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Cognitive impairment and psychiatric symptoms in Normal Tension Glaucoma (NTG) - A naturalistic study

Mohammad Z Mustafa

Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, United Kingdom

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Tej Rane-Malcolm

Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, United Kingdom

Andrew J Tatham

Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, United Kingdom

Bal Dhillon

Princess Alexandra Eye Pavilion, Chalmers Street, Edinburgh, United Kingdom

Amanda Cotton

Royal Edinburgh, Department of Psychiatry, Edinburgh, United Kingdom

Premal Shah

Royal Edinburgh, Department of Psychiatry, Edinburgh, United Kingdom

Roshini Sanders

Queen Margaret Hospital, Department of Ophthalmology, Dunfermline, United Kingdom

DOI: 10.15761/NFO.1000122

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Purpose:To examine the cognitive and neuropsychiatric characteristics of patients with Normal Tension Glaucoma (NTG).

Methods: A cross-sectional observational study of 99 patients with glaucoma and untreated intraocular pressure consistently <22mmHg on phasing.  All subjects underwent cognitive assessment and psychiatric symptom screening using the minimental state examination (MMSE), adult verbal learning test (AVLT) and general health questionnaire (GHQ). All subjects had comprehensive ophthalmic examination and documentation of past medical and psychiatric history.

Results: Subjects had a mean age of 70.5 years and 59 (59%) were female. 57 (57%) had an advanced visual field defect in the worse eye, 19 (19%) a moderate defect and 23 (23%) a mild defect. There were a high proportion of patients with impaired MMSE, AVLT or GHQ scores. 28 (28%) had significant short-term memory impairment on AVLT, and 28 (28%) scored 5 or more on the GHQ suggesting psychiatric caseness. 12 (12%) scored 24 or less on the MMSE.43 subjects underwent CT or MRI neuroimaging, with 13 (30%) showing age excessive generalised cerebral atrophy and 9 (20%) showing excessive small vessel disease. 41 patients had systemic hypertension, 28 ischaemic heart disease, 21 diabetes, 18 migraine, 13 transient ischaemic attack and 3 Raynaud’s disease.

Conclusion:Patients with NTG had a high prevalence of cognitive impairment and psychiatric symptoms identified using common screening tools, suggesting a possible shared intraocular pressure independent mechanism of disease. Ophthalmologists should be aware of the possibility of undiagnosed cognitive impairment and psychiatric morbidity in some patients with NTG.


normal tension glaucoma, psychiatric disease, cognitive profile, visual field defect


Normal tension glaucoma (NTG) is defined as a form of primary open angle glaucoma (POAG) where intraocular pressure (IOP) is consistently less than 22mmHg. While this definition has limitations, due to population differences in what constitutes a “normal” pressure and diurnal and day-to-day fluctuation in IOP, it is likely that the relative importance of IOP and non-IOP related mechanisms of glaucomatous damage vary between those that develop glaucoma at low and high IOP.  Worldwide the prevalence of NTG varies. In people of European ancestry, NTG is thought to affect as many as 50% of patients suffering with POAG, while in the Japanese population NTG accounts for up to 92% of glaucoma [1,2].

The diagnosis of NTG can be challenging and, perhaps due to the persistent perception that raised IOP and glaucoma are synonymous, patients may present late. Previous studies have shown a disproportionate number of patients with NTG are registered blind. For example, we previously examined a 20-year period of blind registrations in Fife, a region of Scotland with a population of 400000, and found those with NTG were over represented in blind registrations [3,4]. The management of NTG is also challenging. Although studies such as the Collaborative Normal Tension Glaucoma Study have shown that medical or surgical reduction of IOP reduces the risk of disease progression[5], some patients’ progress despite IOP reduction suggesting susceptibility to non-IOP mediated retinal ganglion cell damage[6]. Glaucoma is a neurodegenerative disease characterised by changes to the optic nerve head, however there is growing evidence that the entire visual pathway is affected [7]. This raises the possibility that patients with glaucoma may exhibit non-ocular signs of neurodegeneration. Several studies investigating this theory have suggested an association between glaucoma and neurodegenerative diseases such as dementia [8,9]. For example, the recent Three-City-Alienor Cohort study found a high prevalence of glaucoma in patients with dementia, especially NTG [10]. An association between glaucoma and Alzheimer’s disease (AD) has also been described, and it has been proposed that both conditions involve neuro-inflammation, decreased cerebrospinal fluid pressure and biomechanical stress and that B-amyloid may have a toxic effect on RGC apoptosis[11-13]. There is also evidence that vascular dysfunction contributes to glaucomatous optic neuropathy, with systemic vascular diseases including stroke and ischemic vascular disease, as well as vasospastic conditions such as Raynaud’s disease and migraine, associated with a higher risk of NTG[14-17].

The aim of the current study was to examine the cognitive a