Two-year study results highlight some advantages of steroid treatment for DME.
Take-home message: Two-year study results highlight some advantages of steroid treatment for DME.
Reviewed by Mark Gillies, MBBS, PhD
Sydney-Steroids may offer an alternative to anti-vascular endothelial growth factor (VEGF) therapy in pseudophakic eyes with diabetic macular edema (DME), said Mark Gillies, MBBS, PhD.
A study comparing the two treatments show similar gains in visual acuity, but with fewer treatments required for the steroid over the course of 2 years, said Dr. Gillies, professor of ophthalmology, Save Sight Institute, University of Sydney.
On the other hand, steroid-treated eyes had more cataracts.
“We routinely here treat pseudophakic eyes with steroids,” he said. “For phakic eyes we use anti-VEGFs as first-line treatment."
Dr. Gillies and his colleagues published the 2-year results of the BEVORDEX trial online in the journal Ophthalmology.
"The Save Sight Institute has pioneered the study of steroids in DME," he said.
When faculty there realized that drug companies were not planning head-to-head trials comparing steroids with anti-VEGF treatment, it took the initiative in 2010.
With funding from the Australian government, with support from Allergan, the center recruited 88 study eyes with center-affecting DME. Researchers randomly assigned 42 to bevacizumab as needed up to once eveyr 4 weeks, and 46 to slow-release dexamethasone implants (Ozurdex, Allergan) as needed up to once every 16 weeks.
The two groups were well matched, with mean visual acuity at baseline 56.3 logMAR letters in the bevacizumab group and 55.5 in the dexamethasone group. Central macular thickness was 503 µm in the bevacizumab group and 474 µm in the dexamethasone group. Both groups were about one-third female and had a mean age of 62 years.
At 12 months, the two groups got similar improvement in 10-letter gain in visual acuity. The mean improvement in LogMAR letters was 8.9 for the bevacizumab group, and 5.6 for the dexamethasone group, a difference that was not statistically significant (p = 0.24).
But anatomically, the dexamethasone group improved more. The mean change in central macular thickness for the bevacizumab group was -122 µm for the bevacizumab group and -189 µm for the dexamethasone, which was statistically significant (p = 0.015).
During the second year of the study, with 68 of the original 88 patients still enrolled, visual acuity in both groups continued to improve, with a mean increaese of 10.2 letters for bevacizumab and 5.8 for dexamethasone versus baseline.
The difference was still not statistically significant (p = 0.19), “but a larger study would probably have found in favor of bevacizumab for eyes phakic at baseline,” Dr. Gillies said.
On the other hand, mean central macular thickness continued to decline in the bevacizumab in the second year, reaching -166 µm from baseline, close to the reduction seen in the dexamethasone group of -162 µm from baseline. As a result, there was no longer a significant difference between the two groups using this measure at 2 years (p = 0.50).
A similar pattern emerged regarding the distance of hard exudates from the foveal center.
“At the end of the first year, the response in terms of hard exudates was in favor of steroids,” Dr. Gillies said. “At the end of the second year the difference was not as great.”
Eyes randomly assigned to receive bevacizumab received a mean of 9.1 injections in the first year and 4.8 in the second, compared with 2.8 for the dexamethasone group in the first year and 2.2 in the second.
The principle adverse events were cataracts. At the 2-year mark, 6% of eyes treated with bevacizumab needed cataract surgery versus 37% of dexamethasone treated eyes.
One bevacizumab eye and 5 dexamethasone-treated eyes lost more than 10 letters of visual acuity. Some of this loss of acuity occurred as a result of cataract formation.
“Acuity improved as cataracts came out,” Dr. Gillies said.
One eye treated with dexamethasone developed the rare complication of syphilitic chorioretinitis.
The addition of topical IOP-lowering drops was required in 22% of dexamethasone-treated eyes while no bevacizumab-treated eyes required this.
The study also showed the efficacy of administering dexamethasone implants every 16 weeks, Dr. Gillies said.
Studies in which it has been administered every 6 months have fallen short of expectations, he said.
This study showed that on average the central macular thickness increased 4 months after the previous injection.
“The conclusion from that is that if the patient has the stomach for anti-VEGF monthly, then they may be better off,” Dr. Gillies said. “You get good results in the end, but it might take up to 18 monthly injections.”
But there are some circumstances when steroids might be preferable to anti-VEGF treatments, he said.
First, if patients are unable to visit clinics monthly, they might be better off with dexamethasone implants, he said.
Second, steroids might work in people who do not get much improvement with anti-VEGF treatment.
“The question is: When do you switch to steroid treatment?” Dr. Gillies asked.
Third, steroids might be chosen in someone who has had a stroke or heart attack in the past 3 months because of possible complications from anti-VEGF treatments in these patients, Dr. Gillies added. “We’re unsure what the actual risk is.”
Fourth, if the patient is about to have a cataract removed and has DME, steroids can more quickly diminish the swelling, he said.
On the other hand, he acknowledged that bevacizumab may not be the most potent anti-VEGF treatment.
“With aflibercept or ranibizumab, we might have had a better effect in favor of the VEGF inhibitor,” he said.
Mark Gillies, MBBS, PhD
This article was adapted from Dr. Gillies’ presentation during Retina Subspecialty Day at the 2015 meeting of the American Academy of Ophthalmology. Dr. Gillies did not indicate any proprietary interest in the subject matter.