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Washout Periods for Brimonidine
for latanoprost (n ؍ 17) was 4.4 ؎ 3.2 weeks (P ؍ .24).
0.2% and Latanoprost 0.005%
In all but one patient, brimonidine returned to baseline
by 5 weeks and latanoprost returned by 8 weeks.
William C. Stewart, MD, Keri T. Holmes, and
CONCLUSION: After discontinuing latanoprost or bri-
Mark A. Johnson
monidine, a wide variation exists in washout times among
individuals, with latanoprost demonstrating a trend to a
PURPOSE: To evaluate the intraocular pressure washout
longer washout period.
(Am J Ophthalmol 2001;131:
time after discontinuing brimonidine 0.2% twice daily
798 –799. 2001 by Elsevier Science Inc. All rights
and latanoprost 0.005% once every evening.
reserved.)
METHODS: We discontinued brimonidine or latanoprost
in a masked fashion from primary open-angle glaucoma
or ocular hypertensive patients. The intraocular pressure
was measured twice weekly until patients returned to
THE WASHOUT TIMES FROM THE EYE OF AN OCULAR hypotensive medication after discontinuing its use may untreated baseline.
be important for several reasons. First, when substituting RESULTS: In 32 patients, the mean longest eye washout
medications, a physician should know how long the time for brimonidine (n ؍ 15) was 3.3 ؎ 3.0 weeks and
previous medicine may last to assess the efficacy of the newproduct. Second, for clinical trials, it is important to know Accepted for publication Nov 29, 2000.
the washout period of a medication to determine when an From Pharmaceutical Research Corporation, Charleston, South Caro- untreated baseline should be measured. Unfortunately, lina (W.C.S., K.T.H.), and the Carolina Eye Institute, University of little information is available generally on washout periods South Carolina School of Medicine, Columbia, South Carolina(W.C.S.), Atlanta Research Company LLC, Atlanta, Georgia (M.A.J.).
Supported by Pharmacia, Inc., Peapack, NJ.
This trial was part of a protocol that has been reported Inquiries to William C. Stewart, MD, Pharmaceutical Research Cor- separately.1 After exit from the previous trial, patients poration, 1639 Tatum St, Charleston, SC 29412-2646; fax: (843)762-7444; e-mail: [email protected] were discontinued from their masked study medication, FIGURE 1. Average trough washout pressure from treated baseline after discontinuing latanoprost (squares) or brimonidine
(diamonds). Once a subject returned to baseline, the pressure in the graph is recorded at 0 mm Hg at each subsequent visit. The
“n” values show the number of subjects not returned to baseline for each time point. The graph includes the “longest eye” washout
times only. The trough pressure decrease from baseline at Week 0 was 3.9 ؎ 2.4 mm Hg for brimonidine and 8.5 ؎ 4.3 mm Hg
for latanoprost. IOP ؍ intraocular pressure.
which was either brimonidine 0.2% twice daily or latano- Acute Full-Thickness Macular Hole
prost 0.005% every evening. Patients were followed in a After Uncomplicated
masked fashion with trough (8 AM) Goldmann applanationtonometry in both eyes twice weekly (approximately every Phacoemulsification Cataract Surgery
3 to 4 days), for up to 3 months, until the intraocular Julian A. Patterson, FRCS, FRCOphth,
pressure returned to the 8 AM trough baseline (Ϫ1 mm Hg Eric Ezra, FRCS, FRCOphth, and
Zdenek J. Gregor, FRCS, FRCOphth
Of the 32 subjects in this trial, 15 were discontinued from brimonidine and 17 latanoprost. Ten patients hadocular hypertension, and 22 had primary open-angle glau- PURPOSE: To report the occurrence of a full-thickness
macular hole in the early postoperative period after
coma. Eleven subjects were white, and 22 were black; 16 uncomplicated phacoemulsification cataract surgery.
were women and 16 were men. The average age was METHODS: Retrospective analysis of a consecutive series
of eyes referred for treatment of a full-thickness macular
The mean longest eye washout time for brimonidine was hole after uncomplicated phacoemulsification cataract
3.3 Ϯ 3.0 weeks, and for latanoprost was 4.4 Ϯ 3.2 weeks surgery.
(P ϭ .24). The mean shorter eye washout time for RESULTS: In a 4-year period, five eyes with acute full-
brimonidine was 2.5 Ϯ 1.8 weeks and for latanoprost was thickness macular hole after uncomplicated phacoemulsifi-
3.1 Ϯ 3.2 weeks (P ϭ .38). By 3 weeks, approximately half cation cataract surgery were examined. Metamorphopsia
of the patients in each group had reached baseline. The and vision loss had occurred 2 to 8 (mean, 4.4) days after
mean intraocular pressure had normalized by week 5 for phacoemulsification. All eyes had attained normal corrected
brimonidine and week 8 for latanoprost, except one vision on day 1 postoperatively. A stage 2 full-thickness
patient in each group who completed 3 months without macular hole was present in four of the five, and a stage 3
returning to baseline. The average pressure decrease from full-thickness macular hole in one of the five eyes with
baseline at each time point after discontinuation is shown acuities of 20/60 –20/120 (median, 20/80). All five eyes
in Figure 1. No adverse events were reported during the had successful closure with early primary full-thickness
macular hole surgery with visual improvement to 20/20 –
In a previous study, Alm and associates indicated that 20/60 (median, 20/40).
latanoprost still retained an ocular hypotensive effect 2 CONCLUSION: Full-thickness macular hole may occur
weeks after discontinuation of the medicine.2 However, rarely during the early postoperative period after uncom-
beyond 2 weeks after discontinuing latanoprost, the in- plicated phacoemulsification, and early diagnosis and
traocular pressures were not measured. The washout period full-thickness macular hole surgery carries a favorable
for brimonidine (an ␣ adrenergic agonist) and epineph- prognosis. The mechanisms underlying macular hole
rine (␣- and ␤-adrenergic agonist) in clinical protocols is formation in these eyes are unclear.
(Am J Ophthalmol
usually 2 weeks. However, we have not been able to 2001;131:799 – 800. 2001 by Elsevier Science Inc.
substantiate this 2-week washout from clinical data.
All rights reserved.)
The results of this study showed a statistical similarity for washout times between groups. However, comparedwith brimonidine, a trend existed to a slightly longer mean ALTHOUGH VARIOUS RETINAL COMPLICATIONS, SUCH as aphakic/pseudophakic cystoid macular edema,1 pe- washout period, and among individuals, washout periods ripheral retinal breaks, and retinal detachment,2,3 have were often greater than 1 month for latanoprost. Both been well described after cataract surgery, and they are medications demonstrated a wide variation of the washout thought to be increased by intraoperative breach of the posterior capsule and late posterior capsulotomy for pseu- This study suggests that after discontinuing latanoprost dophakic posterior capsular opacification,1–3 the underly- or brimonidine, a wide variation exists in washout times ing mechanisms remain unclear.1–3 Full-thickness macular among individuals, with latanoprost demonstrating a trend hole formation has also been described after uncompli- cated Nd:YAG laser posterior capsulotomy (PC),4,5 wheretransmission of forces through the vitreous has been implicated,4,5 but its occurrence after uncomplicated cat- 1. Stewart WC, Day DG, Stewart JA, Schuhr J, Latham KE. The efficacy and safety of latanoprost 0.005% once daily versus Accepted for publication Nov 15, 2000.
brimonidine 0.2% twice daily in open-angle glaucoma or From the Vitreoretinal Unit, Moorfields Eye Hospital, London, United Supported by grants 301 and 311 from Guide Dogs for the Blind 2. Linden C, Nuija E, Alm A. Effects on IOP restoration and Association and Moorfields Special Trustees.
blood-aqueous barrier after long-term treatment with latano- Inquiries to Eric Ezra, FRCS, FRCOphth, Massachusetts Eye and Ear prost in open angle glaucoma and ocular hypertension. Br J Infirmary, Retina Service, 243 Charles St, Boston, MA 02114; tel: (617) 573-4008; fax: (617) 573-3698; e-mail: [email protected]

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