Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction

The data from 3,841 patients who were recruited from nine centers (academic, teaching, and non-teaching hospitals) participating in the DUtch Research project on treatment outcome IN Glaucoma patients (DURING) study were used [1, 2]. The DURING study population consisted of glaucoma patients who already used or started to use glaucoma medication. Patients were enrolled between March 2001 and January 2004. The mean age ± standard deviation of patients included was 69 ±12 years, ranging from 21 to 97 years, 1,920 (50%) were male. The majority of patients (85%) were diagnosed with open-angle glaucoma (69%), ocular hypertension (9%), or glaucoma suspect (7%).

The side effects of topical glaucoma medication were registered by asking patients to fill in a questionnaire based on “the Comparison of Ophthalmic Medications for Tolerability” (COMTOL) questionnaire [3]. The COMTOL questionnaire was designed and validated for comparing the tolerability of topical glaucoma medications. Since the COMTOL mainly focuses on side effects of pilocarpine and timolol, the questionnaire was modified for our present purpose. Several items were left out, such as items especially dealing with side effects of pilocarpine and items dealing with limitation in activities. Items dealing with compliance were also left out since it was not the purpose of the present study to thoroughly study compliance. Next, the questionnaire was supplemented with items listed in the Farmacotherapeutisch Kompas, a guide for medical therapy issued by the Dutch Health Care Insurance Board [4]. To ensure content validity, two glaucoma specialists studied these listed items independently of each other, after which the most frequently observed and/or severe side effects of all commonly used glaucoma medications were included in the final patient questionnaire. It was taken into account that patients should be able to notice the side effects themselves.

The ocular symptoms listed were burning, stinging, conjunctival hyperaemia, itching, ocular secretion, ocular pain, tearing, brow ache, dryness, foreign body sensation, eyelid redness, eyelid oedema, blurred vision, visual acuity loss, accommodation difficulties, and night vision problems. For each side effect, the frequency of the symptoms and the severity of bother for the patient were documented. The questions concerning the frequency of effects were graded from ‘Did not experience’, ‘One day’, ‘Several days’, ‘About half of days’, ‘Almost every day’ and ‘Every day’ in the preceding 14 days. The questions concerning the intensity of bother were graded from ‘Not at all bothered’, ‘A little bothered’, ‘Quite bothered’, ‘Much bothered’ and ‘Extremely bothered’.

In addition, questions were asked concerning patient satisfaction with their medication. The patients were asked to indicate their level of satisfaction on a 7-point scale: ‘Very unsatisfied‘, ‘Unsatisfied’, ‘A little unsatisfied, ‘Not unsatisfied nor satisfied’, ‘A little satisfied’, ‘Satisfied’ and ‘Very satisfied’.

To identify as many patients as possible with recent changes in their glaucoma medication, consecutive patients, participating in the DURING study, were asked to fill out the questionnaire at least twice, each time after a visit to their ophthalmologist. They were asked to fill out at least two questionnaires to be able to find reported changes in response. Only the first questionnaire filled out was used in the final analysis to prevent double counting of the same patient. Changes in responses were not analyzed. After collecting all data, only patients who used their current glaucoma medication or combination of medications for the first time since their last or last but one visit to the ophthalmologist (e.g., new patients or patients switching or adding medication) were included in the study. This procedure was chosen to prevent loss to follow-up and to prevent bias originating from differences between patients using medications from a shorter or longer period of time. We wanted to include only subjects that recently started using a particular drug, since it is to be expected that patients who use a certain drug (e.g., timolol) for a longer period of time experience fewer side effects when compared to patients on newer drugs who have not used this drug for such a long period. In this latter group, patients and ophthalmologists are likely to stop the treatment when patients experience a lot of side effects from the beginning of their use. This difference between long-term and short-term users introduces a bias in the comparison of drugs.

The questionnaire was handed to the patients at their visit to the outpatient department. To provide the patients with ample time for answering all questions, they were asked to open the envelope with the questionnaire directly after arriving home, answer the questions, and return the questionnaire within 14 days. The questions asked referred to the period of 14 days preceding their last visit to the ophthalmologist at the outpatient clinic.

In addition, at each patient visit ophthalmologists indicated on a form if they had decided to stop glaucoma medication.

The first questionnaires filled out by the patients were used for analysis. Since patients were considered as satisfied only when they had indicated to be “Satisfied” or “Very satisfied” with their eye drops, for the variable ‘patient satisfaction’ the percentage of patients who filled out “Satisfied” or “Very satisfied” was calculated.

The items concerning the frequency of side effects were scored on a scale from 0 to 5. On this scale, 0 represented ‘Did not experience’ and 5 represented ‘Every day’. Likewise, the items concerning the severity of bother were scored on a scale from 0 (‘Not at all bothered’) to 4 (‘Extremely bothered’). Both scores were multiplied to determine the final score per item on ocular side effects. Next, these final scores per type of side effect were summed over all types of side effects. This sum was used to assess the median value. The next step was to calculate per glaucoma drug the percentage of patients with a lower or higher score than this median value. For the variable ‘stopping glaucoma medication due to side effects’, the percentage of visits to the outpatient clinic during which the ophthalmologist decided to stop the use of a certain glaucoma medication was calculated. In this analysis, all the visits during which the ophthalmologist had filled out a form were included to a maximum of two visits per patient.