Rapamycin exerts positive effect on diabetic macular edema

June 28, 2008

Intravitreal and subconjunctival injections of rapamycin (Sirolimus, Wyeth) are both effective against diabetic macular edema. Interestingly, the subconjunctival route had a greater beneficial effect and the lower doses were more effective, said Mark Blumenkranz, MD, professor and chairman, Department of Ophthalmology, Stanford University, Stanford, CA.

Intravitreal and subconjunctival injections of rapamycin (Sirolimus, Wyeth) are both effective against diabetic macularedema. Interestingly, the subconjunctival route had a greater beneficial effect and the lower doses were more effective, saidMark Blumenkranz, MD, professor and chairman, Department of Ophthalmology, Stanford University, Stanford, CA.

A study in rabbits showed that the drug had sustained delivery in the retinal and choroidal tissue, which prompted phase Itrials of the subconjunctival and intravitreal injections in human diabetic macular edema, he explained.

Phase I trials indicated that the drug has a positive safety profile with no serious adverse events, toxicity, or elevatedIOP, and importantly no immunosuppressive effects. In the patients who received the intravitreal injection,the doses ranged from 44 to 352 micrograms, and in the patients who received a subconjunctival injection, the doses rangedfrom 220 to 1,760 micrograms.

In both groups, the visual acuity increased by about four letters and the macular thickness decreased by about 50 µm. Inthe patients who received the subconjunctival injection the results were slightly better and the lowest dose produced thebest result. Surprisingly, the effect was sustained through 6 months after one subconjunctival injection as evidenced byresolution of a macular cyst 180 after the injection, Dr. Blumenkranz demonstrated.

"The formulation of rapamycin was clinically safe, there was negligible systemic exposure, and both types of injections wereeffective, but the subconjunctival injection was more so," Dr. Blumenkranz said. "We are optimistic about the potential ofthis drug in diabetic macular edema. The effect of the drug on choroidal neovascularization is also going to be studied."