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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
CXL Group
Control Group
Exclusion Criteria (Both Groups):
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
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| 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 |
| Name | Affiliation | Role |
|---|---|---|
| Eric A Moulton, OD PhD | Boston Children's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Boston Children's Hospital | Recruiting | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26000205 | Background | 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. | |
| 30234696 | 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. |
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All IPD that underlie results in a publication
Starting 6 months after publication, until 5 years after.
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.
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| ID | Term |
|---|---|
| D010149 | Pain, Postoperative |
| D059350 | Chronic Pain |
| D059787 | Acute Pain |
| D007431 | Intraoperative Complications |
| D000072836 | Surgical Wound |
| D065306 | Corneal Injuries |
| D003316 | Corneal Diseases |
| D007640 | Keratoconus |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010146 | Pain |
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| 27771327 | 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. |
| 29550279 | 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. |
| 22547128 | 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. |
| 29490476 | 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. |
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| 16698416 | 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. |
| 3513592 | 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. |
| 25828778 | 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. |
| 30503915 | 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. |
| 19674842 | 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. |
| 31718074 | 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. |
| 27723896 | 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. |
| 10815152 | 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. |
| 9787000 | 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. |
| 2282506 | 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. |
| 7980137 | 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. |
| 35211480 | 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. |
| 34901466 | 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. |
| 33931393 | 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. |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D014947 | Wounds and Injuries |
| D005131 | Eye Injuries |
| D005151 | Facial Injuries |
| D006259 | Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D009422 | Nervous System Diseases |
| D005128 | Eye Diseases |