Prognostic biomarkers in treatment-naïve central retinal vein occlusion with macular edema

Abstract

Significance of this study: Reduced pulse pressure (PP) reflects impaired systemic perfusion and may exacerbate retinal ischemia in central retinal vein occlusion-induced macular edema (CRVO-ME) by compromising ocular blood flow autoregulation. This hemodynamic dysfunction is hypothesized to worsen clinical outcomes and neovascular risks.

Purposes: To investigate the associations between potential prognostic biomarkers and clinical outcomes in treatment-naïve CRVO-ME and assess their predictive utilities.

Methods: In this retrospective cohort study conducted from March 2019 to March 2024, we analyzed 101 treatment-naïve CRVO-ME patients stratified by outcomes: favorable (endpoint best-corrected visual acuity [BCVA] ≥ 20/100 without CRVO-induced neovascular glaucoma [CRVO-NVG]) versus unfavorable (endpoint BCVA < 20/100 or CRVO-NVG development). We compared demographic characteristics, baseline blood pressures, ocular features, and systemic biomarkers between groups.

Results: Multivariable logistic regression analysis identified two independent predictors of unfavorable outcomes: suboptimal 1-month post-injection BCVA (odds ratio [OR] = 1.824 per 0.1 log MAR unit increase, 95% confidence intervals [CI] 1.236-2.691, P = 0.002) and diminished PP (OR = 1.147 per mmHg decrease, 95% CI 1.028-1.279, P = 0.015). Receiver operating characteristic analysis demonstrated strong predictive accuracy for both parameters (1-month post-injection BCVA: area under the receiver operating characteristic curve [AUROC] = 0.843, cutoff 0.85 logarithm of the minimum angle of resolution [log MAR], P = 0.000; PP: AUROC = 0.812, cutoff 57 mmHg, P = 0.000). In the ischemic CRVO-ME subgroup (n = 27), the optical coherence tomography (OCT)-defined "over-response to the first intravitreal injection (ORIVI)" emerged as the sole significant predictor of CRVO-NVG development (OR = 15.167, 95% CI 1.509-152.464, P = 0.026).

Conclusion: This study establishes baseline PP < 57 mmHg and suboptimal 1-month post-injection BCVA > 0.85 log MAR as key prognostic indicators in CRVO-ME, while identifying the ORIVI sign as a specific predictor of CRVO-NVG in ischemic cases. These findings introduce easily obtainable systemic parameter (PP) for risk assessment, define 1-month visual response as key treatment evaluation point, propose ORIVI sign as an imaging biomarker for ischemic CRVO complications.

Keywords: Central retinal vein occlusion-induced macular edema; Neovascular glaucoma; Non-invasive acquired risk factors; Pulse pressure; Unfavorable outcomes.

Fig. 1

Participant screening and grouping flowchart. BCVA best-corrected visual acuity, CRVO central retinal vein occlusion, CRVO-ME central retinal vein occlusion-induced macular edema, CRVO-NVG CRVO-induced neovascular glaucoma

Fig. 2

Representative OCT images demonstrating ORIVI signs. A–C A 49-year-old male presenting with 1-month history of blurred vision (BCVA 20/1000) in the left eye, diagnosed with CRVO. CFP (A) revealed characteristic flame-shaped hemorrhages, optic cup enlargement, and complete whitening of temporal branch retinal arteries (yellow arrows). Baseline OCT (B) showed CRT of 837 μm, which decreased to 292 μm at 1-month post-injection follow-up (C) without concomitant visual improvement. D–F An 88-year-old male with CRVO in the right eye (BCVA 20/500) for ≥ 1 month. Initial CFP (D) demonstrated flame-shaped hemorrhages, arterial narrowing, venous tortuosity, and extensive cotton-wool spots (blue arrows). Baseline OCT (E) revealed CRT of 913 μm, reducing to 265 μm post-IVI (F) without visual acuity improvement. BCVA best-corrected visual acuity, CFP color fundus photography, CRT central retinal thickness, CRVO central retinal vein occlusion, HM hand movement, IVI intravitreal injection, OCT optical coherence tomography, ORIVI over-response to the first intravitreal injection

Fig. 3

Visual acuity outcomes and predictive performance. A Longitudinal BCVA changes in favorable (blue line) and unfavorable (orange line) groups throughout follow-up. B ROC curve analysis evaluating predictive accuracy of 1-month post-injection BCVA (green line) and pulse pressure (red line) for distinguishing outcome groups. AUC area under the curve, BCVA best-corrected visual acuity, CI confidence interval, IVI intravitreal injection, log MAR logarithm of the minimum angle of resolution, ROC receiver operating characteristic