<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03760770</url>
  </required_header>
  <id_info>
    <org_study_id>CEI-2018/10/01</org_study_id>
    <nct_id>NCT03760770</nct_id>
  </id_info>
  <brief_title>Riboflavin at 4ºC for the Management of Pain After Crosslinking for Keratoconus Patients</brief_title>
  <official_title>Riboflavin at 4ºC for the Management of Pain After Crosslinking for Keratoconus Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto de Oftalmología Fundación Conde de Valenciana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto de Oftalmología Fundación Conde de Valenciana</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: The objective of corneal collagen crosslinking (CXL) is to increase the binding&#xD;
      of intrafibrillary and interfibrillary covalent bonds to improve the mechanical stability of&#xD;
      the cornea and thus to stop the progression of corneal ectasias. Although the vast majority&#xD;
      of studies have described pain after photorefractive keratectomy (PRK), the&#xD;
      pathophysiological principle of pain is similar in CXL. From the anatomical point of view,&#xD;
      the corneal epithelium is the most densely innervated and sensitive surface of the body,&#xD;
      being 300-600 times greater than in the skin. The pain after CXL comes from several routes,&#xD;
      the process begins with the epithelial rupture that generates exposure of the nerve endings,&#xD;
      induces apoptosis and necrosis of the epithelial cells. Subsequently an inflammatory cascade&#xD;
      is initiated in which the different cytokines stimulate the nerve terminals. Inflammatory&#xD;
      mediators also activate the ion channels in the nerve membrane, and this process continues&#xD;
      until the epithelium heals. Additionally, exposure to UVA rays can also cause nerve damage.&#xD;
      The effect of local cold for pain management has already been reported in PRK. By cooling the&#xD;
      cornea, the release of chemical mediators and inflammation can be reduced. In the CXL&#xD;
      radiation is transformed into several forms of energy: fluorescent radiation, chemical energy&#xD;
      and, to a small extent, heat. The CXL process is energetically comparable to photosynthesis,&#xD;
      in which the radiation energy is transformed into chemical energy (glucose) with the help of&#xD;
      pigments (chlorophyll). The thermal effect is negligible in the photochemical method of CXL.&#xD;
      Justification: No method for the control of pain after crosslinking is considered ideal or&#xD;
      universally accepted, the importance of this study lies in looking for an additional tool to&#xD;
      reduce the most common postoperative complaint in a highly performed procedure worldwide.&#xD;
      Hypothesis: The application of riboflavin at 4oC reduces the pain assessment after the CXL.&#xD;
      Purpose: to evaluate the effect of the application of riboflavin at 4oC in the assessment of&#xD;
      postoperative pain in patients undergoing CXL. Materials and methods: Prospective and&#xD;
      interventional clinical study in patients older than 18 years with a diagnosis of keratoconus&#xD;
      who underwent CXL, in the cornea and refractive surgery service of the Ophthalmology&#xD;
      institute Fundación Conde de Valenciana.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2018</start_date>
  <completion_date type="Anticipated">February 1, 2019</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change pain perception in patients undergoing crosslinking with riboflavin at 4ºC</measure>
    <time_frame>2 postoperative hours and from day 1 to 5 postoperative.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Keratoconus</condition>
  <condition>Crosslinking</condition>
  <arm_group>
    <arm_group_label>Riboflavin at 4ºC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients treated with Riboflavin at 4ºC in crosslinking (cases).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Riboflavin at room temperature</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>patients treated with Riboflavin at room temperature in crosslinking (controls)</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>corneal collagen crosslinking</intervention_name>
    <description>Crosslinking in patients with progressive keratoconus.</description>
    <arm_group_label>Riboflavin at 4ºC</arm_group_label>
    <arm_group_label>Riboflavin at room temperature</arm_group_label>
    <other_name>No Cold riboflavin (Riboflavin at room temperature)</other_name>
    <other_name>Cold riboflavin (Riboflavin at 4ºC)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients of any gender&#xD;
&#xD;
          -  older than 18 years&#xD;
&#xD;
          -  diagnosis of keratoconus who require management with crosslinking in both eyes for&#xD;
             evidence of progression.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  crosslinking without removal of epithelium or unilateral crosslinking.&#xD;
&#xD;
          -  patients with other ocular conditions different from keratoconus.&#xD;
&#xD;
          -  cognitive disability that limits the compression of the pain test as Down syndrome,&#xD;
             etc.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>laura Toro, MD</last_name>
    <phone>+52154421700</phone>
    <phone_ext>3710</phone_ext>
    <email>lauratorog@hotmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Enrique Graue Hernandez, MD, MSc</last_name>
    <phone>+52154421700</phone>
    <phone_ext>3710</phone_ext>
    <email>egraueh@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto de oftalmología conde de Valenciana</name>
      <address>
        <city>Mexico City</city>
        <zip>06800</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Enrique Graue Hernandez, MD MSc</last_name>
      <phone>+52 5554421700</phone>
      <phone_ext>3710</phone_ext>
      <email>egraueh@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Laura Toro, MD</last_name>
      <phone>+52 5554421700</phone>
      <phone_ext>3710</phone_ext>
      <email>lauratorog@hotmail.com</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <results_reference>
    <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>
    <PMID>25648281</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>17531694</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>27504514</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>24160728</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>21763309</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>10511934</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>23583042</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>29758268</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>27755195</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>28039037</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>22547128</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>12719068</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>27027629</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>18226798</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>21366172</PMID>
  </results_reference>
  <results_reference>
    <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>
    <PMID>27695286</PMID>
  </results_reference>
  <results_reference>
    <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.</citation>
    <PMID>22767165</PMID>
  </results_reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 30, 2018</study_first_posted>
  <last_update_submitted>November 29, 2018</last_update_submitted>
  <last_update_submitted_qc>November 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Crosslinking</keyword>
  <keyword>Keratoconus</keyword>
  <keyword>Cold</keyword>
  <keyword>Pain</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratoconus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Riboflavin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03760770
org study id: CEI-2018/10/01
nct id: NCT03760770
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change pain perception in patients undergoing crosslinking with riboflavin at 4ºC
time frame: 2 postoperative hours and from day 1 to 5 postoperative.
description: 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.
arm group label: Riboflavin at 4ºC
arm group type: Experimental
description: patients treated with Riboflavin at 4ºC in crosslinking (cases).
arm group label: Riboflavin at room temperature
arm group type: Experimental
description: patients treated with Riboflavin at room temperature in crosslinking (controls)
intervention type: Procedure
intervention name: corneal collagen crosslinking
description: Crosslinking in patients with progressive keratoconus.
arm group label: Riboflavin at 4ºC
arm group label: Riboflavin at room temperature
other name: No Cold riboflavin (Riboflavin at room temperature)
other name: Cold riboflavin (Riboflavin at 4ºC)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: laura Toro, MD
phone: +52154421700
phone ext: 3710
email: lauratorog@hotmail.com
last name: Enrique Graue Hernandez, MD, MSc
phone: +52154421700
phone ext: 3710
email: egraueh@gmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
country: Mexico
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.
PMID: 25648281
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.
PMID: 17531694
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.
PMID: 27504514
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.
PMID: 24160728
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.
PMID: 21763309
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.
PMID: 10511934
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.
PMID: 23583042
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.
PMID: 29758268
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.
PMID: 27755195
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.
PMID: 28039037
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.
PMID: 22547128
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.
PMID: 12719068
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.
PMID: 27027629
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.
PMID: 18226798
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.
PMID: 21366172
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.
PMID: 27695286
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.
PMID: 22767165
responsible party type: Sponsor
mesh term: Keratoconus
mesh term: Riboflavin
sharing ipd: No