WGA subcommittee on Screening for OAG

The advanced stage of symptomatic open-angle glaucoma (OAG) and high rates of undiagnosed disease raise the question of whether we can improve the health of our communities by screening for OAG. This question was first addressed by government in North America almost twenty years ago and has been reviewed several times since. This issue has also been discussed in a number of national and regional practice guidelines for glaucoma.^1,2 With a new US statement on OAG screening published in March 2005,³ the WGA subcommittee for Screening for OAG decided to review the important issues in OAG screening and ask what we have done and what we still have to do to answer the question of whether screening for OAG is worthwhile.

The Committee recognized that it would be very unwieldy to consider all of the different possible screening activities in completing its task. The Committee also recognized that screening for open-angle glaucoma has been controversial, but that much of the controversy centered on the value of mass or community screening for open-angle glaucoma. Mass or community screenings are typically performed on unselected populations such as community centers, shopping centers, churches, or on partially selected populations, such as all volunteer employees working in a large corporate building. The Committee decided to narrow its task to a consideration of mass or community screenings in the context of an economically developed country.

While there are many important considerations in determining whether some form of screening for a disease is worthwhile, there are six critical questions, published by Wilson and Junger,⁴ that must be answered first.

Wilson and Junger's criteria for a screenable disease

1. The condition sought should be an important health problem.
2. There must be an accepted and effective treatment for patients with the disease, that must be more effective at preventing morbidity when initiated in the early, asymptomatic stage than when begun in the later, symptomatic stages.
3. Facilities for diagnosis and treatment should be available.
4. There must be an appropriate, acceptable, and reasonably accurate screening test.
5. The natural history of the condition, including development from latent to manifest disease, should be adequately understood.
6. The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.

Governmental Reports on Screening for OAG

In the 1980s, the United States government requested its Office of Technology Assessment (OTA) to assess the effectiveness and costs of providing a number of preventive health services to the elderly under the government-funded Medicare program. A document, 'Screening for Open-Angle Glaucoma in the Elderly,' was published in October of 1988.⁵
Below is a summary of the main conclusions of the OTA document.

1. Open-Angle Glaucoma screening programs were expensive.
2. There was little data on whether treatment of people with ocular hypertension or open-angle glaucoma altered the course of the disease.
3. The natural history of the disease was 'perplexing' and the natural history of untreated open-angle glaucoma was unknown.
4. There existed scarce data on screening test accuracy (sensitivity, specificity, predictive value of positive test).

Based on the above, OTA concluded that both the benefits of screening - i.e., visual impairment prevented - and the costs of screening and resultant treatment were highly uncertain. It should be emphasized that the OTA task was specifically to assess the potential benefits and costs if glaucoma screening were offered as a covered service by Medicare. However, the influence of this document was far reaching and subsequent opinions related to the value of general screening for open-angle glaucoma were based, in large part, on issues raised by the OTA document. Many of these issues were also considered by the Canadian Task Force on Preventative Services, which took no definitive position on the advisability of performing glaucoma screening on a general population basis.⁶

Recently, the United States Preventive Services Task Force (UPSTF) provided a new Recommendation Statement for OAG screening. A previous 1996 statement⁷ found insufficient evidence to recommend for or against glaucoma screening in primary care practice. The USPSTF noted that although glaucoma treatment with medication or surgery to lower intraocular pressure had been the standard of care for years, definitive evidence supporting the benefit of treating persons with early glaucoma and minimal visual impairment was not available.

For its latest recommendation (released March 2005),³ the USPSTF critically reviewed the literature for new evidence on the effectiveness of screening and treatment for early POAG. It found good evidence that early treatment of adults with increased IOP detected by screening reduces the number of persons who develop small, visual field defects, and that early treatment of those with early, asymptomatic POAG decreases the number of those whose visual field progress. However, the USPSTF concluded that the evidence is insufficient to determine the extent to which screening - leading to earlier detection and treatment of people with elevated IOP or OAG - would reduce impairment in vision-related function or quality or life. Given the uncertainty of the magnitude of benefit from early treatment and given the known harms of early treatment (i.e., local eye irritation and an increased risk for cataracts), the USPSTF could not determine the balance between the benefits and harms of screening for glaucoma. It concluded that the evidence is insufficient to recommend for or against routine screening. The new statement thus represents no change from the Task Force's 1996 recommendation. In formulating its new recommendation, the USPSTF focused its review only on studies of glaucoma treatment. Other criteria on the screenability of a disease were not considered.

WGA Review

The WGA subcommittee on Screening for OAG decided to re-evaluate the evidence upon which the OTA recommendation was based. Specifically, it sought to apply updated data to Wilson and Junger's criteria for a screenable disease and to determine whether this new evidence changes the rationale for open-angle glaucoma screening.

1. The condition sought should be an important health problem.
   • OTA used data from the Framingham study⁸ to estimate prevalence and incidence of open-angle glaucoma. Total prevalence in people over age 52 estimated at 1.2% and prevalence in people over age 65 estimated at between 2 to 3%.
   • More recent studies suggest that the overall prevalence is higher, probably between 1.5 and 2.0% in persons over 40 years of age and the prevalence among the elderly is markedly higher.^9-20
   • Quality of life data, though not extensive, is only recently available.
   • OTA did appreciate the burden of blindness from glaucoma and racial difference in prevalence and blindness from glaucoma.
   • Overall conclusion is that glaucoma is an important health problem, particularly in Americans of African descent, though perhaps not as important as diseases with equally high prevalence that results in mortality.
   • Overall summary: not much change from the 1980s.
2. There must be an accepted and effective treatment for patients with the disease that must be more effective at preventing morbidity when initiated in the early, asymptomatic stage than when begun in the later, symptomatic stages.
   • Newer topical medications that are more effective, easier to use, and better tolerated are now available.
   • The Ocular Hypertension Treatment Study (OHTS) showed that treatment of elevated IOP is effective in delaying onset of POAG.²¹
   • The Early Manifest Glaucoma Treatment Trial (EMGT) showed that treatment of early glaucoma is effective in slowing progression.²²
   • The Collaborative Initial Glaucoma Treatment Study (CIGTS) showed health-related quality of life is comparable between medically and surgically treated patients.²³
   • We still do not know whether delaying treatment of elevated IOP affects the rate of progression to POAG (currently being investigated in OHTS II) and whether delaying treatment of POAG affects rate of visual field progression
   • We still do not know whether health-related quality of life differs between treated and untreated glaucoma patients.²⁴
   • Overall summary: much stronger support for this criterion since 1980s
3. Facilities for diagnosis and treatment should be available.
   • Almost all developed countries have appropriate facilities for diagnosis and treatment
   • However, access can be a major issue, particularly in countries where there is no national health insurance, such as the U.S.A.
   • Some programs, such as EyeCare America, Glaucoma Project, were not available previously.
   • Overall summary: not much change from the 1980s.
4. There must be an appropriate, acceptable, and reasonably accurate screening test.
   • Glaucoma screening technologies assessed by OTA were tonometry, direct ophthalmoscopy, and manual and early automated perimetry. The best results found were sensitivity of 93% and specificity of 88% for automated perimetry (Humphrey perimeter).
   • A major advance in automated perimetry over the past decade has been development of shorter testing algorithms, such as SITA as well as frequency doubling perimetry.^25-27
   • There have been major advancements in testing for structural damage with optic disc and nerve fiber layer photography and imaging technologies.²⁸
   • However, the sensitivity and specificity of all these tools for population-based screening is uncertain, as some have been tested only on selected groups, not populations.
   • The question of how to set optimum criteria for sensitivity/specificity is another unresolved issue, which has major implications for cost.
   • Overall summary: major improvements have been made in perimetry, particularly with regard to portability, speed, and perhaps also accuracy as well as major improvements in assessment of structural damage. However, their utility in population-based screening has not yet been fully defined.
5. The natural history of the condition, including development from latent to manifest disease, should be adequately understood.
   • More data on risk factors for development and progression of OAG are now available.
   • We are better able to predict who, with ocular hypertension, is more likely to develop glaucoma, but still very imprecise (OHTS).^21,29
   • We are better able to predict who, with early glaucoma, is more likely to progress, but still very imprecise (EMGT).²²
   • We now have longitudinal data on likelihood of progressing to blindness (Olmsted study).³⁰
   • We now have longitudinal data on what happens with untreated glaucoma, long-term in the St. Lucia Study, ³¹ and short-term with determination of rates of progression in EMGT22 and CNTGS.³²
   • Overall Summary: Since the 1980s, knowledge of natural history of open-angle glaucoma better understood, particularly of untreated glaucoma. However, still considerable imprecision in identifying (1) who will develop glaucoma and who will not, and (2) among those with glaucoma, who will progress and at what rate.
6. The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care
   as a whole.
   • A limited number of cost-effectiveness and value-based analyses are now available.
   • We need to better understand: benefits of early detection (in terms of decreased morbidity) weighed against the toll on available resources, the risks, and the inconvenience of screening; impact of false positives subjected to wasteful diagnostic work-ups; impact of false negatives not seeking further care and presenting later at more advanced symptomatic stage.
   • Overall summary: We are in the early stages of acquiring new data on this topic.

Summary

In summary, an updated review of the evidence shows improvement in some of the screening criteria and no improvement in others. A summary is provided below. A score of 1 denotes no evidence for meeting criteria and a score of 5 denotes fully meeting criteria.

The WGA subcommittee on Screening for OAG felt that there are at least two other rationales for glaucoma screening, and both of these have received relatively little attention. One of these is that of promoting public awareness of the disease. In this regard, screening has been particularly effective when directed at legislators and physicians.

Another rationale is that in many medically underserved communities, ophthalmologic services are not readily available and glaucoma screening may offer an avenue for detecting vision disorders and getting those who require attention into appropriate evaluation and treatment. This is particularly true in many rural areas.

Additional screening issues

Because the prevalence of primary open-angle glaucoma in the general population is not high, screening (even with a highly valid test) results in a low predictive value of a positive test. Thus among individuals who test positive based on the screening, only a small percentage will actually have the disease, and most will have undergone costly, unproductive diagnostic work-ups. This has led to the suggestion by several organizations and individuals that screening may only be justified in certain 'high-risk' groups (i.e., elderly, specific races, persons with glaucoma family history) in which the yield per positive test would be expected to be higher.

From an economic standpoint, such a recommendation is reasonable since the costs per case decrease as the predictive value increases. The Committee felt this to be a very important consideration, and one that was applicable to most developed societies. However, the Committee felt that the direct and indirect costs for glaucoma case-finding as well as the direct and indirect costs for glaucoma treatment needed to be considered before making a definitive recommendation on what constituted an acceptable predictive value. The currently available literature does not permit a sufficiently detailed assessment in this regard.

Even among developed economy countries, considerable differences exist in the health care delivery system and, specifically, in the provision of ophthalmic care. One such example is in the role provided by opticians, optometrists, ophthalmologists, and primary care doctors in different countries. The Committee felt that a general recommendation on the desirability of population screening for glaucoma may not be equally applicable to all countries, regardless of similarities in state of economic development.

Committee consensus

1. Evidence to justify glaucoma screening is considerably stronger than it was a couple of decades ago.
2. Other rationale, besides the traditional guidelines advocated by Wilson and Junger exists and further strengthens the justification for glaucoma screening.
3. Justification for glaucoma screening is most strongly supported in high-risk groups. However, the cut-off level of glaucoma prevalence needed to make screening desirable is not known.
4. Other types of glaucoma screening - besides mass or community screening - are feasible in different societies and should be considered within the constraints of the societal health care delivery system.
5. Evidence weakly supports justification for community glaucoma screening on a limited scale and for specific purposes.

References

1. Asia Pacific Glaucoma Guidelines. Sydney: South East Asian Glaucoma Interest Group (Internet Access: http://www.seagig.org), 2003-4.
2. Preferred Practice Pattern: Primary Open-Angle Glaucoma, American Academy of Ophthalmology (Internet Access: http://www.aao.org). 2005.
3. Fleming C, Whitlock EP, Beil T, et al. Screening for primary open-angle glaucoma in the primary care setting: an update for the US Preventive Services Task Force. Ann Fam Med 2005;3(2):167-70.
4. Wilson JMG, Jungner G. Principles and Practice of Screening for Disease. WHO Chronicle 1968;22(11):473.
5. Office of Technology Assessment: Screening for Open-Angle Glaucoma in the Elderly. Preventive Health Services Under Medicare. Washington, D.C.: Congress of the United States, 1988.
6. Periodic health examination, 1995 update: 3. Screening for visual problems among elderly patients. Canadian Task Force on the Periodic Health Examination. CMAJ 1995;152(8):1211-22.
7. Guide to Clinical Preventive Services, 2nd Edition. Washington, D.C.: U.S. Preventive Services Task Force, 1996.
8. Leibowitz HM, Krueger DE, Maunder LR, et al. The Framingham Eye Study monograph: An ophthalmological and epidemiological study of cataract, glaucoma, diabetic retinopathy, macular degeneration, and visual acuity in a general population of 2631 adults, 1973-1975. Surv Ophthalmol 1980;24(Suppl):335-610.
9. Buhrmann RR, Quigley HA, Barron Y, et al. Prevalence of glaucoma in a rural East African population. Invest Ophthalmol Vis Sci 2000;41(1):40-8.
10. Cedrone C, Culasso F, Cesareo M, et al. Prevalence of glaucoma in Ponza, Italy: a comparison with other studies. Ophthalmic Epidemiol 1997;4(2):59-72.
11. Klein BE, Klein R, Sponsel WE, et al. Prevalence of glaucoma. The Beaver Dam Eye Study. Ophthalmology 1992;99(10):1499-504.
12. Leske MC, Connell AM, Schachat AP, Hyman L. The Barbados Eye Study. Prevalence of open angle glaucoma. Arch Ophthalmol 1994;112(6):821-9.
13. Mason RP, Kosoko O, Wilson MR, et al. National survey of the prevalence and risk factors of glaucoma in St. Lucia, West Indies. Part I. Prevalence findings. Ophthalmology 1989;96(9):1363-8.
14. Mitchell P, Smith W, Attebo K, Healey PR. Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. Ophthalmology 1996;103(10):1661-9.
15. Quigley HA, West SK, Rodriguez J, et al. The prevalence of glaucoma in a population-based study of Hispanic subjects: Proyecto VER. Arch Ophthalmol 2001;119(12):1819-26.
16. Ramakrishnan R, Nirmalan PK, Krishnadas R, et al. Glaucoma in a rural population of southern India: the Aravind comprehensive eye survey. Ophthalmology 2003;110(8):1484-90.
17. Shiose Y, Kitazawa Y, Tsukahara S, et al. Epidemiology of glaucoma in Japan--a nationwide glaucoma survey. Jpn J Ophthalmol 1991;35(2):133-55.
18. 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(3):369-74.
19. Wensor MD, McCarty CA, Stanislavsky YL, et al. The prevalence of glaucoma in the Melbourne Visual Impairment Project. Ophthalmology 1998;105(4):733-9.
20. Wolfs RC, Borger PH, Ramrattan RS, et al. Changing views on open-angle glaucoma: definitions and prevalences--The Rotterdam Study. Invest Ophthalmol Vis Sci 2000;41(11):3309-21.
21. Kass MA, Heuer DK, Higginbotham EJ, 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; discussion 829-30.
22.  Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120(10):1268-79.
23. Feiner L, Piltz-Seymour JR. Collaborative Initial Glaucoma Treatment Study: a summary of results to date. Curr Opin Ophthalmol 2003;14(2):106-11.
24. Hyman LG, Komaroff E, Heijl A, et al. Treatment and vision-related quality of life in the early manifest glaucoma trial. Ophthalmology 2005;112(9):1505-13.
25. Anderson AJ, Johnson CA. Frequency-doubling technology perimetry. Ophthalmol Clin North Am 2003;16(2):213-25.
26. Bengtsson B, Heijl A. SITA Fast, a new rapid perimetric threshold test. Description of methods and evaluation in patients with manifest and suspect glaucoma. Acta Ophthalmol Scand 1998;76(4):431-7.
27. McKendrick AM. Recent developments in perimetry: test stimuli and procedures. Clin Exp Optom 2005;88(2):73-80.
28. Zangwill LM, Medeiros FA, Bowd C, Weinreb RN. Optic nerve imaging devices: recent advances. In: Grehn F, Stampher R, eds. Essentials in Ophthalmology: Glaucoma. Heidelberg: Springer-Verlag & Co., 2004.
29. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120(6):714-20; discussion 829-30.
30. Schoff EO, Hattenhauer MG, Ing HH, et al. Estimated incidence of open-angle glaucoma in Olmsted County, Minnesota. Ophthalmology 2001;108(5):882-6.
31. Wilson MR, Kosoko O, Cowan CL, Jr., et al. Progression of visual field loss in untreated glaucoma patients and glaucoma suspects in St. Lucia, West Indies. Am J Ophthalmol 2002;134(3):399-405.
32. Drance S, Anderson DR, Schulzer M; Collaborative Normal-Tension Glaucoma Study Group
    Risk factors for progression of visual field abnormalities in normal-tension glaucoma Am J Ophthalmol. 2001 Jun;131(6):699-708

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