Clinical Effects and Safety of 3% Diquafosol After Cataract Surgery

Dry Eye Syndromes Clinical Trial

Official title:

Clinical Effects and Safety of 3% Diquafosol Ophthalmic Solution for Patients With Dry Eye After Cataract Surgery: A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02608489
• Other study ID #: SCHUH 2013-12-012
• Status: Completed
• Phase: N/A
• First received: November 14, 2015
• Last updated: November 20, 2015
• Start date: January 2014
• Est. completion date: January 2015

Study information

• Verified date: November 2015
• Source: Soonchunhyang University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is determine whether 3% diquafosol and 0.1% sodium hyaluronate are effective and safe in the treatment of patients with dry eye after cataract surgery.

Description:

Study group and protocol: This was a prospective open-label randomized study. All patients were given a full explanation of the study, and written informed consent was obtained from all participants. The study protocol adhered to the tenets of the Declaration of Helsinki. The Institutional Review Board and Ethics Committee, Soonchunhyang University Seoul Hospital, approved this study (SCHUH 2013-12-012). Patients were randomly allocated into the diquafosol group (D group) or the hyaluronate group (H group) using a simple unrestricted randomization method by the controller. The D group used 3% diquafosol tetrasodium ophthalmic solution (Diquas®; Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times a day and the H group used 0.1% sodium hyaluronate ophthalmic solution (Hyalein®; Santen Pharmaceutical Co., Ltd., Osaka, Japan) six times a day. Both groups instilled each eye drop from postoperative day 1 to postoperative week 12.

Participants: 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 2014 and January 2015 were enrolled. The inclusion criteria were patients with mild to moderate dry eye (level 1 or 2) based on the dry eye severity scale adopted by the Dry Eye Workshop (DEWS) report and who used only artificial tears occasionally1, and patients without or with mild blepharitis.18 The exclusion criteria were presence of any complications after cataract surgery such as cystoid macular edema, patients using any topical eye drops on a regular basis, treatment history of dry eye beyond artificial tears, any ocular surgery within the prior 6 months, contact lens wear, serious ocular surface disease (e.g., Sjögren's syndrome, ocular pemphigoid, conjunctival scarring, chemical injury), lacrimal or eyelid disease (e.g., moderate to severe blepharitis18), use of concomitant medications that could cause dry eye (e.g., antihistamines, antidepressants, decongestants, anticholinergic drugs), and allergy to any of the study medications.

Objective and subjective clinical assessments of dry eye: All patients underwent ophthalmic examinations preoperatively and postoperatively in the order of following : uncorrected distant visual acuity (UDVA) test, an ocular surface disease index (OSDI) questionnaire, Schirmer I test without anesthesia, changes in HOAs after blinking, tear break-up time (TBUT), corneal fluorescein staining, and lissamine green (LG) conjunctival staining. Eyelid and anterior chamber cells were evaluated by slit-lamp biomicroscopy to assess the presence of blepharitis/meibomian gland plugging and intraocular inflammation. Routine postoperative examinations were scheduled for 1 week, 4 weeks, and 12 weeks after surgery.

Efficacy and safety evaluation: To evaluate the efficacy of the two different eye drops, we compared each measurement between the two groups throughout the study period, and at each follow-up, and also compared the patterns of changes in each group to identify which group recovered earlier. we evaluated the safety of the two eye drops, including anterior chamber inflammation and discontinuation of the eye drops due to drug-related discomfort. 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.

Surgical procedure: A 2.8 mm clear corneal incision was made at the location of the steep corneal astigmatism axis. A standard phacoemulsification technique was used with topical anesthesia with 2% lidocaine. A foldable IOL was implanted into the capsular bag. There was no suture at the corneal incision site. Patients received moxifloxacin (Vigamox; Alcon, Fort Worth, TX), which is a preservative-free formulation, and rimexolone (Vexol; Alcon), which contains 0.01% BAK, four times a day after surgery for 4 weeks.

Statistical analysis: For statistical analysis, UDVA was converted from Snellen into logMAR values. Baseline data were compared between the groups using the Mann-Whitney U-test, Fisher's exact test, and the linear mixed model after adjusting for inter-eye correlations, age, and sex. In addition, another mixed model was used to compare measurement data between the two groups by considering the correlation between both eyes of each patient at each follow-up. To obtain an overall comparison between treatment responses throughout the study period considering the two levels of correlation in subjects and follow-up, a bivariate generalized linear mixed (GLM) model with asymmetric random effects was used. In the last step, a bivariate GLM model was also used to identify the patterns of changes in measured data throughout the study period. The intergroup differences in adverse events were analyzed using Fisher's exact test. SPSS software (version 21, SPSS, Inc., Chicago, IL) was used for all statistical analyses, and P < .05 was taken to indicate statistical significance.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 90 Years

Eligibility

Inclusion Criteria:

• Bilateral or unilateral cataract undergoing phacoemulsification and intraocular lens (IOL) implantation at Soonchunhyang University Hospital between January 2014 and January 2015

• Patients with mild to moderate dry eye (level 1 or 2) based on the dry eye severity scale adopted by the Dry Eye Workshop (DEWS) report and who used only artificial tears occasionally

Exclusion Criteria:

• Presence of any complications after cataract surgery such as cystoid macular edema

• Patients using any topical eye drops on a regular basis

• Treatment history of dry eye beyond artificial tears

• Any ocular surgery within the prior 6 months

• Contact lens wear

• Serious ocular surface disease (e.g., Sjögren's syndrome, ocular pemphigoid, conjunctival scarring, chemical injury)

• Eyelid or lacrimal disease

• Use of concomitant medications that could cause dry eye and allergy to any of the study medications

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Capsule Opacification
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Drug:
• Diquafosol (Diquas)
Diquafosol group used diquafosol 6 times a day during study period.
• Sodium Hyaluronate (Hyalein)
Hyaluronate group used sodium hyaluronate 6 times a day during study period.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Soonchunhyang University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	an ocular surface disease index (OSDI) questionnaire that is related to dry eye severity.	The OSDI questionnaire consists of 12 questions that evaluate subjective symptoms related to dry eye and vision	1 year	No
Primary	Schirmer I test without anesthesia that is related to dry eye severity.	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.	1 year	No
Primary	changes in HOAs after blinking that is related to dry eye severity.	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.	1 year	No
Primary	tear break-up time (TBUT) that is related to dry eye severity.	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.	1 year	No
Primary	corneal fluorescein staining, and lissamine green (LG) conjunctival staining that are related to dry eye severity.	Ocular surface damage was assessed by the National Eye Institute (NEI) workshop grading system, and corneal fluorescein staining and conjunctival LG staining were evaluated. The maximum staining score is 15 for the cornea and 18 for the conjunctiva.	1 year	No
Secondary	number of participants with anterior chamber inflammation.	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.	1 year	Yes
Secondary	number of participants who stop using the eye drops due to drug-related discomfort	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.	1 year	Yes