From tumor microenvironment to ocular hypertension: unraveling the pathogenesis and therapeutic strategies of cancer-related glaucoma

Abstract

Cancer is a global health threat, and its incidence and mortality are increasing annually. Cancer-related glaucoma, a severe complication caused by primary or metastatic tumors and their treatments, has complex pathogenic mechanisms. This review aims to clarify the risk factors, classification, diagnosis, and treatment progress of this glaucoma type. Mechanisms include mechanical obstruction, secondary angle closure, neovascularization, inflammation and cytokine release, alterations in aqueous humor dynamics, and secondary hemosiderosis. Clinical manifestations are diverse, such as rapid intraocular pressure increase, neovascular changes, and tumor-related characteristic signs. Treatment requires multidisciplinary cooperation, with primary tumor control as the core, combined with drugs like anti-VEGF agents and targeted therapies, and modified surgeries. Future research should focus on personalized therapeutic strategies, gene therapy applications, integration of multimodal imaging, and optimization of AI models to optimize early intervention and reduce the risk of irreversible optic nerve damage.

Keywords: cancer-related glaucoma; clinical manifestation; multidisciplinary collaboration; pathogenesis; treatment strategies.

FIGURE 1

Common pathogenic mechanisms of tumor-related secondary glaucoma. The blue arrows in the figure simulate the production and drainage pathways of intraocular aqueous humor. Part A illustrates that under the influence of iris tumors, the posterior chamber space becomes narrow, the anterior chamber angle is narrowed, and the aqueous humor produced by the ciliary body is difficult to reach the anterior chamber due to pupillary block. At the same time, the fluid in the anterior chamber also struggles to get through the trabecular meshwork through the narrowed angle. Part B shows that secondary angle closure prevents aqueous humor from being drained through the trabecular meshwork. Part C illustrates the neovascular changes in the iris and anterior chamber angle, with the disease progression depicted in this static image encompassing three distinct phases: In the first phase, new vessels emerge on the trabecular meshwork without elevated IOP; in the second phase, fibrous tissue surrounds these vessels, impairing filtration and increasing IOP; in the third phase, fibrovascular contraction causes irreversible angle closure. Responses to anti-VEGF therapy vary across these stages. Part D illustrates that the ciliary body, stimulated by inflammatory factors, leads to increased concentrations of inflammatory factors and proteins in the aqueous humor (indicated by brown dots), resulting in blockage and fibrosis of the trabecular meshwork.