Faculty Bibliography

Purpose: To determine the impact of coadminstration of systemic beta-blockers on the ocular hypotensive efficacy and safety of topical timolol, a nonselective beta-blocker, and that of brimonidine, an alpha(2)-selective adrenergic agonist, in patients with glaucoma or ocular hypertension. Design: Post hoc evaluation of data collected from two prospective, multicenter, randomized, double-masked, parallel-group, actively-controlled, 12-month clinical trials. Participants: Of the 926 subjects with ocular hypertension or glaucoma that were enrolled in the two prospective trials, 66 (7.1%) were concurrently maintained on systemic beta-blocker therapy. Of these patients, 34 had been assigned to the brimonidine group and 32 to the timolol group. Methods: Subjects instilled into each eye either 1 drop of brimonidine 0.2% or timolol 0.5% twice daily for 1 year. Study subjects within medication treatment groups were classified as to their use or nonuse of concurrent systemic beta-blockers, and mean intraocular pressure (IOP) reduction, adverse events, heart rate, and blood pressure were compared,. Main Outcome Measures: Mean IOP reduction from baseline was the primary efficacy variable. Adverse events and mean changes in heart rate and blood pressure from baseline were the primary safety variables. Results: Timolol-treated subjects concurrently taking systemic beta-blockers had smaller decreases in IOP, a greater mean change in systolic (at week 2, months 1, 2, 6, and 9; P less than or equal to 0.001) and diastolic blood pressure (months 2 and 6; P less than or equal to 0.02), and a significantly greater mean decrease in heart rate (month 6; P = 0.004) compared with timolol subjects not taking systemic beta-blockers, By contrast, there was a modest enhancement of IOP-lowering efficacy at trough and no effect on blood pressure or heart rate in brimonidine-treated subjects who were concurrently receiving systemic beta-blocker therapy compared with brimonidine subjects not receiving systemic beta-blockers. Conclusions: Concurrent systemic beta-blocker therapy had no deleterious effect on ocular hypotensive efficacy and no impact on systemic safety parameters with topical brimonidine, whereas efficacy was reduced and systemic safety parameters were impacted with topical timolol. Ocular hypotensive agents other than beta-blockers, such as the alpha(2) agonist brimonidine, may be a more appropriate first-line therapy for ocular hypertension and glaucoma patients concurrently taking systemic beta-blockers. Ophthalmology 2000;107: 1171-1177 (C) 2000 by the American Academy of Ophthalmology.

Background: Much experience has been gained with the use of older classes of antiglaucoma agents-topical beta-adrenergic-receptor antagonists, nonselective adrenergic-receptor agonists, oral carbonic anhydrase inhibitors, and cholinergic agents. In the past decade, new drugs and classes of drugs used to treat glaucoma have become available, including topical carbonic anhydrase inhibitors, prostaglandin analogues, and alpha(2)-adrenergic-receptor agonists. Extensive community-based use of antiglaucoma medications has led to an increased understanding of the acute and long-term safety and tolerability issues associated with their use. Objective: This paper reviews the side effects associated with the various classes of topical antiglaucoma drugs, with a particular focus on long-term safety issues.

PURPOSE/OBJECTIVE:Sialyl Lewis X (sLex), Lewis X (Lex), and N-acetyllactosamine are carbohydrate chains of neolactoglycoconjugates which are expressed by specific cell types and are important in the functioning of cells within an organism. This study attempts to determine the expression of these glycoconjugates on the conjunctiva, cornea, and trabecular meshwork (TM) of both normal and glaucomatous eyes. METHODS:Frozen anterior segment sections of both normal and glaucomatous human cadaver eyes, as well as rabbit eyes, were stained with a panel of monoclonal antibodies (mAbs) to neolactoglycoconjugates using an Avidin Biotin Peroxidase Complex/Alkaline Phosphatase staining method. RESULTS:SLex characteristically stained both human conjunctival and corneal epithelia in normal (n=5) and glaucomatous (n=5) sections. SLex stained corneal and conjunctival epithelia of glaucomatous eyes much more intensely than normal eyes. Rabbit cornea sections stained for sLex, Lex, and N-acetyllactosamine. However, human cornea only consistently stained with sLex. Normal and glaucomatous human TM sections did not stain for sLex, Lex, or N-acetyllactosamine. CONCLUSIONS:The expression of glycoconjugates with sLex side chains appears to be upregulated in the conjunctival and corneal epithelia of glaucomatous eyes. Distinct species specific differences were noted in Lex and N-acetyllactosamine staining patterns in rabbit and human corneal epithelia.

OBJECTIVE:To report two cases of a malignant glaucoma-like syndrome following pars plana vitrectomy. DESIGN/METHODS:Two interventional case reports. INTERVENTION/METHODS:The first patient was treated with a neodymium:YAG laser peripheral iridectomy with hyaloidectomy and with intracameral tissue plasminogen activator. The second patient was treated with a posterior approach iridectomy through residual hyaloid, zonules, and iris. MAIN OUTCOME MEASURES/METHODS:Axial anterior chamber depth and intraocular pressure (IOP). RESULTS:The interventions resulted in deepening of the anterior chambers and normalization of IOPs. CONCLUSION/CONCLUSIONS:A pseudomalignant glaucoma syndrome may be related to obstruction of aqueous flow, either by residual anterior hyaloid or by fibrin and other inflammatory debris at the level of the ciliary body-zonular apparatus. Treatment of this syndrome involves restoring aqueous flow to the anterior chamber by disrupting the residual anterior hyaloid or clearing fibrin or inflammatory debris. The clinician should not disregard the possibility of a pseudomalignant glaucoma syndrome following vitrectomy despite the fact that vitrectomy has traditionally been considered a curative treatment for malignant glaucoma.

PURPOSE/OBJECTIVE:To develop a protocol for testing glaucoma implant devices and to use this protocol to characterize devices currently available. METHODS:The following devices were obtained: Ahmed Glaucoma Valve Implant, Baerveldt Implant, Krupin Eye Valve, Joseph Valve, and OptiMed Glaucoma Pressure Regulator. Pressure per unit time was measured in real-time during ramped pressure perfusion of the implant devices with an open-manometer system. Each device was measured during a 10 minute interval while a constant flow of fluid was pumped into the system. The open manometer allowed the resistance of the devices to generate a pressure head which was monitored by computer. Four independent runs were averaged for each device. RESULTS:The Ahmed devices demonstrated reliable valve performance with a mean opening pressure of 13.65 mm Hg, a facility flow of 1.2 microL/min/mm Hg and a closing pressure of 6.1 mm Hg. The Baerveldt devices had a mean facility flow of 7.56 microL/min/mm Hg. The Joseph devices had the most variable performance, opening from 2.05 to 6.21 mm Hg. Two of 4 Joseph devices had high facility of flow (5 microL/min/mm Hg). The Krupin devices had a mean opening pressure of 6.25 mm Hg in 3 of 4 devices. The remaining Krupin device did not exhibit valve behavior. The OptiMed device did not reveal an opening pressure, and had a mean facility of flow of 7.08 microL/min/mm Hg for high flow and 6.20 microL/min/mm Hg for low flow. CONCLUSION/CONCLUSIONS:An objective test protocol for glaucoma implant devices was demonstrated. All implant devices had high facility of flow compared to the normal eye and can be grouped into very high facility (Baerveldt and OptiMed), and high facility (Ahmed, Joseph and Krupin). Only the Ahmed device had consistent valve behavior. None of the devices created enough resistance to explain long-term clinical failure of glaucoma drainage device surgery.