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

ABSTRACT: 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.

SUBMITTER: Hong EH

PROVIDER: S-EPMC9800359 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Hong Eun Hee EH Yeom Hoseok H Yu Hyo Seon HS Park Jong Eun JE Shin Yong Un YU Bang So-Young SY Cho Heeyoon H

Scientific reports 20221229 1

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 the ...[more]

PMID: 36581632

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Project description:BackgroundDiabetic macular edema (DME) is an important cause of vision loss and despite the anatomical and functional improvement achieved with treatment, there are reports of persistent DME regardless of continuous anti-VEGF therapy. The purpose of this study is to examine the effect of patients with DME previously treated with other anti-VEGF agents who are transitioned to intravitreal aflibercept (IAI) on a fixed dosing regimen.MethodsThis prospective study included 20 patients presenting with DME with a history of previous anti-VEGF treatment with ranibizumab or bevacizumab. Patients received a 2 mg (0.05 mL) IAI every 4 weeks until no evidence of fluid by optical coherence tomography (OCT) followed by a fixed dosing schedule of 2 mg IAI once every 8 weeks through 24 months. There was a pre-planned interim analysis of the mean absolute change from baseline central foveal thickness at month 6 as measured by OCT. Secondary outcomes included mean change from baseline in ETDRS visual acuity and anatomic parameters. Optical Coherence tomography angiography (OCTA) capillary perfusion density (CPD) after transitioning to IAI therapy were also reported.ResultsAverage central subfield thickness on OCT at baseline was 419.7 ± 92.0 and improved to 303.8 ± 73.1 at 6-months (p < 0.001). At 6 months after IAI treatment, BCVA increased + 1.5 letters from baseline (p = 0.38). OCTA CPD analysis revealed significant increase from baseline in the foveal avascular zone in non-proliferative diabetic retinopathy group (p = 0.02).ConclusionsPatients with prior anti-VEGF therapy who were transitioned to IAI therapy revealed significant anatomic improvements through 6 months.Trial registration Treatment of Diabetic Macular Edema With Aflibercept in Subjects Previously Treated With Ranibizumab or Bevacizumab (SwapTwo), Trial registration number: NCT02559180. Date of registration: September 24, 2015.https://clinicaltrials.gov/ct2/show/NCT02559180.

Project description:IntroductionWith the increasing use of intravitreal administration of corticosteroids in macular edema, steroid-induced intraocular pressure (IOP) rise is becoming an emergent issue. However, for patients in whom intravitreal steroids are indicated, there are no specific recommendations for IOP monitoring and management after intravitreal administration of corticosteroids.MethodAn expert panel of European ophthalmologists reviewed evidence on corticosteroid-induced IOP elevation. The objective of the panel was to propose an algorithm based on available literature and their own experience for the monitoring and management of corticosteroid-induced IOP elevation, with a focus on diabetic patients.ResultsData from trials including diabetic patients with a rise of IOP after intravitreal steroid administration indicate that IOP-lowering medical treatment is sufficient for a large majority of patients; only a small percentage underwent laser trabeculoplasty or filtering filtration surgery. A 2-step algorithm is proposed that is based on the basal value of IOP and evidence for glaucoma. The first step is a risk stratification before treatment. Patients normotensive at baseline (IOP ≤ 21 mmHg), do not require additional baseline diagnostic tests. However, patients with baseline ocular hypertension (OHT) (IOP > 21 mmHg) should undergo baseline imaging and visual field testing. The second step describes monitoring and treatment after steroid administration. During follow-up, patients developing OHT should have baseline and periodical imaging and visual field testing; IOP-lowering treatment is proposed only if IOP is >25 mmHg or if diagnostic tests suggest developing glaucoma.ConclusionThe management and follow-up of OHT following intravitreal corticosteroid injection is similar to that of primary OHT. If OHT develops, IOP is controlled in a large proportion of patients with standard IOP treatments. The present algorithm was developed to assist ophthalmologists with guiding principles in the management of corticosteroid-induced IOP elevation.FundingAlimera Sciences Limited.

Dataset Information

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

Publications

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

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