February 04, 2016
4 min read

Triple therapy reduces frequency, cost of neovascular AMD treatment

The addition of zeaxanthin significantly reduced the formation of CNV in the second eye.

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Triple combination therapy for neovascular age-related macular degeneration reduced the treatment burden and was more cost-effective than monotherapy, according to a study.

The addition of oral zeaxanthin to triple combination therapy further reduced the frequency of treatment and may have lowered the risk for choroidal neovascularization in fellow eyes, the study authors reported.

“First of all, this therapy significantly reduces the treatment burden for the patient and for the doctor,” lead investigator R. Joseph Olk, MD, told Ocular Surgery News. “I think this treatment will significantly alter the need for the patient and for the doctor to have quite as many treatment visits. This is very important if you think about the fact that most of these patients are in their 70s and their 80s. They don’t drive themselves and their family has to bring them, so it’s really a big burden for these patients to come in month after month. I think this form of therapy will hopefully be able to help reduce that burden alone.”

Study design

The study, published in the International Journal of Retina and Vitreous, included 543 eyes of 424 patients with subfoveal CNV secondary to AMD. All eyes underwent triple combination therapy, which comprised reduced-fluence photodynamic therapy with verteporfin, intravitreal Avastin (bevacizumab, Genentech) and intravitreal dexamethasone.

A subgroup of 290 eyes of 210 patients underwent triple therapy without oral zeaxanthin. Mean patient age in this cohort was 82 years.

A second subgroup of 253 eyes of 214 patients underwent triple therapy with a daily supplement of 20-mg oral zeaxanthin. Mean patient age in this cohort was 80 years.

All patients took a multivitamin and an AREDS1 antioxidant supplement during the trial.

“These patients were all placed on the AREDS1 formulation. At the time we started this trial, the AREDS2 was not available, so we were using AREDS1,” Olk said. Patients did not switch to the AREDS2 formula when it became available.

All patients underwent re-treatment when necessary and were followed for 2 years.

Investigators used a standardized cost-utility model to gauge incremental and average cost-utility. They compared triple therapy with zeaxanthin to no treatment and triple therapy alone to no treatment.

Results and conclusions

The mean number of treatment cycles at 2 years was 2.8 in the first subgroup without zeaxanthin and 2.1 in the second subgroup with zeaxanthin.

In the first subgroup, mean visual acuity improved from 20/250 at baseline to 20/200 at 12 months and 24 months, with a mean gain of six ETDRS letters (P < .0001). Vision was stable or improved in 87% of eyes at 2 years.

In the second subgroup, mean visual acuity improved from 20/200 at baseline to 20/160 at 12 months and 24 months, with an average gain of seven ETDRS letters (P < .0001). Vision was stable or improved in 83% of eyes at 2 years.

CNV developed in 12.5% of fellow eyes in the first subgroup and 6.25% of fellow eyes in the second subgroup over 2 years; the difference was statistically significant (P = .03).

“This is a very significant finding because many of these patients who develop exudation in one eye go on to get it in the other eye,” Olk said. “What I think this study showed more than anything is that this high-dose carotenoid zeaxanthin significantly reduced the formation of exudation in the second eye. I think that’s going to be very important in the long run for these patients.”

Triple combination therapy with zeaxanthin improved quality of life 2.5% compared with triple therapy alone (P < .0001).

The average cost-utility ratio was $26,574/quality-adjusted life-years (QALY) in the first subgroup and $19,962/QALY in the second subgroup.

“[Triple therapy] significantly reduces the cost compared to all types of monotherapy regimens that are out there. I think this, again, will be a very big benefit not only to the patients and the costs, but to the insurance companies and to the overall health system in this country,” Olk said.


A randomized masked placebo-controlled trial is near completion, the authors said.

“It certainly looks, at least from a preliminary analysis of the data, that we’ll be able to confirm everything we found in this study,” Olk said. – by Matt Hasson

Disclosure: Olk reports he holds stock in Zea-Vision.