John S. Cohen

Trabeculectomy with intraoperative mitomycin C versus 5-Fluorouracil: Prospective randomized clinical trial

OBJECTIVE To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN Prospective multicenter, randomized clinical trial. PARTICIPANTS One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.

Prosthetic iris implantation for congenital, traumatic, or functional iris deficiencies

Purpose: To determine the efficacy and safety of surgical implantation of prosthetic iris devices in patients with anatomic or functional iris deficiencies. Setting: Cincinnati Eye Institute, Cincinnati, Ohio, USA. Methods: Twenty‐five patients were enrolled in an interventional prospective noncomparative case series. Twenty‐eight eyes had prosthetic iris diaphragm implantation for traumatic iris defects, congenital aniridia or iris coloboma, herpetic iris atrophy, surgical iris loss, or ocular albinism. Prosthetic iris implantation was performed with phacoemulsification and intraocular lens (IOL) implantation in 20 eyes, secondary IOL implantation in 6 eyes, and IOL exchange in 1 eye. A single pseudophakic eye with disabling glare secondary to traumatic aniridia had secondary prosthetic iris implantation alone. The surgical ease of insertion, intraoperative and postoperative complications, postoperative anatomic results, visual acuity, and subjective glare reduction were evaluated. Results: Patients were followed postoperatively for a mean of 10.2 months (range 1.4 to 25.7 months). All eyes achieved the desired anatomic result. Visual acuity was improved in 22 of 28 eyes (79%), unchanged in 5 eyes, and worsened by a single line in 1 eye. Patients were surveyed postoperatively to determine the change in glare disability. The severity of glare disability was subjectively improved in 23 of 24 patients (96%) who responded to the survey. Intraoperative complications included 3 fractured implants as well as an incomplete or torn capsulorhexis in 3 eyes. Postoperative complications included transient hypotony in 2 eyes, mild persistent inflammation in 1 eye, and macular edema followed by a retinal detachment in 1 eye with recent severe trauma. Conclusions: Implantation of prosthetic iris devices improved postoperative outcomes by reducing glare disability and, in selected cases, by correcting aphakia. Although operating on traumatized, congenitally aniridic, or uveitic eyes presents special challenges, implantation of prosthetic iris devices appears to be a safe and effective method for reducing the ubiquitous glare in patients with iris deficiency.

A Placebo-controlled, Double-masked Evaluation of Mitomycin C in Combined Glaucoma and Cataract Procedures

PURPOSE This study was performed to determine if adjunctive use of mitomycin C (MMC) would increase the success of combined phacoemulsification, intraocular lens implantation, and trabeculectomy surgery with releasable sutures. METHODS Seventy-two eyes with cataract and glaucoma, requiring surgery for decreased vision, uncontrolled intraocular pressure, or to obtain a better view of the optic nerve, were randomized to receive a 2.5-minute subconjunctival exposure to either MMC (0.5 mg/ml) or placebo balanced salt solution. Postoperative evaluations at 3, 6, and 12 months were performed by a masked observer who recorded visual acuity, intraocular pressure, glaucoma medications, presence of filtering blebs, and complications. Endothelial cell counts were measured before and 3 months after surgery. RESULTS The MMC group had significantly greater reduction in mean intraocular pressure through the first 12 months of follow-up (7.05-7.65 mmHg versus 2.62-3.84 mmHg; P = 0.001-0.028). In addition, through the first 6 months of follow-up, the MMC group required significantly fewer medications (0.4-0.5 versus 1.1-1.2; P = 0.002-0.004). Requirements for additional glaucoma surgery were less in the MMC group (4/ 36) than in the placebo group (7/35) (P = 0.301). Filtering blebs were significantly larger at 6 and 12 months (P = 0.002 and P = 0.001, respectively), and would leaks were more common (P = 0.101) in the MMC group. The mean decrease in endothelial cell count at month 3 was slightly, although not significantly, greater in the MMC treatment group (206.9 versus 91.3 cells/mm2* P = 0.377). CONCLUSION The increased success of the glaucoma procedure in the MMC group together with relatively minor toxicity, suggests its use is beneficial in combined glaucoma-cataract surgery.

Twelve-Month, Randomized, Controlled Trial of Bimatoprost 0.01%, 0.0125%, and 0.03% in Patients with Glaucoma or Ocular Hypertension

PURPOSE To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of ophthalmic formulations of bimatoprost 0.01% and 0.0125% compared with bimatoprost 0.03%. DESIGN Prospective, randomized, double-masked, multicenter clinical trial. METHODS Patients with glaucoma or ocular hypertension were randomized to receive once-daily bimatoprost 0.01% (n = 186), bimatoprost 0.0125% (n = 188), or bimatoprost 0.03% (n = 187) for 12 months. The primary efficacy measure was IOP. Safety measures included adverse events and an objective assessment of conjunctival hyperemia. RESULTS Baseline mean IOPs were similar among treatment groups. Differences in mean IOP between the bimatoprost 0.01% or 0.0125% groups and the bimatoprost 0.03% group were less than 0.9 mm Hg throughout follow-up. Bimatoprost 0.01%, but not bimatoprost 0.0125%, was equivalent in efficacy to bimatoprost 0.03% based on predetermined criteria (limits of the 95% confidence interval of the between-group difference in mean IOP within +/- 1.5 mm Hg at all time points and within +/- 1 mm Hg at most time points). The overall incidence of treatment-related adverse events was reduced significantly in the bimatoprost 0.01% and bimatoprost 0.0125% groups compared with the bimatoprost 0.03% group (P < or = .034). The percentage of patients with a moderate to severe increase from the baseline macroscopic hyperemia score was: bimatoprost 0.01%, 3.2%; bimatoprost 0.0125%, 9.0%; bimatoprost 0.03%, 9.1% (P = .019 for bimatoprost 0.01% vs 0.03%). CONCLUSIONS Bimatoprost 0.01% was equivalent to bimatoprost 0.03% in lowering IOP throughout 12 months of treatment and demonstrated improved tolerability, including less frequent and severe conjunctival hyperemia. Bimatoprost 0.01% demonstrated a better benefit-to-risk ratio than bimatoprost 0.0125%.

Laser treatment in fellow eyes with large drusen: Updated findings from a pilot randomized clinical trial

PURPOSE To update the findings from the Choroidal Neovascularization Prevention Trial (CNVPT) with respect to resolution of drusen, incidence of choroidal neovascularization, and visual function. DESIGN A multicenter, randomized, controlled, pilot clinical trial. PARTICIPANTS The 120 patients enrolled in the CNVPT. Patients had signs of choroidal neovascularization or retinal pigment epithelial detachment in 1 eye and had >/=10 large (>63- micro m) drusen in the contralateral, or fellow, eye. INTERVENTION The fellow eye of 59 patients was assigned randomly to argon green laser treatment consisting of multiple 100- micro m spots at least 750 micro m from the center of the fovea. The fellow eye of the remaining 61 patients was assigned randomly to observation. MAIN OUTCOME MEASURES Change in visual acuity was the primary outcome measure. Incidence of choroidal neovascularization, resolution of drusen, change in contrast threshold, change in critical print size for reading, and incidence of geographic atrophy were secondary outcome measures. RESULTS Throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity, contrast threshold, critical print size, or incidence of geographic atrophy. With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the two treatment groups was the same. Most drusen resolution in treated eyes occurred within 24 months of the initial treatment. Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization. Among eyes developing choroidal neovascularization in each treatment group, most lesions (two thirds or more) were composed of occult neovascularization only. CONCLUSIONS Laser treatment as applied in the CNVPT caused an excess risk of choroidal neovascularization in the first year or so after treatment. The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study.

A 3-month comparison of 1% and 2% carteolol and 0.5% timolol in open-angle glaucoma

AbstractCarteolol, a nonselective beta-adrenergic antagonist with intrinsic sympathomimetic activity, was compared in 1% and 2% topical solutions with 0.5% timolol in 105 patients with primary open-angle glaucoma. In this double-masked, randomized 3-month trial, all three preparations significantly lowered intraocular pressure throughout the study, with no significant differences being observed. There were also no significant differences among the three preparations with regard to ocular or systemic adverse reactions, including heart rate and blood pressure. Offprint requests to: M.B. Shields

Cardiovascular Effects of Topical Carteolol Hydrochloride and Timolol Maleate in Patients With Ocular Hypertension and Primary Open-angle Glaucoma

PURPOSE To compare the effects of topical timolol maleate 0.5% and carteolol hydrochloride 1% on pulse rate and blood pressure. METHODS In a randomized, double-masked, parallel-design, multicenter clinical trial, we compared the effects of timolol and carteolol on pulse rate and blood pressure measured by 24-hour ambulatory blood pressure monitoring in 169 adult patients with either ocular hypertension or primary open-angle glaucoma. RESULTS From noon to 8 PM, baseline mean pulse rate of 82 to 83 beats per minute (bpm) had decreased by 4 to 6 bpm in both groups after 4 weeks of therapy with timolol or carteolol. From midnight to 4 AM, the pulse rate in the carteolol group was significantly above baseline (P = .005), while the timolol group was significantly below baseline (P < .001). Four times as many patients became bradycardic (heart rate, < 60 bpm) on timolol (18.4%) as did patients on carteolol (4.5%) from midnight to 4 AM. More than twice as many patients exhibited a resolution of their bradycardia with carteolol (46.7%) as did patients treated with timolol (18.2%) from midnight to 4 AM. Overall cardiovascular adverse effects were reported significantly more frequently in the timolol than the carteolol group (P = .002). CONCLUSIONS Timolol causes significantly lower mean heart rate during the nighttime and more nocturnal bradycardia than carteolol does in patients with ocular hypertension and primary open-angle glaucoma. These differences may be because of the intrinsic sympathomimetic activity of carteolol.

Efficacy of carteolol hydrochloride 1% vs timolol maleate 0.5% in patients with increased intraocular pressure

PURPOSE To evaluate the ocular hypotensive effect and safety of carteolol hydrochloride 1% vs timolol maleate 0.5%. METHODS One hundred seventy-six patients with ocular hypertension or primary open-angle glaucoma were randomly assigned to receive either carteolol 1% twice a day or timolol maleate 0.5% solution twice a day in a randomized, double-masked, multicenter, parallel-group, active-control comparison trial during a 3-month period. RESULTS After 12 weeks, carteolol 1% reduced the mean +/- SE intraocular pressure from 25.0 +/- 0.3 to 19.5 +/- 0.3 mm Hg; timolol maleate 0.5% reduced the mean intraocular pressure from 25.2 +/- 0.3 to 19.6 +/- 0.3 mm Hg. The mean difference in trough intraocular pressure between carteolol and timolol maleate of -0.14 mm Hg was not significantly (P = .745) different (95% confidence limits, -0.97 to 0.70 mm Hg). Trough pulse and blood pressure also showed no consistent statistically significant differences between groups. The 2-hour postdose pulse, however, demonstrated a greater decrease in the timolol maleate than in the carteolol group (P < .001). Systemic and ocular signs and symptoms were similar between the groups except that the number of treatment-emergent reports of bradycardia was greater in the timolol maleate group (P = .039), and the carteolol group reported fewer ocular symptoms than the timolol maleate group did (P < .01). CONCLUSIONS Both carteolol 1% and timolol maleate 0.5% are highly effective in lowering intraocular pressure when measured at the end of the dosing interval. Carteolol 1% demonstrates an ocular hypotensive effect and safety profile similar to those of timolol maleate 0.5% solution.

The role of mitomycin treatment duration and previous intraocular surgery on the success of trabeculectomy surgery.

PurposeThis study was performed to determine the effect of duration of mitomycin exposure during trabeculectomy surgery on filtration success in eyes that had and had not been subjected to previous surgery. MethodsOne hundred six eyes of 92 patients were retrospectively reviewed. The effect of previous surgery and exposure duration of mitomycin 0.5 mg/ml on outcomes of trabeculectomy surgery were evaluated. ResultsThe mean duration of mitomycin exposure was 0.7 ± 0.02 min (mean ± SEM) in the eyes that had not been subjected to previous surgery and 1.5 ± 0.11 min in the eyes that had (p < 0.001). The mean follow-up times were 14 months in both groups. The mean decrease in intraocular pressure was 13.6 ± 1.25 mm Hg in the group that had not been subjected to previous surgery and 13.9 ± 1.45 mm Hg in the group that had been subjected to previous surgery. Analysis of variance techniques demonstrated no predictive value of demographics, history of previous surgery, or duration of mitomycin exposure with results of trabeculectomy surgery. Hypotony was the most frequent complication in both the no previous surgery and the previous surgery groups. The incidence of complications was numerically greater in the group that had not been subjected to previous surgery. ConclusionsThe duration of mitomycin exposure and the history of previous surgery did not correlate with postoperative intraocular pressure, medications, or incidence of complications. The exposure duration response curve of mitomycin 0.5 mg/ml in these patients appears to be flat through the time evaluated. Lower concentrations of mitomycin and shorter exposure should be used to maintain efficacy with reduced risk of complications.

Re-forming the flat anterior chamber with Healon

Abstract A shallow or flat anterior chamber may occur after complicated cataract surgery, a filtering procedure for glaucoma, or combined surgery. We describe a technique for injecting sodium hyaluronate (Healon®) into the anterior chamber through the previous paracentesis tract in the operating room or at the slitlamp microscope. Re‐forming the anterior chamber with Healon may pre‐empt the anatomical sequelae of prolonged anterior chamber shallowing and prevent the need for more invasive surgery.