GLAUCOMA SYMPOSIUM
From Glaucoma Update 2007, presented by the Glaucoma Research and Education Group, San Francisco, CA
| DIAGNOSTIC TOOLS FOR GLAUCOMA—Marc F. Lieberman, MD, Clinical Professor of Ophthalmology, University
Of California, San Francisco, School of Medicine, and Director, Glaucoma Services, California Pacific Medical Center, San
Francisco
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| Facts: majority of open-angle glaucoma (OAG) pressure-dependent; intraocular pressure (IOP) key parameter for developing
primary OAG; interrupting IOP elevations (ie, lowering IOP) statistically appears to stop glaucoma progression;
visual field (VF) loss important functional parameter (higher IOP, worse VF loss); response of glaucoma to lowering of
IOP dependent on stage of disease (in early glaucoma, if IOP lowered by 20%, most glaucoma stops progressing; later in
disease, greater reduction in IOP [eg, 30%-40%] required for similar effects); at macro level, lowering IOP only neuroprotective
intervention applicable to OAG
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| Questions: how often to measure IOP? what instrument best for measuring IOP? most important thing about pressure
(eg, fluctuation between morning and afternoon visits)? do hormones, other physiologic parameters, or season of year affect
IOP? relative importance of mean IOP over time vs fluctuations? until continuous IOP recording possible, most of
these questions not answerable
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| Clinical suspicion: fluctuation of pressure probably takes greater toll on eye than mean pressure; greatest virtue of trabeculectomy
may be elimination of pressure fluctuation; IOP fluctuations under normal conditions—interobserver variability
of Goldmann applanation tonometry, 2 mm Hg; pressure fluctuation while lying down, 7.3 mm Hg; fluctuation after
sitting up, 5 mm Hg in same patient, same instrument, same observer over time; central corneal thickness not fixed number
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| Measuring IOP: best estimation with manometer; study of patients who underwent phacoemulsification showed pneumatonometer
most accurate way to measure pressure; Goldmann aplanation tonometer (in operating room, Perkins aplanation
tonometer) second most accurate; Tono-Pen and Shiötz tonometers less accurate; central corneal thickness helpful
in choosing target pressure (if thickness >600 µm, overestimating IOP; if <500 µm, underestimating IOP)
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| Advising patients: avoid Valsalva maneuver; avoid being upside down for extended periods (eg, headstands in yoga); no
strong evidence that free-weight bench pressing or neckties create problem; patients with Pickwickian symptoms or sleep
apnea potentially benefit from evaluation (continuous positive airway pressure can help break cycle of Valsalva maneuvers)
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| Which pressure being measured: higher pressure in posterior chamber necessary for aqueous to penetrate through
pupil and exit into anterior chamber; potential for microgradients of pressure throughout eyeball; pressure at optic nerve
unknown; lamina cribrosa potential site of action; question of interplay between IOP and intracranial pressure; apoptosis
fundamental means of cell death in glaucoma (no ischemic signs in glaucoma retinas); ganglion cells die, leaving traces
of glutamate
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| ETHNIC CONSIDERATIONS IN GLAUCOMA DIAGNOSIS—Kuldev Singh, MD, Professor of Ophthalmology, Director
of Glaucoma Services, Stanford University School of Medicine, Stanford, CA
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| Blacks, whites, and Hispanics: study in Baltimore (1980s)—prevalence of glaucoma 4 times higher in blacks than
whites (>40 yr of age); difference increased with higher IOP; relationship between glaucoma prevalence and IOP continuous;
study in Arizona—looked at prevalence of glaucoma in Hispanics (possible European, American Indian, and African
ancestry); compared to whites, prevalence increased significantly in older age groups; overall prevalence higher in Hispanics;
combination of 2 studies, comparing Hispanics to blacks, found that in younger age groups, blacks had higher prevalence;
in older group (70- to 80-yr-olds), no difference between Hispanics in Arizona and blacks in Baltimore; many
individuals (75% in Arizona and 50% in Baltimore) unaware that they had glaucoma; Los Angeles Latino Eye Survey—
greater glaucoma prevalence among Latinos in Los Angeles, relative to those in Arizona; prevalence summary—4% to
8% in blacks; 2% to 4.5% in Hispanic whites; 1% to 3% in non-Hispanic whites; limitation that data from different studies;
question whether progression of glaucoma differs according to ethnicity
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| Chinese ancestry: in early 1990s, speaker noted cluster of patients with Chinese ancestry who had tilted-appearing optic
nerves (some with peripapillary atrophy); most myopic
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 | Retrospective review (in press): background—16 Chinese men, mean age 39 yr, diagnosed with glaucoma, followed (annual
VF fields; optic disc photographs when change suspected based on examination) for 7 yr; observed
characteristics—patients had open angles on gonioscopy; majority had tilted-appearing optic nerves and myopia; 25%
had family history of glaucoma; VF loss and nonprogression—evidence that some younger patients with severe VF
loss, in absence of documented progression, may not benefit from filtering surgery; studies show VFs vary in these types of
patients (VF reverts to baseline when tested enough)
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| Model to explain condition: not scientifically proven; tensile strength of various ocular tissues measured in laboratory;
found that, particularly with tilted nerve, normally nonload-bearing structure of prelaminar nerve fiber layer susceptible
to damage, regardless of IOP; hypothesis—progressive axial myopia puts strain on nerve, resulting in focal death;
creates stretched appearance to nerve in particular area, and causes focal damage to nerve fiber layer, resulting in VF
defects (remainder of nerve remains fine); question whether lowering IOP of benefit in these patients
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| Why condition not recognized in China? few non-Chinese people with whom to compare; researcher in Singapore reviewed
optic disc photos of national military recruits and found high percentage of patients with this type of nerve appearance
and VF defects; when these photos (of young myopes) mixed with those of older people with glaucoma,
speaker able to identify (with >80% sensitivity and specificity) which group each belonged to; prevalence of this condition
or cluster of findings not known; confounding factor—some of patients 80- to 90-yr- of age with glaucoma also
myopic and may have had this condition earlier and been stable, and now being treated as if they have glaucoma
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| Prevalence survey: underway at Stanford; 100 graduate students of Chinese ancestry; prevalence of glaucoma 15% by
current definition (patients unaware of problem); majority of young Chinese people myopic; male-to-female ratio unknown;
long-term natural history of condition unknown (in patients speaker has seen, no progression to central vision
loss and blindness); some may potentially have classic glaucoma as well, but difficult to distinguish; unknown whether
genetic susceptibility involved
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| Postulation: myopia associated with lengthening of eyes, which causes strain on optic nerve head; results in nerve damage
and VF loss ( may remain static or slowly progress in later years)
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| Clinical implications: cannot assume rate of progression even with severe VF loss in early ages, especially in this population;
using target IOP strictly (ie, assuming IOP of 12.3 mm Hg necessary to arrest glaucoma) will result in some unnecessary
filtering surgery
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| ARE RISK FACTORS RISKY?—H. Dunbar Hoskins, Jr, MD, Clinical Professor of Ophthalmology, University of California,
San Francisco, School of Medicine
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| Well-known findings: Laplace’s law—pressure has greater effect on highly myopic eye (larger radius) than on hyperopic
eye (smaller radius); similarly, with small or no glaucoma cup, impact of pressure less on small radius than on
larger radius; people with severe cupping need much lower pressures than people with normal cups (noted in 1940s);
50% of nerve loss before VF loss noticeable
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| Assimilating data: large databases being created for longitudinal analysis; selection of time period for review critical
(eg, which section of area under curve [AUC]? data from only few VFs potentially misleading); studies ultimately lead to
conclusion that individualized treatment important; IOP quantifiable piece of data; automated perimetry easily handled
by technician and brings mathematical quantification to process
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| Risk calculator: only as good as data put in; different ways of looking at nerves and measuring and recording diameters;
quantifiable measures—include untreated IOP, corneal thickness, vertical cup-to-disc ratio by contour, and pattern
standard deviation in VF; all fluctuate over time; entering single slice in time into calculator gives single result (may or
may not have meaning for patient)
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| Ocular Hypertension Treatment Study (OHTS): true evidence for managing glaucoma; various factors weighted, eg, age,
IOP, corneal thickness, vertical cup-to-disc ratio, VF; points assigned according to numeric ranges; determines risk of
developing glaucoma in 5 yr; question of what to do with information; most agree level of risk <5% low
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| Suggested treatment algorithm: particular risk calculator suggests observe and monitor when risk <5%; consider treatment
when risk 5% to 15%, and treat when risk >15%; speaker’s comments—at this threshold for treatment, 85% potentially
treated unnecessarily; side effect and cost concerns
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| Conclusions: ideal device would—give consistently reproducible measurements; express likelihood of disease or
change from previous state; accurately predict that future change; in meantime—physician’s knowledge and examination
best tool available today; because glaucoma slowly progressive, ample time for observation
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| Sanford R. Gifford Lecture (1960): conclusions still viable today; patients with advanced disease and large cupping need very
low pressures; patients with notch at one end and relatively healthy nerve above do not need such low pressures; patients
with normal discs can withstand pressures for long time
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| TO TUBE OR NOT TO TUBE?—Terri Pickering, MD, Clinical Instructor, California Pacific Medical Center, San Francisco
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| Introduction: members of American Glaucoma Society surveyed in 1996 and 2002; in 2002, members still favored
trabeculectomy with mitomycin C for complex cases, but use of tube shunt surgery significantly increased; preference for
tube surgery increased from 7% to 22% in patients who had previous trabeculectomy; recent studies showed favorable data
for tubes, encouraging some surgeons to prefer for complex cases; consideration for potential complications necessary
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| Patient selection: those requiring further pressure reduction—despite treatment with medication, laser, and filtering
surgery with antimetabolites; patients with poor prognosis for filtering surgery—due to type of glaucoma or previous
surgery; children with pediatric glaucoma—study showed success rate at 1 yr 78%, and at 2 yr 61%; 3 of 21 children
required removal of plate due to extrusion of implant from under conjunctiva; ethnicity-related considerations—blacks
respond, but tend to need more medications to achieve success than whites (success rates still lower); study in Hong
Kong showed success rate in Chinese eyes comparable to non-Asian eyes (but greater tendency toward bleb encapsulation)
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| Implant selection: single-plate Ahmed, double-plate Ahmed, and Baerveldt implants have similar success rates; study
showed Ahmed implants provided better pressure control in early postoperative period, but associated with more bleb encapsulations
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| Previous comparative studies: 2 randomized clinical trials; success rates similar, but patients undergoing trabeculectomy
appeared to have lower final IOP; patients undergoing tube surgery needed more glaucoma medications; longer
follow-up showed IOP and success rates similar
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| Current “trab vs tube” study: under way; randomized multicenter clinical trial (212 patients, aged 32 to 85 yr, with previous
trabeculectomy and plus-or-minus cataract surgery); IOP ranged from 18 mm Hg to 40 mm Hg on maximum medical
treatment; randomized to receive either trabeculectomy with mitomycin C or Baerveldt tube
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| One-year results: excluding death, 97% of follow-up visits completed; group undergoing tube surgery experienced decrease
in IOP, from baseline of 25.1 mm Hg to 12.4 mm Hg; group undergoing trabeculectomy also experienced decrease
in IOP, from baseline of 25.6 mm Hg to 12.7 mm Hg; no statistically significant difference in mean IOP
between treatment groups at 1 yr; in general, patients receiving tube implants required more medication drops
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| Treatment failure: defined as—IOP persistently >21 mm Hg or IOP not reduced by 20% from baseline; IOP <5 mm Hg
after 3 mo; reoperation for glaucoma; or loss of light perception vision; probability of failure significantly higher for
patients undergoing trabeculectomy (13.5% vs 3.9%); higher failure rate for trabeculectomy—potentially due to arbitrary
definition of hypotony; hypotony accounted for 3 trabeculectomy failures, but no tube failures; known that patients
who had trabeculectomy can have IOP <5 mm Hg with no visual symptoms (representing surgical success, not
failure); potentially due to infrequent follow-up during first postoperative month (trabeculectomy requires more frequent
postoperative visits in first months, and success depends on close postoperative care and monitoring)
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| Complications: intraoperative complication rates similar; higher rate of postoperative complications in trabeculectomy group
(57% vs 34%); these higher rates may be because refinement during surgery not allowed (ie, no adjustment of mitomycin
C for age, ethnicity, thickness of tenons, and prior surgery; in group receiving tubes, surgeon could choose whether to fenestrate
tube); rate of postoperative complications in patients receiving tubes lower in this study than in previous studies
(more difficult glaucoma diagnoses excluded)
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| Serious complications: complications leading to vision loss and/or reoperation for glaucoma; tendency for higher rate of
serious complication in trabeculectomy group; complete occlusion of tube during surgery contributed to low complication
rate; 3 scleral perforations (requiring intraoperative cryotherapy) in group receiving tubes; only patients receiving
tubes required anterior chamber reformation; additional potential complications—overall rate possibly 49%; intraoperatively,
can experience leakage around tube or damage to lens, cornea, or iris; epithelial ingrowth; postoperative
obstruction; possible late erosion of tube through conjunctiva; tube may migrate; corneal decompensation (risk for corneal
transplant patients); diplopia (frequently occurs transiently, resolving when postoperative edema subsides); permanent
strabismus; cataract
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| Conclusion: study does not demonstrate superiority of one procedure over other; awaiting long-term results; surgeon’s
skill and experience with both operations critical in choosing surgical procedure
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Suggested Reading
Boland MV, Quigley HA: Risk Factors and Open-angle: Classification and Application. J Glaucoma 16:406, 2007;
Doshi A et al: Nonprogressive glaucomatous cupping and visual field abnormalities in young Chinese males. Ophthalmology
114:472, 2007; Fraser RG et al: The reengineering of a software system for glaucoma analysis. Comput Methods Programs
Biomed 79:97, 2005; Friedman DS et al: The prevalence of open-angle glaucoma among blacks and whites 73 years
and older: the Salisbury Eye Evaluation Glaucoma Study. Arch Ophthalmol 124:1625, 2006; Gedde SJ et al: Treatment
outcomes in the tube versus trabeculectomy study after one year of follow-up. Am J Ophthalmol 142:9, 2007; Gedde SJ et
al: Surgical complications in the Tube Versus Trabeculectomy Study during the first year of follow-up. Am J Ophthalmol
143:23, 2007; Gedde SJ et al: The tube versus trabeculectomy study: design and baseline characteristics of study patients. Am
J Ophthalmol 140:275, 2005; Giangiacomo A et al: Diagnosing glaucoma progression: current practice and promising
technologies. Curr Opin Ophthalmol 17:153, 2006; Higginbotham EJ: Treating ocular hypertension to reduce glaucoma
risk: when to treat? Drugs 66:1033, 2006; Huang ML, Chen HY: Development and caparison of automated classifiers for
glaucoma using Stratus optical coherence tomography. Invest Ophthalmol Vis Sci 46:4121, 2005; Jamil AL, Mills RP:
Glaucoma tube or trabeculectomy? That is the question. Am J Ophthalmol 143:141, 2007; Kosoko-Lasaki O et al:
Race, ethnicity and prevalence of primary open-angle glaucoma. J Natl Med Assoc 98:1626, 2006; Kwartz AJ et al: The effectiveness
of the Heidelberg Retina Tomograph and laser diagnostic glaucoma scanning system (GDx) in detecting and monitoring
glaucoma. Health Technol Assess 9:1, 2005; Mansberger SL et al: Comparison of initial intraocular pressure
response with topical beta-adrenergic antagonists and prostaglandin analogues in African American and white individuals in the
Ocular Hypertension Treatment Study. Arch Ophthalmol 125:454, 2007; Nduaguba C, Lee RK: Glaucoma screening:
current trends, economic issues, technology, and challenges. Curr Opin Ophthalmol 17:142, 2006; Ojima T et al: Measurement
of retinal nerve fiber layer thickness and macular volume for glaucoma detection using optical coherence tomography. Jpn
J Ophthalmol 51:197, 2007; Weale RA: Ethnicity and glaucoma: Higher environmental temperatures may accelerate the onset,
and increase the prevalence, of primary open-angle glaucoma. Med Hypotheses 69:432, 2007.
Educational Objectives
| The goal of this program is to improve the diagnosis, management, and surgical treatment of glaucoma. After hearing and assimilating
this program, the clinician will be better able to:
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| Evaluate the roles of mean intraocular pressure (IOP) and IOP fluctuations and determine the most accurate means of measuring
IOP in the clinical setting.
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| Describe the influence of patient ethnicity on the diagnosis and prevalence of glaucoma.
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| Assimilate available data on glaucoma and apply the principles of Laplace’s law in evaluating IOP in individual patients.
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| Consider the pros and cons of using risk calculators when determining a treatment plan.
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| Summarize current study data comparing tube shunt surgery to trabeculectomy.
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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 following has been disclosed: Dr. Singh is a consultant/advisor for Alcon,
Pfizer, Santen, and Novartis. Dr. Pickering is a consultant for Alcon.
Acknowledgements
All speakers were recorded at Glaucoma Update 2007, The 11th Annual Glaucoma Symposium, held February 10,
2007, in San Francisco, CA, and presented 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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