Gene Polymorphisms of Corticosteroid-induced Ocular Hypertension

NCT03250819 | Completed

• 1 other identifier: NL58992.068.17
• Study Type: observational
• Target: 370
• Locations: 1 country
• Sites: 1

Brief Summary

Glaucoma is one of the most prevalent eye diseases and the second most common cause of blindness worldwide. The most common form is primary open angle glaucoma (POAG). Glaucoma is a slowly progressing neuropathy of the optic nerve that causes loss of visual field and eventually blindness. Elevated intra-ocular pressure (IOP) is the most important risk factor. Corticosteroids, which are often used for the treatment of many diseases in ophthalmology and other specialities, may cause an elevation of the IOP. It is estimated that corticosteroids induce ocular hypertension in approximately 18%-36% of the general population and in patients with POAG this percentage can be as high as 92%. When the treatment is sustained, this can cause a glaucomatous neuropathy of the optic nerve (corticosteroid-induced glaucoma). The precise pathogenic mechanism isn't clear yet. Genetic factors are likely to affect the susceptibility to corticosteroid response. Therefore, an overview of the genetic mechanisms of corticosteroid-induced glaucoma can give more insight in the pathogenesis. In this study the researchers investigate the occurrence of SNPs (single nucleotide polymorphisms) in 150 cases with a steroid-response in comparison with 300 controls exposed to corticosteroids without a steroid-response. Up to now, one small GWAS has been conducted comparing 32 patients with and without corticosteroid-induced ocular hypertension after treatment with intravitreal triamcinolone. In this study, two SNPs proximal of the transcriptional start site (near the 5') of HCG22 on chromosome 6 were identified. However, this is a rather small sample population and the investigators didn't match for the underlying disease. Further, in another small study, Hogewind et al. performed SNP analysis in multiple genes (SFRS3, FKBP4, FKBP5, and NR3C1) in corticosteroid-induced ocular hypertension. This study enables the investigators to identify patients at risk for developing corticosteroid-induced glaucoma and to gain a better insight in the pathogenesis. This may also lead to the discovery of biomarkers that indicate an increased risk of developing a steroid-induced glaucoma and new prevention and treatment strategies, which are necessary as the treatment of corticosteroid induced-glaucoma now only focuses at lowering the IOP and can still be challenging.

Conditions

Corticosteroid Induced Ocular Hypertension/Glaucoma

Outcome Measures

Primary Outcomes (1)

• Differences in SNP's in corticosteroid responders and non-responders

  What are the differences in SNPs in patients with corticosteroid-induced ocular hypertension in comparison with patients exposed to corticosteroids who do not respond with an IOP increase

  At the time of inclusion

Study Arms (2)

Corticosteroid responders

Patients who develop an increase in eye pressure after the use of corticosteroids

Other: SNP analysis

Non-corticosteroid responders

Patients who use/used corticosteroids but didn't develop an increase in eye pressure

Other: SNP analysis

Interventions

SNP analysis OTHER

The collected blood samples will be used to investigate the occurrence of SNPs (single nucleotide polymorphisms) in both study groups

Corticosteroid responders; Non-corticosteroid responders

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients who started topical, intravitreal or subconjunctival corticosteroids will be included at the University Eye Clinic Maastricht of the Maastricht University Medical Centre+, the Netherlands. The participants will be divided in two groups: cases who are corticosteroid responder (n=150) and controls exposed to corticosteroids who did not respond with an IOP increase (n=300).

You may qualify if:

• Use of corticosteroids:
• Patients treated with Ozurdex (an intravitreal dexamethasone implant
• Patients treated with subconjunctival Triamcinolone/ Celestone injections
• Patients treated with corticosteroids after a corneal surgery
• Patients treated with corticosteroids after a refractive surgery
• Patients treated with corticosteroids after a cataract surgery
• Patients treated with corticosteroids for macular edema
• Patients exposed to corticosteroids for other diseases such as uveitis
• When using topical corticosteroids, time of use \> 3 months
• Age \> 18 year and mentally competent
• Patient from the Maastricht University Medical Centre+ (MUMC+), the Netherlands

You may not qualify if:

• Age \< 18 year
• Mentally not able to participate or give permission
• Not able to communicate in Dutch
• Patients with a type of uveitis that might cause a decrease of the IOP
• When using topical corticosteroids, time of use \< 3 months.

Sponsors & Collaborators

• Maastricht University Medical Center: lead

Study Sites (1)

University Eye Clinic Maastricht, Maastricht UMC+

Maastricht, Limburg, 6229 HX, Netherlands

Location

Related Publications (2)

• Jeong S, Patel N, Edlund CK, Hartiala J, Hazelett DJ, Itakura T, Wu PC, Avery RL, Davis JL, Flynn HW, Lalwani G, Puliafito CA, Wafapoor H, Hijikata M, Keicho N, Gao X, Argueso P, Allayee H, Coetzee GA, Pletcher MT, Conti DV, Schwartz SG, Eaton AM, Fini ME. Identification of a Novel Mucin Gene HCG22 Associated With Steroid-Induced Ocular Hypertension. Invest Ophthalmol Vis Sci. 2015 Apr;56(4):2737-48. doi: 10.1167/iovs.14-14803.

  PMID: 25813999 BACKGROUND

• Fini ME, Schwartz SG, Gao X, Jeong S, Patel N, Itakura T, Price MO, Price FW Jr, Varma R, Stamer WD. Steroid-induced ocular hypertension/glaucoma: Focus on pharmacogenomics and implications for precision medicine. Prog Retin Eye Res. 2017 Jan;56:58-83. doi: 10.1016/j.preteyeres.2016.09.003. Epub 2016 Sep 22.

  PMID: 27666015 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood

MeSH Terms

Conditions

Glaucoma

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Study Officials

• Johannes SA Schouten, MD, PhD

  Maastricht University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2017
• First Posted: August 16, 2017
• Study Start: September 13, 2017
• Primary Completion: February 6, 2019
• Study Completion: May 1, 2020
• Last Updated: June 1, 2020

Record last verified: 2020-05

Locations

NL (1)