Combination Therapy for Choroidal Neovascularisation

Abstract

Choroidal neovascularisation (CNV) often leads to severe vision loss and is becoming increasingly prevalent as the aging population grows. Age-related macular degeneration (AMD) is the most common cause of CNV, but CNV also affects younger people with pathological myopia, ocular histoplasmosis syndrome, angioid streaks and idiopathic disorders. The monotherapies available worldwide to treat patients with CNV have primarily been studied in CNV due to AMD, and all have their drawbacks. Combination therapy takes advantage of the strengths of each therapy and their different mechanisms of action to achieve good treatment outcomes with few repeated treatments. For example, combination (triple) therapy with verteporfin photodynamic therapy, anti-vascular endothelial growth factor (VEGF) therapy and anti-inflammatory therapy addresses three main targets of CNV development: the CNV itself, VEGF expression (which promotes CNV growth) and inflammation (which exacerbates the disease process). Such triple therapy has been shown to result in sustained improved vision after only one treatment. Vision outcomes similar to those observed with ranibizumab, the most promising and rigorously proven anti-VEGF monotherapy, may be possible with combination therapy without the need for continued monthly intravitreal injections, which are required if sustained outcomes are to be achieved with ranibizumab. The goal of CNV therapy is improved vision outcomes after one course of treatment. Combination therapy may lead to this goal. Such treatment could also result in fewer safety issues (fewer treatments are required and the unknown effects of continued long-term treatment are avoided), lower cost to both the patient and the medical system and greater convenience for patients (fewer clinic visits). However, combination therapy is beset with several challenges: different therapies, doses, timing and treatment sequences are possible, and it is therefore difficult to conduct large, definitive clinical trials to determine which treatment regimen is safest and most effective. Large controlled studies are needed to more clearly define effective and safe combination regimens for CNV.

Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years

“…The pathogenesis of CNV is complex, consisting of a cascade of retinal changes in which ischemia or hypoxia leads to the upregulation of growth factors, such as VEGF, and atrophy of the choroidal vasculature [27][28][29]. This causes inflammation, angiogenesis, and subsequently neovascularization [30]. It is possible that treatment strategies might derive benefit by targeting various components of this cascade to achieve additive or even synergistic effects [31].…”

Quadruple Therapy Leads to a Sustained Improvement of Vision in Patients with Wet Age-Related Macular Degeneration

“…Combination therapy aims not only at the prevention of angiogenesis but also at the regression of existing CNV by using multiple pharmacological agents, which work synergistically and typically include the VEGF inhibitor bevacizumab [5,6]. Recently, Augustin et al [7] evaluated a combination of photodynamic therapy (PDT) with verteporfin and intravitreal treatment with bevacizumab and dexamethasone in patients with CNV secondary to AMD.…”

Combined Intravitreal Pharmacosurgery in Patients with Occult Choroidal Neovascularization Secondary to Wet Age-Related Macular Degeneration

“…A combination therapy including photodynamic therapy with verteporfin and intravitreal treatment with bevacizumab and dexamethasone was recently evaluated in patients with CNV secondary to AMD [6]. …”