Abstract
Purpose: :
Age related macular degeneration is a complex disorder with a multifactorial aetiology. An increasing body of evidence is gathering which implicates low grade systemic inflammation as having an important role in the pathophysiology of the disease. At a local level , structural changes in Bruch’s membrane contribute to neovascular AMD. Extracellular matrix dysregulation, due to aberrant activity of matrix metalloproteinases (MMP's) and their inhibitors plays a role in this pathology. Previous studies have demonstrated a significant difference in MMP activity at a local and systemic level in disease compared to controls. We therefore wanted to evaluate if serum MMP profile can be used to predict disease state.
Methods: :
Two hundred and forty eight Caucasian patients were recruited. Classification of the cohort by disease state (controls, drusen and neovascular age related macular degeneration) was made by biomicroscopy and fundal photography. Serum samples from the cohort were analysed to determine the MMP profile (seven MMP’s, three TIMPS’s) using a human MMP protein array.
Results: :
Discriminant analysis was used to build a "model" that could best predict to which group (AMD, drusen, control) a case belongs. Using all cases in the study the whole panel of MMP/TIMP was used to group cases into healthy controls, AMD or drusen. The MMP/TIMP panel correctly classified 45% of AMD cases.Using a stepwise model with MMP 8, TIMP1 and TIMP 2 retained 65% of AMD cases were correctly classified with a positive predictive value of 73.2%
Conclusions: :
Neovascular AMD remains a devastating disease for many,despite the arrival of new modalities of treatment. Genetic and environmental risk factors have been identified for the disease. A number of studies have developed models using these factors as variables in risk and classification based analyses.From previous work, serum MMP levels, have been found to correlate with disease and from this study discriminates effectively. Further work needs to be done to assess if modelling including genetic, environmental variables and MMP profile improves on discriminative ability.
Keywords: age-related macular degeneration • retina • Bruch's membrane