The risk profile of glaucoma filtration surgery.

Glaucoma surgery has evolved over the past 30 years from the full-thickness procedure to the guarded filtration procedure. However, many of the risks and complications attendant with the full-thickness procedure, including endophthalmitis, hypotony, cataract progression, and filtration failure, continue to plague the glaucoma surgeon performing the guarded filtration procedure, although at lower incidences. With proper modification of technique, such as with postoperative bleb titration and use of adjunctive antifibrotic therapy based on prognosticators for failure, the success rates of trabeculectomy reoperations can approach those of primary trabeculectomy. Such risk factors for failure include African-American race, higher preoperative intraocular pressures, previously failed filters, younger age, and uveitic and neovascular glaucomas. In this paper, we review a number of studies that analyze the risks, complications, and long-term results of glaucoma filtration surgery and discuss different surgical recommendations based on risk factors for failure as well as for performing concomitant cataract and glaucoma surgery.

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Combined trabeculectomy and phacoemulsification: a one-site vs a two-site approach.

PURPOSE: To compare the results of combined trabeculectomy and phacoemulsification surgery with intraocular lens implant by means of a one-site vs a two-site approach. METHODS: Glaucomatous patients with a coexisting cataract were randomly assigned to undergo either a one-site or two-site combined procedure. One-site surgery was performed with a limbus-based conjunctival flap and scleral tunnel at the 12-o'clock position. Two-site surgery was performed with a limbus-based conjunctival flap for the trabeculectomy in the superior nasal quadrant and a temporal clear cornea incision for phacoemulsification. Mitomycin C (0.4 mg/ml for 2 minutes) was applied to the scleral surface at the trabeculectomy site for both approaches. All patients received intraocular lens implants at the time of combined surgery. RESULTS: Thirty-three eyes of 33 patients were included in this study. Preoperative intraocular pressure and number of glaucoma medications were similar in the two groups. Corrected visual acuity improved similarly in both groups. Intraocular pressure decreased in both groups at last follow-up but was not significantly different (P = .129) between the one-site and two-site groups. At last follow-up, the one-site group required significantly more (P = .030) medications than did the two-site group. CONCLUSIONS: Combined trabeculectomy and phacoemulsification surgery in which one-site and two-site techniques were used yielded similar improvements in corrected visual acuity and intraocular pressure reduction. However, the one-site group required more medication to maintain intraocular pressure control than did the two-site group.

Effect of beta-adrenergic agents on intracellular potential of rabbit ciliary epithelium.

PURPOSE: To study the effects of beta-adrenergic agents on intracellular potential (Vm) of the isolated and intact rabbit ciliary epithelium. METHODS: Vm was measured on the isolated intact ciliary epithelium superfused with adrenergic agents and cyclic AMP modulators. RESULTS: The nonselective beta-adrenergic agonist isoproterenol depolarized Vm in a dose-dependent fashion. beta-adrenergic antagonists alone had no effect on baseline Vm. The isoproterenol response was blocked by the nonselective antagonist timolol (5 x 10(-5) M). The selective beta 2-antagonist ICI 118-551 caused a greater inhibition (IC50 approximately 7 x 10(-7)) than the selective beta 1-antagonist betaxolol (IC50 approximately 6 x 10(-6)). The isoproterenol response was also significantly (p < 0.03) blocked by the non-selective alpha-antagonist phentolamine. Cyclic AMP and phosphodiesterase inhibitors significantly decreased Vm. Pretreatment with these inhibitors potentiated the agonist-induced depolarization. Barium, a blocker of Ca(2+)-sensitive K+ channels, significantly decreased baseline Vm. Barium pretreatment blocked the beta-agonist and cAMP induced depolarization of Vm, suggesting that the K+ current is necessary for the observed isoproterenol response. Pretreatment with the cotransport inhibitor bumetanide had no effect on the isoproterenol-induced response. CONCLUSIONS: The beta-adrenergic agonist isoproterenol affects ionic transport processes across the ciliary epithelium (beta 2 > beta 1). This effect is likely mediated through adenylate cyclase coupled to adrenoreceptors and requires the presence of the K+ current. Blockage of the isoproterenol-induced decrease in Vm by a nonselective alpha-adrenergic antagonist indicates an interaction between the two adrenergic systems in the ciliary epithelium.

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.

Vacuolar H+-ATPase in ocular ciliary epithelium.

The mechanisms controlling the production of aqueous humor and the regulation of intraocular pressure are poorly understood. Here, we provide evidence that a vacuolar H+-ATPase (V-ATPase) in the ocular ciliary epithelium is a key component of this process. In intracellular pH (pHi) measurements of isolated ciliary epithelium performed with 2',7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF), the selective V-ATPase inhibitor bafilomycin A1 slowed the recovery of pHi in response to acute intracellular acidification, demonstrating the presence of V-ATPase in the plasma membrane. In isolated rabbit ciliary body preparations examined under voltage-clamped conditions, bafilomycin A1 produced a concentration-dependent decrease in short-circuit current, and topical application of bafilomycin A1 reduced intraocular pressure in rabbits, indicating an essential role of the V-ATPase in ciliary epithelial ion transport. Immunocytochemistry utilizing antibodies specific for the B1 isoform of the V-ATPase 56-kDa subunit revealed localization of V-ATPase in both the plasma membrane and cytoplasm of the native ciliary epithelium in both rabbit and rat eye. The regional and subcellular distribution of V-ATPase in specific regions of the ciliary process was altered profoundly by isoproterenol and phorbol esters, suggesting that change in the intracellular distribution of the enzyme is a mechanism by which drugs, hormones, and neurotransmitters modify aqueous humor production.

Topical carbonic anhydrase inhibitors.

Dorzolamide, a topically active carbonic anhydrase inhibitor, is an effective new glaucoma medication that creates a decrease in intraocular pressure similar to that produced by beta-blockers. When beta-blockers are contraindicated, dorzolamide may be used as a first-line therapy. It has excellent additivity with other topical ocular hypotensive medications, including beta-blockers and pilocarpine. Systemic side effects are minimal, particularly compared with those of oral carbonic anhydrase inhibitors. However, local side effects, including corneal edema in patients with borderline endothelial function, may occur. Decreased visual acuity and allergic reactions, which occur frequently, may curtail the use of dorzolamide in some patients.

Cyclocryotherpay and noncontact Nd:YAG laser cyclophotocoagulation in cats.

PURPOSE: To investigate physiological and histologic alterations of the cat eye in response to cyclocryotherapy (CCT) and noncontact transscleral Nd:YAG laser cyclophotocoagulation (TSNYC). METHODS: One eye of 29 cats was treated with 12 applications (1 minute, -80 degrees C) of CCT or 80 applications of noncontact TSNYC (7 to 9 J, retrofocus 3.6 mm). Blood-aqueous barrier function was studied measuring aqueous protein and fluorescein concentration after intravenous dye injection. Ocular blood flow was determined using 85Sr microspheres. RESULTS: Intraocular pressure after CCT was 29% lower in the treated than in the control eye after 3 and 12 weeks. After TSNYC, pressure was reduced by 34% at 3 weeks and by 27% after 12 weeks. Aqueous protein concentration was elevated in all treated eyes. Neither technique altered tonographic outflow facility or episcleral venous pressure. Calculated aqueous flow was lower in the treated eye than in the control eye 3 and 12 weeks after each cyclodestructive procedure. After CCT, anterior chamber fluorescein concentration was 2.5 times greater in 3-week and 3 times greater in 12-week eyes. After TSNYC, fluorescein concentration was 3 and 3.5 times greater at 3 and 12 weeks, respectively. Ciliary body blood flow in control eyes was similar to CCT and TSNYC eyes. Histopathology 12 weeks after CCT and TSNYC showed pigment dispersion, disorganized architecture, and cystic elevation of the nonpigmented ciliary epithelium. Areas of absent pigmented and nonpigmented epithelium at the ciliary process base were more discrete in TSNYC eyes. Electron microscopy demonstrated normal junctional complexes. CONCLUSIONS: CCT and TSNYC lower pressure by reducing aqueous formation. Ciliary body blood flow is not altered after either technique. Both techniques result in similar histologic disruption of the ciliary epithelium, resulting in breakdown of the blood-aqueous barrier.

Prolonged intraocular pressure reduction following intravitreal barium injection in rabbits.

The isolated ciliary epithelium contains barium-inhibitable potassium channels. The present study was aimed at testing the in vivo effects of barium on aqueous humor dynamics in rabbits. BaCl2 was administered to one eye by topical delivery or intravitreal injection. Dynamic measurements included intraocular pressure, outflow facility, episcleral venous pressure and aqueous flow (fluorophotometry). Barium dynamics were studied using 133Ba. Intraocular pressure was not altered after topical administration of BaCl2. 133Ba was not detected in the aqueous after delivery of eyedrops containing the radiochemical. Intraocular pressure decreased following intravitreal injection of BaCl2 (0.15 microgram). The onset of this pressure reduction was 12 to 16 hr, the maximum decrease (-11.3 mmHg) occurred at 2 days, and the effect persisted (-4.2 mmHg) for approximately 12 days after the injection. Outflow facility and episcleral venous pressure were not altered. However, aqueous humor flow 5 to 6 days after the injection was decreased by 42% to 63% as determined by fluorophotometry or calculated tonographic data. The injection was not associated with findings of intraocular inflammation. Radioactivity was detected in the vitreous within the first 3 days after the injection; however, activity was present in the ciliary body, equally distributed between the cell membrane and soluble fractions, seven days after the injection. Intravitreally injected BaCl2 results in a prolonged intraocular pressure decrease relating to reduced aqueous formation. While the mechanism(s) for the BaCl2-induced decrease in pressure are not clear, possibilities include a Ba2+ interaction with ciliary epithelial K+ or N-type Ca2+ channels.

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.

Cat model for intraocular pressure reduction after transscleral Nd:YAG cyclophotocoagulation.

Transscleral neodymium:yttrium-aluminum-garnet (Nd:YAG) laser cyclophotocoagulation (TSNYC) is used to lower intraocular pressure (IOP) in glaucoma patients refractory to conventional medical and surgical therapy. Our study investigates the ability of TSNYC to lower IOP in normal cats. One eye of 13 cats was treated with non-contact TSNYC. Mean pretreatment IOP was 25 mm Hg (vs. 25.3 mm Hg in contralateral control eyes). Eyes received 80 laser applications over 360 degrees delivered at least 3 mm posterior to the limbus with maximum power (8 to 9 joules) and maximum retrofocus (3.6 mm). Eyes were retreated if IOP was not reduced below baseline after 2 weeks. By 4 weeks, IOP was decreased in all treated eyes by a mean of 29.2% and was maintained as long as 20 weeks (mean decrease 14.8%). IOP in 10 eyes was lowered after a single treatment session. Of these, 2 eyes had IOP spikes > 10 mm Hg prior to IOP reduction. Three cats required retreatment to maintain IOP reduction. All eyes developed transient (< 4 weeks) postoperative uveitis and 3 eyes developed rubeosis iridis which resolved with topical corticosteroids. Histologic examination (6 weeks post-treatment) showed focal disruption of the pigment epithelium and to a lesser degree the nonpigmented epithelium at the base of the ciliary body and in the valleys of the pars ciliaris. The epithelium at the apices of the ciliary processes appeared intact. Vascular engorgement was variably present. This study demonstrates that TSNYC lowers IOP in cats. This animal model will be useful for investigating mechanism(s) responsible for TSNYC-induced IOP reduction.

Effects of topical k-strophanthin on aqueous humor and corneal dynamics.

PURPOSE: Sodium-potassium-activated adenosine triphosphatase (Na/K ATPase) is present in the ciliary epithelium, where it serves a regulatory role in fluid transport and the production of aqueous humor. The present study investigates the ability of topical k-strophanthin, a water-soluble mixture of glycosides, to lower intraocular pressure. METHODS: K-strophanthin was topically administered to one eye and vehicle to the fellow control eye of rabbits, cats, and human volunteers. RESULTS: Single drop 0.01 M k-strophanthin delivery lowered pressure in rabbits and cats to a maximal decrease of 5-6 mm Hg 3-4 h after drug administration. Higher drug concentrations irritated the eye, whereas lower concentrations had no effect. Pressure reduction in rabbits was associated with decreased aqueous humor formation, and no change in outflow facility and episcleral venous pressure. Drug delivery in humans had a minimal intraocular pressure effect. Slit-lamp and histologic examination of rabbit eyes after chronic drug administration was normal. However, single drop administration of 0.01 M drug was found to significantly increase corneal thickness, the aqueous to cornea fluorescein transfer coefficient, and the corneal endothelial permeability coefficient. CONCLUSIONS: Topical k-strophanthin lowers pressure via reduction of aqueous production and most probably by inhibition of the enzyme Na/K ATPase in the ciliary epithelium. The drug's effect on corneal function probably relates to a similar block of this enzyme in the epithelial layers of the cornea, which limits the usefulness of k-strophanthin and other previously studied Na/K ATPase inhibitors as an ocular hypotensive agent.

5-Fluorouracil in initial trabeculectomy. A prospective, randomized, multicenter 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.

Dye coupling of rabbit ciliary epithelial cells in vitro.

PURPOSE: To examine the in vitro properties of gap junctions on the isolated rabbit ciliary epithelium. METHODS: Intracellular potential was measured and lucifer yellow (5% in 1 M LiCl) was iontophoretically injected into a ciliary epithelial cell. Fixated tissue was examined with a laser confocal microscope. RESULTS: Dye spread was observed throughout both layers (horizontally and vertically) of the ciliary epithelium adjacent to the injected cell that was more intensely labeled. Dye reflux did not occur at the site of microimpalement. Microiontophoretic dye injection in a bathing solution with a high Ca2+ (10 mM) or an acidic pH (6.3) completely inhibited cell-cell dye coupling in the rabbit ciliary epithelial cells. CONCLUSIONS: Laser confocal microscopy of intracellularly injected lucifer yellow dye demonstrates the physiologic presence of gap junctions between both ciliary epithelial layers. Extracellular acidosis and high concentration of extracellular Ca2+ cause loss of cell-cell coupling in the rabbit ciliary epithelium.