Age-Related Macular Degeneration

N Engl J Med 2008; 359:1735-1736October 16, 2008

Article

To the Editor:

The review of age-related macular degeneration by Jager et al. (June 12 issue)1 does not refer to an editorial accompanying the report of the Age-Related Eye Disease Study (AREDS) in the Archives of Ophthalmology in 2001 and two subsequent letters,2-4 all of which criticized the study analysis for setting aside a negative result in which dietary supplementation with high doses of vitamins and minerals was ineffective and instead reporting on a subgroup in which the result was positive. The investigators argued that the excluded patients had too few end points to be eligible for treatment. However, the group of patients who received the supplement had greater disease progression and provided valuable data regarding early intervention.

Discarding prespecified negative analyses and reporting on positive subgroup analyses has been repeatedly discouraged.5 The omission of the above information perpetuates the myth that the supplement used in the AREDS was effective, at the price of a treatment that has no benefit and carries undetermined risks.

Daniel Seigel, Sc.D.
1135 Pleasant Pt. Rd., Cushing, ME 04563
dseigel@midcoast.com

5 References

1
Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008;358:2606-2617
Full Text | Web of Science | Medline

2
Jampol LM. Antioxidants, zinc, and age-related macular degeneration: results and recommendations. Arch Ophthalmol 2001;119:1533-1534
Web of Science | Medline

3
Seigel D. AREDS investigators distort findings. Arch Ophthalmol 2002;120:100-101
Web of Science | Medline

4
Ambati J, Ambati BK. Age-Related Eye Disease Study caveats. Arch Ophthalmol 2002;120:997-997
Web of Science | Medline

5
Wang R, Lagakos SW, Ware JH, Hunter DJ, Drazen JM. Statistics in medicine -- reporting of subgroup analyses in clinical trials. N Engl J Med 2007;357:2189-2194
Full Text | Web of Science | Medline

To the Editor:

The review of age-related macular degeneration contains one problem: the inaccurate use of the term “legal blindness.” The authors imply that decreased vision in one eye may make that eye legally blind. This is incorrect: one eye cannot be legally blind, but a person may be legally blind. In the United States, “Statutory blindness is defined in the law as central visual acuity of 20/200 or less in the better eye with the use of [a] correcting lens.”1 Additional qualifications apply in the case of restricted visual fields.1,2 The proper definition is of financial and sociological importance to patients.

Robert J. Herm, M.D.
Robert E. Lee Ln., Bluffton, SC 29909
b2herm@hargray.com

2 References

1
Social Security Administration, 20 C.F.R.§ 404.1581 (1983).

2
Tax and credits: line 39a. In: Form 1040 instructions. Internal Revenue Service, 2008:31. (Accessed September 26, 2008, at http://www.irs.gov/pub/irs-pdf/i1040gi.pdf.)

Author/Editor Response

With regard to Seigel's comments, we believe that the authors of the report of the AREDS1 responded adequately to any concerns raised in correspondence after publication of their article. The authors of that report recognized the potential perils of subgroup analyses of nonprespecified groups and were not issuing a blanket recommendation for megadose supplements.2,3 Our review also acknowledges that the supplementation used in the AREDS may not be appropriate for all patients. Instead, we believe that the decision to initiate this supplementation should be based on a coordinated effort among the vitreoretinal specialist, the primary care physician, and the patient.

We disagree with the assertion that this supplementation has no benefit. In our opinion, it has clearly been shown to decrease the rate of visual loss in selected patients with age-related macular degeneration. Recommendations from the report of the AREDS are part of the evidence-based preferred practice patterns of the American Academy of Ophthalmology for the management of age-related macular degeneration, and they were rated as having the highest strength of evidence (based on study design) as well as being most important for the care process.4

Herm raises an important point. Indeed, one can easily infer from the article that an eye can become legally blind: “Although neovascular age-related macular degeneration represents only 10 to 15% of the overall prevalence of age-related macular degeneration, it is responsible for more than 80% of cases of severe visual loss or legal blindness (i.e., visual acuity of 20/200 or worse) resulting from age-related macular degeneration.” The words “or legal blindness” should have been omitted from the article. Herm is correct, and his point is well taken.

Rama D. Jager, M.D.
University of Chicago, Chicago, IL 60637
rjager@uretina.com

William F. Mieler, M.D.
University of Illinois, Chicago, IL 60612

Joan W. Miller, M.D.
Harvard University, Boston, MA 02115

4 References

1
Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol 2001;119:1417-1436
Web of Science | Medline

2
Seigel D. AREDS investigators distort findings. Arch Ophthalmol 2002;120:100-101
Web of Science | Medline

3
Ambati J, Ambati BK. Age-Related Eye Disease Study caveats. Arch Ophthalmol 2002;120:997-997
Web of Science | Medline

4
The Ophthalmic News & Education Network, American Academy of Ophthalmology. Age-related macular degeneration. (Accessed September 26, 2008, at http://one.aao.org/CE/PracticeGuidelines/PPP_Content.aspx?cid=0e2b5946-d493-4a4a-80fa-6f40841b1405#section5.)

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