Showing papers by "Brenda J. Tripathi published in 1992"

Cytotoxicity of ophthalmic preservatives on human corneal epithelium.

Abstract: Because the corneal epithelium invariably encounters the full concentration of the preservative that is contained in multi-dose topical ophthalmic preparations, we investigated the cytotoxicity of several of these agents by using a sensitive model of human corneal epithelial cells in vitro. Primary cultures of epithelial cells were prepared from freshly enucleated globes. At confluence, all experimental cultures received a single dose of preservative at the concentration present in marketed formulations. The serum in the culture medium simulated the possible neutralizing effect of proteins present in the tear film in vivo. The cells were observed continuously by phase-contrast microscopy and time-lapse videomicrography for 24 hrs. Benzalkonium chloride at a concentration of 0.01% and chlorobutanol at 0.5% caused immediate cell retraction, as well as cessation of normal cytokinesis, cell movement, and mitotic activity; the epithelial cells degenerated within 2 hrs and 8 hrs, respectively. Cultures treated with chlorobutanol developed conspicuous blebs on the cell surface after 3 to 5 hrs of exposure. Thimerosal (0.001%) caused cell retraction, cessation of mitotic activity, and total cell destruction within 9 hrs. Sorbic acid (0.1% and 0.2%) greatly reduced cell movement and suppressed mitotic activity, but no cell death occurred. At concentrations of 50 ppm and 30 ppm, H2O2 instantaneously caused a marked retraction of the cells, followed by cessation of cytokinesis, cell movement, and mitosis. Retraction and death of the epithelial cells occurred within 12-24 hrs after exposure to 1 ppm H2O2 in serum-free medium. Polyquaternium ammonium chloride (0.001%) and polyaminopropyl biguanide (0.00005%) had no discernible effects on cytokinetic movement or on the mitotic activity of the epithelial cells. We relate our findings in vitro to those reported in vivo and discuss the mechanism of cytotoxicity of the various preservatives.

Ocular toxicity of prednisone in pediatric patients with inflammatory bowel disease.

Abstract: We performed ocular examinations on 58 corticosteroid-treated pediatric patients with inflammatory bowel disease (IBD) and on 58 age-matched controls. Posterior subcapsular cataracts (PSC) were detected in 12 of the 58 treated patients (20.7%) and in none of the controls. The difference in mean intraocular pressure (IOP) between the treated patients (15.89 +/- 4.11 mm Hg) and control subjects (13.63 +/- 2.35 mm Hg) was significant statistically (P or = 20 mm Hg, change in IOP > or = 6 mm Hg between visits, or a difference in IOP > or = 6 mm Hg between the two eyes). Formation of PSC was not correlated significantly (P > 0.05) with the total dose of prednisone, duration of treatment, average daily dose, or number of days on high doses (> or = 25 mg). Raised IOP was correlated (P = 0.005) only with average daily dose (12.4 +/- 10.9 mg/day; range, 0-47 mg/day) 30 days before examination. When the dose of corticosteroid was reduced to < 10 mg/day, 2 patients manifested regression of PSC, and 12 IOP responders showed a decrease in IOP to within 2 SD of the mean control IOP. Only 3 of the 58 treated patients (5.2%) manifested both PSC and raised IOP. A significant inverse correlation (P = 0.02) was established between IOP at first examination and formation of PSC. We propose that the mechanisms for steroid-induced lens opacities and raised IOP do not share the same genetic basis. Because 52% of these children developed either PSC or raised IOP with prednisone therapy, we advocate careful ophthalmologic monitoring of pediatric patients receiving corticosteroids for IBD or any other condition.

Role of receptors in the trabecular meshwork of the eye as targeted to the development of antiglaucoma therapy

Abstract: The major pathway for the outflow of aqueous humor from the anterior chamber of the eye is the trabecular meshwork/Schlemm's canal system. The meshwork is composed of connective tissue beams that are ensheathed by trabecular cells; these cells derive their nutrition from the aqueous humor and thus are uniquely susceptible to morphologic and biochemical regulation by bioactive substances that are present or released in this fluid and to pharmacologic agents that are targeted to act on the tissue. The receptors that have been detected on trabecular cells include those for growth modulatory peptides (bFGF, TGF-βI, transferrin, IGF-1, and EGF), epinephrine, dopamine, glucocorticoids, benzodiazepines, prostanoids, biogenic amines, the Fc portion of IgGs, and probably those for molecules of the extracellular matrix (integrins). Selective up- or down-regulation of the receptors on the trabecular cells would facilitate an effective control of the intraocular pressure in diseased conditions of the eye. We discuss the prospects and hurdles in the utilization of receptor targeting as a therapeutic modality for trabecular cell regeneration in glaucoma as well as for pharmacologic trabeculectomy and as a treatment for hypotony after glaucoma filtration surgery. We believe that regulation of receptor expression is a novel method for the development of new antiglaucoma agents and for minimizing the side effects of drugs that are administered topically and systemically for the control of the intraocular pressure. © 1992 Wiley-Liss, Inc.

Use of tissue plasminogen activator for rapid dissolution of fibrin and blood clots in the eye after surgery for glaucoma and cataract in humans

Abstract: We treated 10 patients with tissue plasminogen activator (tPA) for complications that threatened the successful outcome of anterior segment surgery for glaucoma and/or cataract, and that endangered the structural and functional integrity of the eye. Eight patients who had developed massive fibrin or blood clots in the anterior chamber each received 10–20 μg of tPA intracamerally, and two patients who had and extensive subconjunctival blood clot that blocked the filtration site received 25 or 30 μg of tPA subconjunctivally. The clots dissolved within 30 min to a few hours in all patients. Except in one patient who developed a 10% hyphema after the tPA injection, we observed no ocular complications in any of our patients during a follow-up period that ranged from 2–22 months. Our preliminary investigations show that intracameral injection of tPA is highly effective and safe for the rapid dissolution of fibrin and blood clots in the anterior chamber that obstruct the visual axis, obscure the view of the fundus, or cause failure of filtering blebs, and for lysis of synechiae of 2 to 3 days duration. Optimal results were obtained with intracameral injection of ≥ 10 μg tPA at 4 to 10 days after surgery. However, tPA should be regarded as an acute therapy and adjunctive modality for the treatment of fibrin and blood clots in the anterior segment of the eye. To avoid possible drug-induced complications, we advocate titration of the dose and repeat injection rather than a single large bolus of the drug. © 1992 Wiley-Liss, Inc.