qualitative corneal sensitivity assessment for diagnosing ocular surface diseases

Assessing the Health of the Corneal Nerves in Ocular Surface Diseases

The main functions of the cornea are to protect the contents of the eye and to focus light on the retina1. The cornea is the most densely innervated structure in the human body, with 7000 nerve receptors per mm2, and, consequently, is one of its most sensitive tissues2,3. The corneal nerves originate from the ophthalmic branch of the trigeminal nerves and play a key role in maintaining corneal homeostasis and integrity by mediating protective reflexes such as blinking and tear production, providing trophic support to the ocular surface, and stimulating wound healing by releasing neuromediators1,4,5,6.
Damage with subsequent dysfunction of corneal nerves (hypersensitivity or hyposensitivity) can contribute to ocular surface diseases3,7,8. In fact, neurosensory abnormalities have been recognized as potential contributors to dry eye disease symptoms and signs and were incorporated into the 2017 Tear Film and Ocular Surface definition of dry eye disease: &#34;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 play etiological roles6,9,10.&#34; Additionally, injury or dysfunction anywhere along the trigeminal nerve pathway can lead to neurotrophic keratitis (NK)11, a degenerative condition of the cornea; its stages include epithelial keratopathy, ulceration, and perforation, which may result in subsequent vision loss3.
Ocular surface pain can be categorized as nociceptive or neuropathic in origin8. In neuropathic ocular surface pain, nerves become hypersensitive because of the effects of a lesion or disease of the somatosensory pathway, which is often caused by maladaptive healing after trauma or surgery8. Abnormalities in corneal nerves have also been reported in other eye diseases, including glaucoma, thyroid eye disease, keratoconus, diabetic keratopathy, and Fuch&#39;s endothelial dystrophy12,13,14,15, and these findings are reproducible in animal models6,16,17. Notably, nerve abnormalities are not always identified as a component of eye disease, and a neurotrophic or neuropathic component to pain is often missed, underscoring the need for more diagnostic procedures to assess for the presence of nerve abnormalities18. Since ocular surface diseases may involve or induce corneal nerve dysfunction, a concise technique to assess corneal nerve function provides considerable diagnostic value.
Corneal sensitivity testing assesses a patient&#39;s reaction to brief corneal stimulation, providing functional insight into the status of the corneal nerves (absent, reduced, normal, or increased sensitivity)13,19. For example, in patients with neurotrophic keratitis, studies have found positive relationships between corneal sensitivity and parameters of corneal nerve innervation as assessed using in vivo confocal microscopy20,21, including corneal nerve fiber length (R2 = 0.2951, P = 0.0016)21. A positive correlation between corneal sensitivity and corneal nerve density has also been observed in herpes simplex keratitis (r = 0.55, P &#60; 0.001) and dry eye disease (r = 0.644; P = 0.045)22,23. However, abnormal corneal innervation does not always correlate with aberrant corneal sensitivity13.
Alterations in corneal sensitivity have been reported in dry eye disease (including both Sj&#246;gren&#39;s dry eye disease and diabetes mellitus-related dry eye disease); ocular neuropathic pain; neurotrophic keratitis; Fuch&#39;s endothelial dystrophy; and ocular treatments for glaucoma including topical drops, laser trabeculoplasty, slow coagulation transscleral cyclophotocoagulation, and micropulse ciliary body ablation3,8,12,24,25,26,27,28,29. Additionally, short-term hypoesthesia can be secondary to refractive surgery30. Reduced or absent corneal sensitivity is a hallmark of neurotrophic keratitis and is key to its diagnosis3,11,31. Reduced corneal sensitivity often presents with low tear production and epithelial disruption, and increased sensitivity can signal ocular neuropathic pain, although neuropathic mechanisms can contribute to pain even in individuals with reduced or normal corneal sensitivity9,32.
Corneal sensitivity can be assessed using either qualitative or quantitative methods, although quantitative methods are primarily limited to research settings2,8,11,31,33,34,35. Quantitative assessments are made using either the Cochet-Bonnet esthesiometer or Belmonte&#39;s gas esthesiometer; a new non-contact esthesiometer, the Corneal Esthesiometer Brill, was recently registered by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for corneal sensitivity testing36,37,38,39. The limitations associated with the Cochet-Bonnet and Belmonte&#39;s gas esthesiometers, including the cost and the challenge of maintaining sterility, render their use infrequent in clinical practice3. Qualitative methods can be easily performed by eye care providers or physician extenders, as they are low cost, readily available, and require little training and time8,33,37. Furthermore, there is insufficient published guidance on how to conduct corneal sensitivity testing and how corneal sensitivity scores as part of a clinical workup may inform diagnosis. Here, we detail a protocol for corneal sensitivity testing that is cost-effective, easy to comprehend, accessible, and can be readily adopted by eye care providers across clinical settings.

 Author Spotlight: Establishing a Practical and Cost-Effective Protocol for Corneal Sensitivity Testing in Clinical Settings

Corneal Sensitivity Testing Procedure for Ophthalmologic and Optometric Patients

Despite evidence of altered corneal sensitivity in a wide variety of ocular conditions, there is limited published guidance on corneal sensitivity testing and interpretation. This research establishes a protocol for corneal sensitivity testing that is simple, cost-effective and easily implemented by eyecare providers across clinical settings. Ocular pain and dry eye disease can arise from multiple factors, including abnormal nerve function.Precision-based medicine requires diagnostic tests like corneal sensitivity to identify contributors. This test can detect decreased sensation, which suggests neurotrophic keratitis, or increased sensation, which suggests neuropathic-nociplastic pain as a contributor to symptoms. Quantitative methods for corneal sensitivity testing, such as with aesthesiometers, are infrequently used in clinical practice due to cost and challenges maintaining sterility.While qualitative methods such as ours offer an inexpensive and accessible alternative, there is insufficient guidance on their implementation and interpretation. Our protocol is low cost, readily available, and requires little training and time, meaning it could be performed by eyecare providers across clinical settings. Based on our experience, the results are consistent and the procedure can be easily incorporated into the existing workflow to support clinical diagnosis.It will help pave the way for further research and further clinical studies to continue to advance the importance of corneal sensitivity testing in our patients. The more interest and the more research on corneal sensitivity will only enhance our understanding of the importance of this critical test for our patients.

Qualitative Corneal Sensitivity Assessment for Diagnosing Ocular Surface Diseases

qualitative-corneal-sensitivity-assessment-for-diagnosing-ocular

Research

JoVE Journal

Medicine

The cornea is the most densely innervated structure in the human body, making it one of the most sensitive tissues. Changes in corneal nerve sensitivity can be observed in several ocular surface diseases. Nerve sensitivity may be increased, as is often seen in patients with a neuropathic component to ocular pain, or decreased, as is seen in patients with neurotrophic keratitis. Corneal sensitivity testing involves assessing a patient's reaction to brief corneal stimulation, yields insight into the health of the corneal nerves, and provides diagnostic value for evaluating the health of the nerves and the interplay with the ocular surface. Currently, there is limited published guidance on how to conduct corneal sensitivity testing in a clinical setting. This article presents a protocol for testing corneal sensitivity using easy-to-use, low-cost materials that are readily accessible to eye care providers (either a cotton swab, a piece of dental floss, or a finely tapered tissue). This protocol allows for qualitative assessment of corneal sensitivity in which responses to corneal stimulation are rated from 0 (no response) to 3 (hypersensitive response). This test can be performed quickly (in approximately 30 s). Given its diagnostic value and accessibility, corneal sensitivity testing should be included as part of the standard eye examination for any patient undergoing an ocular surface examination.

Corneal sensitivity testing provides insight into the health of the corneal nerves and helps diagnose ocular surface diseases. We present a concise protocol to qualitatively assess corneal sensitivity that can be readily used by eye care providers across clinical settings.

The cornea is the most densely innervated structure in the human body, making it one of the most sensitive tissues. Changes in corneal nerve sensitivity ...