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

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.

Study Overview

• Status: Recruiting
• Conditions: Glaucoma
• Intervention / Treatment: Other: Blood sample

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Gerhard Garhöfer; Phone Number: 0140 400 29880; Email: gerhard.garhoefer@meduniwien.ac.at
• Study Contact Backup: Name: Doreen Schmidl; Phone Number: 0140 400 29880; Email: doreen.schmidl@meduniwien.ac.at

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Recruiting
    • Department of Clinical Pharmacology, Medical University of Vienna
    • Contact: Doreen Schmidl, MD; Phone Number: 29880 00431 40400; Email: doreen.schmidl@meduniwien.ac.at
    • Contact: Gerhard Garhofer, MD; Phone Number: 29810 00431 40400; Email: gerhard.garhoefer@meduniwien.ac.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 105 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

1. Normal Healthy group
2. Patients with Pseudoexfoliation Glaucoma
3. Patients with Angle closure Glaucoma
4. Patients with Primary open-angle Glaucoma

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls; Healthy subjects with age more than 60 years	Other: Blood sample; Blood sample
Pseudoexfoliation Glaucoma; Already diagnosed Pseudoexfoliation glaucoma patients with age more than 50 years	Other: Blood sample; Blood sample
Angle closure Glaucoma; Already diagnosed Angle closure Glaucoma patients with age more than 21 years	Other: Blood sample; Blood sample
Primary open-angle Glaucoma; Already diagnosed primary open-angle glaucoma with age more than 30 years	Other: Blood sample; Blood sample

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genetic markers	To identify the genetic markers in a whole genome association screen which show very strong association with PXF, ACG and POAG. The genomic regions identified from the above analyses will be analyzed using high density single nucleotide polymorphism (SNP) chips and/or sequencing of positional candidate genes to identify causal variants.	1 day

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Gerhard Garhöfer, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2017
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 23, 2025
• Last Update Submitted That Met QC Criteria: May 20, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Pseudoexfoliation Glaucoma, Angle block glaucoma, Primary Open-Angle Glaucoma, Genetic
• Additional Relevant MeSH Terms: Eye Diseases; Uveal Diseases; Ocular Hypertension; Iris Diseases; Glaucoma; Glaucoma, Open-Angle; Exfoliation Syndrome; Glaucoma, Angle-Closure
• Other Study ID Numbers: OPHT-271016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No