performance and fertility (i.e., ability of female ratl to become pregnant). However, thele dOlel were hlghfy toXiC and had lignificant to,ic eflectl on the pregnanciel, and the lurvival and devefopment of the offlpring. Maternal tO'icity, pOllible occurrence of abnormahtiel and growth retardation Itarted at to timel the Alre,' clinical dOle.

Neurologic Dilturbancel and lupprellion of the Hypothalamic-Pituitary-Adrenal (HPA) a,il can occur with IYltemic e'polure to cortieolteroidl. However, given the very low IYltemic e'polure to loteprednol etabonate when uling Alre,' al directed, thele pOllible effectl are not likely.

Indocrine and Metabolism Glucocorticoid" mOltly when IYltemic e'polure occurs, decreale the hypoglycemic activity of inlulin and oral hypoglycernicl, 10 that a change in dOle of the antidiabetic drugl may be necellitated. In high dOlel, glucocorticoidl allo decreale the relponle to lomatotropin. The ulual dOlel of mineralocorticoidl and large dOlel of lome glucocortlcoidl caule hypokalemia and may e,aggerate the hypokalemic effectl of thiazidel and high-ceiling diureticl. In combination with amphotericin-B, they allo may caule hypokalemia. Glucocorticoidl appear to enhance the uleerogenrc effectl of non-steroidal anti-inflammatory drugl. They decrease the plalma level I of lalicylatel, and salicylism may occur on discontinuing steroids. Glucocorticoids may increase or decreale the eflectl 01 prothrombopenic anticoagulantl. Estrogens, phenobarbital, phenytoin and rifampin increale the metabolic clearance of adrenal Iteroidl and hence necellitate dOle adjultmentl. However, given the very low IYltemic "polure to loteprednol etabonate when uSing Air .. ' al directed, thele pOllible effectl are not likely.

tmmune Cortllol and the Iynthetic analogI 01 cortilol have the capacity to prevent or lupprell the development 01 the local heat, redne", Iwelling, and tendernell by which inflammation il recognIZed. At the mlcrolcoplC level, they inhibit not only the early phenomena of the inflammatory procell (edema, fibrin depolition, capillary dilation, migration of leukocytel into the inflamed area, and phagocytic activity) but allo the later manrfeltationl, luch al capillary prolileratlon, fibroblalt proliferation, depolition of collagen, and, Itililater, cicatrilatlon. ®!ilJI Trial Adverse Drug Reactions POllibly or probably related adverse eventl from two Phale III Itudiel are lilted below:

Alrex' 0_2'" Placebo N-133 N-135

SPICIAl SIN515 (IYI DtSORDIRS) tntraocular Pressure - elevation of 6 to 9mm Hg" 2% to 12%' 0% to 6%' - ele.ation of .10mm Hg 1 (1%) 1 (1%) Chemosis 6 (5%) 7 (5%) Yision Abnormal or Blurred 4 (3%) 5 (4%) Burning/Stinging. on instillation 3 (2%) 6 (4%) ftching lye 3 (2%) 3 (2%) Dry lye 2 (2%) 4 (3%) Burning/Stinging, not on instillation 2(2%) 211%J Ipiphora 1 (1%) 9 (7%) Dlscharae 1 (1%) 3 (2%) Foreign Body Sensation 1 (1%) 1 (1%) Discomfort lye 1 (1%) 0(0%) fnjection 1 (1%) 0(0%) lye Pain 1 (1%) 0(0%) Sticky lye 0(0%) 7(5%) Irythema Iyelids 0(0%) 2(1%) lye Disorder 0(0%) 2(1%)

BODY AS A WHOll Face Idema (HeadJ 1 (1%) 0(0%) Allergic Reaction 1 (1%) 0(0%)

MUSCUlOSKllITAl SYSTIM Twitching 0(0%) 1 (1%)

ror lOP rncrease 0 6 to 9 mm Hg, p,eale lee DelOW

One patient 10 the Alre,' group and one patient in the placebo group e'perienced increalel in lOP of >10 mm Hg. Among thele, one in each group had an lOP increale of > 15 mm Hg, reaching lOP valuel over 30 mm Hg. In both Itudiel, there were more patlentl With lOP increasel of 6 to 9 mm Hg in the Alre,' group than in the placebo group (lee table below). In Itudy A, among the patientl with lOP Increalel of 6 to 9 mm Hg, four reached an lOP value of 22 to 23 mm Hg, and one patient reached 29 mm Hg and wal dilcontinued (clinically Significant increale in lOP). All these five patientl were from the Alre,' groupl.

Incidence 01 lOP increases of 6 to 9 mm Hg from baseline (number of patientl and percentagel)

Duration of treatment Day 7 Day 14 Day 28

Alrex' Study-A 6 ~9%l 6 ~9%l 8 (12%) Study-B 3 5% 1 2% 4 (6%)

Placebo Study-A 0(0%) 4 (6%) 1 (2%) Study-B 0(%) 0(%) 0(%)

Due to the lample lize for each arm of the two phale III Itudiel in SAC, all eventl captured are greater than 1% of n.

SYMPTOMS AND TREATMINT OF OYIRDOSAGI For management of IUlpected accidental oral ingeltlon or drug overdole, conlull your regional pOllon control centre. No calel of overdole have been reported. Full Product Monograph available for heallh profellionafl at: http://www.baulch.ca

BAUSCH+LOMB

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,. flO) Denote trademarks of Bausch & lomb Incorporated or itl affiliatel.

CALENDAR OF EVENTS

September 9-1 I, 2010 28th Annual Meeting of the European Society of Ophthalmic Plastic and Reconstructive Surgery Munich, Germany http://www.esoprs20 1 O,org/

September 10-11, 2010 Adantic Eye Symposium Halifax, NS http://www.atlanticeye.ca

September 16--20, 2010 APAO-AAO Joint Congress Beijing, China http://www,apao20 1 Obeijing,org/indexOO_1 ,shtml

September 22-25,2010 XIth Meeting of the International Strabismological Association Istanbul, Turkey http://www,isa20 1 O,org/

September 24-26, 2010 Ophthalmic Anesthesia Society 24th Annual Meeting Chicago,IL http://www.eyeanesthesia.org/

September 30-0ctober 2, 2010 Sally Letson Symposium Pediatric Ophthalmology and Genetics Update Ottawa, ON http://www.eyesite.ca/SallyLetson/

October 3-5,2010 International Conference on Physician Health: "Physician Health and Resiliency in the 21st Century" Chicago,IL http://www,ama-assn ,org/ ama/ pub/ ph ysician-resources/ physician-health.shtml

October 16--19, 2010 AAO-MEACO Joint Meeting Chicago,IL http://www.aao.org/ meetings/ann uaLmeeting/

October 21-24, 2010 23rd International Congress of German Ophthalmic Surgeons Hamburg, Germany http://www.doc-nuernberg.de/

October 22, 2010 35th Annual Pediatric Ophthalmology Day Sainte-Justine Montreal, Quebec http://www.phamel.com/jop2005/flash.htm