Style Sampler

Layout Style

Patterns for Boxed Mode

Backgrounds for Boxed Mode

All fields are required.

Close Appointment form

Patients as Teachers

  • Home
  • Patients as Teachers
Patients as Teachers

No Comments

Long-standing Corneal Neuropathic Pain Following LASIK

A 44 y.o. male reported the rapid onset of progressively disabling corneal pain and photoallodynia 5 years following LASIK that had persisted for 3 years at the time of our initial examination. Except for typical LASIK scars, external examinations of his eyes were normal as were his tear metrics. Nevertheless, in vivo laser scanning confocal microscopy (IVCM) revealed a striking increase in the density of activated dendritic cells. Topical corneal anesthetic fully suppressed all symptoms, which were significantly mitigated by wearing scleral lenses. Unfortunately, the development of intolerance to these devices limited their usefulness. Notably, this patient volunteered that his responses to traumatic injuries since childhood and until the onset of corneal neuropathic pain had always been strikingly less painful than that of his peers.

Discussion: This patient teaches us that active subclinical immune-based corneal inflammation can persist for many years following the extensive axotomies performed during LASIK and presumably become the driver of delayed-onset chronic corneal pain. He also demonstrates the commonly found latency between the surgery and onset of neuropathic pain (see posted LASIK paper). Symptoms of photoallodynia also support the active participation of the central corneal nociceptive circuitry in this disease.

It is interesting to note that this patient’s level of endogenous analgesia appears to have been unusually robust as suggested by his history of diminished responses to painful stimuli during the years prior to and 5 years following LASIK surgery until the onset of the neuropathic pain. It can be argued that his presumed high level of endogenous analgesia was eventually overcome by the persistence of incoming barrages of ectopic corneal pain suggested by the presence of continued immune-based inflammation. This case reflects the complexity of factors that contribute to a patient’s risk for developing CCNP and suggests that the level of endogenous analgesia is but one of a number of risk factors, including some not yet known.

CCNP and Sjogren’s Syndrome

We first examined this 51 y.o. woman with Sjogren’s syndrome (SS) in 2005 at which time she reported a 3 year history of chronic dry eye-like symptoms that had suddenly increased in severity following an acute exposure to fumes of wet paint. On examination, her corneas showed fluorescein dye staining disproportionately modest when compared to the intensity of her symptoms. Subsequent IVCM images of her corneal nerves revealed prominent axon. She became pain-free during scleral lens wear except for continuing hypersensitivity to certain fumes to which these devices are permeable.

3 years later she reported the onset of rapidly escalating breakthrough corneal pain and photosensitivity while wearing these devices that escalated to a level of 10/10 on the numeric scale (worse possible imaginable pain) after their removal. She also developed hyperalgesia and allodynia of the skin of her forehead. Slit lamp examination of her corneas were normal (she had been wearing scleral lenses during her waking hours) and IVCM images of the corneal subbasal plexus OU showed no obvious changes from those captured prior to the onset of the break-through pain.

Following informed consent, her right scleral lens was medicated with sterile, non-preserved bupivacaine 0.004%. Moments after its open label insertion she reported total resolution of pain and photophobia in that eye despite Corneal Cochet-Bonnet esthesiometry measurements performed within 5 minutes after inserting the medicated scleral lens being essentially unchanged from those measured immediately prior to its insertion. Subsequent daily treatment of both corneas with an arbitrarily chosen mixture of ropivacaine 0.005% and lacosamide 0.05% in the scleral lens chambers strikingly suppressed symptoms of photosensitivity, DELP and hypersensitivity to fumes. This analgesic effect continued for 2 years at which time the drugs in the scleral lenses were deliberately discontinued. Pain and photophobia returned to its previous levels within 2 weeks. Reinstitution of the treatment again suppressed the neuropathic symptoms.

Discussion: Sjogren’s syndrome is considered the classic example of desiccating ocular surface disease. Nevertheless, signs of corneal axon regeneration [1, 2] and depressed corneal sensitivity [3] present in many of these patients suggest that corneal neuropathy may play an important role in the pathogenesis of chronic corneal pain associated with this disease. This is not surprising in view of the known association of SS with peripheral neuropathies [4, 5]. The message is that the pathophysiology of chronic DELP associated with autoimmune diseases is more complex than tear deficiency alone. Its apparent transition to centralized pain in this case may demonstrate a pattern: Her corneal pain began as mild symptoms of CEH that intensified to a level requiring the use of scleral lenses. The subsequent loss of much of their analgesic effectiveness can be interpreted as indicating a change in the pain mix, plausibly due the sustained increased excitability of the central trigeminal synapses that required more than blocking corneal evaporative hyperalgesia to suppress (centralized corneal neuropathic pain). This hypothesis is supported by its subsequent association with tactile allodynia of the skin of her forehead.

Centralized Corneal Pain Preceded by Soft Contact Lens Intolerance

A 30 y.o. woman in otherwise good health became soft contact lens intolerant after having worn them comfortably for 5 years. Subsequent refitting with other brands including daily disposables failed to improve their wearing comfort. Over time she began to experience escalating symptoms of burning eye pain OU during contact lens wear that subsequently continued in their absence. At one point she was informed that her corneas exhibited dense corneal staining OU. She reported significant mitigation of her eye symptoms for 1 week following the insertion of plugs in all 4 puncta. At the time of our initial examination she rated the average burning pain in each eye as 7-8 on the visual analogue scale (0 representing no pain and 10 representing worse imaginable pain). These symptoms were unresponsive to topical corneal anesthesia and she denied dry eye-like pain.

Examination revealed white eyes, generous tear menisci at both lower lid margins (the 4 punctal plugs were in place) and absence of fluorescein dye staining of her ocular surfaces. IVCM images of her nerve fibers were normal.

Discussion: Increased levels of proinflammatory cytokines reported in the tears of patients with compromised soft contact lens tolerance [6] suggest the presence of subclinical corneal inflammation and consequent sensitization of corneal nerve terminals. Its evolution to centralized corneal pain in this case is supported by the intensification of symptoms despite her having discontinued lens wear, the presence of generous tears, absence of supporting signs, ineffectiveness of scleral lenses, normal corneal nerve fiber morphology as imaged by in vivo laser scanning confocal microscopy (IVCM) and failure of her eye symptoms to respond to corneal anesthesia.

Patient With CCNP and Eyes With Overflowing Tears that Subsequently Became Dry

We examined this 45 y.o. female 30 months after she was accidentally exposed to ultraviolet-B radiation. Despite the uneventful resolution of bilateral actinic keratoconjunctivitis, she reported increasing burning eye pain exacerbated by exposure to light. In the absence of visible signs of ocular surface perturbations, five ophthalmologists independently concluded that she was malingering.

We examined her eyes 3 years after the incident and confirmed that they looked normal and that her tears were overflowing. Nevertheless, despite the absence of any outward signs of inflammation, IVCM images of her corneas revealed striking nerve fiber loss, mature dendritic cells and signs of active nerve regeneration. She reported complete suppression of all corneal symptoms immediately on the insertion scleral lenses and while they were worn. However, their striking analgesic effect lasted only 3 weeks. Breakthrough symptoms of ocular burning pain and photosensitivity continued to escalate over the following 3 years and topical anesthetic drops subsequently failed to suppress the corneal pain. Today, 7 years later, she describes exposure to the faintest glimmer of light as provoking symptoms similar to that of a “red-hot poker” being pressed into her eyes. Moreover her ocular surfaces have become dry and stain with fluorescein despite her wearing scleral lenses all her working hours. Today she is confined to her home with blacked-out windows.

Discussion: This case illustrates the striking disparity between signs and symptoms characteristic of neuropathic pain and the persistence of active corneal neuropathy at least several years after the initial injury Moreover, the subsequent failure of corneal anesthesia to mitigate these symptoms also supports our belief that her symptoms of burning eye pain and photoallodynia are projected from the central nervous system. Nevertheless, the most important lesson that we have learned from this patient is that the functional failure of the tear supply system can be the consequence of painful corneal neuropathy.

Unexplained CCNP

An otherwise healthy 47 y.o. male reported the acute onset of stabbing pain OS>OD provoked and exacerbated by exposure to light and reading. He denied any prior noxious corneal events. His symptoms rapidly evolved to constant asymmetrical burning eye pain and he described episodes of nausea associated with increased stabbing pain in his occipital and frontal skull areas. He also recalled that a previous Schirmer’s test was followed by severe ocular burning pain that lasted three days and that cycloplegia had exacerbated symptoms of photosensitivity. He denied dry eye-like symptoms and reported being in otherwise good health.

External examination of his eyes was normal. Tear menisci were generous; central corneal sensitivities (Cochet-Bonnet esthesiometry) were mildly depressed OU and IVCM images were unremarkable. An in-office trial of scleral lenses was terminated because of wearing discomfort and their failure to mitigate the ocular pain.

Discussion: Absence of external signs of ocular surface disease, evidence of neuropathic activity in IVCM images and incomplete eye pain mitigation during corneal anesthesia are consistent with CCNP. Moreover, we argue that otherwise unexplained scleral lens intolerance is the consequence of secondary hyperalgesia involving the underlying supporting surface of the eyes which is believed by some to be due to dysfunctional changes in the central nociceptor pathways [7, 8]. The absence of a known trigger supports our theory that the disease in this patient represents a neurological disorder of the central nervous system.

CCNP and Dystonia

An otherwise healthy 60 y.o. woman reported the onset of chronic burning corneal pain following a transient episode of unexplained photophobia and confusion in 2007 that had been recently preceded by the onset of blepharospasm. Her eye pain was exacerbated during episodes of focal dystonia and to exposure to light and moving air.

Examination 3 years after its onset revealed white eyes and absent corneal and conjunctival fluorescein staining. Blepharospasm and burning eye pain were suppressed during corneal anesthesia. IVCM images revealed increased branching and varicosities of subbasal nerve fibers and a striking increase in the density of activated dendritic cells OU.

Symptoms of eye pain and blepharospasm were completely suppressed during scleral lens wear. However, these striking effects lasted for only 1 week following which the focal dystonia became refractory to these devices and their analgesic effectiveness was significantly reduced. Eventually, her corneal pain became unresponsive to topical corneal anesthesia.

Discussion: The association of disorders of the basal ganglia and neuropathic pain has been previously reported [9] as has blepharospasm and ocular neuropathic pain [10]. It is notable that the striking suppression of her burning eye pain and blepharospasm during scleral lens wear was temporary as was their responsiveness to corneal anesthesia, indicating the progressive nature of her CCNP disease.

This patient teaches us that cornea-projected pain can be initiated and sustained by primary disorders of the brain, in this case the region of the subbasal ganglia, and that initial positive responses to scleral lenses and corneal anesthesia may be temporary.


1.            Tuisku IS, Konttinen YT, Konttinen LM, Tervo TM: Alterations in corneal sensitivity and nerve morphology in patients with primary Sjogren’s syndrome. Exp Eye Res 2008, 86(6):879-885.

2.            Villani E, Galimberti D, Viola F, Mapelli C, Ratiglia R: The cornea in Sjogren’s syndrome: an in vivo confocal study. Investigative ophthalmology & visual science 2007, 48(5):2017-2022.

3.            Adatia FA, Michaeli-Cohen A, Naor J, Caffery B, Bookman A, Slomovic A: Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjogren’s syndrome. Can J Ophthalmol 2004, 39(7):767-771.

4.            Barendregt PJ, van den Bent MJ, van Raaij-van den Aarssen VJ, van den Meiracker AH, Vecht CJ, van der Heijde GL, Markusse HM: Involvement of the peripheral nervous system in primary Sjogren’s syndrome. Ann Rheum Dis 2001,             60(9):876-881.

5.            Gemignani F, Marbini A, Pavesi G, Di Vittorio S, Manganelli P, Cenacchi G, Mancia D: Peripheral neuropathy associated with primary Sjogren’s syndrome. J Neurol Neurosurg Psychiatry 1994, 57(8):983-986.

6.            Thakur A, Willcox MD: Contact lens wear alters the production of certain inflammatory mediators in tears. Exp Eye Res 2000, 70(3):255-259.

7.            Klede M, Handwerker HO, Schmelz M: Central Origin of Secondary Mechanical Hyperalgesia. Journal of Neurophysiology 2003, 90(1):353-359.

8.            Cervero F, Laird JM, Garcia-Nicas E: Secondary hyperalgesia and presynaptic inhibition: an update. Eur J Pain 2003, 7(4):345-351.

9.            Borsook D, Upadhyay J, Chudler EH, Becerra L: A key role of the basal ganglia in pain and analgesia–insights gained through human functional imaging. Molecular pain 2010, 6:27.

10.          Borsook D, Rosenthal P: Chronic (neuropathic) corneal pain and blepharospasm: five case reports. Pain 2011.

  • Share This

Related Posts

Submit a comment

Your email address will not be published. Required fields are marked *

Leave a Reply

You may use these HTML tags and attributes:

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>