Best Ways to Tell if Chronic Eye Pain is From Dry Eye?

Patients with chronic eye pain can have initial symptoms ranging from irritation and burning extending to severe pain. When a patient presents with severe eye pain “without stain,” meaning there is little to no abnormal findings nor abnormal staining is seen with Fluorescein on the slit lamp microscope, it can be a challenge to determine the underlying cause and the best treatment. 
Reliable diagnostic tests to assess symptoms and clinical signs for these patients is still controversial. In most clinical practices, the diagnosis of corneal neuropathy and/or dry eye disease is made on the basis of patients’ symptoms.
The cornea is highly innervated by sensory nerves including polymodal nociceptors, mechanonociceptors, and thermoreceptors. Normally, activation of thermoreceptors gives one a sensation of cooling, whereas activation of mechanoreceptors or polymodal receptors can result in ocular surface discomfort and pain. 
When environmental stimuli activate sensory afferent nerves (meaning going toward the central brain/nerve complex), a series of coordinated reflexes, including reflex tearing (which can be counterintuitive–“why am I tearing if my eyes are dry?”–trigger to protect the eye from potential damage.
One of the sensory receptors, nociceptors generally are quiet electrically and transmit all-or-none action potentials only when stimulated.  These receptors are can be activated by heat or cold, intense pressure or squeezing, and irritating chemicals. The known chemical nociceptor activators are capsaicin, bradykinin, histamine, and prostaglandins.
The below paper points to a new way to potentially determine if the underlying cause to chronic eye pain is Dry Eye Disease: PGE2 and PGD2 levels.
It will take years to be able to test a patient in my office for this, but there are many new technologies coming in the pipeline that hope to help surgeons & eye doctors figure out the cause of chronic pain in our patients. 


Volume 119, Issue 11, November 2012, Pages 2211-2219

Original article

Change in Prostaglandin Expression Levels and Synthesizing Activities in Dry Eye Disease

Referred to by

Carrie Huisingh, Gerald McGwin

Change in Prostaglandin Expression Levels and Synthesizing Activities

Ophthalmology, Volume 120, Issue 9, September 2013, Pages e59

Download PDF


To investigate the expression level of prostaglandins (PGs) and their de novo synthesis in dry eye (DE) disease.


Cross-sectional case-control study and in vivo mouse experimental study.


Forty-six eyes from 23 DE patients and 33 eyes from 17 age- and sex-matched controls were studied. Also, DE-induced murine eyes were compared with control eyes.


Patients completed a symptom questionnaire using a 100-mm visual analog scale (VAS). Nano-liquid chromatography tandem mass spectrometry was used for the quantification of PGE2 and PGD2. A DE disease environmental chamber was used to induce DE in mice. One week after induction, enzyme expressions of cyclooxygenase-1, cyclooxygenase-2 (COX-2), PG E synthase (PGES), and PG D synthase (PGDS) in the lacrimal glands, meibomian glands, and corneas were examined using immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR).

Main Outcome Measures

The mean PGE2 and PGD2 levels in the tears of DE patients were measured and compared with symptom severity scores. Immunohistochemistry staining patterns and qRT-PCR data of DE mice were quantified.


The mean PGE2 level in the tears of DE patients (2.72±3.42 ng/ml) was significantly higher than that in the control group (0.88±0.83 ng/ml; P = 0.003). However, the mean PGD2 level in the tears of DE patients (0.11±0.22 ng/ml) was significantly lower (0.91±3.28 ng/ml; P = 0.028). The mean PGE2-to-PGD2 ratio correlated strongly with VAS scoring (P = 0.008). In DE mice, COX-2 mRNA was significantly higher in ocular surface tissue and lacrimal glands. Furthermore, PGES mRNA was significantly higher in ocular surface tissue, whereas PGDS mRNA was decreased. Immunohistochemistry staining showed elevated COX-2 expression in the lacrimal glands, meibomian glands, corneas, and conjunctivas. Furthermore, PGES expression was found in periductal infiltrated cells of the lacrimal glands and conjunctival epithelium. Also, PGDS expression was decreased in meibomian glands and increased focally in the conjunctival epithelium.


A reciprocal change in PGE2 and PGD2 levels was found in the tears of DE patients, which correlated with patients’ symptom scores. These clinical results were supported by increased COX-2 and PGES expression levels found in tear-producing tissues of DE mice. 

Shopping Cart