Study of the efficacy and the mechanism of action of lanreotide for the treatment of persistent diabetic macular edema

Abstract

The current treatments for diabetic macular edema (DME) include laser, steroids or vascular endothelial growth factors inhibitors (antiVEGF). Some DME are resistant to these treatments, which can respond to somatostatin inhibitors such as lanreotide. These drugs appear to influence the development of diabetic retinopathy (DR) and DME either through a direct antiVEGF effect or through the inhibition of growth hormone (GH), endothelial cell apoptosis and anti-inflammatory effect. It was conducted a study of the effects of lanreotide in retinal pigment epithelial cell cultures and a clinical study in patients with DME resistant to conventional treatments in order to better understand the usefulness of this drug. Lanreotide showed antiapoptotic effects and significantly improved visual acuity. Lanreotide could be applied in non-respondent patients to other treatments as an alternative in refractory DME patients.

Fig. 1

Immunohistochemical staining (A) Analysis with VEGF marker to validate the angiogenic response. The cells which are stained in brown indicate positivity for VEGF. (B) Expression of the angiogenesis marker VEGF. (C) Analysis with Caspase-3 marker to validate the antiapoptotic response. The cells which are stained in brown indicate positivity for Caspase-3. (D) Expression of the apoptotic marker Caspase-3 in each one of the four groups. (E) Analysis with JNK marker to validate the oxidative stress response. The cells which are stained in brown indicate positivity for JNK. (F) Expression of the oxidative stress marker JNK in each one of the four groups. *p < 0.05 C: control; D: diabetic; C + L: Control + lanreotide; D + L: Diabetic + lanreotide.

Fig. 2

Dispersion graphs. (A) Direct correlation between VEGF and Caspase-3 with a p value of 0.025 (B) Direct correlation between Caspase-3 and JNK with a p value of 0.029 (C) Direct correlation between VEGF and JNK with a p value of 0.016.

Fig. 3

Changes in total cholesterol and average triglycerides (A) and albuminuria (B) between the basal visit and 12 months visit in patients with DME under lanreotide treatment. *p < 0.05.

Fig. 4

Visual and anatomical improvements. (A) Average VA in the number of letters read at a distance of 4 m (ETDRS scale) from baseline to end of study at 12 months. (B) Evolution of the average central macular thickness from baseline to end of study at 12 months (*p < 0.05). (C) Variation in the central macular thickness from baseline to end of study at 12 months.