Neuropathic pain is caused by a lesion or disease of the somatosensory system.¹ The mechanisms involved in this process are damaged neurons and proinflammatory mediators that cause sensitization of the nerves.

Ocular symptoms may include: hyperalgesia, allodynia, photoallodynia, spontaneous pain, or a vague sensation of pressure, with or without significant clinical signs.² Symptoms may stem from dry eye disease, infection, herpetic disease, or they may occur after cataract or refractive surgery. Some systemic diseases, such as small-fiber polyneuropathy and trigeminal neuralgia, are also implicated. Comorbidities include anxiety, depression, and post-traumatic stress disorder.³

Neuropathic corneal pain affects a wide range of daily activities, such as reading, driving, and computer use. More severe cases result in impaired social function and increased physical suffering, which may lead to depression, anxiety, and a cycle of increasingly severe symptoms.

DIAGNOSIS

Patients with neuropathic corneal pain typically are symptomatic, but their symptoms are often out of proportion to their signs. They may have dry eye-like symptoms without relevant signs, and they may have unexplained corneal pain without clear findings on examination. Ocular comorbidities, such as conjunctivochalasis, allergy, meibomian gland dysfunction, and recurrent erosion, may be present.

Assessments of these patients usually begin with a questionnaire to determine severity, followed by functional somatosensory tests, a proparacaine challenge test, and other nerve function tests. A diagnosis of neuropathic pain needs to be confirmed by an optical biopsy via in vivo confocal microscopy or in systemic cases by skin biopsies.

TREATMENT OPTIONS

A proparacaine challenge test will determine whether neuropathic corneal pain is peripheral, mixed, or centralized, which then determines treatment: topical therapy for peripheral pain; topical and systemic pharmacotherapies for mixed or combined pain; and systemic pharmacotherapy for centralized pain, for which topical therapy is ineffective.

For peripheral pain that is typically not responding to conventional treatments, neuroregenerative therapy has been shown to be effective. Auto-logous serum tears or cryopreserved amniotic membrane, which contains neurotrophic factors, may aid in nerve regeneration and promote epithelial healing. These are typically used in conjunction with low dose anti-inflammatory therapy.

RETROSPECTIVE EFFICACY STUDY

A recent retrospective study was conducted to evaluate the efficacy of cryopreserved amniotic membrane to treat neuropathic corneal pain.⁴ The study evaluated 10 eyes of nine patients (eight females; one male), between 50 and 60 years old. Despite conventional treatments, their severe pain persisted or subsequent flares were not controlled by the current regimens. At baseline, the average pain score was 6 on a scale from 0 to 10.

Within 1 week of treatment with cryopreserved amniotic membrane (PROKERA® Slim or PROKERA® Clear), average pain scores were less than 2. Some patients experienced ring dysesthesia, requiring early removal of the membrane, but even in that subgroup, which had slightly higher pain levels at baseline, the pain scores decreased to 2. Patients who had 1-week planned retention had baseline pain scores between 5 and 6, and those scores decreased to one within the 1-week period.

After one application of cryopreserved amniotic membrane, near-normal levels of corneal nerves were evident in the treated eyes, and a decrease in inflammatory cells was seen in the study.⁴ Two patients required retreatment.

STUDY SUMMARY

The study concluded that placement of cryopreserved amniotic membranes is appropriate for neuropathic patients. Future controlled randomized trials are needed to confirm the findings from this initial case series. ●

REFERENCES

1. Treede RD, et al. Neurology. 2008;70:1630-1635.
2. Rosenthal P, et al. Br J Ophthalmol. 2016;100:128-134.
3. Dieckmann G, et al. Ophthalmology. 2017;124:S34-S47.
4. Morkin MI, et al. Ocul Surf. 2018;16:132-138.