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number ofbottles dispensed ineach category per year. Thecom-bination therapies were classified as follows: Combigan (0.2%brimonidine tartrate and 0.5% timolol maleate) as an 2-agonist, Cosopt (dorzolamide hydrochloride and 0.5% timo-lol maleate) as a topical CAI, Timpilo (2% or 4% pilocarpinehydrochloride and 0.5% timolol maleate) as a parasympatho-mimetic, and Xalacom (0.005% latanoprost and 0.5% timololmaleate) as a prostaglandin analogue. The number of ophthal-mologists and optometrists in Ontario per year from 1992through 2004 was obtained from the Ontario Medical Asso-ciation and the Ontario Association of Optometrists.

Statistical analyses included regression analysis, with filtra-tion surgery rate as the outcome variable, and Pearson corre-lation matrix between pairs of variables. The variables consid-ered were filtrationsurgery rate, time in years,and total numberof glaucomamedicationsdispensedoverall andwithin eachnewmedication group. One bottle of any of the medications was1 months supply. Other variables considered were number of ophthalmologists and optometrists. The filtrationsurgery rateswere used as the outcome variable.

The t statistic used to calculate confidence intervals (CIs)is based on 12 years of data, but the percentage of drugs dis-pensed for each of the new drugs is zero before 1996. This fact

will distort the estimated regression coefficients for year andpercentage of total drugs because the regression assumed astraight-line relationship.

RESULTS

The total number of trabeculectomies increased from1735 in 1992 to 2647 in 1997 (52.6% increase) andthen remained stable for the remainder of the study(Figure 1 ). During this time, the population in On-tario increased from 10257 047 in 1992 to 12246600in 2004 (19.4% increase; 1.5% increase per year). Forthose aged 40 years and older, the population increasedfrom 4136704 in 1992 to 5556600 in 2004 (34.3% in-

crease; 2.7% increase per year). The estimated preva-lence of POAG increased from 51 727 (0.5% of the totalpopulation and 1.25% of the population older than 40years) in 1992 to 69 154 (0.57% of total population and1.25% of the population older than 40 years) in 2004(33.7% increase; 2.4% increase per year). The numberof trabeculectomies per 1000 individuals at risk forPOAG increased from 33.5 in 1992 to 46.2 in 1996(37.7% increase; 6.6% increase per year) and thensteadily decreased to 38.2 in 2004 (17.0% decrease;2.7% decrease per year) ( Figure 2 ).

Newmedications for the treatment of glaucoma wereintroduced in Ontario as follows: dorzolamide hydro-chloride,May1996; 0.005% latanoprost, June1997; 0.2%

brimonidine tartrate, November 1997; Cosopt,May1999;travaprost, November 2001; bimatoprost, May 2002;Xalacom, October 2002; andCombigan,December 2003.The total number of prescriptions for glaucoma medi-cations dispensed in Ontario increased from 766 000 in1992 to 1 466543 in 2004 (91.5% increase; 10.5% in-creaseper year) ( Figure3 ). For 1992and 1996, -block-ers represented the greatest market share (59.5% and52.7%, respectively) followed by parasympathomimet-ics (24.8% and 28.2%, respectively) and, to a lesser ex-tent, sympathomimetics andoral CAIs. In 1997, thenewglaucoma medications, topical CAIs and prostaglan-dins, represented 16.2% of dispensedglaucomamedica-tions. In 1998, with the introduction of 2-agonists, the

new antiglaucoma medications accounted for 26.9% of dispensed glaucoma therapy. In 2004, 2-agonists ac-counted for 64.3% of the dispensed glaucoma medica-tions in Ontario.

Thehighest increaseoccurred in theprostaglandinana-logue category, and specifically with latanoprost, whichincreased from 12000 bottles when introduced in 1997to529 600 bottles in 2004, a 44-fold increase ( Figure4 ).In 1998, latanoprost accountedfor5.7% of the total num-berof glaucoma medicationsdispensedand increased to36.1% in 2004.

3000

2000

2500

1500

1000

500

01992 199519941993 1996 1997 1998 1999 2000 2001 2002 2003

Year

N o

. o

f T r a

b e c u

l e c t o m

i e s

Figure 1. Number of trabeculectomies per year in Ontario from April 1, 1992,through March 31, 2004.

48

44

46

42

40

36

38

3432

301992 199519941993 1996 1997 1998 1999 2000 2001 2002 2003

Year

N o

. o

f T r a

b e c u

l e c t o m

i e s

Figure 2. Number of trabeculectomies per year per 1000 population at riskfor primary open-angle glaucoma.

1600

1200

1400

1000

800

6001992 1994 1996 1998 2000 2002 2004

Year

N o

. o

f B o t t

l e s (

i n T h o u s a n

d s

)

Figure 3. Number of glaucoma medications dispensed in Ontario per yearfrom April 1, 1992, through March 31, 2004.

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Thedata were analyzed forcorrelations between timein years, filtration surgery rates, cataract surgery rates,total medications dispensed, and each new medicationgroup ( Table 1 ). There was a high positive correlationbetween time in years and both the increasing numberof total medications dispensed and each new medica-

tion group. There was a nonsignificant ( P=.88) nega-tivecorrelation between filtration surgery ratesand totalmedications dispensed ( r =0.05). However, when eachgroup wasevaluatedseparately, there wasa stronger, al-though not significant, negative correlation between fil-tration surgery rates and dispensed prostagladins(r =0.35; P=.27). The correlation for 2-agonists was0.23 and for topical CAIs, 0.06, which were alsonot sig-nificant. The total glaucoma medications dispensed ratehad a high positive correlation with every new medica-tion group.

Regression analysis ( Table 2 ) indicated no evi-dence of an association between the filtrationsurgery rateand the number of glaucoma medications dispensed be-

fore 1997 ( P=.23; 95% CI, 0.002 to 0.006). There wasa slight trend between filtration rate and time in years(P=.07; 95% CI, 0.74 to 10.37). There was no evi-dence of an association between filtration surgery rateand time in years, nor was there for filtration surgeryrate and the number of glaucoma medications dis-pensed after 1997 ( P=.25; 95% CI, 3.25 to 1.12 andP=.87; 95% CI, 0.001 to 0.0031, respectively).

Regression models were used to examine the associa-tion of specificdrug classes as a percentage of totalmedi-cations dispensed, controlling for overall drug dis-

pensed rate and year ( Table 3 ). We found a strongrelationship between the decreasing numberof trabecu-lectomies and the increasing dispensed rate of prosta-glandin analogues ( b=0.63; P .001; 95% CI, 0.87 to0.40). There wasno evidence of association between thedecreasing number of trabeculectomies and the ratesfor CAI (b=0.41; P=.31; 95% CI, 0.47 to 1.31) and for

2-agonists ( b=0.87; P=.19; 95% CI, 2.28 to 0.53).Thenumberofophthalmologists inOntariovaried little

during this time, increasing from 409 in 1992 to 431 in1997 (5.4% increase)andthen decreasingto 419 in 2004(2.9% decrease). Despite this increase and decrease, thenumber of ophthalmologists per million population peryear isstronglyassociated ( r =0.87) with thefiltration sur-gery rateandstrongly negatively associated with the totalnumber of medications dispensed ( r =0.99) after 1997(Table 1).

The number of optometrists practicing in Ontario hasvariedmore, increasing from857 in1992 to1365 in2004(59.3% increase; 4.0% increase per year). The numberof optometrists per million population per year is nega-tively associated( r =0.93) with thefiltrationsurgery rateandassociated with the total numberof medications dis-pensed ( r =0.94) after 1997 (Table 1).

COMMENT

There has been a substantial decrease in the number of trabeculectomies in Ontario coinciding with the intro-duction of medications for the treatment of glaucoma inDecember 1996. This change highly correlated with theintroduction of prostaglandin analogues and thedecreas-

ingnumber of ophthalmologists from1997 through2004.Previous publications of the trends in glaucoma sur-gery showed a 15% to 73% decrease in the number of glaucoma surgical procedures across various periodsfrom 1994 through 2003. 2,4,5,20,21 The medical system inCanada is government funded and managed provin-cially. Virtually all residents have a provincial healthcard that must be presented to receive medical servicesfunded by the provinces; therefore, there is an accurateregistry of all surgical procedures performed on Cana-dian residents.

600

400

500

300

200

100

0 1992 1995 1998 2001 2004Year

N o

. o

f B o t t

l e s

( i n

T h o u s a n

d s )

Prostaglandins

-Agonists

Topical CAIs-Blockers

Parasympathomimetics

Sympathomimetics

System CAIs

Figure 4. Number of bottles (in thousands) of glaucoma medicationsdispensed in Ontario from 1992 through 2004 according to drug class.CAI indicates carbonic anhydrase inhibitor.

Table 1. Correlations ( r Values) Between Different VariablesRelated to Filtration Surgery Rate, AntiglaucomaMedications, and Cataract Surgery Rate

Variable Year

FiltrationSurgery

RateMedicationsDispensed

Year 1.0Filtration surgery rate 0.01 1.0Medications dispensed 0.98 0.05 1.0Prostaglandin analogue per 100 0.91 0.35 0.89Carbonic anhydrase inhibitor per 100 0.90 0.06 0.92

2-Agonist per 100 0.89 0.23 0.94Ophthalmologists rate* 0.95 0.87 0.99Optometrists rate* 0.998 0.93 0.94

* Indicates rate during 1997 and thereafter.



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We found that the total number of trabeculectomiesin Ontario increased by 52.6% from 1992 through 1997and then remained stable for the remainder of the study(Figure 1).Wecalculated theestimatedpopulation at riskof having glaucoma in Ontario by using a composite

POAGprevalencecurve.7-9

When wecorrected forchangesin the population, we found that the number of trabecu-lectomies per 1000 individuals at risk for POAG in-creased by 37.7% from 1992 to 1996 and then steadilydecreased by 17.0% to 2004 (2.7% decrease per year),similar to the trends indicated in other studies. 2,4,5,20-23

When changes are observed in the volume of a givensurgical procedure, multiple factors are potentially re-sponsible, includingchanges in disease management, ac-cessibility to operatingroomtime, reimbursement rates,incidence and prevalence of a disease, and changes in pa-tient and physician perceptions regarding treatment op-tions. Paikal et al 4 proposed that the introduction of bri-monidine and latanoprost could affect the rate of

trabeculectomiesand trabeculoplastiesperformed. In Scot-land, Bateman et al 2 found an increase of 24.9% in pre-scribed glaucoma medications per 1000 population es-timated to have glaucoma from 1994 through 1999. By1999, only the beginning of the effect of these medica-tions would be realized. In a recent study published inAustralia, thenumber ofprescriptions issuedto treat glau-comaincreased by73.2%from1992to2003. 5 In theNeth-erlands, van der Valk et al 21 found a decrease of 45% inthe number of glaucoma surgical procedures from 1997(the introduction year of topical CAIs) until 2000. From

2000 on, the number of surgical procedures stabilized.The total number of prescriptions increased by 20% in1999 compared with 1998 in the Dutch study.

We found an increaseof 91.5%in the number of glau-coma medications prescribed in Ontario from 1992

through 2004. During this time, the estimated preva-lence of glaucoma in the population of Ontario in-creased 33.7%. From 1992 through 1996, the total num-ber of glaucoma medications dispensed in Ontarioincreased 22.3%. After the introduction of several newglaucoma medications since December 1996, the num-ber of medications dispensed increased by 56.6% until2004. Explanations for the increase in the total numberof glaucoma medications dispensed include the im-proved and maintained ocular hypotensive efficiency of the newer glaucoma medications, improved compli-ance, and more patients being treated with lower targetpressures. 2

Walland 5 presented a decrease of 57.6% in rates of tra-

beculectomysurgery duringthe studied periodand a 61.7%decrease if measured from the peak rate in 1996. He as-sumed that increased medical treatment mirrored the de-crease in surgical procedures but was unable to correlatethistrend statistically. Ourfindingsthat prescribingchangeshave been accompanied by a reduction in the number of trabeculectomies in the same period suggest an associa-tion with the effectiveness of the new glaucoma medica-tions that has been sustained across the period.

Our data were analyzed statistically for correlationsbetween time in years, filtrationsurgery rates, total medi-

Table 3. Regression Analyses for the Association Between Specific Drug Groups and Filtrations Surgery Rate,Controlling for Year and Total Drugs Dispensed

Regression Model CoefficientStandard

Error t Statistic P Value95% Confidence

Interval

Prostaglandin analoguesYear 3.87 0.83 4.65 .002 1.95 to 5.80Drugs per million 0.003 0.001 2.56 .03 0.005 to 0.001Percentage that are prostaglandin analogues 0.63 0.10 6.33 .001 0.87 to 0.40

Carbonic anhydrase inhibitorsYear 1.98 1.76 1.13 .29 2.07 to 6.04Drugs per million 0.004 0.003 1.40 .20 0.01 to 0.002Percentage that are carbonic anhydrase inhibitors 0.41 0.38 1.08 .31 0.47 to 1.31

2-AgonistsYear 0.35 1.89 0.19 .88 4.01 to 4.71Drugs per million 0.001 0.003 0.39 .71 0.007 to 0.01Percentage that are 2-agonists 0.87 0.61 1.43 .19 2.28 to 0.53

Table 2. Regression Analyses for Filtration Surgery Rates, Year, and Total Prescriptions Dispensed of Glaucoma Medications

Regression Model CoefficientStandard

Error t Statistic P Value95% Confidence

Interval

Data for 1996 and before (n = 6)Year 4.82 1.74 2.76 .07 0.74 to 10.37Drugs per million population 0.005 0.003 1.50 .23 0.005 to 0.01

Data for 1997 and after (n = 7)Year 1.06 0.79 1.35 .25 3.25 to 1.12

Drugs per million population 0.0002 0.001 0.17 .87 0.01 to 0.01



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cations dispensed, and each new medication group(Table 1).The correlations among the percentagesof dif-ferent drugs were high, which may be because the val-ues of each are zero before 1996 before they were intro-duced. The filtration surgery rates were not stronglyassociated with any one of the other variables, r 0.35in all cases. Our statistical analysis across the 12 yearsof the study revealed that the filtration rate was notstrongly associated with drug use, controlling for year.

Analyzingthe data separately for 1992 to 1996 and from1997 to 2004 showed a trend of increased filtration sur-gery rate before1997anddecreasedfiltrationsurgeryrateafter1997. This analysis, however, is limitedby thesmallnumber of observations.

We used regression models to examine the associa-tion of specific medication classesas a percentage of totalmedications dispensed, controlling for overall medica-tions dispensed and year (Table 3). We found a strongcorrelation between the decreasing number of trabecu-lectomies and the increase in medications dispensed.These analyses look at the role of the changing percent-ageof the total medicationsdispensedattributableto eachof the 3 classes of new glaucoma medications, control-

ling for year and total medications dispensed. Only themodel including prostaglandins was strongly signifi-cant ( P .001; 95% CI, 0.87 to 0.40). However, be-cause the increase in prostaglandins was large (44times),this result, although statistically significant,maynothavebeen due to a cause-and-effect relationship.

In contrast to thenumber of trabeculectomies, thean-nual number of cataract surgical procedures per 1000population with cataract in Ontario increased from 64.6in 1992 to 109.4 in 2003 (69.3% increase; 6.0% increaseper year). 24 These data suggest that economic influ-ences of thehealth systemsuch as possibledecreasedac-cess to operating room facilities cannot be responsiblefor the trends found for trabeculectomies.

Paikal et al4

and Strutton and Walt23

included eco-nomic influences orchanges indisease management (otherthan those related to the new medications) as factors thatmay influence the glaucoma surgery trend. They showedthat the changes in reimbursement rates in the US Medi-care population were not responsible for the decrease inglaucoma surgical procedures in this population.

In Ontario, the reimbursement rates for cataract andfiltration surgery did not dramaticallychange from1992to 2004. Filtration procedures in Ontario are reim-bursedat approximately 70% of the rate for cataract sur-gery.Thesurgicaltime is longer than that of cataract sur-gery andhas a more demandingpostoperative schedule,which may have some influence on the rates, although

this is hard to prove.Strutton and Walt 23 suggested other explanations forthe reduction in glaucoma surgical procedures: changesin disease incidence or prevalence and the possibilitythat the individuals who needed the procedures re-ceived them and this trend is simply the supply dimin-ishing across time. In our study, using the censusdata 6,25 to estimate the prevalence of POAG, we foundan increase of 33.7% in the number of individuals atrisk for POAG. Therefore, we should expect to have anincrease in the number of surgical procedures. The sig-

nificant increase in number of glaucoma medicationsdispensed further weakens the hypothesis of supply di-minishing across time.

Another factor that may affect the filtration surgeryrates is the number of ophthalmologists and optom-etrists. We found a strongcorrelation between the num-ber of ophthalmologists in Ontario and the decreasingfiltration surgery rates after 1997. These data were morecomplicated when we used regression analysis to see if

the supply of ophthalmologists was associated with therelationbetween trabeculectomies and the proportion of prostaglandin analogues among thedrugs usedafter 1997.

The growing number of optometrists probably hassome influence on the referral of patients with glau-coma. Wefound a negative association between thenum-ber of optometrists and the decreasing number of trab-eculectomies.

There are some limitations to this study. The filtra-tion surgerynumbers include allfiltrationproceduressuchas trabeculectomies, combined cataract and trabeculec-tomy, andseton surgical procedures. In addition, we arenot able to discriminate on the basis of glaucoma diag-nosis.To understand theserates,one must consider popu-

lation dataandchanges inagedistribution. BecausePOAGrepresents a significant proportion of glaucoma cases andprevalence estimates havebeendefinedpreviously for thisgroup, we thought this would be a reasonable denomi-nator toconsider,understandingthe limitations.Wefounda 17.0% decrease in thenumberof trabeculectomies sincethe introduction of new medications for the treatmentof glaucoma in December 1996. This decrease was sus-tained until March 2004, the most recent data available. We found a strong statistical correlation ( P .001) be-tween the increasing number of new medications dis-pensed (with the prostaglandin medications represent-ing the majority of newly dispensed treatments) and thedecreasingnumber of trabeculectomies. The most likely

explanation for this change is the improved effective-ness of ocularhypotensive therapy. It remains to be seenif this trend will be maintained across time.

Submitted for Publication: October 17, 2005; final re-vision received January 30, 2006; accepted March 14,2006.Correspondence: Rony Rachmiel, MD, Toronto West-ern Hospital, New East Wing, 399 Bathurst St, 6-405,Toronto,Ontario,Canada M5T 2S8([email protected]).Financial Disclosure: The authors donot have any com-mercialorproprietary interest inanyof theproducts men-tioned in the article.

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