# Trends in Glaucoma Medication Expenditures under Universal Health Coverage: A National Population-Based Longitudinal Survey in Taiwan

Authors: Shin-Lin Chiu; Chiao-Lee Chu; Chih-Hsin Muo; Chiu-Liang Chen; Shou-Jen Lan
Journal: Journal of Ophthalmology
 (2015)

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## Abstract

Medical care in Taiwan is well known for its low cost, high efficiency, high quality, excellent medical accessibility, and high equity. We investigate the trends in medication expenditures for glaucoma from 1997 to 2010. The results show that higher medical expenditures were incurred by patients who were aged ≥40 years, male patients, and patients in the highest salary population whereas lower medical expenditures were incurred by blue-collar workers. The medications with the most significant increases in expenditure were prostaglandin analogs (PGAs),α-agonists, and fixed combinations, whereas the medications with the most significant decreases in expenditure were β-blockers and cholinergic agonists. The number of trabeculectomies shows two downward break points in 1999 and 2000 when PGAs were listed and were reimbursed. These results suggest socioeconomic disparities in glaucoma care, as well as understanding of the changes in the expenditure of glaucoma medications under such universal health insurance coverage system.


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## Body

## 1. Introduction

Glaucoma is the second leading cause of blindness, affecting approximately 60.5 million people worldwide or about 2.6% of the population over the age of 40 [1]. Although the most prevalent form of glaucoma in western countries and in many other parts of the world is open-angle glaucoma (OAG) [1], angle-closure glaucoma (ACG) is the most common type of glaucoma among the Han Chinese [2].Blindness due to glaucoma may be preventable if patients are given adequate treatment. Factors associated with the development of glaucoma include increased intraocular pressure (IOP), higher cup-to-disc ratio, aging, thinner central corneal thickness, family history of glaucoma, myopia, and chronic and systemic diseases such as diabetes [3, 4]. Most ophthalmologists treat glaucoma by lowering the IOP using one of three modalities—topical antiglaucoma drugs, laser treatment, or glaucoma surgery. Types of topical medication include β-blockers, α-agonists, prostaglandin analogs (PAGs), carbonic anhydrase inhibitors (CAIs), cholinergic agonists, and adrenergic agonists [5]. Because some patients require multiple daily dosing, fixed combination eye drops have been developed to enhance and reinforce patient compliance [6].Recent studies have shown that glaucoma treatment in some developed countries causes a significant financial burden on the health care system [7–9]. In this study, we used the National Longitudinal Health Insurance Database 2000 (LHID2000) to examine trends in glaucoma medication expenditure in Taiwan from 1997 to 2010. The Taiwan National Health Insurance (NHI) program is a mandatory single-payer health insurance system under which all residents are covered. The NHI program has been in existence since 1995 and by the end of 2010 the coverage rate was 99% of Taiwan’s population of 23.1 million. Health spending accounted for 6.9% of GDP in Taiwan. Medical care in Taiwan is well known for its low cost, convenience, high efficiency, high quality, and excellent medical accessibility [10–12]. The nationwide population-based dataset provides an opportunity to explore the trends in glaucoma medication expenditure.


## 2. Materials and Methods

### 2.1. Database

This study was designed as a population-wide retrospective review using the Taiwan National Health Insurance Research Database (NHIRD). The NHIRD contains a large number of computerized records including registration files, medication and treatment regimens, and information on surgery. Claim reimbursement data from patients since 1999 are provided to researchers in an electronically encrypted form. Data contained in the LHID2000 are randomly selected from one million subjects from the NHIRD and are made available for research purposes [13]. Data from the LHID2000 used in this study included patient identification numbers, gender and age, monthly salary, occupation type, diagnostic data, antiglaucoma drug codes, and surgery codes. Diseases are defined in accordance with A codes (A230) before 2000 and International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM365), after 2000.The study received approval from the Ethics Committee of the Institutional Review Board of the Changhua Christian Hospital and was conducted in accordance with the tenants of the Declaration of Helsinki.


### 2.2. Study Sample

This study group comprised all patients with glaucoma during the period 1997 to 2010. Topical glaucoma medications included PGAs,β-blockers, α-agonists, CAIs, cholinergic agonist, β-blockers/CAIs fixed combinations, β-blockers/α-agonists fixed combination, β-blockers/PGAs fixed combinations, and adrenergic agonists. Data on frequency of trabeculectomy were also collected.


### 2.3. Statistical Analyses

The annual expenditures for glaucoma patients were adjusted for inflation as of 2011. The trend test for expenditure was analyzed with linear regression weighted with the inverse of squares residual. The associations between increase and decline in medication costs were analyzed with Pearson correlation. The trend test for frequency of trabeculectomy was analyzed with the Chow test [14]. We also assessed the effect of demographic factors on glaucoma expenditure using a generalized estimating equation regression model (GEE). A P value <0.05 was considered to indicate statistical significance; all tests were two-tailed. All statistical analyses were conducted using the statistical package SAS for Windows (Version 9.2).


## 2.1. Database

This study was designed as a population-wide retrospective review using the Taiwan National Health Insurance Research Database (NHIRD). The NHIRD contains a large number of computerized records including registration files, medication and treatment regimens, and information on surgery. Claim reimbursement data from patients since 1999 are provided to researchers in an electronically encrypted form. Data contained in the LHID2000 are randomly selected from one million subjects from the NHIRD and are made available for research purposes [13]. Data from the LHID2000 used in this study included patient identification numbers, gender and age, monthly salary, occupation type, diagnostic data, antiglaucoma drug codes, and surgery codes. Diseases are defined in accordance with A codes (A230) before 2000 and International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM365), after 2000.The study received approval from the Ethics Committee of the Institutional Review Board of the Changhua Christian Hospital and was conducted in accordance with the tenants of the Declaration of Helsinki.


## 2.2. Study Sample

This study group comprised all patients with glaucoma during the period 1997 to 2010. Topical glaucoma medications included PGAs,β-blockers, α-agonists, CAIs, cholinergic agonist, β-blockers/CAIs fixed combinations, β-blockers/α-agonists fixed combination, β-blockers/PGAs fixed combinations, and adrenergic agonists. Data on frequency of trabeculectomy were also collected.


## 2.3. Statistical Analyses

The annual expenditures for glaucoma patients were adjusted for inflation as of 2011. The trend test for expenditure was analyzed with linear regression weighted with the inverse of squares residual. The associations between increase and decline in medication costs were analyzed with Pearson correlation. The trend test for frequency of trabeculectomy was analyzed with the Chow test [14]. We also assessed the effect of demographic factors on glaucoma expenditure using a generalized estimating equation regression model (GEE). A P value <0.05 was considered to indicate statistical significance; all tests were two-tailed. All statistical analyses were conducted using the statistical package SAS for Windows (Version 9.2).


## 3. Results

The number of beneficiaries included in the LHID2000 sample declined from 916,626 persons in 1997 to 859,913 persons in 2010. The number of patients receiving antiglaucoma drugs increased from 3105 in 1997 to 7033 in 2010 (Table1).Table 1
Total and mean glaucoma medication expenditure (USD, adjusted for inflation to the 2011 Consumer Price Index of Taiwan), LHID2000.
Total glaucoma medication cost (mean cost per person)
Characteristic
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
Slope
P value
(n
∗
=
3105)
(n
=
3503)
(n
=
3662)
(n
=
3689)
(n
=
3824)
(n
=
4118)
(n
=
4419)
(n
=
5049)
(n
=
5410)
(n
=
5633)
(n
=
5932)
(n
=
6298)
(n
=
6745)
(n
=
7033)
Total expenditure
208,858
212849
249,959
291,523
333,204
397,456
414,489
495,927
552,024
591,417
589,885
614,044
611,331
633,151
37,618
<0.001
(67.3)
(60.8)
(68.3)
(79.0)
(87.1)
(96.5)
(93.8)
(98.2)
(102.0)
(105.0)
(99.4)
(97.5)
(90.6)
(90.0)
2.8
<0.001
Gender
Male
100,245
104,485
123,542
147,789
167,646
202,446
214,111
258,024
285,850
307,655
312,891
325,681
325,892
337,195
20,567
<0.001
(68.1)
(62.7)
(70.9)
(84.1)
(90.6)
(99.9)
(100.1)
(105.5)
(108.3)
(111.0)
(109.1)
(105.0)
(97.9)
(95.7)
3.5
<0.001
Female
108,613
108,364
126,417
143,734
165,558
195,010
200,379
237,903
266,174
283,762
276,994
288,364
285,439
295,956
17,013
<0.001
(66.6)
(59.0)
(65.9)
(74.4)
(83.9)
(93.3)
(87.8)
(91.4)
(96.1)
(99.1)
(90.4)
(90.2)
(83.6)
(84.3)
2.2
0.004
Age
<40
21,558
22,522
23,960
28,747
37,071
47,405
46,926
55,595
60,910
63,110
61,386
62,593
58,693
58,665
3,965
<0.001
(46.3)
(40.1)
(42.2)
(49.5)
(66.8)
(74.5)
(71.8)
(71.4)
(74.1)
(80.2)
(77.6)
(74.8)
(67.9)
(67.5)
2.6
0.001
40–64
81,136
81,205
93,961
113,495
126,037
142,456
147,223
174,562
194,788
208,877
206,852
215,594
221,214
228,075
12,963
<0.001
(64.7)
(59.6)
(65.8)
(78.1)
(83.6)
(90.8)
(85.0)
(89.2)
(93.5)
(95.9)
(90.5)
(89.5)
(83.9)
(84.3)
2.0
0.003
≥65
106,165
109,121
132,038
149,281
170,096
207,595
220,340
265,770
296,327
319,430
321,647
335,858
331,424
346,410
20,982
<0.001
(76.7)
(69.1)
(79.3)
(90.2)
(96.6)
(108.5)
(108.4)
(114.9)
(118.3)
(119.8)
(112.6)
(110.0)
(102.2)
(100.2)
3.3
<0.001
Monthly income
≤610
121,072
117,866
135,830
158,382
183,680
216,500
225,130
263,846
287,919
300,211
291,968
299,156
288,696
292,996
17,296
<0.001
(73.7)
(65.6)
(71.6)
(84.7)
(94.1)
(102.7)
(100.1)
(103.8)
(108.0)
(109.4)
(102.9)
(100.6)
(92.3)
(92.2)
2.5
0.005
611–1220
71,896
77,079
92,189
102,596
114,674
137,747
142,387
172,602
194,157
211,463
214,992
228,099
232,210
242,717
14,528
<0.001
(58.9)
(55.2)
(64.5)
(71.0)
(76.3)
(85.2)
(82.3)
(88.5)
(90.5)
(95.1)
(91.0)
(91.0)
(85.1)
(84.3)
2.9
<0.001
>1220
15,889
17,904
21,940
30,546
34,850
43,209
46,972
59,480
69,948
79,743
82,926
86,789
90,426
97,439
6,867
<0.001
(65.7)
(57.9)
(65.3)
(82.1)
(94.2)
(109.7)
(107.0)
(106.8)
(117.0)
(119.9)
(113.1)
(106.2)
(102.1)
(99.7)
4.0
0.001
Occupation
White-collar
90,794
92,736
108,883
127,199
147,618
172,884
176,803
215,931
248,346
268,507
273,476
287,715
289,024
303,343
18,495
<0.001
(69.5)
(62.4)
(69.0)
(80.2)
(88.3)
(95.9)
(90.7)
(93.5)
(100.2)
(103.6)
(99.8)
(96.5)
(90.3)
(90.1)
2.5
0.001
Blue-collar
67,431
69,645
81,244
91,903
102,067
123,503
128,240
153,700
172,262
188,362
188,384
196,023
195,304
205,480
11,985
<0.001
(58.7)
(53.2)
(60.8)
(68.1)
(74.3)
(83.4)
(81.6)
(86.7)
(88.9)
(93.0)
(88.1)
(87.2)
(81.3)
(82.1)
2.7
<0.001
Other
50,633
50,468
59,832
72,422
83,519
101,069
109,446
126,296
131,416
134,548
128,025
130,307
127,004
124,328
7,902
<0.001
(78.0)
(71.4)
(79.9)
(96.2)
(107.4)
(120.9)
(121.9)
(130.6)
(132.2)
(132.4)
(121.6)
(122.1)
(111.1)
(107.0)
4.0
0.002
Glaucoma medicationa
PGAs
19,283
72,406
120,877
141,191
185,021
221,495
241,386
248,635
259,079
242,699
250,057
23,779
<0.001
(80.0)
(138.2)
(150.2)
(127.0)
(127.0)
(132.8)
(135.2)
(130.9)
(129.2)
(116.5)
(112.6)
0.4
0.787
β-blockers
200,229
204,690
219,951
217,671
199,730
198,074
179,209
176,870
166,256
155,935
127,751
123,041
111,916
95,682
−10,152
<0.001
(67.3)
(60.4)
(62.1)
(61.4)
(57.1)
(56.1)
(50.3)
(46.3)
(43.9)
(41.5)
(34.5)
(32.2)
(28.2)
(24.3)
−0.5
<0.001
α-agonists
180
9,720
26,053
33,311
50,288
58,937
66,428
71,139
74,891
80,729
90,018
8,697
<0.001
(18.0)
(37.4)
(52.6)
(54.3)
(54.8)
(54.5)
(55.2)
(52.2)
(50.5)
(48.0)
(48.4)
1.5
0.194
CAIs
21,002
46,907
45,410
46,897
53,271
61,980
57,895
53,574
52,206
57,326
52,120
53,699
648
0.303
(72.2)
(92.9)
(83.0)
(83.0)
(84.3)
(91.8)
(90.0)
(85.4)
(81.1)
(84.9)
(75.0)
(70.9)
−1.5
0.060
Cholinergic
agonist
8,629
8,159
9,005
7,483
5,939
5,554
4,530
4,863
4,978
4,751
3,747
3,331
3,138
3,166
−432
<0.001
(10.9)
(9.5)
(11.5)
(10.5)
(9.8)
(9.4)
(8.0)
(8.2)
(8.4)
(8.1)
(6.9)
(6.3)
(5.9)
(5.9)
−0.5
<0.001
β-blockers/
CAIs
2,951
14,553
29,437
47,992
60,413
66,376
72,166
73,586
11,526
<0.001
(57.9)
(77.8)
(87.3)
(93.2)
(99.2)
(93.1)
(95.7)
(90.4)
3.0
0.072
β-blockers/
α-agonists
34
1,134
3,373
12,115
24,760
5,750
0.028
(17.1)
(51.5)
(54.4)
(64.8)
(79.9)
12.6
0.076
β-blockers/
PGAs
26
2,351
13,026
21,316
24,860
26,603
36,433
42,184
8,042
<0.001
(25.8)
(58.8)
(105.9)
(134.9)
(146.2)
(116.2)
(121.4)
(114.9)
9.8
0.079
Number of trabeculectomies
124
126
100
69
73
65
64
66
63
70
75
61
70
68
PGAs, prostaglandin analogues; CAIs, carbonic anhydrase inhibitors; LHID2000, National Longitudinal Health Insurance Database 2000.
n
∗, number of patients under glaucoma medication.
aAdrenergic agonists not shown because of small sample sizes.


### 3.1. Overall Costs

After adjusting for inflation, the total annual medical expenditures increased from $0.21 million in 1997 to $0.63 million in 2010 (slope =$37,618/year, P
<
0.001) (Table 1). The increase in total expenditures was remarkable in both genders, every age group, every income group, and every occupation group (P
<
0.05). Annual glaucoma medication expenditures for men were higher than those for women after 2000. The annual glaucoma medication expenditures were most prominent in the age group ≥65 years, followed by the age group 40–64 years and the age group <40 years (Figure 1). The lowest income group spent more money on antiglaucoma medications than other income groups. The white-collar occupation group spent more money on medications than the other occupation groups.Figure 1
Plot of annual total expenditure of glaucoma medication, by age group.


### 3.2.  Per Capita Expenditure Costs

The mean medication expenditure per person increased from $67.3 in 1997 to $90 in 2010 after adjusting for inflation (slope =$2.8/year, P
<
0.001) (Table 1). The mean cost per capita increased year on year from 1997 to 2006 and then decreased gradually after 2007. The trend in mean medication expenditures per person was similar in each category (gender, age, income, and occupation group). Estimates from the GEE conducted to determine demographic variables associated with the increase in glaucoma medication expenditure indicate that patients ≥40 years incurred higher costs for medication than patients under the age of 40 years (P
<
0.001). In the same analysis, men incurred higher costs than women (P
<
0.05), populations with higher income incurred higher costs for medications than populations with lower income (P
<
0.05), glaucoma medication expenditures increased year on year (P
<
0.001), and blue-collar workers had lower expenditures than the other types of workers (P
<
0.001) (Table 2).Table 2
The results of generalized estimating equations regression model (USD/year).
Estimate
SE
P value
Intercept
33.4
1.5
<0.001
Age, year (versus <40)
40–64
10.4
1.4
<0.001
≥65
18.5
1.5
<0.001
Gender (versus female)
2.2
1.1
0.041
Income, USD (versus ≤610)
611–1220
−3.2
1.3
0.015
>1220
6.7
2.0
<0.001
Occupation (versus white-collar workers)
Blue-collar workers
−6.7
1.3
<0.001
Other types of workers
6.8
1.6
<0.001
Year
1.0
0.1
<0.001


### 3.3. The Changes of Expenditure between Different Glaucoma Medications

The annual expenditures for most classes of glaucoma medications increased during the study period, except forβ-blockers (slope = −$10,152/year, P
<
0.001) and cholinergic agonists (slope = −$432/year, P
<
0.001) (Table 1). The decrease in expenditure for β-blockers was associated with the administration of PGAs (P
=
0.002), and α-agonists (P
<
0.001). A significant increase in expenditures on PGAs (slope = $23,779/year, P
<
0.001) was also noted. Medications containing PGAs accounted for 46% of the total glaucoma medication expenditure in 2010 (Table 1) (Figure 2).Figure 2
Plot of total expenditure of glaucoma medication, by medication class.We also found a decreasing trend in per capita medication expenditures forβ-blockers (slope = −$0.5/year, P
<
0.001) and cholinergic agonists (slope = −$0.5/year, P
<
0.001). However, the trends for other glaucoma medications were not significant (Table 1).


### 3.4. The Change of Trabeculectomy Number during the Study Period

The numbers of trabeculectomies performed during the study period are shown in Table1. During the period 1997–2010, we found that the frequency of trabeculectomy had two break points, one in the year 1999 and the other in the year 2000 based on the Chow test [14].


## 3.1. Overall Costs

After adjusting for inflation, the total annual medical expenditures increased from $0.21 million in 1997 to $0.63 million in 2010 (slope =$37,618/year, P
<
0.001) (Table 1). The increase in total expenditures was remarkable in both genders, every age group, every income group, and every occupation group (P
<
0.05). Annual glaucoma medication expenditures for men were higher than those for women after 2000. The annual glaucoma medication expenditures were most prominent in the age group ≥65 years, followed by the age group 40–64 years and the age group <40 years (Figure 1). The lowest income group spent more money on antiglaucoma medications than other income groups. The white-collar occupation group spent more money on medications than the other occupation groups.Figure 1
Plot of annual total expenditure of glaucoma medication, by age group.


## 3.2.  Per Capita Expenditure Costs

The mean medication expenditure per person increased from $67.3 in 1997 to $90 in 2010 after adjusting for inflation (slope =$2.8/year, P
<
0.001) (Table 1). The mean cost per capita increased year on year from 1997 to 2006 and then decreased gradually after 2007. The trend in mean medication expenditures per person was similar in each category (gender, age, income, and occupation group). Estimates from the GEE conducted to determine demographic variables associated with the increase in glaucoma medication expenditure indicate that patients ≥40 years incurred higher costs for medication than patients under the age of 40 years (P
<
0.001). In the same analysis, men incurred higher costs than women (P
<
0.05), populations with higher income incurred higher costs for medications than populations with lower income (P
<
0.05), glaucoma medication expenditures increased year on year (P
<
0.001), and blue-collar workers had lower expenditures than the other types of workers (P
<
0.001) (Table 2).Table 2
The results of generalized estimating equations regression model (USD/year).
Estimate
SE
P value
Intercept
33.4
1.5
<0.001
Age, year (versus <40)
40–64
10.4
1.4
<0.001
≥65
18.5
1.5
<0.001
Gender (versus female)
2.2
1.1
0.041
Income, USD (versus ≤610)
611–1220
−3.2
1.3
0.015
>1220
6.7
2.0
<0.001
Occupation (versus white-collar workers)
Blue-collar workers
−6.7
1.3
<0.001
Other types of workers
6.8
1.6
<0.001
Year
1.0
0.1
<0.001


## 3.3. The Changes of Expenditure between Different Glaucoma Medications

The annual expenditures for most classes of glaucoma medications increased during the study period, except forβ-blockers (slope = −$10,152/year, P
<
0.001) and cholinergic agonists (slope = −$432/year, P
<
0.001) (Table 1). The decrease in expenditure for β-blockers was associated with the administration of PGAs (P
=
0.002), and α-agonists (P
<
0.001). A significant increase in expenditures on PGAs (slope = $23,779/year, P
<
0.001) was also noted. Medications containing PGAs accounted for 46% of the total glaucoma medication expenditure in 2010 (Table 1) (Figure 2).Figure 2
Plot of total expenditure of glaucoma medication, by medication class.We also found a decreasing trend in per capita medication expenditures forβ-blockers (slope = −$0.5/year, P
<
0.001) and cholinergic agonists (slope = −$0.5/year, P
<
0.001). However, the trends for other glaucoma medications were not significant (Table 1).


## 3.4. The Change of Trabeculectomy Number during the Study Period

The numbers of trabeculectomies performed during the study period are shown in Table1. During the period 1997–2010, we found that the frequency of trabeculectomy had two break points, one in the year 1999 and the other in the year 2000 based on the Chow test [14].


## 4. Discussion

During the study period, the total expenditures for glaucoma medications significantly increased by 3.03-fold because of an increase in patient numbers and an increase in mean medication expenditures per person. The increase in patient numbers may be related to the early diagnosis due to advanced diagnostic modalities (e.g., optical coherence tomography), more accurate diagnosis, overdiagnosis, aging population, or good medical accessibility in Taiwan [10, 11, 15]. The increase in mean medication expenditure per person may be associated with the administration of PGAs and more aggressive glaucoma treatment [5]. The rising cost of glaucoma drugs after PGAs launching also occurred in Ireland, Scotland, Australia, Denmark, and France [16].As seen in Table2, mean glaucoma medication expenditures increased markedly after the NHI system began covering treatment with PGAs in 2000. The reduction of expenditure per capita after 2007 and the mean medication cost in Taiwan was much lower than in Denmark and the United States [8, 9] reflecting the success of bargaining medication cost and prescription policy (beta-blocker should be first-line drug) by Taiwan NHI. However, the increasing total medication expenditure imaged that the cost down policy could not offset the growing medical demand.In this study, expenditures for glaucoma medications were significantly higher for men than for women, whereas in the USA the opposite is true [8]. The possible reasons are differences in knowledge of health issues between genders in different societies and the higher prevalence of ACG in Taiwan [2, 17]. Women are at higher risk of ACG [18] that can be treated with laser iridotomy or cataract surgery rather than glaucoma medications. Cataract surgery is readily available in Taiwan and the procedure reduces the likelihood of developing the disease [13, 19].It is not surprising that glaucoma medical expenditures were highest among patients ≥65 years because aging is one of the risk factors for developing glaucoma. In this study, the glaucoma medical expenditures for the age group over 65 years significantly increased and accounted for more than half the amount of medical expenditures; a reflection of Taiwan’s aging population has great financial burden in glaucoma care. Furthermore, we also found that expenditures for glaucoma medications increased significantly for patients in the age group <40 years, possibly because of advanced diagnostic tools, more aggressive glaucoma treatment, and the high prevalence of myopia among younger people in Taiwan [5, 15, 20].The study results show that blue-collar workers have lower glaucoma medical expenditures, while higher income families incur higher glaucoma medical expenditures, indicating inequality in health care services under universal health coverage in Taiwan. Such inequality may be the result of differences in general knowledge of health care, out-of-pocket payment policy, and other socioeconomic disparities [10, 21, 22].The total expenditure forβ-blockers decreased because of the reduction in cost by the bureau of NHI and the decrease in usage of β-blockers, mainly due to the increased availability of PGAs and α-agonists. However, considering the drug price, the Taiwan NHI stipulates that β-blockers are first-line medications and PGAs, CAIs, and fixed combinations are second-line medications. Therefore, β-blockers still have a considerable market share in Taiwan, despite the fact that PGAs are more effective, are associated with fewer adverse effects, require only once-a-day dosing, and are associated with greater patient compliance [23]. The medical expenditures in the USA have also undergone similar changes relative to insurance coverage [8].Cholinergic agonists are mainly used for ACG. Even though most people in Taiwan are Chinese in origin and have a higher prevalence of ACG [2, 17], there has been a decreasing trend in the application of cholinergic agonists, which may be offset by the increased availability of other drugs like PGAs and the increase in frequency of cataract surgery in Taiwan [13, 23]. The trend in increasing expenditures for fixed combinations of medications during the period of study can be attributed to patients’ preference, because the fixed combinations improve medical adherence and reduce eye discomfort [6].Trabeculectomy is the most common glaucoma surgery in Taiwan. Our study reveals that the number of trabeculectomies decreased significantly in 1999 and 2000, at the time when PGAs were launched and the Taiwan NHI began to reimburse expenses for PGAs. A similar situation of decreasing the number of trabeculectomies after PGAs listing was also reported in Scotland, France, and Australia [16]. Trabeculectomy is more effective in reducing IOP and lowering diurnal tension than PGAs [24]. However, the side effects of trabeculectomy are greater than those associated with PGAs. According to Cutler and McClellan [25], technological change affects treatment in two ways—treatment substitution and treatment expansion or both. Treatment substitution implies a new technology in place of an old one. Treatment expansion takes place when treatments become safer and easier, and patients pay more attention to their conditions when therapy is more effective or less side effective. Based on the results of this study, we presume that PGAs may have the effect of treatment expansion for trabeculectomy under universal health coverage.There are several limitations to this study. First of all, the study ignored patient adherence and disease severity. Poor patient adherence may reduce medication expenditures at first but eventually will increase medical and surgical expenditures due to symptom complications. Realistically, severities of glaucoma are related to medical expenditures. Secondarily, insured salary is not necessarily truly representative of patients’ socioeconomic status. Most people are employees and pay the insurance fee according to their salary. However, the health insurance fee is lower for those living on their investments. We cannot definitely determine the interaction between socioeconomic status and glaucoma medical expenditures. Thirdly, we did not characterize which types of glaucoma and which education levels contributed to medical expenditures.


## 5. Conclusions

This nationwide population-based study demonstrated an increasing trend in glaucoma medical expenditures from 1997 to 2010 in Taiwan. The main factors contributing to these trends include administration of brand-name drug products such as PGAs, the increasing glaucoma population, good medical accessibility, and possibly more aggressive treatment. PGAs may have the effect of treatment expansion for trabeculectomy. Expenditures were highest among men, patients over 40 years of age, and patients with higher incomes and were lowest among blue-collar workers. The inequality of health care in different socioeconomic disparities may still exist in Taiwan.



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