CLINICAL PEARLS IN THE TREATMENT OF GLAUCOMA
From the Annual Clinical Conference, presented by the Kansas City Society of Ophthalmology and Otolaryngology,
Kansas City, MO
Norman A. Zabriskie, MD, Associate Professor, Vice Chair, and Medical Director of Clinical Services, Moran Eye
Center, University of Utah, Salt Lake City
| Baltimore Eye Survey: JAMA (1991); conducted by Johns Hopkins University; ≈5000 examinations; first study—
showed definite differences in prevalence of open-angle glaucoma in United States based on race; in whites >80 yr
of age, adjusted prevalence ≈2%, in blacks, 11%; second study (1991)—clearly established relationship between
intraocular pressure (IOP) and open-angle glaucoma (prevalence increased as IOP increased); from epidemiologic
standpoint, did not show any support for distinguishing between normal-tension glaucoma and high-pressure glaucoma
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| Normal-Tension Glaucoma Treatment Trial: first results published in 1998; randomized 140 eyes of 140 patients to
no treatment (continued observation) or 30% lowering of IOP; randomization occurred once progression documented
or initially if fixation threatened; once baseline established, 35% of control eyes reached progression end
points, compared to 12% of treated eyes; conclusion—IOP definitely part of pathogenic process of normal-tension
glaucoma; mean IOP reduced from 16 mm Hg (pretreatment) to 11 mm Hg; 30% reduction in IOP decreased risk
for progression to end point; looking at original baseline (when subjects entered study before being randomized),
favorable effect of IOP lowering found only after cataract impact removed (through surgery)
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| Advanced Glaucoma Intervention Study (AGIS): >700 eyes; specific entry criteria with rigorous follow-up; initially
designed to test 2 treatment algorithms; AGIS report 7 looked at 2 analyses; predictive analysis—whether patient’s
response after 18 mo of treatment can predict long-term results; divided patients into 3 groups by IOP (<14
mm Hg, 14-17 mm Hg, and >17 mm Hg); associative analysis—follow-up (6-yr) data; divided patients into 4
groups according to percentage of visits with IOP <18 mm Hg; results of predictive analysis—eyes with IOP >17
mm Hg had more visual field worsening than those with IOP <14 mm Hg; visual field worsening greater at end of
follow-up period than after 18-mo initial period; concluded that those with pressure >17 mm Hg would predictably
have more visual field progression at end of follow-up period; results of associative analysis—group with IOP <18
mm Hg 100% of time had visual field progression close to 0; within that group, average IOP 12 to 13 mm Hg; those
with IOP >18 mm Hg 50% of time had visual progression that increased throughout course of study
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| Collaborative Initial Glaucoma Treatment Study (CIGTS): enrolled new patients with moderate glaucoma; randomized
to medical therapy or trabeculectomy (with or without 5-fluorouracil [5-FU]); mean IOP in surgery group
slightly lower than in medicine group (3-point difference); in both groups, reduction in IOP significant (48% in surgery
group; 35% in medical group); attributed to prostaglandins (used at discretion of physician); results—in both
groups, at initial data release (at 5-yr follow-up), no net visual field progression; visual acuity loss greater initially
in surgery group, but about even at 5-yr data point; vision loss about same; more cataracts in surgery group;
conclusion—present data do not support altering current treatment approaches to primary open-angle glaucoma
(POAG); specifically, data do not support notion of performing surgery first, and using medicines resulted in 5 yr
of no visual field loss
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| Early Manifest Glaucoma Trial (EMGT): National Institutes of Health (NIH)-funded study done in Sweden; used
defined characteristics and criteria to randomize patients to treatment or observation; treatment arm received regimented
treatment of argon laser trabeculoplasty (ALT) and betaxolol; treatment adjusted only if IOP in treatment
group consistently stayed >25 mm Hg (then prostaglandin added); followed for 6 yr with rigorous end point criteria;
results—treatment resulted in 25% reduction in IOP; progression less frequent in treatment group; both groups
(treatment and control) progressed more than patients in Ocular Hypertension Treatment Study (OHTS; considered
partly due to less aggressive IOP lowering); 25% reduction in IOP resulted in less and delayed progression; increase
in cataracts in treatment group; treatment effects (eg, pigmentary, exfoliation, POAG) present in all groups
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| Ocular Hypertension Treatment Study: entry criteria—40 to 80 yr of age, normal visual fields, normal optic discs;
for entry, untreated IOP 24 to 33 mm Hg in qualifying eye, 21 to 32 mm Hg in fellow eye; in medication or treatment
group, ≈4% progression rate from ocular hypertension to definable open-angle glaucoma; in observation
group, ≈11% (ie, ≈50% reduction in risk with treatment); age, IOP, central corneal thickness, visual field parameter,
and increased cup-to-disc ratio all predictive of developing open-angle glaucoma
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| General consensus from trials: Palmberg—adequate glaucoma therapy extremely effective and can markedly reduce
or halt glaucomatous damage at any stage of disease; today’s medicines can result in significant IOP lowering
and effective glaucoma treatment; surgery equally effective; medicine and surgery have side effects (can induce
cataracts), but when applied appropriately, potential benefits outweigh risks; question of whether difference exists
between normal-tension glaucoma and high-pressure glaucoma—from Baltimore Eye Survey, no epidemiologic
evidence; from Normal-Tension Glaucoma Study, normal-tension glaucoma patients responded to IOP-lowering in
similar way to high-pressure glaucoma patients; Caprioli—in editorial, proposed that in glaucoma, at any given
time, 2 forces (pressure-independent and pressure-dependent) acting on optic nerve; pressure-independent forces
poorly characterized (eg, vascular factors, genetic susceptibility) and active at all times; pressure-dependent factors
increase as pressure increases; worsening of disease at low pressures due to pressure-independent factors; clinical
application—speaker treats normal-pressure patient like progressing open-angle glaucoma patient; observation not
uncalled for, but once progression observed, need to lower IOP; perform surgery if necessary; speaker believes no
medication should be withheld if it can lower IOP; consider nonpressure-related treatments (eg, calcium channel
blockers, gingko), but not as substitute for maximally lowering IOP
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| Central corneal thickness: in OHTS, most prominent factor for predicting which patients will progress to glaucoma
over 5 yr; if baseline entry IOPs in OHTS stratified against central corneal thickness, for any given IOP, risk for
progressing to glaucoma higher in those with thinner central corneas; also true for progression in patients already
diagnosed with glaucoma; in patients with high cup-to-disc ratio also, those with thinner corneas progress more;
confirmed by other studies; might also predict response to medication; must be measured in all glaucoma-related
patients; use to decide how aggressively patient should be treated
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| Pressure variability: study (2000)— 64 glaucoma patients using home tonometry; had normal IOP measured in office;
large fluctuations in diurnal IOP significant risk factor, independent of risk factors measurable at one-time office
visit; suggests that IOP variability, by itself, important; study by Caprioli—reanalyzed subset of patients from
AGIS; evaluated with slightly different visual field algorithm, looking for progression; looked at predictive factors
for visual field progression and determined that older age first and IOP fluctuation second (intervisit fluctuation);
study—done in and around Olmstead county, MN; looked longitudinally at glaucoma patients who became blind;
patients who became blind had lower mean IOP but higher IOP variability (intervisit) than those who remain
sighted; emerging area of study in glaucoma; prostaglandins—truly 24-hr drugs; excellent for lowering IOP evenly
for 24 hr; studies show that variability blunted (diurnal or intervisit) after surgery, compared to medicine
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| Trabeculectomy: good IOP lowering (48% in CITGS study); advantages—less IOP variability; decreased medicine
requirement; disadvantages—failure; hypotony; long-term infection risk; bleb dysesthesia; Moorfields Safe Surgery
System—technique-based; Khaw works with technique to change morphology of bleb; uses fornix-based conjunctival
flap; wide area of antimetabolite (mitomycin) application key; scleral flap constructed for posterior flow,
to prevent fluid from coming out anteriorly; dissection not taken to limbus; tight sutures used at corners and sides
(as needed) to get flow going back; small scleral punch and adjustable sutures; topical anesthesia; uses wide
spreading to create large pocket; also uses anterior chamber maintainer with infusion cannula to maintain chamber
(thought to help with postoperative visual acuity); many tight sutures used but not tied securely so they can be adjusted
postoperatively; Moorfields system—easily implemented; need not be followed exactly, as long as wide area
of mitomycin used and flow directed posteriorly
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| Nonpenetrating surgery: 2 fundamental procedures viscocanalostomy and deep sclerectomy; common steps—unroof
Schlemm’s canal by cutting superficial flap, then deep flap (≈90% depth); carry dissection forward until creation of
“trabecular descemetic window,” down to Descemet’s membrane into clear cornea with egress of fluid;
viscocanalostomy—cut ends of Schlemm’s canal cannulated with special cannula, and viscoelastic injected into
Schlemm’s canal to expand it and help decrease resistance of canal; flap tied down tightly; in purest form, viscocanalostomy
not bleb-forming procedure; deep sclerectomy—cut ends of Schlemm’s canal not necessarily cannulated,
but canal unroofed and window cut; scleral flap tied down loosely; in purest form, bleb-forming procedure;
modifications include removal of inner wall of Schlemm’s canal; further modification involves putting in collagen
wick (space maintainer) sewn down in base of deep flap, and superficial flap brought back over top; results for deep
sclerectomy—early outcome papers (2001); 105 eyes had deep sclerectomy; mean IOP at 48 mo ≈12 mm Hg; success
defined as IOP <21 mm Hg without medication; 60% success rate; 94% of patients had qualified success (with
addition of medication); few postoperative complications; 46% had yttrium aluminum garnet (YAG) laser goniopuncture
to increase flow; outcomes for viscocanalostomy—Stegmann’s early results published in 1999; 214 eyes
followed for 35 mo; mean IOP ≈17 mm Hg; 83% had IOPs <22 mm Hg without medicine
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| Trabeculectomy compared to nonpenetrating surgery: in 1999-2000, 3 glaucoma specialists suggested looking at
procedures in prospective randomized way, comparing them to trabeculectomy; viscocanalostomy vs
trabeculectomy—in all studies, trabeculectomy more effective at lowering IOP; viscocanalostomy had significantly
more pressure-lowering effect from baseline, but not as good as trabeculectomy; also fewer side effects
with viscocanalostomy; deep sclerectomy vs trabeculectomy—deep sclerectomy compares more favorably with
trabeculectomy for lowering pressure; no study found any significant difference between 2 procedures, except
study by Chiselita (2001) where trabeculectomy found more effective; in Mermoud study (1999), trend toward
deep sclerectomy being more effective
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 | Summary: IOP lowering inferior in these procedures, compared to trabeculectomy (especially true of viscocanalostomy);
can get significant IOP lowering with these procedures compared to baseline, but not as good as trabeculectomy;
fewer postoperative complications; one small study randomized patients to deep sclerectomy or
modified trabeculectomy (Khaw system) and found trabeculectomy more effective at lowering IOP and had
fewer complications; long learning curve for these procedures; speaker’s opinion—consider using these procedures
if target IOP in middle to high teens; also if high risk for complications present; not considered in advanced
disease where target IOP low; case 1—woman 57 yr of age; monocular (had suprachoroidal hemorrhage in other
eye during trabeculectomy); presents with IOP of 40 mm Hg on maximum medication; optic nerve shows cupping
(documented to progress by digital photography); visual field normal; had nonpenetrating surgery; IOP stabilized
in upper teens; case 2—man, 44 yr of age, has traumatic glaucoma; documented visual field loss at IOP
of 18 mm Hg on medication; patient requested nonpenetrating surgery; IOP stabilized at 16 mm Hg; had progression;
consented to trabeculectomy with mitomycin; IOP reduced to 9 mm Hg and has had stabilization of visual
field for >5 yr
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Suggested Reading
AGIS Investigators: The Advanced Glaucoma Intervention Study (AGIS): 12. Baseline risk factors for sustained
loss of visual field and visual acuity in patients with advanced glaucoma. Am J Ophthalmol 134:499, 2002; AGIS Investigators:
The Advanced Glaucoma Intervention Study (AGIS): 11. Risk factors for failure of trabeculectomy and
argon laser trabeculoplasty. Am J Ophthalmol 134:481, 2002; Anis S et al: Surgical reduction of symptomatic, circumferential,
filtering blebs. Arch Ophthalmol 124:890, 2006; Barkana Y et al: Clinical utility of intraocular pressure
monitoring outside of normal office hours in patients with glaucoma. Arch Ophthalmol 124:793, 2006; Heijl A et al:
Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch
Ophthalmol 120:1268, 2002; Hong S et al: Central corneal thickness and visual field progression in patients with
chronic primary angle-closure glaucoma with low intraocular pressure. Am J Ophthalmol 143:362, 2007; Jampel HD
et al: Perioperative complications of trabeculectomy in the collaborative initial glaucoma treatment study (CIGTS).
Am J Ophthalmol 140:16, 2005; Leske MC et al: Factors for glaucoma progression and the effect of treatment: the
early manifest glaucoma trial. Arch Ophthalmol 121:48, 2003; Libre PE: Nonpenetrating filtering surgery and goniopuncture
(staged trabeculectomy) for episcleral venous pressure glaucoma. Am J Ophthalmol 136:1172, 2003; Lichter
PR: Expectations from clinical trials: results of the Early Manifest Glaucoma Trial. Arch Ophthalmol 120:1371,
2002; Rosenbaum LJ: Management of patients with ocular hypertension: a cost-effectiveness approach from the Ocular
Hypertension Treatment Study. Am J Ophthalmol 143:191, 2007; Spratt A et al: What's in a name? New glaucoma
drugs. Lancet 368:826, 2006
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. Summarize and apply the results and conclusions of the main glaucoma studies.
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| 2. Recognize the factors for predicting which patients will progress to glaucoma.
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| 3. Describe the advantages and disadvantages of trabeculectomy.
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| 4. Compare viscocanalostomy with deep sclerectomy.
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| 5. Compare trabeculectomy with deep sclerectomy and viscocanalostomy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members 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, the faculty reported nothing to disclose.
Acknowledgements
Dr. Zabriskie was recorded at the Annual Clinical Conference, held January 5-6, 2007, in Kansas City, MO, and sponsored
by the Kansas City Society of Ophthalmology and Otolaryngology. The Audio-Digest Foundation thanks Dr.
Zabriskie and the sponsor for their cooperation in the production of this program.
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