fMRI and IVCM Cornea Microscopy of CXL in Keratoconus

NCT04439552 | Recruiting

• 1 other identifier: IRB-P00035185
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Pain, Postoperative; Pain, Chronic; Pain, Acute; Surgical Injury; Surgical Wound; Cornea Injury; Cornea; Keratoconus

Keywords

fMRI; Corneal Microscopy; IVCM; Neuroimaging

Outcome Measures

Primary Outcomes (2)

• Neural activity related to pain.

  Pain-related brain activation measured with fMRI.

  1 year

• Corneal nerve morphology.

  Afferent nerve fiber morphology measured with IVCM.

  1 year

Study Arms (2)

CXL group

Patients who are about to undergo a corneal cross-linking (CXL) surgery to treat keratoconus.

Control group

Healthy volunteers age and sex matched to the CXL group.

Eligibility Criteria

• Age: 8 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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)
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (21)

• 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.

  PMID: 26000205 BACKGROUND

• 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.

  PMID: 30234696 BACKGROUND

• 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.

  PMID: 27771327 BACKGROUND

• 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.

  PMID: 29550279 BACKGROUND

• 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 BACKGROUND

• 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.

  PMID: 29490476 BACKGROUND

• 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.

  PMID: 25350076 BACKGROUND

• 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.

  PMID: 16698416 BACKGROUND

• 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.

  PMID: 3513592 BACKGROUND

• 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.

  PMID: 25828778 BACKGROUND

• 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.

  PMID: 30503915 BACKGROUND

• 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.

  PMID: 19674842 BACKGROUND

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

  PMID: 31718074 BACKGROUND

• 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.

  PMID: 27723896 BACKGROUND

• 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.

  PMID: 10815152 BACKGROUND

• Simone DA, Nolano M, Johnson T, Wendelschafer-Crabb G, Kennedy WR. Intradermal injection of capsaicin in humans produces degeneration and subsequent reinnervation of epidermal nerve fibers: correlation with sensory function. J Neurosci. 1998 Nov 1;18(21):8947-59. doi: 10.1523/JNEUROSCI.18-21-08947.1998.

  PMID: 9787000 BACKGROUND

• Sjoberg J, Kanje M. The initial period of peripheral nerve regeneration and the importance of the local environment for the conditioning lesion effect. Brain Res. 1990 Oct 8;529(1-2):79-84. doi: 10.1016/0006-8993(90)90812-p.

  PMID: 2282506 BACKGROUND

• Tervo K, Latvala TM, Tervo TM. Recovery of corneal innervation following photorefractive keratoablation. Arch Ophthalmol. 1994 Nov;112(11):1466-70. doi: 10.1001/archopht.1994.01090230080025.

  PMID: 7980137 BACKGROUND

• Pondelis NJ, Moulton EA. Supraspinal Mechanisms Underlying Ocular Pain. Front Med (Lausanne). 2022 Feb 8;8:768649. doi: 10.3389/fmed.2021.768649. eCollection 2021.

  PMID: 35211480 BACKGROUND

• van der Valk Bouman ES, Pump H, Borsook D, Severinsky B, Wisse RP, Saeed HN, Moulton EA. Pain mechanisms and management in corneal cross-linking: a review. BMJ Open Ophthalmol. 2021 Nov 29;6(1):e000878. doi: 10.1136/bmjophth-2021-000878. eCollection 2021.

  PMID: 34901466 BACKGROUND

• Dieckmann G, Borsook D, Moulton E. Neuropathic corneal pain and dry eye: a continuum of nociception. Br J Ophthalmol. 2022 Aug;106(8):1039-1043. doi: 10.1136/bjophthalmol-2020-318469. Epub 2021 Apr 30.

  PMID: 33931393 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative; Chronic Pain; Acute Pain; Intraoperative Complications; Surgical Wound; Corneal Injuries; Corneal Diseases; Keratoconus

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms; Wounds and Injuries; Eye Injuries; Facial Injuries; Craniocerebral Trauma; Trauma, Nervous System; Nervous System Diseases; Eye Diseases

Study Officials

• Eric A Moulton, OD PhD

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesia

Study Record Dates

• First Submitted: June 17, 2020
• First Posted: June 19, 2020
• Study Start: October 4, 2021
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Starting 6 months after publication, until 5 years after.
• Access Criteria: Direct request to study personnel via email, letter, phone, or in-person communication. Information will be shared with requesting parties for the purposes of expanding on this research or re-analysis. Neuroimaging data and corneal microscopy data will be shared via secure digital electronic transfer.

Locations

US (1)