Abstract
Purpose.:
To compare the mydriatic effect and the short-term corneal endothelial safety of intracamerally injected N-methyl-3,4-dihydroxyphenylamine (epinine) to phenylephrine in a porcine eye model.
Methods.:
One hundred twelve eyes from newly slaughtered pigs were used in this study. After pretreatment with 20 mg intracameral acetylcholine to give miosis, 0.15 mL epinine or phenylephrine 0.3%, 1.5%, or 3.0% was given as an intracameral injection. The pupils were filmed during 90 seconds with a video camera connected to an operation microscope, and the mean pupil diameters were measured from the video recordings. In 37 additional eyes, 0.15 mL vehicle, 1.5% epinine, or 1.5% phenylephrine was injected intracamerally, and the eyes were kept on ice overnight. Corneal endothelial morphology was assessed before and after the treatment. Ten eyes were given no injection and served as controls.
Results.:
Epinine had a significantly larger mydriatic effect than phenylephrine at equal concentrations. Endothelial cell loss was equal with both substances and did not exceed that of the vehicle.
Conclusions.:
Epinine was a more potent mydriatic than phenylephrine in this porcine eye model. The porcine eye model appears suitable as a first efficacy screening of substances for intraocular use. Epinine is a promising candidate substance for intraoperative (e.g., cataract surgery) intracameral use in humans.
Adequate mydriasis is a prerequisite for intraocular surgery and is traditionally achieved by preoperative topical anticholinergic and sympathomimetic mydriatic agents such as cyclopentolate and phenylephrine. A more rapid and logistically more efficient alternative is using intracameral mydriatics (ICM)
1 ; 150 μL solution containing lidocaine 1% and phenylephrine 1.5% is injected into the eye's anterior chamber at the start of the surgical procedure. Although proven safe and reliable in routine cataract surgery,
1,2 ICM with phenylephrine has a weaker mydriatic effect than traditional topical mydriatics, rendering pupil sizes approximately 1 mm smaller,
1 which may be perceived as disadvantageous. We therefore wanted to evaluate an alternative, potentially more efficient dilating substance than the α
1-stimulator phenylephrine for intracameral use.
Epinine (
N-methyl-3,4-dihydroxyphenethylamine) is a substance with both adrenergic and dopaminergic properties.
3,4 It stimulates all six known receptors—α
1, α
2, β
1, β
2, DA
1 and DA
2—in cardiovascular tissues
5 and was suggested early as a treatment for heart conditions. Numerous studies have been performed with epinine and its orally active 3,4-diisobutyryl ester, ibopamine,
6–11 for heart conditions. Ibopamine is rapidly hydrolyzed to epinine by esterases and exerts all its pharmacologic effects as epinine.
12 In ophthalmology, ibopamine eyedrops have been successfully used to dilate the pupil for fundus examinations and surgery.
13,14 Ibopamine is hydrolyzed to epinine during its passage through the cornea and, analogous to the cardiovascular system, exerts its pharmacologic effects within the eye as epinine.
15 Topical ibopamine has an interesting pharmacologic profile: 2% ibopamine is more potent than 10% phenylephrine in producing mydriasis,
16 and the mydriatic effect is reversed within 4 hours,
13 making ibopamine the most short-acting and most effective topical mydriatic agent studied thus far. Epinine is poorly absorbed through the cornea and is, therefore, not useful for topical application but is likely to have pharmacologic effects identical to those of topical ibopamine if injected directly into the anterior chamber of the eye. Based on this background, we decided to evaluate the mydriatic effect and the corneal endothelial safety of intracamerally injected epinine 0.3% to 3% and to compare this effect with that of phenylephrine at the same concentrations. For the study, we used a model involving postmortem porcine eyes.