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| |  Variations in Biomarker Levels in Human Vitreous May Explain Differences in Response to Therapy With Anti-Vascular Endothelial Growth Factor: Presented at ARVO By Cameron Johnston FT. LAUDERDALE, Fla -- May 8, 2009 -- A biomarker measured in the vitreous of patients with macular degeneration as well as in other patients with diabetic retinopathy demonstrates distinct biochemical activities in these 2 diseases that may lead to different inflammatory responses and explain why not all patients have the same response to treatment, researchers suggested here at the Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting. There are considerable variations in the levels of vascular endothelial growth factor (VEGF) in the vitreous of patients with age-related macular degeneration (AMD) compared with patients who have diabetic retinopathy (DR), explained lead investigator, Albert Augustin, MD, Augenklinik, Karlsruhe University, Karlsruhe, Germany, speaking here at a presentation on May 3. VEGF concentrations among patients with AMD may range from less than 10,000 pg/mL to over 225,000 pg/mL, whereas, among patients with DR, the range is less extreme -- from approximately 20,000 to 90,000 pg/mL. In the current study, the differences in VEGF concentrations in both groups were significantly greater than those seen in patients with macular holes and macular pucker who served as controls. There are also differences in the levels of myeloperoxidase (MPO), a pro-inflammatory enzyme, which is converted into a highly potent oxidative molecule in patients with each condition, Dr. Augustin stated. The levels of this enzyme correlate closely with lesion size in patients with AMD. The samples of MPO were derived from vitreous samples taken from 31 treatment-naïve patients with AMD. Dr. Augustin presented data from an ongoing study of 152 patients who were treated with reduced light-dose photodynamic therapy (rPDT) together with bevacizumab (1.50 mg) and a corticosteroid, and followed for a mean of 74 weeks. These patients received 70 seconds of rPDT at 42 J/cm2. Sixteen hours later, they received intravitreal injections of either dexamethasone or triamcinolone. Baseline visual acuity was 0.802 logMAR (logarithm of the minimum angle of resolution), and at follow-up was 0.59 logMAR. This represents a mean improvement of 2.07 lines or 10.35 Early Treatment Diabetic Retinopathy Study letters (P < .01). Retinal thickness also decreased by a mean of 167 microns (P < .01). This analysis demonstrates that there are different biochemical processes at work in both DR and AMD. Greater variability is shown in the expression of VEGF -- one of the main stimulators of endovascular proliferation -- between patients with AMD compared with those with DR. While the MPO variations seen between the 2 groups were not as remarkable, noted Dr. Augustin, those variations were still associated with differences in lesion size. Overall, the authors concluded, this research may help explain why some patients respond differently to therapy than others -- because anti-VEGF drugs such as ranibizumab and bevacizumab will be less effective among patients who have lower levels of VEGF in the vitreous. For this reason, combination therapy with an anti-VEGF drug plus photodynamic therapy and a corticosteroid may be more beneficial than monotherapy in treating AMD; each of the components in combination therapy attacks a different part of the disease process and therefore the treatment is more complete. A larger prospective trial should be conducted to determine whether this theory holds true in clinical practice, Dr. Augustin added.
[Presentation title: Intravitreal VEGF Values and Inflammatory Parameters - Rationale and Clinical Results of an Individualized Combination-Treatment of Wet AMD. Abstract 953-D839]
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