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` Primary
`Open-Angle
`Glaucoma
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`ALCON 2011
`Apotex Corp. v. Alcon Research, Ltd.
`Case IPR2013-00428
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`Prepared by the American Academy of
`Ophthalmology Glaucoma Panel
`
`Glaucoma Panel Members
`Bruce E. Prum, Jr., MD, Chair
`David S. Friedman, MD, MPH, PhD, American
`Glaucoma Society Representative
`Steven J. Gedde, MD
`Leon W. Herndon, MD
`Young H. Kwon, MD, PhD
`Michele C. Lim, MD
`Lisa F. Rosenberg, MD
`Rohit Varma, MD, MPH, Methodologist
`
`Preferred Practice Patterns Committee
`Members
`Christopher J. Rapuano, MD, Chair
`David F. Chang, MD
`Emily Y. Chew, MD
`Robert S. Feder, MD
`Stephen D. McLeod, MD
`Bruce E. Prum, Jr., MD
`R. Michael Siatkowski, MD
`David C. Musch, PhD, MPH, Methodologist
`
`Academy Staff
`Flora C. Lum, MD
`Nancy Collins, RN, MPH
`Doris Mizuiri
`Medical Editor: Susan Garratt
`Design:
`Socorro Soberano
`Reviewed by: Council
`Approved by: Board of Trustees
`
`September 11, 2010
`
`Copyright © 2010
`American Academy of Ophthalmology
`All rights reserved
`
`AMERICAN ACADEMY OF OPHTHALMOLOGY
`and PREFERRED PRACTICE PATTERN are
`registered trademarks of the American Academy
`of Ophthalmology. All other trademarks are the
`property of their respective owners.
`
`This document should be cited as:
`American Academy of Ophthalmology
`Glaucoma Panel. Preferred Practice Pattern®
`Guidelines. Primary Open-Angle Glaucoma.
`San Francisco, CA: American Academy of
`Ophthalmology; 2010. Available at:
`www.aao.org/ppp.
`
`
`
`
`
`
`
`
`
` As a service to its members and the public, the American Academy of
`Ophthalmology has developed a series of guidelines called Preferred Practice
`Patterns that identify characteristics and components of quality eye care.
`(See Appendix 1.)
`
`The Preferred Practice Pattern® guidelines are based on the best available
`scientific data as interpreted by panels of knowledgeable health professionals.
`In some instances, such as when results of carefully conducted clinical trials
`are available, the data are particularly persuasive and provide clear guidance.
`In other instances, the panels have to rely on their collective judgment and
`evaluation of available evidence.
`
`Preferred Practice Pattern guidelines provide the pattern of practice, not
`the care of a particular individual. While they should generally meet the
`needs of most patients, they cannot possibly best meet the needs of all patients.
`Adherence to these PPPs will not ensure a successful outcome in every
`situation. These practice patterns should not be deemed inclusive of all proper
`methods of care or exclusive of other methods of care reasonably directed at
`obtaining the best results. It may be necessary to approach different patients’
`needs in different ways. The physician must make the ultimate judgment about
`the propriety of the care of a particular patient in light of all of the
`circumstances presented by that patient. The American Academy of
`Ophthalmology is available to assist members in resolving ethical dilemmas
`that arise in the course of ophthalmic practice.
`
`Preferred Practice Pattern guidelines are not medical standards to be
`adhered to in all individual situations. The Academy specifically disclaims
`any and all liability for injury or other damages of any kind, from negligence or
`otherwise, for any and all claims that may arise out of the use of any
`recommendations or other information contained herein.
`
`References to certain drugs, instruments, and other products are made for
`illustrative purposes only and are not intended to constitute an endorsement of
`such. Such material may include information on applications that are not
`considered community standard, that reflect indications not included in
`approved U.S. Food and Drug Administration (FDA) labeling, or that are
`approved for use only in restricted research settings. The FDA has stated that it
`is the responsibility of the physician to determine the FDA status of each drug
`or device he or she wishes to use, and to use them with appropriate patient
`consent in compliance with applicable law.
`
`Innovation in medicine is essential to assure the future health of the American
`public, and the Academy encourages the development of new diagnostic and
`therapeutic methods that will improve eye care. It is essential to recognize that
`true medical excellence is achieved only when the patients’ needs are the
`foremost consideration.
`
`All PPPs are reviewed by their parent panel annually or earlier if developments
`warrant and updated accordingly. To ensure that all PPPs are current, each is
`valid for 5 years from the ―approved by‖ date unless superseded by a revision.
`Preferred Practice Pattern guidelines are developed by the Academy’s H.
`Dunbar Hoskins Jr., M.D. Center for Quality Eye Care without any external
`financial support. Authors and reviewers of PPPs are volunteers and do not
`receive any financial compensation for their contributions to the documents.
`The PPPs are externally reviewed by experts and stakeholders before
`publication.
`
`
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`FINANCIAL DISCLOSURES
`
`
`
`
`The panel and committee members have disclosed the following financial relationships occurring from January 2009
`to September 2010:
`
`
`David F. Chang, MD: Advanced Medical Optics – Consultant/Advisor; Alcon Laboratories, Inc. –
`Consultant/Advisor; Allergan, Inc. – Lecture fees; Calhoun Vision, Inc. – Consultant/Advisor, Equity owner;
`Eyemaginations, Inc. – Consultant/Advisor, Patent/Royalty; Ista Pharmaceuticals – Consultant/Advisor, Grant
`support; LensAR – Consultant/Advisor; Hoya – Consultant/Advisor; Peak Surgical – Consultant/Advisor; Revital
`Vision – Equity owner; SLACK, Inc. – Patent/Royalty; Transcend Medical – Consultant/Advisor; Visiogen, Inc. –
`Consultant/Advisor, Equity owner
`
`Emily Y. Chew, MD: No financial relationships to disclose.
`
`Robert S. Feder, MD: No financial relationships to disclose.
`
`David S. Friedman, MD, MPH, PhD: Alcon Laboratories, Inc. – Grant support; NiCox – Consultant/Advisor;
`Novartis Pharmaceuticals Corp. – Consultant/Advisor; ORBIS International – Consultant/Advisor; Pfizer, Inc. –
`Consultant/Advisor, Lecture fees, Grant support; Promedior – Consultant/Advisor; Zeiss Meditec – Grant support
`
`Steven J. Gedde, MD: Lumenis, Inc. – Lecture fees
`
`Leon W. Herndon, MD: Alcon Laboratories, Inc. – Consultant/Advisor, Lecture fees; Allergan, Inc. – Lecture fees;
`iScience – Lecture fees; Ista Pharmaceuticals – Consultant/Advisor, Lecture fees; Merck & Co., Inc. – Lecture fees;
`Optonol, Ltd. – Lecture fees; Pfizer, Inc. – Lecture fees; Reichert, Inc. – Lecture fees
`
`Young H. Kwon, MD, PhD: Allergan, Inc. – Consultant/Advisor; Free Educational Publications, Inc. – Equity
`owner; Pfizer, Inc. – Consultant/Advisor
`
`Michele C. Lim, MD: No financial relationships to disclose.
`
`Stephen D. McLeod, MD: Abbott Medical Optics – Consultant/Advisor, Equity owner; Visiogen, Inc. –
`Consultant/Advisor, Equity owner
`
`David C. Musch, PhD, MPH: Glaukos Corp. – Consultant/Advisor; MacuSight, Inc. – Consultant/Advisor; National
`Eye Institute – Grant support; NeoVista, Inc. – Consultant/Advisor; Neurotech USA, Inc. – Consultant/Advisor;
`OPKO Health, Inc. – Consultant/Advisor; Oraya Therapeutics, Inc. – Consultant/Advisor; Pfizer Ophthalmics –
`Grant support; Washington University – Grant support
`
`Bruce E. Prum Jr., MD: Alcon Laboratories, Inc. – Grant support; Allergan, Inc. – Consultant/Advisor
`
`Christopher J. Rapuano, MD: Alcon Laboratories, Inc. – Lecture fees; Allergan, Inc. – Consultant/Advisor, Lecture
`fees; Bausch & Lomb – Lecture fees; Inspire – Lecture fees; EyeGate Pharma – Consultant/Advisor; Inspire –
`Lecture fees; Rapid Pathogen Screening – Equity owner; Vistakon Johnson & Johnson Visioncare, Inc. – Lecture
`fees
`
`Lisa F. Rosenberg, MD: No financial relationships to disclose.
`
`R. Michael Siatkowski, MD: National Eye Institute – Grant support
`
`Rohit Varma, MD, MPH: Alcon Laboratories, Inc. – Consultant/Advisor, Lecture fees; Allergan, Inc. –
`Consultant/Advisor, Grant support; Aquesys – Consultant/Advisor, Equity owner, Grant support; Bausch & Lomb
`Surgical – Consultant/Advisor; Genentech, Inc. – Consultant/Advisor, Grant support; Merck & Co., Inc. –
`Consultant/Advisor; National Eye Institute – Grant support; Optovue – Grant support; Pfizer, Inc. –
`Consultant/Advisor, Lecture fees, Grant support; Replenish, Inc. – Consultant/Advisor, Equity owner, Grant support
`
`
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`TABLE OF CONTENTS
`
`INTRODUCTION ......................................................................................................................... 2
`ORIENTATION ............................................................................................................................ 3
`Disease Definition ........................................................................................................................ 3
`Clinical Findings Characteristic of Primary Open-Angle Glaucoma ............................................ 3
`Patient Population ........................................................................................................................ 4
`Activity.......................................................................................................................................... 4
`Purpose........................................................................................................................................ 4
`Goals............................................................................................................................................ 4
`BACKGROUND .......................................................................................................................... 4
`Epidemiology ............................................................................................................................... 4
`Risk Factors ................................................................................................................................. 6
`Intraocular Pressure ....................................................................................................................... 6
`Age .................................................................................................................................................... 8
`Family History .................................................................................................................................. 9
`Race or Ethnicity ............................................................................................................................. 9
`Central Corneal Thickness ............................................................................................................ 9
`Low Ocular Perfusion Pressure .................................................................................................... 9
`Type 2 Diabetes Mellitus ....................................................................................................10
`Myopia ................................................................................................................................10
`Genetic Factors ............................................................................................................................. 10
`Other Factors ................................................................................................................................. 11
`POPULATION SCREENING FOR GLAUCOMA ......................................................................11
`CARE PROCESS ......................................................................................................................12
`Patient Outcome Criteria ...........................................................................................................12
`Diagnosis ...................................................................................................................................12
`Evaluation of Visual Function ...................................................................................................... 12
`Ophthalmic Evaluation .......................................................................................................12
`Supplemental Ophthalmic Testing .....................................................................................14
`Management ..............................................................................................................................16
`Goals ............................................................................................................................................... 16
`Target Intraocular Pressure for Patients with POAG ............................................................... 16
`Therapeutic Choices ..................................................................................................................... 17
`Follow-up Evaluation .................................................................................................................... 24
`Risk Factors for Progression ..............................................................................................26
`Adjustment of Therapy ................................................................................................................. 26
`Provider and Setting ..................................................................................................................26
`Physician Quality Reporting Initiative ........................................................................................27
`Counseling/Referral ...................................................................................................................27
`APPENDIX 1. QUALITY OF OPHTHALMIC CARE CORE CRITERIA ...................................28
`APPENDIX 2. MAJOR RECOMMENDATIONS FOR CARE ....................................................30
`APPENDIX 3. TREATMENT ALGORITHM FOR PATIENTS WITH PRIMARY
`OPEN-ANGLE GLAUCOMA ............................................................................................34
`APPENDIX 4. INTERNATIONAL STATISTICAL CLASSIFICATION OF DISEASES AND
`
`RELATED HEALTH PROBLEMS (ICD) CODES .............................................................35
`SUGGESTED REFERENCE TEXTS ........................................................................................35
`RELATED ACADEMY MATERIALS ........................................................................................36
`REFERENCES ..........................................................................................................................37
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`INTRODUCTION
`
`The Preferred Practice Pattern® (PPP) guidelines have been written on the basis of three principles.
`
` Each PPP should be clinically relevant and specific enough to provide useful information to
`practitioners.
` Each recommendation that is made should be given an explicit rating that shows its importance to
`the care process.
` Each recommendation should also be given an explicit rating that shows the strength of evidence
`that supports the recommendation and reflects the best evidence available.
`
`In the process of revising this document, a literature search of the Cochrane Library and PubMed
`was conducted on December 3, 2008 and April 28, 2009 on the subject of primary open-angle
`glaucoma (POAG) for the years 2004 to the date of the search. In addition, the evidence synthesis1
`prepared by the British National Collaborating Centre for Acute Care for the National Institute for
`Health and Clinical Excellence clinical guideline on Glaucoma: diagnosis and management of
`chronic open-angle glaucoma and ocular hypertension clinical guideline was reviewed.2 Details of
`the literature search are available at www.aao.org/ppp. The results were reviewed by the Glaucoma
`Panel and used to prepare the recommendations, which they rated in two ways. The panel first rated
`each recommendation according to its importance to the care process. This ―importance to the care
`process‖ rating represents care that the panel thought would improve the quality of the patient’s care
`in a meaningful way. The ratings of importance are divided into three levels.
`
` Level A, defined as most important
` Level B, defined as moderately important
` Level C, defined as relevant but not critical
`
`The panel also rated each recommendation on the strength of evidence in the available literature to
`support the recommendation made. The ―ratings of strength of evidence‖ also are divided into three
`levels.
`
` Level I includes evidence obtained from at least one properly conducted, well-designed,
`randomized, controlled trial. It could include meta-analyses of randomized controlled trials.
` Level II includes evidence obtained from the following:
` Well-designed controlled trials without randomization
`
` Well-designed cohort or case-control analytic studies, preferably from more than one center
`
` Multiple-time series with or without the intervention
`
` Level III includes evidence obtained from one of the following:
` Descriptive studies
`
` Case reports
`
` Reports of expert committees/organizations (e.g., PPP panel consensus with peer review)
`
`Evidence is that which supports the value of the recommendation as it relates to the quality of care.
`The committee believes that it is important to make available the strength of the evidence
`underlying the recommendation. In this way, readers can appreciate the degree of importance the
`committee attached to each recommendation, and they can understand what type of evidence
`supports the recommendation.
`
`The ratings of importance and the ratings of strength of evidence are given in bracketed superscripts
`after each recommendation. For instance, ―[A:II]‖ indicates a recommendation with high importance
`to clinical care [A], supported by sufficiently rigorous published evidence, though not by a
`randomized controlled trial [II].
`
`The sections entitled ―Orientation‖ and ―Background‖ do not include recommendations; rather they
`are designed to educate and provide summary background information and rationale for the
`recommendations that are presented in the Care Process section. A summary of the major
`
`2
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`recommendations for care is included in Appendix 2. Appendix 3 has an algorithm for the
`management of POAG. Appendix 4 contains the International Statistical Classification of Diseases
`and Related Health Problems (ICD) codes for the disease entities that the PPP covers.
`
`
`
`ORIENTATION
`
`
`
`DISEASE DEFINITION
`Primary open-angle glaucoma is a progressive, chronic optic neuropathy in adults in which
`intraocular pressure (IOP) and other currently unknown factors contribute to damage and in which,
`in the absence of other identifiable causes, there is a characteristic acquired atrophy of the optic
`nerve and loss of retinal ganglion cells and their axons. This condition is associated with an anterior
`chamber angle that is open by gonioscopic appearance.
`
`CLINICAL FINDINGS CHARACTERISTIC OF PRIMARY OPEN-ANGLE GLAUCOMA
`Primary open-angle glaucoma is a chronic ocular disease process that is progressive, generally
`bilateral, but often asymmetric. It is associated with the following characteristics.
`
` Evidence of optic nerve damage from either, or both, of the following:
` Optic disc or retinal nerve fiber layer structural abnormalities
`- Diffuse thinning, focal narrowing, or notching of the optic disc rim, especially at the
`inferior or superior poles
`- Documented, progressive thinning of the neuroretinal rim with an associated increase in
`cupping of the optic disc
`- Diffuse or localized abnormalities of the peripapillary retinal nerve fiber layer, especially at
`the inferior or superior poles
`- Disc rim or peripapillary retinal nerve fiber layer hemorrhages
`- Optic disc neural rim asymmetry of the two eyes consistent with loss of neural tissue
` Reliable and reproducible visual field abnormality considered a valid representation of the
`subject’s functional status
`- Visual field damage consistent with retinal nerve fiber layer damage (e.g., nasal step,
`arcuate field defect, or paracentral depression in clusters of test sites)3
`- Visual field loss in one hemifield that is different from the other hemifield, i.e., across the
`horizontal midline (in early/moderate cases)
`- Absence of other known explanations
` Adult onset
` Open anterior chamber angles
` Absence of other known explanations (i.e., secondary glaucoma) for progressive glaucomatous optic
`nerve change (e.g., pigment dispersion, pseudoexfoliation [exfoliation syndrome], uveitis, trauma,
`and corticosteroid use)
`
`Primary open-angle glaucoma represents a spectrum of disease in adults in which the susceptibility
`of the optic nerve to damage varies among patients. While many POAG patients present with
`elevated IOP, a substantial minority with otherwise characteristic POAG may not have elevated IOP
`measurements.4 The vast majority of patients with POAG have disc changes or disc and visual field
`changes,5 but there are rare cases where there may be early visual field changes before there are
`detectable changes to the optic nerve.
`
`The severity of glaucoma damage can be estimated using the following:
`
` Mild: optic nerve abnormalities consistent with glaucoma as detailed above and a normal visual
`field as tested with standard automated perimetry
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` Moderate: optic nerve abnormalities consistent with glaucoma as detailed above, and visual field
`abnormalities in one hemifield that are not within 5 degrees of fixation as tested with standard
`automated perimetry
` Severe: optic nerve abnormalities consistent with glaucoma as detailed above, and visual field
`abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least one hemifield as
`tested with standard automated perimetry
`
`PATIENT POPULATION
`The patient population consists of adults 18 or older with POAG.
`
`ACTIVITY
`Identification and management of a patient with POAG.
`
`PURPOSE
`To identify and treat POAG and to preserve visual function while minimizing adverse effects of
`therapy, thereby enhancing the patient’s health and quality of life.
`
`GOALS
` Document the status of optic nerve structure and function on presentation
` Estimate an IOP below which further optic nerve damage is unlikely to occur (see discussion of
`target pressure in the Care Process section)
` Attempt to maintain IOP at or below this target level by initiating appropriate therapeutic
`intervention(s)
` Monitor the structure and function of the optic nerve for further damage and adjust the target IOP to
`a lower level if deterioration occurs
` Minimize the side effects of treatment and their impact on the patient’s vision, general health, and
`quality of life
` Educate and involve the patient and appropriate family members/caregivers in the management of
`the disease
`
`
`
`BACKGROUND
`
`
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`EPIDEMIOLOGY
`Primary open-angle glaucoma is a significant public health problem. It is estimated that 45 million
`people in the world have open-angle glaucoma (OAG).6 Glaucoma (both open-angle and angle-
`closure) is the second leading cause of blindness worldwide, with approximately 8.4 million people
`blind from glaucoma.6 Overall in 2004, the prevalence of POAG for adults 40 and older in the
`United States was estimated to be about 2%.7 Open-angle glaucoma affects an estimated 2.2 million
`people in the United States, and that number is likely to increase to 3.3 million in 2020 as the
`population ages. However, large differences exist in the prevalence of glaucoma among different
`ethnic groups (see Table 1 and Figure 1). Overall, there appears to be a threefold higher prevalence
`of OAG in African Americans relative to non-Hispanic Whites in the United States.7,8 It is also the
`leading cause of blindness in African Americans.8 Further, the prevalence of OAG is even higher in
`Afro-Caribbeans relative to African Americans. Recent evidence on Hispanics/Latinos suggests that
`they have high prevalence rates of OAG that are comparable to African Americans.9 There are no
`data on the prevalence of OAG in Asians in the United States.
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`TABLE 1
`
`THE PREVALENCE OF DEFINITE OPEN-ANGLE GLAUCOMA AS REPORTED IN OTHER STUDIES
`
`Study
`
`Racial/Ethnic Group
`
`Age-Specific Prevalence
`
`Age Groups (yrs)
`
`
`
`40–49
`
`50–59
`
`60–69
`
`70–79
`
`80+
`
`Total
`
`Baltimore Eye Study1
`
`African American
`
`Barbados Eye Study2
`
`Afro-Caribbean
`
`LALES
`
`Proyecto VER3
`
`Baltimore Eye Study1
`
`Latino
`
`Latino
`
`NHW
`
`1.27
`
`1.4
`
`1.32
`
`0.50
`
`0.18
`
`4.15
`
`4.1
`
`2.92
`
`0.59
`
`0.32
`
`6.19
`
`6.7
`
`7.36
`
`1.73
`
`1.53
`
`8.88
`
`14.8
`
`14.72
`
`5.66
`
`3.33
`
`12.87
`
`23.2
`
`21.76
`
`12.63
`
`1.94
`
`4.97
`
`6.8
`
`4.74
`
`1.97
`
`1.44
`
`Blue Mountains Eye Study4
`
`Visual Impairment Project5
`
`Beaver Dam Eye Study6
`
`Roscommon7
`
`NHW
`
`NHW
`
`NHW
`
`NHW
`
`0.4*
`
`0.5
`
`
`
`
`
`1.5
`
`
`
`0.72
`
`1.3
`
`4.5
`
`
`
`1.76
`
`4.7
`
`8.6
`
`
`
`3.2
`
`11.4
`
`9.9
`
`
`
`3.0
`
`3.4
`
`2.1
`
`3.05
`
`1.88
`
`
`
`LALES = Los Angeles Latino Eye Study; NHW = non-Hispanic White
`
`* The study combined ages 40–59 into one group.
`
`
`
`NOTE: The studies reporting prevalence used different definitions of disease; therefore, caution should be exercised when comparing these studies.
`
`SOURCE: Adapted with permission from Varma R, Ying-Lai M, Francis B, et al, Los Angeles Latino Eye Study Group. Prevalence of open-angle
`glaucoma and ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology 2004;111:1445.
`
` 1. Tielsch JM, Sommer A, Katz J, et al. Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA
`1991;266:369-74.
`
`
`
`
`
`
`
`
`
` 2. Leske MC, Connell AM, Schachat AP, Hyman L. The Barbados Eye Study. Prevalence of open angle glaucoma. Arch Ophthalmol
`1994;112:821-9.
`
` 3. Quigley HA, West S, Rodriguez J, et al. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch
`Ophthalmol 2001;119:1819-26.
`
` 4. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology
`1996;103:1661-9.
`
` 5. Wensor MD, McCarty CA, Stanislavsky YL, et al. The prevalence of glaucoma in the Melbourne Visual Impairment Project. Ophthalmology
`1998;105:733-9.
`
` 6. Klein BE, Klein R, Sponsel WE, et al. Prevalence of glaucoma: the Beaver Dam Eye Study. Ophthalmology 1992;99:1499-1504.
`
` 7. Coffey M, Reidy A, Wormald R, et al. Prevalence of glaucoma in the west of Ireland. Br J Ophthalmol 1993;77:17-21.
`
`
`
`
`FIGURE 1. Comparison of age-specific prevalence of open-angle glaucoma in Latinos (Los Angeles Latino Eye Study), African Americans/Blacks
`and non-Hispanic Whites (the Baltimore Eye Study)1
`
`* The data shown from LALES is from a different study.
`
`SOURCE: Adapted with permission from Varma R, Ying-Lai M, Francis B, et al, Los Angeles Latino Eye Study Group. Prevalence of open-angle glaucoma and
`ocular hypertension in Latinos: the Los Angeles Latino Eye Study. Ophthalmology 2004;111:1446.
`
`1. Tielsch JM, Sommer A, Katz J, et al. Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA 1991;266:369-74.
`
`
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`
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`RISK FACTORS
`The findings of epidemiological investigations and clinical trials provide a framework for assessing
`the risk factors associated with POAG. The important risk factors associated with POAG are as
`follows:
`
` Intraocular pressure level
` Older age
` Family history of glaucoma
` African ancestry or Latino/Hispanic ethnicity
` Thinner central cornea10
` Low ocular perfusion pressures11,12
` Type 2 diabetes mellitus13-15
` Myopia12,16-18
` Genetic mutations19
`
`
`
`
`
`Intraocular Pressure
`Several population-based studies have demonstrated that the prevalence of POAG4,20-26 increases as
`the level of IOP increases (see Figures 2 and 3). These studies provide strong evidence that IOP
`plays an important role in the neuropathy of POAG. Furthermore, studies have demonstrated that
`reduction in the level of IOP lessens the risk of visual field progression in OAG (see Table 2).27-32 In
`addition, treated eyes that have a greater IOP fluctuation may be at increased risk of progression,
`although this has not been shown consistently.33-37
`
`
`
`
`
`
`
`
`
`
`
`FIGURE 2. Prevalence of Primary Open-Angle Glaucoma in
`Relation to Screening Intraocular Pressure
`
`African American subjects, n = 4,674 eyes (closed circles);
`
`Caucasian American subjects, n = 5,700 eyes (open
`circles).
`
`SOURCE: Sommer AE, Tielsch JM, Katz J, et al. Relationship between
`intraocular pressure and primary open angle glaucoma among white
`and black Americans. Arch Ophthalmol 1991;109:1092. Copyright 1991.
`Reprinted with permission from the American Medical Association. All
`rights reserved.
`
`
`
`FIGURE 3. The relationship between prevalence of open-angle
`glaucoma and intraocular pressure (measured using Goldmann
`applanation tonometry) in Latinos (n=5970) in the Los Angeles
`Latino Eye Study.
`
`SOURCE: Adapted with permission from Francis B, Varma R, Chopra V,
`et al, Los Angeles Latino Eye Study Group. Intraocular pressure, central
`corneal thickness, and prevalence of open-angle glaucoma: the Los
`Angeles Latino Eye Study. Am J Ophthalmol 2008;146:743.
`
`6
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`

`No. of
`Patients
`
`Follow-up
`Duration
`(years)
`
`116
`
`4.6 (mean)
`
`168
`
`5+
`
`230
`
`5+
`
`Finding
`
`Trabeculectomy lowered IOP (-58%) more
`than medicine (-42%); medical therapy
`group had more deterioration in visual fields
`than trabeculectomy group.
`
`Trabeculectomy lowered IOP the most
`(-60%); laser trabeculoplasty (-38%) and
`medical therapy groups (-49%) had more
`deterioration in visual fields than
`trabeculectomy group.
`
`Lowering IOP (-37%) retarded the
`progression rate of visual field loss
`compared with untreated eyes (-1%).
`
`255
`
`8 (median)
`
`Lowering IOP with medical therapy and
`trabeculoplasty (-25%) slowed progression
`of optic disc and visual field damage.
`
`607
`
`5+
`
`Lowering IOP with initial filtering as surgery
`(-46%) was as effective as medical therapy
`(-38%) to inhibit progression of visual field
`damage, though the amount of reduction
`was slightly greater after surgery.
`
`Surgical outcome varied by race; patients
`with African ancestry did better with laser
`trabeculoplasty as first surgery (-30% IOP),
`while in the longer term (4+ years)
`Caucasian American patients did better
`with trabeculectomy as first surgery (-48%
`IOP). Lowest IOP group during follow-up
`after surgical interventions (-47%)
`prevented further visual field deterioration in
`advanced glaucoma patients.
`
`
`
`TABLE 2
`
`RANDOMIZED CLINICAL TRIALS WITH PUBLISHED RESULTS
`
`Name
`
`Study Design
`
` Scottish Glaucoma
` Trial1,2
`
`Newly diagnosed POAG:
`medical therapy vs.
`trabeculectomy
`
` Moorfields Primary
` Treatment Trial3
`
`Newly diagnosed POAG:
`medical therapy vs. laser
`trabeculoplasty vs.
`trabeculectomy
`
` Collaborative Normal-
`Tension Glaucoma
`Study4
`
` Early Manifest
` Glaucoma Trial5,6,7
`
`
` Collaborative Initial
` Glaucoma Treatment
`Study8
`
`POAG in eyes with normal
`IOP: rate of progression, effect
`of IOP reduction on
`progression rate
`
`Newly diagnosed POAG:
`medical therapy and laser
`trabeculoplasty vs. no
`treatment
`
`Newly diagnosed POAG:
`medicine vs. trabeculectomy
`
` Advanced Glaucoma
` Intervention Study
` (AGIS)9,10
`
`POAG after medical therapy
`failure with no previous
`surgery: laser trabeculoplasty
`vs. trabeculectomy
`
`591
`
`10–13
`
`IOP = intraocular pressure; POAG = primary open-angle glaucoma
`
`
`
`1. Jay JL, Allan D. The benefit of early trabeculectomy versus conventional management in primary open angle glaucoma relative to severity of
`disease. Eye 1989;3:528-35.
`
`2. Jay JL, Murray SB. Early trabeculectomy versus conventional management in primary open angle glaucoma. Br J Ophthalmol 1988;72:881-9.
`
`3. Migdal C, Gregory W, Hitchings R. Long term functional outcome after early surgery compared with laser and medicine in open-angle
`glaucoma. Ophthalmology 1994;101:1651-7.
`
`4. Collaborative Normal-Tension Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension
`glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998;126:487-97.
`
`5. Heijl A, Leske MC, Bengtsson B, et al, Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression.
`Results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120