Myopia May Be Pharmacologically Controlled

Laurie Barclay, MD

May 08, 2003

May 8, 2003 -- Two studies presented at the Association for Research in Vision and Ophthalmology annual meeting from May 4 through May 8 show the potential benefit of pirenzepine in reducing progression of myopia in children. A third study, the largest randomized trial of its kind to date, shows the benefits of topical atropine. The investigators suggest that these findings provide strong evidence that myopia can be pharmacologically controlled.

"Pirenzepine (PIR), a relatively selective M1-muscarinic antagonist, reduces form-deprivation myopia in animal models by attenuating axial length," write R. Siatkowski, from Dean A. McGee Eye Institute, in Oklahoma City. "A 2% ophthalmic gel has been shown to be safe in children when used twice daily for 28 days."

This multicenter, controlled U.S. trial randomized 174 myopic children, aged 8 to 12 years, on a 2:1 basis to receive either PIR 2% gel or placebo twice daily for one year. At baseline, mean refractive error was -2.10 D in the PIR group and -1.93 D in the placebo group ( P = .221).

At 12 months, mean myopic progression was -0.26 D in the PIR group and -0.53 D in the placebo group ( P < .001). Only 2% of PIR subjects had more than 1D of myopic progression compared with 20% of the placebo group ( P < .001). Frequency of adverse events was 98% in the PIR group and 93% in the placebo group ( P = .091).

Dropout rate due to adverse events was 11% in the PIR group and 0% in the placebo group. The most common adverse events were gel residue on the eyelids, blurred near vision, and asymptomatic conjunctival reactions.

"PIR 2% gel used twice daily in moderately myopic children reduced the rate of myopic progression at one year by 50% (0.26 D) compared to placebo. Safety profile was acceptable," the authors write. "Phase 3 studies will examine varying doses of PIR used over a broader age range. PIR is an exciting, novel, and effective approach to the pharmacologic treatment of myopia."

The second study was a one-year, double-masked, placebo-controlled, parallel group study conducted at seven sites in Asia. D. T. Tan and colleagues from the Asian Pirenzepine Study Group randomized 353 children aged 6 to 12 years at a ratio of 2:2:1 to treatment with PIR 2% twice daily, placebo in the morning and 2% PIR in the evening, or placebo twice daily.

From a mean baseline of -2.3 to -2.4D, differences favoring PIR began at three months. After one year, the mean progression in myopia was -0.47D with PIR twice daily ( P < .001 vs. PIR once daily and vs. placebo), -0.70D with PIR once daily, and -0.84D with placebo twice daily.

"The difference between PIR b.i.d. and placebo represents approximately a 50% reduction in progression," the authors write. "Mydriatric and accommodative effects were present, but relatively mild, as were adverse events. However, there was a dosing-related incidence of follicles and papillae that were often asymptomatic."

All of the authors of each of these studies have a commercial relationship with Valley Forge Pharmaceuticals.

In a third study, the Atropine in the Treatment Of Myopia (ATOM) trial enrolled 400 eligible children aged 6 to 12 years, with myopia of -1 D to -6 D. Subjects were randomized in double-masked fashion to receive in one eye either 1% atropine eye drops or Isoptotears once nightly.

Of 359 subjects (90%) who returned for one-year follow-up, 331 (83%) also completed the two-year study. Of the 69 subjects who did not complete the study, 21 were from the placebo group and 48 were from the atropine group.

At one year, mean myopia progression in eyes treated with placebo was -0.76 D ± 0.44 D. In the atropine-treated eyes, myopia regressed by +0.3 D ± 0.50 D ( P < .0001), and there was a reduction in axial length by -0.14 mm ± 0.28 mm, compared with a mean axial elongation in theplacebo-treated eyes of +0.20 mm ± 0.30 mm ( P < .0001).

After two years, the mean myopia progression and axial elongation in the placebo-treated eyes were -1.20 D ± 0.69 D and +0.38 mm ± 0.38 mm, respectively. In the atropine-treated eyes, myopia progression was -0.25 D ± 0.92 D, and the axial length remained essentially unchanged compared with baseline (-0.02 mm ± 0.35 mm; P < .0001 for both comparisons).

"The ATOM study is the largest randomized controlled trial of its kind to date, and the results provide strong evidence that childhood myopia progression and axial elongation can be controlled through pharmacological means such as topical atropine," write W. H. Chua, from the Singapore Eye Research Institute, and colleagues.

None of this study's authors disclosed any significant financial interests.

ARVO 2003 Annual Meeting: Abstracts 44778/B437, 801/B776, 3119. Presented May 4-8, 2003.

Reviewed by Gary D. Vogin, MD