Long-term corneal subbasal nerve plexus regeneration after laser in situ keratomileusis

García-González, Montserrat; Cañadas, Pilar; Gros-Otero, Juan; Rodriguez-Perez, Isabel; Cañones-Zafra, Rafael; Kozobolis, Vassilios; Teus, Miguel A.

doi:10.1016/j.jcrs.2019.02.019

Cited by 25 publications

(26 citation statements)

References 25 publications

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“…Clinical studies show that it can take several years for corneal nerves to completely regenerate after Table 2. Legend: DCN, decorin; Gel, fluid gel surgical-induced ablation [14,15,50], potentially leading to secondary ocular surface conditions, such as dry eye disease and neurotrophic keratopathy [17,49,51]. Despite the clinical importance of treatments to promote corneal nerve regeneration, there are relatively few therapeutic approaches.…”

Section: Discussionmentioning

confidence: 99%

The neuroregenerative effects of topical decorin on the injured mouse cornea

Downie

Grover

et al. 2020

J Neuroinflammation

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Background: The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. Methods: Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1 gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. Results: At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1 gfp/gfp mice treated with decorin. Conclusions: Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.

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Section: Discussionmentioning

confidence: 99%

The neuroregenerative effects of topical decorin on the injured mouse cornea

Downie

Grover

et al. 2020

J Neuroinflammation

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“…The Ocular Surface Disease Index (OSDI) questionnaire was self-administered, and based on the score, each patient was categorized as having no symptoms (score 0-12) or as having mild (score [13][14][15][16][17][18][19][20][21][22], moderate (score 23-32 points), or severe (score 33-100) ocular surface-related symptoms. [9] After that, we asked each patient which eye he considered the most symptomatic.…”

Section: Ocular Surface-related Symptom Questionnairementioning

confidence: 99%

“…Two masked observers analyzed the following: (1) nerve morphology parameters of density, length, branching density, and grade of tortuosity; (2) density of dendritic cells; (3) presence of neuromas; and (4) re ectivity from the confocal images, as an index of optic densitometry or transparency of cornea. [17] The mean value between the two observers for each parameter was computed for statistical analysis.…”

Section: In Vivo Confocal Microscopy (Ivcm)mentioning

confidence: 99%

“…The histogram of each image based on the ImageJ plugin was used to obtain the mean re ectivity or optic densitometry. [17] These parameters were compared with well-established values for normal corneas and performed with the same type of confocal microscope. Speci cally, we used data from Giannacare et al [20] for nerve length, and from our group for nerve density, density of nerve branches, density of dendritic cells, [18] and nerve tortuosity and re ectivity.…”

Section: In Vivo Confocal Microscopy (Ivcm)mentioning

confidence: 99%

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Ocular Surface Pathology in Patients Suffering From Mercury Intoxication Is Consistent With Neurogenic Dry Eye Disease

Cañadas¹,

Dorville²,

Salamanca³

et al. 2021

Preprint

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Purpose: To report ocular surface pathology of patients with acute/subacute mercury intoxication.Methods: Male workers intoxicated with inorganic mercury were examined for dry eye (DE)-related symptoms. Examinations included Ocular Surface Disease Index questionnaire; tear osmolarity, tear break-up time (T-BUT) and production; mechanical and thermal corneal sensitivity; corneal nerve and dendritic cell density analysis; and analysis of 23 tear cytokines.Results: Most patients, 63.6%, had severe DE-related symptoms. Tear osmolarity was elevated in 83.4%, and T-BUT was low in 22.7% of patients. Tear production and tear lysozyme concentration were low in 13.6% and 27.3% of cases, respectively. Corneal sensitivity thresholds for mechanical, heat and cold stimuli were higher than controls. Densities of nerves, nerve branching, and dendritic cells were lower than in controls. Patient tear levels of IL-12p70, IL1-RA, RANTES, and VEGF were increased, whereas EGF, IL-6, and IP-10/CXCL10 were decreased. Based on cytokine levels, two clusters of patients were identified. Cluster 2 patients had significantly increased tear levels of 18 cytokines, decreased tear lysozyme, lower nerve branching density, fewer dendritic cells, and higher urine mercury levels.Conclusions: Mercury poisoning produced previously undescribed ocular surface pathology, similar to neurogenic inflammatory type of DE and different from the more common DE subtypes.

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“…There is a broad range of experimental and clinical applications on corneal analysis with CSLM. The imaging procedure may assess stromal changes in keratoconus patients [4], experimental full-thickness corneal 3D imaging [5], the quantification of morphological features of epithelial cell layers, and the subbasal nerve plexus [6][7][8][9][10] that has become very popular in recent years.…”

Section: Introductionmentioning

confidence: 99%

Confocal Scanning Laser Microscopy in Medicine

Kızıltoprak¹,

Ozkoyuncu²,

Tekin³

et al. 2021

Biomedical Signal and Image Processing

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Confocal Scanning Laser Microscopy (CSLM) offers high resolution morphological details and generates en-face images with excellent depth discrimination for visualizing different structures of the living human body non-invasively. There have been significant advances in technology since the CSLM was first defined. It has been used commonly, especially in ophthalmological area, in order to diagnose and give direction for the treatment of corneal pathologies. Ocular surface, corneal subbasal nerve plexus, filtering blebs of glaucoma surgery were also investigated widely by CSLM. With the improvements in CSLM technology over time, it is widely used in other fields than ophthalmology. The combined use of CSLM with the slit lamp biomicroscopy and optical coherence tomography will also lead to significant advances in the diagnosis and treatment of more diseases in the future.

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Long-term corneal subbasal nerve plexus regeneration after laser in situ keratomileusis

Cited by 25 publications

References 25 publications

The neuroregenerative effects of topical decorin on the injured mouse cornea

The neuroregenerative effects of topical decorin on the injured mouse cornea

Ocular Surface Pathology in Patients Suffering From Mercury Intoxication Is Consistent With Neurogenic Dry Eye Disease

Confocal Scanning Laser Microscopy in Medicine

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