A study recently published in Eye evaluated the demographic, ocular, and genetic risk factors for beta-zone peripapillary atrophy (beta-zone PPA) in Black individuals with primary open-angle glaucoma (POAG).
Give me some background.
PPA is a morphological change to the optic nerve head (ONH) characterized by atrophy of the retinal pigment epithelium, photoreceptors, and choriocapillaris—resulting in visible choroidal vessels and sclera.
In Bruch’s membrane: PPA is called beta-zone PPA and has been described as a risk factor for POAG-related visual field (VF) loss.
- How: Beta-zone PPA location has correlated spatially with the region of most rapid future VF loss progression in POAG patients.
And take note: POAG remains understudied in Black individuals—despite having the highest incidence and most severe progression and outcomes of the disease as well as a higher prevalence of beta-zone PPA.
Now talk about the study.
POAG cases were included from the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study.
- For a refresher on this: The POAAGG study enrolled more than 10,250 patients of African ancestry aged 35+ from the Philadelphia, Pennsylvania, community between 2010 and 2019 to identify the genes involved in glaucoma.
For the purposes of this research: Beta-zone PPA was defined as hypopigmentation with visible choroidal vessels and sclera adjacent to the optic disc.
And the findings?
Among 3,381 eyes, 969 (28.6%) had beta-zone PPA.
As for the specifics: Beta-zone PPA was associated with:
- Older age (odds ratio [OR]: 2.90, p<0.001)
- Larger vertical cup-to-disc ratio (CDR, OR: 1.58, p=0.007)
- Being less common in females (OR: 0.53, p<0.001)
Any its negative associations?
Beta-zone PPA presence was negatively associated with the following ONH anatomical changes,:
- Bean-pot-cupping (OR: 0.59, p<0.001)
- Cylindrical (OR: 0.55, p<0.001)
- Grey crescent (OR: 0.47, p=0.01)
- Neural-rim notching (OR: 0.43, p<0.001)
Tell me more.
Larger beta-zone PPA area was not only linked to older age (p=0.008) but also large vertical CDR (p=0.03).
Conversely: It was less likely to develop with the following ONH features:
- Conus pigmentosus (p=0.001)
- Deeper cup depth (p=0.006)
- Higher intraocular pressure (IOP, p=0.005)
- Rounder discs (p=0.01)
Anything else?
Higher polygenic risk score (PRS, p=0.007) and the presence of the single-nucleotide polymorphism (SNP) rs34957764 in ROCK1P1 (p=0.053) were associated with beta-zone PPA—however, the same SNP was also associated with lesser area of beta-zone PPA (p=0.03).
Regions of beta-zone PPA correlated with greater retinal nerve fiber layer (RNFL) loss (p<0.01).
- Take note: This observation was in accordance with prior research, which demonstrated that the spatial extent of beta-zone PPA corresponded to the spatial extent of RNFL thinning in the classic ISNT (inferior, superior, nasal, temporal) pattern that describes glaucomatous RNFL thinning.
Meaning: These findings support the conclusion that beta-zone PPA may be an aspect of glaucomatous change.
Expert opinion?
The research team found that a higher PRS—previously developed and validated in the POAAGG cohort to predict POAG risk—was significantly associated with the presence of beta-zone PPA.
“This finding supports a growing body of evidence that genetic predisposition to POAG may also influence ONH structural features, such as beta-zone PPA, further linking genetic risk burden to clinical phenotypes of glaucomatous damage,” the study authors explained.
Any limitations to note?
Quite a few, including:
- Uncertainty still exists around the clinical utility of beta-zone PPA in POAG, as several studies have failed to report an association between the two while others have commented on the little incremental clinical value
- This study only included individuals with POAG and did not incorporate a control group without glaucoma
- Subjective grading of optic nerve parameters could have impacted data collection
- Subjects without or with low-quality images were excluded, introducing the potential for selection bias
- Genetic analyses were restricted to individuals with POAG, so it was not possible to determine whether SNP associations were specific to beta-zone PPA or reflected a broader genetic risk for glaucoma
- The generalizability of this study suffered from the exclusive focus on POAG patients of African ancestry. Interestingly, this decision was meant to address disparities faced by this vastly understudied population in terms of prevalence of the condition and vision loss
Take home.
These findings suggest that beta-zone PPA was strongly associated with older age and high CDR among Black individuals with POAG.
- And while the research team failed to identify clear genetic associations with beta-zone PPA, they did find an association with RNFL loss.
Next steps: Further investigation is required to elucidate the clinical utility of beta-zone PPA in predicting glaucoma progression and which specific characteristics indicate glaucomatous degeneration.