Free radicals, ocidative stress and cataract

In the more developed countries of the world, cataract accounts for approximately 20% of all registered cases of blindness. The development of cataract may be associated with many factors including ageing, trauma, burns, extreme heat or cold, certain systemic diseases such as diabetes, and inflammatory processes within the eye. However, recent evidence suggests that oxidative damage to the lens by free radicals may also be involved in the development of certain types of cataract. The objective of this article is to describe the formation and action of free radicals within the body and review the evidence that the development of cataract may be linked to oxidative processes.

Autonomic dysfunction and systemic oxidative stress associated with glaucomatous optic neuropathy

There were four principal sections to the work: 1. Investigation of ocular and systemic vascular risk factors in POAG. The principal findings of this work were: a). Glaucoma patients exhibit an anticipatory reaction to the physical stress, similar to subjects at risk for cardiovascular diseases; a blunted BP response and a reduction in ONH blood flow in response to cold provocation was also recorded. b). Silent myocardial ischaemic episodes occurred during peaks in systemic BP and HR. c). Independent of a positive history for cardiovascular diseases, patients suffering from POAG demonstrate a blunt circadian rhythm of the ANS. 2. Assessment of the relationship between vascular and systemic vascular risk factors in GON. The principal findings of this work were: a). POAG patients demonstrate a high sympathetic tonus over a 24-h period. b). POAG patients with lower OBF demonstrate both 24-h systemic BP and HRV abnormalities. c). OBF alterations observed in some glaucoma patients could be either primary or secondary to systemic haemodynamic disturbances and not a consequence of ONH damage. 3. Assessment of the level of systemic anti-oxidant defence in POAG patients. The principal finding of this work was: Patients suffering from POAG demonstrated significantly lower GSH and t-GSH levels than normal controls. 4. Investigation of the effect of treatment with latanoprost 0.005% on visual function and OBF. The findings of this work were: a). Treatment with latanoprost 0.005% resulted in a significant decrease in IOP and increase in OPP. VF damage progression has also been stopped. b). Treatment with latanoprost 0.005% resulted in a significant increase in the OBF parameters measured at the ONH and peripapillary retina levels. Finally, the importance of a clear protocol for managing new POAG cases is highlighted and a clinical conduit is proposed.

Ocular and systemic vascular dysfunction in neurodegenerative disease

The important role played by vascular factors in the pathogenesis of neurodegenerative disease has been increasingly realised over recent years. The nature and impact of ocular and systemic vascular dysfunction in the pathogenesis of comparable neurodegenerative diseases such as glaucoma and Alzheimer’s disease (AD) has however never been fully explored. The aim of this thesis was therefore to investigate the presence of macro- and micro-vascular alterations in both glaucoma and AD and to explore the relationships between these two chronic, slowly progressive neurodegenerative diseases. The principle sections and findings of this work were: 1. Is the eye a window to the brain? Retinal vascular dysfunction in Alzheimer’s disease · Mild newly diagnosed AD patients demonstrated ocular vascular dysfunction, in the form of an altered retinal vascular response to flicker light, which correlated with their degree of cognitive impairment. 2. Ocular and systemic vascular abnormalities in newly diagnosed normal tension glaucoma (NTG) patients · NTG patients demonstrated an altered retinal arterial constriction response to flicker light along with an increased systemic arterial stiffness and carotid artery intima-media thickness (IMT). These findings were not replicated by healthy age matched controls. 3. Ocular vascular dysregulation in AD compares to both POAG and NTG · AD patients demonstrated altered retinal arterial reactivity to flicker light which was comparable to that of POAG patients and altered baseline venous reactivity which was comparable to that of NTG patients. Neither alteration was replicated by healthy controls. 4. POAG and NTG: two separate diseases or one continuous entity? The vascular perspective · POAG and NTG patients demonstrated comparable alterations in nocturnal systolic blood pressure (SBP) variability, ocular perfusion pressure, retinal vascular reactivity, systemic arterial stiffness and carotid IMT. · Nocturnal SBP variability was found to correlate with both retinal artery baseline diameter fluctuation and carotid IMT across the glaucoma groups.