Riboflavin at 4ºC for the Management of Pain After Crosslinking for Keratoconus Patients

NCT03760770 | Unknown DMC

• 1 other identifier: CEI-2018/10/01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The objective of corneal collagen crosslinking (CXL) is to increase the binding of intrafibrillary and interfibrillary covalent bonds to improve the mechanical stability of the cornea and thus to stop the progression of corneal ectasias. Although the vast majority of studies have described pain after photorefractive keratectomy (PRK), the pathophysiological principle of pain is similar in CXL. From the anatomical point of view, the corneal epithelium is the most densely innervated and sensitive surface of the body, being 300-600 times greater than in the skin. The pain after CXL comes from several routes, the process begins with the epithelial rupture that generates exposure of the nerve endings, induces apoptosis and necrosis of the epithelial cells. Subsequently an inflammatory cascade is initiated in which the different cytokines stimulate the nerve terminals. Inflammatory mediators also activate the ion channels in the nerve membrane, and this process continues until the epithelium heals. Additionally, exposure to UVA rays can also cause nerve damage. The effect of local cold for pain management has already been reported in PRK. By cooling the cornea, the release of chemical mediators and inflammation can be reduced. In the CXL radiation is transformed into several forms of energy: fluorescent radiation, chemical energy and, to a small extent, heat. The CXL process is energetically comparable to photosynthesis, in which the radiation energy is transformed into chemical energy (glucose) with the help of pigments (chlorophyll). The thermal effect is negligible in the photochemical method of CXL. Justification: No method for the control of pain after crosslinking is considered ideal or universally accepted, the importance of this study lies in looking for an additional tool to reduce the most common postoperative complaint in a highly performed procedure worldwide. Hypothesis: The application of riboflavin at 4oC reduces the pain assessment after the CXL. Purpose: to evaluate the effect of the application of riboflavin at 4oC in the assessment of postoperative pain in patients undergoing CXL. Materials and methods: Prospective and interventional clinical study in patients older than 18 years with a diagnosis of keratoconus who underwent CXL, in the cornea and refractive surgery service of the Ophthalmology institute Fundación Conde de Valenciana.

Conditions

Keratoconus; Crosslinking

Keywords

Crosslinking; Keratoconus; Cold; Pain

Outcome Measures

Primary Outcomes (1)

• Change pain perception in patients undergoing crosslinking with riboflavin at 4ºC

  A previously validated numerical pain scale questionnaire was applied. Patients are asked to indicate their pain intensity on a scale of 0 to 10, explaining that 0 does not represent pain at all and 10 is a severe and disabling pain.

  2 postoperative hours and from day 1 to 5 postoperative.

Study Arms (2)

Riboflavin at 4ºC

EXPERIMENTAL

patients treated with Riboflavin at 4ºC in crosslinking (cases).

Procedure: corneal collagen crosslinking

Riboflavin at room temperature

EXPERIMENTAL

patients treated with Riboflavin at room temperature in crosslinking (controls)

Procedure: corneal collagen crosslinking

Interventions

corneal collagen crosslinking PROCEDURE

Crosslinking in patients with progressive keratoconus.

Also known as: No Cold riboflavin (Riboflavin at room temperature), Cold riboflavin (Riboflavin at 4ºC)

Riboflavin at 4ºC; Riboflavin at room temperature

Eligibility Criteria

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

You may qualify if:

• patients of any gender
• older than 18 years
• diagnosis of keratoconus who require management with crosslinking in both eyes for evidence of progression.

You may not qualify if:

• crosslinking without removal of epithelium or unilateral crosslinking.
• patients with other ocular conditions different from keratoconus.
• cognitive disability that limits the compression of the pain test as Down syndrome, etc.

Sponsors & Collaborators

• Instituto de Oftalmología Fundación Conde de Valenciana: lead

Study Sites (1)

Instituto de oftalmología conde de Valenciana

Mexico City, 06800, Mexico

RECRUITING

Related Publications (17)

• Spadea L, Salvatore S, Paroli MP, Vingolo EM. Recovery of corneal sensitivity after collagen crosslinking with and without epithelial debridement in eyes with keratoconus. J Cataract Refract Surg. 2015 Mar;41(3):527-32. doi: 10.1016/j.jcrs.2014.06.030. Epub 2015 Jan 30.

  PMID: 25648281 RESULT

• Mencucci R, Mazzotta C, Rossi F, Ponchietti C, Pini R, Baiocchi S, Caporossi A, Menchini U. Riboflavin and ultraviolet A collagen crosslinking: in vivo thermographic analysis of the corneal surface. J Cataract Refract Surg. 2007 Jun;33(6):1005-8. doi: 10.1016/j.jcrs.2007.03.021.

  PMID: 17531694 RESULT

• Garcia R, de Andrade DC, Teixeira MJ, Nozaki SS, Bechara SJ. Mechanisms of Corneal Pain and Implications for Postoperative Pain After Laser Correction of Refractive Errors. Clin J Pain. 2016 May;32(5):450-8. doi: 10.1097/ajp.0000000000000271.

  PMID: 27504514 RESULT

• Woreta FA, Gupta A, Hochstetler B, Bower KS. Management of post-photorefractive keratectomy pain. Surv Ophthalmol. 2013 Nov-Dec;58(6):529-35. doi: 10.1016/j.survophthal.2012.11.004.

  PMID: 24160728 RESULT

• Xia Y, Chai X, Zhou C, Ren Q. Corneal nerve morphology and sensitivity changes after ultraviolet A/riboflavin treatment. Exp Eye Res. 2011 Oct;93(4):541-7. doi: 10.1016/j.exer.2011.06.021. Epub 2011 Jul 13.

  PMID: 21763309 RESULT

• Kitazawa Y, Maekawa E, Sasaki S, Tokoro T, Mochizuki M, Ito S. Cooling effect on excimer laser photorefractive keratectomy. J Cataract Refract Surg. 1999 Oct;25(10):1349-55. doi: 10.1016/s0886-3350(99)00207-2.

  PMID: 10511934 RESULT

• Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet A. I. Principles. Ocul Surf. 2013 Apr;11(2):65-74. doi: 10.1016/j.jtos.2013.01.002. Epub 2013 Jan 24.

  PMID: 23583042 RESULT

• Sharif R, Bak-Nielsen S, Hjortdal J, Karamichos D. Pathogenesis of Keratoconus: The intriguing therapeutic potential of Prolactin-inducible protein. Prog Retin Eye Res. 2018 Nov;67:150-167. doi: 10.1016/j.preteyeres.2018.05.002. Epub 2018 Jul 13.

  PMID: 29758268 RESULT

• Galvis V, Tello A, Carreno NI, Berrospi RD, Nino CA. Risk Factors for Keratoconus: Atopy and Eye Rubbing. Cornea. 2017 Jan;36(1):e1. doi: 10.1097/ICO.0000000000001052. No abstract available.

  PMID: 27755195 RESULT

• Godefrooij DA, de Wit GA, Uiterwaal CS, Imhof SM, Wisse RP. Age-specific Incidence and Prevalence of Keratoconus: A Nationwide Registration Study. Am J Ophthalmol. 2017 Mar;175:169-172. doi: 10.1016/j.ajo.2016.12.015. Epub 2016 Dec 28.

  PMID: 28039037 RESULT

• 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 RESULT

• 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 RESULT

• Peyman A, Nouralishahi A, Hafezi F, Kling S, Peyman M. Stromal Demarcation Line in Pulsed Versus Continuous Light Accelerated Corneal Cross-linking for Keratoconus. J Refract Surg. 2016 Mar;32(3):206-8. doi: 10.3928/1081597X-20160204-03.

  PMID: 27027629 RESULT

• Kymes SM, Walline JJ, Zadnik K, Sterling J, Gordon MO; Collaborative Longitudinal Evaluation of Keratoconus Study Group. Changes in the quality-of-life of people with keratoconus. Am J Ophthalmol. 2008 Apr;145(4):611-617. doi: 10.1016/j.ajo.2007.11.017. Epub 2008 Jan 28.

  PMID: 18226798 RESULT

• Lichtinger A, Purcell TL, Schanzlin DJ, Chayet AS. Gabapentin for postoperative pain after photorefractive keratectomy: a prospective, randomized, double-blind, placebo-controlled trial. J Refract Surg. 2011 Aug;27(8):613-7. doi: 10.3928/1081597X-20110210-01. Epub 2011 Feb 28.

  PMID: 21366172 RESULT

• Spadea L, Tonti E, Vingolo EM. Corneal stromal demarcation line after collagen cross-linking in corneal ectatic diseases: a review of the literature. Clin Ophthalmol. 2016 Sep 19;10:1803-1810. doi: 10.2147/OPTH.S117372. eCollection 2016.

  PMID: 27695286 RESULT

• Yam JC, Chan CW, Cheng AC. Corneal collagen cross-linking demarcation line depth assessed by Visante OCT After CXL for keratoconus and corneal ectasia. J Refract Surg. 2012 Jul;28(7):475-81. doi: 10.3928/1081597X-20120615-03.

  PMID: 22767165 RESULT

MeSH Terms

Conditions

Keratoconus; Common Cold; Pain

Interventions

Corneal Cross-Linking

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases; Respiratory Tract Infections; Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Photochemotherapy; Combined Modality Therapy; Therapeutics; Drug Therapy; Phototherapy

Central Study Contacts

laura Toro, MD

CONTACT

+52154421700; lauratorog@hotmail.com

Enrique Graue Hernandez, MD, MSc

CONTACT

+52154421700; egraueh@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2018
• First Posted: November 30, 2018
• Study Start: February 1, 2018
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: November 30, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)