Research describes a novel biomarker of tissue hypoxia in PDR and RVO

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A new study published in the International Journal of Retina and Vitreous identified what the authors described as a novel biomarker of tissue hypoxia in patients with branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO) and proliferative diabetic retinopathy (PDR), namely, the sum of the gain of perfusion/loss of perfusion (GoPLoP).¹

The investigators, led by co-authors Mahadev Bhalla, MD, and Farhad Ghaseminejad, MSc, from the Department of Ophthalmology and Vision Sciences, Eye Care Centre, University of British Columbia, Vancouver, Canada, reported that the GoPLoP values were significantly higher in the patients than in the controls in the macular and temporal retinal regions.

Study background

The investigators explained that because the retina compensates for its relatively limited blood supply via vasomotion, which they defined as physiologic oscillation of vascular tone to redirect blood flow. "The vasomotion exerts local and dynamic vascular control of perfusion to the different regions of retinal tissue, according to their varying and immediate metabolic demand," the authors reported.²

Based on these mechanics, the retinal perfusion, therefore, is not continuous, but it fluctuates over periods ranging from seconds to minutes.³ “A corollary of this dynamic mechanism is that retinal regions may experience transient episodes of non-perfusion and subsequent re-perfusion, which, while a normal physiologic process, may be erroneously perturbed in retinal vascular diseases and predispose to retinal ischemia,"^2,4 they said.

Considering this knowledge of the retina, the investigators conducted a study in which the goals were to detect and quantify intermittent capillary perfusion over time using optical coherence tomography angiography in nine patients with BRVO, eight with CRVO, eight with PDR, and 10 healthy control eyes.

They explained that because vasomotion is primarily driven by tissue oxygen levels, they hypothesized that the quantified intermittent capillary perfusion may be an objective biomarker for retinal vascular ischemia and capillary dropout. They also hypothesized that pathological eyes would exhibit a significantly greater burden of intermittent capillary perfusion variability compared to healthy controls.

The authors recounted that five 6 × 6-mm scans were registered and averaged at baseline (T0) and 30 minutes after (T30) into single en-face images of the superficial and deep vascular complexes (SVC and DVC), and pixels were labeled as vessels or non-vessels.

The study defined the LoP as the percentage of vessel pixels present in the T0 image that disappeared at T30; the GoP was defined as the percentage of vessel pixels that appeared in the T30 image. The amount of intermittent capillary perfusion was the sum of GoPLoP.

What did the OCTA images show?

The investigators reported, “Patients with PDR, CRVO, and BRVO showed significantly higher GoPLoP values than controls in both the macular and temporal regions. The temporal region generally exhibited significantly greater GoPLoP values than the macular region. Layer analysis indicated a significantly higher GoPLoP within the DVC compared to the SVC. There was a significant negative correlation between perfusion density and perfusion variability.”

They concluded, “Our results highlight significant GoPLoP in BRVO, CRVO, and PDR patients compared to controls, and this novel measure may be a candidate biomarker for capillary perfusion heterogeneity disturbances secondary to low tissue oxygen levels. This study lends further support to the suggestion that monitoring intermittent capillary perfusion in patients with retinal vascular diseases could provide utility in monitoring of the disease and in evaluating treatment efficacy.”

References

1. Bhalla M, Ghaseminejad F, Burdett T, et al. Quantification of intermittent retinal capillary perfusion in retinal vein occlusion and proliferative diabetic retinopathy. Int J Retin Vitr. 2025;11:102. https://doi.org/10.1186/s40942-025-00720-2

2. Yu D-Y, Cringle SJ, Yu PK, et al. Retinal capillary perfusion: Spatial and Temporal heterogeneity. Prog Retin Eye Res. 2019;70:23–54.

3. Guyton A. Textbook of medical physiology. Elsevier Saunders. 2006;11.

4. Yuan PHS, Athwal A, Shalaby M, et al. Retinal capillary perfusion heterogeneity in diabetic retinopathy detected by optical coherence tomography angiography. Int J Retin Vitr. 2024;10:12.