Title
Progression in Preperimetric Glaucoma Eyes With and Without Microvasculature Dropout
Summary
This study found that eyes with preperimetric glaucoma and baseline microvasculature dropout lost capillary density faster and were more likely to develop visual field damage over time, suggesting microvascular assessment may help predict glaucoma progression.
Background
Glaucoma is a chronic eye disease that damages the optic nerve and can lead to irreversible vision loss. In many patients, structural damage to the optic nerve and retinal nerve fiber layer appears before standard visual field testing shows clear abnormalities. This early stage is often called preperimetric glaucoma, or PPG. People with PPG already have a glaucomatous-looking optic disc, but their visual field remains normal on repeat testing.
Because glaucoma progression can be slow and difficult to detect early, clinicians increasingly rely on imaging tools such as optical coherence tomography, or OCT, and OCT angiography, or OCTA. OCT measures the thickness of retinal structures, including the circumpapillary retinal nerve fiber layer, or cpRNFL. OCTA, on the other hand, evaluates blood flow in the retinal and peripapillary microvasculature and can estimate circumpapillary capillary density, or cpCD.
One OCTA feature of interest is microvasculature dropout, abbreviated MvD. MvD refers to a localized area where microvascular perfusion appears absent or markedly reduced, often around the optic nerve head. Prior research has suggested that MvD may be associated with glaucoma severity, but its value in predicting future progression in patients with preperimetric glaucoma has been less clear.
Why This Study Matters
A major challenge in glaucoma care is deciding which patients are at greatest risk for future damage and therefore need closer monitoring or earlier treatment. If a finding such as baseline MvD reliably identifies patients who are more likely to progress, it could help ophthalmologists personalize follow-up intervals and management decisions.
This study examined whether eyes with PPG and MvD at baseline were more likely to show later structural loss, vascular loss, and visual field deterioration than eyes without MvD.
Study Design and Methods
This was a subgroup analysis of prospective cohort study data. The investigators followed 93 eyes from 70 participants who had a glaucomatous optic disc appearance but no repeatable visual field defects at the start of the study. The mean follow-up period was 4.9 years, which is long enough to observe meaningful change in many glaucoma patients.
All eyes were monitored with three key tests:
1. OCT to assess retinal nerve fiber layer thickness, especially cpRNFL.
2. OCTA to measure circumpapillary capillary density, especially cpCD.
3. Visual field testing to detect emerging functional loss.
At baseline, eyes were divided into two groups based on whether microvasculature dropout was present or absent. The researchers then used mixed-effects models, a statistical method well suited to repeated measurements over time, to identify factors linked to progression.
Key Findings
The average age of participants was 67.7 years. Of the 93 eyes studied, 32 had baseline MvD and 61 did not.
The main result was that eyes with baseline MvD lost capillary density more quickly than eyes without MvD. Specifically, the cpCD decline was -0.88% per year in eyes with MvD compared with -0.23% per year in eyes without MvD. This difference suggests that baseline microvascular dropout is a marker of ongoing vascular compromise in PPG.
In multivariable analysis, which adjusts for other relevant factors, the presence of MvD remained independently associated with faster cpCD loss. The estimated additional rate of decline was -0.63% per year, and this result was highly statistically significant.
In contrast, baseline MvD was not associated with faster cpRNFL thinning. The cpRNFL change was 0.03 µm per year, which was not statistically significant. This finding suggests that vascular change may be more sensitive than structural thinning in some early glaucoma eyes, or that vascular abnormalities may precede measurable nerve fiber layer loss in certain patients.
Importantly, eyes with baseline MvD were also much more likely to develop visual field loss during follow-up. Visual field damage occurred in 62.5% of eyes with MvD, compared with 26.2% of eyes without MvD. This difference was statistically significant and clinically meaningful.
What the Results Mean
These findings support the idea that microvascular abnormalities are not just a bystander effect in glaucoma. Instead, MvD may reflect a biologically important process related to disease progression. In practical terms, an eye with PPG and detectable MvD may be at higher risk of future functional decline even if standard visual field testing is still normal at baseline.
The study also suggests that OCTA-based vascular metrics can add information beyond conventional structural measurements. While cpRNFL thickness remains an important marker in glaucoma care, capillary density may reveal risk earlier in some patients, especially those in the preperimetric stage.
The lack of a significant association between MvD and cpRNFL loss is also notable. It may mean that vascular dropout can be present before clear nerve fiber thinning becomes measurable, or that cpRNFL change requires a longer observation period to detect. Another possibility is that structural and vascular changes do not progress in exactly the same way in every eye.
Clinical Implications
For eye care specialists, this study adds support for incorporating OCTA into the evaluation of patients with early glaucoma or suspicious optic nerve changes. If MvD is present at baseline, clinicians may consider the patient higher risk for progression and may choose:
1. More frequent follow-up visits
2. Closer visual field monitoring
3. Repeated imaging with OCT and OCTA
4. Earlier discussion of treatment options, including lowering intraocular pressure if clinically appropriate
It is important to note that the study does not prove that MvD causes glaucoma progression. Rather, it shows that MvD is a useful predictor or marker of risk. In clinical practice, decisions should still be based on the full picture, including optic nerve appearance, intraocular pressure, corneal thickness, family history, age, and the pattern of structural change over time.
How This Fits Into Glaucoma Care
Glaucoma management is increasingly moving toward risk stratification. Not every patient with PPG progresses at the same rate, and some may remain stable for years. A biomarker such as MvD may help identify which eyes need extra attention.
This is particularly relevant because visual field loss can appear late. By the time standard perimetry detects defects, significant optic nerve injury may already have occurred. Tools that identify higher-risk eyes earlier could improve long-term preservation of vision.
The study also reinforces an important concept in glaucoma: structural, vascular, and functional assessments each provide different pieces of the puzzle. Combining them may lead to better individualized care than relying on a single test.
Limitations
As with any study, there are limitations to keep in mind. This was a subgroup analysis rather than a randomized trial, so it can show association but not definite causation. The sample size was modest, and the findings may not apply equally to all glaucoma populations or imaging platforms.
Also, MvD detection depends on imaging quality and interpretation. Different OCTA systems and analysis methods may produce slightly different results. Long-term reproducibility and standardization remain important issues for broader clinical adoption.
Bottom Line
In preperimetric glaucoma, baseline microvasculature dropout appears to identify eyes at higher risk of faster capillary density loss and future visual field damage. Although it did not predict retinal nerve fiber layer thinning in this study, MvD may still be a valuable risk marker for glaucoma progression.
For clinicians, assessing MvD may help guide how closely patients with PPG should be followed. For patients, the study highlights why early imaging and regular monitoring matter even when visual field testing is still normal.
Reference
Hashemi SM, Nishida T, Moghimi S, Soltani G, Pereira AO, Micheletti E, Mittal R, Zangwill LM, Weinreb RN. Progression in Preperimetric Glaucoma Eyes with and Without Microvasculature Dropout. American Journal of Ophthalmology. 2026-05-28. PMID: 42214583.
