Vascular, Immunological, and Mechanical Factors in Normal Tension Glaucoma: A Multidimensional Approach to Pathogenesis

Glaucoma is characterized by progressive degeneration of retinal ganglion cells leading to optic neuropathy and visual field loss. The major risk factor for glaucoma is elevated intra-ocular pressure (IOP) (Fig. 1). However, 30-40% of patients with glaucoma have normal IOP, leading to the classification of normal-tension glaucoma (NTG) (Fig. 1 C, E).1,2 The prevalence of NTG varies between populations, with Asians having the highest prevalence (77- 92%), followed by Africans (57%), and Caucasians (30-39%).3 In a landmark study, the collaborative normal tension glaucoma study group (CNTGS) showed that a 30% reduction in IOP in NTG patients slowed the rate of vision loss over 5 years.4 However, reducing IOP did not stop progression of disease in all NTG patients (22/66), suggesting that IOP alone cannot explain the pathology.4 As such, NTG is recognized as a multifactorial pathology with vascular, immunological, and mechanical drivers. Here we summarize the leading hypotheses in each category and review recent research that sheds light on novel mechanisms and therapeutic targets for NTG.