GLAUCOMA SYMPOSIUM
From the 12th Annual Glaucoma Symposium, presented by the Glaucoma Research and Education Group, San Francisco,
CA
| IMAGING GLAUCOMA: CURRENT TECHNOLOGIES AND RECENT ADVANCES —H. George Tanaka, MD, Clinical
Instructor, California Pacific Medical Center, San Francisco
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| Structural assessment of optic nerve involves 2 tasks
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 | Make definitive diagnosis at single point in course of disease; advanced disease—diagnosis straightforward when obvious
structural changes accompanied by functional abnormalities (imaging not needed to make diagnosis); early-stage
disease—diagnosis more challenging; physician aided by databases that define limits of normalcy in optic nerve structure
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| Document changes in optic nerve structure over time; by definition, glaucoma progressive optic neuropathy; if physician
can document structural deterioration, diagnosis clinched
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| Types of imaging (overview): Heidelberg retinal tomography (HRT)—provides topographic optic nerve-head analysis,
from which other optic structural parameters derived; optical coherence tomography (OCT)—circular scans taken
around optic nerve to measure thickness of peripapillary retinal nerve fiber layer (RNFL); speaker’s experience—OCT
better for initial diagnosis, HRT superior for detecting progression
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High-Resolution OCT
| Time domain OCT: mirrors used to scan tissue and to provide cross-sectional image of optic nerve; 400 A-scans/sec (10-
µm resolution); disadvantages—technique slow; problem of significant eye movement; variations in RNFL thickness with
each scan; issue of distinguishing true progression from artifact
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| Overview: does not involve movement of mirrors; reflected signal contains structural information of tissue encoded from
frequency components of received signal; frequency information used to derive structural information needed to form
OCT image
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| Advantage: simultaneous B-scans produced in rapid succession, giving “cube” of data (3-dimensional data sets); many
more scans performed (thousands per second; resolution down to 5 µm) in less time than with time domain OCT; less
motion artifact, since scans obtained in shorter time; marked qualitative improvement in images obtained
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| Specific products: Cirrus HD-OCT (Carl Zeiss Meditec)—high-definition version of Stratus OCT; Spectralis HRA+OCT
(Heidelberg Engineering)—combines several features of OCT imaging and fluorescein angiography; only device that
has eye-tracking capability (eliminates artifact seen with time domain); 3D OCT-1000 (Topcon); Spectral SLO/OCT
(OPKO Health)—device also offers anterior segment OCT capabilities; others—RTVue-100 (Optovue); SOCT Copernicus
Spectral OCT System (Reichert)
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| Comparative analysis: all have same order of magnitude of scans/sec (18,000-27,000; Spectralis highest at 40,000 scans/
sec); range of resolution, 5 to 7 µm; all perform 3-D B-scanning; all combine OCT with fundus imaging modality
(scanning laser ophthalmoscopy [SLO] or infrared technology); caution—laser hardware similar (distinguishing characteristics
differences in software reliability and ease of use); glaucoma software still in initial phases and expensive
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| CORNEAL THICKNESS: THROUGH THICK AND THIN —Shan C. Lin, MD, Associate Professor, Department of Ophthalmology,
University of California, San Francisco, School of Medicine
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| Issues: 1) is central corneal thickness (CCT) risk factor for progression in patients with ocular hypertension? (answer,
“yes”); 2) is CCT risk factor for glaucomatous optic neuropathy? 3) is CCT risk factor for progression of damage in glaucoma?
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| Ocular Hypertension Treatment Study (OHTS): CCT affected risk for progression among ocular hypertensives;
if CCT high, risk for progression to glaucoma low (regardless of intraocular pressure [IOP]); if CCT low, risk for progression
high (regardess of IOP)
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| CCT and visual field (VF) loss (Herndon et al, 2004): 350 eyes from 200 patients; lower CCT at presentation associated
with worsened Advanced Glaucoma Intervention Study (AGIS) score, worsened mean deviation of VF, and increased
cup-to-disc ratios
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| Early Manifest Glaucoma Trial (EMGT): patients with early open-angle glaucoma (VF loss already present); patients
randomized to observation or treatment with argon laser trabeculoplasty (ALT) and betaxolol; end point progression
of VF loss; lower CCT group had higher risk for progression, but risk not statistically significant (statistical
significance probable if cohort size larger); Lalezary, Medeiros, Weinreb et al, 2006—issue whether glaucoma suspects
would develop VF loss; 4.5-yr end point; low CCT group had much higher risk of developing VF loss; Kim and Chen,
2004—VF progression in patients with open-angle glaucoma significantly associated with thinner CCT; high CCT group
relatively protected, compared to low CCT group; Jonas in Europe—CCT associated with VF loss and optic disc parameters
at baseline, but no correlation with VF loss; patients with low CCT had same rate of developing progression; study
by Han—found baseline correlation of CCT with glaucoma severity, but not with progression; Shah et al, 2007—CCT
associated with baseline VF loss, but not with VF progression; summary—numerous studies support lack of correlation
between CCT and VF loss; fewer studies support proposition that lower CCT associated with greater VF loss
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| CCT and race (Aghaian et al, 2004): CCT in Chinese, whites, Filipinos, and Hispanics not statistically significantly
different; on average, black Americans and Japanese patients had lower CCT
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| Summary: CCT strongly correlated with development of glaucoma if ocular hypertension present; CCT correlated with higher
baseline VF loss if CCT lower at baseline; equivocal whether relationship exists between CCT and glaucoma progression
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| GLAUCOMA AND PREGNANCY —Terri Pickering, MD, Clinical Instructor, California Pacific Medical Center, San
Francisco,
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| Ocular hypertension in pregnant women (studies): IOP decreases as pregnancy progresses (decrease from first
to third trimesters statistically significant); proposed mechanisms—increased outflow facility; decreased episcleral
venous pressure; mild metabolic acidosis
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| Course of glaucoma during pregnancy (Brauner et al, 2006): retrospective case series; 28 eyes of 15 pregnant
women with glaucoma; 13 of 15 patients used glaucoma medications during pregnancy; in 57% of eyes, IOP stable with
no VF progression; in 18%, IOP increased during pregnancy, but VF remained stable; in 18%, VF loss progressed during
pregnancy, while IOP remained stable or increased; medications used most frequently— β-blockers; α-agonists; cholinergics;
topical carbonic anhydrase inhibitors; conclusion—course of glaucoma during pregnancy highly variable, and
pregnant women must be monitored closely; physicians cannot assume that glaucoma improves or stabilizes during pregnancy
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| Food and Drug Administration (FDA) categories for drug use in pregnancy
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| Category A: adequate well-controlled studies in pregnant women show increased risk for fetal abnormalities; no medication
prescribed for glaucoma within category A
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| Category B: 1) animal studies reveal no evidence of harm to fetus; however, no adequate well-controlled studies in pregnant
women, or 2) animal studies show adverse effect, but adequate well-controlled studies in pregnant women have failed to
demonstrate risk to fetus; eg, dipivefrin, brimonidine
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| Category C: 1) animal studies show adverse effect and no adequate well-controlled studies in pregnant women, or 2) no
animal studies conducted and no adequate well-controlled studies in pregnant women
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| Standard rule: avoid medications with pregnancy concerns unless potential benefit to patient justifies potential risk to fetus
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| Specific medications: oral β-blockers—frequently prescribed to control hypertension in pregnant women, despite potential
for systemic side effects; topical β-blockers—topical timolol associated with fetal bradycardia and arrhythmia
(consider brimonidine); topical carbonic anhydrase inhibitors—no reports of adverse effects during pregnancy; oral
carbonic anhydrase inhibitors—associated with sacrococcygeal teratoma and transient renal tubular acidosis; cholinergic
agents—avoid (associated with neonatal hypothermia, restlessness, seizures, and diaphoresis when given to women approaching
term)
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| Prostaglandins: may be considered, but “jury still out”; in general, prostaglandins avoided because of similarities to oxytocin
(drug used to induce labor); De Santis et al, 2004—11 pregnant women exposed to latanoprost (Xalatan); study
found no evidence of risk to fetus or to course of pregnancy
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| Conclusion: use caution in prescribing glaucoma medications for use during pregnancy; some topical medications used
for years or decades without reports of fetal harm; teach patients punctal occlusion to reduce systemic absorption and
minimize fetal exposure; whenever possible, address treatment options before pregnancy occurs
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| CAN GLAUCOMA PROGRESSION BE HALTED ?—Kuldev Singh, MD, Professor of Ophthalmology and Director,
Glaucoma Service, Stanford University School of Medicine, Palo Alto, CA
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| Introduction: glaucoma defined by loss of retinal ganglion cells and axons; as process independent of IOP, all patients
lose 5000 to 10,000 retinal ganglion cells every year due to aging; patients who present in advanced stages of disease
sometimes continue to do poorly no matter what physician does for them, including lowering IOP; every patient has theoretic
IOP below which further IOP lowering not helpful (physician cannot know threshold, prospectively, in given patient);
clinical pearl—rate of progression may be slow enough that treatment worse than disease (especially if other eye
healthy)
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| Factors that guide clinical approach: rate of VF loss; life expectancy; status of other eye; most importantly, does patient
consent to filter? best approach takes whole patient into account
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| Binary end points vs trend-based changes in VF:
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| Binary model: components—1) “all or nothing” (VF either stable or progressing); 2) current consensus that glaucoma
progresses if IOP above target (if IOP below target, glaucoma stabilizes)
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| American Academy of Ophthalmology (AAO): target IOP defined as range of IOP adequate to stop progressive IOP-induced
injury; speaker’s view—AAO definition excellent; use range (not single number); range more flexible and acknowledges
possibility of non-IOP induced injury
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| Role of side effects in decision making: weight given to side effects determined largely by risk for vision loss over
patient’s lifetime
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| Alternative to target IOP as all-encompassing guide to management: optimal IOP has expected marginal
benefit of further IOP lowering, weighed against expected risk of therapy and extent of patient’s disease; risks associated
with lowering IOP may not be justified by expected benefit; bottom line—no therapy can completely stop glaucomatous
progression
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| Advanced Glaucoma Intervention Study (AGIS): issue—should physician choose laser therapy or surgery if
medical therapy fails? initial answer—IOP lowering and VF progression better with surgery than with laser
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| Post hoc analyses of combined laser and surgery groups: if IOP <18 mm Hg on all visits, suggests glaucoma progression
stopped (however, some patients likely still progressing but changes masked due to noise in VF data); patients
who maintained IOPs <18 mm Hg probably did better than those with intermittent IOPs >18 mm Hg; unfortunately,
this led some to believe that average of average IOPs (12.3 mm Hg) “magic number” in glaucoma (ie, belief that glaucoma
progression halted at 12.3 mm Hg); AGIS predictive analysis—when look at first 3 IOPs over 18 mo, if average
IOP <14 mm Hg within first 3 mo, likelihood of VF progression less than if IOP ≥18 mm Hg; the more IOP lowered,
the slower disease progresses (group with lower IOPs progressed at slowest rate), but all patients worsen to some degree
(ie, lowering IOP slows progression but does not halt it)
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| Summary: ganglion cell death caused by IOP-dependent and IOP-independent factors (eg, aging); physician cannot completely
stabilize glaucomatous VFs or glaucoma (no level 1 evidence shows that lowering IOP can completely halt progression)
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| WHO’S ON FIRST: MEDICATIONS OR LASERS ?—Andrew G. Iwach, MD, Associate Clinical Professor of Ophthalmology,
University of California, San Francisco, School of Medicine, and Executive Director, Glaucoma Center of San
Francisco
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| “It’s not only the eye, it’s the patient”: asking right questions critical in assessing patient’s status and progress; if
patient has, eg, 6 mo to live, ophthalmologist must adjust management priorities; goal to preserve vision for remainder of
patient’s life
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Glaucoma Medications
| Prostaglandin analogues: as percentage of all glaucoma medications prescribed, prostaglandin analogues increasing
( β-blockers also effective); latanoprost remains good choice; bimatoprost (Lumigan) good alternative as first-line therapy;
some patients respond better to one drug or another (physician’s task to customize treatment); side effects—risk for
hyperemia varies among individuals and with different molecules; travoprost (Travatan Z)—newer medication; may offer
advantage for some patients with dry eyes (does not contain benzalkonium chloride [BAK])
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| Combined medications: convenient; avoid washout effect; for some patients, financial advantage of single copayment;
dorzolamide and timolol (Cosopt)—in recent study, some patients did much better, some much worse; on average, slight
improvement in IOP control; brimonidine and timolol (Combigan)—contains BAK; looking at peak dosing, combination
better than brimonidine or timolol alone; slight fluctuation in IOP control over time, compared to more steady curve with
β-blocker; based on initial data, allergy rate lower than that seen with brimonidine alone (reason unclear)
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Laser Therapy
| Overview: ALT has similar wavelength as selective laser trabeculoplasty (SLT), but longer pulse; micropulse laser trabeculoplasty
(MLT)—newer technology; longer wavelength; longer and slower micropulse application; power profiles—
fluency for SLT and MLT much lower than with ALT; total energy delivered greater with MLT, but delivered over longer
period; spot size—50 µm for ALT (400 µm for SLT; 300 µm for MLT); with MLT, energy applied in small bursts to minimize
collateral damage; SLT and MLT preserve architecture of trabecular meshwork; benefit of MLT—difficult to see
initially, but procedure can lower IOP
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| Iridex IQ 810 810-nm micropulse laser (study): spot size 300 µm; 50 to 70 applications over 180°; end points 2
to 4 wk (long-term results needed); patients on variety of medications; one patient had previous ALT (one had SLT); at
least initially, each patient had some decrease in IOP (some may be related to inflammatory reaction)
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| Complications: after filtering surgery, look at eyelids (physician may see underlying blepharitis); in speaker’s experience,
rates of blebitis and endophthalmitis low (close monitoring key; if signs of significant complications develop, patients
need attention sooner rather than later); useful antibiotics—moxifloxacin (eg, Vigamox); gatifloxacin (Zymar);
levofloxacin (eg, Quixin)
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Suggested Reading
Aghaian E et al: Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese
in a glaucoma clinic. Ophthalmology 111:2211, 2004; Brauner SC et al: The course of glaucoma during pregnancy:
a retrospective case series. Arch Ophthalmol 124:1089, 2006; De Santis M et al: Latanoprost exposure in pregnancy. Am
J Ophthalmol 138:305, 2004; Herndon LW et al: Central corneal thickness as a risk factor for advanced glaucoma damage.
Arch Ophthalmol 122:17, 2004; Jonas JB et al: Central corneal thickness correlated with glaucoma damage and rate
of progression. Invest Ophthalmol Vis Sci 46:1269, 2005; Kim JW, Chen PP: Central corneal pachymetry and visual
field progression in patients with open-angle glaucoma. Ophthalmology 111:2126, 2004; Lalezary M et al: Baseline optical
coherence tomography predicts the development of glaucomatous change in glaucoma suspects. Am J Ophthalmol
142:576, 2006; Punjabi OS et al: Topographic comparison of the visual function on multifocal visual evoked potentials
with optic nerve structure on heidelberg retinal tomography. Ophthalmology 115:440, 2008; Shah H et al: Role of central
corneal thickness on baseline parameters and progression of visual fields in open angle glaucoma. Eur J Ophthalmol 17:545,
2007.
Educational Objectives
| The goal of this program is to improve the management of patients with glaucoma through surgical and laser techniques,
and glaucoma medications. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe advantages and disadvantages of current technologies for imaging glaucoma.
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| 2. Assess the role of corneal thickness as a predictor of glaucomatous progression.
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| 3. Choose appropriate therapy for managing glaucoma in pregnant women.
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| 4. Formulate a realistic approach to visual field preservation in patients with ocular hypertension or glaucoma.
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| 5. Describe advantages of micropulse laser trabeculoplasty over argon laser trabeculopolasty and selective laser
trabeculoplasty.
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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, the following has been disclosed: Dr. Pickering has been a consultant
for Alcon and Allergan; Dr. Singh has been a consultant for Alcon, Allergan, Pfizer, Santen, and Novartis; Dr. Iwach
has participated in the Speakers’ Bureaus for Merck, Alcon, Allergan, Lumenis, Zeiss, ISTA, and Pfizer. Drs. Tanaka and Lin
and the planning committee reported nothing to disclose.
Acknowledgments
Drs. Tanaka, Lin, Pickering, Singh, and Iwach were recorded at the 12th Annual Glaucoma Symposium, presented February
9, 2008, in San Francisco, CA, by the Glaucoma Research and Education Group. The Audio-Digest Foundation thanks the
speakers and the Glaucoma Research and Education Group for their cooperation in the production of this program.
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