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

NCT04168112 | Completed Phase 4 Results FDA Drug

• 1 other identifier: LINK1
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Keratoconus, Unstable; Collagen Crosslinking; Postoperative Pain

Keywords

Collagen Crosslinking; Keratoconus; Dexamethasone; Intracanalicular Insert

Outcome Measures

Primary Outcomes (2)

• Change in Degree of Postoperative Pain Between Groups From Date of Surgery Through 1 Month Post-CXL (Day of Surgery, Postoperative Days 1 ,3, 7, Postoperative Weeks 2 ,3 and 4)

  Utilizing the standardized Wong-Baker visual analog pain scale, graded from 0 to 10 (no pain to increasingly worse pain (worst at 10/10))

  Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

• Degree and Improvement of Ocular Surface Inflammation Between Groups From Date of Surgery Through 1 Month Post-CXL (Day of Surgery, Postoperative Days 1 ,3, 7, Postoperative Weeks 2 ,3 and 4)

  Assessment of corneal edema/cells (if any), degree of conjunctiva injection (if any) Grading will be from 0 to 4, with "0" being no conjunctival injection, and "4" indicating severe, diffuse conjunctival injection. Presence of corneal cells will be noted if present or absent.

  assessed at day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)

Secondary Outcomes (3)

• 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)

• Subjective 'Ease of Postoperative Care' for Patients Receiving Standard Topical Steroid Eye Drop Taper vs. Dexamethasone Insert

  postoperative week 4 (POW4)

• 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)

Study Arms (2)

Group A

EXPERIMENTAL

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

Group B

ACTIVE COMPARATOR

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

Interventions

Dextenza DRUG

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

Also known as: Intracanalicular dexamethasone insert

Group A

Prednisolone Acetate DRUG

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

Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sight Medical Doctors PLLC: lead
• Ocular Therapeutix, Inc.: collaborator

Study Sites (1)

SightMD

Babylon, New York, 11702, United States

Location

Related Publications (13)

• Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319. doi: 10.1016/s0039-6257(97)00119-7.

  PMID: 9493273 BACKGROUND

• Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984 Jan-Feb;28(4):293-322. doi: 10.1016/0039-6257(84)90094-8.

  PMID: 6230745 BACKGROUND

• Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.

  PMID: 12719068 BACKGROUND

• Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet A light. J Cataract Refract Surg. 2006 Feb;32(2):279-83. doi: 10.1016/j.jcrs.2005.12.092.

  PMID: 16565005 BACKGROUND

• Hoyer A, Raiskup-Wolf F, Sporl E, Pillunat LE. [Collagen cross-linking with riboflavin and UVA light in keratoconus. Results from Dresden]. Ophthalmologe. 2009 Feb;106(2):133-40. doi: 10.1007/s00347-008-1783-2. German.

  PMID: 18604541 BACKGROUND

• Wollensak G, Sporl E, Seiler T. [Treatment of keratoconus by collagen cross linking]. Ophthalmologe. 2003 Jan;100(1):44-9. doi: 10.1007/s00347-002-0700-3. German.

  PMID: 12557025 BACKGROUND

• Snibson GR. Collagen cross-linking: a new treatment paradigm in corneal disease - a review. Clin Exp Ophthalmol. 2010 Mar;38(2):141-53. doi: 10.1111/j.1442-9071.2010.02228.x.

  PMID: 20398104 BACKGROUND

• Peyman A, Kamali A, Khushabi M, Nasrollahi K, Kargar N, Taghaodi M, Razmjoo H, Fazel F, Salesi A. Collagen cross-linking effect on progressive keratoconus in patients younger than 18 years of age: A clinical trial. Adv Biomed Res. 2015 Nov 23;4:245. doi: 10.4103/2277-9175.170240. eCollection 2015.

  PMID: 26693470 BACKGROUND

• Ghanem VC, Ghanem RC, de Oliveira R. Postoperative pain after corneal collagen cross-linking. Cornea. 2013 Jan;32(1):20-4. doi: 10.1097/ICO.0b013e31824d6fe3.

  PMID: 22547128 BACKGROUND

• Zarei-Ghanavati S, Jafarpour S, Radyn-Majd A, Hosseinikhah-Manshadi H. Evaluation of early postoperative ocular pain after photorefractive keratectomy and corneal crosslinking. J Cataract Refract Surg. 2018 May;44(5):566-570. doi: 10.1016/j.jcrs.2018.02.019. Epub 2018 May 9.

  PMID: 29753555 BACKGROUND

• Serna-Ojeda JC, Santana-Cruz O, Quiroz-Casian N, Gonzalez-Mendoza E, Mercado-Orozco JL, Navas A, Lichtinger A, Graue-Hernandez EO. Pain Management in Corneal Collagen Crosslinking for Keratoconus: A Comparative Case Series. J Ocul Pharmacol Ther. 2019 Jul/Aug;35(6):325-330. doi: 10.1089/jop.2019.0021. Epub 2019 Jun 19.

  PMID: 31216215 BACKGROUND

• Kocluk Y, Cetinkaya S, Sukgen EA, Gunay M, Mete A. Comparing the effects of two different contact lenses on corneal re-epithelialization after corneal collagen cross-linking. Pak J Med Sci. 2017 May-Jun;33(3):680-685. doi: 10.12669/pjms.333.12241.

  PMID: 28811794 BACKGROUND

• Nattis AS, Rosenberg ED, Rasool F. Intracanalicular dexamethasone insert for post-corneal crosslinking inflammation and pain: the LINK study. J Cataract Refract Surg. 2023 Nov 1;49(11):1114-1119. doi: 10.1097/j.jcrs.0000000000001279.

  PMID: 37532250 DERIVED

MeSH Terms

Conditions

Keratoconus; Pain, Postoperative

Interventions

Calcium Dobesilate; prednisolone acetate

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

The biggest limitation of this study is the small sample size; 20 eyes in each group limit findings of statistical significance; larger future studies may help more definitively illuminate differences between groups. We also had 2 patients in the control group who dropped out of the study early on-data from their experiences would have been valuable in terms of comparisons between groups.

Results Point of Contact

• Title: Dr. Alanna Nattis
• Organization: SightMD

anattis@sightmd.com

631-957-2816

Study Officials

• Alanna Nattis, DO

  Sight Medical Doctors PLLC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ophthalmologist, Director of Clinical Research

Model Details: 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).

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 19, 2019
• Study Start: February 12, 2020
• Primary Completion: October 24, 2022
• Study Completion: April 5, 2023
• Last Updated: January 30, 2024
• Results First Posted: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)