Effect of Inhaled Anticholinergic Drugs on Intraocular Pressure in Patients with Chronic Obstructive Pulmonary Disease Patients

Effect of Inhaled Anticholinergic Drugs on Intraocular Pressure in Patients with Chronic Obstructive Pulmonary Disease Patients

Dr Amit Kumar Pandey*1, Dr Richa Tripathi2

1. 1Department of Respiratory medicine, GSVM medical college, Kanpur

Correspondence to: Dr Amit Kumar Pandey, N9/29 J-8 janki nagar colony , patiya  p.o. bazrardiha ,kakarmatta Varanasi 221002,Uttar Pradesh


Copyright.

© 2024 Dr. Amit Kumar Pandey. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 29 March 2024

Published:  01 May 2024


Effect of Inhaled Anticholinergic Drugs on Intraocular Pressure in Patients with Chronic Obstructive Pulmonary Disease Patients

Introduction

Nebulized Beta2 agonists and ipratropium bromide used for the treatment of COPD patients are known to cause glaucoma due to accidental instillation in eyes. Significance of anticholinergic drugs used as pressurised metered dose inhalers (pMDI) or dry powder inhalers (DPI) by patients with Chronic Obstructive Pulmonary Disease (COPD) causing raised intraocular pressure is unknown in patients with risk factors for glaucoma.

 

Material and Methods

Initially 126 patients were  included. 6 were taking oral antihistamine cetrizine did not fulfil the protocol. 10 patients were excluded because they were not co-operating with the study protocol. There remained 110 patients on whom study was done. These 110 patients were divided  into study group (70) received Ipratropium 40µg eight hourly or Tiotropium 18 µg once a day and Formoterol 6 µg twice a day plus Fluticasone 125 µg twice a day.and control group (40) received above medicines minus Ipratropium or  Tiotropium. All the inhalers were given as metered dose Inhaler (pMDI) with spacer device. Ophthalmic examination and  Gonioscopy  were  done as  pre-treatment. Intra ocular pressure (IOP) measurements were done by Applanation tonometer before starting treatment, and thereafter weekly for four weeks at 4.00pm every day.

 

Observation and Result

In study group maximum change in intraocular pressure at 28th day was +7.4 mmHg in left eye and +7.0 mmHg in right eye in one patient. In control group maximum change in intraocular pressure was 3 mmHg in right  eye and 3.70 mmHg in left eye in one patient.

In study group patients, mean change in intraocular pressure was 3.25±2.3 mmHg right ,3.52±2.2mmHg left ,more in grade 2 than in grade 3 which was 1.52±1.5 mmHg right,1.55±1.3 mmHg left  and least in grade 4 (1.37±1.06 mmHg right,1.38±1.2 mmHg left) mmHg. Also the change was statistically significant (p=0.035).

In control group the change was found to be almost same among different angles.

4 patients with narrow angle (grade 2) and 3 with open angle (grade 3) developed intraocular pressure (IOP) beyond normal range (>20 mmHg), but all were normal on fundoscopic examination (Ocular Hypertension).

Mean change in intraocular pressure (IOP) was more in female population (2.18±1.76 right eye and 2.21±1.46 left eye) than in male population (1.60±1.71 right eye , 1.66±1.72  left eye) in study group .The change was not statistically significant .The change was almost same in control group.

In study group there were 4 patients with ocular symptoms at the end of 28th day which disappeared after discontinuing Tiotropium  inhaler .

Table 1: Intra Ocular  Pressure   Before   Starting  Anticholinergic  Inhaler

Intraocular pressure (iop)

Study group

Control group

Right eye

Left eye

Right eye

Left eye

mmHg

No. (%)

No. (%)

No. (%)

No. (%)

10-13

24 (34.28)

24 (34.28)

06 (15)

05 (12.5)

13-15

29 (41.42)

31 (44.28)

17(42.5)

19 (47.5)

15-17

09 (12.85)

09 (12.85)

13(32.5)

14 (35)

17-19

07 (10)

06 (8.57)

04 (10)

02(5)

More than 20

01(1.42)

01 (1.42)

00

00

Mean IOP

13.931 ±1.968

13.931 ±2.221

13.774±1.540

13.689±1.789

 

Table 2: Intraocular Pressure  28th Day  After   Starting Anticholinergic Inhaler

Intraocular Pressure (IOP)

Right eye

Control group

mmHg

No. (%)

No. (%)

No. (%)

No. (%)

10-13

06 (8.57%)

03 (4.28%)

04 (10%)

04(10)

13-15

23 (32.85%)

21 (30%)

21 (52.50%)

22 (55%)

15-17

30(42.85%)

34 (48.57%)

11 (27.5%)

12(30%)

17-19

07 (10%)

08 (11.42%)

04 (10%)

02(5%)

>20

05(7.14%)

05 (7.14%)

00

00

Mean IOP

15.701±2.405

15.755±2.370

14.305±1.365

14.128±1.709

 

Table 3: Change In Intraocular Pressure (Iop) At 28th Day

Change in intraocular pressure (iop)

Study group

Control group

mmHg

Right eye

Left eye

Right eye

Left eye

1-2

18

19

2

2

2-3

12

14

1

1

3-4

6

6

0

1

>4

4

5

0

0

TOTAL

40

44

3

4

 

Table 4; Mean Change In Intraocular Pressure Among Different Angles

 

Angle of anterior chamber (grade)

Study group

Control group

Right eye

Left eye

Right eye

Left eye

No.of patients

Mean change

No.of patients

Mean change

No.of patients

Mean change

No.of patients

Mean change

2

13

3.25±2.3

11

3.52±2.2

3

0.53±0.3

3

0.56±0.8

3

38

1.52±1.5

42

1.55±1.3

21

0.54±0.7

21

0.58±0.8

4

19

1.37±1.06

17

1.38±1.2

16

0.48±0.6

16

0.03±0.9

TOTAL

70

70

40

40

 

Table 5: Distribution Of Change In Intraocular Pressure According To Sex

Change in intraocular pressure

(iop)

Study group

Control group

Male

(n=50)

Female

(n=20)

Male

(n=30)

Female

(n=10)

Right eye

Left eye

Right eye

Left eye

Right eye

Left eye

Right eye

Left eye

Increase

44

44

17

20

27

24

10

10

Decrease

6

6

3

0

6

6

0

0

 
Table 6: Distribution Of Angle And Intraocular Pressure Beyond Normal At 28th Day After Inhaled Anticholinergics

Angle of anterior chamber(grade)

Number of patients with intraocular pressure beyond normal(>20mmhg)

Fundoscopy

2

4

NORMAL

3

3

NORMAL

4

0

NORMAL

Table 7: Distribution Of Mean Change In Intraocular Pressure With  Sex

 

Study group

Control group

 

Mean change in intraocular pressure(mmhg)

Mean change in intraocular pressure(mmhg)

 

Right eye

Left eye

Right eye

Left eye

MALE (n=50)

1.60±1.71

1.66±1.72

0.56±0.73

0.31±0.98

FEMALE (n=20)

2.18±1.76

2.21±1.46

0.41±0.24

0.82±1.08

 

Fig 1, Fig 2, Fig 3, Fig 4, Fig 5, Fig 6

 

Conclusion

1. The inhaled anticholinergics (Tiotropium) once in a day given along with Formetrol and Fluticasone twice a day in COPD patients, all by Metered Dose Inhalers with spacer led to  significant change (mainly increase) in intraocular pressure (IOP) after 4th week of starting treatment.

2. In control group where COPD patients were given only  Formoterol plus Fluticasone by Metered Dose Inhalers  did not lead to any  significant change in intraocular pressure (IOP) after 4th week of starting treatment. Minor changes seen in some patients were within clinical therapeutic range.

3. Inhaled Anti-cholinergic drugs given as Metered Dose  Inhalers can lead to Ocular Hypertension in COPD patients whose eyes were normal at initial clinical examination.

4. Increase  in intraocular pressure was more in patients   with  narrow  angle of anterior chamber in eyes  than in open angle. Therefore, narrow  angle of anterior chamber appeared to be a risk factor for intra ocular hypertension.          

5.Increase in intraocular in study group was more among females (100%).

 

Recommendation

Initial evaluation of angle of anterior chamber and intraocular pressure and regular follow up monitoring of intraocular pressure is recommended in COPD patients receiving Tiotropium metered dose inhalers. This would possibly apply to DPIs as well.


References

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3. Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE. et al. The effects of smoking cessation intervention on 14.5 year mortality: a randomized clinical trial. Ann Intem Med 2005;142(4):2339.

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8. Brusasco V,  Hodder B, Miraitles M, Korducki L, Towse L; Kester S.: Health outcomes following treatment for six  months with once daily  tiotropium  compared with twice  daily salnetherel in patients with COPD:  Thorax 2003 May; 58(5) ; 399 – 404.

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