Triple combination therapy and zeaxanthin for the treatment of neovascular age-related macular degeneration: an interventional comparative study and cost-effectiveness analysis

Abstract

BackgroundReports of triple combination therapy for neovascular age-related macular degeneration (AMD) suggest a benefit, as do reports for zeaxanthin. An interventional comparative study was thus undertaken to evaluate the efficacy of triple combination therapy with and without zeaxanthin, as well as the economic viability of the therapies.MethodsThe cases of 543 consecutive eyes of 424 patients with subfoveal choroidal neovascularization (CNV) secondary to AMD were reviewed. All eyes were treated with triple combination therapy (triple therapy) consisting of: (1) reduced-fluence photodynamic therapy with verteporfin, (2) intravitreal bevacizumab and (3) intravitreal dexamethasone. Therapy was repeated as necessary. One cohort of patients was also given supplementation with 20 mg of oral zeaxanthin (Zx) daily.ResultsThe triple therapy group without Zx received a mean of 2.8 treatment cycles and 87 % of patients had stable or improved vision at 24 months. In the triple therapy group with Zx, the mean number of treatment cycles was 2.1, with 83 % of patients having stable or improved vision at 24 months. At 24 months, CNV developed in 12.5 % of fellow eyes treated with triple therapy alone; CNV developed in 6.25 % of eyes treated with triple therapy with Zx (p = 0.03). An average cost-utility analysis revealed that triple therapy was cost-effective with a cost-utility ratio of $26,574/QALY, while triple therapy with Zx was more cost-effective with an average cost-utility ratio of $19,962/QALY. The incremental cost-utility analysis assessing the addition of Zx to triple therapy disclosed Zx supplementation was very cost-effective at $5302/QALY. When it was assumed that triple therapy with Zx reduced fellow eye CNV development by 30.3 %, the incremental cost-utility dropped to (−$6332/QALY), indicating that adding Zx to triple therapy yielded greater patient value, and was also less expensive than using triple therapy alone.ConclusionsTriple therapy is comparatively effective and cost-effective. Considerably less treatment is needed than reported in monotherapy studies. The addition of oral Zx appears to further reduce the treatment cycles required, and possibly reduce the risk of CNV development in the fellow eye.

A Systematic Review of Carotenoids in the Management of Age-Related Macular Degeneration

“…This may be attributed, at least in part, to advanced stages of disease and by poor micronutrient absorption rates, which likely represents a limiting factor and should not be ruled out from clinical trials [ 122 , 326 ]. However, one preliminary report indicated that oral zeaxanthin supplementation, as an adjunct to an aggressive triple combination therapy regimen (including bevacizumab, steroid, and photodynamic therapy with verteporfin) for patients with subfoveal choroidal neovascularization, enhanced therapeutic efficiency and decreased the number of treatment cycles required [ 327 ]. Similar benefits were reported in cultured human RPE cells, following hypoxia-induced VEGF secretion, whereby treatment with zeaxanthin was suggested to offer direction protection against the pro-angiogenic factors contributing to neovascular lesions [ 328 ].…”

Daily zeaxanthin supplementation prevents atrophy of the retinal pigment epithelium (RPE) in a mouse model of mitochondrial oxidative stress

“…A recent clinical study involving combinational therapy showed that zeaxanthin did protect the macula in already diseased eyes [ 43 ]. These studies in advanced AMD were different from AREDS2 in that they used 10-fold higher (and putatively more effective) doses of zeaxanthin (20 mg vs 2).…”

Restoration of Central Macular Pigment Dip with Dietary RR Zeaxanthin Supplementation in Patients with AMD

“…Supplementation with Z has been shown to improve visual performance and suppress retinal neovascularization that is characteristic of advanced AMD [38] while yielding a lower costutility ratio than identical treatments without Z supplementation [39]. The authors believe this paper provides the first evidence of resolution of a central dip in macular pigment density from dietary Z supplementation.…”