PI si leaving institution. This study will likely be transferred to USF but study activity is not continuing at TMC.

The aim of this study is establish the reliability and clinical utility of microneuromas as identified via in vivo confocal microscopy as the diagnostic biomarker for NCP.

Dry Eye Disease (DED) is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities.

Neuropathic corneal pain (NCP), an ocular and severe type of neuropathic pain describes patients with symptoms of ocular discomfort out of proportion with clinical signs. The lack of clinical signs observed by standard ophthalmic examination has resulted in underdiagnosis of NCP or misdiagnosis as dry eye disease. Thus, having a biomarker for NCP is critical to identify and treat these patients. No biomarker or clinical signs exists to identify NCP patients.

Investigating corneal neurosensory abnormalities could help to diagnose NCP and potentially differentiate these patients from those with DED. In vivo confocal microscopy (IVCM) allows for real-time optical biopsies at a quasi-histological level, allowing for assessment of corneal nerves. IVCM non-invasive diagnostic imaging across NCP, DED, and healthy individuals will be analyzed to validate corneal microneuromas as a biomarker for NCP.

Inclusion Criteria:

All Subjects:

1. 18 years of age or older
2. Ability to consent
3. Best corrected visual acuity of 20/40 or better in each eye

Dry Eye Disease Group:

1. Chief complaint is ocular surface discomfort or dry eye disease, but subject reports no ocular pain on OPAS questionnaire

2. Symptoms lasting at least 3 months

3. Presence of at least two of the following within the same eye:

   1. Anesthetized Schirmer score =/< 10mm
   2. Corneal staining of >3/15 based on NEI scale
   3. Tear break up time < 10 seconds

Neuropathic Corneal Pain Group:

1. Chief complain is ocular surface discomfort or dry eye disease

2. Symptoms lasting at least 3 months

3. All of the following in both eyes:

   1. Corneal staining of less than or equal to 3/15 based on NEI scale
   2. Tear break up time =/> 10 seconds

4. Must have at least 25% peripheral pain

5. Subject reported discomfort prior to drop response testing of at least 3 out of 10

Control Group:

1. No symptoms of ocular surface discomfort or dry eye disease

2. All of the following in both eyes

   1. Anesthetized Schirmer score > 10 mm
   2. Corneal staining of less than or equal to 3/15 based on NEI scale
   3. Tear break up time > 10 seconds

3. The same sex and within 5 years of age of a patient within the NCP group.

Exclusion Criteria:

1. Pregnant or nursing
2. Irregular corneal disease
3. Ocular surgery in the past 3 months
4. Ocular infection in the past 3 months
5. Active ocular allergies
6. Participation in a study that could potentially impact the IVCM in the opinion of the investigator
7. Current use of corneal nerve regeneration therapy that has been on-going for 3 months or more.
8. For NCP group only, patients for whom their pain and symptoms can be attributed to other causes in the opinion of the investigator

We will not be limiting the inclusion of the NCP or DED groups for this study. We will be recruiting from two Cornea Clinics in diverse large cities of Boston and Philadelphia. Thus, the sample collected from this group is expected to be representative of the population for each of these groups. We will be limiting inclusion of the control group to those age and sex matched controls as described above. This will allow for the conclusions drawn from this study to be more applicable in clinical practice. Without an age and sex matched control group, one could attribute differences in IVCM to these two variables instead of the disease(s).