Hypoxic effects on corneal morphology and function

Abstract

Normal corneal metabolism depends on a critical level of oxygen, below which a series of acute corneal responses occur, including an increase in stromal lactate, a reduction in intercellular pH, and an increase in corneal hydration. These acute responses are reversible when normal oxygen is restored; however, it has been shown that chronic exposure to low oxygen levels can result in permanent morphologic changes in the corneal endothelium. Clinicians have expressed concern that these observed structural changes may also be accompanied by alterations in corneal physiology. Whether such effects occur is not known, since it has been difficult to assess human corneal function accurately. Recently, we have developed an in vivo test, able to measure overall corneal hydration control, that can be used to study the effects of hypoxia on corneal function. This test provides information on several characteristics of hydration control, one of which is the percent corneal thickness recovery per hour (PRPH) after inducing corneal swelling. In this study, we assumed that corneal hypoxia accompanies both extended and polymethylmethacrylate (PMMA) contact lens wear and that the dose received is related to the years of past lens wear. Using this paradigm, we explored the relationship of hypoxic dose to an endothelial polymegethism index (EPI), endothelial cell density (ECD), and PRPH in 36 subjects with varying contact lens wearing histories. Based on multiple regression analysis, the relative change (expressed as percent per year) associated with hypoxic dose (adjusted for age and gender) was found to be dose-dependent and corresponded to estimated changes of 1.70%/yr, -0.25%/yr, and -1.26%/yr, with 95% confidence limits of (-0.3, 3.7), (-1.4, 0.9), and (-2.6, 0.06) for EPI, ECD, and PRPH, respectively. These preliminary data suggest that hypoxic exposure alters endothelial morphology and reduces corneal function; however, it is important to indicate that this was a exploratory investigation with several limitations, and that therefore these results should be viewed as preliminary until more definitive studies are completed.