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Pain, PostoperativeNCT04439552

fMRI and IVCM Cornea Microscopy of CXL in Keratoconus

An observational study of Pain, Postoperative and Pain, Chronic, run by Boston Children's Hospital at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Evaluation of neuroplasticity of pain pathways and corneal afferent nerve regeneration following corneal crosslinking (CXL) in keratoconus patients using fMRI and corneal In Vivo Confocal Microscopy (IVCM). Read more about this study

Who is it for?
Ages 8 to 35 yearsHealthy volunteers can take part
Conditions the study is for
Pain, Postoperative, Pain, Chronic, Pain, Acute
How many people
60 participants
Where
1 siteUnited States
Study dates
4 Oct 2021to Dec 2027
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 35 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Study population: The population under study are patients with keratoconus who are undergoing a corneal cross-linking (CXL) procedure. Keratoconus is an eye condition where the cornea progressively develops abnormally into a cone shape, which can lead to distorted vision and irreversible vision loss The CXL procedure is designed to restore and maintain the shape of the cornea to avoid these complications.

Who may be able to join

  • CXL Group
  • Age 8-35 years
  • Clinical diagnosis of keratoconus and seeking CXL treatment
  • English speaking ability sufficient to comprehend consent with parental assistance
  • MRI compatible
  • Ability to lie still for an MRI session (60 minutes)
Show all 12Show fewer
  • Control Group
  • Age 8-35 years
  • No diagnosis of keratoconus
  • English speaking ability sufficient to comprehend consent with parental assistance
  • MRI compatible
  • Ability to lie still for an MRI session (60 minutes)

Who cannot join

  • Claustrophobic
  • Weight > 285 lbs (weight limit of the MRI table)
  • Significant medical history, including:
  • Current DSM-IV-TR axis I psychiatric disorders. Chronic pain Significant head injury Seizures Brain tumor Cerebrovascular accident Neurological disease aside from migraine HIV-AIDs Prescription medication strongly implicated in causing dry eyes
  • Magnetic implants or metal-containing tattoos on their chest or above
  • Pregnancy
  • History of contact lens wear
  • Any allergic response to a numbing eyedrop in the past

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Eric A Moulton, OD PhD contact

617-919-6827

eric.moulton@childrens.harvard.edu

Nicholas J Pondelis, BA contact

617-919-1895

nicholas.pondelis@childrens.harvard.edu

United States1 site, 1 recruiting

  • Boston Children's Hospital

    Boston, Massachusetts, 02115

    Nicholas J Pondelis, BA, 617-919-1895, nicholas.pondelis@childrens.harvard.edu

    Recruiting

Other trials in United States

About this study

Official title: Neuroplasticity of Pain Pathways and Corneal Afferent Regeneration Following Corneal Crosslinking (CXL) in Keratoconus

Evaluation of neuroplasticity of pain pathways and corneal afferent nerve regeneration following corneal crosslinking (CXL) in keratoconus patients using fMRI and corneal In Vivo Confocal Microscopy (IVCM).

Read the detailed description

Our long-term goal is to evaluate the transition from acute to chronic pain that sometimes occurs following CXL in keratoconus patients. This study will determine whether these changes can be structurally and functionally quantified using functional neuroimaging and in vivo corneal microscopy (IVCM), and whether they can be predicted based on predisposing biological and psychological factors. Our central hypothesis is that CXL produces acute pain through activation of trigeminal afferents, and that post-operative chronic pain outcomes are related to neuroplastic changes in trigeminal circuitry, corneal afferent regeneration, and psychological factors.

Keywords
fMRI, Corneal Microscopy, IVCM, Neuroimaging
Medical subject headings
Pain, Postoperative, Chronic Pain, Acute Pain, Intraoperative Complications, Surgical Wound, Corneal Injuries, Corneal Diseases, Keratoconus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04439552
Study groupRoleWhat they receive
CXL groupPatients who are about to undergo a corneal cross-linking (CXL) surgery to treat keratoconus.
Control groupHealthy volunteers age and sex matched to the CXL group.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neural activity related to pain.

    Pain-related brain activation measured with fMRI.

    Measured: 1 year

  2. Corneal nerve morphology.

    Afferent nerve fiber morphology measured with IVCM.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jun 2020
  2. Study start4 Oct 2021
  3. Primary completionAug 2027 (estimated)
  4. Study completionDec 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04439552
Sponsor's protocol ID
IRB-P00035185
Status last verified
Dec 2025
First submitted
17 Jun 2020
Last updated
19 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication

Publications

  • Belmonte C, Acosta MC, Merayo-Lloves J, Gallar J. What Causes Eye Pain? Curr Ophthalmol Rep. 2015;3(2):111-121. doi: 10.1007/s40135-015-0073-9.

    PubMed 26000205

  • Borsook D, Youssef AM, Simons L, Elman I, Eccleston C. When pain gets stuck: the evolution of pain chronification and treatment resistance. Pain. 2018 Dec;159(12):2421-2436. doi: 10.1097/j.pain.0000000000001401.

    PubMed 30234696

  • Cruzat A, Qazi Y, Hamrah P. In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease. Ocul Surf. 2017 Jan;15(1):15-47. doi: 10.1016/j.jtos.2016.09.004. Epub 2016 Oct 19.

    PubMed 27771327

  • Downie LE, Naranjo Golborne C, Chen M, Ho N, Hoac C, Liyanapathirana D, Luo C, Wu RB, Chinnery HR. Recovery of the sub-basal nerve plexus and superficial nerve terminals after corneal epithelial injury in mice. Exp Eye Res. 2018 Jun;171:92-100. doi: 10.1016/j.exer.2018.03.012. Epub 2018 Mar 14.

    PubMed 29550279

  • 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.

    PubMed 22547128

  • Hruschak V, Cochran G. Psychosocial predictors in the transition from acute to chronic pain: a systematic review. Psychol Health Med. 2018 Dec;23(10):1151-1167. doi: 10.1080/13548506.2018.1446097. Epub 2018 Feb 28.

    PubMed 29490476

  • Hasenbring MI, Chehadi O, Titze C, Kreddig N. Fear and anxiety in the transition from acute to chronic pain: there is evidence for endurance besides avoidance. Pain Manag. 2014;4(5):363-74. doi: 10.2217/pmt.14.36.

    PubMed 25350076

  • Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006 May 13;367(9522):1618-25. doi: 10.1016/S0140-6736(06)68700-X.

    PubMed 16698416

  • Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986 Mar 15;101(3):267-73. doi: 10.1016/0002-9394(86)90817-2.

    PubMed 3513592

  • Kinard KI, Smith AG, Singleton JR, Lessard MK, Katz BJ, Warner JE, Crum AV, Mifflin MD, Brennan KC, Digre KB. Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye. Headache. 2015 Apr;55(4):543-9. doi: 10.1111/head.12547. Epub 2015 Mar 31.

    PubMed 25828778

  • Larbig W, Andoh J, Huse E, Stahl-Corino D, Montoya P, Seltzer Z, Flor H. Pre- and postoperative predictors of phantom limb pain. Neurosci Lett. 2019 May 29;702:44-50. doi: 10.1016/j.neulet.2018.11.044. Epub 2018 Nov 29.

    PubMed 30503915

  • Moulton EA, Becerra L, Borsook D. An fMRI case report of photophobia: activation of the trigeminal nociceptive pathway. Pain. 2009 Oct;145(3):358-363. doi: 10.1016/j.pain.2009.07.018. Epub 2009 Aug 11.

    PubMed 19674842

  • Moulton EA, Borsook D. C-Fiber Assays in the Cornea vs. Skin. Brain Sci. 2019 Nov 12;9(11):320. doi: 10.3390/brainsci9110320.

    PubMed 31718074

  • Rosenthal P, Borsook D, Moulton EA. Oculofacial Pain: Corneal Nerve Damage Leading to Pain Beyond the Eye. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5285-5287. doi: 10.1167/iovs.16-20557.

    PubMed 27723896

  • Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000 May;118(5):615-21. doi: 10.1001/archopht.118.5.615.

    PubMed 10815152

Questions about this trial

What is this clinical trial studying?

An observational study of Pain, Postoperative and Pain, Chronic, run by Boston Children's Hospital at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Eric A Moulton, OD PhD (617-919-6827, eric.moulton@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neural activity related to pain. (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04439552, which also lists 21 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.

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