FOCUS ON GLAUCOMA
From Glaucoma Management in 2008: Pearls and Pitfalls, presented by the Cole Eye Institute of the Cleveland Clinic
Foundation, Cleveland, OH
Dale K. Heuer, MD, Professor and Chair, Department of Ophthalmology, Medical College of Wisconsin, and Director, the
Froedtert and the Medical College of Wisconsin Eye Institute, Milwaukee
Educational Objectives
| The goal of this program is to improve the management of glaucoma. After hearing and assimilating this program, the clinician
will be better able to:
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 | 1. Identify the factors that predict risk for progression and use models to optimize treatment and follow-up regimens
for patients with elevated intraocular pressure.
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| 2. Choose appropriate therapy to prevent progression in patients with existing glaucoma.
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| 3. Describe the advantages of laser trabeculoplasty and distinguish between argon and selective laser trabeculoplasty.
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| 4. Evaluate the data on the use of laser trabeculoplasty as primary and/or second-line therapy for glaucoma.
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| 5. Differentiate between various methods of nonpenetrating surgery, such as subconjunctival filtration, uveoscleral
outflow, and Schlemm’s canal procedures.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, Dr. Heuer and the planning committee reported nothing to disclose.
Acknowledgements
Dr. Heuer’s lectures were recorded at Glaucoma Management in 2008: Pearls and Pitfalls, held January 12, 2008, in
Cleveland, OH, and presented by the Cole Eye Institute of the Cleveland Clinic Foundation. The Audio-Digest Foundation
thanks Dr. Heuer and the Cole Eye Institute of the Cleveland Clinic Foundation for their cooperation in the
production of this program.
| Incorporating the Results of Glaucoma Clinical Trials into Practice
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| Ocular Hypertension Treatment Study (OHTS): objective—determine efficacy and safety of treatment to reduce
risk of developing glaucoma for patients with ocular hypertension (OHT) at moderate risk; results—at 5 yr, treatment
reduced relative risk for glaucoma developing from OHT by ≈60%, and reduced absolute risk by ≈5%; risk
reduction 62% in patients who were not black; risk reduction among black patients (who had higher risk) ≈50%; safety—
no increase in mortality, hospitalizations, or worsening of preexisting medical conditions
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| Factors that predict risk: central corneal thickness important predictor of development of glaucoma in patients with OHT;
risk increased 70% for every 40-µm difference in thickness; cup-to-disc (C/D) ratio, pattern standard deviation (PSD),
age, and intraocular pressure (IOP) also predict increased risk; self-proclaimed history of diabetes found to be protective
(not factor in later studies using more rigorous definition of diabetes)
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| Significance of risk factors: previously believed that risk for glaucoma in patients with OHT 0.5% to 1% per year in those
without family history, and 2% per year in those with family history; OHTS trial showed risk 35% over 5 yr (7% per
year) for patients with thin corneas and high IOPs; with relatively small C/D ratio (>0.3) and thin cornea, 5-yr risk 20%;
prediction model based on data from treated and untreated patients
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| Risk factors model for patients with IOP: European Glaucoma Prevention Study (EGPS)—patients with OHT randomized
to placebo or dorzolamide; similarity of protocols allowed comparison to OHTS; results—5 main risk factors
identified in both studies; among untreated patients, only IOP (in OHTS), central corneal thickness (CCT; in both studies),
and vertical C/D ratio (in both studies) reached statistical significance
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| Generalizability of predictions: OHTS required IOP of 24 mm Hg, but EGPS used IOP of 21 mm Hg for enrollment;
therefore, conclusions from combined data relevant for more patients; combined results identified 5 statistically significant
risk factors (ie, age, IOP, CCT, vertical C/D ratio, and PSD); additional statistical analyses confirmed these factors
and excluded others (eg, diabetes, heart disease, ethnicity); accuracy of prediction—value of C-statistic for pooled
data from OHTS and EGPS ranged from 0.7 to 0.8 on a theoretic scale of 0.5 to 1.0 (compared to Framingham Heart
Study, in which C value 0.6-0.8); model now available online to calculate risk—most rigorous uses 3 measurements of
IOP, corneal thickness, and 2 fields for PSD measurement
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| Utility of model: assessment of risk drives follow-up schedule and treatment decisions; application of model potentially
reduces medical costs by decreasing unnecessary treatment; optimal threshold—one model showed cost benefit in
treating patients who had 5-yr risk of 10%; however, limited by assumptions and extent of similarity between individual
patient and those in study; unclear whether applicable for predicting progression in patients with existing glaucoma;
model does not account for disc hemorrhages; age and health status of patient also contribute to therapy decision
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| Patients with existing glaucoma: Early Manifest Glaucoma Trial (EMGT)—compared effects of immediate vs delayed
(or undelayed) therapy on progression; treatment group received laser trabeculoplasty and betaxolol; 4-yr risk for
progression reduced to 30% with treatment (vs 50% without treatment); however, more progression of nuclear cataracts
with treatment also seen; factors associated with progression—higher IOP, pseudoexfoliation, age, lower systemic perfusion
pressure, and initial mean deviation (significance borderline); important to evaluate pseudoexfoliation with slit-lamp
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| Patients with normal-tension glaucoma: Collaborative Normal-Tension Glaucoma Study—examined whether
treatment beneficial for patients with glaucoma and normal IOP; goal of treatment to reduce IOP by 30%; patients who
developed cataracts censored; at 5 yr, rate of progression 20% with treatment vs 40% without treatment; risk for progression
slightly higher for women, 2.5-fold higher for patients with migraines, and almost 3 times higher for patients with
disc hemorrhages at entry; for most patients in untreated arm, progression relatively slow
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| Patients for whom medical therapy fails: Advanced Glaucoma Intervention Study (AGIS)—looked at best course
of action after failure of medical therapy (ie, trabeculoplasty or laser trabeculectomy [LT]); found black patients did better
with trabeculoplasty first (however, trabeculectomy done without wound-healing modulation, so many failures seen);
post hoc analyses showed patients with IOP consistently <18 mm Hg had little overall progression; also, IOP variation
strong predictor for progression (30% increased risk for 1-mm change in standard deviation of fluctuation)
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| Glaucoma Laser Trial (GLT): argon laser trabeculoplasty (ALT) as primary therapy compared to topical medication;
group with laser treatment first had lower IOP; limitations—patients not randomized (only eyes randomized); crossover
effect of medications in fellow eye not excluded; results—field loss approximately equal over 5 yr; those in ALT
group had more initial symptoms
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| Fluorouracil Filtering Surgery Study (FFSS): showed that using 5-fluorouracil (5-FU) to modulate wound-healing
response resulted in increased rate of success but also increased complications; better wound-closure techniques (no
leakage) improved outcome
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| Unpublished results from Collaborative Initial Glaucoma Treatment Study (CIGTS): reducing IOP
consistently to <16 to 18 mm Hg more important than average IOP; patients with more advanced damage possibly do better
with LT
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| SLT VS ALT: IS THERE A DIFFERENCE?
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| Advantages of laser trabeculoplasty: effective in most patients with open-angle glaucoma; relatively noninvasive;
rate of complications low; duration of effect 24 hr; independent of adherence
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| Differences between ALT and selective laser trabeculoplasty (SLT): large difference between total energy
delivered and size of field; SLT technically easier; gonioscopy increase in 1980s stimulated by development of laser trabeculoplasty;
any thermal laser energy delivered to meshwork lowers IOP (likely stimulates endothelial function,
changes extracellular matrix, and stretches meshwork between burns); SLT breaks up pigment and may stimulate change
that increases outflow; both lower IOP by 20% to 30%
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| Long-term outcomes study: retrospective chart review showed no difference in outcomes between ALT and SLT (powered
to detect 20% difference), using cutoffs of either 3 mm Hg or 20% reduction of IOP
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| Study of SLT vs medical therapy: at 1 yr, fewer than 25% of patients had controlled IOP after addition of SLT to
medical therapy; at end of study, only 10% to 15% had IOP controlled by laser; therefore, SLT cannot replace medications;
if IOP not controlled, SLT not likely to forestall incisional surgery (if IOP not reduced to target 8-12 wk after SLT,
proceed to incisional surgery)
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| Retreatment: poor success rate seen with retreatment by ALT; however, if SLT used after ALT, success rate similar to
that with SLT alone
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| Randomized trial of ALT vs SLT: 90 patients per group; baseline IOP in both groups 23 to 24 mm Hg, and reduced
to 18 mm Hg at 12 mo; no difference seen in patients who had not had previous ALT; possible slight advantage for ALT
in patients with previous 180° ALT, and for SLT in patients with previous 360° ALT; overall, no difference in success or
complication rates; traditionally, ALT used after medications (including oral carbonic anhydrase inhibitors); American
Academy of Ophthalmology (AAO) Preferred Practice Pattern recommends considering laser trabeculoplasty as initial
therapy; may reduce dependence on medications but unlikely to eliminate need for them altogether (only 20% of patients
who had LT as initial therapy able to control IOP without medications)
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| SLT as primary therapy: good response seen in study; comparison to steroid (latanoprost) as initial treatment showed
30% reduction in IOP, although reduction not as prominent if patient already using other medications (ie, drops)
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| Early Manifest Glaucoma Trial: patients received primary treatment with ALT and topical betaxolol; 30% reduction
in IOP seen in patients whose initial IOP >21 mm Hg (in patients with normal-pressure glaucoma, reduction only
20%); however, even with treatment, many patients progressed (30% after 4 yr)
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| Summary: LT effectively controls IOP; ALT and SLT equally effective and safe; theoretically, SLT repeatable because
it does not destroy tissue (no supporting data); SLT may have advantage in patients who had previous 360° ALT
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| GLAUCOMA FILTERING SURGERY: TRABECULECTOMY VS NONPENETRATING SURGERY
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| Goals of ideal glaucoma surgery: alternative therapies needed because outcome of LT not sufficiently predictable;
reduce IOP to episcleral venous pressure without medications, and without circadian variation; completely preserve visual
function; eliminate cataracts, hypotony maculopathy, induction of 15 diopters of cylinder, or other complications
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| Progress: shift from full-thickness procedures; coverage with scleral flap (with inner block smaller than outer); laser sutures
have enabled tighter flap closure; postoperative manipulations developed to improve healing; modulating healing
more important than changing size and/or shape of surgery site; however, success rate still not 100%, and increased success
may lead to oversuccess (eg, hypotony maculopathy, bleb dysesthesia, bleb leaks, infections)
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| Alternatives approved or waived by Food and Drug Administration (FDA): LT—speaker prefers SLT
over ALT because SLT causes less damage to Schlemm’s canal and may allow subsequent canal procedures; endocyclophotocoagulation
possibly gentler and provides better pressure control in combined procedures, but little supporting data
published; other procedures—subconjunctival filtration; uveoscleral outflow; Schlemm’s canal procedures
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| Subconjunctival filtration: eg, deep sclerectomy (DS), viscocanalostomy, Ex-PRESS implant
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| Advantages: no entry of anterior chamber or need for iridectomy; fewer initial complications; IOP controlled with thicker
or no bleb (possibly result of using mitomycin); however, results subject to variations in technique, follow-up, definition
of success, and possible publication bias
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| Studies: show effectiveness of DS comparable to LT, whereas viscocanalostomy less effective; nonpenetrating procedures
technically more difficult; LT had slightly higher rate of initial complications, but visual acuity approximately
similar for all; speaker’s opinion—avoidance of bleb complications not yet proven because of use of mitomycin-C;
consider nonpenetrating procedures only for patients with mild to moderate damage because IOP not greatly reduced
and procedure uses upper limbus
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| Ex-PRESS implant: study showed extensive early hypotony and fair number of late erosions; later modified to put implant
under scleral flap; less rapid but more predictable; relatively good control of IOP observed, but some development
of hypotony and choroidals also seen, and reform of anterior chamber necessary in 2 patients
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| Other innovative procedures
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| Uveoscleral tubes, shunts, and dialysis: cyclodialysis abandoned because of unpredictability of IOP outcome; gold implant
may improve this, but not yet approved
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| Schlemm’s canal procedures: Trabectome and viscocanalostomy available currently; iStent device and excimer laser trabeculotomy
(similar to focal form of Trabectome) expected in future; Trabectome—electrocautery approach cannulates
canal and insulates against damage to distal wall; early study showed good outcomes, but reduced IOPs to mid to
upper teens only (possibly suboptimal for patients with more than mild to moderate damage); success rate ≈75% (IOP
<21 mm Hg)
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| Science fiberoptic probe: achieves 360° viscocanalostomy; involves 3-layered flap, and uses probe to identify and cannulate
Schlemm’s canal (possible future application in children with 360° trabeculotomy with optional gonioscopy); uses
tensioning sutures to maintain patency; study found similar overall outcomes with and without sutures; complications
minimal; in 75% of patients, IOP controlled with medications after 1 yr; patients who experienced distention from suture
appeared to have lower IOPs (middle or lower-middle teens) than those with suture but no distention
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Suggested Reading
Barkana Y, Belkin M: Selective laser trabeculoplasty. Surv Ophthalmol 52:634, 2007; Brandt JD: Central corneal
thickness, tonometry, and glaucoma risk—a guide for the perplexed. Can J Ophthalmol 42:562, 2007; Chihara E: Assessment
of true intraocular pressure: the gap between theory and practical data. Surv Ophthalmol 53:203, 2008;
Choudhary A, Wishart PK: Non-penetrating glaucoma surgery augmented with mitomycin C or 5-fluorouracil in
eyes at high risk of failure of filtration surgery: long-term results. Clin Experiment Ophthalmol 35:340, 2007; Filippopoulos
T, Rhee DJ: Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery. Curr Opin Ophthalmol
19:149, 2008; George MK et al: Evaluation of a modified protocol for selective laser trabeculoplasty. J Glaucoma
17:197, 2008; Hondur A et al: Nonpenetrating glaucoma surgery: meta-analysis of recent results. J Glaucoma 17:139,
2008; Lin SC: Endoscopic and transscleral cyclophotocoagulation for the treatment of refractory glaucoma. J Glaucoma
17:238, 2008; Mansouri K et al: Quality of diurnal intraocular pressure control in primary open-angle patients treated
with latanoprost compared with surgically treated glaucoma patients: a prospective trial. Br J Ophthalmol 92:332, 2008;
Mearza AA, Aslanides IM: Uses and complications of mitomycin C in Ophthalmology. Expert Opin Drug Saf 6:27,
2007; Mincione F et al: The development of topically acting carbonic anhydrase inhibitors as antiglaucoma agents. Curr
Pharm Des 14:649, 2008; Minckler DS et al: Aqueous shunts in glaucoma: a report by the American Academy of Ophthalmology.
Ophthalmology 115:1089, 2008; Moreno-Montanes J et al: Prognostic value of gonioscopy after deeop
sclerectomy. Eur J Ophthalmol 17:702, 2007; Ritch R: Exfoliation syndrome: beyond glaucoma. Arch Ophthalmol
126:859, 2008; Rivera JL et al: Risk factors for primary open angle glaucoma progression: what we know and what we
need to know. Curr Opin Ophthalmol 19:102, 2008; Sarodia U et al: Nonpenetrating glaucoma surgery: a critical evaluation.
Curr Opin Ophthalmol 18:152, 2007; Shields MB: Normal-tension glaucoma: is it different from primary open-angle
glaucoma? Curr Opin Ophthalmol 19:85, 2008; Stein JD, Challa PL: Mechanisms of action and efficacy of argon
laser trabeculoplasty and selective laser trabeculoplasty. Curr Opin Ophthalmol 18:140, 2007; Uhler TA, Piltz-Seymour
J: Optic disc hemorrhages in glaucoma and ocular hypertension: implications and recommendations. Curr Opin
Ophthalmol 19:89, 2008; Whitson JT: Glaucoma: a review of adjunctive therapy and new management strategies. Expert
Opin Pharmacother 8:3237, 2007.
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