Primary Open Angle Glaucoma is Associated with MR Biomarkers of Cerebral Small Vessel Disease

Glaucoma describes a group of optic neuropathies, characterised by slow progressive degeneration of retinal ganglion cells and their axons. This results in a characteristic appearance of the optic disc and progressive visual loss. Patients with glaucoma may show elevation of intra-ocular pressure (IOP) although in others the IOP is within normal limits Traditionally the term primary open and glaucoma (POAG) has been used to describe glaucoma associated with elevated IOP and treatment is directed towards normalisation of the pressure. However, apparently elevated IOP is relatively common in the normal population, many patients who fulfil the other clinical criteria of POAG have normal IOP and in many cases, glaucoma continues to progress, despite maintaining target IOP1. The term normal tension glaucoma (NTG) has been used to describe glaucoma where the IOP is within normal limits. However, there is considerable controversy in the literature over whether these disorders truly represent separate entities or simply extreme ends of a single distribution2. These entities do appear to differ in other ways, with different patterns and progression of field defects and the identification of risk factors such as migraine and nocturnal systemic hypotension in NTG3. Recent research has supported the hypothesis that the relationship between IOP and CSF pressure may be of importance in glaucoma since it will directly affect the pressure gradient across the lamina cribrosa3,4,5,6. Previous experimental studies have shown that some patients with POAG have abnormally low cerebrospinal fluid pressure3 but identified significant overlap between normal and glaucomatous groups, suggesting that additional factors, other than trans-laminar pressure gradient, must play a factor. It is clear that there are factors other than IOP involved in the pathogenesis of POAG which can impact the apoptotic process7. Factors that have been implicated include low ocular perfusion pressure, reduced ocular blood flow, low systolic blood pressure, cardiovascular disease, migraine, smoking and vasospasm disorders8,9,10. The identification of multiple vascular risk factors in association with glaucoma has led some authors to study the relationship between glaucoma and cerebral small vessel disease. A previous study by Stroman et al. found larger numbers of white-matter lesions in patients with NTG than controls11 and a recent study demonstrated that intraocular pressure was higher in normal individuals with evidence of cerebral white-matter lesions12. This is a preliminary hypothesis generating study that asks: 1) is glaucoma associated with evidence of cerebral small vessel disease; 2) do imaging biomarkers of cerebral small vessel disease in POAG and NTG show different characteristics.