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JAMA Ophthalmol. 2013 Mar;131(3):335-40. doi: 10.1001/jamaophthalmol.2013.818.

Progression of lesion size in untreated eyes with exudative age-related macular degeneration: a meta-analysis using Lineweaver-Burk plots.

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Edward Harkness Eye Institute, Department of Ophthalmology, Columbia University College of Physicians and Surgeons, New York, NY, USA.



To test the hypothesis that the natural history of choroidal neovascularization lesion size is uniform across prior randomized controlled clinical trials of exudative age-related macular degeneration (AMD), with apparent differences arising from different entry times of eyes into clinical trials.


We conducted a retrospective meta-analysis of control eye data from 5 age-related macular degeneration trials (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy; Verteporfin in Photodynamic Therapy; VEGF Inhibition Study in Ocular Neovascularization; Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration; and Phase 3b, Multicenter, Randomized, Double-masked, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab in Subjects with Subfoveal Choroidal Neovascularization with or without Classic Choroidal Neovascularization Secondary to AMD Study), which were plotted on a double reciprocal plot of 1 / lesion size (disc area) vs 1 / time (months after enrollment). To account for the different entry times, we introduced a horizontal translation factor to shift each data subset until r2 was maximized for the cumulative trend line.


Cumulative data for untreated control eyes fit a straight line on a double reciprocal plot (r2 = 0.98) after the introduction of horizontal translation factors. Our model predicts that a choroidal neovascular lesion will eventually enlarge to a size of 10.6 disc areas without treatment and that the lesion will reach half of its maximum size within 14.0 months after onset of exudation. The linear expansion rate of untreated lesions is approximately 26.0 μm per day for the smallest lesions and decreases gradually as the lesions enlarge.


The pattern of choroidal neovascularization lesion size enlargement in AMD eyes is uniform across a wide range of clinical trials, with apparent differences arising from different entry times of patients into various trials. The main determinant of choroidal neovascularization lesion size enlargement is the duration of exudative disease.

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