Evaluation of a new artificial tear formulation for the management of tear film stability and visual function in patients with dry eye

Figures & data

Table 1 Schedule of visits and proceduresa

Procedures	Visit 1 Day 1		Visit 2 Day 15±2	Visit 3 Day 29±2
	Predosing	Postdosing
Informed consent/HIPAA	X
Medical/medication history and demographic	X
Study drug collection			X	X
Diary collection			X	X
Medical/medication history update			X	X
Adverse event query			X	X
Pregnancy test	Xb			X
Ora Calibra™ symptom assessments
Ocular Discomfort Scale	X	Xc,d	X	X
Ocular Discomfort and 4-Symptom Questionnaire	X	Xc,d	X	X
Quality of Life Questionnaire	X		X	X
OSDI^© questionnaire	X		X	X
Visual acuity	X		X	X
Visual function assessments	X	Xd		X
Slit-lamp biomicroscopy	X		X	X
TFBUT	X	Xc,d	X	X
Fluorescein staining	X		X	X
Lissamine green staining	X		X	X
Review of qualification criteria	X
Ora Calibra drop comfort scale and questionnaire		X
All day relief questionnaire				X
Study drug dispensation	X		X
Diary dispensation		X	X
Exit subject from the study				X

Notes:

a Some clinical measures that showed no significant differences between groups have been omitted for clarity.

b For females of childbearing potential.

c Measurements performed at 5 and 20 minutes post-instillation at Visit 1.

d Measurements performed at 60 minutes post-instillation at Visit 1.

Abbreviations: HIPAA, Health Insurance Portability and Accountability Act; OSDI, Ocular Surface Disease Index; TFBUT, tear film break-up time.

Table 2 Enrolled subject demographics

	Total	Male	Female	Mean age
Rohto Dry-Aid	39	13	26	61
Systane Ultra	41	16	25	62
Total	80	29 (36%)	51 (64%)	62

Table 3 Ocular comfort scores

	Visit 1				Visit 2	Visit 3
	Predose	5 minutes	20 minutes	60 minutes
Rohto Dry-Aid	2.59	1.51	1.77	1.54	2.00	1.85
Systane Ultra	2.61	1.41	1.71	1.73	2.29	2.05
p-values
Rohto vs Systane	0.905	0.683	0.776	0.364	0.135	0.317
Same test agent vs predose		All t-tests significant at p<0.001

Notes: Subjects were asked to score their level of discomfort using the Ora Calibra Ocular Discomfort Scale (0–4, where 0 is no discomfort and 4 is constant discomfort) prior to drop instillation and at 5, 20, and 60 minutes after instillation at Visit 1; single measures were collected at Visits 2 and 3.

Table 4 Mean corneal fluorescein staining by visit

	Inferior	Superior	Central	Temporal	Nasal
Rohto Dry-Aid
Visit 1	2.04	2.27	0.97	1.92	1.96
Visit 2	2.09	1.86	0.88	1.82	1.86
Visit 3	2.23	2.15	1.14	2.15	2.21
Systane Ultra
Visit 1	1.93	2.01	0.79	1.63	1.80
Visit 2	1.66	1.57	0.59	1.43	1.46
Visit 3	2.07	1.96	0.91	1.88	1.89

Notes: Scores listed for the worst eye, which was defined as the eye with the highest staining score in inferior, superior, or central regions at Visit 1. Both Rohto and Systane groups exhibited modest improvement in staining scores.

Table 5 Tear film break-up time

	Visit 1
	Predose	5 minutes	20 minutes	60 minutes
Rohto Dry-Aid	2.44	3.32	3.84	3.27
p-value vs baseline		0.011	0.006	0.012
Systane Ultra	2.27	3.09	2.87	2.75
p-value vs baseline		0.018	0.206	0.442

Notes: Mean break-up time, in seconds, scored for the worst eye only; p-values vs baseline. Mean values were significantly increased for both groups at 5 minutes, but the mean scores of the Rohto group only maintained the increased break-up time at 20 and 60 minutes. p-values in bold indicate significance (p<0.05).

Table 6 Ora Calibra Ocular Discomfort and 4-Symptom Questionnaire

	Rohto Dry-Aid	Systane Ultra	Ocular Discomfort	Burning	Dryness	Grittiness	Stinging
Visit 1 pre-dosing	Rohto		2.95	1.64	3.21	1.67	1.18
		Systane	2.83	1.49	2.90	2.05	1.24
	p-value		0.478	0.593	0.114	0.197	0.815
Visit 1 5 Min Post-Dose	Rohto		1.74	0.90	1.54	0.59	0.82
		Systane	1.68	0.80	1.68	1.27	1.05
	p-value		0.815	0.698	0.599	0.012	0.374
Visit 2	Rohto		2.23	1.31	2.26	1.15	0.85
		Systane	2.17	1.17	2.20	1.63	0.85
	p-value		0.772	0.594	0.790	0.062	0.972
Visit 3	Rohto		1.97	0.97	2.15	1.36	0.79
		Systane	2.15	1.22	2.29	1.59	0.85
	p-value		0.420	0.341	0.519	0.386	0.802

Notes: Subjects rated the severity of each of the following symptoms with regards to how both their eyes felt, in general: overall ocular discomfort, burning, dryness, grittiness, and stinging, according to a 6-point (0–5) scale, where 0= none and 5= worst. Scores were collected before and after dosing at Visit 1 and at Visits 2 and 3. Both agents reduced mean discomfort scores postdosing at Visit 1; the decrease in mean grittiness score in the Rohto group was significantly greater than that seen in the Systane group. p-values in bold indicate significance (p<0.05).

Table 7 Ora Calibra™ Quality of Life Questionnaire

In the past week	Visit 1	Visit 2	Visit 3
	Mean score (p-value vs Visit 1)
How much has your eyesight impacted your daily activity?
Rohto	1.08	0.77 (0.012)	0.74 (0.014)
Systane	1.05	0.93 (0.281)	0.73 (0.036)
How troubled have you been reading at night?
Rohto	1.54	1.56 (0.893)	1.77 (0.270)
Systane	1.78	1.88 (0.660)	1.71 (0.734)
How troubled have you been watching television or movies at night?
Rohto	1.31	1.0 (0.123)	0.85 (0.016)
Systane	1.27	0.98 (0.096)	1.02 (0.168)
How troubled have you been driving at night?
Rohto	1.85	1.62 (0.284)	1.44 (0.034)
Systane	1.78	1.71 (0.660)	1.61 (0.342)

Notes: Subjects were asked to indicate how troubled they have been during the prior week while performing specific visual tasks described in the questions, using a 0–4 scale, where 0= minimal and 3= severe; a score of 4 indicated the question was not applicable. Scores were collected at Visits 1, 2, and 3. Mean scores for three of the four questions were significantly reduced at Visit 2 in the Rohto group and in one of the four questions in the Systane group. p-values in bold indicate significance (p<0.05).

Figure 1 Self-reported symptom scores: comparison of mean AM vs PM scores.

Notes: Subjects used the Ora Calibra Ocular Discomfort & 4-Symptom Questionnaire to rate their symptoms in a daily diary; ratings were collected in the morning and evening over the 4-week course of the study. Graph shows the percent change in mean scores between AM and the PM for each of the five symptoms. Positive values indicate a worsening of symptoms in the evening, which was observed for 4 of the 5 symptom scores for Systane.