CD36 gene is associated with intraocular pressure elevation after intravitreal application of anti-VEGF agents in patients with age-related macular degeneration: Implications for the safety of the therapy

ABSTRACT

Background: The wet form of age-related macular degeneration (AMD) is characterized by pathological vascularization of the outer retinal layers. The condition responds to treatment with antibodies against vascular endothelial growth factor (VEGF), but the patients receiving such anti-VEGF therapy sometimes show undesirable acute short-term increases in the intraocular pressure (IOP). The cause of this adverse effect is unknown, and here, we are testing a hypothesis that it is related to CD36 gene polymorphisms.

Materials and Methods: A group of 134 patients with AMD were given three therapeutic doses of anti-VEGF antibody (ranibizumab) at monthly intervals. Their IOP was measured immediately before and 30 min after each injection. Patients’ DNA was analyzed, and the changes in IOP were matched against seven polymorphisms of the CD36 gene.

Results: Three polymorphisms were found to be associated with increases in IOP: rs1049673 (p = 0.006), rs3211931 (p = 0.01), and rs1761667 (p = 0.043) at the time of the third injection only. Pronounced elevations (IOP > 25 mmHg) were associated with rs1049673 polymorphism: GC genotype (p < 0.01) and CC genotype (p < 0.05); both increasing the risk 2.6-fold, the presence of C-allele conferring a 1.5-fold greater risk and with rs3211931 polymorphism: AG genotype (p < 0.01) and GG genotype (p < 0.05); increasing the risk 2.6-fold (AG) and 2.7-fold (GG).

Conclusions: CD36 receptor may be involved in mediating the effects of VEGF on IOP. The findings will help to identify the patients at risk of acutely elevated IOP following the anti-VEGF therapy.

KEYWORDS:

• Glaucoma
• polymorphism
• receptor
• Schlemm´s canal
• thrombospondin

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding

This work has been supported by Agency for Healthcare Research, Czech Republic (AZV CR)—Grant Project No. 16-31207A and by Ministry of Health of the Czech Republic—conceptual development of research organization (FNBr, 65269705).

Additional information

Funding

This work has been supported by Agency for Healthcare Research, Czech Republic (AZV CR)—Grant Project No. 16-31207A and by Ministry of Health of the Czech Republic—conceptual development of research organization (FNBr, 65269705).