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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.

In the rat, sciatic and saphenous nerve section resulted in self-mutilation of the ipsilateral limb. Fifteen and 60 days after surgery, monoamine levels were altered not only in the spinal cord but also in supraspinal structures. Thus, in the ipsi- and contralateral sides of the spinal lumbar region, an increase in the levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed 15 days after surgery and in the levels of serotonin (5-HT) and noradrenaline 60 days later. Changes in the content of 5-HT and its metabolite were also evident, at these time points, in periaqueductal gray matter and trigeminal nucleus. Chemical sympathectomy carried out by administering guanethidine to neonatal rats reduced the degree of autotomy and suppressed the changes in monoaminergic systems following peripheral neurectomy. This study supports the hypothesis that the local noradrenaline outflow from sympathetic fibers in the neuroma is one of the causal factors in autotomy and it indicates that autotomy is under the control of descending monoaminergic pathways originating in brain-stem nuclei.

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