Investigating the Genetic Basis of Pseudoexfoliation Syndrome, Angle-closure Glaucoma and Primary Open-angle Glaucoma

Overview

There is increasing evidence that there are genetic risk factors for several forms of glaucoma, such as glaucoma caused by pseudoexfoliation syndrome (PXF) ,primary angle closure glaucoma (PACG) and primary open-angle glaucoma (POAG). The aim of the present prospective, multi-center, case-control study is to identify susceptibility genes/loci for PXF, PACG and POAG using a whole genome association (WGA) approach.

Description

As worldwide populations become older because of shifts in demography, PXF may become a matter of greater concern. The search for genes responsible for PXF may lead to the identification of key molecules in pathways critical to the normal functioning of the eye. A better understanding of normal eye function may in turn lead to more accurate diagnosis and prognosis of ocular development, and inevitably to the emergence of novel classifications based on knowledge of the molecular pathology. Such knowledge may lead to more rational disease classification, better diagnostic tests, and improved prognostic accuracy. This is of particular relevance to PXF since there is a shortage of early reliable diagnostic tests and much evidence that the early commencement of treatment can arrest progressive asymptomatic loss of vision due to PXF-related glaucoma.

The search for genes responsible for PACG may lead to the identification of key molecules in pathways critical to the normal development of the eye. A better understanding of eye development may in turn lead to more accurate diagnosis and prognosis of ocular development, and inevitably to the emergence of novel classifications based on knowledge of the molecular pathology. Such knowledge may lead to more rational disease classification, better diagnostic tests, and improved prognostic accuracy. This is of particular relevance to glaucoma since there is a shortage of early reliable diagnostic tests and much evidence that the early commencement of treatment can arrest progressive asymptomatic loss of vision for which the disease is renowned.

Identification of responsible genes for POAG development can on one hand broaden our knowledge on disease pathophysiology and on the other hand open new doors in the search for pharmacological disease modification. Especially the latter is urgently needed as IOP has for many years been the only pharmacological target and fails to prevent disease progression in a certain proportion of POAG patients.

Eligibility

Inclusion Criteria:

1. For patients with PXF:
   • Patients with confirmed pseudoexfoliation syndrome (exfoliation glaucoma / pseudoexfoliation of the lens) in the medical history
   • Informed consent
   • Age 50 years or more
2. For patients with PACG:
   • Patients with confirmed acute primary angle closure (PAC) or primary angle closure glaucoma (PACG) in the medical history
   • Informed consent
   • Age 21 years or more
3. For healthy controls:
   • No evidence of PXF, glaucoma or uveitis during clinical examination or in the medical history
   • No evidence of major ocular disease such as diabetic retinopathy, age related macular degeneration or conditions with genetic background during clinical examination or in the medical history
   • Age more than 60 years
   • Informed consent
4. For patients with POAG:
   • Patients with confirmed primary open angle glaucoma (POAG)
   • No evidence of exfoliation glaucoma / pseudoexfoliation of the lens or pigment glaucoma
   • Informed consent
   • Age 30 or more

Exclusion Criteria:

• Patients and subjects will be excluded if one or more of the following criteria

  apply

• Neovascular glaucoma
• Active or history of uveitis
• Secondary angle closure such as neovascular glaucoma or uveitis/inflammatory eye disease
• Inability to give informed consent