Altitude-related illness and retinal vascular geometry: a hypothesis.

341 RETINAL HEMORRHAGES form part of the cluster of signs of high altitude retinopathy (HAR) (Morris et al., 2006). It is unclear why hemorrhages occur only in some individuals. Could interindividual variation in retinal vascular topography influence susceptibility to HAR? Risk factors for HAR can be considered as local or systemic and environmental or genetic. For example, abnormal retinal arteriolar hemodynamic responses to hypobaric hypoxia may occur (Mullner-Eidenbock et al., 2000). Age, disease, medications, smoking, and the nature of an individual’s Valsalva effects may have a role. If vascular topography alters the risk of HAR, can a plausible mechanism be suggested? Retinal vascular topographical features such as vessel tortuosity, arteriovenous ratio, junctional exponent, bifurcation angles, and fractal dimension influence local shear stress levels (Patton et al., 2006). Capillary walls are thin enough to allow gaseous diffusion, but this property compromises their strength. Increased capillary pressure can rupture vessel walls (West, 2000). For example, hemoptysis occurs when the pulmonary capillary vascular bed is placed under high pressure in left ventricular failure. Retinal blood flow is increased by two systemic factors present at high altitude: lower partial pressure of oxygen (Strenn et al., 1997) and exercise (Dumskyj et al., 1996). Shear stress failure might occur in the retina of geometrically predisposed individuals, resulting in hemorrhages. The geometric pattern of an individual’s vascular bed tends toward the topographical pattern that optimizes certain parameters, including shear stress. Deviations from optimal patterns have been observed in disease states (Patton et al., 2006). Increased retinal vascular tortuosity has been noted at altitude (Rennie and Morrissey, 1975). Tortuosity occurs because of longitudinal elongation. Because the blood has a longer distance to travel in a tortuous vessel than in a straight vessel, for a given vessel diameter the intravascular pressure and shear stress on capillary walls are lower. Retinal vascular diameters also increase in those visiting high altitude (Rennie and Morrissey, 1975). Increased shear wall stress leads to acute vessel dilatation and, in the long term, to structural changes and increased vessel diameter (Pries and Secomb, 2002). If such structural changes are the net effect of chronically altered hemodynamic forces at high altitude, they may be protective because they lower shear stress. As well as diameter changes in individual vessels, long-term residents at high altitude would be expected to develop different protective topographical vascular patterns from those living at lower altitudes. Postnatal adaptation of microvasculature has been observed with acclimatization to altitude in pigeon pectoralis muscle (Mathieu-Costello et al., 1995), and vascular remodeling can be driven by shear stress (Urbich et al., 2003). However, the pertinent question relates not to those chronically adapted, but to those visiting high altitude; if topographic and structural changes are common in the latter, why do only some (Rennie and Morrissey, 1975) develop HAR? Local autoregulatory mechanisms serve to limit fluctuations in retinal blood flow and mechanical pressure on delicate capillary walls (Scholfield et al., 2007). Pressure autoregulation occurs when retinal arterioles dilate or constrict in response to changes in perfusion pressure (Dumskyj et al., 1996). The vascular glycocalyx translates mechanical changes in blood flow into altered production of vasoregulatory agents, such as nitric oxide (Pournaras et al., 2008). In certain individuals, variation in vascular geometry could permit local peaks in shear stress on vessel walls and, coupled with mechanotransduction efficiency at the lower end of the normal range, normal pressure autoregulatory abilities, already stretched, may be exceeded. Such individuals will have greater risk of HAR on any visit to high altitude. This hypothesis is speculative. However, future studies of altitude-related illness should consider retinal vascular topographical features as being worthy of study. Retinal circulation is easily accessible in vivo, and automated methods exist to quantify retinal vascular geometric features such as tortuosity (Martinez-Perez et al., 2002). Comparisons could be made between those who live at high altitude, those who travel to high altitudes and develop HAR, and those who travel to high altitudes and do not develop HAR. The same factors may influence the development of high altitude pulmonary or cerebral edema.