If liquefaction of the vitreous body is a significant risk factor for nuclear cataract, it is important to identify the changes that follow the destruction of the vitreous gel, either during aging or after vitrectomy, that contribute to the opacification of the lens nucleus. Several possibilities can be considered.
It is possible that one or more essential metabolites may be lost after vitreous degeneration and the absence of this material may contribute to the formation of nuclear cataracts. Although this possibility cannot be ruled out at this time because the composition of the vitreous body is complex, examination of gel and liquid vitreous has found that they have similar composition.
28
It is also possible that the factors responsible for the liquefaction of the vitreous body independently cause nuclear opacification or that opacification and hardening of the lens nucleus somehow lead to degeneration of the vitreous body. The causes of age-related vitreous liquefaction are not known, although it has been suggested that light, oxidative damage, or increased proteolytic activity may be responsible.
28 40 41 42 43 Several studies have shown that increased sunlight exposure is not associated with increased risk of nuclear cataracts.
5 6 52 Therefore, sunlight exposure is not likely to explain the relationship between vitreous liquefaction and opacification of the lens nucleus. Oxidative damage to lens proteins and lipids is a hallmark of nuclear cataracts. Therefore, increased oxidative stress in the eye may contribute to vitreous degeneration and formation of nuclear cataract. It is not apparent how elevated levels of proteases could lead to selective damage to the lens nucleus without damaging the outer cells of the lens, or how opacification and hardening of the lens nucleus might alter the properties of the vitreous, although these possibilities cannot be ruled out.
Nuclear opacities occur frequently in the first 2 years after vitrectomy, as well as being more prevalent in eyes with liquefaction of the vitreous body. Therefore, it seems possible that it is the loss of the gel state of the vitreous body that increases the risk of nuclear cataract. In an eye with an intact vitreous gel, soluble substances, such as growth factors, ions, and metabolites, are redistributed by the relatively slow process of diffusion. The concentration of these molecules should be highest near the tissues that produce them or transport them into the eye and lowest near tissues that consume them or transport them out of the eye. Liquefaction or removal of the vitreous body, which permits the fluid in different regions of the eye to intermix rapidly, would prevent the formation of these gradients and rapidly distribute solutes throughout the posterior segment of the eye.
One solute that should be significantly altered in its distribution in the eye after loss of the vitreous gel is oxygen. Oxygen diffuses from the retinal arterioles into the vitreous body and the cells of the inner retina consume oxygen, removing it from the vitreous body.
53 These competing processes result in a steep, standing oxygen gradient within the narrow band of vitreous gel that is closest to the retinal arteries and arterioles
(Fig. 6A) .
53 54 55
Consistent with these studies, the oxygen concentration measured around the lens is remarkably low in the intact human eye. Throughout the central and anterior vitreous body the partial pressure of oxygen is approximately 16 mm Hg (∼2% O
2).
56 57 Comparably low oxygen levels (∼1.8%) have been measured in the anterior chamber near the surface of the lens capsule.
58 Most tissues show signs of hypoxia when oxygen levels fall below 5%. Thus, the lens is normally exposed to especially low levels of oxygen.
When the retina is not bounded by the vitreous gel, as occurs after vitrectomy or posterior vitreous detachment, oxygen from the retinal vessels would be carried away from the surface of the retina by fluid movement and distributed throughout the liquefied portion of the vitreous
(Figs. 6B 6C) .
59 Fluid movement over the unbounded inner surface of the retina should occur frequently (for example, after most movements of the head or eyes). Redistribution of oxygen from well oxygenated (perfused) to hypoxic (nonperfused) areas of the retina has been demonstrated after vitrectomy or posterior vitreous detachment and is believed to explain the beneficial effects of these conditions in diabetic retinopathy and branch retinal vein occlusion.
59 60 61 In a similar manner, circulation of the vitreous fluid after vitrectomy or degeneration of the vitreous gel could expose the lens to higher concentrations of oxygen than in an eye with an intact vitreous gel
(Figs. 6B 6C) . In agreement with these predictions, our recent studies demonstrate that, in human eyes, vitrectomy leads to loss of the normal gradient of oxygen in the eye and increases the level of oxygen close to the lens (Shui Y-B, et al.
IOVS 2003;44:ARVO E-Abstract 3022). An increase in oxygen around and within the lens is also found in rabbits after vitrectomy (Dillon J, et al.
IOVS 2003;44:ARVO E-Abstract 3501).
Exposure of the lens to elevated levels of oxygen can cause cataracts. Patients treated with hyperbaric oxygen therapy for 1 hour each day for a year or more showed frank nuclear cataract or early signs of nuclear opacification, including a myopic shift.
62 Studies of shorter duration have also shown that hyperbaric oxygen treatments cause a shift toward myopia.
63 64 Precataractous changes are also seen in the lenses of experimental animals if they are regularly exposed to hyperbaric oxygen.
65 66 67 68
Based on these observations, we suggest the intact vitreous gel normally helps to maintain the low level of oxygen around the lens by preventing bulk flow of the vitreous fluid. Degeneration or destruction of the vitreous gel would allow more oxygen to reach the lens, and increased exposure of the lens to oxygen causes nuclear cataract
(Fig. 6C) .