NEW HAVEN, CT — Symptoms of epiretinal member (MRM), sometimes called macular pucker, can be severe and require surgery. Patients often complain of loss of central vision and/or visual distortion (i.e. metamorphopsia or “wavy vision”).
According to a new report in Cell Genomics, ERM is characterized by the proliferation of cells on the retinal surface and diagnosed by ophthalmoscopy, fundus photography and optical coherence tomography (OCT).1
Its prevalence is about 2% in patients 50 and older and about 20% in those older than 75. “Age is associated with increased risk, and smoking may be associated with decreased risk,” explained researchers from Yale School of Medicine in New Haven, CT; the VA Connecticut Healthcare Center in West Haven and colleagues. “The most common cause is posterior vitreous detachment, an age-related separation of the vitreous from the retina.”
VA healthcare systems in Boston and San Diego also participated.
Typical treatment for symptomatic ERM is vitrectomy with epiretinal membrane peeling. Results of the highly invasive treatment are variable, and no nonsurgical treatment is available, according to the researchers.
“While many of the pathophysiological processes that lead to ERM are known and there is considerable knowledge of its biology, the underlying molecular genetic risk factors are not understood,” the study team pointed out, adding, “Genome-wide association studies (GWASs) are presently the most useful, and most universally applicable, tools to understand the biology underlying genetically complex traits such as ERM.”
The authors noted that, while large GWASs have been previously performed to identify common variant associations with defects related to the macula, those primarily have focused on age-related macular degeneration (AMD), including the first major GWAS.
Because the study team was seeking to identify a large number of risk genes, novel biology and phenotypic subtypes, it used the VA’s Million Veteran Program (MVP), which is one of the world’s largest biobanks including genetic, environmental and medical information, based on data from U.S. military veterans.
The MVP has enrolled more than 900,000 participants, many of them with non-European-ancestry participants. Genotype data are currently available for >650,000 participants.
This study team focused on European American (EUR), African-American (AFR) and Latino (admixed American, AMR) ERM participants in the MVP for genome-wide association analysis—a total of 38,232 case individuals and 557,988 control individuals.
A genomewide association study (GWAS) was completed in each population separately, and then results were meta-analyzed.
The results indicated that genomewide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR and 2 in AMR, with 48 in trans-ancestry meta-analysis.
“Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula,” the researchers concluded. “ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.”
- Gelernter J, Levey DF, Galimberti M, Harrington K, Zhou H, Adhikari K, Gupta P; VA Million Veteran Program; Gaziano JM, Eliott D, Stein MB. Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations. Cell Genom. 2024 Jun 12;4(6):100582. doi: 10.1016/j.xgen.2024.100582. PMID: 38870908; PMCID: PMC11228954.
