The new Definition and Classification Subcommittee of the Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) recently reformulated the definition of the disease.3 Given mounting evidence of the role of local nerve damage in eliciting and potentiating ocular pain, neurosensory abnormalities have been introduced as part of its pathophysiology.
Furthermore, a new categorization algorithm that primarily focuses on the assessment of ocular surface symptoms and signs was introduced. Therefore, when symptoms are disproportionate to clinical signs, neurosensory abnormalities should be suspected. To incorporate this group of patients into the clinical decision-making algorithm, a new subcategory named “neuropathic dry eye” was proposed.
Neuropathic dry eye can be due to diverse ocular conditions (e.g., DED, infectious/herpetic keratitis, radiation keratopathy), as well as surgical interventions (e.g., cataract and refractive surgery).4,5,6 Systemic conditions, such as fibromyalgia and Sjögren’s disease, also cause neuropathic dry eye.4 Symptoms can be potentiated by comorbidities like anxiety and depression.
As a result of the causes mentioned, nociceptors can undergo a plasticity process called “peripheral sensitization,” in which nerve injury and inflammatory mediators result in pathological structural changes of corneal nerves, lowering the threshold for pain and causing ectopic discharge of the nociceptors even with non-noxious stimuli.7 Over time, peripheral sensitization leads to a similar process in the central nervous system (CNS), called central sensitization, in which the CNS neurons’ responses are disproportionate to peripheral pain signaling, resulting in inappropriate amplification and prolongation of pain duration.8
Differentiating peripheral from central pain is crucial to guide appropriate treatment. This can be done through an in-office test, the instillation of topical 0.5% proparacaine hydrochloride.4 If pain resolves or partially improves after instillation, the patient likely suffers from a peripheral or mixed etiology. If pain remains unchanged, the patient likely has a central component.
For both central and peripheral neuropathies, treatment often involves a combined multistep strategy,4,5 starting with the treatment of associated conditions (such as DED, conjunctivochalasis, blepharitis/MGD, or predisposing systemic conditions).
Neuro-regenerative therapies intended to restore neuronal integrity and functionality (20% autologous serum eye drops, topical nerve growth factor) and anti-inflammatory agents that minimize nerve injury and sensitization from uncontrolled inflammation (e.g., corticosteroids) are more effective if peripheral neuropathy is present. Systemic pharmacotherapies (such as first-line agents, nortriptyline [tricyclic antidepressant] and carbamazepine [anticonvulsant], or second-line agents, low-dose naltrexone and tramadol), and even alternative medicine, are more favorable in central neuropathic patients.4
Given the compelling outcomes with the concurrent use of low-dose steroids and serum tears in corneal nerve regeneration,9 20% autologous serum tears (AST) eight times daily and loteprednol 0.5% two times weekly were started (an initial regimen of loteprednol 0.5% QID, followed by a bi-weekly taper is usually recommended).
By the 6-week follow-up, symptoms had begun to decrease and IVCM demonstrated increased nerve density with improved morphology in the affected eye (Figure 1C/D.
At his last appointment 18 months after his first visit, the patient reported an 80% to 90% subjective improvement of symptoms. OSDI decreased to 8 (from 65 initially). OPAS indicated a 0/10 pain intensity in the prior 24 hours and 2 weeks, a 0.1/10 impact in QoL, and 20% worsening only in windy/dry conditions. UCVA improved to 20/20 in OD. Ocular surface examination revealed trace SPK in OD only. IVCM showed near complete regeneration of subbasal nerves in OD, and normal density in OS (Figure 1E/F). The patient was tapered off AST.