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 neuro-regenerative and anti-inflammatory agents, whilst first-line systemic pharmacotherapy includes tricyclic antidepressants and the anticonvulsant. Second line oral treatments recommended include the opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardio-exercise, acupuncture, omega-3 fatty acid, and gluten-free diet, may have additional benefits, as do potential non-invasive 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.

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