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L. V. Del Priore, O. Biscette, A. Shah; Mathematical Modeling of the Effects of Ranibizumab on Visual Acuity in Subfoveal Exudative AMD: Evidence for a Biphasic Response. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3351.
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To use double reciprocal (Lineweaver-Burke) plots to examine the nature and time course of the treatment effect of ranibizumab in patients with subfoveal choroidal neovascularization in age related macular degeneration (AMD), and to determine whether long-term visual acuity predictions can be made from the available data.
Previously published visual acuity data from the ANCHOR and the MARINA trials were plotted on a double reciprocal plot of 1/ [letters lost] versus 1/ [months of treatment]; number of letters lost was based on a visual acuity score of 85 letters = 20/20 on a Bailey-Lovie chart. A horizontal translation factor (expressed in months) was added to shift the control data subset horizontally in order to maximize the correlation coefficient (r2) and the best polynomial fit was then determined.
For untreated control eyes in the MARINA trial, 1/ [letters lost] versus 1/time fits a straight line with a high correlation efficient (r2 =0.9958); 24 month MARINA treatment data suggests that after an initial improvement in vision (slope = - 0.0886), there is a slight decline in the visual acuity with a slightly lower slope than untreated controls (slope = 0.0536 vs. control slope = 0.1103). Extrapolation reveals that the final visual acuity would approach 64.2 letters if the treatment effect did not decrease as a function of time; continued treatment with ranibizumab could be expected to achieve a final average visual acuity score of 59.3. For PDT treated (control) eyes in the ANCHOR trial, 1/ [letters lost] versus 1/time fits a straight line with a high correlation efficient (r2 =0.9192); 12 month ANCHOR TRIAL data suggests that after the initial improvement in visual acuity (slope = -0.5588), the visual acuity in treated eyes continues to improve but with slowing of this response (slope = -0.0235). Extrapolation reveals that the final visual acuity would approach 73.8 letters if the initial treatment effect was maintained; continued treatment with ranibizumab achieves a final average visual acuity score of 58.8 letters.
The effect of ranibizumab treatment on visual acuity appears to have 2 distinct phases; namely, an initial moderate improvement in visual acuity over the first few months followed by a decline in the rate of visual improvement for minimally classic or occult lesions and starting at 1.4 months for predominantly classic lesions. With sufficient long term data we may be able to make accurate visual acuity predictions using our model.
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