BMJ  2005;331:E376-E377 (17 September), doi:10.1136/bmj.331.7517.E376

BMJ USA: Editorial

Editorial

Screening for glaucoma

Waiting until our vision clears

Deciding about screening can be complex. First, we must distinguish screening from case-finding. It is always important for primary care physicians to ask appropriate questions and listen carefully to detect early symptoms that patients may not immediately offer—case-finding. All agree that people with signs or symptoms need to be evaluated. Screening as used here involves people with no signs or symptoms of the problem being discussed.

Although it is difficult to be opposed to finding disease earlier—screening sometimes does extend life and/or improve the quality of life—screening also has its down side. The harder we look for disease in asymptomatic people, the more we find not only the diseases that we seek, but also "pseudo-disease"—conditions that have some appearance of disease but never cause problems for real people. There are many examples: early cervical dysplasia, small (less than 5 mm) colonic polyps, many cases of ductal carcinoma in situ of the breast, small (3 to 3.9 cm) abdominal aortic aneurysms, many cases of prostate cancer, and probably many of the "abnormalities" found on total body computerized tomography screening. It is difficult to think of a screening situation where there is not some degree of detection of "pseudo-disease."

Ideally, we would recognize pseudo-disease for what it is—a "lesion" that needs no treatment. Unfortunately, this is often difficult to do. First, we often do not have enough information to distinguish pseudo-disease from real disease with confidence. Second, our current medico-legal climate limits the degree to which we can ignore pseudo-disease. As a result, many cases of pseudo-disease are thoroughly investigated, monitored, and even treated. Overtreatment of people with lesions that in truth need no treatment is a major downside of many screening situations. The best way to control detection of pseudo-disease and overtreatment is to control screening in the first place.

An interesting example of our struggle to understand the most appropriate situation to screen is the issue of screening for glaucoma. Visual impairment due to glaucoma is an important problem for many older people, especially African-Americans. Our best estimates are that glaucoma is responsible for about 14% of cases of low vision (< 20/40) and 26% of blindness in African-Americans; the corresponding figures for non-Hispanic whites are 3.3% and 6.4%.¹ This is a condition worthy of our attention and continued research.

For years, however, evidence-based medicine review groups have pointed out the lack of evidence that reducing intra-ocular pressure (IOP), the primary treatment for primary open-angle glaucoma, improves vision.² To their credit, the ophthalmological community has responded with several important randomized controlled trials of this question.

In this issue, Maier et al present a meta-analysis of the best of these trials (p 389). The authors divide the trials into two groups, corresponding to the two different questions about lowering IOP. The first question is whether lowering IOP among people who have increased IOP but no visual field defects reduces the development of visual field defects. Driven by a single large trial,³ Maier et al find that treatment of patients with increased IOP reduces the development of visual field defects by more than 40%.

The second question is whether lowering IOP among people with early, asymptomatic visual field defects would reduce the development of further visual field defects. Again, the authors' answer was yes; again, the meta-analysis was driven by a single large trial.⁴ Maier's study found that treatment reduces the development of further visual field defects by about 35%.

In both of these trials, it is important to understand what they are measuring when they discuss "visual field defects." Each of these studies used very sensitive instruments to find small defects that were generally unknown to the patient. The extent to which these small defects predict future development of symptomatic visual problems for the patient is largely unknown. Thus, when Maier et al say that lowering IOP "is beneficial in reducing the risk of visual field loss in the long term," they are talking about a benefit that patients would not notice.

We are really asking to what extent screening for glaucoma leads to reduction in pseudo-disease as opposed to disease that matters to patients.

In fact, in neither of the large trials that dominated the meta-analysis was there a difference between treated and untreated groups in visual acuity. One of the trials has also recently published a study that found, after six years of follow-up, no difference between treated and untreated patients in vision-related quality of life.⁵

Thus, we are left to wonder to what extent a reduction in small, asymptomatic visual field defects after five to six years of treatment would benefit our patients. It may help us to recall that primary open-angle glaucoma is a chronic condition that does its damage over many years. Older people have a higher prevalence of this disease than younger people; some may not live long enough to develop visual problems from glaucoma even though they have early field defects.^6,7 We also know that the natural history of primary open-angle glaucoma is variable; some people develop important visual problems while others do not. We do not know enough at this point to reliably distinguish one group from the other.

Does this sound familiar? We are really asking to what extent screening for glaucoma leads to a reduction in pseudo-disease as opposed to disease that matters to patients. Unfortunately, we do not know the answer. One hopes that longer follow-up of the research studies that assess vision-related quality of life will help us answer this critical question. There are other problems with screening for glaucoma as well. Most of the screening tests are not feasible, accurate, or reliable in primary care. There are adverse effects of screening on many patients' psychology, and topical agents often cause local eye irritation.⁸ To benefit from treatment, patients must use eye drops and be monitored regularly by an ophthalmologist. But none of this matters if the treatment doesn't work in a way that patients care about.

Earlier this year, the US Preventive Services Task Force, after reviewing all of the evidence in the Maier analysis and more, declined to recommend screening for glaucoma because of insufficient evidence.^9,10 With further follow-up of current studies and additional research, maybe our vision will clear and we will be able to conclude that screening for increased IOP and for early glaucoma leads to treatment that improves vision in a way that our patients will notice and appreciate. But initiating widespread screening at present is premature. Treating pseudo-disease helps no one.

University of North Carolina School of Medicine Sheps Center for Health Services Research, CB# 7590 Chapel Hill, NC 27599-7590 russell_harris{at}med.unc.edu

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Paper p 389

Competing interests: RH is a member of the US Preventive Services Task Force.

References

1. The Eye Diseases Prevalence Research Group. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 2004;122: 477-485.[Abstract/Free Full Text]
2. US Preventive Services Task Force. Guide to Clinical Preventive Services, 2nd edition. Chapter 34: Screening for Glaucoma. Alexandria, Virginia: International Medical Publishing, 1996.
3. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, et al. The ocular hypertension treatment study: a randomized controlled trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120: 701-713.[Abstract/Free Full Text]
4. Heijl A, Leske MC, Bengtsson B, Hyman L, Bengtsson B, Hussein M, for the Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120: 1268-1279.[Abstract/Free Full Text]
5. Hyman LG, Komaroff E, Heijl A, Bengtsson B, Leske MC for the Early Manifest Glaucoma Trial Group. Treatment and vision-related quality of life in the early manifest glaucoma trial. Ophthalmology 2005;(in press, released online).
6. Quigley HA, Tielsch JM, Katz J, Sommer A. Rate of progression in open-angle glaucoma from cross-sectional prevalence of visual field damage. Am J Ophthal 1996;122: 355-363.[Web of Science][Medline]
7. Quigley HA. Proportion of those with open-angle glaucoma who become blind. Letter to the editor. Ophthalmology 1999;106: 2039.[CrossRef][Web of Science][Medline]
8. Odberg T, Jakobsen JE, Hultgren SJ, Halseide R. The impact of glaucoma on the quality of life of patients in Norway. Acta Ophthalmol Scand 2001;79: 116-120.[Medline]
9. US Preventive Services Task Force. Screening for glaucoma: recommendation statement. Ann Fam Med 2005;3: 171-172.[Free Full Text]
10. Fleming C, Whitlock EP, Beil T, Smit B, Harris RP. Screening for open-angle glaucoma in the primary care setting: an update for the US Preventive Services Task Force. Ann Fam Med 2005; 3: 167-170.[Abstract/Free Full Text]

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Screening for glaucoma -- Waiting until our vision clears

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