular edema (DME) is a common sight-threatening complication of diabetic retinopathy (DR) and the leading cause of severe visual impairment among the working-age population. Several therapeutic options are available for the management of DME, including intravitreal corticosteroids. They have been traditionally used as second-line treatment, due to the risk of intraocular pressure increase and cataract-related adverse events. However, attention has recently been focused on the primary or early use of intravitreal corticosteroids, due to growing evidence of the crucial role of inflammation in the pathogenesis of DME. Furthermore, intravitreal steroid implants offer the additional advantage of a longer duration of action compared to anti-vascular endothelial growth factor agents (anti-VEGF). This review aims to summarize the available evidence on the efficacy and safety profile of dexamethasone (DEX) intravitreal implant, with a specific focus on clinical scenarios in which it might be considered or even preferred as first-line treatment option by adequate selection of patients, considering both advantages and possible adverse events. Patients with contraindications to anti-VEGF, DME with high inflammatory OCT biomarkers, pseudophakic patients and phakic patients’ candidates to cataract surgery as well as vitrectomized eyes may all benefit from first-line DEX implant. Additionally, DME not responders to anti-VEGF should be considered for a switch to DEX implant and a combination therapy of DEX implant and anti-VEGF could be a valid option in severe and persistent DME.

Switching to an Intravitreal Dexamethasone Implant after Intravitreal Anti-VEGF Therapy for Diabetic Macular Edema: A Review

“…Nonetheless, patients with a history of significant cardiovascular events and those who are unable to attend monthly or more frequent appointments are seen as the most suitable candidates for first-line treatment [ 78 ]. In particular, patients with high-risk cardiovascular disease, poor compliance, severe macular edema (more than 500 microns), a history of cataract surgery or vitrectomy, or scheduled cataract surgery are advised to use the DEX implant as first-line treatment [ 79 , 80 ]. Other alternative treatments for refractory DME are represented by the use of different intravitreal steroids or subthreshold micropulse laser (SML) therapy.…”

“…Nevertheless, the DEX implant is preferred in cost–benefit analyses [ 79 , 84 , 85 , 86 ]. According to international guidelines, the best DME treatment for a diabetic patient will therefore depend on numerous factors, including the patient’s baseline status, the identification of predictive biomarkers, and the patient’s responsiveness to individual treatment [ 78 ].…”

“…Conversely, the response of other DME parameters, including progressive ischemic maculopathy, appears to be almost the same for both DEX and anti-VEGF [ 15 , 16 ]. In patients who have not received therapy yet, corticosteroid implants have shown acceptable clinical results and a positive safety profile [ 79 ]. Following a switch to corticosteroids after anti-VEGF therapy, there have been observed modifications in particular inflammatory parameters in the inner retina, such as decreases in HRFs, DRIL extension, and CST [ 15 ].…”

“…Furthermore, DEX is highly soluble in water, exhibiting faster clearance from the eye compared to other steroids, which can impact its binding properties to intraocular tissues and potentially reduce the incidence of local events. Nonetheless, the affinity of intravitreal steroids for lens and trabecular meshwork cells can lead to complications such as cataract progression and an IOP increase [ 79 ]. The latter is usually manageable with topical IOP-lowering medications, with few cases requiring filtration surgery [ 89 ].…”

“…The latter is usually manageable with topical IOP-lowering medications, with few cases requiring filtration surgery [ 89 ]. Additionally, although the higher incidence of cataract development in patients receiving DEX implants compared with anti-VEGF therapy is still discussed, this complication is easily manageable with cataract surgery, with a preference to avoid or postpone the DEX implant in phakic patients [ 79 , 90 , 91 ].…”