Understanding Neuropathic Corneal Pain—Gaps and Current Therapeutic Approaches

Abstract

The richly innervated corneal tissue is one of the most powerful pain generator in the body. Corneal neuropathic pain results from dysfunctional nerves causing perceptions such as burning, stinging, eye-ache and pain. Various inflammatory diseases, neurological diseases, and surgical interventions can be the underlying cause of corneal neuropathic pain. Recent efforts have been made by the scientific community to elucidate the pathophysiology and neurobiology of pain resulting from initially protective physiological reflexes, to a more persistent chronic state. The goal of this clinical review is to briefly summarize the pathophysiology of neuropathic corneal pain, describe how to systematically approach the diagnosis of these patients, and finally summarizing our experience with current therapeutic approaches for the treatment of corneal neuropathic pain.

Reduced intraepithelial corneal nerve density and sensitivity accompany desiccating stress and aging in C57BL/6 mice

“…Pain can be caused by increased friction between the eyelid and cornea due to reduced tear volume or quality and is exacerbated by inflammation (Goyal and Hamrah, 2016; Rosenthal and Borsook, 2016). The discomfort associated with dry eye disease has been proposed to represent, in some patients, ocular small fiber neuropathy (Andersen et al, 2017).…”

Neuropathic Corneal Pain

“…NCP may have a peripheral origin (e.g, ocular surgery 9,21 or herpes zoster ophthalmicus 22 ) or a systemic origin (e.g, small-fiber polyneuropathy or fibromyalgia). 4,13 Additional underlying causes include DED, infectious keratitis, recurrent erosions, radiation keratopathy, contact lens wear, and many others as summarized in Table 1. Important co-morbid conditions include, anxiety, 23,24 depression, 23–25 and post-traumatic stress disorders.…”

“…Topical 0.5% proparacaine hydrochloride (Alcaine, Alcon, Fort Worth, TX) allows for differentiation of central from peripheral sources of pain. 13 While proparacaine abolishes peripheral pain, it has no effect on pain from central sensitization. Patients experiencing complete or partial relief with proparacaine challenge, likely suffer from peripheral or mixed combined NCP.…”

“…While recent articles have attempted to elucidate the pathophysiology behind NCP, very limited literature exists on the management of NCP. 6,13 This review article provides an evidence-based approach on management strategies for NCP, and further reflects our own extensive clinical experience on a large cohort of NCP patients. We have been treating NCP patients since late 2008.…”

“…8 Neuropathic corneal pain (NCP) remains an ill-defined entity (also termed corneal neuralgia, keratoneuralgia, corneal allodynia or corneal neuropathy), 3–7 and can be perceived as pain, 9 discomfort, 10 aching, 11 photoallodynia, 6 burning, 10 irritation 10 , dryness, 11 and grittiness; 11 symptoms that may overlap with diseases such as dry eye disease (DED). 12 NCP can result from both peripheral nerve injury 5–7, 9 or systemic etiologies, 4,10, 9,13 and owes much of its understanding to advances in the pathophysiology and neurobiology of systemic neuropathic pain. While recent articles have attempted to elucidate the pathophysiology behind NCP, very limited literature exists on the management of NCP.…”