Disposition of vitamin E in the eye.

To study the effect of exogenous vitamin E on its plasma and eye tissue levels, we administered 100 mg/kg of dl-alpha-tocopherol either by intravenous, intramuscular, or oral routes in 3-day-old newborn kittens. Controls did not receive the drug. alpha-Tocopherol levels in the plasma, retina, choroid, and vitreous were analyzed by high-performance liquid chromatography at selected intervals following drug administration. Our results showed that after intravenous administration of vitamin E, the retinal alpha-tocopherol levels increased 300 and 500% the baseline value at 2 and 4 h, respectively. By contrast, comparable retinal levels were achieved at 24 h following intramuscular administration and 72 h following oral administration. In the intravenous group high retinal levels were maintained up to 168 h, while in the intramuscular and oral groups retinal levels continued to increase up to 192 h. Irrespective of route of administration, the retinal concentration of alpha-tocopherol remained high even when the plasma levels were declining; plasma levels did not reflect retinal levels at any time. Following exogenous vitamin E administration, alpha-tocopherol levels increased both in the choroid (4 to 6 times the control) and in the vitreous (1.5 to 4 times the control). Significant differences in tocopherol levels were also seen between the eyes in the same animal in all groups. Our studies suggest a single dose of vitamin E by intravenous, intramuscular, or oral routes increases retinal levels from 3 to 5 times the control levels. However, peak retinal levels are achieved earlier by parenteral than by the oral route.(ABSTRACT TRUNCATED AT 250 WORDS)

Clearance of intravitreal 3H-fluorouracil.

The clearance of intravitreally administered 5-fluorouracil (5-FU) was studied under five experimental conditions. The same nontoxic dose resulted in similar initial intravitreal concentrations and cleared rapidly from all eyes (approximately 90% clearance within eight hours). Half-life values ranged from 46 to 168 minutes. The longest half-life occurred in aphakic-vitrectomized eyes in which hyaluronic acid (Healon) was substituted for vitreous (168 minutes). A similar half-life was found in normal eyes (150 minutes). The shortest half-life occurred in aphakic-vitrectomized eyes postoperatively (46 minutes). Intermediate half-life values occurred in vitrectomized but phakic eyes postoperatively (67 minutes) and in aphakic-vitrectomized "quiet" eyes (at least two weeks postoperatively) (82 minutes).

Toxicity of antineoplastic drug combinations in vitrectomy infusion fluid.

We evaluated a combination of various antineoplastic drugs used in vitrectomy infusion fluid for toxicity. A combination of 250 micrograms/ml of 5-fluorouracil with each of the following agents, 8.0 micrograms/ml of thiotepa or 40 micrograms/ml of etoposide, or 0.1 micrograms/ml doxorubicin, or 0.1 microgram/ml vincristine was tolerated well in the rabbit eyes.

Evaluation of intravitreal 5-fluorouracil, vincristine, VP 16, doxorubicin, and thiotepa in primate eyes.

A single intravitreal dose of 750 micrograms 5 fluorouracil (5 FU) or 5 micrograms doxorubicin were nontoxic to primate eyes. A concentration of 250 micrograms/ml of 5 FU in the vitrectomy infusion fluid in combination with 8 micrograms/ml of thiotepa, with 40 micrograms/ml of VP16 (etoposide), or with either .04 or .02 microgram/ml of vincristine was also well tolerated by the primate eye. 5 micrograms/ml of doxorubicin in the vitrectomy infusion fluid did not cause apparent toxicity to the retina. Toxic effects were noted in eyes receiving 250 micrograms of 5 FU in combination with either .15 or .1 microgram/ml of vincristine.

Retinochoroidectomy ab interno.

We evaluated the possibility of using an internal approach to surgically remove a part of the retina and choroid. Preoperative photocoagulation and the use of an endolaser and the vitrophage enabled us to perform retinochoroidectomy ab interno successfully in experimental animals.

Limitation of iris and ciliary body resection in primates.

The authors evaluated the limitation of iridocyclectomy in primate eyes. Six-clock-hour resections were tolerated and the intraocular pressure was reestablished to preoperative levels (17 mm Hg) within 1 month after surgery. Seven- to eight-clock-hour resections were also tolerated by the eyes, but the intraocular pressure remained low (7-10 mm Hg) for the extent of the study (5 months). Eyes in which the vitreous fluid was replaced with Healon showed a trend toward faster recovery of the intraocular pressure than those having a physiologic saline solution.

Toxicity of antineoplastic drugs in vitrectomy infusion fluids.

Twelve antineoplastic drugs were evaluated for their toxicity when used in vitrectomy infusion fluid. These drugs may have implications in the prevention of cellular proliferation inside the eye.