Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, controlled, parallel-group study.
BACKGROUND
Intraocular inflammation is typically treated with a combination of anti-inflammatory and anti-infective drugs. Tobramycin-dexamethasone (TD) has not been associated with any serious adverse events, indicating good tolerability.


OBJECTIVE
The aims of this study were the following: (1) to demonstrate noninferiority of TD compared with dexamethasone-neomycin-polymyxin (DNP) in terms of anti-inflammatory efficacy, (2) to compare the anti-inflammatory efficacy of TD and DNP with that of a "placebo" control (antibiotic without anti-inflammatory agent), and (3) to provide additional safety data on TD.


METHODS
This prospective, double-masked, parallel-group study was conducted at 22 ophthalmology clinics across Europe and Brazil. Patients aged > 18 years undergoing cataract surgery were randomly assigned, in a 2:2:1 ratio, to receive tobramycin 3 mg/mL plus dexamethasone 1 mg/mL, dexamethasone 1 mg/mL plus neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 6000 IU/mL, or neomycin sulfate 3500 IU/mL plus polymyxin B sulfate 7500 IU/mL plus gramicidin 20 microg/mL. All treatments were given as 1 drop instilled in the operated eye q.i.d. for 21 days. The primary efficacy end point, intraocular inflammation (determined using the sum of scores on anterior chamber cells and aqueous flare), was assessed at days 3, 8, 14, and 21 after surgery.


RESULTS
A total of 271 patients were enrolled (158 women, 113 men; age range 42-90 years) (TD, 104 patients; DNP, 110 patients; and neomycin-polymyxin-gramicidin [NPG], 57 patients). Intraocular inflammation was similar in the TD and DNP groups at all time points. At days 8, 14, and 21, inflammation scores were significantly lower with TD than with NPG (all, P < 0.05). At day 8, the inflammation score was significantly lower with DNP than with NPG (P < 0.05). A greater number of patients receiving NPG experienced treatment-related ocular allergic reactions compared with patients receiving TD (P < 0.05). One patient receiving TD (1.0%) and 5 given NPG (9.0%) were withdrawn due to ocular allergic reactions. None of the patients experienced an increase in intraocular pressure > or =10 mm Hg from baseline.


CONCLUSIONS
In this study of patients undergoing cataract surgery combination therapy with TD was noninferior to DNP and was well tolerated.
Notivol
Ricardo
R
Clinical Research Department, Alcon Cusí, SA, Barcelona, Spain. ricardo.notivol@alconlabs.com
Bertin
Donata
D
Amin
Dina
D
Whitling
Anna
A
Kennedy
Margaret
M
Cockrum
Paul C
PC
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001938:Brazil; D002387:Cataract Extraction; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006096:Gramicidin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009355:Neomycin / Q000008:administration & dosage / Q000627:therapeutic use; D011113:Polymyxins / Q000008:administration & dosage / Q000627:therapeutic use; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control*; D011446:Prospective Studies; D014031:Tobramycin / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D011113:Polymyxins; D006096:Gramicidin; D003907:Dexamethasone; D009355:Neomycin; D014031:Tobramycin