EL CAMINO RECORRIDO EN ESTA EXPERIENCIA

In conclusion, the literature review into the effect of hypoxia on visual function found that all aspects of visual function are affected by hypoxia. Some functions, including visual fields and contrast sensitivity are preserved until lower oxygen concentrations/ higher altitudes are reached, whereas dark adaptation, colour vision and electrophysiological responses appear to be more sensitive indicators of hypoxia.

There is yet to be a consensus on which layer or cell type of the retina is most susceptible to hypoxia. Some studies conclude that the photoreceptors may be vulnerable due to the changes in visual function relating to the metabolic demand of the rods in mesopic studies (Connolly et al. 2009b; Connolly et al. 2008b; Connolly et al. 2008a), others that there is a preferential postreceptoral susceptibility (Feigl et al. 2007; Kang Derwent and Linsenmier 2000; Smith et al. 1976; Vingrys et al. 1987; Tinjust et al. 2002; Kergoat et al. 2006), and some that both are affected (Pavlidis et al. 2005). Kang Derwent and

Linsenmeier (2000) suggested that the function of the photoreceptors may be preserved under hypoxemia as when oxidative metabolism is affected; they switch to glycolysis for energy production.

Considering the central and peripheral retina, there is some dispute as to the area most affected by hypoxia, dependant on the visual function being tested. Some studies conclude that the peripheral retina, out to 40-45° is more sensitive to changes in

et al. (2005) and Klemp et al. (2007) suggested that it is the macula. This may depend on the function being assessed and the state of retinal adaptation.

All of the visual functions were affected by hypoxia more in scotopic and mesopic than photopic conditions. This can be explained by the increased metabolic activity of the retina in the dark.

There are a few points to note in the comparison of the data. Ernest and Krill (1971) and Vingrys and Garner (1987) cautioned against comparing studies conducted by the dilution of oxygen with those which altered the atmosphere, such as using a decompression chamber, due to the possible independent effect of barometric pressure. A review comparing hypobaric hypoxia (a low barometric pressure and low oxygen level) to

normobaric hypoxia (normal barometric pressure and low oxygen levels) found that SpO2 was lower in hypobaric hypoxia for the same partial pressure of oxygen for short term exposure (Coppel et al. 2015). The control of the test environment could also have influenced results in some experiments (Bouquet et al. 2000; Schmeisser et al. 1997), which may make it difficult to compare climbing studies on foot with those conducted in the laboratory.

The possibility of carbon dioxide affecting results is something studies have aimed to control (Ernest et al. 1971; Vingrys et al. 1987). Hyperventilation has been found to raise visual thresholds short term by as much as 0.7- 1.0 log units (Wald et al. 1942a). This shows the potential impact of breathing patterns on results. More recent studies have

used subjects who are experienced in hypoxic environments, or provided training to minimise these effects (Leid et al. 2001; Pavlidis et al. 2005; Connolly 2011; Connolly et al. 2006).

The review into the role of hypoxia in the pathogenesis of AMD provided evidence that there is an altered blood supply to the outer retina in AMD. However, although the change in circulation has been shown in studies looking at the retrobulbar and the

choroidal circulation, there is some question as to whether these changes lead to hypoxia (Campochiaro 2000). Thickening and deposition of Bruch’s membrane in early AMD is hypothesised to exacerbate any hypoxia by increasing the distance over which oxygen must travel to reach the retina (Wangsa-Wirawan et al. 2003). Further research is required to conclusively determine whether hypoxia results from the reduced blood supply and from sub-retinal deposits in AMD (Harris et al. 1999).

Hypoxia is known to prevent the degradation of HIF, which leads to the up-regulation of growth factors including VEGF, stimulating neovascularisation in nAMD. A reduction in growth inhibitors, including PEDF, also influences the progression of neovascularisation (Bhutto et al. 2006). Hypoxia also influences the regulation of other proteins and cell regulators, which can also promote neovascularisation (Dong et al. 2011). There is new evidence that a reduction in the synthesis of haemoglobin by the RPE may also result in hypoxia in AMD (Tezel et al. 2009).

The visual deficits seen in AMD are also seen in normal participants during a hypoxic episode, suggesting that hypoxia could be the cause of these of deficits in AMD. This is evidenced by the co-localisation of changes in visual function with alterations in choroidal perfusion.

The evidence in the literature to date suggests that hypoxia may be involved in the pathogenesis of AMD, both in the early stages and in nAMD and GA. However, there is currently only circumstantial evidence to link the changes in visual function associated with AMD to the onset of hypoxia. This thesis aims to probe this relationship by

investigating the effect of transient systemic hyperoxia and hypoxia on visual function in AMD.

3 Effect of respired oxygen

concentration on SpO2 and scotopic

thresholds in healthy controls

This chapter presents studies to investigate the effect of breathing 60% and 14% oxygen on scotopic thresholds in healthy controls, and the effect of the retinal location of the stimulus on the response to the hypoxia / hyperoxia. Studies also investigate the changes in SpO2 levels over time when breathing 10% and 14% oxygen.