Comparison of clinical characteristics of post-refractive surgery-related and post-herpetic neuropathic corneal pain

Abstract

Purpose: To compare the clinical characteristics and in vivo confocal microscopy (IVCM) findings of patients with neuropathic corneal pain (NCP) due to refractive surgery (RS-NCP) and herpetic eye disease (H-NCP) to controls. Methods: Sixteen patients with RS-NCP and 7 patients with H-NCP, and 37 healthy reference age- and sex-matched healthy controls were included to the study. The medical records were reviewed for demographic features, detailed disease history, ocular surface disease index (OSDI), ocular pain assessment survey (OPAS) scores. IVCM images of patients were analyzed and compared to reference controls by two masked observers. Results: The mean pain intensity score for the last 24 h (5.1 ± 2.4 vs. 3.9 ± 1.2; p = 0.27), last 2 weeks (6.1 ± 2.5 vs. 4.8 ± 2.3; p = 0.13) for RS-NCP vs. H-NCP respectively, and quality of life scores (p = 0.23) were similar in both groups. Quality of life, especially mood (p = 0.06) and enjoying life/relations to others (p = 0.10) were affected in both groups, but were not statistically significant between groups. The mean total nerve density was lower in RS-NCP (5,702.4 ± 4,599.0 μm/mm 2 ) compared to their respective controls (26,422.8 ± 4,491.0; p < 0.001) and in the H-NCP group (2,149.5 ± 2,985.9) compared to their respective controls (22,948.8 ± 3,169.0; p < 0.001). Alterations in DC density were similar between all groups (38.3 ± 48.0 cells/mm 2 in RS-NCP, 61.0 ± 76.9 in H-NCP, p = 0.95). Conclusion: Neuropathic corneal pain patients due to refractive surgery show similar clinical characteristics, pain levels, quality of life impact, and IVCM findings as patients with NCP due to herpetic eye disease.

Ocular Surface Changes Associated with Ophthalmic Surgery

“…Post-LASIK DED is thought to be a neuropathic-related disease [ 59 ]. Other refractive surgery can also cause corneal nerve damage and neuropathic corneal pain [ 60 ]. Vestergaard et al compared corneal subbasal nerve morphology, corneal sensation, tear osmolarity, tear film break-up time and Schirmer’s test among patients who underwent FLEX and small SMILE.…”

Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities

“…These functional changes are the consequence of altered expressions of ion channel proteins in the soma and in regenerating nerve terminals. Neuroma structures have emerged as other important morphological changes in corneal nerves and have been suggested as clinical imagining biomarkers (hallmark) of corneal neuropathic pain (Aggarwal et al, 2019 ; Bayraktutar et al, 2020 ; Moein et al, 2020 ). Taken together, these studies suggest that a corneal neuroma may represent an important pathological feature of peripheral nerve abnormalities in patients with ocular pain.…”

Corneal Nerve Abnormalities in Painful Dry Eye Disease Patients

“…In the present context of DED-related NCP, IVCM identified significantly diverse corneal nerve alterations, different between the painful neuropathic and painless conditions but also between the two DED subsets, suggestive of such aforementioned neuropathic phenotypic diversity. Based on data from the relevant literature [2,19,31,39,40] and from the results of this study, DED-related NCP patients could be stratified based on IVCMidentified corneal nerve alterations, as illustrated in Table 4. Further studies will be needed to determine whether this stratification provides new insights into the management of NCP.…”

“…In the clinical setting, NCP has been investigated using ocular surface pain questionnaires (such as the Ocular Pain Assessment Survey [OPAS]) [17], corneal esthesiometry, proparacaine challenge test (to ascertain the peripheral and/or central origin of the NCP) [18], and finally, in vivo confocal microscopy (IVCM), allowing non-invasive imaging of the cornea at the cellular level [14,[19][20][21][22][23].…”