Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability. The disease can significantly decrease quality of life as it impacts an individual’s ability to perform activities of daily living and negatively affects emotional health.

“An important consideration is that dry eye is an umbrella term, with different subtypes that have different underlying pathophysiologies,” explains Anat Galor, MD, MSPH, from the Miami VA and Bascom Palmer Eye Institute. “As such, the subtypes respond differently to different therapies,” “Specifically, when we see patients with ocular discomfort or pain—which can be characterized as dryness, burning, aching, or tenderness, to name a few—we need to put on our detective hats and figure out what is causing pain. There may be problems with moisture on the ocular surface, which can be anatomic abnormalities, but there may also be dysfunction within the nerves themselves, in which case there is neuropathic ocular pain. This differentiation is important because different dry eye types require different treatment paths.”

Currently, there is no standardized method or test to diagnose neuropathic ocular pain. “However, research has shown that individuals with suspected neuropathic ocular pain often characterize their pain as burning and report pain associated with wind and light,” says Dr. Galor. “For example, we might suspect that the pain started after surgically-induced nerve injury or because there is a disconnect between symptoms and objective signs of disease.” Comorbidities associated with neu­ropathy—such as depression, anxiety, fibromyalgia, and migraine—are also common in patients with suspected neuropathic ocular pain.

New Data

Dr. Galor was part of a study team that presented data from a retrospective study at the 2020 American Academy of Ophthalmology (AAO) Annual Meeting that evaluated the frequency of these anatomic findings, termed “microneuromas,” on in-vivo confocal microscopy (IVCM) and their relationship to dry eye parameters in 153 patients. Her co-authors included Jodi Hwang, BS; Harrison Dermer, MD; and Adam Karp Cohen.

The new study investigated whether certain nerve features apparent on IVCM, a technology that provides high resolution images of corneal nerves, can identify individuals with features consistent with neuropathic ocular pain. Previous work has suggested that hyperreflective enlargement at the end of an abrupt corneal nerve termination at the level of the sub-basal plexus was suggestive of a microneuroma and could be a useful clinical sign for corneal neuropathic pain.

According to the results, the frequency of microneuromas in study patients was as follows:

  • 1% in patients without dry eye symptoms (n=18)
  • 8% in patients with dry eye symptoms and no history of refractive surgery (n=119)
  • 3% in patients with dry eye symptoms and a history of refractive surgery (n=16)

“Our study found that dry eye symptoms and signs—including features suggestive of neuropathic ocular pain—in symptomatic patients did not differ by the presence of microneuromas,” Dr. Galor says. “Overall, microneuromas were present in patients with and without dry eye symptoms and could not differentiate between dry eye subtypes. Our data highlight the complexity of dry eye and the challenges to detecting neuropathic ocular pain.”

Assessing Implications

The study results highlight the need to better standardize the terminology and diagnostic criteria of these anatomic findings because current grading schemes are qualitative and non-standard between groups. Overall, Dr. Galor says the bigger message is that in appropriate individuals, nerve dysfunction must be considered as a contributor to dry eye symptoms. “Ophthalmologists play an important role in diagnosing and treating dry eye, especially in addressing nociceptive sources of pain,” she says. “However, it may also be beneficial to involve other specialists when individuals are suspected of having neuropathic ocular pain. This can include primary care physicians, neurologists, and pain specialists. Mechanisms driving neuro­pathic ocular pain are similar to those driving neuropathic pain elsewhere in the body. As such, treatments that are used to treat neuropathic pain may be applied to the treatment of neuropathic ocular pain in appropriate individuals in a multidisciplinary fashion.”

References

Corneal Microneuromas: Markers of Neuropathic Corneal Pain? Presented at: American Academy of Ophthalmology 2020 Virtual Congress. Session: PO095. November 2020. Available at: https://aaommg.apprisor.org/apsSession.cfm?id=PO095.

Belmonte C, Nichols JJ, Cox SM, et al. TFOS DEWS II pain and sensation report. Ocul Surf. 2017;15(3):404-437. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706540/.

Galor A, Levitt RC, Felix ER, Martin ER, Sarantopoulos CD. Neuropathic ocular pain: an important yet underevaluated feature of dry eye. Eye (Lond). 2015;29(3):301-312. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366454/.

Crane AM, Feuer W, Felix ER, et al. Evidence of central sensitisation in those with dry eye symptoms and neuropathic-like ocular pain complaints: incomplete response to topical anaesthesia and generalised heightened sensitivity to evoked pain. Br J Ophthalmol. 2017;101(9):1238-1243.

Dieckmann G, Goyal S, Hamrah P. Neuropathic corneal pain: approaches for management. Ophthalmology. 2017;124(11 Suppl):S34-S47. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5743225/.