A recent study published in BMJ Open Ophthalmology evaluated the causal link between ametropia and diabetic retinopathy (DR) and assessed genetic associations between these two conditions.
Give me some background.
The relationship between DR and myopia has long been a topic of contention among researchers, with some observational studies suggesting that myopia may impede the onset and progression of DR.
- However: A subset of investigations maintain that no discernible association exists between the two.
As such: Mendelia randomization (MR) studies are required to verify the causal relationship between myopia and DR.
What is Mendelian randomization?
MR is a method that uses genetic variation associated with modifiable exposures (or risk factors) to assess their possible causal relationship with outcomes, with the intent to reduce bias from confounding factors.
How: By using genetic variants—typically single-nucleotide polymorphisms (SNPs)—associated with exposures of interest but do not vary with the correlated lifestyle or socioeconomic factors that may confound conventional observational associations.
Now talk about the study.
In this study, investigators utilized publicly accessible genome-wide association studies (GWAS) data.
- Specifically, these included SNPs that exhibited a strong association with ametropia—myopia, hypermetropia, and astigmatism.
Subsequently: A two-sample MR approach was employed to examine the causal relationship between different types of ametropia and DR.
Findings?
In total, 38 SNPs were included. The results of the analysis indicated that myopia may exert an inhibitory effect on the development of DR (odds ratio [OR]: 0.596, 95% confidence interval [CI]: 0.371-0.957, p < 0.05).
However: Other forms of ametropia did not exhibit a causal relationship with the risk of DR, including:
- Hypermetropia (OR: 8.882, 95% CI: 0.389 x 10-3 to 2.06 x 105, p > 0.05)
- Astigmatism (OR: 1.004, 95% CI: 0.888-1.135, p > 0.05)
Expert opinion?
While the research team analyzed myopia, hypermetropia, and astigmatism as distinct exposures, they emphasized recognizing that refractive errors are multifaceted and interdependent in clinical practice.
- As such, “treating them as separate entities may oversimplify their biological interplay, potentially limiting the generalizability of the findings,” the study authors explained.
Limitations?
These included:
- The sample size of SNPs associated with hypermetropia (three SNPs) and astigmatism (four SNPs) was relatively limited
- The MR method assumed a linear relationship between exposure and outcome, so if a non-linear relationship existed between different types of ametropia and DR, the applicability could be compromised
- The two-sample MR study required the absence of any overlap between the subjects exhibiting ametropia and those displaying DR
- However: The ametropia data samples originated from the UK Biobank while DR data samples were from the FinnGen database—so the independence of the two samples could not be strictly guaranteed
Take home.
These findings provide evidence that myopia may have a protective effect against DR development, while hypermetropia and astigmatism showed no significant causal effects.
- Though: This analysis treated refractive errors as independent entities, which may not reflect their clinical interdependence.
For the future: The study authors advised that further investigations are warranted to elucidate myopia’s potential protective mechanisms.