Analgesic efficacy and safety of ketorolac after photorefractive keratectomy. Ketorolac Study Group.

PURPOSE: The analgesic efficacy and safety of topical ketorolac tromethamine 0.5% ophthalmic solution (Acular) in photorefractive keratectomy was compared to its vehicle. METHODS: Double-masked, multicenter, study of 200 patients dosed with 1 drop of study medication (ketorolac or vehicle) in the operated eye immediately after surgery (eye patched), with four-times daily dosing for the next 3 days starting 3 hours after surgery. Mepergan Fortis was available as an escape pain medication. RESULTS: Patients (102) in the ketorolac group reported significantly greater pain relief and less pain intensity than the vehicle group (98) at several time points (P < or = .039). Time to first use of escape medication was significantly longer in the ketorolac than the vehicle group (mean, 16.0 vs 5.5 hr; P =.001). Time to complete pain relief was significantly shorter in the ketorolac than the vehicle group (mean, 41.3 vs 50.3 hr; P =.022). Significantly fewer patients in the ketorolac group reported sleep difficulties, ocular discomfort, or other difficulties. Few adverse events were reported with ketorolac treatment (less than with vehicle), and there were no clinically significant changes in any of the safety variables monitored. CONCLUSIONS: Ketorolac tromethamine 0.5% ophthalmic solution (Acular) is safe and significantly more effective than vehicle in alleviating pain following photorefractive keratectomy.

Results of alloplastic tube shunt procedures before, during, or after penetrating keratoplasty.

The association of glaucoma and penetrating keratoplasty presents a difficult management problem, particularly when medical therapy and conventional glaucoma surgery have failed. We have found alloplastic tube shunt surgery to be an effective method for intraocular pressure control in glaucomatous eyes subjected to penetrating keratoplasty. We report 46 patients who underwent alloplastic tube shunt implantation before (13 patients, group A), in combination with (17 patients, group B), or after (16 patients, group C) penetrating keratoplasty. All groups had significantly lowered intraocular pressure postoperatively. The most common complication was graft failure, in 31% of patients in group A, 29% in group B, and 44% in group C. Other postoperative complications and results including visual outcome are reviewed. Because the management of advanced glaucoma in patients undergoing keratoplasty is difficult, alloplastic tube shunt implantation should be considered.

The use of confocal microscopy in evaluating corneal wound healing after excimer laser keratectomy.

Corneal wound healing following excimer laser keratectomy is the major cause of regression of treatment results. The amount of anterior stromal haze that develops may be influenced by topical medications. Over a period of 6 months, we followed 15 New Zealand white rabbit eyes that underwent excimer laser keratectomy with the VISX 193-nm ArF laser at a fluence of 150 mJ/cm2 for a depth of 130 microns. Eyes were randomized to treatment with prednisolone acetate, diclofenac sodium (Voltaren), a combination of both, and a control group. Drops were administered four times a day for 1 week, two times a day for 3 weeks, and the drops were then tapered. All eyes were reepithelialized by 5 to 7 days. The tandem scanning confocal microscope (TSCM) was used to evaluate the corneal wound in vivo weekly for a month and monthly for 6 months. During the early postoperative period, the TSCM revealed significant anterior stromal keratocyte activation with cell elongation and the spindle-shaped appearance of fibroblasts in all groups. Collagenous stromal scarring was evident initially, then slowly decreased in all treatment groups. This study shows that TSCM is clinically useful for successive in vivo examinations of corneal wounds after excimer laser keratectomy and for comparing the effects of various topical medications.

Glaucoma in the immediate postoperative period after penetrating keratoplasty.

In a prospective study 155 consecutive patients undergoing penetrating keratoplasty were examined for postoperative increase in intraocular pressure to determine the frequency and duration of intraocular pressure spikes, risk factors, and response to treatment. Patients were maintained on preoperative glaucoma medications except miotics. Additional medications to lower intraocular pressure perioperatively were not given. Intraocular pressure was measured two to five hours, one day, and one week postoperatively. An intraocular pressure of 30 mm Hg or greater was considered an increase in pressure and was treated according to a standardized protocol. The results were analyzed by procedure as well as by variables commonly perceived to be associated with intraocular pressure increase (history of glaucoma, use of hyaluronate, lysis of the synechiae, or vitrectomy at the time of the operation). Overall, intraocular pressure increases in the early postoperative period occurred in 18 of 155 patients (12%). Pressure increases occurred in ten of 48 patients (21%) with a history of glaucoma; five of 24 patients (21%) undergoing combined penetrating keratoplasty, extracapsular cataract extraction, and posterior chamber intraocular lens implantation; and ten of 43 patients (23%) undergoing vitrectomy at the time of penetrating keratoplasty.

Results of penetrating keratoplasty in aniridia.

Eight aniridic patients with bilateral corneal scarring, vascularization, or edema underwent corneal transplantation in one or both eyes (11 eyes). Follow-up ranged from eight months to 5 1/2 years (average, three years). Six of 11 eyes (55%) had at least a two-line improvement in visual acuity and eight of 11 (73%) had at least one line of improvement. Best-corrected visual acuity was 20/200 or worse in nine of 11 eyes (82%), however. Postoperative complications included whorl keratopathy, persistent epithelial defects, central subepithelial scarring, peripheral vascularization with pannus, and graft rejection. Glaucoma was well controlled medically but five of nine patients (56%) with preexisting glaucoma needed an increase in medication for intraocular pressure control. Graft rejection occurred in seven of 11 eyes (64%) and three of these eyes required repeat transplantation.

The relationship of SR-2508 sensitizer enhancement ratio to cellular glutathione levels in human tumor cell lines.

We have recently demonstrated that intracellular elevation of glutathione (GSH) by oxothiazolidine 4-carboxylate lessens SR-2508 hypoxic cell radiosensitization in Chinese hamster cells. This observation, coupled with the fact that GSH depletion potentiates SR-2508 hypoxic radiosensitization, prompted a study of human tumor cell lines whose inherent GSH levels are high compared to normal human cell lines or rodent cell lines. Sensitizer enhancement ratios (SER) for a range of SR-2508 concentrations were determined for human tumor cell lines varying in inherent GSH levels. The SER (at the 1% survival level) for 1 mM SR-2508 was found to decrease as the inherent intracellular GSH level increased, particularly for clinically relevant SR-2508 concentrations. All human tumor cell lines studied yielded lower SER values than Chinese hamster V79 cells over the SR-2508 concentrations studied. GSH depletion by buthionine sulfoximine (BSO) of a human tumor line (A549) particularly high in GSH resulted in potentiation of SR-2508 effects. Maximal sensitization occurred when extremely low GSH levels were attained; however, enhancement was observed for a drop of only 30% in GSH levels. Should these high GSH levels seen in human tumor cell lines also apply to clonogenic or potentially clonogenic cells in human tumors in vivo, these findings might explain, in part, the negative results of some human nitroimidazole clinical trials.