Presidential Symposium: Is normal tension glaucoma a separate entity from primary open-angle glaucoma (POAG)?
Prof. Jeffrey Liebmann started his talk by noting that glaucoma is a controversial disease. He noted that this question is important because it affects clinical care, research and public health. In answering this question, it is important to consider the following factors: intraocular pressure (IOP), risk factors for glaucoma, optic nerve structure-function and genetics. He noted that to measure the true IOP the eye will need to be cannulated.
He explained that the transcorneal IOP measurement is not a true IOP and it is affected by many factors such as corneal thickness and hysteresis. He also stated that although Goldman’s tonometer is a reference standard, it is not a gold standard and there is no perfect tonometer. Therefore, an inaccurate measurement cannot be used to define two different diseases. He also mentioned that risk factors (age, IOP factors, perfusion, myopia, biomechanics, retinal ganglion cell health etc.) could also not be used to differentiate POAG and NTG as these factors affect glaucoma patients in different ways.
In addition, he stated that the appearance of the optic nerve and the visual field cannot help to differentiate NTG and POAG. He noted that genomics and precision medicine may be very helpful in providing a better understanding of these two entities of glaucoma in the future. He concluded that NTG and POAG are part of the same clinical spectrum comprising optic neuropathy, progressive structural and functional damage to the optic nerve, and pressure-dependent and pressure-independent risk factors and they are both pressure-sensitive diseases therefore, lowering IOP slows progression.
Ocular blood flow and translaminar cribrosa gradient in the pathogenesis of NTG
This was discussed by Dr. Jost Jonas. High-pressure glaucoma (HPG) and normal tension glaucoma (NTG) can have strikingly similar optic nerve head morphology. He described the clear morphological differences between glaucomatous optic neuropathy and any vascular optic neuropathy. Although there is loss of neuroretinal rim (NRR) and deepening of the optic cup in all glaucoma types, rim loss is found in glaucoma but not in vascular optic neuropathies (except giant cell arteritis). The beta zone is also found in all glaucoma types but not in vascular optic neuropathies.
He noted that intraocular pressure (IOP) is positively correlated with blood pressure (BP) and cerebrospinal fluid (CSF) pressure and BP is positively correlated with CSF pressure. Therefore, all the pressures in the 3 fluid-filled compartments (blood, brain, and eye) are associated with one another and potentially driven by the BP. He concluded that in glaucoma, IOP may be elevated or orbital CSF pressure may be low. In patients with arterial hypotension (nocturnal dippers), reduction in CSF pressure is greater than the simultaneous reduction of IOP leading to translaminar pressure differences.
He concluded that the morphologic differences between glaucomatous and vascular-associated optic neuropathy contradict a primary role of vasculopathy in the pathogenesis of glaucomatous optic nerve damage. Rather this may be related to orbital CSF pressure.
Systemic and ocular risk factors in NTG
Prof. Ki Ho Park discussed the systemic risk factors (Aberrant immunity, inflammatory cytokines and systemic vascular abnormality) and ocular risk factors (IOP fluctuations, intraocular factor, extraocular factor or posture related) in NTG.
He noted that there were several pieces of evidence of aberrant immunity in glaucoma, one of which is the antibodies against HSP60 in NTG patients. Optic nerve head (ONH) glial cells is also a key player in immune responses. He discussed the possible relationship between H Pylori and glaucoma. He noted that the breakdown of the blood-brain barrier is essential in aberrant immunity in glaucoma. Disc haemorrhage and parapapillary atrophy indicate the locations of the breakdown of the blood-brain barrier (BBB).
Other risk factors associated with NTG are the presence of silent cerebral infarct or small vessel disease which are associated with visual field progression in newly diagnosed NTG. He mentioned that the preferred sleeping position was associated with asymmetric VF loss in OAG patients. Fluctuation of 24-hour IOP measurement by contact lens sensor was greater in NTG eyes than in healthy controls. During sleep time the IOP-related values were greater in NTG eyes than in healthy controls. NTG patients were more likely to assume the decubitus posture during their sleep than were the healthy controls.