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 28^th 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 28^th day which disappeared after discontinuing Tiotropium  inhaler .

Table 1: Intra Ocular  Pressure   Before   Starting  Anticholinergic  Inhaler

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

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

Table 4; Mean Change In Intraocular Pressure Among Different Angles

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

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

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 4^th 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 4^th 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.

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