Epithelial Dendritic Cell Distribution in Normal and Inflamed Human Cornea: In Vivo Confocal Microscopy Study

Mastropasqua, Leonardo; Nubile, Mario; Lanzini, Manuela; Carpineto, Paolo; Ciancaglini, Marco; Pannellini, Tania; Nicola, Marta Di; Dua, Harminder S.

doi:10.1016/j.ajo.2006.06.057

Cited by 189 publications

(185 citation statements)

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“…Of paramount importance is the subbasal layer, in which epithelial immune dendritiform cells (DCs) and the subbasal nerve plexus can be clearly visualized. [5][6][7][8][9] Dentritic cells are the professional antigen-presenting cells of the cornea and have a critical function in activation of the immune system in the ocular surface, playing a role in both suppression and induction of inflammation. [10][11][12][13] Furthermore, in addition to providing trophic and sensory functions, corneal nerves have been shown to play an important role in the maintenance of ocular surface epithelial health and function.…”

Section: Purposementioning

confidence: 99%

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Kheirkhah

Müller

Mikolajczak

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images.METHODS. This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping.RESULTS. There were no statistically significant differences between the average of three representative standard images (0.16 mm 2 each) and the wide-field composite images (1.29 6 0.64 mm 2 ) in terms of mean subbasal nerve density (17.10 6 6.10 vs. 17.17 6 5.60 mm/mm 2 , respectively, P ¼ 0.87) and mean subbasal DC density (53.2 6 67.8 vs. 49.0 6 54.3 cells/mm 2 , respectively, P ¼ 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density.CONCLUSIONS. There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer.

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Section: Purposementioning

confidence: 99%

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Kheirkhah

Müller

Mikolajczak

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…While dendritic cell density in aniridia exceeded the density in controls and in previous reports of normal subjects, 22,23 the value was below the density reported in clinically inflamed corneas. 23 The absence of overt signs of inflammation in this study suggests the mature dendritic cell population is indicative of a chronic, subclinical form of inflammation in early-stage ARK.…”

Section: Discussionmentioning

confidence: 57%

“…Orbscan II topographer (Bausch & Lomb) was used to document corneal topography and in-vivo confocal microscopy (IVCM; HRT3-RCM, Heidelberg Engineering, Germany) was used to evaluate cellular changes in the cornea including quantification of subbasal nerve density 21 and Langerhans/dendritic cell density in the central cornea. 22,23 IVCM images were coded to blind examiners to the subject's diagnosis (aniridia or healthy control). For dendritic cell density, only mature dendritic cells, consisting of cell bodies and processes, were counted, as an indication of the presence of antigen-presenting cells involved in inflammation.…”

Section: Examinationsmentioning

confidence: 99%

“…For dendritic cell density, only mature dendritic cells, consisting of cell bodies and processes, were counted, as an indication of the presence of antigen-presenting cells involved in inflammation. 23,24 For quantification, from each subject, clear, high-contrast images of the central subbasal nerve plexus with the greatest number of visible nerves and the greatest number of visible dendritic cells were selected. These images were used to assess subbasal nerve density and mature dendritic cell density, respectively.…”

Section: Examinationsmentioning

confidence: 99%

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Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

et al. 2012

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Objective: To document the clinical and morphologic corneal findings in the early stages of congenital aniridic keratopathy in Swedish families. less thanbrgreater than less thanbrgreater thanDesign: Prospective, observational, comparative case series. less thanbrgreater than less thanbrgreater thanParticipants: A total of 16 eyes of 16 subjects with congenital aniridic keratopathy and a clear central cornea, and 6 eyes from 6 healthy controls (unaffected relatives). Nine of the 16 eyes with aniridia came from 5 families with a documented familial history of aniridia. less thanbrgreater than less thanbrgreater thanMethods: Detailed ophthalmic examinations included best spectacle-corrected visual acuity (BSCVA), tear film production, tear break-up time (BUT), corneal touch sensitivity, intraocular pressure measurement, ultrasound pachymetry, slit-lamp biomicroscopy, and laser scanning in vivo confocal microscopy (IVCM). less thanbrgreater than less thanbrgreater thanMain Outcome Measures: Confirmed stage of aniridic keratopathy, clinical parameters of cornea and tear film (visual acuity, sensitivity, corneal thickness, tear production, and BUT), and the morphologic status of corneal epithelium, sub-basal nerves, and limbal palisades of Vogt. less thanbrgreater than less thanbrgreater thanResults: In early-stage aniridic keratopathy, BSCVA and tear BUT were reduced relative to controls (P andlt; 0.001 for both), and corneal thickness was increased (P = 0.01). Inflammatory dendritic cells were present in the central epithelium in aniridia, with significantly increased density relative to controls (P = 0.001). Discrete focal opacities in the basal epithelial region were present in 5 of 11 aniridia cases with an otherwise clear cornea. Opacities were associated with dendritic cells and harbored structures presumed to be goblet cells. Sub-basal nerves were extremely dense in 3 aniridia cases, and a prominent whorl pattern of nerves and epithelial cells was observed in 1 case. Normal limbal palisade morphology was absent in aniridia but present in controls. less thanbrgreater than less thanbrgreater thanConclusions: Early-stage aniridic keratopathy is characterized by the development of focal opacities in the basal epithelium, altered sub-basal nerves, infiltration of the central epithelium by dendritic cells, tear film instability, and increased corneal thickness and degradation of limbal palisade architecture. These findings may help to elucidate the pathogenesis of aniridic keratopathy. less thanbrgreater than less thanbrgreater thanFinancial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Funding Agencies|European Union||Crown Princess Margaretas Foundation for the Visually Impaired||Swedish Eye Fund||Carmen and Bertil Regners Foundation||David and Beth Dahlins Foundation||King Gustav V and Queen Victorias Freemasons Foundation||County Council of Ostergotland||Association of the Blind in Ostergotland||

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“…IVCM has allowed visualization of cellular detail in the evaluation of both the conjunctiva 23,24,27,28 and cornea, 29,30 which is comparable to and correlates strongly with ex vivo histological techniques such as immunohistochemistry 31 and conjunctival impression cytology. 32,33 This provision made by IVCM has allowed clinical research to spearhead, where previously obtaining * * epithelium epithelium stroma stroma epithelium epithelium stroma stroma stroma stroma air Figure 4 Qualitative features of the palpebral conjunctiva and associated glands in MGD-associated persistent dry eye symptoms using in vivo confocal microscopy (IVCM).…”

Section: Discussionmentioning

confidence: 99%

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

Qazi

Kheirkhah

Blackie

et al. 2015

Eye

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Purpose The utility of in vivo confocal microscopy (IVCM) in the investigation of palpebral conjunctival and corneal inflammation in patients with meibomian gland dysfunction (MGD)-associated refractory dry eye symptoms following gland expression, despite objective clinical improvement. Methods A retrospective, observational pilot study was conducted evaluating five patients with MGD-associated refractory dry eye symptoms and three control groups: symptomatic untreated MGD patients (n = 3), treatment-responsive MGD patients with improved symptoms (n = 3) and asymptomatic healthy normals (n = 11). Ocular surface disease index (OSDI) scores, tear break-up time (TBUT), the number of meibomian glands yielding liquid secretion (MGYLS), palpebral conjunctival epithelial and substantia propria immune cell (EIC, SIC), and corneal dendritic cell (DC) densities were measured. Results Despite clinical improvement (TBUT: 6.4 ± 1.2 s to 10.1 ± 2.1 s, P = 0.03; MGYLS: 3.5 ± 0.8 glands to 7.0 ± 1.1 glands, P = 0.13) and a normal clinical examination post treatment, MGD patients remained symptomatic. IVCM revealed increased immune cells in the palpebral conjunctiva (refractory MGD EIC = 592.6 ± 110.1 cells/ mm 2 ; untreated MGD EIC = 522.6 ± 104.7 cells/mm 2 , P = 0.69; responsive MGD EIC = 194.9 ± 119.4 cells/mm 2 , Po0.01; normals EIC = 123.7 ± 19.2 cells/mm 2 , Po 0.001), but not the cornea (refractory MGD DC = 60.9 ± 28.3 cells/mm 2 ; normals DC = 25.9 ± 6.3 cells/mm 2 ; P = 0.43). EIC did not correlate with TBUT (R s = − 0.26, P = 0.33). OSDI scores correlated with both EIC (R s = 0.76, Po0.001) and TBUT (R s = − 0.69, Po0.01) but not SIC. Intraglandular immune cells were also seen. Conclusion MGD-associated refractory symptoms and the symptom-sign disparity may be explained by clinically non-apparent, active inflammation of the palpebral conjunctiva as detected by IVCM. These patients may benefit from anti-inflammatory therapy.

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Epithelial Dendritic Cell Distribution in Normal and Inflamed Human Cornea: In Vivo Confocal Microscopy Study

Cited by 189 publications

References 42 publications

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Pathologic Epithelial and Anterior Corneal Nerve Morphology in Early-Stage Congenital Aniridic Keratopathy

In vivo detection of clinically non-apparent ocular surface inflammation in patients with meibomian gland dysfunction-associated refractory dry eye symptoms: a pilot study

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