In this study, corneal sensitivity was measured with a new noncontact esthesiometer, demonstrating that it is reduced in both DED patients and those using ocular hypotensive drops, compared to healthy controls. It is known that corneal damage caused by ocular surface diseases or topical medications may produce damage to the corneal nerve endings (6, 9, 10, 12). This may develop an irreversible neurotrophic keratopathy if the factors that damage the cornea are not modified (20, 21). For this reason, corneal esthesiometry screening may play a crucial role in this patient population.
Corneal sensitivity has already been evaluated in other studies but with other devices. The most commonly used is Cochet-Bonnet, which tests predominantly mechanoreceptors using a nylon thread whose length can be modified (25, 26). The first difference between the Brill device and Cochet-Bonnet esthesiometer, is that the former uses an air puff instead of mechanical contact, so it may be stimulating different corneal nociceptors (mechanoreceptors, thermoreceptors and polymodal receptors). For this reason, the results obtained with this esthesiometer cannot be compared with those obtained with Cochet-Bonnet or other mechanical esthesiometers. Other authors report the use of different noncontact esthesiometers (29–37) that can measure thermal, chemical or mechanical sensitivity using compressed air or gas. However, these devices are difficult to use in daily practice. In contrast, Brill’s non-contact esthesiometer is portable, minimally invasive and easy to use by physicians, optometrist or ophthalmic technicians.
In our study there were statistically significant differences in age and sex distributions between the three groups. The ocular surface parameters measured with keratography (Keratograph 5M, Oculus) were NIBUT, TMH, conjunctival redness and CS. NIBUT was significantly lower in the DED and glaucoma group compared to controls, as shown in other previous studies (43, 44). The TMH was significantly lower in the glaucoma group. This result is the same obtained by other groups (43, 45). Compared to healthy patients, conjunctival redness and CS was also higher in both DED and glaucoma patients but was statistically significant only in the DED group.
DED eyes had significantly higher OSDI test scores compared to controls. It is interesting how in these patients, symptoms are greater than in healthy subjects despite having decreased corneal sensitivity. This has already been shown in some studies that have observed that there is no correlation between symptoms and signs in patients with OSD (7, 8). But on the other hand, the OSDI score was lower in the glaucoma group than in the DED group. The reason could be a greater damage of the corneal nerves in these patients, demonstrated by the fact that they are the group with the most reduced corneal sensitivity. This demonstrates the importance of screening these patients, since despite having damaged corneas, they do not present the same ocular symptoms as patients with DED.
Corneal sensitivity measured with this novel noncontact esthesiometer was reduced in DED patients compared to controls. This finding is consistent with prior studies in which esthesiometry was analyzed (15, 29, 46, 47). In contrast, other studies found that DED patients had significantly higher sensitivity than controls (48). This may be due to corneal nerves present in corneal epithelium are more exposed secondary to corneal injury and instability of the tear film, so they perceive sensations more intensely. Is possible that corneal sensitivity might be higher in the early stages of the disease, while it may decrease in the chronic stage. The nerves endings suffer damage by continued irritation of the ocular surface, that together with local inflammation and the inflammatory mediators that are released, cause the destruction and loss of the ability to perceive sensations in the cornea (9, 12).
Sensitivity was also significantly reduced in glaucoma patients who used ocular hypotensive eye drops, compared to dry eye patients and controls, which has been reported previously by other groups (18, 19). It is known that many patients using these medications present with OSD (6, 10). Prolonged use of these eye drops is thought to induce neurotrophic keratopathy, affecting the corneal sensitivity of patients, and increasing their risk of developing epithelial damage and ulcers that can become complicated. The damage caused by these medications is due both to the presence of preservatives (2, 3, 6) and to the adverse effects of the antiglaucoma medications themselves. For example, timolol has been shown in previous studies to have an anesthetic effect on the corneal surface (49, 50), and the proinflammatory effect of prostaglandins is a well-known adverse effect of these medications (5).
Non-contact corneal esthesiometry may be an excellent diagnostic tool, which can be easily performed by any ophthalmic technician, to determine when corneal sensitivity starts to decline in patients using topical glaucoma medications. At this point, it may be appropriate to switch these patients to preservative-free hypotensive medications, perform laser trabeculoplasty or consider surgical intervention to eliminate or reduce the number of glaucoma medications. This strategy may avoid causing an irreversible neurotrophic keratopathy (51).
This study also evaluated whether corneal sensitivity levels had a relationship with topical medications used in the glaucoma group. For the analysis we have utilized two different metrics, the number of drops applications daily and the number of different IOP-lowering medications. For example, a patient on timolol twice daily and latanoprost nightly would have 3 drop administrations daily but would only be on two medications. On one hand, the relationship between the number of daily drop instillations and corneal sensitivity showed a significant reduction in those who used ≥ 3 IOP-lowering drops per day. On the other hand, when examining the relationship between the number of medications used and corneal sensitivity, a tendency to lower sensitivity was observed in patients using ≥ 3 different medications, but it was not statistically significant. These differences in results may be because the use of a greater number of drops per day also involves a greater application of preservatives, which have been associated with corneal nerve damage in glaucoma patients (52). Therefore, corneal damage may be more related to the preservatives than to the active ingredients themselves, as reported in other studies, in which patients treated with preservative free IOP-lowering drops had less damage to the ocular surface (6, 10).
There are various limitations to this study. First, sensitivity testing is subjective because the patient determines whether they perceive the stimulus or not. The differences between esthesiometry levels are minimal and sometimes patients did not perceive the air puff, but when repeating the measurement with the same pressure they did feel it. For this reason, the measurement was repeated three times at each level. Second, patients in this study were not separated based on the type or duration of the hypotensive eye drops they were using. Further studies will be required to elucidate this aspect.