Genome-wide association study of the response of patients with diabetic macular edema to intravitreal Anti-VEGF injection

Diabetic macular edema (DME), a complication of diabetes mellitus, is a leading cause of adult-onset blindness worldwide. Recently, intravitreal anti-VEGF injection has been used as a first-line treatment. This study analyzed the association between the genetic profile of patients with DME and their response to treatment. Intravitreal anti-VEGF injections were administered monthly for three months to Korean patients diagnosed with DME, who were classified into two groups depending on whether they responded to anti-VEGF therapy or showed recurrence within six months. Peripheral blood samples were used for genetic analyses. Genome-wide association analysis results sowed that the genes DIRC3 on chromosome 2 (rs16857280, p = 1.2 × 10 –6 ), SLCO3A1 on chromosome 15 (rs12899055, p = 2.5 × 10 –6 ), and RAB2A on chromosome 8 (rs2272620, p = 4.6 × 10 –6 ) were associated with treatment response to intravitreal anti-VEGF injection. SLC35F1 , TMEM132D , KIAA0368 , HPCAL1 , IGF2BP3 , SPN2S , COL23A1 , and CREB5 were also related to treatment response ( p < 5.0 × 10 –5 ). Using the KEGG pathway analysis, RAB2A and CREB5 were found to be associated with AMPK signaling related to VEGF ( p = 0.018). The identified genetic biomarkers can elucidate the factors affecting patient response to intravitreal anti-VEGF injection and help select appropriate therapeutic strategy.