Gene Polymorphisms of Corticosteroid-induced Ocular Hypertension
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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.
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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.
Trial design
370 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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