In-Office Pain Tests for Neuropathic Corneal Pain

We propose to develop an economic in-office pain tests that may help screen and differentiate patients with neuropathic corneal pain (NCP) that could be used at any ophthalmic office. These five in-office pain tests include response with filter glasses, moisture googles, cold saline, hypertonic saline and topical proparcaine. The current study will serve as validation for clinical diagnosis of NCP among dry eye disease (DED) patients and will subsequently be conducted in larger population studies. Identification of patients with NCP would prevent unnecessary drug treatment failures and improved response rate of DED patients to therapies, such as Lifitigrast.

Inclusion Criteria

Group 1 (Dry Eye Disease):

• Age > 18 years
• Ability to consent
• Diagnosis of DED based on:
  o Symptoms of DED, shown with Ocular Surface Disease Index (OSDI) score > 32
  o Two or more of the following objective signs:
  • Schirmer's II test < 10 mm at 5 minutes
  • Tear break-up time (TBUT) of <10 seconds in one eye
  • Corneal fluorescein staining of 4 (National Eye Institute grading scheme, 0-15) in at least one eye
  • Conjunctiva! lissamine green staining of the nasal and temporal conjunctiva (National Eye Institute grading scheme, 0-18) in at least one eye

Group 2 (Neuropathic Corneal Pain):

• Age > 18 years
• Ability to consent
• Diagnosis of DED based on:
  o Symptoms of ocular pain and/or discomfort >3 months
  o No clinical signs (Schirmer's > 10, corneal fluorescein staining < 4, conjunctival lissamine green staining < 4, TBUT > 10 seconds) in at least one eye
  o Presence of microneuromas and decreased nerve density by in vivo confocal microscopy

Exclusion Criteria

• Age < 18 years
• History of diabetes
• History of ocular surgery, corneal infection, or corneal injury within the last 3 months
• Systemic anti-inflammatory therapy in the last 3 months
• Active ocular allergies
• For the DED group, IVCM findings consistent with NCP (presence of microneuromas)

Study Requirements

This is a single site, prospective, cross-sectional, controlled clinical study on a total of 90 patients. The patients are divided into two arms: DED (45 patients) and NCP (45 patients). After completion of OPAS and OSDI questionnaires, the patients will be tested for best corrected acuity. Then, they shall undergo the in-office pain tests, followed by regular ophthalmic examination and finally undergo IVCM and slit lamp imaging. This study will consist of one screening visit and one study visit; if time allows, these visits can be performed in the same day.