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Retinal Nerve Fiber Wedge Defects In Glaucoma And Heart Disease

Retinal Nerve Fiber Wedge Defects In Glaucoma And Heart Disease

The Study

The study aimed to investigate the connection between localized vascular and retinal nerve fiber layer (RNFL) loss and an individual’s genetic predisposition to both glaucoma and cardiovascular disease. Researchers used a statistical tool called polygenic risk scores (PRS) to assess this relationship.


Glaucoma is a complex group of eye conditions. While high pressure inside the eye has been linked to damaging the optic nerve in some cases, it’s not the sole factor responsible for all glaucoma cases or their progression. On the other hand, the vascular theory suggests that glaucomatous damage can occur due to issues with small blood vessels and insufficient blood flow to the eye, independent of eye pressure. Research also shows that certain cardiovascular risk factors can increase the likelihood of developing glaucoma.

The study utilized a technique called Optical Coherence Tomography Angiography (OCTA) to non-invasively and with high precision examine the retinal vasculature, especially the inner retina. OCTA has gained attention in glaucoma research, as it has revealed changes in vessel density that are associated with glaucoma. However, there have been varying reports about its diagnostic capabilities when compared to conventional measurements like retinal nerve fiber layer (RNFL) thickness.

Recent research has expanded its focus to explore localized patterns of vascular loss in eye diseases, such as the enlargement and irregularity of the foveal avascular zone and localized wedge defects. Wedge-shaped vascular defects have been reported in early primary open-angle glaucoma (POAG) eyes, but why some individuals develop these defects while others don’t remains unclear. The study aimed to investigate whether these defects are linked to known glaucoma-related genes.


In this research, a total of 858 eyes from 455 individuals with suspected and early-stage primary open-angle glaucoma were included. The eyes were characterized based on the presence of localized vascular or retinal nerve fiber layer (RNFL) wedge-shaped defects. This characterization was done by closely examining images obtained through Optical Coherence Tomography Angiography (OCTA) and Optical Coherence Tomography (OCT).

The study also involved assessing the connections between these defects and pre-existing scores that indicate the genetic risk of developing glaucoma and cardiovascular disease. These assessments were carried out in the context of glaucoma risk factors and the potential impact on systemic vascular disease outcomes.

In this study, the focus was on identifying the presence or absence of localized vascular wedge defects. To confirm the presence of these defects, two unbiased investigators (Saks and Schulz) examined OCTA scans of the macula and optic nerve head. Their assessments demonstrated a high level of agreement at 96%. In cases of any disagreement, the investigators collectively reviewed the cases until a consensus was reached.

Wedge defects were defined as darkened regions that extended outward from the optic nerve head in an arcuate shape. The examination was conducted using two different OCTA devices, specifically the Spectralis OCTA macula and Angio-Plex optic nerve head and macula scans. The documentation indicated whether wedge defects were present or absent, but they were not quantified in terms of size or area. This decision was made due to the use of different OCTA devices at different locations, which introduced variability. All visits were retrospectively analyzed to determine when these vascular wedge defects first appeared during the observation period.

Limitations of the Study 

One limitation of this study is that it utilizes PRS scores that were originally validated for individuals of European ancestry. While this aligns with the ancestry of most of our study participants, we chose not to exclude individuals based on their ethnicity to ensure that our findings could be more broadly applicable. However, it’s important to acknowledge that this approach may potentially impact the results. It’s necessary to validate these findings in individuals from other ethnic backgrounds, as suggested by Cooke Bailey and colleagues in 2023.


The study found that individuals with a higher genetic risk for glaucoma were more likely to have both vascular wedge defects and RNFL defects (p<0.001 and p=0.020, respectively). A greater genetic risk for glaucoma was also linked to the presence of multiple vascular wedges in the same eye (p=0.005).

When looking at glaucoma progression based on global RNFL loss, it was associated with both vascular and RNFL wedge defects (p≤0.001 and p=0.008, respectively). Additionally, the genetic risk score for glaucoma (PRS) was significantly associated with vascular wedge defects, even when considering disc hemorrhages (p=0.007), but not with RNFL wedge defects (p=0.070).

However, it’s important to note that vascular wedge defects were not found to be related to the genetic risk score for cardiovascular disease.


In essence, individuals with a higher genetic risk of developing glaucoma, as indicated by their genetic risk score (PRS), were more prone to having retinal vascular defects and experiencing structural glaucomatous damage. However, this genetic risk for glaucoma didn’t seem to have any connection to the risk of systemic cardiovascular issues.

This suggests that there may be a localized cause behind the vascular defects in some cases, and this finding could be clinically significant, especially in the early stages of glaucoma and for individuals with a high genetic predisposition to the condition.

The use of a glaucoma genetic risk score (PRS) has previously proven beneficial in identifying individuals at risk of developing progressive glaucoma (as demonstrated by Craig and colleagues in 2020). This current study suggests that such individuals are more likely to exhibit a vascular phenotype. Detecting this predisposition early on could significantly impact treatment decisions and clinical care, highlighting the potential advantage of incorporating OCTA monitoring into clinical practice.

It’s worth noting that both vascular wedge defects and RNFL wedge defects were more common in individuals who were older, had lower intraocular pressure (IOP), higher vertical cup-to-disc ratio (VCDR), thinner central corneal thickness (CCT), lower visual acuity, worse mean deviation, and were receiving treatment for glaucoma. While this might imply that vascular wedge defects are typically associated with advanced stages of glaucoma, these defects were also found in eyes with suspicion of glaucoma and in the early stages of manifest glaucoma, often before significant functional damage occurred (eyes with an average mean deviation of -3.61 dB for vascular wedge defects and -3.04 dB for RNFL wedge defects).

It’s worth mentioning that localized RNFL wedge defects are frequently reported in normal tension glaucoma. This could explain why both vascular and RNFL wedge defects were linked to lower IOP in eyes with localized defects. However, it’s also plausible that individuals with these defects had lower IOP as a result of receiving more aggressive IOP-lowering treatment. Many patients were already undergoing treatment, and those with more evident disc damage may have been receiving more rigorous IOP management.

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