Topical medicine instillation techniques for glaucoma

What is the aim of this review?
The aim of this Cochrane Review was to find out if the way that people with glaucoma put eye drops in makes a difference in how well the eye drops work. Cochrane researchers collected and analyzed all relevant studies to answer this question and found two studies.

Key messages
It is unclear if the way that people with glaucoma put their eye drops in makes a difference in how well the drops work.

What did this review study?
Glaucoma is a leading cause of blindness worldwide. In eyes with glaucoma, the ability to see may be lost because of damage to the optic nerve. The optic nerve is the part of the eye that sends visual information from the eye to the brain. Sometimes such damage occurs when there is too much pressure in the eye (called intraocular pressure or IOP). Sometimes eyes may have too much pressure without damage to the optic nerve (called ocular hypertension). The main goal of glaucoma and ocular hypertension treatment is to lower IOP. Topical medicines, such as eye drops, are most often used as the first treatment. Encouraging specific ways of applying the drops, such as closing your eyes or nasolacrimal occlusion (closing the eye and pressing a finger on the inside corner, by the nose) aims to increase how much medicine is absorbed into the eye and reduce how much medicine is absorbed into the body.

What are the main results of the review?
We found two studies that compared different ways of putting in eye drops. Both studies used prostaglandin alone for glaucoma or ocular hypertension. One study, in the US, evaluated the effect of closing the eyes for one and three minutes after putting in eye drops on lowering IOP. The second study, in Italy, looked at whether wiping off the excess fluid, after putting in the eye drops, led to fewer changes in the skin surrounding the eye.

After one to two weeks in the US study, closing the eyelid for one to three minutes after putting in the eye drops found no difference on IOP compared with not closing the eyelid for a specified amount of time. After four months in the Italian study, eyelashes were shorter when participants had wiped their eyes to remove excess fluid when compared with participants who did not wipe their eyes.

We found two ongoing studies that do not have results yet.

Based on only two studies and uncertain results, it is unclear if different ways of putting in eye drops have any effect on people with glaucoma.

How up-to-date is this review?
Cochrane researchers searched for studies that had been published up to 8 December 2016.

Authors' conclusions: 

Evidence to evaluate the effectiveness of topical medication instillation techniques for treatment of glaucoma is lacking. It is unclear what, if any, effects instillation techniques have on topical medical therapy for glaucoma.

Read the full abstract...

Glaucoma is a leading cause of irreversible blindness worldwide and the second most common cause of blindness after cataracts. The primary treatment for glaucoma aims to lower intraocular pressure (IOP) with the use of topical medicines. Topical medication instillation techniques, such as eyelid closure and nasolacrimal occlusion when instilling drops, have been proposed as potential methods to increase ocular absorption and decrease systemic absorption of the drops.


To investigate the effectiveness of topical medication instillation techniques compared with usual care or another method of instillation of topical medication in the management of glaucoma or ocular hypertension.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 12), MEDLINE Ovid (1946 to 8 December 2016), Embase Ovid (1947 to 8 December 2016), PubMed (1948 to 8 December 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 8 December 2016), International Pharmaceutical Abstracts Database (1970 to 8 December 2016), the metaRegister of Controlled Trials (mRCT) ( (last searched 13 May 2013), ( (searched 8 December 2016) and the WHO International Clinical Trials Registry Platform (ICTRP) ( (searched 8 December 2016). We did not use any date or language restrictions in the electronic searches for trials.

Selection criteria: 

We included randomized controlled trials which had compared any topical medication instillation technique with usual care or a different method of instillation of topical medication.

Data collection and analysis: 

Two review authors independently screened records from the searches for eligibility, assessed the risk of bias, and extracted data. We followed methods recommended by Cochrane.

Main results: 

We identified two trials (122 eyes of 61 participants) that had evaluated a topical medication instillation technique. We also identified two ongoing trials. Both included trials used a within-person design and administered prostaglandin monotherapy for glaucoma or ocular hypertension. Because the trials evaluated different instillation techniques and assessed different outcomes, we performed no meta-analysis.

One trial, conducted in the US, evaluated the effect of eyelid closure (one and three minutes) versus no eyelid closure on lowering IOP. At one to two weeks' follow-up, reduction in IOP was similar in the eyelid closure group and the no eyelid closure group (mean difference (MD) -0.33 mmHg, 95% confidence interval (CI) -0.8 to 1.5; 51 participants; moderate-certainty evidence).

The second trial, conducted in Italy, evaluated the effect of using an absorbent cloth to wipe excess fluid after instillation (fluid removal) versus not using an absorbent cloth (no removal) on reducing dermatologic adverse events. At four months' follow-up, eyelashes were shorter among eyes in the fluid removal group compared with the no fluid removal group (MD -1.70 mm, 95% CI -3.46 to 0.06; 10 participants; low-certainty evidence). Fewer eyes showed skin hyperpigmentation in the eyelid region towards the nose in the fluid removal group compared with the no removal group (RR 0.07, 95% CI 0.01 to 0.84; 10 participants; low-certainty evidence); however, the difference was uncertain in the eyelid region towards the temples (RR 0.44, 95% CI 0.07 to 2.66; 10 participants; low-certainty evidence). The effect hypertrichosis (excessive hair growth) was uncertain between groups (RR 1.00, 95% CI 0.17 to 5.98; 10 participants; low-certainty evidence).

Neither trial reported other outcomes specified for this review, including the proportion of participants with IOP less than 21 mmHg; participant-reported outcomes related to the ease, convenience, and comfort of instillation techniques; physiologic measurements of systemic absorption; escalation of therapy; mean change in visual fields; optic nerve progression; mean change in best-corrected visual acuity; proportion in whom glaucoma developed; quality of life outcomes; or cost-effectiveness outcomes. Neither trial reported data at follow-up times of more than four months.

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