To evaluate the safety and efficacy of the relatively selective M(1) antagonist pirenzepine hydrochloride in slowing the progression of myopia in school-aged children.
This was a parallel-group, placebo-controlled, double-masked study in healthy children, aged 8 to 12 years, with a spherical equivalent of -0.75 to -4.00 diopters (D) and astigmatism of 1.00 D or less. Patients underwent a baseline complete eye examination and regular examinations during a 1-year period. The setting was 13 US academic clinics and private practices. Patients were randomized in a 2:1 ratio to receive 2% pirenzepine ophthalmic gel or a placebo control twice daily for 1 year.
At study entry, the spherical equivalent was mean +/- SD -2.098 +/- 0.903 D for the pirenzepine group (n = 117) and -1.933 +/- 0.825 D for the placebo group (n = 57, P = .22). At 1 year, there was a mean increase in myopia of 0.26 D in the pirenzepine group vs 0.53 D in the placebo group (P < .001). No patients in the placebo group and 13 (11%) of 117 patients in the pirenzepine group discontinued participation in the study because of adverse effects (5 [4%] of 117 due to excessive antimuscarinic effects).
Pirenzepine is effective and relatively safe in slowing the progression of myopia during a 1-year treatment period.
"Another class of agents shown to inhibit myopia is antimuscarinic agents (Luft et al. 2003; Schmid and Wildsoet 2004; Siatkowski et al., 2004); drugs in this group include atropine and pirenzepine. Although much studied, the mechanism for the anti-myopia effect of these agents is still subject to debate (Lind et al. 1998; Truong et al. 2002; Bitzer et al. 2006; Qu et al. 2006; Liu et al. 2007; Barathi et al. 2009; McBrien et al. 2009). "
[Show abstract][Hide abstract] ABSTRACT: J. Neurochem. (2011) 118, 281–287.
rho1 GABAC receptor antagonists inhibit myopia in chick but the site of this effect is not known. The sclera ultimately determines the shape and size of the globe and thus an untested possibility is that GABA agents have a scleral mechanism. Whether rho1 GABAC receptors are expressed and located in chick sclera is unknown. Real-time PCR, western blot and immunohistochemistry were used to determine whether rho1 GABAC receptors are expressed and located in chick fibrous and cartilaginous sclera. Both layers of the chick sclera were positive for rho1 GABAC receptor mRNA (PCR) and protein (western blot) expression and labeling was observed in both fibroblasts and chondrocytes of the fibrous and cartilaginous layers (immunohistochemistry). These investigations clearly show that chick sclera possesses rho1 GABAC receptors. The sclera is thus a potential previously unrecognized site for activity of rho1 GABAC agents.
Journal of Neurochemistry 05/2011; 118(2):281-7. DOI:10.1111/j.1471-4159.2011.07300.x · 4.28 Impact Factor
"Siatkowski et al22 for the US Pirenzepine Study Group and Tan et al23 for the Asian Pirenzepine Study Group reported that 2% pirenzepine ophthalmic gel, a subtype selective M1 anti-muscarinic agent, used twice daily was associated with less increase in myopia, 0.26 D and 0.47 D respectively, over a 1-year treatment period as compared to their placebo-controlled groups who demonstrated mean increase in myopia of 0.53 D and 0.84 D, respectively. Chua et al24 in Singapore used 1% atropine to treat myopia and reported that myopia progression was only −0.28±0.92 "
[Show abstract][Hide abstract] ABSTRACT: To investigate whether seasonal modification in the concentration of atropine drops is effective in retarding the progression of myopia.
Two hundred and forty eyes of 120 healthy preschool- and school-age children in Chiayi region, Taiwan were recruited. The treatment group consisted of 126 eyes of 63 children who received atropine eye drops daily for one year and the control group included 114 eyes of 57 children who received nothing. The concentration of atropine eye drops was modified by seasonal variation as follows: 0.1% for summer, 0.25% for spring and fall, and 0.5% for winter. Refractive error, visual acuity, intraocular pressure (IOP), and axial length were evaluated before and after intervention.
Mean age was 9.1±2.8 years in the atropine group versus 9.3±2.8 years in controls (P=0.88). Mean spherical equivalent, refractive error and astigmatism were -1.90±1.66 diopters (D) and -0.50±0.59 D in the atropine group; corresponding values in the control group were -2.09±1.67 D (P=0.97) and -0.55±0.60 D (P=0.85), respectively. After one year, mean progression of myopia was 0.28±0.75 D in the atropine group vs 1.23±0.44 D in controls (P<0.001). Myopic progression was significantly correlated with an increase in axial length in both atropine (r=0.297, P=0.001) and control (r=0.348, P<0.001) groups. No correlation was observed between myopic progression and IOP in either study group.
Modifying the concentration of atropine drops based on seasonal variation, seems to be effective and tolerable for retarding myopic progression in preschool- to school-age children.
"Topically applied muscarine acetylcholine antagonists have been shown to reduce myopia progression and axial eye growth [24-26]. The mechanism of action of atropine and pirenzepine has not been established, but M1 to M5 muscarinic acetylcholine receptors have been identified in HSF, and HSF are therefore a potential site of action of these drugs [27-29]. "
[Show abstract][Hide abstract] ABSTRACT: Systemic treatment with adenosine receptor antagonists has been reported to affect the biochemistry and ultrastructure of rabbit sclera. This study was conducted to determine whether adenosine receptors (ADORs) are present in human scleral fibroblasts (HSF).
Primary HSF were cultured in vitro and identified with anti-vimentin, anti-keratin, anti-desmin, and anti-S-100 antibodies. Confocal fluorescence microscopy was used to study the distribution of ADORs in the HSF cell lines and in the frozen human scleral sections. ADOR protein expression in HSF and human sclera was confirmed by western blot analysis of cell lysates.
ADORs were expressed in both HSF and human sclera. This was confirmed by western blot. ADORA1 expression was concentrated in the nucleus. ADORA2A was concentrated mainly in one side of the cytoplasm, and ADORA2B was found both in the nucleus and the cytoplasm. ADORA3 was expressed weakly in the cytoplasm.
All four subtypes of ADOR were found in HSF and may play a role in scleral remodeling.
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