Clinical trial NCT03250819: Gene Polymorphisms of Corticosteroid-induced Ocular Hypertension
Official title: Genetic Association Study on Corticosteroid-induced Elevation of the Intraocular Pressure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Corticosteroid Induced Ocular Hypertension/Glaucoma
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2017-08-16
Enrollment: 370
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
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).

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Differences in SNP's in corticosteroid responders and non-responders
timeFrame: At the time of inclusion
Secondary outcomes:
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: University Eye Clinic Maastricht, Maastricht UMC+
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Johannes SA Schouten, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.