Effect of low-dose atropine eyedrops on pupil metrics: results after half a year of treatment and cessation.

PURPOSE: To evaluate the effect of low-dose atropine eyedrops on pupil metrics. METHODS: This study was based on a randomized, double-masked, placebo-controlled, and cross-over trial in mainland China. In phase 1, subjects received 0.01% atropine or placebo once nightly. After 1 year, the atropine group switched to placebo (atropine-placebo group), and the placebo group switched to atropine (placebo-atropine group). Ocular parameters were measured at the crossover time point (at the 12th month) and the 18th month. RESULTS: Of 105 subjects who completed the study, 48 and 57 children were allocated into the atropine-placebo and placebo-atropine groups, respectively. After cessation, the photopic pupil diameter (PD) and mesopic PD both decreased (- 0.46 ± 0.47 mm, P < 0.001; - 0.30 ± 0.74 mm, P = 0.008), and the constriction ratio (CR, %) increased (4.39 ± 7.54, P < 0.001) compared with values at the crossover time point of the atropine-placebo group; pupil metrics of the atropine-placebo group had no difference from the values at the crossover time point of the placebo-atropine group. After 6 months of treatment, the photopic PD and the mesopic PD increased (0.54 ± 0.67 mm, P < 0.001; 0.53 ± 0.89 mm, P < 0.001), the CR (%) decreased (- 2.53 ± 8.64, P < 0.001) compared with values at the crossover time point of the placebo-atropine group. There was no significant relationship between pupil metrics and myopia progression during 0.01% atropine treatment. CONCLUSION: Pupil metrics and the CR could return to pre-atropine levels after cessation. Pupil metrics had no significant effect on myopia progression during treatment.

Effect of 0.01% atropine eyedrops on intraocular pressure in schoolchildren: a randomized clinical trial.

AIM: To assess the effect of 0.01% atropine eye drops on intraocular pressure (IOP) in myopic children. METHODS: A placebo-controlled, double-masked, randomized study. Totally 220 children aged 6 to 12y with myopia ranging from -1.00 to -6.00 D in both eyes were enrolled. Children were randomized in a 1:1 ratio to either 0.01% atropine eye drops or a placebo group using generated random numbers. All participants underwent the examination of IOP and cycloplegic refraction at baseline, 6 and 12mo. The change of IOP and the proportion of subjects with increased IOP in atropine and placebo groups were compared. RESULTS: Of 220 children, 117 were boys (53.2%). A total of 159 (72.3%) participants completed the follow-up at the 1-year study. At baseline, the mean IOP was 15.74 mm Hg (95%CI, 15.13 to 16.34 mm Hg) for the 0.01% atropine group and 15.59 mm Hg (95%CI, 15.00 to 16.19 mm Hg) for placebo group (mean difference, 0.14 mm Hg; P=0.743) after adjusting for central corneal thickness at baseline. At one year follow-up, the mean change of IOP was 0.16 mm Hg (95%CI, -0.43 to 0.76 mm Hg) for the 0.01% atropine group and -0.11 mm Hg (95%CI, -0.71 to 0.50 mm Hg) for placebo group (mean difference, 0.27 mm Hg; P=0.525) after adjusting for central corneal thickness. The 51.4% of children have increased IOP in the 0.01% atropine group, compared with 45.9% in the placebo group (P=0.511). CONCLUSION: The 0.01% atropine eye drops do not significantly affect the risk of elevated IOP. It is relatively safer to use in the studies that try to minimize myopia progression. However, a further long-duration study is required to be validated.

Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as multi-targeted compounds against Alzheimer's disease.

A series of benzoates (or phenylacetates or cinnamates) - tacrine hybrids (7a-o) were designed, synthesized and evaluated as multi-potent anti-Alzheimer drug candidates. The screening results showed that most of them exhibited a significant ability to inhibit ChEs, certain selectivity for AChE over BuChE and strong potency inhibitory of self-induced ß-amyloid (Aß) aggregation. All IC50 values of biological activity were at the nanomolar range. Especially, compound 7c displayed the greatest ability to inhibit AChE with an IC50 value of 5.63 nM and the highest selectivity with ratio of BuChE/AChE value of 64.6. Moreover, it also exhibited a potent inhibitory of Aß aggregation with an IC50 value of 51.81 nM. A Lineweaver-Burk plot and molecular modeling study showed that compound 7c targeted both the CAS and PAS of ChEs. A structure-activity relationship analysis suggested that the electron density of aromatic ring which was linked with tacrine through acetyl group played a significant role in determining the inhibitory activity.