Various inflammatory diseases, neurological diseases, or surgical interventions can be the underlying cause of corneal neuropathic pain (Table 8.1). Some of them include refractive surgery [26], dry eye disease [27, 28], Sjögren’s syndrome [29, 30], neuralgia associated with herpes virus [31], benzalkonium chloride (BAK) preserved eye drops, accutane, chemotherapy, and radiotherapy to mention a few [3]. In addition to refractive surgery, particularly LASIK, we have also observed cataract surgery—clear cornea incision—to also trigger neuropathic corneal pain.

Corneal nerve damage may be associated with symptoms of pain, light sensitivity, irritation, and sometimes a vague sensation of pressure. As a physician, one must understand that pain does not affect the patient alone, but it affects the entire social structure of the patient. Eye pain decreases work performance and can have huge impact on aspects of physical, social, and psychological functioning [32, 33]. Crucial daily activities like reading, driving, and computer work are affected giving a sense of handicap [33]. Severe cases with photoallodynia may require dark glasses indoors affecting social quality of life. Many patients are unable to work and go on disability. Unfortunately, we have witnessed many patients with severe form of pain where anxiety and depression have forced them to contemplate and even seek ending their own life.

As outlined earlier, after a complete ocular exam, IVCM should be done. In this patient, IVCM examination revealed an increase in the presence of dendritic cells, neuromas, and nerve tortuosity, while also revealing a reduction in nerve density (Fig. 8.2a). A diagnosis of corneal neuropathy was made. The pain was significantly reduced with proparacaine drops, confirming the theory of peripheral corneal neuropathy following LASIK surgery.

The patient was prescribed autologous serum tears (20%) eight times a day and loteprednol etabonate 0.5% drops four times a day for a week, tapering to a drop each week. After 6 months, the patient reported significant resolution of his symptoms and occasional flare-ups. Ocular examination was normal, and IVCM revealed no neuromas but persistent inflammation with a maintained reduction of nerve density (Fig. 8.2b ). The previous treatment was maintained.

In our experience, patients with corneal neuropathic pain typically require chronic use of anti-inflammatory agents (Table 8.2) to prevent recurrent episodes. Steroids are the main stay of treatment, especially for initial rapid relief. The authors prefer loteprednol 0.5% at an initial qid dose with biweekly taper to once or twice a week over a 6–8 week period. For severe refractory cases, we might add Anakinra (Kineret) human IL-1 receptor antagonist 2.5% at TID dosing for 3–6 months or Tacrolimus (calcineurin inhibitor) 0.03% at bid dosing for 3–6 months as they tend to be efficacious in reducing corneal surface inflammation and epitheliopathy [35, 36]. In addition, topical azithromycin 1% application at bedtime is a very effective and well-tolerated therapy of lid margin disease and meibomian gland dysfunction [37, 38]. It is both an anti-inflammatory, inhibiting pro-inflammatory cytokines, and an effective antibacterial agent. Likewise, oral doxycycline is an antimicrobial that also inhibits matrix metalloproteinases that degrade connective tissue [39]. We use oral doxycycline at a dose of 100 mg once or twice a day for 2–3 months followed by daily dosing for another 3 months.

Autologous serum tears (ASTs) are the mainstay of therapy for these patients. They contain a variety of pro-epithelial and pro-neural factors like epidermal growth factor (EGF), NGF, insulin-like growth factor (IGF-1), etc. [3, 40]. Concentrations from 20 to 100% have been shown to encourage epithelial healing, increase nerve density, and decrease nerve tortuosity [3]. IVCM has demonstrated significantly improved nerve parameters including total length, number, reflectivity, and also reduction of beading and neuromas in patients treated with ASTs [3]. Recent studies with the help of IVCM have shown a substantial correlation between the increase in dendritic cell numbers and decreased subbasal corneal nerves signifying a possible interaction between the immune and nervous system in the cornea [16]. In our experience, the combination of steroids with ASTs is extremely synergistic as steroids decrease the initial inflammation on the ocular surface, providing an environment conducive to neuronal regeneration with the help of ASTs.