Parallel human and primate studies of the pathophysiologic mechanisms of ocular hypotony in eyes with ciliochoroidal detachment, cyclodialysis, iridocyclitis, and retinal detachment will be undertaken. Primate models of each of these disorders have been developed. Previous studies have indicated a key role for uveoscleral outflow in the pathogenesis of hypotony. Therefore, characterization of the physiology and anatomy of the uveoscleral outflow pathway will be performed. The intraocular pressure dependence, suprachoroidal hydrostatic pressure, and permeability of the ciliary musle interstitial spaces will be evaluated with fluorophotometry and flurorescence microccopy in normal eyes. The extravascular protein concentration and vascular permeability of the uvea will also be determined. In monkey eyes with ciliochoroidal detachment of iridocyclitis, the uveoscleral outflow rate and extravascular protein concentration and ciliary muscle permeability will be measured. The underlying hypothesis to be studied in the pathogenesis of hypotony is increased fluid permeability of the ciliary muscle interstitial spaces due to an increase in extravascular protein concentration due to abnormal vascular permeability. In a model of chronic rhegmatogenous retinal detachment, previous studies have strongly argued for the presence of posterior fluid movement through the virtreous, into the subretinal space, and across the RPE. From vitreous fluorophotometry, measurement of the inward and outward permeability of the blood retinal barrier (RPE) of carboxyfluorescein allows calculation of five physiologic parameters: (1) diffusional permeability of RPE to carboxyfluorescein, (2) rate of solute-linked water transport, (3) osmotic fluid permeability of the RPE, (4) hydrostatic fluid permeability of the RPE, and (5) active carboxyfluorescein transport of the RPE. These parameters will be measured in monkeys with normal eyes, eyes with acute, sub-acute, or chronic retinal detachment, following cryopexy, and after retinal detachment repair. The effects of various drugs will also be studied. Patients with hypotony from ciliochoroidal detachment, cyclodialysis or chronic iridocyclitis will be studied with aqueous fluorophotometry to measure the aqueos flow rate. The episcleral venous pressure will also be measured. In summary, the pathophysiologic mechanisms of ocular hypotony will be studied with special emphasis on unconventional aqueous outflow pathways.
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