Intravitreal bevacizumab injection alone or combined with triamcinolone versus macular photocoagulation in bilateral diabetic macular edema; application of bivariate generalized linear mixed model with asymmetric random effects in a subgroup of a clinical trial

Abstract

Purpose: To compare the efficacy of intravitreal bevacizumab (IVB) injection alone or with intravitreal triamcinolone acetonide (IVB/IVT) versus macular photocoagulation (MPC) in bilateral diabetic macular edema (DME).

Methods: In this study we revisited data from a subset of subjects previously enrolled in a randomized clinical trial. The original study included 150 eyes randomized to three treatment arms: 1.25 mg IVB alone, combined injection of 1.25 mg IVB and 2 mg IVT, and focal or modified grid MPC. To eliminate the possible effects of systemic confounders, we selected fellow eyes of bilaterally treated subjects who had undergone different treatments; eventually 30 eyes of 15 patients were re-evaluated at baseline, 6, 12, 18, and 24 months. Using mixed model analysis, we compared the treatment protocols regarding visual acuity (VA) and central macular thickness (CMT).

Results: Improvement in VA in the IVB group was significantly greater compared to MPC at months 6 and 12 (P = 0.037 and P = 0.035, respectively) but this difference did not persist thereafter up to 24 months. Other levels of VA were comparable at different follow-up intervals (all P > 0.05). The only significant difference in CMT was observed in favor of the IVB group as compared to IVB/IVT group at 24 months (P = 0.048).

Conclusion: Overall VA was superior in IVB group as compared to MPC up to 12 months. Although the IVB group showed superiority regarding CMT reduction over 24 months as compared to IVB/IVT group, it was comparable to the MPC group through the same period of follow up.

Keywords: Asymmetric Random Effects; Bivariate Generalized Linear Mixed Model; Diabetic Macular Edema.

Figure 1

Flowchart for enrolled subjects throughout the trial.

Figure 2

Mean best-corrected visual acuity changes in relation to baseline values in the logarithm of the minimum angle of resolution notations in the three groups at different time points. IVB, intravitreal bevacizumab injection; IVB/IVT, IVB/intravitreal triamcinolone injection; MPC, macular photocoagulation; BCVA, best-corrected visual acuity; logMAR, logarithm of the minimum angle of resolution.

Figure 3

Mean central macular thickness changes in relation to baseline values in micron in the three groups at different time points. IVB, intravitreal bevacizumab injection; IVB/IVT, IVB/intravitreal triamcinolone injection; MPC, macular laser photocoagulation; CMT, central macular thickness.