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

Postoperative Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04168112
• Other study ID #: LINK1
• Status: Completed
• Phase: Phase 4
• Start date: February 12, 2020
• Est. completion date: April 5, 2023

Study information

• Verified date: January 2024
• Source: Sight Medical Doctors PLLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 5, 2023
• Est. primary completion date: October 24, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Collagen Crosslinking
• Inflammation
• Keratoconus
• Keratoconus, Unstable
• Postoperative Pain

Intervention

Drug:
• Dextenza
Placement of intracanalicular dexamethasone insert for post-crosslinking inflammation and pain
• Prednisolone Acetate
post-crosslinking eye drop prednisolone acetate given in a tapering schedule over 1 month

Locations

Country	Name	City	State
United States	SightMD	Babylon	New York

Sponsors (2)

Lead Sponsor	Collaborator
Sight Medical Doctors PLLC	Ocular Therapeutix, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Rate of Corneal Re-epithelialization	Evaluation of rate of corneal re-epithelialization post-crosslinking at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4	Assessed at 1 day of surgery, postoperative days 1 ,3, 7, postoperative weeks 2 ,3 and 4 (7 visits total)
Secondary	Subjective 'Ease of Postoperative Care' for Patients Receiving Standard Topical Steroid Eye Drop Taper vs. Dexamethasone Insert	Questionnaire at final visit regarding ease of postoperative eye drop use	postoperative week 4 (POW4)
Secondary	Notation of Need for Use of "Rescue" Pain Medication	Use of oral non-steroidal anti-inflammatory (NSAID), acetaminophen, prescribed pain medication) between groups	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)