Intravitreal Steroids Show Benefit in Diabetic Retinopathy

Intravitreal Steroids Show Benefit in Diabetic Retinopathy
Intravitreal triamcinolone acetonide reduced progression of diabetic retinopathy more than laser photocoagulation, analysis of data from a randomized trial found.
The cumulative probability of progression from nonproliferative to proliferative diabetic retinopathy at two years was:
• Photocoagulation, 31%
• 1 mg triamcinolone, 29%, P=0.64 compared with the laser group
• 4 mg triamcinolone, 21%, P=0.005 compared with the laser group
Still, corticosteroids cannot be recommended at this time because of the exploratory nature of this analysis and the heightened risk of glaucoma and cataracts, Neil M. Bressler, MD, of Johns Hopkins, and colleagues wrote in the December Archives of Ophthalmology.
Panretinal photocoagulation "markedly reduces" the rate of vision loss in diabetic patients with retinopathy when performed when the eye reaches the threshold for high risk (having three or four high-risk characteristics).
However, the procedure can result in adverse outcomes, such as macular edema with visual loss, and close observation is needed for timely implementation. An alternative treatment therefore would be desirable, the investigators said.
Numerous basic scientific findings support the hypothesis that treatment with an anti-inflammatory agent, such as a steroid, could reduce the risk of retinal neovascularization and progression to the high-risk threshold.
For example, steroids exhibit antiangiogenic properties, and they can downregulate vascular endothelial growth factor.
To test their hypothesis, Bressler and colleagues analyzed data from a randomized trial conducted by the Diabetic Retinopathy Clinical Research Network that included 840 eyes in 693 patients, divided almost evenly by gender.
Participants' mean age was 63 years. Some 95% had type 2 diabetes.
Eyes were randomized to focal/grid photocoagulation or triamcinolone acetonide in a dose of 1 mg or 4 mg as often as every four months.
The original study's primary finding was that photocoagulation was more effective at two years, and had fewer side effects than either 1 mg or 4 mg of triamcinolone in the treatment of diabetic macular edema.
In the exploratory analysis, patients were considered to have had progression if they experienced vitreous hemorrhage, worsening of two or more levels on the diabetic retinopathy scale, or the decision was made to proceed with photocoagulation.
The one-year cumulative progression was:
• Photocoagulation, 21%, P=0.71
• 1 mg triamcinolone, 19%, P=0.03
• 4 mg triamcinolone, 14%, P=0.08
And the three-year cumulative progression was:
• Photocoagulation, 37%, P=0.73
• 1 mg triamcinolone, 35%, P=0.02
• 4 mg triamcinolone, 30%, P=0.07
The investigators noted that during the second year most eyes randomized to the steroid groups did not receive the drug as often as every four months, and fewer than half received the drugs at all during the third year because the study had been closed.
"Theoretically, it is possible the reduction in risk of retinopathy progression may have been even greater if intravitreal triamcinolone had been given more frequently," they wrote.
On the other hand, they suggested, the injections may have been discontinued because the retinopathy was less severe, edema had resolved, and the eyes were generally healthier.
They pointed out that interpretation of the results must be tempered by recognition of the higher rates of cataract extraction at two and three years, respectively, with steroid treatment:
• Photocoagulation, 13% and 21%
• 1 mg triamcinolone, 23% and 35%
• 4 mg triamcinolone, 51% and 64%
Strengths of the investigation include the prospective collection of data and randomization of treatment. Also, some patients had one eye randomized to laser treatment and the other to steroids, which would control for systemic factors that could influence progression.
But the investigators noted that the study also has weaknesses: It was not designed to investigate the progression of retinopathy, data for many patients were censored before completion of the study, and comparative progression of retinopathy was not a primary or secondary outcome of the original design.
Therefore, despite the potential benefits of corticosteroid treatment, investigators concluded that it is not warranted at this time because of the risks, although further investigation of the pharmacotherapy does appear warranted.
"Any treatment to be used routinely to prevent [proliferative diabetic retinopathy] likely needs to be relatively safe because the condition already can be treated successfully and safely with [panretinal photocoagulation]," they wrote.
The study was funded by the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.
Bressler has received research grants from multiple pharmaceutical companies, including Allergan. Financial disclosures for all Diabetic Retinopathy Clinical Research Network investigators is available on the group's public Web site, at http://public.drcr.net/FinDisclosures.aspx.