PXG Associated with Higher Risk of Developing CSCR

Findings of a recent study suggest that the vascular instability, inflammation and oxidative stress inherent to PXG may contribute to choroidal vascular dysregulation, creating a susceptibility to CSCR. Photo: Henrietta Wang, BOptom, MPH, and Jack Phu, OD, PhD. Click image to enlarge. Although the association between pseudoexfoliative glaucoma (PXG) and central serous chorioretinopathy (CSCR) has not been previously evaluated, both conditions share vascular and endothelial features. Prior studies examining glaucoma risk among patients with CSCR have yielded conflicting results, so in a recent study researchers evaluated whether PXG is associated with an increased hazard of developing CSCR compared with primary open-angle glaucoma (POAG). The team—comprised of ophthalmologists from Bascom Palmer, UCLA, Harvard and the University of Arkansas—found that the vascular instability, inflammation and oxidative stress inherent to PXG may contribute to choroidal vascular dysregulation, creating a susceptibility to CSCR. The findings were reported earlier this week in American Journal of Ophthalmology.Data from 10,347 patients with PXG and 205,065 POAG patients were included. Individuals with a history of age-related macular degeneration (AMD) or prior anti-VEGF therapy were excluded. The primary outcome was the development of CSCR within one- and five-year follow-up periods following the glaucoma diagnoses.PXG was significantly associated with a higher risk of developing CSCR compared to POAG. The adjusted hazard ratio for CSCR was 1.807 at one-year follow-up and 1.631 at five-year follow-up.Inflammatory and ischemic biomarkers have been increasingly implicated in both the development of PXF and its progression to PXG, and early biochemical studies showed a systemic redox imbalance in pseudoexfoliation syndrome. “In PXG, this imbalance appears further amplified, with significantly elevated serum levels of oxidative and inflammatory markers (inducible nitric oxide synthase, SCUBE-1, galectin-3 and malondialdehyde),” the authors wrote in their AJO paper. “These findings suggest a potential link between oxidative stress and structural, as well as vascular, alterations in PXG, supporting their relevance in the underlying pathophysiological mechanisms of the disease.”The paper goes on to explain that these perfusion abnormalities parallel key choroidal disturbances observed in CSCR, as chronic venous congestion, impaired choroidal autoregulation and inflammatory and oxidative stress are hallmark features of CSCR pathogenesis. “The presence of analogous vascular instability in PXF, including microstructural remodeling, elastin degradation and heightened inflammatory stress suggests a converging mechanistic pathway between these diseases,” the researchers wrote. Microvascular instability and impaired autoregulatory capacity associated with PXG may diminish the resilience of the RPE-choroid interface.” This is also borne out by the enhanced inflammatory response pseudoexfoliation syndrome patients experience after cataract surgery, they noted.A previous study highlighted in the paper provided additional evidence of vascular fragility by showing a tendency for spontaneous hyphema after pupillary dilation in PXG, particularly when posterior synechiae and systemic anticoagulation are present, indicating compromised vascular integrity. “This offers a biologically plausible explanation for the elevated CSCR hazard observed in patients with PXG compared with those with POAG,” the authors proposed in their paper.Male sex was associated with an approximately 2.5-fold increased hazard, consistent with previous studies. “The sex disparity has been attributed to hormonal and autonomic influences, including androgen-mediated vasoreactivity and heightened hypothalamic-pituitary-adrenal axis responses that may increase choroidal vascular tone,” the authors wrote.Obesity, phobic anxiety disorders, retinal vascular disease and the use of corticosteroids or sympathomimetics were also associated with an increased risk of CSCR, and the authors recommend heightened clinical vigilance for posterior segment pathology in patients with PXG, particularly those with these existing CSCR risk factors.Click here for the journal source. Abboud I, Fam A, Almobayed A, et al. Association between pseudoexfoliation glaucoma and central serous chorioretinopathy. Am J Ophthalmol. March 10, 2026. [Epub ahead of print.]  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.