Intracanalicular Dexamethasone Insert for Post-Corneal Cross-Linking Inflammation and Pain- The LINK Study

Sponsor

Sight Medical Doctors PLLC (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT04168112

Collaborator

Ocular Therapeutix, Inc. (Industry)

Enrollment

Location

Arms

33.6

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

There is no standard of care medication regimen for the management of pain and inflammation post-corneal crosslinking (CXL), although most cornea specialists agree on use of an antibiotic and steroid eye drop in the immediate postoperative period. However, steroid tapering schedule and use of additional topical non-steroidal anti-inflammatory (NSAID) eyedrops vary amongst practitioners. The goal of this study is to compare postoperative pain scores between patients receiving a tapering dose of topical steroids over 1-month post-CXL, versus those receiving an intracanalicular dexamethasone insert.

Condition or Disease	Intervention/Treatment	Phase
Keratoconus, Unstable Collagen Crosslinking Postoperative Pain	Drug: Dextenza Drug: Prednisolone Acetate	Phase 4

Detailed Description

Keratoconus is a progressive ectatic disease of the cornea, leading to worsening of astigmatism and vision over time. With FDA approval of corneal collagen cross-linking (CXL), we now have the ability to halt the progression of keratoconus and prevent further vision loss in these patients. Although CXL has now become standard of care, the immediate post-operative period can be quite painful despite use of anti-inflammatory medications/eye drops. The goal of this study is to evaluate the efficacy of an intracanalicular dexamethasone insert in reduction of post-CXL pain as compared to routine steroid eye drop therapy.

To date, no studies have been performed evaluating the success of an intracanalicular dexamethasone insert for the treatment of postoperative inflammation and pain in corneal cross-linking patients. Oftentimes, patients experience a great deal of discomfort post-CXL, which may also make it difficult to apply eye drops in the correct fashion. Use of a dexamethasone insert alleviates the need for postoperative steroid eye drops and may provide increased pain relief post-CXL as compared to topical therapy. This will be a head-to-head study where steroid therapy (topical or insert) will begin in a standard fashion on the date of CXL. This will allow for accurate comparison of a 4-week taper of topical steroids, versus a dexamethasone insert designed to release steroid for 30 days.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Two cohorts of patients will be studied (10 patients each group). Cohort A: intracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or another class if allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily x 10 days). Cohort B: Patients are placed on standard postoperative regimen of postoperative fluoroquinolone antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily (QID) x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: 4 times daily x1 week, three times daily (TID) x 1 week, twice daily (BID) x 1 week, and once daily (QD) x 1 week).Two cohorts of patients will be studied (10 patients each group). Cohort A: intracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or another class if allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily x 10 days). Cohort B: Patients are placed on standard postoperative regimen of postoperative fluoroquinolone antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye 4 times daily (QID) x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: 4 times daily x1 week, three times daily (TID) x 1 week, twice daily (BID) x 1 week, and once daily (QD) x 1 week).

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

Intracanalicular Dexamethasone Insert for Post-Corneal Cross-Linking Inflammation and Pain- The LINK Study

Actual Study Start Date :

Feb 12, 2020

Anticipated Primary Completion Date :

Apr 1, 2022

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A Intracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days).	Drug: Dextenza Placement of intracanalicular dexamethasone insert for post-crosslinking inflammation and pain Other Names: Intracanalicular dexamethasone insert
Active Comparator: Group B Patients are placed on standard postoperative regimen of postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: QID x1 week, TID x 1 week, BID x 1 week, and Qday x 1 week.	Drug: Prednisolone Acetate post-crosslinking eye drop prednisolone acetate given in a tapering schedule over 1 month

Arm

Intervention/Treatment

Experimental: Group A

Intracanalicular dexamethasone insert is placed on day of crosslinking (CXL); patients will still receive postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days).

Drug: Dextenza

Placement of intracanalicular dexamethasone insert for post-crosslinking inflammation and pain

Other Names:

Intracanalicular dexamethasone insert

Active Comparator: Group B

Patients are placed on standard postoperative regimen of postoperative fluoroquinolone (or other class in case of allergy) antibiotic eye drops with instructions for use (i.e. 1 drop in operative eye QID x 10 days) and Prednisolone acetate 1% ophthalmic solution tapered over 1 month in the following schedule: QID x1 week, TID x 1 week, BID x 1 week, and Qday x 1 week.

Drug: Prednisolone Acetate

post-crosslinking eye drop prednisolone acetate given in a tapering schedule over 1 month

Outcome Measures

Primary Outcome Measures

Change in degree of postoperative pain between groups from date of surgery to 1 month post-CXL [Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)]
Utilizing the standardized Wong-Baker visual analog pain scale, graded from 0 to 10 (no pain to increasingly worse pain (worst at 10/10))
Degree and improvement of ocular surface inflammation between groups from date of surgery to 1 month post-CXL [assessed at baseline, 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (8 visits total)]
Assessment of corneal edema/cells (if any), degree of conjunctival injection (if any) Grading will be standardized according to the Brien Holden Vision Institute grading system

Secondary Outcome Measures

Rate of corneal re-epithelialization [Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)]
Evaluation of rate of corneal re-epithelialization post-crosslinking
Subjective 'ease of postoperative care' for patients receiving standard topical steroid eye drop taper vs. dexamethasone insert [postoperative week 4 (POW4)]
Questionnaire at final visit regarding ease of postoperative eye drop use
Notation of need for use of "rescue" pain medication [Assessement of use of additional/adjunctive pain/antiinflammatory medications will be done for each patient at postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)]
Use of oral non-steroidal antiinflammatory (NSAID), acetaminophen, prescribed pain medication) between groups

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Progressive keratoconus with planned corneal cross-linking in one or both eyes
Age 18 years and older
Ability to provide informed consent for procedures
Ability to attend scheduled follow up visits

Exclusion Criteria:

Age less than 18
Pregnancy/currently breast-feeding
Inability to provide informed consent
Documented adverse reaction to steroid (e.g. "steroid responder", allergy, etc)
Punctal stenosis
Previous corneal transplant surgery
Systemic concomitant use of controlled substance for pain management (i.e. oxycodone)
Concurrent use of topical steroid eye drops
Systemic, topical or intravitreal steroid use within 1 month of baseline
Active history of chronic or recurrent inflammatory eye disease in either eye
History of ocular herpetic infection (inclusive of Herpes Simplex 1/2, Varicella Zoster, Epstein Barr, Cytomegalovirus)
History of neurotrophic keratitis, uncontrolled diabetes, or other disease entities that may preclude proper healing