Antivascular Endothelial Growth Factor Treatment in Pseudoxanthoma Elasticum Patients

Abstract

The eye in patients with pseudoxanthoma elasticum, an autosomal recessive disease, shows several lesions, like peau d'orange, angioid streaks, comet lesions, and paired hyperpigmented smudges. The most devastating ocular complication is the development of choroidal neovascularizations (CNV). This exudative disease of the central retina leads to loss of visual acuity, and results of treatments in the past have been disappointing. From the present evidence it may be concluded that intravitreal antivascular endothelial growth factor (anti-VEGF) therapy with ranibizumab or bevacizumaab is beneficial for the treatment of CNV secondary to angioid streaks associated with PXE. Especially in the early stages of the disease, visual acuity can be maintained or even improved over a prolonged period of time, even with a low number of injections. Later in the course of the disease, when more widespread atrophic changes have occurred, the perspective is more bleak. Although there seem to be arguments to treat selected patients with a maintenance treatment of intravitreal injections once every 2 months, an as-needed regimen is the most used strategy. Patients need to be aware of the off-label nature of the treatment with anti-VEGF and also need to be informed about the possible increased risk of cardiovascular and/or thromboembolic events, although at present no definite proof has been documented of this higher risk in patients with or without PXE treated with intravitreal anti-VEGF. Overall, based on the evidence available, intravitreal treatment with anti-VEGF seems to be the best choice at present to treat patients with CNV secondary to angioid streaks and PXE.

Perturbation of specific pro-mineralizing signalling pathways in human and murine pseudoxanthoma elasticum

“…PXE patients often suffer subretinal neovascularisation and haemorrhaging as a complication of the PXE retinopathy [110,111]. VEGF-A, a potent mediator of angiogenesis, is assumed to play a role in this neo-angiogenesis, as treatment of PXE patients with anti-VEGF injections has been very successful [112]. However, the mechanism behind VEGF-A involvement has not yet been uncovered.…”

Administration of vitamin K does not counteract the ectopic mineralization of connective tissues inAbcc6-/-mice, a model for pseudoxanthoma elasticum

“…While identification of specific mutations in the ABCC6 gene has assisted in diagnosis and allowed presymptomatic identification of individuals at risk for PXE, 1,20 relatively little progress has been made towards treatment of this complex, often devastating disease. In fact, while vascular endothelial growth factor antagonists have shown promise for treatment of the ophthalmologic complications due to neovascularization in the retina, 21,22 no global, pathophysiology related approaches are currently available for treatment of PXE.…”

Pseudoxanthoma elasticum

“…Intravitreal treatment with vascular endothelial growth factor (VEGF) inhibitors (such as bevacizumab) has rapidly become an effective treatment for stopping choroidal neovascularization – often the most critical symptom of PXE [136–138]. Accordingly, physical treatments such as photodynamic therapy have become less extensively used.…”