Trial Outcomes & Findings for Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery (NCT NCT02608489)

NCT ID: NCT02608489

Last Updated: 2016-10-17

Results Overview

The OSDI questionnaire consists of 12 questions that evaluate subjective symptoms related to dry eye and vision The score ranges were between 0 and 100 scores and the higher scores represent a worse outcome.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 86 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2016-10-17

Participant Flow

Consecutive patients aged 20-90 years with bilateral or unilateral cataract undergoing uncomplicated phacoemulsification and intraocular lens (IOL) implantation at Soonchunhyang University Hospital between January 1, 2014 and January 31, 2015 were enrolled.

Participant milestones

Measure	Diqufosol 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Overall Study STARTED	43	43
Overall Study COMPLETED	30	33
Overall Study NOT COMPLETED	13	10

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery

Baseline characteristics by cohort

Measure	Diqufosol n=30 Participants 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=33 Participants 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.	Total n=63 Participants Total of all reporting groups
Age, Continuous	65.53 years STANDARD_DEVIATION 11.15 • n=5 Participants	65.37 years STANDARD_DEVIATION 10.02 • n=7 Participants	65.45 years STANDARD_DEVIATION 10.62 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	24 Participants n=7 Participants	42 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Obstructive Meibomian Gland Dysfunction (MGD) None	17 participants n=5 Participants	19 participants n=7 Participants	36 participants n=5 Participants
Obstructive Meibomian Gland Dysfunction (MGD) Mild	13 participants n=5 Participants	14 participants n=7 Participants	27 participants n=5 Participants
Ocular Surface Disease Index ± SD	22.23 Scores on a scale STANDARD_DEVIATION 14.65 • n=5 Participants	23.64 Scores on a scale STANDARD_DEVIATION 16.62 • n=7 Participants	22.96 Scores on a scale STANDARD_DEVIATION 15.11 • n=5 Participants
tear Break-Up Time ± SD	4.88 seconds STANDARD_DEVIATION 2.52 • n=5 Participants	4.54 seconds STANDARD_DEVIATION 1.85 • n=7 Participants	4.70 seconds STANDARD_DEVIATION 2.06 • n=5 Participants
Schirmer test ± SD	3.52 mm STANDARD_DEVIATION 4.13 • n=5 Participants	3.67 mm STANDARD_DEVIATION 2.88 • n=7 Participants	3.58 mm STANDARD_DEVIATION 3.31 • n=5 Participants
Fluorescein staining score ± SD	1.62 score STANDARD_DEVIATION 1.77 • n=5 Participants	1.77 score STANDARD_DEVIATION 1.73 • n=7 Participants	1.69 score STANDARD_DEVIATION 1.75 • n=5 Participants
Lissamine green staining score ± SD	1.55 score STANDARD_DEVIATION 1.19 • n=5 Participants	1.94 score STANDARD_DEVIATION 1.56 • n=7 Participants	1.79 score STANDARD_DEVIATION 1.38 • n=5 Participants
Total High Order Aberration (HOA) changes ± SD	0.042 microns STANDARD_DEVIATION 0.041 • n=5 Participants	0.041 microns STANDARD_DEVIATION 0.048 • n=7 Participants	0.041 microns STANDARD_DEVIATION 0.045 • n=5 Participants
Uncorrected visual acuity (LogMAR) ± SD	0.80 logMAR STANDARD_DEVIATION 0.52 • n=5 Participants	0.77 logMAR STANDARD_DEVIATION 0.45 • n=7 Participants	0.78 logMAR STANDARD_DEVIATION 0.47 • n=5 Participants
Grade of anterior chamber cells	0 grade STANDARD_DEVIATION 0 • n=5 Participants	0 grade STANDARD_DEVIATION 0 • n=7 Participants	0 grade STANDARD_DEVIATION 0 • n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

The OSDI questionnaire consists of 12 questions that evaluate subjective symptoms related to dry eye and vision The score ranges were between 0 and 100 scores and the higher scores represent a worse outcome.

Outcome measures

Measure	Diqufosol n=45 Eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 Eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. Baseline	21.09 scores on a scale Standard Deviation 3.86	23.00 scores on a scale Standard Deviation 2.66
an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. Postoperative week 1	31.28 scores on a scale Standard Deviation 5.49	20.31 scores on a scale Standard Deviation 4.63
an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. Postoperative week 4	20.31 scores on a scale Standard Deviation 4.63	23.00 scores on a scale Standard Deviation 3.19
an Ocular Surface Disease Index (OSDI) Questionnaire That is Related to Dry Eye Severity. Postoperative week 12	9.76 scores on a scale Standard Deviation 7.95	16.92 scores on a scale Standard Deviation 13.11

PRIMARY outcome

Timeframe: 12 weeks

Schirmer paper strips were placed into the temporal one third of the lower conjunctival sac for 5 min and the wetness on the strips was measured.

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. Baseline	3.61 mm Standard Deviation 0.84	3.69 mm Standard Deviation 0.58
Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. Postoperative week 1	2.03 mm Standard Deviation 0.37	1.76 mm Standard Deviation 0.25
Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. Postoperative week 4	3.22 mm Standard Deviation 0.62	2.59 mm Standard Deviation 0.43
Schirmer I Test Without Anesthesia That is Related to Dry Eye Severity. Postoperative week 12	4.10 mm Standard Deviation 2.87	2.52 mm Standard Deviation 2.08

PRIMARY outcome

Timeframe: 12 weeks

Corneal HOAs and serial measurement of ocular total HOAs were evaluated using a KR-1W wavefront analyzer (Topcon Medical System, Inc., Tokyo, Japan). Serial measurement of total ocular HOAs was measured every second for 10 s after complete blinking in continuous measurement mode. The difference between the fifth and first HOA was used to evaluate the tear film instability.

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Changes in HOAs After Blinking That is Related to Dry Eye Severity. Postoperative week 4	0.067 microns Standard Deviation 0.029	0.074 microns Standard Deviation 0.043
Changes in HOAs After Blinking That is Related to Dry Eye Severity. Baseline	0.042 microns Standard Deviation 0.010	0.041 microns Standard Deviation 0.007
Changes in HOAs After Blinking That is Related to Dry Eye Severity. Postoperative week 1	0.153 microns Standard Deviation 0.057	0.260 microns Standard Deviation 0.040
Changes in HOAs After Blinking That is Related to Dry Eye Severity. Postoperative week 12	0.034 microns Standard Deviation 0.040	0.039 microns Standard Deviation 0.147

PRIMARY outcome

Timeframe: 12 weeks

TBUT was assessed by instillation of a drop of 2% sterile fluorescein into the conjunctival sac and recording the interval between the last complete blink and the first appearance of a dry spot or disruption of the tear film.

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. Postoperative week 1	3.50 seconds Standard Deviation 1.35	3.00 seconds Standard Deviation 1.16
Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. Postoperative week 4	5.64 seconds Standard Deviation 1.89	3.96 seconds Standard Deviation 1.46
Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. Baseline	4.98 seconds Standard Deviation 0.53	4.50 seconds Standard Deviation 0.36
Tear Break-up Time (TBUT) That is Related to Dry Eye Severity. Postoperative week 12	6.69 seconds Standard Deviation 2.23	4.38 seconds Standard Deviation 1.92

PRIMARY outcome

Timeframe: 12 weeks

Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and corneal fluorescein staining was evaluated. Instillation of fluorescein in both eyes. After 1 or 2 full blinks, the intensity of staining of both cornea was scored. According to the National Eye Institute (NEI) workshop grading system, the cornea was divided into five sections. The minimum staining score was 0 and the maximum staining score was 15 points (up to 3 points for each section).

0 : best score (no corneal damage) 15 : worst score (severe corneal damages)

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Corneal Fluorescein Staining That is Related to Dry Eye Severity. Baseline	1.52 scores Standard Deviation 0.41	1.78 scores Standard Deviation 0.28
Corneal Fluorescein Staining That is Related to Dry Eye Severity. Postoperative week 1	2.09 scores Standard Deviation 0.45	2.88 scores Standard Deviation 0.31
Corneal Fluorescein Staining That is Related to Dry Eye Severity. Postoperative week 4	1.09 scores Standard Deviation 0.33	1.73 scores Standard Deviation 0.23
Corneal Fluorescein Staining That is Related to Dry Eye Severity. Postoperative week 12	0.48 scores Standard Deviation 0.77	1.21 scores Standard Deviation 1.45

PRIMARY outcome

Timeframe: 12 weeks

Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and conjunctival LG staining were evaluated. Instillation of 1% lissamine green in both eyes. After 1 or 2 full blinks, the intensity of staining of both medial and lateral bulbar conjunctiva was cored. According to the National Eye Institute (NEI) workshop grading system, the conjunctiva was divided into six sections. The minimum staining score was 0 and the maximum staining score was 18 points (up to 3 points for each section).

0 : best score (no conjunctival damage) 18 : worst score (severe conjunctival damages)

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Lissamine Green (LG) Conjunctival Staining That is Related to Dry Eye Severity Postoperative week 4	0.86 Scores on a scale Standard Deviation 1.18	2.31 Scores on a scale Standard Deviation 2.12
Lissamine Green (LG) Conjunctival Staining That is Related to Dry Eye Severity Baseline	1.40 Scores on a scale Standard Deviation 0.32	1.91 Scores on a scale Standard Deviation 0.22
Lissamine Green (LG) Conjunctival Staining That is Related to Dry Eye Severity Postoperative week 1	2.56 Scores on a scale Standard Deviation 0.73	3.86 Scores on a scale Standard Deviation 0.50
Lissamine Green (LG) Conjunctival Staining That is Related to Dry Eye Severity Postoperative week 12	0.36 Scores on a scale Standard Deviation 0.76	1.33 Scores on a scale Standard Deviation 2.04

SECONDARY outcome

Timeframe: 12 weeks

Anterior chamber inflammation was examined with a slit-lamp clinically, and divided into six grades using the Standardization of Uveitis Nomenclature (SUN) working group grading scheme.

grade 0 : <1 cell in field, grade 0.5 : 1-5 cells in field, grade 1 : 6-15 cells in field, grade 2 : 16-25 cells in field grade 3 : 26-50 cells in field, grade 4 : >50 cells in field Field size is a 1 mm X 1 mm slit beam

Outcome measures

Measure	Diqufosol n=45 eyes 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=49 eyes 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Grades of Anterior Chamber Cells. Baseline	0 grade Standard Deviation 0	0 grade Standard Deviation 0
Grades of Anterior Chamber Cells. Postoperative week 1	1.54 grade Standard Deviation 0.34	1.78 grade Standard Deviation 0.25
Grades of Anterior Chamber Cells. Postoperative week 4	0.16 grade Standard Deviation 0.26	0.36 grade Standard Deviation 0.22
Grades of Anterior Chamber Cells. Postoperative week 12	0 grade Standard Deviation 0	0 grade Standard Deviation 0

SECONDARY outcome

Timeframe: 12 weeks

Population: Overall, 1 of 31 patients (3.22%), a 64-year-old man who underwent bilateral sequential same-day cataract surgery, stopped using the study eye drops owing to severe irritation in the D group.

Drug-related discomfort is defined as having started after eye drop instillation and lasting several minutes, occurring every time during instillation at any time up to 12 weeks into the follow-up period. Patients that had any adverse events or wanted to stop using the eye drops were excluded from the study, but these patients were included in the safety evaluation.

Outcome measures

Measure	Diqufosol n=31 Participants 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=33 Participants 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Number of Participants Who Stop Using the Eye Drops Due to Drug-related Discomfort	1 participants	0 participants

Adverse Events

Diqufosol

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Hyaluronate

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Diqufosol n=31 participants at risk 3% Diquafosol Tetrasodium Ophthalmic Solution Diquafosol (Diquas): Diquafosol group used diquafosol 6 times a day during study period.	Hyaluronate n=33 participants at risk 0.1% Sodium Hyaluronate Ophthalmic Solution Sodium Hyaluronate (Hyalein): Hyaluronate group used sodium hyaluronate 6 times a day during study period.
Eye disorders Severe irritation	3.2% 1/31 • Number of events 1 • 12 weeks Patients that had any adverse events or wanted to stop using the eye drops were excluded from the study, but these patients were included in the safety evaluation.	0.00% 0/33 • 12 weeks Patients that had any adverse events or wanted to stop using the eye drops were excluded from the study, but these patients were included in the safety evaluation.

Additional Information

Dr. JinKwon Chung

Soonchunhyang University Hospital

Phone: 82-2-709-9354

Email: schcornea@schmc.ac.kr

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place