Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration

Abstract

The most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12–0.32] and 0.09 [95% CI, 0.04–0.21] (P < 0.001), and odd ratios of 0.24 [95% CI, 0.15–0.39] and 0.03 [95% CI, 0.01–0.11] (P < 0.001). These pharmacogenetic findings indicate a rational basis to optimize the future clinical application of PDT-V during the combined treatments of AMD-related CNV, highlighting the role of thrombophilia to be aware of the efficacy profile of photodynamic therapy.

Novel Programmed Cell Death as Therapeutic Targets in Age-Related Macular Degeneration?

“…However, the recurrence of the neovascularization is high in both PDT and thermal laser therapy. Moreover, PDT cannot restore the damaged macula, and has the risk of causing vascular occlusion, and thereby can further impair the vision [ 80 ].…”

Implanted, Wireless, Self‐Powered Photodynamic Therapeutic Tablet Synergizes with Ferroptosis Inducer for Effective Cancer Treatment

“…However, the clinical application of PDT is affected by the depth of light penetration and the hypoxic TME. [27][28][29][30] In our previous work, we developed a selfpowered implantable PDT tablet for treating deep tumors, which overcomes the limitations of conventional PDT and extends its clinical applications using the piezoelectric effect. [31] In this study, we optimized the design of the tablet to enhance its efficiency, sensitivity, and stability in generating ROS and depleting GSH.…”