GLAUCOMA MANAGEMENT
From Glaucoma: Current Management and Updates, presented May 21, 2005, by the University of Cincinnati College of Medicine and the Cincinnati Eye Institute
| FERTILE GROUND FOR GLAUCOMA MEDICAL THERAPY —Linda J. Greff, MD, Volunteer Associate Professor of Ophthalmology, University of Cincinnati College of Medicine |
Decreasing Aqueous Production | β-adrenergic antagonists: long history; highly efficacious; side effects—affected patients mostly older (problems with cardiovascular and pulmonary diseases; may be mistakenly attributed to fact that patient elderly); topical β-blocker less effective with concomitant use of systemic β-blocker |
| Adrenergic agonists (α-selective): apraclonidine—also increases outflow facility; high rate of allergic reactions and tachyphylaxis; brimonidine—more α2 selective than apraclonidine; decreases aqueous production and increases uveoscleral outflow; highly efficacious |
| Carbonic anhydrase inhibitors (CAIs): oral—side effects may include decreased appetite, metabolic acidosis, worsening sickle cell crises, kidney stones, and blood dyscrasias; topical—better tolerated, but less efficacious; use cautiously in patients with sulfa allergy |
Increasing Aqueous Outflow | Miotics: increase facility of outflow; side effects vary by dose and vehicle, but may include gastrointestinal (GI) effects; caution with using succinylcholine; useful in select cases |
| Prostaglandin analogues: new gold standard; in 2 of 3 recent trials, efficacy surpassed that of timolol (Timoptic); superior systemic side-effect profile; increases uveoscleral outflow (perhaps facility of outflow); document that patient aware of possible permanent iris color and lash changes; possible association with cystoid macular edema (CME); high rate of nonresponders to latanoprost |
| Bimatoprost (study by Brubaker): prostamide; 50% increase in uveoscleral outflow and 35% increase in facility of outflow; efficacy similar to prostaglandin analogues; hyperemia may be of greater concern than with latanoprost |
Fixed Combination Medications | Ocular Hypertension Treatment Study (OHTS): 40% of treated patients needed >1 medication to achieve 20% reduction in intraocular pressure (IOP) |
| Advantages: increased convenience and decreased cost; decreased washout effect and improved compliance; decreased preservative exposure may improve future surgical outcome; disadvantages—cannot individualize dosing; overuse of unnecessary medication |
| Specific therapy: timolol-dorzolamide—in phase III trials, efficacy equal to concomitant therapy (in later studies, decrease in IOP superior to concomitant therapy; may be due to increased compliance and decreased washout effect; efficacy similar to latanoprost, timolol–unoprostone, and timolol–brimonidine; less efficacious than latanoprost– brimonidine; latanoprost–timolol—not approved in United States; in study by Higgenbotham, not much advantage over latanoprost alone (2.9 mm Hg advantage over timolol alone); timolol–brimonidine—in phase III studies, ≈40% of patients achieved IOP <18 mm Hg (brimonidine alone and timolol alone less effective) |
New Therapies | Neuroprotection: goals—after injury, decrease apoptosis (programmed cell death); inhibit glutamate; recent research—memantine (recent evidence suggests excitotoxicity not major mechanism for retinal ganglion cell death); nitric oxide synthase (NOS) inhibitors |
| Altering trabecular meshwork: statins—decrease cholesterol production; stabilize plaques; decrease inflammation; inhibition of rho kinase increases trabecular meshwork outflow and decreases apoptosis |
| Altering aqueous humor dynamics: outflow pathways—trabecular (pressure-sensitive); uveoscleral (pressure-insensitive); IOP fluctuation may be independent risk factor for glaucoma progression; future therapies may be better directed towards enhancing flow through trabecular meshwork, rather than decreasing aqueous formation and diverting flow away from trabecular meshwork |
| ANTIFIBROTIC USE WITH PRIMARY TRABECULECTOMY —Kuldev Singh, MD, Professor of Ophthalmology, Stanford University School of Medicine, Stanford, California |
| Off-label use: adjunctive use of antifibrotic agents with glaucoma filtration surgery not approved by Food and Drug Administration (FDA) |
| Factors affecting choice of antifibrotic: age and race of patient (elderly patients have less vigorous wound healing response; blacks have greater wound healing response); surgical technique; postoperative follow-up schedule; surgeon’s experience with fluorouracil (5-FU) and mitomycin-C (MMC) |
| Postoperative application: generally, 5-FU at 5-mg dose; problems—epithelial problems related to dose; side effects associated with keratopathy |
| Intraoperative application: American Glaucoma Society Survey (study by Chen)—in United States, slight but growing preponderance of MMC use; overwhelming majority use 5-FU or MMC on sponge at time of surgery; study by Minckler—subscleral application increases aqueous concentration of drug; because of potential toxicity in anterior chamber, trend favoring suprascleral application |
| Risks: hypotony and maculopathy; late wound leaks (especially with MMC); endophthalmitis; intraocular toxicity |
| Primary Trabeculectomy Antimetabolite Study (PTAS) |
 | Question: which antifibrotic drug is ideal adjunct to primary trabeculectomy in eyes not at high risk for failutre of filtration surgery? |
| Study design: exfoliative pigmentary chronic angle closure and primary open-angle glaucoma eyes (all >40 yr of age); primary outcome variable was proportion of eyes with final postoperative IOP <15 mm Hg |
| Surgical technique: limbus-based trabeculectomy; 5-FU and MMC at concentrations commonly used by investigators |
| Early and intermediate-term results: IOP 12.5 mm Hg in both groups; proportion of eyes with 30% reduction in IOP same in 2 groups (78% vs 72%; no differences in acuity or postoperative medications; trend toward greater proportion of eyes having IOP <12 mm Hg in MMC group; (not statistically significant); no differences in adverse outcomes between treatment groups; only 1 patient in each group had hypotony maculopathy; no difference in rates of cataract surgery; no significant difference in slope of survival between groups; interpretation of results—at dosages used, both drugs equally safe and effective adjuncts to primary trabeculectomy in hands of experienced glaucoma surgeons; complications rare in both groups |
| Suggestions: choice of antifibrotic drug based on likelihood of vision loss from glaucoma over lifetime and improved success rate with medication; modify trabeculectomy technique (do not leave eyes “soft”); be flexible at time of surgery (be prepared to change plan, based on intraoperative observation); important not to vary concentration of drug (problem of 10- fold dilutional errors in mixing MMC); consider supplementing intraoperative application with postoperative 5-FU injections |
| ANGLE-CLOSURE GLAUCOMA —Anup K. Khatana, MD, Volunteer Clinical Assistant Professor of Ophthalmology, University of Cincinnati College of Medicine |
| Dynamic dark-room gonioscopy: start with full slit beam, then shorten almost to spot with low ambient illumination; watch angle close as pupil dilates |
| Acute angle-closure glaucoma (ACG): if fellow eye has normal chamber depth and angle width or configuration, question diagnosis (unless there is marked anisometropia); chronic—closure more gradual; apposition usually leads to peripheral anterior synechiae (PAS) formation with more gradual increase in IOP; usually asymptomatic unless marked visual field loss; cornea usually clear |
| Persistent and recurrent IOP elevation after peripheral iridectomy (PI) for ACG (differential diagnosis): PAS or undetected trabecular meshwork injury; underlying or residual open-angle glaucoma component; nonpupillary block angle closure; aqueous misdirection; incomplete or occluded iridotomy |
| ACG laser therapy in refractory cases: argon laser—helpful to perform iridoplasty (directly treat peripheral iris with Abraham lens); gonioplasty—treating peripheral iris with gonioscopy lens; pupilloplasty—peak pupil to break refractory pupillary block |
| Surgical management: clear corneal surgical PI—used in rare case where peripheral iridotomy not possible; make incision vertical, not horizontal, to allow access to basal iris; goniosynechialysis—usually using cyclodialysis or iris spatula to break; PAS effective as long as PAS present <6 to 9 mo (some have reported success at up to 12 mo; usually difficult to pinpoint exact duration of angle closure); phacoemulsification with lens implantation—next option if there is phacomorphic component; trabeculectomy—risk for complications greater when doing filtering surgery on angle closure, compared to open-angle glaucoma; increased risk for flat anterior chamber and malignant glaucoma |
| Plateau iris configuration: usually affects younger patients who are less hyperopic (possibly myopic), compared to those with primary angle-closure glaucoma; ciliary process more anteriorly positioned, pushing peripheral iris anteriorly to close angle; treatment—initially, laser peripheral iridotomy (LPI) to eliminate pupillary block; if angle still extremely narrow or closed, next option usually argon laser peripheral iridoplasty or long-term miotic therapy |
Case 1 | Presentation: 57-yr-old white male patient with 2-day history of pain and blurred vision; vision 20/25 in right eye (OD) and counting fingers in left eye (OS); IOP 15 mm Hg OD and 50 mm Hg OS; left eye—pupil 6 mm and unreactive; 2 to 3+ injection; diffuse corneal edema; shallow anterior chamber; lacy glaukomflecken; nuclear sclerosis; gonioscopy— right eye closed; Spaeth classification (A)C5b (see Table 1); scleral spur visible with indentation |
| Treatment: maximal topical medical therapy (including glycerin to clear cornea); oral acetazolamide (Diamox) and glycerin (Osmoglyn); bilateral yttrium-aluminum-garnet (YAG) LPI; 1 wk later, vision 20/20 OD and 20/50 at pinhole, and 20/20 OS; IOP 14 mm Hg OD and 12 mm Hg OS using only timolol and dorzolamide (Cosopt) in left eye; right eye quiet with patent LPI; left eye had trace injection, residual corneal edema, and anterior chamber cell; gonioscopy—right angle open but still narrow; (B)C15-20p; plateau iris configuration more easily visible with iridotomy; angle in left eye closed 360°; cup-to-disk ratio (CDR) 0.4 OD/0.35 OS |
| Follow-up: angle in right eye at risk for chronic angle closure; argon laser peripheral iridoplasty and gonioplasty OD; 1 wk after iridoplasty, IOP 14 mm Hg OD and 32 mm Hg OS; left eye still only on Cosopt; right eye—angle widened; C25f/p (Spaeth); excellent response to argon laser; left eye—angle closed; pupil 6 to 7 mm and unreactive |
| Management (continued): IOP increasing and more medications added; on follow-up, IOP 23 mm Hg in right eye, but 30 mm Hg in left eye; patient on brimonidine (Alphagan), Cosopt, and latanoprost (Xalatan); anterior chamber—quiet in both eyes (OU); patient iridotomy OU; glaukomflecken OS; gonioscopy—angle in right eye widened further; ≈2 mo after iridoplasty, 30° approach; left eye still closed; left disk had developed vertical elongation (CDR increased to 0.6); next step—phacoemulsification; goniosynechialysis; surgical iris repair/pupilloplasty to reduce pupil size |
| Most recent examination: vision 20/15 OU; IOP 14 mm Hg OD and 12mm Hg OS (no drops in either eye); anterior segment—clear and quiet OU; iris sutures intact with round, unreactive pupil; gonioscopy—open angles of D40f/p OD and D35p OS; left eye full plateau iris configuration; disks stable (CDR 0.4 and 0.6); visual fields normal |
Case 2 | Presentation: 64-yr-old woman developed acute ACG in right eye; partial medical treatment; ocular history negative, but mother had glaucoma with vision loss in 1 eye; 1 mo after initial attack, vision 20/30 OD and 20/60 OS; IOP 35 mm Hg OD and 9 mm Hg OS on Alphagan and Cosopt OU; anterior segment—2+ injection; clear cornea; shallow anterior chamber with occasional cell in right eye; moderate nuclear sclerosis OU; gonioscopy—almost closed angles; A/B 15B OU; right eye mostly synechially closed; disks—CDR 0.75 OD and 0.35 OS |
| Intervention: phacoemulsification with IOL, and goniosyn-echiolysis OD; Nd:YAG LPI on fellow eye next day; at 1 wk— IOP 14 mmHg OD and 9 mmHg OS (no IOP medication); angles open; Spaeth classification (C)D30f OU; 1 localized area of PAS in right eye; at 5 wk—IOP 39 mm Hg OD using only prednisolone (Pred Forte); right angle open; Spaeth classification (B)C temporally |
| Follow-up: topical medical therapy added; 2 wk later, IOP 32 mm Hg OD on Alphagan and Cosopt; rear anterior chamber cell and extensive posterior synechiae with early iris bombe; angle mostly closed; Spaeth classification (A)B30f |
| Why did angle reclose? combination of factors; inflammation; iris can have “memory” and may seek earlier position; mid-dilated pupil unreactive with loss of iris tone; speaker elected not to perform pupilloplasty |
| Retreatment: repeat goniosynechialysis; peripheral iridectomy and iris repair/pupilloplasty; at 1 wk—IOP 17 mm Hg (OD) (no IOP medications); angle open for 360°; 3 wk later—IOP 18 mm Hg OD (no IOP medications); most of angle open, but broad low PAS starting to develop; next step—360°-argon laser peripheral iridoplasty and gonioplasty; at 1 wk, IOP increased to 25 mm Hg (no IOP medications), but angle wide open; PAS lysis and addition of Alphagan P |
| Most recent examination: vision 20/40 OD and 20/60 OS; IOP 20 mm Hg OD and 16 mm Hg OS using only Alphagan P in right eye; right anterior segment clear with only few cells; patent surgical PI OD and laser iridotomy OS; angles wide open OU with no recurrence of PAS; disks—stable in both eyes; CDR 0.75 OD and 0.35 OS |
Educational Objectives
| The goal of this program is to educate the listener about glaucoma management. After hearing and assimilating this program, the clinician will be better able to: |
| 1. Identify newer medications for managing glaucoma. |
| 2. Describe advantages of fixed combination therapy for managing glaucoma. |
| 3. Assess the safety and efficacy of using antifibrotic medication as an adjunct to trabeculectomy. |
| 4. Evaluate patients for angle-closure glaucoma. |
| 5. Describe techniques for managing angle-closure glaucoma. |
Discussed on This Program
Acetazolamide [Dazamide, Diamox, Diamox Sequels] Apraclonidine hydrochloride [Iopidine] Bimatoprost [Lumigan] Brimonidine tartrate [Alphagan, Alphagan P] Dorzolamide [Trusopt] Dorzolamide HCl and timolol maleate [Cosopt] Fluorouracil (5-fluorouracil, 5-FU) [Adrucil, Carac, Efudex, Fluoroplex] Glycerin (glycerol; several formulations and trade names) Latanoprost [Xalatan] Memantine HCl [Axura, Namenda] Mitomycin (mitomycin-C; MTC) [Mutamycin] Prednisolone (several formulations and trade names) Succinylcholine chloride [Anectine, Anectine Flo-Pack, Quelicin] Timolol maleate (several trade names)
Table 1: Spaeth Gonioscopic Grading System Iris Insertion
| Angular Approach
| Peripheral Iris
|
| Pigmentation of Trabecular Meshwork
|
|---|
| A. Anterior to Schwalbe’s line |
| | | r regular |
| | f flat |
| | 0 no pigment |
| | B. Between Schwalbe’s line and sceral spur |
|
| | s steep |
| | b bowed anteriorly |
| | 1+ minimal |
| | C. Scleral spur visible |
| | 0° to 50° |
| | | p plateau iris |
| | 2 + mild |
| | D. Deep with ciliary body visible |
|
| | q queer |
| | c concave |
| | 3+ moderate |
| | E. Extremely deep with >1 mm of ciliary body visible |
|
| | | | 4+ intense |
|
* Evaluating iris insertion, angular approach, peripheral iris configuration and degree of trabecular meshwork pigmentation
Suggested Reading
Asrani S et al: Large diurnal fluctuations in intraocula.pressure are an independent risk factor in patients with glaucoma. J Glaucoma 9:134, 2000; Aung T et al: Configuration of the drainage angle, intraocular pressure, and optic disc cupping in subjects with chronic angle-closure glaucoma. Ophthalmology 112:28, 2005; Aung T et al: Degree of angle closure and the intraocular pressure-lowering effect of latanoprost in subjects with chronic angle-closure glaucoma. Ophthalmology 112:267, 2005; Bacharach J et al: Comparison of the efficacy of the fixed-combination timolol/dorzolamide versus concomitant administration of timolol and dorzolamide. J Ocul Pharmacol Ther 19:93, 2003; Brubaker RF et al: Effects of AGN 192024, a new ocular hypotensive agent, on aqueous dynamics. Am J Ophthalmol 131:19, 2001; Crowston JG, Weinreb RN: Glaucoma medication and aqueous humor dynamics. Curr Opin Ophthalmol 15:132, 2004; Fechtner RD, Realini T: Fixed combinations of topical glaucoma medications. Curr Opin Ophthalmol 15:132, 2004; Higgenbotham EJ et al: Latanoprost and timolol combination therapy vs monotherapy: one-year randomized trial. Arch Ophthalmol 120:915, 2002; Joshi AB et al: 2002 survery of the American Glaucoma Society: practice preferences for glaucoma surgery and antifibrotic use. J Glaucoma 14:172, 2005; Kass MA et al: The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open- angle glaucoma. Arch Ophthalmol 120:701, 2002; Kook MS et al: Efficacy of latanoprost in patients with chronic angle- closure glaucoma and non visible ciliary-body face: a preliminary study. J Ocul Pharmacol Ther 21:75, 2005; Lai JS et al: Diode laser transscleral cyclophotocoagulation as primary surgical treatment for medically uncontrolled chronic angle closure glaucoma: long-term clinical outcomes. J Glaucoma 14:114, 2005; Sall KN et al: Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability. Ophthalmology 110:615, 2003; Yip LW et al: Optical coherence tomography of optic disc swelling in acute primary angle- closure glaucoma. Arch Ophthamol 123:567, 2005; Yoon PS, Singh K: Update on antifibrotic use in glaucoma surgery, including use in trabeculectomy and glaucoma drainage implants and combined cataract and glaucoma surgery. Curr Opin Ophthalmol 15:141, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship with the manufacturer or provider of any commercial product or service discussed. Dr Greff has participated in the Speaker’s Bureau for Alcon, Allergan, and Pfizer and has been a clinical investigator for Allergan; Dr. Singh has been a consultant for Alcon, Johnson and Johnson, Pfizer, Santen, and Vistakon.
Drs. Greff, Singh, and Khatana were recorded at Glaucoma: Current Management and Updates, presented May 21, 2005, in Cincinnati by the University of Cincinnati College of Medicine and the Cincinnati Eye Institute. The Audio-Digest Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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