Glaucoma and high IOP closely associated with risk of diabetic retinopathy, suggests study

A recent study published in the journal of BMC Diabetology & Metabolic Syndrome revealed a reciprocal causal relationship between glaucoma and diabetic retinopathy (DR), with intraocular pressure (IOP) potentially acting as a mediating factor.

Diabetic retinopathy (DR) is the primary cause of avoidable blindness in people between the ages of 20 and 74. Therefore, it is essential to identify potential risk factors and control how they contribute to the emergence of DR. Glaucoma is a series of progressive optic neuropathies that produce visual impairments and are primarily defined by the degeneration of retinal ganglion cells (RGCs), and is the largest cause of permanent blindness in the world.

Axonal fibers from ganglion cells in the retina merge to form the optic nerve, which sends visual signals to the visual center via the optic disc. Defects in the retinal nerve fiber layer (RNFL) and an elevated cup-to-disc ratio are two signs of glaucoma-related abnormalities in the optic disc. Lowering intraocular pressure is the cornerstone of glaucoma therapy.

Thus, to analyze the causal relationship between glaucoma and its related characteristics and DR, this study is the first to apply bidirectional mendelian randomization (MR). Additionally, the MVMR approach is used to rule out pleiotropy. Also, the possible causal link between IOP and glaucoma with DR was investigated using two-step MR.

This research used mediation analysis, multivariable Mendelian randomization (MVMR), and bidirectional two-sample Mendelian randomization. MR-Egger, weighted median, weighted mode, and simple mode were added to the Inverse-Variance-weighted approach, which was chosen as the primary MR method.

According to the findings of the forward MR study, intraocular pressure and glaucoma are risk factors for DR. And, according to the reverse MR, DR increased the risk of both IOP and glaucoma. The findings of the MVMR analysis showed that glaucoma was still a risk factor for DR on its own.

The outcomes of the two-step MR study indicate that IOP mediates the bidirectional link between glaucoma and DR. Furthermore, the favorable causal relationship between IOP and DR was facilitated by glaucoma. Overall, the outcomes of this study found glaucoma and IOP to be risk factors for DR based on the findings of this investigation. In particular, the reciprocal causal link between glaucoma and DR is mediated by IOP.

Source:

Chen, S., Lin, M., & Hong, Y. (2025). The causal effect of glaucoma and diabetic retinopathy: a Mendelian randomization study. Diabetology & Metabolic Syndrome, 17(1), 80. https://doi.org/10.1186/s13098-025-01652-5