Jon M. Ruderman

A Randomized Study of 5-Fluorouracil and Filtration Surgery

We conducted a randomized study of 26 patients with a poor prognosis undergoing filtration surgery with and without a low dose of 5-fluorouracil. Mean preoperative intraocular pressure (+/- S.E.M.) in the 5-fluorouracil group (n = 14) was 38.4 +/- 3.08 mm Hg; in the control group (n = 12) it was 41.2 +/- 5.0 mm Hg. Mean postoperative intraocular pressure (+/- S.E.M.) at six to 18 months was 14.4 +/- 1.4 mm Hg in the 5-fluorouracil group and 30.7 +/- 3.9 mm Hg in the control group (P less than .01). Of 14 patients in the 5-fluorouracil group, 12 had a successful outcome at 12 months. Of 12 patients in the control group, three had a successful outcome during this same interval.

5-Fluorouracil in Initial Trabeculectomy: A Prospective, Randomized, Muldcenter Study

PURPOSE Postoperative subconjunctival 5-fluorouracil (5-FU) injections increase the success of filtration surgery in eyes with prior filtration failure or cataract removal and in eyes with secondary glaucoma. The authors evaluate the safety and benefit of adjunctive 5-FU in eyes undergoing initial trabeculectomy. METHODS Patients with phakic, uncontrolled, open-angle glaucoma who were undergoing initial trabeculectomy were prospectively assigned to the 5-FU group on the first postoperative day. Patients in this group received five 5-mg injections during 2 weeks after surgery. Patients in the control group received no injections. RESULTS Preoperative intraocular pressure (IOP) and number of antiglaucoma medications were similar in the 5-FU (n = 32) and control (n = 30) groups. Transient superficial punctate keratopathy was the only postoperative complication that occurred more frequently (P < 0.05) in the 5-FU (14 eyes) than in the control eyes (3 eyes). Patients were followed for a minimum of 1 year or until a study endpoint was reached: IOP of 21 mmHg or greater with maximum medical therapy (2 5-FU eyes and 8 control eyes; P < 0.03) or cataract removal after filtration (5 treated and 3 control eyes). At last follow-up (mean, > 20 months), IOP and the number of antiglaucoma medications were significantly lower (P < 0.02) in the 5-FU eyes (IOP, 12.0 +/- 1.3 mmHg; medications, 0.2 +/- 0.1) than in the control eyes (IOP, 16.8 +/- 1.3 mmHg; medications, 0.8 +/- 0.2). Intraocular pressure was 20 mmHg or lower in 94% of 5-FU eyes and in 73% of control eyes (P < 0.03) and 16 mmHg or lower in 84% of 5-FU eyes and in 57% of control eyes (P < 0.02). CONCLUSIONS Adjunctive 5-fluorouracil increases the rate of success, decreases the level of postoperative IOP, and reduces the need for postoperative antiglaucoma medication in eyes with open-angle glaucoma undergoing initial trabeculectomy.

Krupin Eye Valve with Disk for Filtration Surgery

PURPOSE The authors evaluate a long posterior tube shunt device with a pressure sensitive valve for filtration surgery in eyes with recalcitrant glaucoma. METHODS The device consisted of an anterior chamber tube connected to an oval (13 x 18 mm) episcleral explant. The explant was designed to maximize the area of surrounding encapsulation while still allowing implantation within one quadrant. A pressure-sensitive and unidirectional slit valve in the tube provided resistance to aqueous humor flow. One-stage implantation without the use of restrictive sutures was performed in 50 eyes with various types of glaucoma unresponsive to prior glaucoma surgery. RESULTS Mean (+/- standard error of the mean) preoperative intraocular pressure (IOP) of 36.4 +/- 1.6 mmHg was reduced significantly (P < 0.001) to 8.3 +/- 1.3 mmHg on the first postoperative day. Mean anterior chamber depth (scale, 0-4+) was 3.4 +/- 0.1. Mean IOP 1 month after surgery was 14.1 +/- 1.3 mmHg. The implant was removed from four eyes due to IOP failure (1 eye), external erosion (2 eyes), or endophthalmitis (1 eye). A suprachoroidal hemorrhage occurred in one eye on the first postoperative day. Diplopia developed in one eye after surgery. Mean IOP at last follow-up examination (mean, 25.4 +/- 2.4 months; range, 16-36 months) was 13.1 +/- 1.3 mmHg. Intraocular pressure was 19 mmHg or lower in 80% of the eyes, 59% of which were without adjunctive antiglaucoma medications. CONCLUSIONS Design features of the Krupin Eye Valve with Disk result in a large area of encapsulation in a single ocular quadrant which functions as an external reservoir for passage of aqueous humor. The valve portion facilitates maintenance of anterior chamber depth during the early postoperative interval. This new therapeutic device can be effective in the long-term control of IOP in glaucomatous eyes not responsive to prior filtration surgery with adjunctive antimetabolite therapy.

Combination of systemic acetazolamide and topical dorzolamide in reducing intraocular pressure and aqueous humor formation

OBJECTIVE The study aimed to determine whether topical dorzolamide and systemic acetazolamide have an additive effect on intraocular pressure (IOP) and aqueous humor formation (AHF). DESIGN This was a prospective, open-label, two-protocol clinical study. PARTICIPANTS Sixteen patients with ocular hypertension or with primary open-angle glaucoma were studied. INTERVENTION Baseline AHF was measured by computerized fluorophotometry and IOP by pneumatonometry without antiglaucoma therapy. In the first protocol, dorzolamide was randomized to one eye (N = 10) and IOP and AHF measurements were repeated. One week later, having used dorzolamide in one eye three times daily, patients had measurements performed before and after the single administration of oral acetazolamide 250 mg. In the second protocol, having used acetazolamide 250 mg four times daily for 4 to 7 days (N = 6), patients had measurements performed before and after a single drop of dorzolamide was instilled randomly into one eye. The patient continued acetazolamide and unilateral dorzolamide for 4 to 7 more days and returned for IOP and AHF measurements. MAIN OUTCOME MEASURES Intraocular pressure and AHF were measured in treated and contralateral control eyes. RESULTS In the first protocol, IOP (mmHg +/- standard deviation) was significantly (P = 0.02) lower in the dorzolamide (16.3 +/- 2.6) than in the contralateral control (19.9 +/- 2.9) eyes. Aqueous humor formation (microliter/minute +/- standard deviation) also was lower (P = 0.02) in dorzolamide eyes (1.79 +/- 0.4 vs. 2.33 +/- 0.5). After oral acetazolamide 250 mg, IOP was unchanged in dorzolamide eyes (17.6 +/- 2.0 preacetazolamide vs. 17.9 +/- 2.0 postacetazolamide), whereas it was reduced (P = 0.003) in control eyes (20.5 +/- 2.2 preacetazolamide vs. 16.9 +/- 2.3 postacetazolamide). Aqueous humor formation was reduced in control eyes (2.31 +/- 0.8 preacetazolamide vs. 1.73 +/- 0.6 postacetazolamide; P = 0.005) but not in dorzolamide-treated eyes (1.56 +/- 0.45 preacetazolamide vs. 1.77 +/- 0.39 postacetazolamide). In the second protocol, acetazolamide 250 mg four times daily symmetrically reduced IOP and AHF in both eyes. After single-drop dorzolamide in one eye, IOP and AHF did not change significantly. After 4 to 7 days of acetazolamide and unilateral dorzolamide, IOP and AHF remained reduced to a similar level in dorzolamide and control eyes not receiving topical therapy. CONCLUSION Topical dorzolamide and oral acetazolamide, in the concentrations and doses used in this study, are not additive. Either drug alone results in maximum reduction in IOP and AHF. Concomitant glaucoma therapy of a topical and systemic carbonic anhydrase inhibitor is not warranted.

5-Fluorouracil After Primary Combined Filtration Surgery

We examined the safety and efficacy of 5-fluorouracil in eyes with open-angle glaucoma undergoing combined cataract removal and filtration surgery. We randomly assigned one eye each of 24 patients to receive 5-fluorouracil (five injections of 5 mg during two weeks after surgery) and one eye each of 20 patients to comprise the control group. Preoperatively, the two groups had similar mean intraocular pressure (P = .8) and number of medications (P = .2). The mean intraocular pressure of the 5-fluorouracil group was 18.6 +/- 1.1 mm Hg, with 2.5 +/- 0.3 medications; that of the control group was 18.2 +/- 1.2 mm Hg, with 2.2 +/- 0.2 medications. One year postoperatively, intraocular pressure and the number of medications were significantly reduced by a similar amount in both groups of patients (5-fluorouracil, 14.2 +/- 0.7 mm Hg, 0.8 +/- 0.2 medications; controls, 14.3 +/- 0.6 mm Hg, 1.0 +/- 0.2 medications). Transient superficial punctate keratopathy occurred more frequently (P = .04) in the 5-fluorouracil group (16 of 24 eyes, 67%) than in the control group (seven of 20 eyes, 35%). In our randomized and prospective study, the adjunctive use of 5-fluorouracil did not result in improved control of intraocular pressure one year after combined surgery in eyes with open-angle glaucoma.

Apraclonidine and Argon Laser Trabeculoplasty

Sixty patients with medically uncontrolled open-angle glaucoma (intraocular pressure greater than 21 mm Hg) were randomly assigned to one of two treatment regimens with apraclonidine before undergoing 360-degree argon laser trabeculoplasty. One drop of apraclonidine 1% was instilled one hour before and immediately after laser treatment in 30 eyes or apraclonidine was delivered only after trabeculoplasty in 30 eyes. Intraocular pressure before laser treatment, number of antiglaucoma medications, and the laser treatment settings were comparable between the two groups. The mean and percent change in intraocular pressures were similar in both treatment groups one and two hours after trabeculoplasty. One drop of apraclonidine 1% instilled immediately after argon laser trabeculoplasty prevented intraocular pressure increase one hour and two hours postoperatively as effectively as its instillation both one hour before and immediately after laser treatment.

Combined phacoemulsification and trabeculectomy with mitomycin-C

Purpose: To examine the safety and efficacy of primary combined phacoemulsification, posterior chamber intraocular lens (IOL) implantation, and trabeculectomy with mitomycin‐C (0.4 mg/ml) in patients with open‐angle glaucoma and visually significant cataract. Setting: University‐hospital‐based glaucoma referral practice. Methods: In this study, data of 43 patients of a single surgeon were retrospectively analyzed. These consecutive patients had combined phacoemulsification, posterior chamber IOL implantation, and trabeculectomy with mitomycin‐C. Results: Thirty‐eight patients (88%) had open‐angle glaucoma and 5 (12%) pseudoexfoliative glaucoma. Thirty‐eight patients (88%) had 12 months of follow‐up; all had at least 6 months follow‐up. Mean preoperative intraocular pressure (IOP) was 21.6 mm Hg ± 6.8 (SD) (range 12.0 to 41.0 mm Hg) with 2.5 ± 1.0 glaucoma medications. At last follow‐up, mean IOP had decreased to 14.2 ± 6.2 mm Hg (range 3.0 to 40.0 mm Hg) with 0.5 ± 0.5 glaucoma medications. Twenty‐one patients (55%) had an IOP of 15 mm Hg or less at 12 months. Best corrected visual acuity was 20/40 or better in 31 of 43 patients (72%) at last follow‐up. A filtration bleb was noted in 33 of 40 patients (83%) at their last visit. Postoperative IOP spikes occurred in 17 patients (40%), transient hyphema in 12 (28%), transient wound leaks in 11 (26%), and superficial punctate keratopathy in 11 (26%). Three cases of persistent hypotony (IOP less than 5 mm Hg) and 1 case of epithelial downgrowth were also noted. Conclusion: Phacoemulsification with IOL implantation and combined trabeculectomy with mitomycin‐C produced good visual acuity and excellent IOP control but resulted in some complications. The use of mitomycin‐C in combined procedures does not appear to confer a significant benefit.

Apraclonidine and Anterior Segment Laser Surgery: Comparison of 0.5% versus 1.0% Apraclonidine for Prevention of Postoperative Intraocular Pressure Rise

PURPOSE To compare the efficacy of 0.5% and 1.0% apraclonidine in preventing laser-induced intraocular pressure (IOP) elevation after trabeculoplasty, neodymium: YAG (Nd: YAG) iridotomy, and capsulotomy. METHODS This is a prospective, masked, and randomized study of 83 patients undergoing trabeculoplasty, 62 patients undergoing iridotomy, and 57 patients undergoing capsulotomy. Surgical eyes received one drop of 0.5% or 1.0% apraclonidine immediately after surgery. RESULTS Intraocular pressure reduced 2 hours after trabeculoplasty in the 0.5% (P = 0.028) and 1.0% (P = 0.004) groups. Intraocular pressure was higher than baseline in a greater number of eyes treated with 0.5% (12 of 39 eyes, 31%) compared with 1.0% apraclonidine (5 of 44 eyes, 11%) (P = 0.032). Intraocular pressure in eyes with a narrow chamber angle was reduced in 16 (85%) of 19 eyes treated with 0.5% and in 10 (84%) of 12 eyes treated with 1.0% apraclonidine after iridotomy. Of patients with chronic angle-closure glaucoma, IOP was similar to prelaser values in 11 (69%) of 16 eyes treated with 0.5% (P > 0.7) and 12 (80%) of 15 eyes treated with 1.0% apraclonidine (P > 0.3). In patients undergoing capsulotomy, pressure was significantly lowered in the 0.5% group (P = 0.04) but not in the 1.0% apraclonidine group. After capsulotomy, both treatment groups had similar (P > 0.3) numbers of eyes with an IOP less than baseline (83% for 0.5% apraclonidine and 81% for 1.0% apraclonidine). CONCLUSION The single postoperative administration of 0.5% apraclonidine is as effective as the 1.0% concentration in preventing IOP elevation immediately after trabeculoplasty, iridotomy, or capsulotomy.

Comparison of the Challenger Digital Applanation Tonometer and the Goldmann Applanation Tonometer

We compared the Challenger electronic tonometer to the Goldmann applanation tonometer in 70 eyes without corneal abnormalities. There was a good overall correlation between the two machines. Correlations between interobserver readings were excellent, demonstrating that obtaining reproducible measurements is possible with either machine. However, the scattergrams indicated that the Challenger tonometer gave consistently lower readings and showed more variability than the Goldmann tonometer. Additionally, the mean underestimation of intraocular pressure increased as the intraocular pressure increased above 20 mm Hg. Therefore, the Challenger electronic tonometer as presently calibrated is not accurate enough for clinical use in the detection and management of glaucoma.

Latanoprost: A Review

Latanoprost is a new topical ocular prostaglandin that decreases intraocular pressure (IOP) by increasing uveoscleral outflow. Its efficacy is comparable with that of timolol and it shows almost complete additivity with timolol. Once daily dosing of 0.005% latanoprost yields a maximal effect with no significant circadian fluctuation in IOP. Local side effects include increased iris pigmentation, conjunctival hyperemia, and punctate epithelial erosions. No significant systemic side effects have been reported. The effect of latanoprost on eyes with compromised blood-aqueous barriers and its additivity to other ocular medications are areas that will require further evaluation.