Clinical trial NCT03760770: Riboflavin at 4ºC for the Management of Pain After Crosslinking for Keratoconus Patients
Official title: Riboflavin at 4ºC for the Management of Pain After Crosslinking for Keratoconus Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Keratoconus
Crosslinking
Keywords: Crosslinking
Keratoconus
Cold
Pain
Lead sponsor: Instituto de Oftalmología Fundación Conde de Valenciana
Sponsor class: OTHER
First posted: 2018-11-30
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change pain perception in patients undergoing crosslinking with riboflavin at 4ºC
timeFrame: 2 postoperative hours and from day 1 to 5 postoperative.
Secondary outcomes:
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: Instituto de oftalmología conde de Valenciana
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.