Prophylactic Effectiveness of Tobramycin-Dexamethasone Eye Drops Compared with Tobramycin/Vehicle Eye Drops in Controlling Post-Surgical Inflammation in Cataract Patients

Ricardo Notivol; Dina Amin; Anna Whitling; David Wells; Margaret Kennedy; Paul C. Cockrum; The International TobraDex Study Group


Clin Drug Invest. 2004;24(9) 

In This Article

Abstract and Introduction

Objective: To demonstrate the superiority of TobraDex® (tobramycin 3 mg/mL, dexamethasone 1 mg/mL) eye drops over Tobrex® (tobramycin 3 mg/mL)/vehicle (placebo) eye drops in the prophylaxis of inflammation after cataract surgery, and to provide additional safety data on TobraDex®.
Setting: Twenty-two ophthalmology clinics from Brazil, Belgium, Germany, Ireland, Portugal, Spain and Sweden.
Patients and methods: Prospective, randomised, double-masked, two-arm, parallel-group, placebo-controlled, multicentre study in 417 patients undergoing extracapsular cataract extraction with intraocular lens implantation. Patients were randomised (1:1) to TobraDex® or to Tobrex®/vehicle. One drop of TobraDex® or Tobrex® was instilled in the operative eye (four times daily) on the day before surgery (day -1), one drop immediately following surgery in the operated eye (day 0), and then treatment (four times daily) was continued until day 7 (inclusive). From day 8 through day 21, patients in the TobraDex® group continued with the same treatment, but patients in the Tobrex®/vehicle arm received the inactive ingredient only. Efficacy was assessed at 1, 3, 8, 14 and 21 days. The primary efficacy variable was the percentage of patients without post-surgical anterior chamber inflammation (i.e. with a sum of cells and flare scores of zero) on the day 8 visit.
Results: TobraDex® was significantly better (p < 0.05) than Tobrex®/vehicle in controlling post-surgical inflammation at day 8 as shown by the percentage of patients with an inflammation score of zero (51% vs 21%, respectively). The percentage of patients with treatment failure was 4% vs 16% (p < 0.001) in favour of TobraDex®. In the safety population (n = 415), 19% of patients reported a total of 52 adverse events while receiving TobraDex® and 35.3% patients reported 103 adverse events while receiving Tobrex®/vehicle. One patient receiving Tobrex®/vehicle discontinued the study due to an ocular allergic reaction. No patient experienced clinically relevant changes in visual acuity, fundus parameters, cup/disc ratio or intraocular pressure related to treatment following the day of surgery.
Conclusions: TobraDex® eye drops were superior to Tobrex®/vehicle in controlling post-surgical inflammation following cataract extraction. TobraDex® administered four times daily over 21 days post-surgery was safe and well tolerated in patients treated for the prevention of post-surgical inflammation following cataract extraction.

Inflammatory conditions of the anterior chamber of the eye are usually treated with eye drops containing a combination of anti-inflammatory and anti-infective drugs.[1,2,3] Anti-infectives are given as a routine part of care in order to prevent the occurrence of a postoperative infection. In fact, the incidence of postoperative endophthalmitis has decreased substantially over the years.[4] Therefore the combined use of anti-infective and anti-inflammatory agents is justified whenever the natural defence barriers of the eye are compromised, either accidentally or through a surgical procedure[5,6,7] such as in patients undergoing cataract surgery.

The positive therapeutic effect on postoperative inflammation and prevention of postoperative infection following cataract surgery with standard formulations of corticosteroids, nonsteroidal anti-inflammatory drugs and antibiotics has been documented extensively in the literature.[8,9,10,11,12,13,14,15,16,17,18,19] The concomitant administration of an anti-inflammatory and antibiotic agent in a single ophthalmic product overcomes any potential 'washout effect' that may be seen when separate medications are used. In addition, a single administration of a combination product leads to better compliance, patient comfort and safety.[20] The reduced number of administrations needed for a combination product may be of particular benefit for elderly patients, who make up the majority of cataract surgery cases.

TobraDex® eye drops (Alcon Couvreur NV, Puurs, Belgium) is a combination of tobramycin 3 mg/mL and dexamethasone 1 mg/mL. The clinical development of TobraDex® was initiated in 1983 and results of various studies including a total of 1309 subjects have confirmed the efficacy of this ophthalmic suspension in controlling inflammation and preventing infection after cataract surgery.[21] An extensive review of the postmarketing surveillance of this antibiotic-corticosteroid combination demonstrated that the occurrence of adverse events associated with the use of TobraDex® have been very rare and resolved quickly without sequelae, indicating that TobraDex® is safe and well tolerated for use in the treatment of inflammation and prophylaxis of infection following cataract surgery.[21]

The present study was conducted with two objectives: (a) to demonstrate the superiority of TobraDex® to Tobrex®/vehicle, an anti-inflammatory 'placebo' in the prevention of post-surgical inflammation after cataract extraction, and (b) to provide additional safety data on TobraDex®. The model chosen was extracapsular cataract extraction, by phacoemulsification, with a posterior chamber intraocular lens (IOL) implantation.

Tobrex® (tobramycin 3 mg/mL) eye drops is a well accepted antibiotic ophthalmic solution used extensively as a standard treatment in the prevention of post-surgical infection.[22] Tobramycin is an antibiotic that is active against most strains of bacteria that infect the eye and has been used in ophthalmology since the mid-1980s.[5,14,23] The use of antibiotic agents as part of routine peri- and postoperative care is common practice and topical instillation of an antibiotic prior to surgery has been shown to reduce conjunctival colonisation and decrease the potential risk of post-surgical infection.[24,25] Therefore, Tobrex® ophthalmic solution was used 1 day before and for 1 week following surgery to prevent post-surgical infection in patients randomised to the control group.