Neuropathic Corneal Pain: Approaches for Management

Abstract

Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage, and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuroregenerative and anti-inflammatory agents, and first-line systemic pharmacotherapy includes tricyclic antidepressants and an anticonvulsant. Second-line oral treatments recommended include an opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and gluten-free diet, may have additional benefits, as do potential noninvasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.

Figure 1. Steps for the Assessment of Patients with Neuropathic Corneal Pain

Flow diagram illustrating initial approach to clinical assessment and diagnosis for patients with neuropathic corneal pain.

Figure 2. Diagnosis of Neuropathic Corneal Pain

Flow diagram illustrating clinical and diagnostic approach for differentiating peripheral and centralized neuropathic corneal pain.

Figure 3. Proposed Treatement Paradigm of Patients with Neuropathic Corneal Pain

Proposed treatment strategy for neuropathic corneal pain.

Figure 4

Corneal laser in vivo confocal microscopy images of patients with neuropathic corneal pain. Images pre-treatment (A and C) demonstrate presence of micro-neuromas (black arrows), decreased nerve density and increased tortuosity. Following 4 and 6 months of treatment with autologous serum tears 8x/day and low dose anti-inflammatory therapy, subbasal corneal nerve density is increased and micro-neuromas are not present (B and D). Size bar =100 μm.