Contradictions in the Amblyopia Treatment Studies

In the article entitled “Two-Year Follow-up of a 6-Month Randomized Trial of Atropine vs Patching for Treatment of Moderate Amblyopia in Children,” the authors in the Pediatric Eye Disease Investigator Group “could identify no sources of bias or confounding to explain our [their] findings.”¹ There are, nonetheless, substantive questions about the study’s methodology.

Among these is that “the study protocol specified retesting of all sound eyes with vision worse than 20/20, whereas amblyopic eyes were not retested.”¹ According to Lancaster, “There is abundant evidence for the general proposition that exercises, repetition, practice, and learning lead to better performance.”² Different testing methods may have increased the disparity between the eyes.

The lack of untreated controls makes it impossible to distinguish the beneficial effects of training and increasing literacy from the presumed benefits of treatment. The Pediatric Eye Disease Investigator Group authors “agree that inclusion of an untreated control group would have been desirable from a scientific point of view.”³ Since “the response to treatment in this study was similar across the age range,”⁴ a 6-month delay would not incur appreciable risk.

The authors observe that anatomic limitations may explain “the persistent deficit in the amblyopic eyes”¹ but leave that possibility unexplored. “Optic nerve hypoplasia is an important cause of childhood visual disability”⁵ requiring precise diagnostic methods. Primary optic nerve defects might also explain the “greater deficit in the 2-year amblyopic eye acuity when the baseline amblyopic eye acuity was worse. . . . ”¹ Subjective evaluation rather than quantifiable optic nerve imaging precludes accurate detection and verification of optic nerve defects. This compromise probably was accepted because many of the Pediatric Eye Disease Investigator Group centers “do not have imaging equipment” (R. W. Beck, MD, PhD, written communication, December 1, 2004) to accurately identify and document optic nerve hypoplasia or dysplasia.

An earlier Pediatric Eye Disease Investigator Group article noted that anisometropia and esotropia do “not become manifest until some time after birth.”⁶ The delayed appearance of these amblyogenic factors challenges the belief that amblyopia is a consequence of an abnormal visual experience early in life. Feedback mechanisms influencing ocular alignment and growth depend on visual acuity. The possibility that congenital optic nerve anomalies impairing vision lead to strabismus and anisometropia should be considered.

The collection and analysis of verifiable, unbiased information is critical to scientific progress.⁷ Inconsistent vision testing, failure to apply modern diagnostic methods, lack of untreated controls, and neglecting alternative explanations for decreased visual acuity diminish the value of this study. Article

Correspondence: Dr Lempert, Park View Health Care Campus, 10 Brentwood Dr, Suite A, Ithaca, NY 14850 (eyechartplus@aol.com).

Financial Disclosure: None.

The ARCHIVES regrets that the letter by Dr Lempert and the reply by Dr Repka and colleagues did not accompany the letter by Kushner (Arch Ophthalmol. 2005;123:1615-1616) in the November 2005 issue on the article (Arch Ophthalmol. 2005;123:149-157) discussed here.

Daniel M. Albert, MD, MS