Intracameral phenylephrine and ketorolac injection (OMS302) for maintenance of intraoperative pupil diameter and reduction of postoperative pain in intraocular lens replacement with phacoemulsification

Figures & data

Figure 1 Patient flow.

Table 1 Demographic and baseline characteristics (full analysis population set)

	Placebo (n=204)	OMS302 (n=202)	Total (n=406)
Age (years)
n	204	202	406
Mean (SD)	67.5 (10.6)	69.2 (9.2)	68.3 (10.0)
Sex, n (%)
Male	78 (38.2%)	85 (42.1%)	163 (40.1%)
Female	126 (61.8%)	117 (57.9%)	243 (59.9%)
Race, n (%)
American Indian or Alaska Native	0	1 (0.5%)	1 (0.2%)
Asian	18 (8.8%)	16 (7.9%)	34 (8.4%)
Black or African American	28 (13.7%)	18 (8.9%)	46 (11.3%)
Native Hawaiian or other Pacific Islander	0	1 (0.5%)	1 (0.2%)
White	158 (77.5%)	165 (81.7%)	323 (79.6%)
Other	0	1 (0.5%)	1 (0.2%)
Nuclear color/opalescence, n (%)
N0	10 (4.9%)	7 (3.5%)	17 (4.2%)
N1	23 (11.3%)	26 (12.9%)	49 (12.1%)
N2	93 (45.6%)	104 (51.5%)	197 (48.5%)
N3	78 (38.2%)	65 (32.2%)	143 (35.2%)

Abbreviation: SD, standard deviation.

Figure 2 Change from baseline in mean (± SE) pupil diameter over time to the end of surgery (full analysis population set). Pupil diameters were measured at one-minute intervals from baseline to the end of the procedure and at the end of cortical clean-up from a video of patients’ intraoperative lens replacement procedures. Variability increased after 21 minutes when only nine placebo-treated patients and five OMS302-treated patients were still undergoing surgery.

Abbreviations: PD, pupil diameter; SE, standard error.

Table 2 Analysis of intraoperative changes in pupil diameter (full analysis population set)

	Placebo (n=200)f	OMS302 (n=195)f
Mean AUCa of change from baseline in pupil diameter (mm)
Mean (SD)	−0.5 (0.57)	0.1 (0.43)
Median	−0.5	0.1
Minimum, maximum	−2.3, 1.5	−2.2, 2.3
Difference in mean AUC
CMH-weighted mean difference (SE)b	0.590 (0.049)
95% confidence interval	0.494, 0.686
P-valuec	<0.0001
Patients with ≥6 mm at cortical clean-up, n/N (%)	154/200 (77.0%)	187/195 (95.9%)
P-valued		<0.0001
Patients with <6 mm at any time during surgery, n/N (%)	76/200 (38.0%)	18/195 (9.2%)
P-valued		<0.0001
Patients with degree of pupillary constriction, n/N (%)e
<0.5 mm	14/200 (7.0%)	92/195 (47.2%)
≥0.5 mm to <1.0 mm	29/200 (14.5%)	58/195 (29.7%)
≥1.0 mm to <1.5 mm	47/200 (23.5%)	26/195 (13.3%)
≥1.5 mm to <2.0 mm	40/200 (20.0%)	13/195 (6.7%)
≥2.0 mm to <2.5 mm	17/200 (8.5%)	4/195 (2.1%)
≥2.5 mm	53/200 (26.5%)	2/195 (1.0%)
P-valued		<0.0001

Notes:

a AUC is calculated by the trapezoidal rule from the baseline to the last post-baseline value. Mean AUC is calculated by dividing the AUC by the duration from the baseline to the last post-baseline value.

b CMH-weighted mean difference (OMS302 – placebo) is adjusted for the randomization strata.

c P-value is based on the generalized CMH test stratified by the randomization strata.

d Chi-square test.

e Maximum decrease in pupil diameter from baseline during surgery.

f Due to poor video recording prohibiting evaluation by the central reader, data from 11 randomized and treated patients (7 in the OMS302 treatment group and 4 in the placebo treatment group) were excluded from these analyses.

Abbreviations: AUC, area under the curve; mm, millimeter; SD, standard deviation; SE, standard error; CMH, Cochran–Mantel–Haenszel.

Figure 3 Mean (± SE) VAS ocular pain scores during the early postoperative period (full analysis population set).

Abbreviations: VAS, visual analog scale; SE, standard error.

Table 3 Analysis of ocular pain VAS scores within 12 hours postoperatively (full analysis population set)

	Placebo (n=204)	OMS302 (n=202)
Mean AUCa of ocular pain VAS score within 12 hours postoperatively
nb	202	202
Mean (SD)	8.9 (15.19)	4.3 (8.75)
Median	2.5	1.0
Minimum, maximum	0.0, 85.8	0.0, 58.4
Difference in mean AUC
CMH-weighted mean difference (SE)c	−4.580 (1.192)
95% confidence interval	−6.917, −2.244
P-valued	0.0002
Patients with pain free (VAS =0) at all time pointse	41/202 (20.3%)	56/202 (27.7%)
P-valuef		0.0806
Patients with maximum VAS score in 12 hours postoperatively
≥0 to ≤5	101/202 (50.0%)	126/202 (62.4%)
>5 to ≤10	21/202 (10.4%)	20/202 (9.9%)
>10 to ≤15	19/202 (9.4%)	14/202 (6.9%)
>15 to ≤20	10/202 (5.0%)	10/202 (5.0%)
>20	51/202 (25.2%)	32/202 (15.8%)
P-valuef		0.0959
Patients with moderate to severe pain (VAS ≥40) at any time point	27/202 (13.4%)	16/202 (7.9%)
P-valuef		0.0760

Notes:

a AUC is calculated by the trapezoidal rule from the first value to the last value within 12 hours postoperatively. Mean AUC is calculated by dividing the AUC by the duration from the first value to the last value within 12 hours postoperatively.

b Two subjects were excluded from this analysis as they did not provide data for this endpoint.

c CMH-weighted mean difference (OMS302 – placebo) is adjusted for the randomization strata.

d P-value is based on the generalized CMH test stratified by the randomization strata.

e Patients with missing VAS during the 12 hours postoperatively are considered as not being pain free.

f Chi-square test.

Abbreviations: VAS, visual analog scale; AUC, area under the curve; SD, standard deviation; SE, standard error; CMH, Cochran–Mantel–Haenszel.

Table 4 Treatment-emergent adverse events occurring in more than 5% of patients in either treatment group (safety population)

Preferred term	Placebo (n=204)	OMS302 (n=202)
Any event	143 (70.1%)	118 (58.4%)
Eye pain	76 (37.3%)	34 (16.8%)
Headache	24 (11.8%)	21 (10.4%)
Posterior capsule opacification	14 (6.9%)	17 (8.4%)
Anterior chamber inflammation	13 (6.4%)	17 (8.4%)
Ocular discomfort	15 (7.4%)	10 (5.0%)
Vision blurred	16 (7.8%)	5 (2.5%)
Conjunctival hyperemia	10 (4.9%)	10 (5.0%)
Photophobia	13 (6.4%)	4 (2.0%)
Intraocular pressure increased	4 (2.0%)	12 (5.9%)