Use of preservative-free multidose dispenser (Comod system) for glaucoma medications
Ahmad Fauzi, MD1, Shamala S. Ganesan, MD1, Mimiwati Zahari, MD1, Mariam Jamaludin, MPH2
A PRESERVATIVE is important for two reasons: to prevent the patient from introducing microbiologically
contaminated drugs into his eye(s) and to maintain the potency of the ophthalmic drug.1, 2 The inclusion of
preservatives in eye-drop dispensers, however, does not guarantee sterility. A high contamination rate was reported by Schein et al.3 (29%), Marion and Tampert4 (27%), Hovding and Sjursen5 (12.9%). The Comod eye-drop dispenser, introduced recently in Malaysia, has a shelf life of 2 years and can be used for 12 weeks after it has been opened.6 As a sealed system, it has an “airless pump” that works without air equalization and prevents the reflux of external air and liquid when the solution is dosed. It also has an average drop size of 32.5 ± 2.5 ul, which is equivalent to the capacity of the inferior conjunctival fornix. Timolol, a commonly used maintenance medication for glaucoma, comes in both the conventional eye-drop dispenser and in Timo-Comod system. We evaluated our experience using both systems. We performed the Schirmer’s test, tear-breakup time (BUT), and graded the conjunctival injection by fluorescein. Culture and sensitivity for bacterial contamination were done for the Comod system.
One hundred twenty patients with open-angle glaucoma were randomly assigned to conventional Timolol
0.25% (Group I, 60 patients) or Comod system (Group II, 60 patients). Patients in both groups were instructed
on the correct method of application especifically in avoiding any contact between the dropper tip and the eye or lid to maintain sterility. This open-label study was divided into two phases: a comparison of the Comod system with the conventional system in phase 1, and determination of sterility of the Comod system in phase 2. Patients were also given a selfadministered questionnaire to grade the convenience of application, severity of ocular stinging, and dryness of eyes. Convenience of application was graded as follows: (1) Difficult—frequent spillage, (2) Moderately difficult— spillage of more than 10 times in a month, (3) Easy— spillage less than 10 times in a month, and (4) Extremely easy—no spillage. Spillage was defined as any drop that overflowed from the conjunctival sac after application.
Ocular stinging was graded as: Grade 0—no stinging, Grade I—mild, Grade II—moderate, and Grade III—
severe. The conjunctival injection was graded as area of injection involving the bulbar conjunctiva: Grade 0–nil, Grade I–1 quadrant, Grade II–2 quadrants, Grade III–3 quadrants, Grade IV–4 quadrants, Grade V–4 quadrants with upper or lower palpebral conjunctival involvement. An assistant wearing a mask and sterile gloves collected samples for culture and sensitivity test. Each bottle was uncapped, the tip swabbed with alcohol and allowed to dry. The first drop of the solution was discarded and the second drop placed onto blood agar plate and sent to the microbiology lab. The plates were incubated at 37o C and bacterial growth was assessed at 24 and 48 hours. Any growth was subjected to standard microbiological testing for identification and antibiotic-sensitivity testing.
Data analysis was done using Statistical Products and Services Solution software. The Schirmer’s tests, tear film BUT, and intraocular pressures (IOP) in the two groups at 3 weeks were compared using the Student’s t-test. The Chi-square test was used to analyze grade of convenience and ocular stinging. A level of significance of p < 0.05 was used. Results indicated no difference in the distribution of the patients in the 2 groups in terms of ethnicity, gender, duration, and types of glaucoma. The mean IOP for both groups at baseline and 3 weeks were similar. Mean tear film BUT were also comparable (Table 1). The Schirmer’s test values indicated diminished tears (< 10 mm) in both groups at baseline, with mild improvement in group II when compared to group I (Table 2) at 3 weeks, but not statistically significant. No group II patients reported ocular stinging during the study, in contrast to those in group I who reported mild (58%) and moderate stinging (25%) (p < 0.001).
Conjunctival injection was negative in both groups and cultures were also negative, even at 11 weeks. Although several patients initially complained of some difficulty in using the Comod system, it becomes easier with repeated use.
1. Ellis PP. Therapeutic Review. Surv Ophthalmol 1973; 17: 469-83.
2. The Pharmaceutical Codex. Eyedrops. 11th ed. London: London Pharmaceutical Press, 1979; 346-349.
3. Schein OD, Hibberd PL, Starck T, et al. Microbial contamination in use of ocular medications. Arch Ophthalmol 1992; 110: 82-85.
4. Marion AD, Tamert MJ. Bacterial contamination of timolol in use by nonselected clinical population. Invest Ophthalmol Vis. Sci 1986; 27: 36.
5. Hovding G, Sjursen H. Bacterial contamination of drops and dropper tips in use of multidose eye-drop bottles Acta Ophthalmol (Copenh) 1982; 60:213-222.
6. Gross D. The Comod System: a preservative-free drug therapy against glaucoma. In: Orgül S, Flammer J, eds. Pharmacotherapy in Glaucoma. Bern, Switzerland: Hans Huber Verlag, 2000; 321-328.