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L. V. Del Priore, A. R. Shah; Combination Therapy of Ranibizumab + PDT Is Not Superior to Ranibizumab Alone: A Meta Analysis Using Lineweaver-Burke Plots. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1171.
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Recently the FOCUS trial showed that final visual acuity score (VAS) for exudative AMD patients treated with ranibizumab + photodynamic therapy (PDT) is better than PDT alone after 12-months. However, it is not known if ranibizumab 0.5 mg + PDT therapy ([ran + PDT]) is superior to ranibizumab alone. Herein we use a post-hoc treatment analysis using Lineweaver-Burke (LB) double reciprocal plots to determine if [ran + PDT] is better than ranibizumab in exudative AMD eyes; this technique has previously been used to demonstrate that the rate of visual loss in untreated control eyes is uniform across clinical trials after adjusting for time of entry into studies.
Visual acuity data from the ANCHOR, MARINA, FOCUS, TAP, and VIP studies were plotted on LB plots against cumulative control data. Best fit lines were determined for each treatment after adjusting for the time of entry into clinical trials; vertical translations were performed to determine the likely outcome if all treatments were initiated at the same visual acuity.
There is a strong correlation between 1/Letters Lost versus 1/Time on a LB plot for PDT (r2 = 0.929 - 1.00), ranibizumab 0.5 mg (r2 = 0.648 - 0.715), ranibizumab 0.3 mg (r2 = 0.715 - 0.728), and [ran + PDT] (r2 = 0.747). Ranibizumab 0.5 mg alone and [ran + PDT] have negative slopes implying their ability to improve vision; PDT alone reduces the rate of visual loss when compared to untreated controls. There is excellent agreement amongst different clinical trials in the relative efficacy of each agent. If treatment is initiated at a VAS of 50 letters (Bailey-Lovie) the expected VAS at 12 months for PDT alone ranges from 46.0 - 47.0 letters read; for ranibizumab 0.5 mg from 52.1 - 53.8 letters read; for ranibizumab 0.3 mg from 51.8 - 52.9 letters read; and for [ran + PDT] is approximately 51.7 letters read. [Ran + PDT] is better than PDT alone and untreated controls (45.6 letters read), but underperforms ranibizumab alone.
For each treatment type there is minimal scatter in the data suggesting consistency in the efficacy of individual treatments (PDT alone, ranibizumab alone) amongst different clinical trials. [Ran + PDT] does not lead to a better visual acuity score than ranibizumab alone. Randomized controlled studies of [ran + PDT] to ranibizumab alone are warranted.
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