Corneal nerve regeneration after herpes simplex keratitis: A longitudinal in vivo confocal microscopy study

Moein, Hamid Reza; Kheirkhah, Ahmad; Müller, Rodrigo; Cruzat, Andrea; Pavan-Langston, Deborah; Hamrah, Pedram

doi:10.1016/j.jtos.2017.12.001

Cited by 48 publications

(25 citation statements)

References 45 publications

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“…Presumably, it may be the subsequent feedback from the nerve injury or degeneration. The morphological characteristics of corneal nerve regeneration remain to be clearly elucidated 17–20. In the present study, increased nerve density, length, branching and tortuosity were observed in the EM patients, indicating an attempt of corneal subbasal nerves to regenerate.…”

Section: Discussionsupporting

confidence: 46%

<p>Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study</p>

Shen¹,

Dong²,

Zhou³

et al. 2019

JPR

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Background and purpose: It has been generally thought that activation and sensitization of the trigeminovascular system may contribute to the pathogenesis of migraine. Nevertheless, there is little evidence on abnormalities in peripheral trigeminal afferent nerves from humans in vivo. Alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve may support the notion that trigeminal afferent nerves are involved in migraine pathophysiology. The aim of the present study was to investigate the structural changes in corneal subbasal nerve plexus in patients with episodic migraine (EM) with in vivo confocal microscope (IVCM). Methods: In this cross-sectional observational study, 10 EM patients and 10 age- and sex-matched healthy controls were included. Analysis of IVCM images with Image J software was performed to quantify the changes in the corneal subbasal nerve plexus. Results: EM patients showed an increase in nerve fiber length (25.0±2.65 vs 22.3±2.41 mm/mm 2 , p =0.047) and nerve fiber density (36.3±7.29 vs 30.5±6.19 fibers/mm 2 , p =0.104) as compared with normal controls, but this difference was not statistically significant. Nerve branching and tortuosity were significantly increased in the EM subjects compared to the normal subjects (91.3±13.8 vs 75.0±14.2 branches/mm 2 , p =0.030 and 2.30±0.46 versus 1.63±0.52, p =0.011, respectively). In addition, nerve sprouts and increased number of Langerhans cells were observed in the EM patients. Conclusion: The morphologic changes of corneal subbasal nerve plexus and Langerhans cell aggregation suggest the presence of nerve regeneration and inflammation in EM. Furthermore, the alterations of corneal nerves from the ophthalmic branch of the trigeminal nerve offer support for the hypothesis that the peripheral trigeminal system may be involved in the pathogenesis of migraine.

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Section: Discussionsupporting

confidence: 46%

<p>Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study</p>

Shen¹,

Dong²,

Zhou³

et al. 2019

JPR

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“…It is well-known that herpes simplex [ 28 ], herpes zoster [ 29 ] and refractive surgery [ 30 ] can cause corneal nerve damage, which can be detected as decreased nerve density by IVCM. Post-herpetic neuralgia stems from damage to peripheral and central neurons that may be due to either inflammation and/or viral infection, and it is known as one of the most painful conditions [ 31 – 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, chronic post-herpetic neuralgia does not develop with all acute episodes and can occur after several acute episodes. Interestingly, even long-term follow-up has shown that nerve density may not be restored to healthy levels after herpetic eye disease [ 28 , 29 ]. Similarly, persistent nerve loss over many years has been shown following refractive surgery [ 17 , 30 , 39 – 41 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, both groups demonstrated significantly lower nerve densities than their respective age- and sex-matched healthy controls groups. Previous studies have shown that although corneal nerve regeneration occurs in patients with herpetic eye disease, it still remains low as compared to age-matched healthy individuals, even after 3 years of follow-up [ 28 ]. Further, it has been reported that reaching normal corneal nerve density levels can be achieved after 2 years of PRK and by 5 years following LASIK surgery [ 55 ].…”

Section: Discussionmentioning

confidence: 99%

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

Bayraktutar¹,

Özmen²,

Muzaaya³

et al. 2020

The Ocular Surface

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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.

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“…There is a significant correlation between corneal nerve abnormalities (decreased corneal nerve density and nerve regeneration) and post-herpetic corneal sensation Hamrah et al, 2013;Cruzat et al, 2016;Moein et al, 2018). Post-herpetic neuralgia (PHN) is a chronic and refractory neuropathic pain that persists for 3 months or more after an outbreak of acute herpes zoster infection.…”

Section: Corneal Neuropathies Associated With Ocular Painmentioning

confidence: 99%

Corneal pain and experimental model development

McKay

Seyed‐Razavi

Ghezzi

et al. 2019

Progress in Retinal and Eye Research

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The cornea is a valuable tissue for studying peripheral sensory nerve structure and regeneration due to its avascularity, transparency, and dense innervation. Somatosensory innervation of the cornea serves to identify changes in environmental stimuli at the ocular surface, thereby promoting barrier function to protect the eye against injury or infection. Due to regulatory demands to screen ocular safety of potential chemical exposure, a need remains to develop functional human tissue models to predict ocular damage and pain using in vitro-based systems to increase throughput and minimize animal use. In this review, we summarize the anatomical and functional roles of corneal innervation in propagation of sensory input, corneal neuropathies associated with pain, and the status of current in vivo and in vitro models. Emphasis is placed on tissue engineering approaches to study the human corneal pain response in vitro with integration of proper cell types, controlled microenvironment, and high-throughput readouts to predict pain induction. Further developments in this field will aid in defining molecular signatures to distinguish acute and chronic pain triggers based on the immune response and epithelial, stromal, and neuronal interactions that occur at the ocular surface that lead to functional outcomes in the brain depending on severity and persistence of the stimulus.

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Corneal nerve regeneration after herpes simplex keratitis: A longitudinal in vivo confocal microscopy study

Cited by 48 publications

References 45 publications

<p>Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study</p>

<p>Corneal subbasal nerve plexus changes in patients with episodic migraine: an in vivo confocal microscopy study</p>

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

Corneal pain and experimental model development

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