Table 1. Characteristics of the 68 patients included in the study. Patient characteristics (n = 68) Subcategory Age (mean6SD) Gender Patients with diabetes Degree of neovascularization Degree of haemorrhage Degree of fibrosis CTGF (geom. mean, 95% CI) VEGF (geom. mean, 95% CI) Ratio CTGF/log10(VEGF) Male Female Total Type I Type II No neovascularization (0) Quiescent neovascularization (1) Active neovascularization (2) No haemorrhage (0) Media little clouded (1) Disc obscured (2) No fundus detail visible (3) No fibrosis (0) Only a few pre-retinal membranes (1) Some proliferative membranes (2) Abundant proliferative membranes (3) 15 21 0 36 36 13 23 15 17 32 16 16 2 11 19 11 4 11 6 0 2 17 13 Angio-Fibrotic Switch Macular hole (n = 13) Macular pucker (n = 23) 66?4614?6 PDR (n = 32) 54?2612?7 13?0 ng/ml [10.8–15.3] 123 pg/ml [95–159] 3.42 [2.7–4.2] 24.1 ng/ml [20.5–27.7] 776 pg/ml [566–1065] 6.2 [5.3–7.1] The Spearman correlation coefficient for CTGF and log10(- VEGF) levels was 0.4 (p = 0.01). Age, gender, degree of haemorrhage did not show an association with CTGF or log10(VEGF) levels (p.0.05). In a separate analysis, an ordinal logistic regression model with degree of fibrosis as dependent (outcome) variable was used to sort out the strongest predictive variable for fibrosis. Univariate ordinal logistic regression model analysis (Table 2) showed that vitreous levels of CTGF and CTGF/log10(VEGF) ratios were associated with fibrosis. The association was not found between log10(VEGF) levels and degree of fibrosis but it was found between log10(VEGF) levels and degree of neovascularization. In a multifactorial model with both CTGF and log10(VEGF) levels as predictors for degree of fibrosis, both CTGF (p = 0.008) and log10(VEGF) (p = 0.033) were associated with degree of fibrosis: CTGF associated positively with an odds ratio of 1.19 (95% CI: 1.05–1.36) whereas log10(VEGF) levels showed a negative association with an odds ratio of 0.06 (95% CI: 0.01–0.80). These findings explain the strong association between CTGF/log10(- VEGF) ratios and fibrosis in the univariate analysis. Clinical course of proliferative retinopathy after laser or anti-VEGF treatment In each of the 4 cases of PDR, we observed a transition from pre-retinal angiogenesis to a temporary phase of progressing pre- retinal fibrosis after pan-retinal laser treatment, or after anti- VEGF treatment followed by pan-retinal laser (Figure 3). In the case of branch retinal vein occlusion complicated by local pre- retinal angiogenesis with leaky vessels due to ischemia, the new Abbreviations: PDR, proliferative diabetic retinopathy; SD, standard deviation; VEGF, vascular endothelial growth factor; CTGF, connective tissue growth factor. doi:10.1371/journal.pone.0002675.t001 Figure 1. Correlation between the levels of CTGF and log10(VEGF) in the vitreous of all 68 patients. A significant (p = 0.01) Spearman’s rank correlation (r = 0.4) within all samples was found. doi:10.1371/journal.pone.0002675.g001 PLoS ONE | www.plosone.org 3 July 2008 | Volume 3 | Issue 7 | e2675