The Antimydriatic Effect of Brimonidine 0.15% on the Dark-adapted Pupil in Dark Brown Irides

Seung Soo Rho; Hong Seok Yang; Ho Min Lew; Jae Hong Ahn

doi:10.3341/jkos.2008.49.10.1649

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Soo Rho, Seok Yang, Min Lew, and Hong Ahn: The Antimydriatic Effect of Brimonidine 0.15% on the Dark-adapted Pupil in Dark Brown Irides

Original Article

Pediatr Emerg Med J 2008;49(10):1649-1657.

Published online: 7 September 2008

DOI: https://doi.org/10.3341/jkos.2008.49.10.1649

The Antimydriatic Effect of Brimonidine 0.15% on the Dark-adapted Pupil in Dark Brown Irides

Seung Soo Rho, M.D, Hong Seok Yang, M.D, Ho Min Lew, M.D, Jae Hong Ahn, M.D

Department of Ophthalmology, Ajou University School of Medicine, Suwon, Korea

Address reprint requests to Jae Hong Ahn, M.D. Department of Ophthalmology, Ajou University School of Medicine #San 5 Wonchon-dong, Youngtong-gu, Suwon 442-721 Korea Tel: 82-31-219-567, Fax: 82-31-219-5259, E-mail: chrisahn@ajou.ac.kr

Received 10 July 2008 Accepted 17 October 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To analyze the effect of the daily use of brimonidine tartrate 0.15% on the dark-adapted pupil diameter in dark brown irides.

Methods

Twenty-five healthy volunteers administered brimonidine tartrate 0.15% to their right eyes once daily for 3 weeks. Infrared digital photographs of the pupil were taken before administration and 1 hour and 4 hours after administration after dark adaptation (at <0.1 lux ambient illumination for 5 minutes). The diameters of both pupils were measured on the first day, on administration days 7 and 21, and on washout day 7.

Results

Four hours after the first administration, pupils showed a decrease of 0.95±0.74 mm, 1.03±0.94 mm, 0.61±0.85 mm on the first day, administration day 7, and administration day 21, respectively ( p<0.01), compared with baseline data. The anti-mydriatic effect of brimonidine was sustained for 3 weeks, but the proportions of the eyes showing a reduction in pupil diameter by 0.5 mm or more were 84%, 76%, 68%, and 52% at 4 hours on the first day, administration days 7 and 21, and washout day 7, respectively.

Conclusions

The anti-mydriatic effect of the daily use of brimonidine 0.15% on dark brown irides in a scotopic condition is maintained during the instillation period but has a tendency to fade over time. This point should be considered when using this compound as a miotic agent.

Keywords: Anti-mydriatic effect, Brimonidine tartrate 0.15%, Brown iris, Dark-adapted pupil

References

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Figure 1.

The effect of brimonidine tartrate 0.15% on the pupil size under scotopic condition. Infrared digital photography was taken under scotopic condition (less than 0.1 lux) before (left column) and 1 hour and 4 hour (right column) after instillation of brimonidine on start day, administration days 7, 21, and washout day 7. The pupil diameter was decreased after instillation of brimonidine compared to before adminstration on each day. The pre-administration diameter of pupil on administration days 7 (6.33±0.73 mm) and 21 (6.18±1.07 mm) was also decreased compared to the baseline pupil diameter of start day(6.66±0.92mm). Note that the pre-administration diameter of pupil on washout day 7 was increased when compared to the baseline of start day.

Table 1.

Comparison of scotopic pupil diameter (PD) of the right eye in the order of time

Measure time		PD (range)	^Δ PD* ( p-value)	^Δ PD^† ( p-value)
	before	6.66±0.92 mm (4.32~8.28)
Start day	1 hr	5.76±1.10 mm (2.48~7.36)	0.90±0.75 mm (<0.001)	0.90±0.75 mm (<0.001)
	4 hr	5.72±1.07 mm (3.16~7.14)	0.95±0.74 mm (<0.001)	0.95±0.74 mm (<0.001)
	before	6.33±0.73 mm (5.07~7.43)		0.33±0.72 mm (0.029)
Administration day 7	1 hr	5.57±0.92 mm (4.14~7.16)	0.76±0.56 mm (<0.001)	1.09±0.79 mm (<0.001)
	4 hr	5.63±1.05 mm (3.30~7.50)	0.70±0.63 mm (<0.001)	1.03±0.94 mm (<0.001)
	before	6.18±1.07 mm (3.39~7.97)		0.48±0.88 mm (0.011)
Administration day 21	1 hr	5.98±1.25 mm (2.99~7.98)	0.20±1.12 mm (0.384)	0.68±0.73 mm (<0.001)
	4 hr	6.06±0.99 mm (3.79~8.10)	0.12±0.70 mm (0.392)	0.61±0.85 mm (0.002)
	before	6.72±0.95 mm (4.33~8.13)		-0.06±0.64 mm (0.672)
Washout day 7	1 hr	5.93±1.28 mm (2.72~7.97)	0.79±0.79 mm (<0.001)	0.74±0.78 mm (<0.001)
	4 hr	6.00±1.06 mm (3.68~8.13)	0.71±0.67 mm (<0.001)	0.66±0.71 mm (<0.001)

^Δ PD=baseline PD-PD after instillation of brimonidine

^* Each data was compared with the data before administration at respective day

^† Each data was compared with the data before administration at start day.

Table 2.

The proportion of significant anti-mydriasis and mydriasis

Measure time		Right eye		Left eye
		Significant	Significant	Significant	Significant
		anti-mydriasis*	mydriasis^†	anti-mydriasis*	mydriasis^†
start day	1 hr	64% (16)	0% (0)	20% (5)	0% (0)
	4 hr	84% (21)	4% (1)	12% (3)	8% (2)
	before	36% (9	8% (2)	12% (3)16% (4)
administration day 7	1 hr	76% (19	0% (0)	40% (10	8% (2)
	4 hr	76% (19	8% (2)	28% (7)	12% (3)
	before	36% (9)	12% (3)	24% (6)	16% (4)
administration day 21	1 hr	68% (17	8% (2)	16% (4	0% (0)
	4 hr	68% (17)	12% (3)	20% (5)	12% (3)
	before	12% (3)	24% (6)	28% (7)	12% (3)
washout day 7	1 hr	52% (13)	4% (1)	24% (6	0% (0)
	4 hr	52% (13)	4% (1)	24% (6	8% (2)

( )=number of eyes

^* pupil size is 0.5 mm smaller than baseline data of start day

^† pupil size is 0.5 mm larger than baseline data of start day.

Table 3.

Comparison of scotopic pupil diameter (PD) of the left eye in the order of time

Measure time		PD (range)	^Δ PD* ( p-value)	^Δ PD^† ( p-value)
	before	6.73±0.97 mm (3.96~8.16)
Start day	1 hr	6.51±1.10 mm (3.46~8.61)	0.22±0.41 mm (0.014)	0.22±0.41 mm (0.014)
	4 hr	6.61±0.86 mm (3.58~8.10)	0.12±0.44 mm (0.173)	0.12±0.44 mm (0.173)
	before	6.80±0.67 mm (5.23~7.95)		-0.07±0.55 mm (0.546)
Administration day 7	1 hr	6.39±0.91 mm (4.31~7.83)	0.41±0.54 mm (0.001)	0.34±0.49 mm (0.002)
	4 hr	6.59±0.77 mm (4.08~7.88)	0.21±0.47 mm (0.034)	0.15±0.75 mm (0.343)
	before	6.61±0.92 mm (3.60~8.28)		0.13±0.64 mm (0.340)
Administration day 21	1 hr	6.49±1.07 mm (3.61~8.26)	0.11±0.76 mm (0.464)	0.24±0.40 mm (0.007)
	4 hr	6.67±0.70 mm (4.45~7.94)	-0.06±0.56 mm (0.589)	0.06±0.79 mm (0.691)
	before	6.66±0.78 mm (4.99~8.16)		0.07±0.65 mm (0.590)
Washout day 7	1 hr	6.47±1.16 mm (3.28~8.10)	0.19±0.65 mm (0.155)	0.26±0.53 mm (0.021)
	4 hr	6.56±0.83 mm (4.15~7.89)	0.10±0.44 mm (0.258)	0.17±0.74 mm (0.259)

^Δ PD=baseline PD-PD after instillation of brimonidine

^* Each data was compared with the data before administration at respective day

^† Each data was compared with the data before administration at start day.

Table 4.

Comparison with other articles about brimonidine effect on pupil size

Author	Pupil	Check	Baseline	Age	Measure	Brown
	change	time	pupil (mm)	(mean age, years)	equipment	iris ratio
McDonald (2001)^*	-1.78 mm	4 hr	5.8±0.7	34.6	Colvard	n-c
Brown (2004)	-1.63 mm	4-6 hr	n-c	31.0	Digital cam	n-c
Kesler (2004)^*	-1.65 mm	4 hr	6.22±0.73	30.2	Colvard	55.6%
Thordsen (2004)	-1.50 mm	4 hr	7.0±0.2	29.0	Colvard	n-c
Marx-Gross (2005)	-2.24 mm	3 hr	6.74	n-c	Procyon	n-c
Current study	-0.95 mm^†	4 hr	6.66±0.92	24.8	Digital cam	100%

^* Brimonidine 0.2% (all others 0.15%)

^† On start day, at 4 hours after first administration; n-c=not commented; Colvard pupillometer (Oasismedical, Glendora, California, USA); Procyon pupillometer (Haag-Streit, UK).

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