Monday, August 31, 2009

Mechanism of Cyclocryotherapy

Mechanism of Action
Cyclocryotherapy presumably destroys the ability of ciliary processes to produce aqueous humor by the biphasic mechanism of intracellular ice crystal formation and ischemic necrosis (13). Initially, freezing of extracellular fluid concentrates the remaining solutes, which leads to cellular dehydration and is the probable mechanism of cell death associated with a slow freeze. When the rate of cooling is rapid, intracellular ice crystals develop. Although these crystals are not always lethal to the cell, a slow thaw leads to the formation of larger crystals, which are highly destructive to the cell by an uncertain mechanism. Maximum cell death is achieved with a rapid freeze and a slow thaw. A second and later mechanism of cryoinduced cell death is a superimposed hemorrhagic infarction, which results from obliteration of the microcirculation within the frozen tissue. Ischemic necrosis is the histologic hallmark of cryoinjured tissue.
Animal studies have revealed significant differences between the temperature of the cryoprobe and the temperature within the treated tissues (14,15). In living eyes, a temperature of 60°C to 80°C over the sclerolimbal area was shown to produce a temperature of approximately 10° C at the tips of the ciliary processes after a lag of 20 to 30 seconds (15). The latter temperature is near the minimum thermogradient at which cryoinjury normally occurs (15). Ciliary body blood flow in rabbits is reduced 50% to 60% when treated with 80° C cryoapplications for 60 seconds (16). Histologic studies of eyes treated with cyclocryotherapy show destruction of vascular, stromal, and epithelial elements of the ciliary processes with replacement by fibrous tissue (4,15,17,18). Ciliary epithelium has been observed to regenerate in monkeys, but not in human eyes (18).
In addition to lowering the IOP, cyclocryotherapy may provide relief of pain by the destruction of corneal nerves. Wallerian degeneration of corneal nerve fibers was observed in rabbits following cyclocryotherapy, although regeneration began within 9 to 16 days (19).