Final Recommendation Statement
July 15, 2013
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
The U.S. Preventive Services Task Force (USPSTF) makes recommendations about the effectiveness of specific clinical preventive services for patients without related signs or symptoms.
It bases its recommendations on the evidence of both the benefits and harms of the service and an assessment of the balance. The USPSTF does not consider the costs of providing a service in this assessment.
The USPSTF recognizes that clinical decisions involve more considerations than evidence alone. Clinicians should understand the evidence but individualize decision making to the specific patient or situation. Similarly, the USPSTF notes that policy and coverage decisions involve considerations in addition to the evidence of clinical benefits and harms.
Open-angle glaucoma affects approximately 2.5 million Americans and is a leading cause of impaired visual function (loss of peripheral vision) and blindness.
The USPSTF found inadequate evidence on the accuracy of screening for POAG in adults. Evidence is limited by the lack of an established gold standard against which individual screening tests can be compared.
Benefits of Detection and Early Treatment
The USPSTF found no direct evidence on the benefits of screening.
The USPSTF found convincing evidence that treatment of increased intraocular pressure (IOP) and early glaucoma reduces the number of persons who develop small, clinically unnoticeable visual field defects and that treatment of early asymptomatic POAG decreases the number of persons whose visual field defects worsen.
However, the USPSTF found inadequate evidence that screening for or treatment of increased IOP or early asymptomatic POAG reduces the number of persons who will develop impaired vision or quality of life.
Harms of Detection and Early Treatment
The USPSTF found no direct evidence on the harms of screening. It found convincing evidence that treatment results in numerous harms, including local eye irritation from medications and risk for complications from surgery, such as early formation of cataracts. The magnitude of these harms for most persons is small. Screening is associated with a risk for false-positive and false-negative results, but the magnitude of this risk is unknown, given the considerable variability in reported test sensitivity and specificity. Screening and treatment are associated with risk for overdiagnosis and overtreatment because some evidence shows that many persons with increased IOP or early POAG have an indolent long-term course yet still receive treatment.
The USPSTF concludes that the evidence of effectiveness of screening for glaucoma on clinical outcomes is lacking and that the balance of benefits and harms therefore cannot be determined.
Patient Population Under Consideration
This recommendation applies to adults who do not have vision symptoms who are seen in a primary care setting.
Assessment of Risk
Increased IOP, family history of glaucoma, older age, and African American race increase a person's risk for open-angle glaucoma1,2. Recent evidence shows that glaucoma may be increased in Hispanics3. Older African Americans have a higher prevalence of glaucoma and perhaps a more rapid disease progression; if screening reduces vision impairment, then African Americans would probably have greater absolute benefit than whites.
Diagnosis of POAG is based on a combination of tests showing characteristic degenerative changes in the optic disc and defects in visual fields (often loss in peripheral vision). Although increased IOP was previously considered an important part of the definition of this condition, it is now known that many persons with POAG do not have increased IOP and not all persons with increased IOP have or will develop glaucoma. Therefore, screening with tonometry alone may be inadequate to detect all cases of POAG.
Measurement of visual fields can be difficult. The reliability of a single measurement may be low; several consistent measurements are needed to establish the presence of defects. Specialists use dilated ophthalmoscopy or slit lamp examination to evaluate changes in the optic disc; however, even experts have varying ability to detect glaucomatous progression of the optic disc. In addition, no single standard exists to define and measure progression of visual field defects. Most tests that are available in a primary care setting do not have acceptable accuracy to detect glaucoma.
The initial aim and efficacy assessment of primary treatments of POAG are reduction of IOP. Treatments include medication, laser therapy, and surgery. These treatments also effectively reduce the longer-term development and progression of small visual field defects as assessed by clinical examination. However, the magnitude of the effectiveness in reducing impairments in patient-reported, vision-related function, including development of blindness, is uncertain.
Suggestions for Practice Regarding the I Statement
Potential Preventable Burden
Approximately 2.5 million persons in the United States have glaucoma, and approximately 1.9% of adults older than 40 years have open-angle glaucoma4. Most persons with glaucoma have POAG. This condition is defined as optic neuropathy with a visibly open anterior chamber angle (between the iris and the anterior sclera or peripheral cornea) that is associated with progressive death of retinal ganglion cells and axons and visual field loss1,2,5.
The goal of screening programs is to identify and treat POAG before visual impairment develops. The proportion of persons who are currently unidentified and who will develop vision problems as a result of a diagnosis obtained through screening is not known. The natural history of glaucoma is heterogeneous and poorly defined.
In some persons, POAG does not progress or progression is so slow that it never has an important effect on vision. The size of this subgroup is uncertain and may depend on the ethnicity and age of the population and initial findings of ophthalmologic testing. Screening in asymptomatic persons is likely to increase the size of this subgroup. Other patients have more rapid progression, as determined by optic nerve damage, visual field defects, and development of visual impairment.
Whether early glaucoma will progress to visual impairment cannot be precisely predicted. Whether the rate of progression of visual field defects remains uniform throughout the course of glaucoma is also not known. Older adults and African Americans seem to be at increased risk and have more rapid progression. Persons with a short life expectancy probably have little to gain from glaucoma screening.
Harms caused by treatment of glaucoma include formation of cataracts and those resulting from surgery and from topical medications. Overdiagnosis and overtreatment are possible because not all persons who are diagnosed with and treated for glaucoma progress to visual impairment; the magnitude of overdiagnosis and overtreatment is unknown.
The cost of screening varies widely depending on the tests used. Testing with hand-held tonometers and ophthalmoscopes can be done quickly and inexpensively. However, the diagnostic accuracy of these inexpensive tests is not known. According to the National Business Group on Health, the average screening eye examination costs $716. Screening with specialized tests for glaucoma and with newer computerized instruments is more expensive.
Approximately 62% of Medicare patients enrolled in an HMO were screened for glaucoma in 20097. In 2008, approximately 53% of whites, 47% of African Americans, and 37% of Hispanics reported an annual eye care visit8.
Research Needs and Gaps
The natural history of glaucoma, particularly the role of IOP and its relationship to optic nerve damage, visual field defects, visual impairment, and blindness, is poorly understood. More evidence is needed on the link between the intermediate glaucoma outcomes of optic nerve damage and visual field loss and the final health outcomes of visual disability and patient-reported outcomes. Evidence for screening would ideally come from a randomized, controlled trial of routine (or targeted) screening versus standard care with long-term follow-up. More studies on treatment that are of adequate duration and size to assess important clinical outcomes (such as visual impairment and vision-related quality of life), or at least greater changes in visual fields, are needed.
Burden of Disease
Glaucoma is characterized as primary (idiopathic) or secondary (resulting from a known cause, such as trauma or inflammation) and as closed- or open-angle. Closed-angle glaucoma may present with acute symptoms, such as eye pain and blurred vision, and is considered an emergency. Primary open-angle glaucoma is the most prevalent type of glaucoma in the United States and the focus of this recommendation. It is defined as optic neuropathy with a visibly open anterior chamber angle (between the iris and the anterior sclera or peripheral cornea) that is associated with progressive death of retinal ganglion cells and axons and visual field loss1,2,5. In most cases, damage to the optic nerve is the result of increased pressure in the eye, also known as IOP.
Approximately 2.5 million persons in the United States have glaucoma, and many are unaware that they have it. Important risk factors include older age, family history of the condition, and African American race8. The overall estimated prevalence of glaucoma in the United States is 1.9%. Age-adjusted estimates are approximately 3 times higher in African Americans than in whites4. A recent study reported a prevalence of 4.7% in Hispanics older than 40 years3.
Scope of Review
To update its 2004 recommendation on screening for glaucoma, the USPSTF reviewed evidence on the benefits and harms of screening and of medical and surgical treatment of early glaucoma. Beneficial outcomes of interest for the USPSTF included improved vision-related quality of life and reduced progression of early asymptomatic glaucoma to vision-related impairment. The USPSTF also considered evidence on the accuracy of screening tests for glaucoma.
Accuracy of Screening Tests
The USPSTF considered evidence on the accuracy of direct and indirect ophthalmoscopy, photography and computerized imaging of the fundus, measurement of corneal thickness combined with another test for glaucoma, perimetry, and tonometry. The USPSTF did not consider evidence on tests that are experimental or no longer commonly used in the screening for or diagnosis of glaucoma.
Evaluating the evidence on screening tests is complicated by the lack of an established standard for the diagnosis of glaucoma and a consequent lack of an established gold standard to evaluate accuracy. The USPSTF reviewed more than 100 studies on the accuracy of various tests for glaucoma1. Instead of an established gold standard, many investigators used confirmation of POAG at follow-up examination, diagnosis of POAG requiring treatment, and other individual tests or combinations of tests as the reference against which to evaluate accuracy.
Tests with the most published studies on accuracy include optical coherence tomography, scanning laser polarimetry, confocal scanning laser tomography, frequency-doubling technology, and the Humphrey visual field analyzer. Studies varied appreciably in the devices, variables, thresholds for diagnosis, and measurement of outcomes used. Many studies had several methodological limitations, including enrollment of participants who were not representative of persons who would be tested in practice.
Most studies did not blind personnel who interpreted test results to the findings of the reference standard and vice versa. Many studies used a reference test that included 1 or more tests comprising the candidate test, resulting in a significant concern about bias. Because of the methodological limitations, variability in study designs, and lack of a diagnostic standard, the USPSTF was not able to make conclusions about the overall accuracy of screening for glaucoma.
Effectiveness of Early Detection and Treatment
No studies directly evaluated whether screening prevents visual field loss, visual impairment, or worsening quality of life. Whereas evidence shows that medical and surgical treatment of early asymptomatic POAG reduce the number of patients whose visual field defects progress, no studies evaluated whether they reduce progression to visual impairment or improve quality of life.
The USPSTF assessed 1 systematic review (of 10 studies) and 19 additional randomized, controlled trials that evaluated whether medical treatment slows the progression of visual field loss2. A systematic review of 10 studies published in 2007 concluded that medical treatment had a significant protective effect on incident worsening of visual field measurements compared with placebo or no treatment (odds ratio, 0.62 [95% CI, 0.47 to 0.81])2,9. Nineteen additional primary studies reported mixed results with treatment; a few reported improvements in visual field measurements with medical treatment, 7 reported no change, and 9 reported worsening of visual field measurements.
Most of these studies were not large or long enough to detect differences in the rates of visual field loss or clinically relevant outcomes related to glaucoma, given the slowly progressive nature of the disease. Three large studies of long duration reported mixed results; 2 studies concluded that medical treatment reduced glaucoma progression, and 1 found no difference between medical treatment and placebo2,10-12. A 2005 systematic review of 5 randomized, controlled trials that assigned participants to medical and/or surgical treatment or to no treatment reported that those receiving medical and/or surgical treatment were less likely to have progression of visual field loss and optic disc damage (hazard ratio for topical medications vs. no treatment, 0.56 [95% CI, 0.39 to 0.81])13.
Potential Harms of Screening or Treatment
No studies addressed the harms of screening. Several assessed the harms of treatment2,5. Eye redness was the most commonly reported adverse effect of topical medical treatments for glaucoma. In observational studies, the percentage of patients reporting eye redness ranged from 2% to 21%, depending on dose, length of use, and type of medication. Eye pain and burning were also commonly reported with topical medications, occurring in 1% to 3% of participants in observational studies. Other reported adverse effects of topical medications included eye irritation, eye dryness, increased iris pigmentation, and cystoid macular edema.
Surgical treatments of glaucoma were associated with hypotony, hyphema, shallow anterior chambers, cataract, and choroidal detachment. Penetrating surgical interventions (trabeculectomy) were associated with more frequent adverse effects than nonpenetrating procedures. Studies of surgical procedures more commonly reported cataracts, infection, bleeding, and synechiae than did studies of medications.
Estimate of Magnitude of Net Benefit
Evidence on the accuracy of screening tests and the benefits of screening or treatment in delaying or preventing visual impairment or improving quality of life is inadequate. Therefore, the overall certainty of the evidence is low, and the USPSTF is unable to determine the balance of benefits and harms of screening for glaucoma in asymptomatic adults.
How Does Evidence Fit With Biological Understanding?
The exact cause of POAG is not known. Diagnosis of glaucoma is usually based on several tests that, when combined, evaluate the biological structure and function of the optic nerve and the IOP. Persons with POAG may not have increased IOP, and increased IOP may not result in nerve damage and eventual visual impairment. This finding limits the development of a single gold standard to evaluate the accuracy of screening tests.
Most persons with glaucoma do not have symptoms. Once vision loss occurs—usually slow loss of side or peripheral vision—the optic nerve is already damaged. When damage is severe enough, loss of vision impairs function and quality of life. Advanced glaucoma can lead to blindness.
Treatments that reduce IOP prevent the decline in the biological structure and function of the optic nerve caused by glaucoma, thus slowing the worsening of visual field loss. However, the slowly progressive nature of glaucoma makes it difficult to evaluate the effectiveness of treatments, especially in preventing or slowing clinically noticeable loss of vision, and screening may lead to detection and treatment of many persons who will remain asymptomatic throughout their life (known as overdiagnosis and overtreatment).
Response to Public Comments
A draft version of this recommendation statement was posted for public comment on the USPSTF Web site from 19 February to 18 March 2013. A few comments noted that important population subgroups are at increased risk for glaucoma. The USPSTF updated the section on risk with new information on Hispanics. A few comments disagreed that there is no accepted gold standard for screening for glaucoma. None of the comments came to a consensus on an accepted standard for screening, and no change was made to the recommendation statement.
A few comments cited studies to provide evidence on the link between visual field loss and quality of life. The USPSTF reviewed these studies and determined that they did not provide the necessary evidence to change its conclusions. The USPSTF made several minor revisions to the recommendation statement in response to requests for corrections and clarifications.
The American Academy of Ophthalmology recommends a comprehensive adult medical eye evaluation, including tests for glaucoma, with frequency depending on the patient's age and other risk factors for glaucoma14. The American Optometric Association recommends eye examinations every 1 to 2 years,
Members of the U.S. Preventive Services Task Force at the time this recommendation was finalized are Virginia A. Moyer, MD, MPH, Chair (American Board of Pediatrics, Chapel Hill, North Carolina); Michael L. LeFevre, MD, MSPH, Co-Vice Chair (University of Missouri School of Medicine, Columbia, Missouri); Albert L. Siu, MD, MSPH, Co-Vice Chair (Mount Sinai School of Medicine, New York, and James J. Peters Veterans Affairs Medical Center, Bronx, New York); Linda Ciofu Baumann, PhD, RN (University of Wisconsin, Madison, Wisconsin); Kirsten Bibbins-Domingo, PhD, MD (University of California, San Francisco, San Francisco, California); Susan J. Curry, PhD (University of Iowa College of Public Health, Iowa City, Iowa); Mark Ebell, MD, MS (University of Georgia, Athens, Georgia); Glenn Flores, MD (University of Texas Southwestern, Dallas, Texas); Francisco A.R. García, MD, MPH (Pima County Department of Health, Tucson, Arizona); Adelita Gonzales Cantu, RN, PhD (University of Texas Health Science Center, San Antonio, Texas); David C. Grossman, MD, MPH (Group Health Cooperative, Seattle, Washington); Jessica Herzstein, MD, MPH (Air Products, Allentown, Pennsylvania); Wanda K. Nicholson, MD, MPH, MBA (University of North Carolina School of Medicine, Chapel Hill, North Carolina); Douglas K. Owens, MD, MS (Veterans Affairs Palo Alto Health Care System, Palo Alto, and Stanford University, Stanford, California); William R. Phillips, MD, MPH (University of Washington, Seattle, Washington); and Michael P. Pignone, MD, MPH (University of North Carolina, Chapel Hill, North Carolina). Former USPSTF members Rosanne Leipzig, MD, PhD; Diana Petitti, MD, MPH; and Timothy Wilt, MD, MPH, also contributed to the development of this recommendation.
This document is in the public domain within the United States.
Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2013;9 Jul).
Disclaimer: Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
Financial Support: The USPSTF is an independent, voluntary body. The U.S. Congress mandates that the Agency for Healthcare Research and Quality support the operations of the USPSTF.
Potential Conflicts of Interest: None disclosed. Disclosure forms from USPSTF members can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0959.
Requests for Single Reprints: Reprints are available from the USPSTF Web site (www.uspreventiveservicestaskforce.org).
- Ervin AM, Boland MV, Myrowitz EH, Prince J, Hawkins B, Vollenweider D, et al. Screening for Glaucoma: Comparative Effectiveness. Comparative Effectiveness Review No. 59. AHRQ Publication No. 12-EHC037-EF. Rockville, MD: Agency for Healthcare Research and Quality; April 2012.
- Boland MV, Ervin AM, Friedman D, Jampel H, Hawkins B, Vollenweider D, et al. Treatment for Glaucoma: Comparative Effectiveness. Comparative Effectiveness Review No. 60. AHRQ Publication No. 12-EHC038-EF. Rockville, MD: Agency for Healthcare Research and Quality; April 2012.
- Kim E, Varma R. Glaucoma in Latinos/Hispanics. Curr Opin Ophthalmol. 2010;21:100-5.
- Friedman DS, Wolfs RC, O'Colmain BJ, Klein BE, Taylor HR, West S, et al; Eye Diseases Prevalence Research Group. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol. 2004;122(4):532-8.
- Boland MV, Ervin AM, Friedman DS, Jampel HD, Hawkins BS, Vollenweider D, et al. Comparative effectiveness of treatments for open-angle glaucoma: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013;158(4):271-9.
- Grosse S, Biernath K. Vision evidence statement: screening. In: Campbell KP, Lanza A, Dixon R, Chattopadhyay S, Molinari N, Finch RA, eds. A Purchaser's Guide to Clinical Preventive Services: Moving Science Into Coverage. Washington, DC: National Business Group on Health; 2011.
- National Committee for Quality Assurance. The State of Health Care Quality: Reform, the Quality Agenda, and Resource Use. Washington, DC: National Committee for Quality Assurance; 2010. Accessed at https://www.ncqa.org/portals/0/state%20of%20health%20care/2010/sohc%202010%20-%20full2.pdf on 11 February 2013.
- Zhang X, Cotch MF, Ryskulova A, Primo SA, Nair P, Chou CF, et al. Vision health disparities in the United States by race/ethnicity, education, and economic status: findings from two nationally representative surveys. Am J Ophthalmol. 2012;154(6 Suppl):S53-62.
- Vass C, Hirn C, Sycha T, Findl O, Bauer P, Schmetterer L. Medical interventions for primary open angle glaucoma and ocular hypertension. Cochrane Database Syst Rev. 2007;(4):CD003167.
- Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-13.
- Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-79.
- Miglior S, Zeyen T, Pfeiffer N, Cunha-Vaz J, Torri V, Adamsons I; European Glaucoma Prevention Study (EGPS) Group. Results of the European Glaucoma Prevention Study. Ophthalmology. 2005;112(3):366-75.
- Maier PC, Funk J, Schwarzer G, Antes G, Falck-Ytter YT. Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ. 2005;331(7509):134.
- American Academy of Ophthalmology. Preferred Practice Pattern Guidelines: Comprehensive Adult Medical Eye Evaluation. San Francisco: American Academy of Ophthalmology; 2010. Accessed at https://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=64e9df91-dd10-4317-8142-6a87eee7f517 on 11 February 2013.
- American Optometric Association. Optometric Clinical Practice Guideline: Comprehensive Adult Eye and Vision Examination. St. Louis, MO: American Optometric Association; 2005. Accessed https://www.aoa.org/documents/optometrists/CPG-1.pdf at on 11 February 2013.