Researchers from Italy have discovered that inter-eye asymmetry in retinal microvasculature increases as diabetic retinopathy (DR) becomes more severe. Using OCT angiography, the study found that bilateral assessments can detect subtle vascular changes and provide prognostic information before differences are visible through conventional fundus examinations.
While diabetic retinopathy typically develops symmetrically in both eyes, new data suggests that significant differences can emerge, particularly in advanced stages. A cross-sectional study of 442 eyes from 221 patients with type 2 diabetes revealed that increasing DR severity, male sex, and the presence of diabetic macular edema (DME) are all associated with a higher risk of developing this inter-eye asymmetry.
Foveal Avascular Zone Asymmetry in Severe DR
The research focused on measuring the area and perimeter of the foveal avascular zone (FAZ), along with vessel density and fractal dimension. While mean perfusion density and fractal dimension remained similar between right and left eyes across most stages, a distinct pattern emerged in patients with proliferative DR (PDR).
In eyes with PDR, the FAZ area and perimeter in the superficial capillary plexus (SCP) and the FAZ area in the deep capillary plexus (DCP) were significantly larger in left eyes than in right eyes. Multivariate analysis confirmed that the severity of DR directly correlated with higher FAZ area asymmetry indexes in both the SCP and DCP.
This asymmetry isn’t just a byproduct of the disease itself. The presence of DME was specifically linked to higher asymmetry indexes within the SCP.
Hemodynamic Stress and the Left Carotid Artery
The researchers proposed a biological explanation for why the left eye may be more susceptible to these changes. The discrepancy may be rooted in the anatomy of the human circulatory system.
This anatomical difference creates a ripple effect in the retina. The SCP is supplied directly by the terminal branches of the central retinal artery, whereas the deeper layers, including the DCP, rely on diffusion from the choroidal circulation and vertical anastomoses from the SCP. Because of this direct link, the authors stated it is plausible that anatomical and hemodynamic differences may exert a more pronounced effect on the SCP.
Other systemic factors were considered, including hypertension (present in 57.9% of the cohort), cardiopathy (33.9%), nephropathy (11.8%), and stroke (6.3%). Although these comorbidities can cause microvascular changes, they did not emerge as statistically independent predictors of asymmetry in the final analysis.
Implications for Clinical Trials and Diagnosis
The finding that microvascular changes are not always symmetric has immediate consequences for how medical research is conducted. In many research protocols, a single eye is randomly selected for enrollment if both eyes are at the same clinical stage of DR.
“if microvascular changes in the macula are not symmetric, the random selection of the enrolled eye with the same clinical stage of DR in a research protocol may not represent the two eyes collectively.”
Study Authors, via Review of Optometry
This suggests that clinical trials involving patients with severe DR may need to evaluate both eyes to ensure data accuracy. Furthermore, because OCT angiography can reveal asymmetry before it is detectable via a standard fundus examination, the technology offers a potential window for earlier prognostic intervention.
The study’s strengths include a large cohort and a balanced distribution of DR stages, though the researchers noted that the retrospective, cross-sectional design prevents them from assessing long-term implications. They also acknowledged that ocular dominance was not evaluated.
Retinal Vascular Development in Early Childhood
While the DR study focuses on adult degeneration, other research highlights the baseline of retinal health in children. A study of 146 normal eyes from children aged birth to 6 years utilized a ResUNet convolutional neural network to compute vascular features.
The data showed that age and gender did not significantly impact optic disc diameter or vessel curvature. However, the research identified two specific developmental trends: a decrease in vessel caliber during the first three years of life and a general decrease in vessel complexity as children age.
Understanding these normal developmental markers is critical for distinguishing healthy growth from pathology. For instance, in pediatric care, certain visual markers like leukokoria (a white reflection in the pupil) can be alarming to parents. While often associated with retinoblastoma, medical experts note that such reflections can also be caused by cataracts, coats disease, retinopathy of prematurity, or persistent hyperplastic primary vitreous (PHPPV).
Because of the complexity of these early ocular developments, specialists recommend that eye examinations continue until a child is 5 or 6 years old to properly monitor growth and health.
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