GLAUCOMA ASSESSMENT AND MANAGEMENT
From the 10th Annual Glaucoma Symposium, presented by the Glaucoma Research and Education Group
| NEW PERSPECTIVES ON TARGET IOP—Kuldev Singh, MD, Professor of Ophthalmology and Director, Glaucoma
Service, Stanford University School of Medicine, Stanford, CA
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| Definition of target intraocular pressure (IOP; American Academy of Ophthalmology): range of IOP
adequate to stop progressive pressure-induced injury (implies that IOP-induced injury can be stopped); in most patients,
not practical to get IOP to 7 or 8 mm Hg because costs and risks may be greater than benefit (especially for patients at
low risk); more practical definition—level of IOP at which marginal benefit of further pressure lowering likely outweighed
by risk associated with therapy; specific risks and benefits not clear until therapy initiated in individual patient
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| Relationship between IOP and primary open-angle glaucoma (POAG): IOP positive risk factor for development
of disease, and lowering IOP slows progression of optic nerve damage; IOP fluctuates over diurnal and nocturnal periods;
Baltimore Eye Survey—higher IOP in population, greater prevalence of disease; nothing magical about 21 mm Hg
(target used in past); subjects with IOP ≤14 mm Hg <50% as likely to have glaucoma as patients with IOP 18 mm Hg; subsequent
studies showed benefit of IOP-lowering therapy, regardless of stage of disease, even in patients who had ocular
hypertension
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| Advanced Glaucoma Intervention Study (AGIS): postoperative predictive analysis looked at mean IOP over
first 3 visits at 6mo intervals; group that had highest mean IOP early in study most likely to develop visual field progression;
patients who had peak IOP <18 mm Hg at all visits did not show progression; individuals who had IOPs >18 mm Hg
had greater rates of progression; post hoc analysis of IOP variability between visits—group that had greatest variability
had much greater rate of visual field progression than those having least variability
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| IOP fluctuation: retrospective analysis of Ocular Hypertension Treatment Study (OHTS)—90 patients treated with
timolol or placebo; diurnal IOP measurements with automated perimetry and disc photos every 3 mo; mean IOP highly
significantly related to risk for progression (however, mean daily range did not correlate); Cox progression analysis used
to correct for IOP; IOP fluctuations increase 0.17 mm Hg for every 1.0 mm Hg increase in IOP (higher mean IOP, greater
likelihood of IOP fluctuation); nocturnal IOP and body position (study 1)—when sitting up, IOP falls (in supine position,
IOP higher); study 2—baseline IOP measurements in 18 patients lying flat in sleep laboratory and IOP measured
with pneumotonometry after patients awakened in middle of night; IOP higher in supine position at night, compared to
sitting position during day; also, timolol does not affect aqueous humor production nocturnally (no effect on IOP in supine
position in nocturnal period); however, significant reduction in IOP during daytime in sitting position with timolol
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| Other limitations of target IOP concept: some patients can lose up to half of ganglion cells and still have relatively
normal visual fields (much variability); rate of ganglion cell death and how cell death occurs (in discrete bundles or more
diffusely) not predictable; information can change over time; all treatment modalities associated with risks and costs
(risks associated with trabeculectomy may outweigh benefit of reduced IOP)
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| VIEWS ON PERIMETRY —Marc F. Lieberman, MD, Clinical Professor of Ophthalmology, University of California, San
Francisco, School of Medicine; Director, Glaucoma Services, California Pacific Medical Center, San Francisco, CA
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| Short-wavelength automated perimetry: advantages—more sensitive than standard perimetry; can predict visual
field loss by several years; in glaucoma suspects, indicators light up earlier; progression more pronounced than on white-
on-white perimetry; most validated visual field test ever studied; disadvantages—mildly affected by cataract; variable;
tedious for patients
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| Humphrey Matrix Perimeter: utilizes frequency-doubling technology for threshold testing; cannot interface with
Humphrey Field Analyzer (HFA) II; smaller targets and grids; can monitor eye position; Zippy Estimation of Sequential
Thresholds (ZEST) program—new algorithm; improved sensitivity; reduced testing time (1 min); numeric scale, gray
scale, and total deviation plot (subtract patient’s results from age-matched database); pattern SD (PSD) plot (“fudge factor”
of small pupil or cataract taken out); developing database based on macular degeneration and diabetic retinopathy to
compare patient’s results against baseline (usefulness not clear); comparison to HFA—good device for screening on
tight budget; if result positive, perform Humphrey field testing (more likely than not to find defect); applications—
angle-closure glaucoma with superior arcuate defect (gold standard is HFA or Octopus visual field analyzer); occipital
stroke (test time 1-3 min); superb for detection surveys when working overseas; lacks capacity to integrate data with
HFA
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| Glaucoma Progression Analysis (GPA) software: replaces Glaucoma Change Probability (GCP) program; allows
use of Swedish Interactive Testing Algorithm (SITA); based on database of clinically stable glaucoma patients; can
compare SITA results against known database; also based on analysis from Sweden of Early Manifest Glaucoma Study
(EMGS); software indicates possible progression or likely progression; can discriminate areas of visual field most likely
to be changing; can prevent overinterpretation (most common problem)
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| Take-home points: if visual field looks worse, repeat test; glaucoma rarely advances symmetrically; if both visual fields
worsen same day, patient having “bad hair day”; repeat 1 mo later (visual field typically reverts on both sides to original appearance)
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| TRABECULECTOMY AND COMBINED SURGERY —John S. Cohen, MD, Head, Glaucoma Service, Cincinnati Eye
Institute, Cincinnati, OH
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| Purpose of recent research: to determine results of trabeculectomy and combined surgery using ocular compression
and releasable sutures
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| Study parameters and results: 49 trabeculectomy eyes; 92 combined surgery eyes; 0.4 mg/mL mitomycin for 2.2
min mean concentration in trabeculectomy group (1.9 min mean concentration in combined surgery group); trabeculectomy
group—preoperative IOP 23.7 mm Hg on 3.3 medications; postoperatively, mean IOP 14.1 mm Hg on 1.1 medication
and change 10 mm Hg with reduction of 2.2 medications; combined surgery group—initial IOP 18.8 mm Hg on
2.6 medications; postoperatively, 13.5 mm Hg on 0.8 medication (reduction of 4.7 mm Hg and 1.8 medications)
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 | Ocular compression: trabeculectomy eyes—about same number of eyes had increase in IOP as decrease at next visit;
range increase to 20 mm Hg, decrease to 20 mm Hg (excursion decreased over time; ocular compression performed
less as healing progressed); combined surgery eyes—similar distribution (about as many eyes had increase in IOP as
reduction at next visit); mostly done in early weeks; less excursion and few outliers
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| Suture release: trabeculectomy eyes—when sutures released, reduction in IOP up to 30 mm Hg in early postoperative
period; combined surgery eyes—about same distribution as in trabeculectomy eyes; much greater distribution of decrease
in IOP than increase (increase almost negligible); greatest reduction in IOP in early postoperative period
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| Does short-term elevation of IOP cause visual field damage? combined surgery—statistically significant
change with increase in mean deviation; statistically significant (although small) worsening of PSD; both groups—
decreased PSD in group with higher IOP and advanced field loss group (not in lower-IOP, less-advanced group); combined
surgery group—mean change <2 dB; trabeculectomy group not statistically different
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| Conclusions: ocular compression and suture release in trabeculectomy and combined surgery improved IOP control; ocular
compression useful to temporarily reduce IOP to determine extent of wound healing (helps predict response to suture
release); suture release produces more sustained IOP reduction; although visual fields usually minimally affected, PSD
worsened in high-IOP group with advanced visual field loss; when IOP elevated in early postoperative period, risk for visual
field damage must be balanced against risk for hypotony when considering suture release
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| PEDIATRIC GLAUCOMA UPDATE —Terri Pickering, MD, Chairperson, Department of Ophthalmology, St. Mary’s
Medical Center, San Francisco, CA
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| Epidemiology of primary congenital glaucoma (PCG): aphakic and pseudophakic glaucoma in infancy second
most common category of pediatric glaucoma; review (Massachusetts Eye and Ear Infirmary)—170 aphakic eyes; after
lensectomy, glaucoma occurred in 37% of eyes by 1 yr (76% by 6 yr; 100% by 33 yr); most cases of PCG diagnosed
during first year after birth
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| Genetic component: large gene involved (CYP1B1 gene on chromosome 2P21); mutations give recessive inheritance
with variable penetrance; PCG not caused by heterozygous CYP1B1 mutations; CYP1B1 belongs to cytochrome P450
family of drug-metabolizing enzymes, but role in glaucoma unclear; myocilin gene or MYOC (Tiger gene)—also may
be involved; theory that mutant myocilin alters protein secretion needed to maintain trabecular meshwork; theory that
myocilin gene interacts with CYP1B1 gene to create some forms of juvenile open-angle glaucoma
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| Diagnosis: some children asymptomatic, but others develop intense symptoms; classic triad (tearing, sensitivity to light,
and lid twitching); case presentations (buphthalmia [enlargement of globe] and red inflamed eye; enlarged cornea and
tearing; cloudy cornea); examination under anesthesia (EUA) necessary for definitive diagnosis; measure IOP as soon as
possible after induction (21 mm Hg useful upper limit but not absolute); in normal newborn, corneal diameter 10 to 10.5
mm (increases to 11-12 mm by 1 yr of age); more signs—Haab striae (railroad track signs) and abnormal trabecular
meshwork with stippled orange-peel appearance; flat iris insertion; optic nerve usually deeply cupped with symmetric
rims (not normal in child); in advanced cases, notching may be present; cup-to-disc asymmetry and cup-to-disc ratio >0.3
rare in infants
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| Goniotomy: procedure of choice if cornea clear; 120° maximum angle that can be treated during any one surgery (if
knife manipulated too much, anterior chamber will collapse); long-term prognosis—favorable; 50 eyes followed for up
to 25 yr; only 3 required medications and complications rare; small hyphema common, but typically brief and self-limited
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| Trabeculotomy: advantages—similar to goniotomy in efficacy and safety; can be used in infants with cloudy corneas;
disadvantages—requires more operating time; quadrant of conjunctiva must be sacrificed
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| Trabeculectomy: many barriers to success in children; infants have thick and active Tenon’s capsule, rapid wound healing
response, thin sclera, and high infection risk; infants <1 yr of age have low success rate (>1 yr of age, success rate only
35%; improves by up to 70% with antimetabolite use); antimetabolites increase complications (rate of late-onset endophthalmitis
as high as 17%); if infant not candidate for trabeculectomy—use drainage device; place in superior temporal
quadrant (antimetabolites not recommended); study—32 infants treated with shunts and 19 treated with trabeculectomy;
at 6 yr, success rate 53% for shunts (19% for trabeculectomies)
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| Medical therapy: usually fails as firstline treatment, but may be needed as adjunctive treatment; infants usually have
immature metabolic enzyme system that prolongs half-life of drugs from 2 to 6 times that of adult (increases risk for systemic
side effects); oral carbonic anhydrase inhibitors (CAIs)—10 to 15 mg/kg per day; safe for short-term use; side
effects of long-term use include metabolic acidosis, kidney stones, fatigue, and growth retardation; topical CAIs—fewer
side effects, but less effective; brimonidine (Alphagan)—should not be used in children <6 yr of age or <45 lb due to
frequency of severe side effects (bradycardia, hypotension, hypothermia, apnea, and unresponsiveness; even in older
children, somnolence and extreme fatigue reported); once IOP controlled—greatest threat to vision amblyopia
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| NEW DEVELOPMENTS IN ANGLE SURGERY —Donald S. Minckler, MD, Doheny Eye Institute, Keck School of
Medicine at the University of Southern California, Los Angeles
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| Newer technologies: laser goniopuncture—still in exploratory phase; exciting concept that may turn out to be useful;
goniocurretage—difficult to control depth of “ice cream scoop” instrument used to strip out trabecular meshwork; trabecular
aspiration—limited applicability; microvacuum cleaner; exfoliative debris shaken out of meshwork
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| Glaucos: in multicenter trial in Europe; pipelike device inserted in meshwork; in autopsy eyes, IOP decreased as low as 8
or 10 mm Hg by installing multiple drains
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| Trabectome (NeoMedix): new technology; paper described first 37 cases; device resembles “micro spark plug”; components
active electrode, return electrode, and ceramic-coated footplate with sharp end; inserted through meshwork into
Schlemm’s canal; in course of swinging through arc with electrocautery unit on, ablate strip of tissue which is aspirated up
center of instrument; phaco-like approach; shaft beyond infusion port shortened to lessen need for viscoelastic; has foot
pedal and can control power and aspiration rate and whether infusion on or off; continual infusion; complications—
hyphema virtually 100% but typically dissipates over 6 days; complications remarkably non–vision-threatening; minor
problems related to cornea; in follow-up, few cases of massive peripheral synechiae formation (extremely common after
goniotomy or trabeculotomy); success rate in first series respectable; some failures; IOP curve stable to 24 mo in 19 patients;
SD of IOP measurements declining (IOP declines over same period); summary—Trabectome new technology applicable
to patients with open-angle glaucoma and reasonable gonioscopic landmarks; use rational if IOP goal in midteens;
safer and simpler with less complex follow-up than trabeculectomy; does not preclude subsequent surgery (does not disturb
conjunctiva)
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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:
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| 1. Describe the role of target intraocular pressure in managing glaucoma.
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| 2. Compare advantages and disadvantages of newer technologies in automated perimetry.
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| 3. Describe the role of suture release and ocular compression in trabeculectomy and combined surgery.
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| 4. Describe effective techniques for managing primary congenital glaucoma.
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| 5. Describe new developments in angle surgery.
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Discussed on This Program
Brimonidine tartrate [Alphagan, Alphagan P]
Brinzolamide [Azopt]
Mitomycin (mitomycin-C; MTC) [Mutamycin]
Suggested Reading
Cheng AC, Lam DS: Diurnal fluctuation of higher order ocular aberrations: correlation with intraocular pressure and
corneal thickness. J Refract Surg 21:201, 2005; Coleman AL et al: Applying an evidence-based approach to the management
of patients with ocular hypertension: evaluating and synthesizing published evidence. Am J Ophthalmol 138:S3,
2004; Francis BA et al: Ab interno trabeculectomy: development of a novel device (Trabectome) and surgery for open-
angle glaucoma. J Glaucoma 15:68, 2006; Lieberman MF: NTG history. Ophthalmology 110:10, 2003; Minckler
DS et al: Clinical results with the Trabectome for treatment of open-angle glaucoma. Ophthalmology 112:962, 2005;
Singh K: The randomized clinical trial: beware of limitations. J Glaucoma 13:87, 2004; Weinreb RN et al: Risk assessment
in the management of patients with ocular hypertension. Am J Ophthalmol 138:458, 2004; Yamada N et al:
Glaucoma screening using the scanning laser polarimeter. J Glaucoma 9:254, 2000; Yoon PS, Singh K: Update on antifibrotic
use in glaucoma surgery, including use in trabeculectomy and glaucoma drainage implants and combined cataract
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. Pickering has been a
consultant to Alcon; Dr. Minckler disclosed a relationship with NeoMedix Corporation.
Drs. Singh, Lieberman, Cohen, Pickering, and Minckler were recorded at the 10th Annual Glaucoma Symposium,
presented February 11, 2006, in San Francisco, CA, by the Glaucoma Research and Education Group. The Audio-Digest
Foundation thanks the speakers and the sponsor for their cooperation in the production of this program.
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