Effect of Phenylephrine on the Accommodative System

Table 1

Summary of the measurements procedures and the observed effects after PHCl instillation for the main reports that have been reviewed. The asterisks denote the studies in which the authors found some effects over the accommodative abilities of the human eye after PHCl instillation (these studies are normally linked to a high level of accommodation response, i.e., high parasympathetic response).

First author (year) (Ref)	Subjects (Age range)	PHCl drops (% concentration)	Measurement procedure	Observed effect after PHCl instillation
Biggs (1959) [6]	5 (n/a)	8 (10%)	Subjective Badal optometer to measure the near point of accommodation (2 mm artificial pupil).	Recession of the near-point averaging 0.66 D.
Leibowitz (1975) [7]	7 (18–34)	2 (10%)	Laser optometer with Badal principle and moving speckle patterns.	No change of either the far point of accommodation or the dark focus was evident in the results.
Garner(1983) [8]	3 (n/a)	2 (10%)	Laser optometer with Badal principle and moving speckle patterns. FPA was measured using a 6/9 Snellen letter. NPA was the closest distance to which a line target could be moved towards the eye without noticeable blur. RPA was determined with the laser optometer after 5 minutes in complete darkness.	Reduction of the NPA in all subjects by 2.5–3.0 D under natural pupils. A typical accommodative lag of 1 D was exhibited by all subjects. The RPA varied between 2.0–2.5 D.
Zetterström (1984) [9]	10 (22–29)	1 (0.1%, 1%, 10%)	The subject looked at the smallest optotype on a RAF near-point rule, beginning from a distance of 50 cm and then slowly moving the text towards the eye until blurring (2 mm artificial pupil).	There were significant differences in the ability to accommodate between the three different solutions. Although great individual differences were found, PHCl has an effect on accommodation that can amount to 2 or 3 D.
Mordi(1986) [10]	5 (25–43)	2 (10%)	Monocular static and dynamic AR were assessed with an infrared optometer. Reaction time and response time were used to characterize the dynamic accommodation.	Cycloplegic effects, including a slowing of the dynamics of the AR, a recession of the NPA and a reduction in the slope of the AR/stimulus curve (50% approx. at two hours after instillation).
Mordi(1986) [11]	10 (20–26)	1 (2.5%)	Donders’ push-up method was used to measure the AA while the subject read the words in the 0.62 M test target at 40 cm.	Accommodation inhibition by about 15% when used alone and by over 25% when preceded by anesthetic instillations.
Zetterström(1988) [12]	8 (34–90)	40 mL organ bath (dose responses: 5⋅10^−6–5⋅10^−3 M)	In vitro pharmacological test using human ciliary muscle tissue. Muscle strips of the meridional and circular portion of the ciliary muscle were attached to a tension gauge in an organ bath. Drug was added to the perfusion medium.	Ciliary muscle from only 3 out of 8 eyes relaxed in response to the drug.
Gimpel (1994) [13]	160 (20–30)	1 (2.5%)	NPA was measured monocularly by Donders’ push-up method. All measurements were assessed through the natural pupil.	At 30 min a net decrease in the subjectively assessed average AA of 1.22 D was obtained. At 60 min, a mean reduction of 1.39 D was recorded.
Eyeson-Annan(1998) [14]	47 (20–79)	3 (10%)	AA was measured binocularly using a near-reading chart at the 0.7 line. Two accommodation levels were measured: (1) the reading distance and (2) the near-chart distance at which the letters began to blur.	PHCl alone had no significant effect on the AA of the subjects, reporting mean values of 1.60 D and 1.57 D at 20 min and 40 min after instillation of dilating drops, respectively, in comparison with a baseline value of 1.53 D.
Culhane(1999) [2]	10 (20–28)	1 (2.5%)	Monocular dynamic AR were measured objectively, in target vergence over a 2- to 4-D range, using a continuously recording infrared optometer (4-mm artificial pupil).	PHCl allowed the accommodative system to track more accurately at low- and mid-temporal frequencies, optimizing then the AR.
Do (2002) [15]	10 (24–28)	n/a (2.5%)	Accommodative amplitude was measured subjectively with the push-up technique and objectively with the Hartinger Coincidence Refractometer.	All subjects showed a mean decrease of 17% in accommodative amplitude measured with the subjective push-up technique. Accommodative amplitude measured objectively with the Hartinger Coincidence Refractometer showed no decrease.
Ostrin (2004) [5]	5 anesthetized rhesus monkeys	0.2 mL (10%)	An electrode implanted in the monkeys’ midbrain was used to stimulate accommodation (this allows for a response that is not affected by pupil size or visual feedback). A Hartinger Coincidence Refractometer measured the AA, and infrared photorefraction was used to assess dynamic responses.	Although there were individual differences before and after the instillation of PHCl, these differences were not systematic, and within the resolution of the methods there were no significant effects of PHCl on accommodative amplitude, dynamics, or resting position.
Sarkar(2012) [16]	16 (21–30)	3 (2.5%, 5%, 10%)	Subjects watched a target displayed on liquid-crystal screens that were placed at 67 and 33 cm. The visual target was electronically switched between the two screens, once every 4 s, thereby creating an accommodative demand of 1.5 D (natural pupil and 8, 6, 4, 1 mm artificial pupils).	PHCl had a small but statistically significant negative impact on the response magnitude and peak velocity of accommodation but not that of disaccommodation. The reduction in accommodative performance is modest and does not carry a large clinical significance.
Richdale(2012) [17]	25 (18–40)	1 (2.5%)	Subjective measurements were obtained using the push-up to blur technique. Objective static AR was measured with an autorefractor. OCT was used to in vivo image the ciliary muscle in relaxed and accommodated states.	Maximum subjective AR was reduced by about 1 D. The drug did not affect the objectively measured AR. Muscle dimensions and contractility to a 4 D stimulus were not altered by the instillation of PHCl.
Bernal-Molina(2016) [18]	8 (n/a)	2 (10%)	Static accommodation (AA and AR) was assessed by a commercial aberrometer computing the stimulus-response curve from the wavefront obtained at different vergence. Dynamic accommodation was also assessed by measuring the AR at 10 Hz to a sinusoidally moving stimulus (3-mm artificial pupil).	Any effect was measured on static or dynamic accommodation when higher-order aberrations were not taken into account in the calculation of AR. As paraxial refraction depends mainly on the ciliary muscle, its function seems to be unaffected by PHCl.

AA: amplitude of accommodation; AR: accommodative response; D: diopters; FPA: far point of accommodation; min: minutes; n/a: not available; NPA: near point of accommodation; OCT: Optical Coherence Tomography; PHCl: Phenylephrine hydrochloride; RPA: resting point of accommodation.