Articles about Eye Health and Disease 2003
 

Nearsightedness May Be Pharmacologically Controlled in Children

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

Two studies presented at the Association for Research in Vision and Ophthalmology (ARVO) annual meeting from May 4 through May 8, 2003 show the potential benefit of pirenzepine in reducing progression of myopia (nearsightedness) 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 was used as a 2% ophthalmic gel given twice a day in children. It blocks parasympathetic nerve receptors in the eye as a relatively selective M1-muscarinic antagonist, and appears to reduce myopia in animal models by limiting growth in the length of the eye. The 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 pirenzepine group and -1.93 D in the placebo group.

At 12 months, average worsening in nearsightedness was -0.26 D in the pirenzepine group and -0.53 D in the placebo group (P < .001). Only 2% of pirenzepine 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 pirenzepine group and 93% in the placebo group (P = .091). Dropout rate due to adverse events was 11% in the pirenzepine 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.

Pirenzepine 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. Phase 3 studies will examine varying doses of pirenzepine used over a broader age range.

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 pirenzepine 2% twice daily, placebo in the morning and pirenzepine PIR in the evening, or placebo twice daily.

From an average baseline of -2.3 to -2.4D, differences favoring pirenzepine began at three months. After one year, the average worsening in nearsightedness was -0.47D with pirenzepine twice daily (P < .001 vs. pirenzepine once daily and vs. placebo), -0.70D with pirenzepine once daily, and -0.84D with placebo twice daily.

The difference between pirenzepine twice a day and placebo represents approximately a 50% reduction in progression. Mydriatric (dilating) 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.

In a third study, the Atropine in the Treatment Of Myopia (ATOM) trial enrolled 400 eligible children aged 6 to 12 years, with nearsightedness of -1 D to -6 D. Subjects were randomized in double-masked fashion to receive in one eye either 1% atropine eye drops or artificial tears 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, average nearsightedness worsening in eyes treated with placebo was -0.76 D ± 0.44 Diopters. In the atropine-treated eyes, nearsightedness improved by +0.3 D ± 0.50 Diopters (P < .0001), and there was a reduction in the axial length of the eye (i.e. the front to back length of the eye) by -0.14 mm ± 0.28 mm, compared with a mean axial length elongation in the placebo-treated eyes of +0.20 mm ± 0.30 mm (P < .0001).

After two years, the average nearsightedness worsening and axial length 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, nearsightedness 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.

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