Brimonidine Topical Eye Drops and Intravitreal Administration Inhibit Form-Deprivation Myopia in Guinea Pigs: Ocular Pharmacokinetics and Irritation

Purpose: This study aims to evaluate the effects of brimonidine eye drops and intravitreal administration in guinea pigs with form-deprivation myopia (FDM) and to analyze the ocular pharmacokinetics and irritation. Methods: The experimental guinea pigs were randomized to the normal control, FDM, FDM brimonidine topical eye drops, and FDM intravitreal injection groups. The experiment period was 13 days. Changes in ocular refraction and axial length were monitored regularly. The ocular pharmacokinetics of brimonidine and its metabolite brimonidine-2,3-dione were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Ocular irritation was assessed by the Draize test, corneal fluorescein staining, and hematoxylin and eosin staining. Results: Two administration methods of brimonidine equally inhibited the increase in refraction and axial length in FDM guinea pigs (P < 0.05). Pharmacokinetic analysis revealed significant and sustained accumulation of brimonidine in the iris and choroid. Brimonidine was preferentially distributed to the cornea, conjunctiva, and sclera when administered topically, and preferentially to the retina and vitreous when administered intravitreally. The total area under the curve values for retinal and scleral tissues demonstrated that continuous topical administration was 1.95 times and 1.36 times that of intravitreal administration, respectively. The concentration of brimonidine-2,3-dione was significantly lower than that of brimonidine. Brimonidine topical eyedrops had less ocular irritation. Conclusions: At the drug concentrations in this study, both topical and intravitreal brimonidine achieved sufficient ocular exposure to exert similar myopia-suppressing effects. Continuous topical administration can maintain higher drug concentrations in the retinal and scleral tissues with less eye irritation.

brimonidine; form-deprivation myopia; guinea pig; intravitreal administration; pharmacokinetics; topical eye drops.