Prophylaxis of Inflammation following Cataract Surgery

Discussion

This study was performed in European countries and in Brazil, with all sites following the same study procedures. The study was conducted in patients scheduled for cataract extraction by phacoemulsification technique followed by implantation of a posterior chamber intraocular lens. Cataract extraction with a posterior chamber intraocular lens implantation was chosen as a routine ocular surgical procedure model as well as a standard controlled, inflammation model. The known cause and onset of ocular clinical inflammation and the high reproducible response are considered the main advantages of this model. Furthermore, the duration of the study (23 days) was sufficient to evaluate the effect of TobraDex® ophthalmic suspension compared with Tobrex®/vehicle. Tobrex®/vehicle was selected for the treatment of the control group instead of placebo, since it was considered unethical to leave patients assigned to this arm with no antibiotic coverage and to put them at risk of endophthalmitis.^[4] For practical logistic reasons, anterior chamber inflammation (the primary efficacy variable) was measured by slit-lamp examination rather than by the laser flare-cell meter.^[26,27] Although flare-cell meters have demonstrated high sensitivity for flare measurements, it has been reported that slit-lamp is highly reliable to detect a low number of cells.^[28]

The two treatment groups were comparable in age, race, iris colour and baseline scores of primary and secondary efficacy parameters, although the number of females in the Tobrex®/vehicle arm was significantly higher than in the TobraDex® group. This finding did not affect the clinical outcome of the study. Efficacy results were consistent at all sites except one; this site (2193) had the lowest rate (14%) of patients completing all study visits.

The primary objective of the study, i.e. to evaluate the superiority of an antibiotic/corticosteroid combination (TobraDex®) compared with an anti-biotic alone (Tobrex®) was met. Cells and flare together are the most reliable measure of ocular inflammation following cataract surgery. The results confirmed the superiority of TobraDex® over Tobrex®/vehicle, both dosed four times daily for 23 days in the primary parameter (anterior chamber inflammation as aqueous reaction, defined as the sum of cells and flare scores). These positive results for TobraDex® in the primary parameter were complemented with similar favourable results in secondary efficacy parameters including physician's impression of inflammatory response.

The higher incidence of adverse events reported in the Tobrex®/vehicle group may be explained by the lack of anti-inflammatory activity in that group resulting in an increased occurrence of hyperaemia, corneal oedema, increased fibrin and conjunctivitis.

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.

Table I. Study design
Parameters	Period 1 (day -1 to day 7)					Period 2 (day 8 to day 21)
Parameters	Screening^a	Day -1	Day 0 (surgery)	Day 1	Day 3 ± 1	Day 8 ± 1	Day 14 ± 2	Day 21 ± 2
General information; medical history	X
Informed consent	X
Pregnancy test, when applicable^b	X							X
Peri-operative medication			X
Ocular surgery			X
Visual acuity	X	X		X	X	X	X	X
Slit-lamp examination	X	X		X	X	X	X	X
Fundus examination (dilated)	X							X
Intraocular pressure measurements	X	X		X	X	X	X	X
Physician's follow-up impression of inflammatory response				X	X	X	X	X
Dispense study medication^c		X				X
Collect study medication^d						X		X
Record adverse events		X	X	X	X	X	X	X
Complete exit form^d								X

Table II. Demographic data of the intent-to-treat patients (n = 401)
	TobraDex®	Tobrex®/vehicle	Total	p-Value
Age (y)
Mean	69.76	68.97	69.37	0.4616^a
SD	10.53	10.91	10.71
n	203	198	401
Sex (no.)				0.0266^b
Male	96	72	168
Female	107	126	233
Race (no.)				0.6129^b
Caucasian	195	191	386
Black	7	7	14
Asian	1		1
Iris colour (n)				0.3611^b
Brown	104	118	222
Blue	63	48	111
Hazel	18	13	31
Green	8	10	18
Grey	10	7	17
Missing		2	2

Table III. Patients discontinued from the study
Reason	TobraDex® (n = 211)	Tobrex®/vehicle (n = 206)	All randomised (n = 417)
Adverse event (related and unrelated to the study medication)	2	11	13
Lost to follow-up	0	2	2
Patient's decision to postpone surgery day	2	5	7
Noncompliance	4	1	5
Treatment failure	9	32	41
Other	6	10	16
Total	23 (11%)	61 (30%)	84 (20%)

Table IV. Patients excluded from per-protocol (PP) data set
Reasons leading to a patient's exclusion^a	TobraDex® (n = 211)	Tobrex®/vehicle (n = 206)	All randomised (n = 417)
Not receiving study drug	0	2	2
Did not meet inclusion criteria^b	13	8	21
History or evidence of ocular or systemic disease that would preclude participation in this study	4	10	14
Use of concomitant anti-inflammatory drugs	8	10	18
Diabetes mellitus	3	1	4
Study medication wrongly dispensed	1	0	1
No follow-up visit available after surgery (day 0)	6	3	9
Total^a	35	34	69
Total^a number of patients excluded from PP	32	32	64

Table V. Results of secondary efficacy variables in the per-protocol data set (mean ± SD)
Parameters/treatment group	Day
Parameters/treatment group	1	3	8	14	21
Cells
TobraDex®	1.20 ± 0.76	0.91^a ± 0.67	0.56^a ± 0.82	0.31^a ± 0.76	0.18^a ± 0.68
Tobrex®/vehicle	1.27 ± 0.82	1.36 ± 1.02	1.25 ± 1.11	0.96 ± 1.13	0.75 ± 1.18
Flare
TobraDex®	0.73 ± 0.89	0.43^a ± 0.70	0.23^a ± 0.66	0.18^a ± 0.63	0.13^a ± 0.59
Tobrex®/vehicle	0.71 ± 0.82	0.72 ± 0.91	0.74 ± 0.97	0.58 ± 0.97	0.50 ± 0.97
Ocular pain
TobraDex®	0.60^a ± 0.74	0.37^a ± 0.67	0.26^a ± 0.64	0.16^a ± 0.59	0.11^a ± 0.57
Tobrex®/vehicle	0.80 ± 0.91	0.92 ± 1.08	0.92 ± 1.16	0.68 ± 1.04	0.54 ± 1.00
Physician's impression of inflammation
TobraDex®	2.40 ± 1.02	1.78^a ± 0.98	1.29^a ± 1.13	0.81^a ± 1.17	0.49^a ± 1.15
Tobrex®/vehicle	2.48 ± 0.98	2.49 ± 1.20	2.46 ± 1.44	2.00 ± 1.63	1.55 ± 1.84

Table III. Patients discontinued from the study
Reason	TobraDex® (n = 211)	Tobrex®/vehicle (n = 206)	All randomised (n = 417)
Adverse event (related and unrelated to the study medication)	2	11	13
Lost to follow-up	0	2	2
Patient's decision to postpone surgery day	2	5	7
Noncompliance	4	1	5
Treatment failure	9	32	41
Other	6	10	16
Total	23 (11%)	61 (30%)	84 (20%)

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

My Alerts

Add to Email Alerts

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

Discussion

Tables

Tables

Tables

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Comments

Email This

Feedback