Abstract
Altitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.
Highlights
Introduction conditions of the Creative CommonsGlaucoma is characterized by the loss of retinal ganglion cells and changes to the optic nerve head that are associated with progressive irreversible vision loss
The results show that changes in osmotic pressure difference (OPD), in conjunction with mean arterial pressure (MAP), capture the decreasing trend of intraocular pressure (IOP) with altichanges in OPD, in conjunction with MAP, capture the decreasing trend of IOP with tude as observed in the Mont Blanc study (MBS)
In order to overcome these limitations, in this study, we used an innovative methodological approach indicated as physiology-enhanced data analytics able to integrate experimental data—derived from the MBS [32]—with validated mathematical models [39,40] in order to shed further light on the physiologic relationships between IOP, blood pressure (BP), and ocular hemodynamics with altitude
Summary
Introduction conditions of the Creative CommonsGlaucoma is characterized by the loss of retinal ganglion cells and changes to the optic nerve head that are associated with progressive irreversible vision loss. Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, with research having established IOP reduction as effective in delaying or preventing the onset and progression of the disease [2]. Currently less-modifiable risk factors have been identified in the disease pathogenesis including deficiencies in both systemic and ocular hemodynamics [3–5]. These risk factors are known to be influenced by altitude; the underlying mechanisms and the clinical significance of altitude’s effects on them have not been established. Oxygen saturation within the blood decreases due to the depressed atmospheric pressure [6,7] This results in a cascade of systemic responses, including an increase in resting blood pressure and heart rate and autoregulatory alterations to cerebral blood flow secondary to hypoxia [8–11]. Several studies have noted ocular vascular changes with ascension including retinal vessel dilation and alterations in retinal and choroidal blood velocity and pressure [8,10,21,33,34]
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