Subramanian Venkatraman

Effects of controlled-released sirolimus from polymer matrices on human coronary artery smooth muscle cells.

Sirolimus-loaded bi-layer polymer matrices were fabricated and the effects of sirolimus release on proliferation and viability of human coronary artery smooth muscle cells (cSMCs) were investigated. Human cSMC recovery after sirolimus treatment and the attachment of human cSMC to sirolimus-eluting films were also studied. It was found that the released sirolimus inhibited growth factor stimulated human cSMC proliferation successfully. However, different drug doses appeared to have the same effect in the extent of inhibition of proliferation in this study. Cell viability was also observed to decrease with the presence of sirolimus and the attachment to sirolimus-eluting films was inhibited. The recovery of human cSMCs was found to be related to the duration of inhibition time by sirolimus. Longer inhibition resulted in a slower recovery, which suggests that sustained release is more effective than rapid release of a higher amount in the inhibition of cSMC proliferation. This observation may be important for the design of a drug-eluting stent.

Randomized, Controlled Trial of a Sustained Delivery Formulation of 5-Fluorouracil for the Treatment of Failing Blebs

PURPOSE To determine the efficacy of a subconjunctival injection of hyaluronic acid (HA) with 5-fluorouracil (5FU) formulation as an adjunct in reviving bleb function by needling. DESIGN Prospective, randomized, controlled trial. PARTICIPANTS Fifty patients with previous trabeculectomy and scheduled by the managing physician for a needling intervention. METHODS One eye of each patient was randomized to receive needling with HA-5FU mixture or needling with subconjunctival injection of 5FU solution alone. MAIN OUTCOME MEASURES The primary outcome was the percentage of subjects with an intraocular pressure (IOP) <15 mmHg without any medications at 3 months. Secondary outcomes included the need for additional needling procedures and changes in bleb morphology. RESULTS Forty-nine subjects (25 in the HA-5FU group and 24 in the 5FU group) completed 3 months of follow-up. At baseline, there was no significant difference between the groups in terms of demographic features, subtype of glaucoma, vertical cup-to-disc ratio, or visual field indices. The mean number of glaucoma medications at baseline was higher in the 5FU group (0.8±1.1 [mean ± standard deviation] vs. 0.2±0.6, P = 0.04). An IOP <15 mmHg without medications was reached in 48.0% of subjects in the HA-5FU group and in 33.3% of subjects in the 5FU group (P = 0.2). At 3 months, both groups demonstrated a significant decrease in IOP from baseline (HA-5FU: decrease of 5.9 mmHg [95% confidence interval, 3.4-8.4]; 5FU: decrease of 6.0 mmHg [95% confidence interval, 3.2-8.2]; P<0.001 for both). Intergroup comparisons for IOP change from baseline was not significant (P = 0.9). However, repeat needling was required more frequently in the 5FU group compared with the HA-5FU group (50.0% vs. 12.0%; P = 0.004). There were no significant differences in the number of reported adverse events, bleb vascularity, or morphology between the 2 groups. CONCLUSIONS Subconjunctival injection of HA-5FU to revive bleb function after bleb needling is as effective as 5FU solution. Fewer repeat needlings were required after treatment with HA-5FU, suggesting that the use of a combined formulation of HA-5FU may improve the overall outcomes of bleb needlings.