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. 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. 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. 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.
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. 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.
Clin Drug Invest. 2004;24(9) © 2004 Adis Data Information BV
Cite this: Prophylactic Effectiveness of Tobramycin-Dexamethasone Eye Drops Compared with Tobramycin/Vehicle Eye Drops in Controlling Post-Surgical Inflammation in Cataract Patients - Medscape - Sep 01, 2004.