Directed Therapy: An Approach to the Improved Treatment of Exfoliation syndrome.

Exfoliation syndrome (XFS) is an age-related, generalized disorder of the extracellular matrix characterized by the production and progressive accumulation of a fibrillar extracellular material in many ocular tissues and is the most common identifiable cause of open-angle glaucoma worldwide. Exfoliation syndrome plays an etiologic role in open-angle glaucoma, angle-closure glaucoma, cataract, and retinal vein occlusion. It is accompanied by an increase in serious complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss. It is associated systemically with an increasing number of vascular disorders, hearing loss, and Alzheimer's disease. Exfoliation syndrome appears to be a disease of elastic tissue microfibrils. Directed therapy simply means devising specific treatments for specific diseases. There was little incentive to attempt to distinguish between various open-angle glaucomas if the treatments were essentially the same. However, this view also prevented the application of directed therapy in those instances in which such was available and applicable. Pilocarpine has multiple beneficial actions in eyes with XFS. Not only does it lower IOP, but by increasing aqueous outflow, it should enable the trabecular meshwork to clear more rapidly, and by limiting pupillary movement, should slow the progression of the disease. Theoretically, miotics should be the first line of treatment. Pilocarpine 2% q.h.s. can provide sufficient limitation of pupillary mobility without causing these side effects. In 2007, two common single nucleotide polymorphisms in the coding region of the lysyl oxidase-like 1 (LOXL1) gene located on chromosome 15 were specifically associated with XFS and XFG. LOXL1 is a member of the lysyl oxidase family of enzymes, which are essential for the formation, stabilization, maintenance, and remodelling of elastic fibers and prevent age-related loss of elasticity of tissues. LOXL1 protein is a major component of exfoliation deposits and appears to play a role in its accumulation and in concomitant elastotic processes in intra- and extraocular tissues of XFS patients. This discovery should open the way to new approaches and directions of therapy for this protean disorder.