Overview
Preperimetric glaucoma (PPG) is an early stage of glaucomatous eye disease in which the optic nerve already looks damaged, but standard visual field testing has not yet shown repeatable vision loss. This stage matters because structural damage may be underway long before a person notices symptoms or develops measurable field defects. Identifying which eyes are more likely to worsen can help clinicians decide how closely to monitor patients and whether treatment should be intensified.
This study examined whether baseline microvasculature dropout (MvD) is linked to later structural and functional progression in PPG eyes. MvD refers to a localized loss or rarefaction of the small blood vessel network around the optic nerve, typically seen on optical coherence tomography angiography (OCTA). In glaucoma, reduced blood supply may reflect or contribute to ongoing tissue injury, making MvD a potentially important biomarker.
Study design and methods
The investigators performed a subgroup analysis of a prospective cohort study. They included 93 eyes from 70 participants who had a glaucomatous optic disc appearance but no repeatable visual field defects at baseline. The average follow-up period was 4.9 years, which allowed the researchers to observe longer-term change rather than short-term fluctuation.
Each eye was monitored using three main tools: optical coherence tomography (OCT), OCT angiography (OCTA), and visual field testing. Two structural measures were emphasized. The first was circumpapillary retinal nerve fiber layer thickness (cpRNFL), which reflects the thickness of the nerve fiber layer around the optic disc. The second was circumpapillary capillary density (cpCD), which reflects the density of small blood vessels in the same region. The presence or absence of MvD at baseline was used to divide eyes into two groups.
To analyze progression, the authors used mixed-effects models. This statistical approach is useful when several observations come from the same person or eye over time, and it helps estimate whether baseline features such as MvD predict faster change after accounting for other factors.
What the study found
The mean age of participants was 67.7 years, with a 95% confidence interval of 65.4 to 70.0 years. Among the 93 eyes, 32 had MvD at baseline and 61 did not.
The key finding was that eyes with baseline MvD lost capillary density more quickly over time than eyes without MvD. In the MvD group, cpCD declined by -0.88% per year, compared with -0.23% per year in eyes without MvD. This difference suggests that the microvascular abnormality was associated with a more rapid decline in local vessel density.
In multivariable analysis, which adjusted for other potential influences, the presence of MvD remained independently associated with faster cpCD loss. The estimated additional decline was -0.63% per year, and this result was highly statistically significant (P<0.001). In practical terms, MvD was not just a marker that happened to coexist with disease; it appeared to identify eyes at higher risk for ongoing vascular deterioration.
Interestingly, MvD was not associated with faster thinning of the retinal nerve fiber layer. The estimated difference in cpRNFL loss was 0.03 µm/year, with a P value of 0.886, indicating no meaningful association in this dataset. This suggests that microvascular loss may be detected earlier or more clearly than nerve fiber layer thinning in some PPG eyes, or that vascular and structural progression do not always move in lockstep.
The functional outcome was also important. Eyes with baseline MvD developed visual field loss more often than eyes without MvD: 62.5% versus 26.2%, respectively. This difference was statistically significant (P<0.001). Thus, baseline MvD was associated not only with faster vessel density loss but also with a greater likelihood of later functional deterioration.
Clinical meaning of microvasculature dropout
MvD is increasingly recognized as a relevant OCTA finding in glaucoma. The optic nerve head and surrounding tissues require an adequate blood supply, and damage to the microvasculature may reflect either reduced perfusion, mechanical stress, or a combination of both. In early glaucoma, these subtle vascular changes can help explain why some eyes progress despite appearing relatively stable on standard testing.
This study supports the idea that MvD may be a prognostic marker in PPG. If an eye already shows MvD, it may be more vulnerable to future change, especially vascular decline and eventual visual field loss. That does not mean every eye with MvD will worsen quickly, but it does suggest a higher-risk profile compared with eyes without this sign.
Why this matters for patients and clinicians
PPG can be challenging because the disease is present before standard visual field damage is confirmed. Many patients at this stage feel well and may not notice any symptoms, yet the optic nerve may already be under stress. Clinicians therefore need ways to estimate which patients need closer surveillance.
This study suggests that assessing MvD at baseline may help stratify risk. For patients with PPG and MvD, more frequent follow-up may be justified, along with careful monitoring of OCTA and OCT changes. In clinical practice, this could influence how soon treatment is initiated or whether pressure-lowering therapy is intensified, especially if other risk factors are present.
However, MvD should be interpreted as part of a broader picture. In glaucoma care, decision-making usually depends on intraocular pressure, optic nerve appearance, OCT findings, visual field results, family history, age, and other risk factors. OCTA findings add useful information, but they do not replace standard examinations.
Limitations to keep in mind
As with any observational study, this research shows association rather than proof of direct cause and effect. Although baseline MvD predicted faster progression, the study does not prove that MvD itself causes worsening. It may instead be a marker of eyes already experiencing more advanced or active disease biology.
Another point is that this was a subgroup analysis from a cohort study, so the findings may not apply equally to all glaucoma populations. The sample size was moderate, and the study focused specifically on eyes with preperimetric glaucoma. Larger studies across diverse populations are needed to confirm how broadly these findings hold.
OCTA also has technical limitations. Image quality, segmentation errors, motion artifacts, and differences between devices can affect measurements. For this reason, clinicians should be cautious about overinterpreting a single scan and should look for consistent patterns over time.
Practical takeaway
The main message from this study is straightforward: in preperimetric glaucoma, baseline microvasculature dropout is a warning sign. Eyes with MvD were more likely to lose capillary density faster and more likely to develop visual field damage during follow-up. By contrast, MvD was not clearly linked to retinal nerve fiber layer thinning in this analysis.
For everyday glaucoma care, this means OCTA assessment of microvascular features may add useful prognostic information. When MvD is present, clinicians may choose closer monitoring and earlier intervention to reduce the chance of avoidable vision loss.
Conclusion
In this prospective cohort analysis, baseline MvD in preperimetric glaucoma was associated with faster circumpapillary capillary density loss and a higher rate of later visual field damage. The finding supports the value of OCTA-based vascular assessment as a risk marker in early glaucoma. While more research is needed, MvD appears to be a clinically meaningful sign that may help guide follow-up intensity and treatment planning in patients with preperimetric glaucoma.