Identifying Genetic Risk Factors for Diabetic Macular Edema and the Response to Treatment

Gurung, Rajya Laxmi; FitzGerald, Liesel M.; McComish, Bennet J; Verma, Nitin; Burdon, Kathryn P.

doi:10.1155/2020/5016916

Cited by 10 publications

(11 citation statements)

References 84 publications

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“…In addition, DMO is a highly complex disease and there may be other unexplored causes of poor outcomes in DMO patients, including genetic, epigenetic and environmental factors. 36 This study is consistent with a similar study by Wecker et al 37 They reported a higher proportion of RVO patients (24%) gained more than 15 ETDRS letters than DMO (13.9%) or nAMD (14.1%) patients after 12 months. While the proportion of nAMD and RVO patients with 15 letters improvement was higher in our study (RVO:43%, nAMD:32%), fewer of our DMO patients (5%) reached this goal.…”

Section: Open Accesssupporting

confidence: 92%

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Comparing vision and macular thickness in neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion patients treated with intravitreal antivascular endothelial growth factor injections in clinical practice

et al. 2021

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ObjectiveTo compare the visual outcomes of intravitreal antivascular endothelial growth factor (anti-VEGF) injections in neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DMO) and retinal vein occlusion (RVO) in a real-world setting.Methods and analysisRetrospective analysis of data from the Tasmanian Ophthalmic Biobank database. The median change in best-corrected visual acuity (BCVA) between baseline and 12 months post initiating intravitreal anti-VEGF treatment were compared between the three diseases. Final BCVA, central macular thickness (CMT), cumulative number of injections and overall predictors of change in BCVA and CMT were also determined.ResultsAt 12 months, change in BCVA was significantly different between nAMD, DMO and RVO cohorts (p=0.032), with lower median change for DMO (2 letters, range −5 to 20) than for RVO (11 letters, range −20 to 35). Likewise, CMT change was significantly different between the three cohorts (p=0.022), with a smaller reduction in CMT in DMO (−54 µm, range −482 to 50) than RVO patients (−137 µm, range −478 to 43; p=0.033). Total number of injections received (p=0.028) and final BCVA score (p=0.024) were also significantly different between the groups. Baseline BCVA was a negative predictor (p=0.042) and baseline CMT a positive predictor (p<0.001) of outcome. After adjusting for baseline BCVA and CMT, diagnosis of nAMD or RVO was a predictor of visual improvement compared with the DMO.ConclusionsAt the end of 12 months, nAMD and RVO cohorts had the greatest improvement in BCVA, however the final BCVA for DMO was significantly better than for nAMD.

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Section: Open Accesssupporting

confidence: 92%

“…In addition, DMO is a highly complex disease and there may be other unexplored causes of poor outcomes in DMO patients, including genetic, epigenetic and environmental factors. 36 …”

Section: Discussionmentioning

confidence: 99%

Comparing vision and macular thickness in neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion patients treated with intravitreal antivascular endothelial growth factor injections in clinical practice

et al. 2021

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“…Therefore, it would be intuitive to hypothesize that EPO gene polymorphisms could be involved in the susceptibility to DME. However, few studies have investigated the association of genetic variants with DME [ 44 , 45 ] and Abhary et al [ 11 ] were the only ones who reported the association of EPO polymorphisms with DME. In their study, the minor alleles of the rs1617640 (G), rs507392 (C), and rs551238 (C) polymorphisms were associated with the increased risk of DME in Australians with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case–control study and systematic review with meta-analysis

et al. 2022

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Background Diabetic retinopathy (DR) is characterized by ischemia, hypoxia, and angiogenesis. Erythropoietin (EPO), an angiogenic hormone, is upregulated in DR, and the association of EPO genetic variants with DR is still uncertain, as conflicting results have been reported. Therefore, we performed a case–control study followed by a meta-analysis to investigate whether the rs1617640, rs507392, and rs551238 polymorphisms in EPO gene are associated with DR. Methods The case–control study included 1042 Southern Brazilians with type 2 diabetes (488 without DR and 554 with DR). Eligible studies for the meta-analysis were searched from electronic databases up to June 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for five genetic inheritance models. Results The minor alleles of the EPO polymorphisms had nearly the same frequency in all groups of patients (35%), and no association was detected with DR in the case–control study. The meta-analysis included 14 independent sets of cases and controls with 9117 subjects for the rs1617640 polymorphism and nine independent sets with more than 5000 subjects for the rs507392 and rs551238 polymorphisms. The G allele of the rs1617640 polymorphism was suggestively associated with DR under the dominant (OR = 0.82, 95% CI: 0.68–0.98), heterozygous additive (OR = 0.82, 95% CI: 0.69–0.97), and overdominant (OR = 0.88, 95% CI: 0.79–0.97) models. In the subgroup analyses, the G allele was also suggestively associated with proliferative DR (PDR), non-proliferative DR (NPDR), and DR (PDR + NPDR) among patients with type 1 diabetes (T1DM) or non-Asian ancestry. After considering the Bonferroni correction for multiple comparisons, the G allele remained associated with NPDR and DR in T1DM. Regarding the rs507392 and rs551238 polymorphisms, no association was found between these variants and DR. Conclusion Our findings provide additional support to EPO as a susceptibility gene for DR, with the rs1617640 polymorphism deserving further investigation.

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“…In a pilot study that performed GWAS to differentiate between bevacizumab responders and non-responders, the majority of expressed genes were in transcriptional regulation or receptor activation pathways 19 . A recent study in a Middle Eastern population investigated the relationship between serum hyperglycemia-related long www.nature.com/scientificreports/ noncoding ribonucleic acid (lncRNA) levels and response to anti-VEGF (aflibercept) injection, but no significant association was found 20,21 . To date, only one recent report has conducted a GWAS to identify genes associated with the response to anti-VEGF treatment in DME, which has been performed in the Australian population 22 .…”

Section: Discussionmentioning

confidence: 99%

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

Hong

Yeom

et al. 2022

Sci Rep

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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.

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Identifying Genetic Risk Factors for Diabetic Macular Edema and the Response to Treatment

Cited by 10 publications

References 84 publications

Comparing vision and macular thickness in neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion patients treated with intravitreal antivascular endothelial growth factor injections in clinical practice

Comparing vision and macular thickness in neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion patients treated with intravitreal antivascular endothelial growth factor injections in clinical practice

Association of polymorphisms in the erythropoietin gene with diabetic retinopathy: a case–control study and systematic review with meta-analysis

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

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